TY - CONF TI - Does contrast ultrasound dispersion imaging reveal changes in tortuosity? A comparison with acoustic angiography AU - Panfilova, A. AU - Shelton, S.E. AU - van Sloun, R.J.G. AU - Demi, L. AU - Wijkstra, H. AU - Dayton, P. AU - Mischi, M. T2 - IEEE International Ultrasound Symposium C2 - 2016/9/18/ C3 - IEEE International Ultrasound Symposium CY - Tours, France DA - 2016/9/18/ PY - 2016/9/18/ ER - TY - JOUR TI - In-vivo quantitative analysis of the angiogenic microvasculature in tumor-bearing rats using multiple scattering: A preliminary study AU - Joshi, Aditya AU - Shelton, Sarah AU - Papadopoulou, Virginie AU - Lindsey, Brooks AU - Dayton, Paul AU - Muller, Marie T2 - Journal of the Acoustical Society of America AB - We propose a method to quantify the vascular density in vascular networks using contrast-enhanced multiple scattering. We measured the diffusion constant D and transport mean free path L* from the time evolution of the incoherent intensity in a rat model of cancer. An 8 MHz linear transducer array was used to record the backscattered signals from subcutaneous fibrosarcoma tumors and control tissue. The coherent and incoherent contributions to the backscattered intensity were separated, and the growth rate of the incoherent contribution was measured, giving the D and L*, knowing the effective speed of sound. By translating the linear array along the tumor, mapping of L* was achieved. Tumors were implanted in the right flank of four rats, and the contralateral side served as control. Acoustic angiography and measurements of the incoherent intensity were performed. The mean L* values in control and tumor tissue were significantly different (105.27 + /- 30.96 micron and 41.28+ /- 14.23 micron, respectively, p = 8.4033 × 10-49). The mean distance between vessels was estimated from acoustic angiography images using Monte-Carlo simulations, and was in agreement with the experimentally calculated values of L* (r = 0.9507, p = 1.4957 × 10-9). DA - 2016/10/1/ PY - 2016/10/1/ DO - 10.1121/1.4970022 VL - 140 IS - 4_Supplement SP - 3187-3187 LA - en OP - SN - 0001-4966 1520-8524 UR - http://dx.doi.org/10.1121/1.4970022 DB - Crossref ER - TY - JOUR TI - Mutations in Mtr4 structural domains reveal their important role in regulating tRNAiMet turnover in saccharomyces cerevisiae and Mtr4p enzymatic activities in vitro AU - Li, Y AU - Burclaff, J AU - Anderson, JT T2 - PLoS ONE AB - RNA processing and turnover play important roles in the maturation, metabolism and quality control of a large variety of RNAs thereby contributing to gene expression and cellular health. The TRAMP complex, composed of Air2p, Trf4p and Mtr4p, stimulates nuclear exosome-dependent RNA processing and degradation in Saccharomyces cerevisiae. The Mtr4 protein structure is composed of a helicase core and a novel so-called arch domain, which protrudes from the core. The helicase core contains highly conserved helicase domains RecA-1 and 2, and two structural domains of unclear functions, winged helix domain (WH) and ratchet domain. How the structural domains (arch, WH and ratchet domain) coordinate with the helicase domains and what roles they are playing in regulating Mtr4p helicase activity are unknown. We created a library of Mtr4p structural domain mutants for the first time and screened for those defective in the turnover of TRAMP and exosome substrate, hypomodified tRNAiMet. We found these domains regulate Mtr4p enzymatic activities differently through characterizing the arch domain mutants K700N and P731S, WH mutant K904N, and ratchet domain mutant R1030G. Arch domain mutants greatly reduced Mtr4p RNA binding, which surprisingly did not lead to significant defects on either in vivo tRNAiMet turnover, or in vitro unwinding activities. WH mutant K904N and Ratchet domain mutant R1030G showed decreased tRNAiMet turnover in vivo, as well as reduced RNA binding, ATPase and unwinding activities of Mtr4p in vitro. Particularly, K904 was found to be very important for steady protein levels in vivo. Overall, we conclude that arch domain plays a role in RNA binding but is largely dispensable for Mtr4p enzymatic activities, however the structural domains in the helicase core significantly contribute to Mtr4p ATPase and unwinding activities. DA - 2016/// PY - 2016/// DO - 10.1371/journal.pone.0148090 VL - 11 IS - 1 SP - 0148090, UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84958211904&partnerID=MN8TOARS ER - TY - CHAP TI - Modeling Murine Gastric Metaplasia Through Tamoxifen-Induced Acute Parietal Cell Loss AU - Saenz, Jose B. AU - Burclaff, Joseph AU - Mills, Jason C. T2 - Gastrointestinal Physiology and Diseases: Methods and Protocols A2 - Ivanov, I. Andrei AB - Parietal cell loss represents the initial step in the sequential progression toward gastric adenocarcinoma. In the setting of chronic inflammation, the expansion of the mucosal response to parietal cell loss characterizes a crucial transition en route to gastric dysplasia. Here, we detail methods for using the selective estrogen receptor modulator tamoxifen as a novel tool to rapidly and reversibly induce parietal cell loss in mice in order to study the mechanisms that underlie these pre-neoplastic events. PY - 2016/// DO - 10.1007/978-1-4939-3603-8_28 SP - 329-339 PB - Springer New York UR - http://dx.doi.org/10.1007/978-1-4939-3603-8_28 ER - TY - JOUR TI - High Resolution Ultrasound Superharmonic Perfusion Imaging: In Vivo Feasibility and Quantification of Dynamic Contrast-Enhanced Acoustic Angiography. T2 - Annals of biomedical engineering AB - Mapping blood perfusion quantitatively allows localization of abnormal physiology and can improve understanding of disease progression. Dynamic contrast-enhanced ultrasound is a low-cost, real-time technique for imaging perfusion dynamics with microbubble contrast agents. Previously, we have demonstrated another contrast agent-specific ultrasound imaging technique, acoustic angiography, which forms static anatomical images of the superharmonic signal produced by microbubbles. In this work, we seek to determine whether acoustic angiography can be utilized for high resolution perfusion imaging in vivo by examining the effect of acquisition rate on superharmonic imaging at low flow rates and demonstrating the feasibility of dynamic contrast-enhanced superharmonic perfusion imaging for the first time. Results in the chorioallantoic membrane model indicate that frame rate and frame averaging do not affect the measured diameter of individual vessels observed, but that frame rate does influence the detection of vessels near and below the resolution limit. The highest number of resolvable vessels was observed at an intermediate frame rate of 3 Hz using a mechanically-steered prototype transducer. We also demonstrate the feasibility of quantitatively mapping perfusion rate in 2D in a mouse model with spatial resolution of ~100 μm. This type of imaging could provide non-invasive, high resolution quantification of microvascular function at penetration depths of several centimeters. DA - 2016/11/10/ PY - 2016/11/10/ DO - 10.1007/s10439-016-1753-9 UR - https://europepmc.org/articles/PMC5682933 ER - TY - JOUR TI - Improving wound healing through the use of tetrazine-modified alginate AU - De Leon Peralta, EJ AU - Brudno, Y AU - Kwee, Bj AU - Mooney, Dj T2 - The FASEB Journal AB - Ischemic diseases, such as myocardial infarction and peripheral arterial disease, are a leading cause of death globally. There has been increasing interest in treating these diseases with factors that induce angiogenesis, the growth of new blood vessels from pre‐existing blood vessels. We have recently shown that alginate linked to tetrazine helps induce a greater recovery in blood perfusion compared to unmodified alginate in a murine model of hindlimb ischemia. The objective of this project is to understand how this biomaterial induces recovery in blood perfusion. Our hypothesis is that tetrazine acts directly on endothelial cells to induce angiogenesis and also activates immune cells that are proangiogenic. To validate our hypothesis, we have performed in vitro angiogenesis assays to study if tetrazine‐modified alginate induces endothelial cell sprouting. Additionally, we have performed histology and immunohistochemistry on ischemic muscles from our in vivo experiments to see if this biomaterial increases blood vessel density, blood vessel remodeling, and the presence of proangiogenic immune cells. Our findings may lead to a novel method for treating people with ischemic diseases. Support or Funding Information Wyss Institute for Biologically Inspired Engineering, Harvard John A. Paulson School of Engineering and Applied Sciences Research Experiences for Undergraduates (SEAS REU) DA - 2016/4// PY - 2016/4// DO - 10.1096/fasebj.30.1_supplement.1177.10 VL - 30 IS - Supplement 1 SP - 1177.10-1177.10 ER - TY - BOOK TI - Power efficiency-based stiffness optimization of a compliant actuator for underactuated bipedal robot AU - Zhang, Q. AU - Xiao, X. AU - Guo, Z. AB - Introducing compliant actuation to robotic joints can obtain better disturbance rejection performance and higher power efficiency than conventional stiff actuated systems. In this paper, inspired by human joints, a novel compliant actuator applied to underactuated bipedal robot is proposed. After modeling the stiffness of the compliant actuator, this paper gives the configuration of the bipedal robot actuated by compliant actuators. Compared with the elastic structure of MABEL, the compliant element of our robot is simplified. Based on the dynamics of the compliant actuator-driven bipedal robot, a feedback linearization controller is presented to implement position control of the compliant actuator for power efficiency analysis and stiffness optimization. Co-simulations of MATLAB and ADAMS are performed under the defined control trajectory by altering actuator stiffness. The simulation results indicate that, compared with the actuator maintaining very high stiffness like a rigid actuator, the power efficiency of the compliant actuator is improved, and the stiffness optimized to 375 N•m/rad can reach the highest power efficiency. DA - 2016/// PY - 2016/// DO - 10.1007/978-3-319-43506-0_16 VL - 9834 LNCS SE - 186-197 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84981200970&partnerID=MN8TOARS KW - Compliant actuator KW - Underactuated bipedal robot KW - Feedback linearization KW - Trajectory tracking KW - Power efficiency ER - TY - JOUR TI - Trajectory tracking control of the bionic joint actuated by pneumatic artificial muscle based on robust modeling AU - Wang, Y. AU - Zhang, Q. AU - Xiao, X. T2 - Jiqiren/Robot DA - 2016/// PY - 2016/// DO - 10.13973/j.cnki.robot.2016.0248 VL - 38 IS - 2 SP - 248-256 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84964403691&partnerID=MN8TOARS ER - TY - JOUR TI - Effects of Ground Compliance on Bipedal Robot Walking Dynamic Property AU - Zhang, Q. AU - Wang, Y. AU - Xiao, X.-H. T2 - Journal of the Chinese Society of Mechanical Engineers, Transactions of the Chinese Institute of Engineers, Series C/Chung-Kuo Chi Hsueh Kung Ch'eng Hsuebo Pao DA - 2016/// PY - 2016/// VL - 37 IS - 4 SP - 335-342 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85025162616&partnerID=MN8TOARS ER - TY - CONF TI - A Flow Bioreactor Enabling Simultaneous High-Resolution Microscopy of Monolayer Cultures C2 - 2016/10// C3 - Biomedical Engineering Society Annual Meeting DA - 2016/10// ER - TY - CONF TI - Comparison of multiple tension band wire configurations on a greater trochanteric osteotomy model AU - Thompson, E AU - Roe, SC AU - Robe, AK AU - Cole, JH C2 - 2016/// C3 - American College of Veterinary Surgeons Surgery Summit, Seattle, WA, October 6-8 DA - 2016/// ER - TY - CONF TI - The angiogenic and osteogenic effects of cyclic tensile strain on a co-culture of human MSCs and HUVECs AU - Steward, AJ AU - Cole, JH AU - Ligler, FS AU - Loboa, EG T2 - http://www.ors.org/Transactions/62/0197.pdf C2 - 2016/// C3 - Orthopaedic Research Society Annual Meeting, Orlando, FL, March 5-8 DA - 2016/// ER - TY - JOUR TI - Thrombin-Responsive Transcutaneous Patch for Auto-Anticoagulant Regulation AU - Zhang, Yuqi AU - Yu, Jicheng AU - Wang, Jinqiang AU - Hanne, Nicholas J. AU - Cui, Zheng AU - Qian, Chenggen AU - Wang, Chao AU - Xin, Hongliang AU - Cole, Jacqueline H. AU - Gallippi, Caterina M. AU - Zhu, Yong AU - Gu, Zhen T2 - Advanced Materials AB - A thrombin-responsive closed-loop patch is developed for prolonged heparin delivery in a feedback-controlled manner. This microneedle-based patch can sense activated thrombin and subsequently releases heparin to prevent coagulation in the blood flow. This “smart” heparin patch can be transcutaneously inserted into skin without drug leakage and can sustainably regulate blood coagulation in response to thrombin. DA - 2016/11/25/ PY - 2016/11/25/ DO - 10.1002/ADMA.201604043 VL - 29 IS - 4 SP - 1604043 J2 - Adv. Mater. LA - en OP - SN - 0935-9648 UR - http://dx.doi.org/10.1002/ADMA.201604043 DB - Crossref ER - TY - JOUR TI - Anticancer Therapy: Light-Activated Hypoxia-Responsive Nanocarriers for Enhanced Anticancer Therapy (Adv. Mater. 17/2016) AU - Qian, Chenggen AU - Yu, Jicheng AU - Chen, Yulei AU - Hu, Quanyin AU - Xiao, Xuanzhong AU - Sun, Wujin AU - Wang, Chao AU - Feng, Peijian AU - Shen, Qun-Dong AU - Gu, Zhen T2 - Advanced Materials AB - A light-activated hypoxia-responsive drug-delivery vehicle is described by Q.-D. Shen, Z. Gu, and co-workers on page 3313. This conjugated-polymer-based nanocarrier can be activated by photoirradiation, producing singlet oxygen (1O2) and inducing hypoxia to promote release of its cargo inside tumor cells for enhanced anticancer efficacy. DA - 2016/4/28/ PY - 2016/4/28/ DO - 10.1002/ADMA.201670115 VL - 28 IS - 17 SP - 3226-3226 J2 - Adv. Mater. LA - en OP - SN - 0935-9648 UR - http://dx.doi.org/10.1002/ADMA.201670115 DB - Crossref ER - TY - SOUND TI - Shared control of functional electrical stimulation and an electric motor in a hybrid neuroprosthesis AU - Sharma, N. DA - 2016/11/16/ PY - 2016/11/16/ ER - TY - SOUND TI - Shared control of functional electrical stimulation and an electric motor in a hybrid neuroprosthesis AU - Sharma, N. DA - 2016/3/1/ PY - 2016/3/1/ ER - TY - SOUND TI - Control methods for shared use of an electrically-stimulated human muscle and a robot in a hybrid neuroprosthetic AU - Sharma, N. DA - 2016/6/18/ PY - 2016/6/18/ ER - TY - CONF TI - Robust compensation of electromechanical delay during neuromuscular electrical stimulation of antagonistic muscles AU - Qiu, Tianyi AU - Alibeji, Naji AU - Sharma, Nitin T2 - 2016 American Control Conference (ACC) AB - Neuromuscular electrical stimulation (NMES) to extend as well as flex a limb joint requires stimulation of an antagonistic muscle pair. This is due to the fact that muscles are unidirectional actuators. The control challenge is to allocate control inputs to antagonist muscles based on the system output, usually a limb angle error. Further, NMES input to each muscle is delayed by an electromechanical delay (EMD), which arises due to the time lag between the electrical excitation and the force development in a muscle. EMD is known to cause instability or performance loss during closed-loop control of NMES. In this paper, a robust delay compensation controller for EMDs in antagonistic muscles is presented. A Lyapunov stability analysis yields uniformly ultimately bounded tracking for a human limb joint actuated by antagonistic muscles. The simulation results indicate that the controller is robust and effective in switching between antagonistic muscles and compensating EMDs during a simulated NMES task. C2 - 2016/7// C3 - 2016 American Control Conference (ACC) CY - Boston, MA DA - 2016/7// PY - 2016/7/6/ DO - 10.1109/acc.2016.7526124 VL - 2016-July SP - 4871-4876 PB - IEEE SN - 9781467386821 UR - http://dx.doi.org/10.1109/acc.2016.7526124 ER - TY - CONF TI - Switching control of functional electrical stimulation and motor assist for muscle fatigue compensation AU - Kirsch, Nicholas AU - Alibeji, Naji AU - Dicianno, Brad E. AU - Sharma, Nitin T2 - 2016 American Control Conference (ACC) AB - The torque generation capability of muscles often reduces during a functional electrical stimulation (FES) session due to the rapid onset of muscle fatigue. Hybrid rehabilitation systems that use FES and electric motor assist may overcome this issue. The primary control challenge in such a system is how to allocate control inputs between electric motor and FES during muscle fatigue and muscle recovery. One strategy is to switch between FES and the electric motor by using an estimate of the muscle fatigue. This would allow the system to switch from using FES to using the electric motor when the muscle torque output has significantly decreased, then switch back to FES once the muscles have sufficiently recovered. This paper uses a second order sliding mode controller cascaded with a feedback linearization controller for a switched, FES and electric motor, system. The second order sliding mode is achieved through the use of a variable-gain super-twisting algorithm. A Lyapunov stability analysis was used to prove asymptotic stability of the switched control system. Simulations of the developed controller on a hybrid knee extension model illustrate that prolonged knee movements can be elicited through the switched system. C2 - 2016/7// C3 - 2016 American Control Conference (ACC) CY - Boston, MA DA - 2016/7// PY - 2016/7/6/ DO - 10.1109/acc.2016.7526123 VL - 2016-July SP - 4865-4870 PB - IEEE SN - 9781467386821 UR - http://dx.doi.org/10.1109/acc.2016.7526123 ER - TY - CONF TI - Dynamic control allocation of a feedback linearized hybrid neuroprosthetic system AU - Bao, Xuefeng AU - Kirsch, Nicholas AU - Sharma, Nitin T2 - 2016 American Control Conference (ACC) AB - Functional electrical stimulation (FES) can be used to restore motor function to individuals with motion impairments; however, the duration of FES usage is limited by the rapid onset of muscle fatigue. A motor-assist can be used to compensate for the muscle fatigue by sharing work load of FES. However, it is unknown how to optimally allocate control effort to the motor-assist and FES as the muscle fatigues. Further, computing an optimal control solution is challenging given the nonlinear dynamics of the human leg system. This paper uses model predictive control (MPC) to solve an optimal control trajectory for the feedback linearized musculoskeletal system, which simplifies the optimal control problem; therefore, may reduce the computational load for MPC. The feedback linearization controller was developed for the nonlinear musculoskeletal model with fatigue dynamics where FES and an electric motor torque are the inputs. Then MPC was used on the linearized musculoskeletal system to allocate control to FES and an electric motor for regulation. Simulations on a musculoskeletal model of knee extension are presented in the paper. C2 - 2016/7// C3 - 2016 American Control Conference (ACC) DA - 2016/7// DO - 10.1109/acc.2016.7525534 VL - 2016-July SP - 3976-3981 PB - IEEE SN - 9781467386821 UR - http://dx.doi.org/10.1109/acc.2016.7525534 DB - Crossref ER - TY - JOUR TI - Paenibacillus larvae Phage Tripp Genome Has 378-Base-Pair Terminal Repeats AU - Abraham, J. AU - Bousquet, A.-C. AU - Bruff, E. AU - Carson, N. AU - Clark, A. AU - Connell, A. AU - Davis, Z. AU - Dums, J. AU - Everington, C. AU - Groth, A. AU - Hawes, N. AU - McArthur, N. AU - McKenney, C. AU - Oufkir, A. AU - Pearce, B. AU - Rampal, S. AU - Rozier, H. AU - Schaff, J. AU - Slehria, T. AU - Carson, S. AU - Miller, E. S. T2 - Microbiology Resource Announcements AB - ABSTRACT Paenibacillus larvae bacteriophage Tripp was isolated from an American foulbrood diseased honey bee hive in North Carolina, USA. The 54,439-bp genome is 48.3% G+C, encodes 92 proteins, no tRNAs, and has 378-bp direct terminal repeats. It is currently unique in Genbank. DA - 2016/// PY - 2016/// DO - 10.1128/genomeA.01498-15 VL - 4 IS - 1 UR - https://mra.asm.org/content/4/1/e01498-15 ER - TY - JOUR TI - Stimuli-responsive delivery of therapeutics for diabetes treatment AU - Yu, Jicheng AU - Zhang, Yuqi AU - Bomba, Hunter AU - Gu, Zhen T2 - Bioengineering & Translational Medicine AB - Abstract Diabetic therapeutics, including insulin and glucagon‐like peptide 1 (GLP‐1), are essential for diabetic patients to regulate blood glucose levels. However, conventional treatments that are based on subcutaneous injections are often associated with poor glucose control and a lack of patient compliance. In this review, we focus on the different stimuli‐responsive systems to deliver therapeutics for diabetes treatment to improve patient comfort and prevent complications. Specifically, the pH‐responsive systems for oral drug delivery are introduced first. Then, the closed‐loop glucose‐responsive systems are summarized based on different glucose‐responsive moieties, including glucose oxidase, glucose binding protein, and phenylboronic acid. Finally, the on‐demand delivery systems activated by external remote triggers are also discussed. We conclude by discussing advantages and limitations of current strategies, as well as future opportunities and challenges in this area. DA - 2016/9// PY - 2016/9// DO - 10.1002/BTM2.10036 VL - 1 IS - 3 SP - 323-337 J2 - Bioengineering & Translational Medicine LA - en OP - SN - 2380-6761 UR - http://dx.doi.org/10.1002/BTM2.10036 DB - Crossref ER - TY - JOUR TI - Introduction to special issue on “Responsive Materials and Systems: Toward Smart and Precision Medications” AU - Gu, Zhen T2 - Bioengineering & Translational Medicine AB - Spurred by advances in materials chemistry, molecular pharmaceutics and micro/nanobiotechnology, stimuli-responsive “smart” materials and systems have been studied extensively for various applications, including drug delivery, diagnosis, tissue engineering, and biomedical devices. In drug delivery, the dosage-, spatial- and/or temporal- controlled release of therapeutics significantly enhances the treatment efficacy in a precise manner. The development of stimuli-responsive materials also allows noninvasive or minimally invasive monitoring in real-time for achieving next-generation diagnostics. In addition, the smart systems with the capability of communicating and interacting with cells are highly desirable for engineering regenerative medications and biomedical devices. This theme issue focuses on the responsive materials and systems for a range of biomedical applications, with a collection of ten relevant research or review papers. For diabetes treatment, Mitragotri and coworkers1 describe a novel mucoadhesive intestinal device entrapped in a capsule with a pH-responsive enteric coating for oral delivery of insulin. This device loaded with insulin can effectively decrease blood glucose levels of diabetic rats. Gu and coworkers2 summarize a variety of stimuli-responsive delivery systems for diabetes treatment, including the pH-sensitive materials for oral delivery, the glucose-responsive delivery systems, and the on-demand delivery approaches by external ultrasound or light. For cancer therapy, Tong and Feng3 discuss general principles in polymer-drug conjugate design such as the synthetic strategies, the choice of the responsive linkers between the drug and polymer, and the in vivo delivery barriers. Liu and Liang4 review reactive oxygen species (ROS)-responsive system as well as multiple stimuli systems for enhanced delivery of therapeutics. For tissue engineering, Hammond and collaborators5 develop nanoscale polyelectrolyte complexes to deliver insulin-like growth factor-1 (IGF-1) for cartilage repair. They demonstrate IGF-1 is released by nanocomplexes within the joint space over four weeks, protecting cartilage from degradation and mitigating joint inflammation. Remote utilization of physical triggers, such as light, magnetic force and temperature to achieve spatiotemporal activation is an emerging research topic in this field. Lovell and Miranda6 discuss different mechanisms of the light-induced liposome permeabilization for controlled drug delivery, including light-induced oxidation, photocrosslinking, photoisomerization, photocleavage, and photothermal release. Xu and coworkers7 describe the development of near-infrared light-responsive liposomes for enhanced gene transfection through the photothermal effect. Gaharwar and coworkers8 review the applications of smart hydrogels based on magnetic nanoparticles and thermoresponsive polymers in therapeutic drug delivery, bioimaging, and regenerative medicine. In the remainder of this issue, Webber9 focuses on the preparation of responsive self-assembled materials for biomedical applications, including engineering therapeutics and devices for biological sensing and disease diagnostics; Cui and coworkers10 review peptide-based supramolecular nanostructures and hydrogels for biological stimuli-triggered delivery of biologics. Collectively, this issue highlights the exciting research work and key advances in leveraging responsive materials for smart and precision medications, the clinical translation of which would revolutionize health care, profoundly enhancing patients’ health and improving their quality of life. Zhen Gu1,2,3 1University of North Carolina at Chapel Hill and North Carolina, State University 2Molecular Pharmaceutics Division, Eshelman School of Pharmacy University of North Carolina at Chapel Hill 3Dept. of Medicine University of North Carolina School of Medicine DA - 2016/9// PY - 2016/9// DO - 10.1002/BTM2.10045 VL - 1 IS - 3 SP - 235-236 J2 - Bioengineering & Translational Medicine LA - en OP - SN - 2380-6761 UR - http://dx.doi.org/10.1002/BTM2.10045 DB - Crossref ER - TY - JOUR TI - Antimicrobial activity of biopolymeric thin films containing flavonoid natural compounds and silver nanoparticles fabricated by MAPLE: A comparative study AU - Cristescu, R. AU - Visan, A. AU - Socol, G. AU - Surdu, A.V. AU - Oprea, A.E. AU - Grumezescu, A.M. AU - Chifiriuc, M.C. AU - Boehm, R.D. AU - Yamaleyeva, D. AU - Taylor, M. AU - Narayan, R.J. AU - Chrisey, D.B. T2 - Applied Surface Science AB - The purpose of this study was to investigate the interactions between microorganisms, including the planktonic and adherent organisms, and biopolymer (polyvinylpyrrolidone), flavonoid (quercetin dihydrate and resveratrol)-biopolymer, and silver nanoparticles-biopolymer composite thin films that were deposited using matrix assisted pulsed laser evaporation (MAPLE). A pulsed KrF* excimer laser source was used to deposit the aforementioned composite thin films, which were characterized using Fourier transform infrared spectroscopy (FT-IR), infrared microscopy (IRM), scanning electron microscopy (SEM), Grazing incidence X-ray diffraction (GIXRD) and atomic force microscopy (AFM). The antimicrobial activity of thin films was quantified using an adapted disk diffusion assay against Gram-positive and Gram-negative bacteria strains. FT-IR, AFM and SEM studies confirmed that MAPLE may be used to fabricate thin films with chemical properties corresponding to the input materials as well as surface properties that are appropriate for medical use. The silver nanoparticles and flavonoid-containing films exhibited an antimicrobial activity both against Gram-positive and Gram-negative bacterial strains demonstrating the potential use of these hybrid systems for the development of novel antimicrobial strategies. DA - 2016/6// PY - 2016/6// DO - 10.1016/J.APSUSC.2015.11.252 VL - 374 SP - 290-296 J2 - Applied Surface Science LA - en OP - SN - 0169-4332 UR - http://dx.doi.org/10.1016/J.APSUSC.2015.11.252 DB - Crossref KW - Flavonoid KW - Quercetin dihydrate KW - Resveratrol KW - Biopolymer KW - Silver nanoparticle KW - Matrix assisted pulsed laser evaporation KW - Antimicrobial activity ER - TY - JOUR TI - Use of Drawing Lithography-Fabricated Polyglycolic Acid Microneedles for Transdermal Delivery of Itraconazole to a Human Basal Cell Carcinoma Model Regenerated on Mice AU - Zhang, Jennifer AU - Wang, Yan AU - Jin, Jane Y. AU - Degan, Simone AU - Hall, Russell P. AU - Boehm, Ryan D. AU - Jaipan, Panupong AU - Narayan, Roger J. T2 - JOM AB - Itraconazole is a triazole agent that is routinely used for treatment of nail infections and other fungal infections. Recent studies indicate that itraconazole can also inhibit the growth of basal cell carcinoma (BCC) through suppression of the Sonic Hedgehog (SHH) signaling pathway. In this study, polyglycolic acid microneedle arrays and stainless steel microneedle arrays were used for transdermal delivery of itraconazole to a human BCC model which was regenerated on mice. One-by-four arrays of 642-μm-long polyglycolic acid microneedles with sharp tips were prepared using injection molding and drawing lithography. Arrays of 85 stainless steel 800-μm-tall microneedles attached to syringes were obtained for comparison purposes. Skin grafts containing devitalized split-thickness human dermis that had been seeded with human keratinocytes transduced to express human SHH protein were sutured to the skin of immunodeficient mice. Mice with this human BCC model were treated daily for 2 weeks with itraconazole dissolved in 60% dimethylsulfoxane and 40% polyethylene glycol-400 solution; transdermal administration of the itraconazole solution was facilitated by either four 1 × 4 polyglycolic acid microneedle arrays or stainless steel microneedle arrays. The epidermal tissues treated with polyglycolic acid microneedles or stainless steel microneedles were markedly thinner than that of the control (untreated) graft tissue. These preliminary results indicate that microneedles may be used to facilitate transdermal delivery of itraconazole for localized treatment of BCC. DA - 2016/2/16/ PY - 2016/2/16/ DO - 10.1007/S11837-016-1841-1 VL - 68 IS - 4 SP - 1128-1133 J2 - JOM LA - en OP - SN - 1047-4838 1543-1851 UR - http://dx.doi.org/10.1007/S11837-016-1841-1 DB - Crossref ER - TY - JOUR TI - 3D-Bioprinting of Polylactic Acid (PLA) Nanofiber–Alginate Hydrogel Bioink Containing Human Adipose-Derived Stem Cells AU - Narayanan, Lokesh Karthik AU - Huebner, Pedro AU - Fisher, Matthew B. AU - Spang, Jeffrey T. AU - Starly, Binil AU - Shirwaiker, Rohan A. T2 - ACS Biomaterials Science & Engineering AB - Bioinks play a central role in 3D-bioprinting by providing the supporting environment within which encapsulated cells can endure the stresses encountered during the digitally driven fabrication process and continue to mature, proliferate, and eventually form extracellular matrix (ECM). In order to be most effective, it is important that bioprinted constructs recapitulate the native tissue milieu as closely as possible. As such, musculoskeletal soft tissue constructs can benefit from bioinks that mimic their nanofibrous matrix constitution, which is also critical to their function. This study focuses on the development and proof-of-concept assessment of a fibrous bioink composed of alginate hydrogel, polylactic acid nanofibers, and human adipose-derived stem cells (hASC) for bioprinting such tissue constructs. First, hASC proliferation and viability were assessed in 3D-bioplotted strands over 16 days in vitro. Then, a human medial knee meniscus digitally modeled using magnetic resonance images was bioprinted and evaluated over 8 weeks in vitro. Results show that the nanofiber-reinforced bioink allowed higher levels of cell proliferation within bioprinted strands, with a peak at day 7, while still maintaining a vast majority of viable cells at day 16. The cell metabolic activity on day 7 was 28.5% higher in this bioink compared to the bioink without nanofibers. Histology of the bioprinted meniscus at both 4 and 8 weeks showed 54% and 147% higher cell density, respectively, in external versus internal regions of the construct. The presence of collagen and proteoglycans was also noted in areas surrounding the hASC, indicating ECM secretion and chondrogenic differentiation. DA - 2016/7/26/ PY - 2016/7/26/ DO - 10.1021/ACSBIOMATERIALS.6B00196 VL - 2 IS - 10 SP - 1732-1742 J2 - ACS Biomater. Sci. Eng. LA - en OP - SN - 2373-9878 2373-9878 UR - http://dx.doi.org/10.1021/ACSBIOMATERIALS.6B00196 DB - Crossref KW - bioprinting KW - knee meniscus KW - alginate KW - nanofibers KW - adipose-derived stem cells KW - musculoskeletal soft tissue ER - TY - JOUR TI - Drug Delivery: Microneedles Integrated with Pancreatic Cells and Synthetic Glucose-Signal Amplifiers for Smart Insulin Delivery (Adv. Mater. 16/2016) AU - Ye, Yanqi AU - Yu, Jicheng AU - Wang, Chao AU - Nguyen, Nhu-Y AU - Walker, Glenn M. AU - Buse, John B. AU - Gu, Zhen T2 - Advanced Materials AB - A bio-responsive microneedle-based patch, integrated with a rhodamine-stained glucose-signal amplifier and calcein-AM-stained pancreatic β-cell capsules, is developed by Z. Gu and co-workers. This “smart cell patch”, described on page 3115, effectively regulates the blood glucose level of type-1 diabetic mice, achieving a reduction for over 10 h. Image credit: Yanqi Ye. DA - 2016/4// PY - 2016/4// DO - 10.1002/ADMA.201670112 VL - 28 IS - 16 SP - 3223-3223 J2 - Adv. Mater. LA - en OP - SN - 0935-9648 UR - http://dx.doi.org/10.1002/ADMA.201670112 DB - Crossref ER - TY - JOUR TI - Data on biodistribution and radiation absorbed dose profile of a novel 64Cu-labeled high affinity cell-specific peptide for positron emission tomography imaging of tumor vasculature AU - Merrill, Joseph R. AU - Krajewski, Krzysztof AU - Yuan, Hong AU - Frank, Jonathan E. AU - Lalush, David S. AU - Patterson, Cam AU - Veleva, Anka N. T2 - Data in Brief AB - New peptide-based diagnostic and therapeutic approaches hold promise for highly selective targeting of cancer leading to more precise and effective diagnostic and therapeutic modalities. An important feature of these approaches is to reach the tumor tissue while limiting or minimizing the dose to normal organs. In this context, efforts to design and engineer materials with optimal in vivo targeting and clearance properties are important. This Data In Brief article reports on biodistribution and radiation absorbed dose profile of a novel high affinity radiopeptide specific for bone marrow-derived tumor vasculature. Background information on the design, preparation, and in vivo characterization of this peptide-based targeted radiodiagnostic is described in the article "Synthesis and comparative evaluation of novel 64Cu-labeled high affinity cell-specific peptides for positron emission tomography of tumor vasculature" (Merrill et al., 2016) [1]. Here we report biodistribution measurements in mice and calculate the radiation absorbed doses to normal organs using a modified Medical Internal Radiation Dosimetry (MIRD) methodology that accounts for physical and geometric factors and cross-organ beta doses. DA - 2016/6// PY - 2016/6// DO - 10.1016/J.DIB.2016.02.080 VL - 7 SP - 480-484 J2 - Data in Brief LA - en OP - SN - 2352-3409 UR - http://dx.doi.org/10.1016/J.DIB.2016.02.080 DB - Crossref KW - Molecular imaging KW - Tumor angiogenesis KW - Radiation absorbed dose KW - Diagnostic radiopharmaceuticals ER - TY - JOUR TI - Structural regulation by a G-quadruplex ligand increases binding abilities of G-quadruplex-forming aptamers AU - Tsukakoshi, Kaori AU - Ikuta, Yuri AU - Abe, Koichi AU - Yoshida, Wataru AU - Iida, Keisuke AU - Ma, Yue AU - Nagasawa, Kazuo AU - Sode, Koji AU - Ikebukuro, Kazunori T2 - Chemical Communications AB - By the binding of a G4 ligand to G4-forming aptamers, their conformations became suitable for binding to the target and their binding ability increased. DA - 2016/// PY - 2016/// DO - 10.1039/c6cc07552e VL - 52 IS - 85 SP - 12646-12649 UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000386220600022&KeyUID=WOS:000386220600022 ER - TY - JOUR TI - Electrochemical sensing system employing fructosamine 6-kinase enables glycated albumin measurement requiring no proteolytic digestion AU - Kameya, Miho AU - Tsugawa, Wakako AU - Yamada-Tajima, Mayumi AU - Hatada, Mika AU - Suzuki, Keita AU - Sakaguchi-Mikami, Akane AU - Ferri, Stefano AU - Klonoff, David C. AU - Sode, Koji T2 - Biotechnology Journal AB - Abstract Currently available enzymatic methods for the measurement of glycated proteins utilize fructosyl amino acid/peptide oxidases (FAOXs/FPOXs) as sensing elements. FAOXs/FPOXs oxidize glycated amino acids or glycated dipeptides but they are not able to accept longer glycated peptides or intact glycated proteins as substrates. Therefore, pretreatment via proteolytic digestion is unavoidable with the current enzymatic methods, and there remains a need for simpler measurement methods for glycated proteins. In this study, in order to develop a novel sensing system for glycated albumin (GA), a marker for diabetes, with no requirement for proteolytic digestion, we created an electrochemical sensor based on fructosamine 6‐kinase (FN6K) from Escherichia coli . Uniquely, FN6K can react directly with intact GA unlike FAOXs/FPOXs. The concentration of GA in samples was measured using a carbon‐printed disposable electrode upon which FN6K as well as two additional enzymes, pyruvate kinase and pyruvate dehydrogenase were overlaid. A clear correlation between the response current and the concentration of GA was observed in the range of 20–100 µM GA, which is suitable for measurement of GA in diluted blood samples from both healthy individuals and patients with diabetes. The sensing system reported here could be applied to point‐of‐care‐testing devices for measurement of glycated proteins. DA - 2016/// PY - 2016/// DO - 10.1002/biot.201500442 VL - 11 IS - 6 SP - 797-804 UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000379785700009&KeyUID=WOS:000379785700009 KW - Diabetes KW - Fructosamine 6-kinase KW - Glycated albumin KW - Glycated protein KW - Proteolytic digestion ER - TY - JOUR TI - Development of a light-regulated cell-recovery system for non-photosynthetic bacteria AU - Nakajima, Mitsuharu AU - Abe, Koichi AU - Ferri, Stefano AU - Sode, Koji T2 - Microbial Cell Factories AB - Recent advances in the understanding of photosensing in biological systems have enabled the use of photoreceptors as novel genetic tools. Exploiting various photoreceptors that cyanobacteria possess, a green light-inducible gene expression system was previously developed for the regulation of gene expression in cyanobacteria. However, the applications of cyanobacterial photoreceptors are not limited to these bacteria but are also available for non-photosynthetic microorganisms by the coexpression of a cyanobacterial chromophore with a cyanobacteria-derived photosensing system. An Escherichia coli-derived self-aggregation system based on Antigen 43 (Ag43) has been shown to induce cell self-aggregation of various bacteria by exogenous introduction of the Ag43 gene.An E. coli transformant harboring a plasmid encoding the Ag43 structural gene under a green light-regulated gene expression system derived from the cyanobacterium Synechocystis sp. PCC6803 was constructed. Ag43 was inserted downstream of the cpcG 2 promoter P cpcG2 , and its expression was regulated by green light induction, which was achieved by the functional expression of cyanobacterial CcaS/CcaR by coexpressing its chromophore synthesis gene cassette in E. coli. E. coli transformants harboring this designed system self-aggregated under green light exposure and precipitated, whereas transformants lacking the green light induction system did not. The green light induction system effectively functioned before the cell culture entered the stationary growth phase, and approximately 80 % of the cell culture was recovered by simple decantation.This study demonstrated the construction of a cell recovery system for non-photosynthetic microorganisms induced by exposure of cells to green light. The system was regulated by a two-component regulatory system from cyanobacteria, and cell precipitation was mediated by an autotransporter protein, Ag43. Although further strict control and an increase of cell recovery efficiency are necessary, the system represents a novel tool for future bioprocessing with reduced energy and labor required for cell recovery. DA - 2016/// PY - 2016/// DO - 10.1186/s12934-016-0426-6 VL - 15 IS - 1 UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000370025700001&KeyUID=WOS:000370025700001 KW - Antigen 43 KW - Green light induction KW - Cell recovery KW - Green light sensor KW - Optogenetics KW - Escherichia coli ER - TY - JOUR TI - Construction of a Miniaturized Chromatic Acclimation Sensor from Cyanobacteria with Reversed Response to a Light Signal AU - Nakajima, Mitsuharu AU - Ferri, Stefano AU - Rogner, Matthias AU - Sode, Koji T2 - Scientific Reports AB - Cyanobacteria harbor unique photoreceptors, designated as cyanobacteriochromes (CBCRs). In this study, we attempted to engineer the chromatic acclimation sensor CcaS, a CBCR derived from the cyanobacterium Synechocystis sp. PCC 6803. The wild-type CcaS induces gene expression under green light illumination and represses it under red light illumination. We focused on the domain structure of CcaS, which consists of an N-terminal transmembrane helix; a GAF domain, which serves as the sensor domain; a linker region (L1); two PAS domains; a second linker region (L2); and a C-terminal histidine kinase (HK) domain. Truncated versions of the photoreceptor were constructed by removing the L1 linker region and the two PAS domains, and fusing the GAF and HK domains with a truncated linker region. Thus constructed "miniaturized CcaSs" were grouped into four distinct categories according to their responses toward green and red light illumination, with some showing improved gene regulation compared to the wild type. Remarkably, one of the miniaturized CcaSs induced gene expression under red light and repressed it under green light, a reversed response to the light signal compared to wild type CcaS. These characteristics of engineered photoreceptors were discussed by analyzing the CcaS structural model. DA - 2016/// PY - 2016/// DO - 10.1038/srep37595 VL - 6 UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000388967600001&KeyUID=WOS:000388967600001 ER - TY - JOUR TI - BioCapacitor: A novel principle for biosensors AU - Sode, Koji AU - Yamazaki, Tomohiko AU - Lee, Inyoung AU - Hanashi, Takuya AU - Tsugawa, Wakako T2 - Biosensors & Bioelectronics AB - Studies regarding biofuel cells utilizing biocatalysts such as enzymes and microorganisms as electrocatalysts have been vigorously conducted over the last two decades. Because of their environmental safety and sustainability, biofuel cells are expected to be used as clean power generators. Among several principles of biofuel cells, enzyme fuel cells have attracted significant attention for their use as alternative energy sources for future implantable devices, such as implantable insulin pumps and glucose sensors in artificial pancreas and pacemakers. However, the inherent issue of the biofuel cell principle is the low power of a single biofuel cell. The theoretical voltage of biofuel cells is limited by the redox potential of cofactors and/or mediators employed in the anode and cathode, which are inadequate for operating any devices used for biomedical application. These limitations inspired us to develop a novel biodevice based on an enzyme fuel cell that generates sufficient stable power to operate electric devices, designated "BioCapacitor." To increase voltage, the enzyme fuel cell is connected to a charge pump. To obtain a sufficient power and voltage to operate an electric device, a capacitor is used to store the potential generated by the charge pump. Using the combination of a charge pump and capacitor with an enzyme fuel cell, high voltages with sufficient temporary currents to operate an electric device were generated without changing the design and construction of the enzyme fuel cell. In this review, the BioCapacitor principle is described. The three different representative categories of biodevices employing the BioCapacitor principle are introduced. Further, the recent challenges in the developments of self-powered stand-alone biodevices employing enzyme fuel cells combined with charge pumps and capacitors are introduced. Finally, the future prospects of biodevices employing the BioCapacitor principle are addressed. DA - 2016/// PY - 2016/// DO - 10.1016/j.bios.2015.07.065 VL - 76 SP - 20-28 UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000364895000003&KeyUID=WOS:000364895000003 KW - BioCapacitor KW - Enzyme fuel cell KW - Charge pump KW - Implantable devices KW - Continuous glucose monitoring ER - TY - JOUR TI - An Fe-S cluster in the conserved Cys-rich region in the catalytic subunit of FAD-dependent dehydrogenase complexes AU - Shiota, Masaki AU - Yamazaki, Tomohiko AU - Yoshimatsu, Keiichi AU - Kojima, Katsuhiro AU - Tsugawa, Wakako AU - Ferri, Stefano AU - Sode, Koji T2 - Bioelectrochemistry AB - Several bacterial flavin adenine dinucleotide (FAD)-harboring dehydrogenase complexes comprise three distinct subunits: a catalytic subunit with FAD, a cytochrome c subunit containing three hemes, and a small subunit. Owing to the cytochrome c subunit, these dehydrogenase complexes have the potential to transfer electrons directly to an electrode. Despite various electrochemical applications and engineering studies of FAD-dependent dehydrogenase complexes, the intra/inter-molecular electron transfer pathway has not yet been revealed. In this study, we focused on the conserved Cys-rich region in the catalytic subunits using the catalytic subunit of FAD dependent glucose dehydrogenase complex (FADGDH) as a model, and site-directed mutagenesis and electron paramagnetic resonance (EPR) were performed. By co-expressing a hitch-hiker protein (γ-subunit) and a catalytic subunit (α-subunit), FADGDH γα complexes were prepared, and the properties of the catalytic subunit of both wild type and mutant FADGDHs were investigated. Substitution of the conserved Cys residues with Ser resulted in the loss of dye-mediated glucose dehydrogenase activity. ICP-AEM and EPR analyses of the wild-type FADGDH catalytic subunit revealed the presence of a 3Fe–4S-type iron–sulfur cluster, whereas none of the Ser-substituted mutants showed the EPR spectrum characteristic for this cluster. The results suggested that three Cys residues in the Cys-rich region constitute an iron–sulfur cluster that may play an important role in the electron transfer from FAD (intra-molecular) to the multi-heme cytochrome c subunit (inter-molecular) electron transfer pathway. These features appear to be conserved in the other three-subunit dehydrogenases having an FAD cofactor. DA - 2016/// PY - 2016/// DO - 10.1016/j.bioelechem.2016.01.010 VL - 112 SP - 178-183 UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000383523800024&KeyUID=WOS:000383523800024 KW - Fe-S cluster KW - Glucose dehydrogenase KW - FAD KW - Direct electron transfer KW - FAD-dependent dehydrogenase ER - TY - JOUR TI - Production of Spherical Ablations Using Nonthermal Irreversible Electroporation: A Laboratory Investigation Using a Single Electrode and Grounding Pad AU - Sano, Michael B. AU - Fan, Richard E. AU - Hwang, Gloria L. AU - Sonn, Geoffrey A. AU - Xing, Lei T2 - Journal of Vascular and Interventional Radiology AB - Purpose To mathematically model and test ex vivo a modified technique of irreversible electroporation (IRE) to produce large spherical ablations by using a single probe. Materials and Methods Computed simulations were performed by using varying voltages, electrode exposure lengths, and tissue types. A vegetable (potato) tissue model was then used to compare ablations created by conventional and high-frequency IRE protocols by using 2 probe configurations: a single probe with two collinear electrodes (2EP) or a single electrode configured with a grounding pad (P+GP). The new P+GP electrode configuration was evaluated in ex vivo liver tissue. Results The P+GP configuration produced more spherical ablation volumes than the 2EP configuration in computed simulations and tissue models. In prostate tissue, computed simulations predicted ablation volumes at 3,000 V of 1.6 cm3 for the P+GP configurations, compared with 0.94 cm3 for the 2EP configuration; in liver tissue, the predicted ablation volumes were 4.7 times larger than those in the prostate. Vegetable model studies verify that the P+GP configuration produces larger and more spherical ablations than those produced by the 2EP. High-frequency IRE treatment of ex vivo liver with the P+GP configuration created a 2.84 × 2.21-cm ablation zone. Conclusions Computer modeling showed that P+GP configuration for IRE procedures yields ablations that are larger than the 2EP configuration, creating substantial ablation zones with a single electrode placement. When tested in tissue models and an ex vivo liver model, the P+GP configuration created ablation zones that appear to be of clinically relevant size and shape. DA - 2016/9// PY - 2016/9// DO - 10.1016/J.JVIR.2016.05.032 VL - 27 IS - 9 SP - 1432-1440.e3 J2 - Journal of Vascular and Interventional Radiology LA - en OP - SN - 1051-0443 UR - http://dx.doi.org/10.1016/J.JVIR.2016.05.032 DB - Crossref ER - TY - JOUR TI - Design and evaluation of an actuated exoskeleton for examining motor control in stroke thumb AU - Wang, Furui AU - Jones, Christopher L. AU - Shastri, Milind AU - Qian, Kai AU - Kamper, Derek G. AU - Sarkar, Nilanjan T2 - Advanced Robotics AB - Chronic hand impairment is common following stroke. This paper presents an actuated thumb exoskeleton (ATX) to facilitate research in examining motor control and hand rehabilitation. The ATX presented in this work aims to provide independent bi-directional actuation in each of the 5 degrees-of-freedom (DOF) of the thumb using a novel flexible shaft based mechanism that has 5 active DOF and 3 passive DOF. A prototype has been built and experiments have been conducted to measure the allowable workspace at the thumb and evaluate the kinematic and kinetic performance of the ATX. The experimental results show that the ATX is able to provide individual actuation at all 5 thumb joints with high joint velocity and torque capacities. Further improvement and future work are discussed. DA - 2016/2// PY - 2016/2// DO - 10.1080/01691864.2015.1105867 VL - 30 IS - 3 SP - 165-177 J2 - Advanced Robotics LA - en OP - SN - 0169-1864 1568-5535 UR - http://dx.doi.org/10.1080/01691864.2015.1105867 DB - Crossref KW - robot-assisted rehabilitation KW - motor control KW - stroke thumb KW - actuated thumb exoskeleton ER - TY - JOUR TI - Signal amplification strategies for microfluidic immunoassays AU - Giri, Basant AU - Pandey, Binod AU - Neupane, Bhanu AU - Ligler, Frances S. T2 - TrAC Trends in Analytical Chemistry AB - Immunoassays have become much more sophisticated since the enzyme linked immunoassays became widely used. Microfluidics in particular, coupled with advanced optical and electrochemical readout systems have reduced the limits of detection, decreased assay time, and simplified automation. Yet the sensitivity of the microfluidic immunoassays is still limited by the ability of the detector to discriminate between signal and background. Three main approaches to produce higher signal/background are reviewed and critiqued: target preconcentration, reaction confinement in a small detection volume and signal amplification strategies. Combinations of these strategies can be used to increase sensitivity and may provide clinical diagnostics for biomarkers present in very low concentrations. DA - 2016/5// PY - 2016/5// DO - 10.1016/J.TRAC.2015.10.021 VL - 79 SP - 326-334 J2 - TrAC Trends in Analytical Chemistry LA - en OP - SN - 0165-9936 UR - http://dx.doi.org/10.1016/J.TRAC.2015.10.021 DB - Crossref KW - Limit of detection KW - Sensitivity KW - Biomarkers KW - Preconcentration KW - Magnetic beads KW - Immuno-PCR ER - TY - JOUR TI - Evanescent wave fluorescence biosensors: Advances of the last decade AU - Taitt, Chris Rowe AU - Anderson, George P. AU - Ligler, Frances S. T2 - Biosensors and Bioelectronics AB - Biosensor development has been a highly dynamic field of research and has progressed rapidly over the past two decades. The advances have accompanied the breakthroughs in molecular biology, nanomaterial sciences, and most importantly computers and electronics. The subfield of evanescent wave fluorescence biosensors has also matured dramatically during this time. Fundamentally, this review builds on our earlier 2005 review. While a brief mention of seminal early work will be included, this current review will focus on new technological developments as well as technology commercialized in just the last decade. Evanescent wave biosensors have found a wide array applications ranging from clinical diagnostics to biodefense to food testing; advances in those applications and more are described herein. DA - 2016/2// PY - 2016/2// DO - 10.1016/J.BIOS.2015.07.040 VL - 76 SP - 103-112 J2 - Biosensors and Bioelectronics LA - en OP - SN - 0956-5663 UR - http://dx.doi.org/10.1016/J.BIOS.2015.07.040 DB - Crossref KW - Optical biosensor KW - Evanescent wave KW - Fluorescence KW - Applications ER - TY - CONF TI - Noninvasive EEG correlates of overground and stair walking AU - Brantley, Justin A. AU - Luu, Trieu Phat AU - Ozdemir, Recep AU - Zhu, Fangshi AU - Winslow, Anna T. AU - Huang, Helen AU - Contreras-Vidal, Jose L. T2 - 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) AB - Automated walking intention detection remains a challenge in lower-limb neuroprosthetic systems. Here, we assess the feasibility of extracting motor intent from scalp electroencephalography (EEG). First, we evaluated the corticomuscular coherence between central EEG electrodes (C1, Cz, C2) and muscles of the shank and thigh during walking on level ground and stairs. Second, we trained decoders to predict the linear envelope of the surface electromyogram (EMG). We observed significant EEG-led corticomuscular coupling between electrodes and sEMG (tibialis anterior) in the high delta (3-4 Hz) and low theta (4-5 Hz) frequency bands during level walking, indicating efferent signaling from the cortex to peripheral motor neurons. The coherence was increased between EEG and vastus lateralis and tibialis anterior in the delta band (<; 2 Hz) during stair ascent, indicating a task specific modulation in corticomuscular coupling. However, EMG was the leading signal for biceps femoris and gastrocnemius coherence during stair ascent, possibly representing afferent feedback loops from periphery to the motor cortex. Decoder validation showed that EEG signals contained information about the sEMG patterns during over ground walking, however, the accuracy of the predicted sEMG patterns decreased during the stair condition. Overall, these initial findings support the feasibility of integrating sEMG and EEG into a hybrid decoder for volitional control of lower limb neuroprostheses. C2 - 2016/8// C3 - 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) DA - 2016/8// DO - 10.1109/embc.2016.7592028 VL - 2016-October SP - 5729-5732 PB - IEEE SN - 9781457702204 UR - http://dx.doi.org/10.1109/embc.2016.7592028 DB - Crossref ER - TY - CONF TI - Effect of environmental factors on level of trip disturbance: A simulation study AU - Liu, Ming AU - Bohlen, Peter AU - Huang, He Helen T2 - 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) AB - Above knee amputees exhibit a higher risk of falling than able-bodied people, so the capacity to recover from trips (a major cause of unintentional falls) is critical for these amputees to prevent fall-related injuries. Although trip recovery approaches using powered prostheses have been proposed, the effectiveness of these approaches has not been evaluated with varied trip-related disturbance levels. Here, we conducted a simulation study to understand the relationship between trip-related disturbance levels and environmental factors. This knowledge could clarify the design space as well as guide design and evaluation techniques of future trip recovery approaches. C2 - 2016/8// C3 - 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) DA - 2016/8// DO - 10.1109/embc.2016.7591859 VL - 2016-October SP - 5038-5041 PB - IEEE SN - 9781457702204 UR - http://dx.doi.org/10.1109/embc.2016.7591859 DB - Crossref ER - TY - CONF TI - Corticomuscular coherence variation throughout the gait cycle during overground walking and ramp ascent: A preliminary investigation AU - Winslow, Anna T AU - Brantley, Justin AU - Zhu, Fangshi AU - Vidal, Jose L Contreras AU - Huang, He T2 - 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) AB - Recent designs of neural-machine interfaces (NMIs) incorporating electroencephalography (EEG) or electromyography (EMG) have been used in lower limb assistive devices. While the results of previous studies have shown promise, a NMI which takes advantage of early movement-related EEG activity preceding movement onset, as well as the improved signal-to-noise ratio of EMG, could prove to be more accurate and responsive than current NMI designs based solely on EEG or EMG. Previous studies have demonstrated that the activity of the sensorimotor cortex is coupled to the firing rate of motor units in lower limb muscles during voluntary contraction. However, the exploration of corticomuscular coherence during locomotive tasks has been limited. In this study, coupling between the motor cortex and right tibialis anterior muscle activity was preliminarily investigated during self-paced over-ground walking and ramp ascent. EEG at the motor cortex and surface EMG from the tibialis anterior were collected from one able-bodied subject. Coherence between the two signals was computed and studied across gait cycles. The EEG activity led the EMG activity in the low gamma band in swing phase of level ground walking and in stance phase of ramp ascent. These results may inform the future design of EEG-EMG multimodal NMIs for lower limb devices that assist locomotion of people with physical disabilities. C2 - 2016/8// C3 - 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) DA - 2016/8// DO - 10.1109/embc.2016.7591760 VL - 2016-October SP - 4634-4637 PB - IEEE SN - 9781457702204 UR - http://dx.doi.org/10.1109/embc.2016.7591760 DB - Crossref ER - TY - CONF TI - Tolerance of neural decoding errors for powered artificial legs: A pilot study AU - Zhang, Fan AU - Liu, Ming AU - Huang, He T2 - 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) AB - Neural-machine interface (NMI) decoding errors challenge the clinical value of neural control of powered artificial legs, because these errors can dangerously disturb the user's walking balance, cause stumbles or falls, and thus threaten the user's confidence and safety in prosthesis use. Although extensive research efforts have been made to minimize the NMI decoding error rate, none of the current approaches can completely eliminate the errors in NMI. This study aimed at improving the robustness of prosthesis control system against neural decoding errors by introducing a fault-tolerant control (FTC) strategy. A novel reconfiguration mechanism, combined with our previously developed NMI decoding error detector, was designed and implemented into our prototypical powered knee prosthesis. The control system with FTC was preliminarily tested on two transfemoral amputees when they walked with the powered prosthesis on different walking terrains. Various NMI errors were simulated when the FTC was enabled and disabled. The preliminary testing results indicated that the FTC strategy was capable of effectively counteracting the disruptive effects of simulated decoding errors by reducing the mechanical work change around the prosthetic knee joint elicited by the NMI error. The outcomes of this study may provide a potential engineering solution to make the neural control of powered artificial legs safer to use. C2 - 2016/8// C3 - 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) DA - 2016/8// DO - 10.1109/embc.2016.7591759 VL - 2016-October SP - 4630-4633 PB - IEEE SN - 9781457702204 UR - http://dx.doi.org/10.1109/embc.2016.7591759 DB - Crossref ER - TY - CONF TI - Does the impedance of above-knee powered prostheses need to be adjusted for load-carrying conditions? AU - Brandt, Andrea AU - Liu, Ming AU - Huang, He Helen T2 - 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) AB - Powered knee prostheses provide substantial advantages for amputees compared to traditional passive devices during basic walking tasks (i.e. level-ground, stairs, ramps), but the impedance control parameters are fixed. For environments that differ from the well-controlled setting of the clinic, amputees must compensate their gait patterns because fixed control parameters ideal for walking on level ground in the clinic do not meet real-life task demands. Load carriage is one instance where fixed control parameters may lead to undesired gait patterns and potentially result in injury. To evaluate the importance of impedance control parameters for different walking tasks, we tested one above-knee amputee walking using an experimental powered prosthesis under four walking conditions. The amputee walked with and without added mass with both load-specific and non-specific impedance control parameters. The load-specific parameters significantly reduced the amputee's intact-leg compensations, asymmetry, and perceived exertion compared to the non-specific control parameters. Powered lower limb prostheses that modulate impedance control parameters for load-carrying tasks may improve the gait performance, safety, and comfort of amputees. C2 - 2016/8// C3 - 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) DA - 2016/8// DO - 10.1109/embc.2016.7591868 VL - 2016-October SP - 5075-5078 PB - IEEE SN - 9781457702204 UR - http://dx.doi.org/10.1109/embc.2016.7591868 DB - Crossref ER - TY - CONF TI - Adaptive control of powered transfemoral prostheses based on adaptive dynamic programming AU - Wen, Yue AU - Liu, Ming AU - Si, Jennie AU - Huang, He Helen T2 - 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) AB - In this study, we developed and tested a novel adaptive controller for powered transfemoral prostheses. Adaptive dynamic programming (ADP) was implemented within the prosthesis control to complement the existing finite state impedance control (FS-IC) in a prototypic active-transfemoral prosthesis (ATP). The ADP controller interacts with the human user-prosthesis system, observes the prosthesis user's dynamic states during walking, and learns to personalize user performance properties via online adaptation to meet the individual user's objectives. The new ADP controller was preliminarily tested on one able-bodied subject walking on a treadmill. The test objective was for the user to approach normative knee kinematics by tuning the FS-IC impedance parameters via ADP. The results showed the ADP was able to adjust the prosthesis controller to generate the desired normative knee kinematics within 10 minutes. In the meantime, the FS-IC impedance parameters converged at the end of the adaptive tuning procedure while maintaining the desired human-prosthesis performance. This study demonstrated the feasibility of ADP for adaptive control of a powered lower limb prosthesis. Future research efforts will address several important issues in order to validate the system on amputees. To achieve this goal, human user-centered performance objective functions will be developed, tested, and used in this adaptive controller design. C2 - 2016/8// C3 - 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) DA - 2016/8// DO - 10.1109/embc.2016.7591867 VL - 2016-October SP - 5071-5074 PB - IEEE SN - 9781457702204 UR - http://dx.doi.org/10.1109/embc.2016.7591867 DB - Crossref ER - TY - CONF TI - Simple EMG-driven musculoskeletal model enables consistent control performance during path tracing tasks AU - Crouch, Dustin AU - Huang, He T2 - 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) AB - Consistent, robust performance is critical for the utility and user-acceptance of neurally-controlled powered upper limb prostheses. We preliminarily evaluated the performance consistency of an electromyography (EMG)-driven controller based on a two degree-of-freedom musculoskeletal hand model, whose simplified structure is more practical for real-time prosthesis control than existing, complex models. Parameters of four virtual muscles were computed by numerical optimization from an able-bodied subject's kinematic and EMG data collected during wrist and metacarpophalangeal (MCP) flexion/extension movements. The subject attempted to trace a series of paths of different complexity (straight and curved) with the fingertip of a virtual hand displayed on a computer screen; the straight-path tracing tasks were repeated on a second test day to evaluate performance consistency over time. The subject's tracing accuracy during the tasks was consistent both between tasks of varying complexity (i.e. straight vs curved) and between test days when tracing the straight paths. Additionally, task duration, straightness, and smoothness did not significantly differ between the two straight-path test days. The consistent performance between days was achieved even with a very short (~15 seconds) calibration period to re-normalize EMG. The subject also coordinated movements of the wrist and MCP joints simultaneously during the task, much like with healthy, intact limb movement. Our promising results suggest that a musculoskeletal model-based controller may provide consistent and effective performance across a range of operating conditions, making it potentially practical for prosthesis control. Further research is needed to determine whether musculoskeletal model-based control (1) is effective for executing real-world tasks, and (2) can be extended to populations with neuromuscular impairment (e.g. amputation). C2 - 2016/8// C3 - 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) DA - 2016/8// DO - 10.1109/embc.2016.7590625 VL - 2016-October SP - 1-4 PB - IEEE SN - 9781457702204 UR - http://dx.doi.org/10.1109/embc.2016.7590625 DB - Crossref ER - TY - JOUR TI - Differential gene expression in human, murine, and cell line-derived macrophages upon polarization AU - Spiller, Kara L. AU - Wrona, Emily A. AU - Romero-Torres, Saly AU - Pallotta, Isabella AU - Graney, Pamela L. AU - Witherel, Claire E. AU - Panicker, Leelamma M. AU - Feldman, Ricardo A. AU - Urbanska, Aleksandra M. AU - Santambrogio, Laura AU - Vunjak-Novakovic, Gordana AU - Freytes, Donald O. T2 - Experimental Cell Research AB - The mechanisms by which macrophages control the inflammatory response, wound healing, biomaterial-interactions, and tissue regeneration appear to be related to their activation/differentiation states. Studies of macrophage behavior in vitro can be useful for elucidating their mechanisms of action, but it is not clear to what extent the source of macrophages affects their apparent behavior, potentially affecting interpretation of results. Although comparative studies of macrophage behavior with respect to cell source have been conducted, there has been no direct comparison of the three most commonly used cell sources: murine bone marrow, human monocytes from peripheral blood (PB), and the human leukemic monocytic cell line THP-1, across multiple macrophage phenotypes. In this study, we used multivariate discriminant analysis to compare the in vitro expression of genes commonly chosen to assess macrophage phenotype across all three sources of macrophages, as well as those derived from induced pluripotent stem cells (iPSCs), that were polarized towards four distinct phenotypes using the same differentiation protocols: M(LPS,IFN) (aka M1), M(IL4,IL13) (aka M2a), M(IL10) (aka M2c), and M(-) (aka M0) used as control. Several differences in gene expression trends were found among the sources of macrophages, especially between murine bone marrow-derived and human blood-derived M(LPS,IFN) and M(IL4,IL13) macrophages with respect to commonly used phenotype markers like CCR7 and genes associated with angiogenesis and tissue regeneration like FGF2 and MMP9. We found that the genes with the most similar patterns of expression among all sources were CXCL-10 and CXCL-11 for M(LPS,IFN) and CCL17 and CCL22 for M(IL4,IL13). Human PB-derived macrophages and human iPSC-derived macrophages showed similar gene expression patterns among the groups and genes studied here, suggesting that iPSC-derived monocytes have the potential to be used as a reliable cell source of human macrophages for in vitro studies. These findings could help select appropriate markers when testing macrophage behavior in vitro and highlight those markers that may confuse interpretation of results from experiments employing macrophages from different sources. DA - 2016/9// PY - 2016/9// DO - 10.1016/J.YEXCR.2015.10.017 VL - 347 IS - 1 SP - 1-13 J2 - Experimental Cell Research LA - en OP - SN - 0014-4827 UR - http://dx.doi.org/10.1016/J.YEXCR.2015.10.017 DB - Crossref KW - Classically activated KW - Alternatively activated macrophages KW - Wound healing KW - In vitro characterization KW - Angiogenesis KW - Tissue engineering KW - Induced pluripotent stem cells KW - Biomaterials ER - TY - JOUR TI - Derivation and characterization of porcine vocal fold extracellular matrix scaffold AU - Wrona, E.A. AU - Peng, R. AU - Born, H. AU - Amin, M.R. AU - Branski, R.C. AU - Freytes, D.O. T2 - Laryngoscope AB - To optimize decellularization of porcine vocal folds (VF) and quantify human bone marrow-derived mesenchymal stem cell (BM-MSC) interactions with this matrix to provide a foundation for regenerative approaches to VF repair.Vocal folds were dissected from porcine larynges and three decellularization protocols were compared, each consisting of washes and mechanical agitations with different combinations of reagents. DNA content was analyzed via Quant-iT Picogreen assay and hematoxylin and eosin staining. Bone marrow-derived MSCs were then seeded onto the decellularized VF matrices. Morphology, metabolic activity, DNA content, and gene expression were assessed using LIVE/DEAD Cell Viability, alamarBlue Cell Viability Assay, Quant-iT Picogreen assay, and quantitative polymerase chain reaction, respectively.The most successful decellularization protocol removed 95% DNA content within 1 day, compared to several days required for previously described protocols. Histology confirmed the retention of extracellular matrix (ECM) and its components, including glycosaminoglycans, collagen, and fibrin, while void of nuclear/cellular content. Decellularized scaffolds were then seeded with BM-MSCs. Similar DNA quantities were observed after 24 hours of seeding within the VF-ECM scaffold when compared to cells on tissue culture plastic (TCP). LIVE/DEAD staining of the seeded VF-ECM confirmed excellent cell viability, and the metabolic activity of BM-MSCs increased significantly on VF-ECM compared to TCP. Endoglin gene expression decreased, suggestive of differentiation.Porcine VFs can be efficiently decellularized within 5 hours using a combination of sodium deoxycholate and peracetic acid. Decellularized VF-ECM supported attachment and growth of human BM-MSCs, with evidence of differentiation.N/A. DA - 2016/// PY - 2016/// DO - 10.1002/lary.25640 VL - 126 IS - 4 SP - 928-935 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84941694990&partnerID=MN8TOARS KW - Vocal fold KW - extracellular matrix KW - mesenchymal stem cells KW - scaffold ER - TY - JOUR TI - Radiation therapy for hepatocellular carcinoma AU - Kennedy, A. S. T2 - Hepatocellular carcinoma: diagnosis and treatment, 3rd edition DA - 2016/// PY - 2016/// SP - 531-546 ER - TY - CONF TI - Cognitive workload in conventional direct control vs. pattern recognition control of an upper-limb prosthesis AU - Zhang, W. J. AU - White, M. AU - Zahabi, M. AU - Winslow, A. T. AU - Zhang, F. AU - Huang, He AU - Kaber, D. AB - The purpose of this study was to compare the cognitive workload of able-bodied individuals when using a myoelectric prosthetic under direct control (DC) or electromyography pattern recognition (PR) control. Different from existing clinical evaluations involving dual-task performance, pupillography measured with an eye-tracking system was used to quantitatively assess user cognitive workload in using a 2 degree-of-freedom prosthesis for a clothespin task. Test results revealed the PR control to produce superior task performance and to require lower cognitive load than demanded of participants under the DC condition. This study provided evidence of both performance and workload advantages of PR control over DC control. PR control was more intuitive to the prosthesis user and, therefore, required less cognitive effort. Furthermore, the study identified a new effective measure of cognitive workload in upper limb prosthesis use via pupillography. C2 - 2016/// C3 - Ieee international conference on systems man and cybernetics conference DA - 2016/// DO - 10.1109/smc.2016.7844587 SP - 2335–2340 ER - TY - JOUR TI - Incorporating concomitant medications into genome-wide analyses for the study of complex disease and drug response AU - Graham, H. T. AU - Rotroff, D. M. AU - Marvel, S. W. AU - Buse, J. B. AU - Havener, T. M. AU - Wilson, A. G. AU - Wagner, M. J. AU - Motsinger-Reif, A. A. T2 - Frontiers in Genetics DA - 2016/// PY - 2016/// VL - 7 ER - TY - JOUR TI - experimental validation of ARFI surveillance of subcutaneous hemorrhage (ASSH) using calibrated infusions in a tissue-mimicking model and dogs AU - Geist, R. E. AU - DuBois, C. H. AU - Nichols, T. C. AU - Caughey, M. C. AU - Merricks, E. P. AU - Raymer, R. AU - Gallippi, C. M. T2 - Ultrasonic Imaging DA - 2016/// PY - 2016/// VL - 38 IS - 5 SP - 346-358 ER - TY - CONF TI - Cell membrane-mediated anticancer drug delivery AU - Hu, Q. Y. AU - Gu, Z. C2 - 2016/// C3 - Nanotechnology: delivering on the promise, vol 2 DA - 2016/// VL - 1224 SP - 197-211 ER - TY - CONF TI - Towards a sweat-based wireless and wearable electrochemical sensor AU - Dieffenderfer, J. AU - Wilkins, M. AU - Hood, C. AU - Beppler, E. AU - Daniele, M. A. AU - Bozkurt, A. C2 - 2016/// C3 - 2016 ieee sensors DA - 2016/// ER - TY - CONF TI - Nanocellulose electrodes for interfacing plant electrochemistry AU - Keller, K. AU - Wilkins, M. AU - Reynolds, J. AU - Dieffenderfer, J. AU - Hood, C. AU - Daniele, M. A. AU - Bozkurt, A. AU - Tunc-Ozdemir, M. C2 - 2016/// C3 - 2016 ieee sensors DA - 2016/// ER - TY - JOUR TI - Cell signaling in tenocytes: Response to load and ligands in health and disease AU - Wall, M. E. AU - Dyment, N. A. AU - Bodle, J. AU - Volmer, J. AU - Loboa, E. AU - Cederlund, A. AU - Fox, A. M. AU - Banes, A. J. T2 - Metabolic influences on risk for tendon disorders DA - 2016/// PY - 2016/// VL - 920 SP - 79-95 ER - TY - CONF TI - Monitoring exercise- and diet-induced changes in tibial blood perfusion with laser doppler flowmetry in mice AU - Hanne, N. AU - Steward, A. AU - Easter, E. AU - Cole, J. C2 - 2016/// C3 - International Bone and Mineral Society Annual Herbert Fleisch Workshop DA - 2016/// ER - TY - JOUR TI - Modeling age-related changes in muscle-tendon dynamics during cyclical contractions in the rat gastrocnemius AU - Danos, Nicole AU - Holt, Natalie C. AU - Sawicki, Gregory S. AU - Azizi, Emanuel T2 - JOURNAL OF APPLIED PHYSIOLOGY AB - Efficient muscle-tendon performance during cyclical tasks is dependent on both active and passive mechanical tissue properties. Here we examine whether age-related changes in the properties of muscle-tendon units (MTUs) compromise their ability to do work and utilize elastic energy storage. We empirically quantified passive and active properties of the medial gastrocnemius muscle and material properties of the Achilles tendon in young (∼6 mo) and old (∼32 mo) rats. We then used these properties in computer simulations of a Hill-type muscle model operating in series with a Hookean spring. The modeled MTU was driven through sinusoidal length changes and activated at a phase that optimized muscle-tendon tuning to assess the relative contributions of active and passive elements to the force and work in each cycle. In physiologically realistic simulations where young and old MTUs started at similar passive forces and developed similar active forces, the capacity of old MTUs to store elastic energy and produce positive work was compromised. These results suggest that the observed increase in the metabolic cost of locomotion with aging may be in part due to the recruitment of additional muscles to compensate for the reduced work at the primary MTU. Furthermore, the age-related increases in passive stiffness coupled with a reduced active force capacity in the muscle can lead to shifts in the force-length and force-velocity operating range that may significantly impact mechanical and metabolic performance. Our study emphasizes the importance of the interplay between muscle and tendon mechanical properties in shaping MTU performance during cyclical contractions. DA - 2016/10/1/ PY - 2016/10/1/ DO - 10.1152/japplphysiol.00396.2016 VL - 121 IS - 4 SP - 1004-1012 SN - 1522-1601 KW - aging KW - elastic energy KW - cost of locomotion KW - fibrosis KW - ankle joint work ER - TY - JOUR TI - Extracellular Matrix for Vocal Fold Lamina Propria Replacement: A Review AU - Wrona, Emily A. AU - Peng, Robert AU - Amin, Milan R. AU - Branski, Ryan C. AU - Freytes, Donald O. T2 - TISSUE ENGINEERING PART B-REVIEWS AB - The vocal folds (VFs) are exposed to a number of injurious stimuli that frequently lead to aberrant structural alterations and altered biomechanical properties that clinically manifest as voice disorders. Therapies to restore both structure and function of this delicate tissue are ideal. However, such methods have not been adequately developed. Our group and others hypothesize that tissue engineering and regenerative medicine approaches, previously described for other tissue systems, hold significant promise for the VFs. In this review, we explore the concept of tissue engineering as it relates to the VFs, as well as recent studies employing both naturally and synthetically derived biomaterials, including those from laryngeal and nonlaryngeal sources, in combination with stem cells for a tissue-engineered approach to VF repair. DA - 2016/12// PY - 2016/12// DO - 10.1089/ten.teb.2016.0015 VL - 22 IS - 6 SP - 421-429 SN - 1937-3376 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85020490144&partnerID=MN8TOARS KW - voice KW - vocal fold KW - extracellular matrix KW - scaffold ER - TY - CONF TI - Bone blood perfusion increases with diet-induced obesity, associated with trabecular deterioration in mice AU - Hanne, NJ AU - Steward, AJ AU - Easter, ED AU - Cole, JH C2 - 2016/// C3 - Biomedical Engineering Society Annual Meeting, Minneapolis, MN, October 5-8 DA - 2016/// ER - TY - CONF TI - Nanocomposite transducer with a laser ultarsound transmitter and a piezoelectric receiver AU - Kim, J. AU - Chang, W. Y. AU - Huang, S. J. AU - Jiang, X. N. AB - Laser ultrasound transducers, converting the laser pulses into acoustic waves with high frequency, broadband and high pressure amplitude, is attractive to many biomedical and industrial applications. In this paper, nanocomposites consisting of carbon nanomaterials, PDMS and PVDF were incorporated into a transducer structure for ultrasound transmitting and receiving. The prototyped nanocomposite transducers were characterized by conducting pulse-echo tests. The obtained center frequency is 12 MHz, -6 dB fractional bandwidth is 138%, and the signal-to-noise ratio of 42 dB with an excitation of ~5 mJ of 532 nm, 6 ns pulsed laser. These initial findings strongly suggest that laser ultrasound transducers are promising for advanced ultrasound imaging applications. C2 - 2016/// C3 - 2016 IEEE 16th International Conference on Nanotechnology (IEEE-nano) DA - 2016/// DO - 10.1109/nano.2016.7751440 SP - 191-192 ER - TY - JOUR TI - Lumped-parameter electromyogram-driven musculoskeletal hand model: A potential platform for real-time prosthesis control AU - Crouch, Dustin L. AU - Huang, He T2 - JOURNAL OF BIOMECHANICS AB - Simple, lumped-parameter musculoskeletal models may be more adaptable and practical for clinical real-time control applications, such as prosthesis control. In this study, we determined whether a lumped-parameter, EMG-driven musculoskeletal model with four muscles could predict wrist and metacarpophalangeal (MCP) joint flexion/extension. Forearm EMG signals and joint kinematics were collected simultaneously from 5 able-bodied (AB) subjects. For one subject with unilateral transradial amputation (TRA), joint kinematics were collected from the sound arm during bilateral mirrored motion. Twenty-two model parameters were optimized such that joint kinematics predicted by EMG-driven forward dynamic simulation closely matched measured kinematics. Cross validation was employed to evaluate the model kinematic predictions using Pearson׳s correlation coefficient (r). Model predictions of joint angles were highly to very highly positively correlated with measured values at the wrist (AB mean r=0.94, TRA r=0.92) and MCP (AB mean r=0.88, TRA r=0.93) joints during single-joint wrist and MCP movements, respectively. In simultaneous multi-joint movement, the prediction accuracy for TRA at the MCP joint decreased (r=0.56), while r-values derived from AB subjects and TRA wrist motion were still above 0.75. Though parameters were optimized to match experimental sub-maximal kinematics, passive and maximum isometric joint moments predicted by the model were comparable to reported experimental measures. Our results showed the promise of a lumped-parameter musculoskeletal model for hand/wrist kinematic estimation. Therefore, the model might be useful for EMG control of powered upper limb prostheses, but more work is needed to demonstrate its online performance. DA - 2016/12/8/ PY - 2016/12/8/ DO - 10.1016/j.jbiomech.2016.10.035 VL - 49 IS - 16 SP - 3901-3907 SN - 1873-2380 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85005810502&partnerID=MN8TOARS KW - Wrist KW - Simulation KW - Amputation KW - Parameter KW - Optimization ER - TY - JOUR TI - Inflammation-Triggered Cancer Immunotherapy by Programmed Delivery of CpG and Anti-PD1 Antibody AU - Wang, Chao AU - Sun, Wujin AU - Wright, Grace AU - Wang, Andrew Z. AU - Gu, Zhen T2 - ADVANCED MATERIALS AB - Inflammation-triggered combination delivery of anti-PD-1 antibody and CpG oligodeoxynucleotides (CpG ODNs) has been demonstrated to prevent cancer relapse utilizing postsurgical inflammatory response. The controlled release of anti-PD1 and CpG ODN by CpG DNA-based "nano-cocoons" can induce considerable immune response, which in turn significantly prolongs the survival time of mice. DA - 2016/10/26/ PY - 2016/10/26/ DO - 10.1002/adma.201506312 VL - 28 IS - 40 SP - 8912-8920 SN - 1521-4095 ER - TY - JOUR TI - Identification and isolation of antigen-specific cytotoxic T lymphocytes with an automated microraft sorting system AU - Attayek, Peter J. AU - Hunsucker, Sally A. AU - Sims, Christopher E. AU - Allbritton, Nancy L. AU - Armistead, Paul M. T2 - INTEGRATIVE BIOLOGY AB - The simultaneous measurement of T cell function with recovery of individual T cells would greatly facilitate characterizing antigen-specific responses both in vivo and in model systems. We have developed a microraft array methodology that automatically measures the ability of individual T cells to kill a population of target cells and viably sorts specific cells into a 96-well plate for expansion. A human T cell culture was generated against the influenza M1p antigen. Individual microrafts on a 70 × 70 array were loaded with on average 1 CD8+ cell from the culture and a population of M1p presenting target cells. Target cell killing, measured by fluorescence microscopy, was quantified in each microraft. The rates of target cell death among the individual CD8+ T cells varied greatly; however, individual T cells maintained their rates of cytotoxicity throughout the time course of the experiment enabling rapid identification of highly cytotoxic CD8+ T cells. Microrafts with highly active CD8+ T cells were individually transferred to wells of a 96-well plate, using a needle-release device coupled to the microscope. Three sorted T cells clonally expanded. All of these expressed high-avidity T cell receptors for M1p/HLA*02:01 tetramers, and 2 of the 3 receptors were sequenced. While this study investigated single T cell cytotoxicity rates against simple targets with subsequent cell sorting, future studies will involve measuring T cell mediated cytotoxicity in more complex cellular environments, enlarging the arrays to identify very rare antigen specific T cells, and measuring single cell CD4+ and CD8+ T cell proliferation. DA - 2016/// PY - 2016/// DO - 10.1039/c6ib00168h VL - 8 IS - 12 SP - 1208-1220 SN - 1757-9708 ER - TY - JOUR TI - Muscle-spring dynamics in time-limited, elastic movements AU - Rosario, M. V. AU - Sutton, G. P. AU - Patek, S. N. AU - Sawicki, G. S. T2 - PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES AB - Muscle contractions that load in-series springs with slow speed over a long duration do maximal work and store the most elastic energy. However, time constraints, such as those experienced during escape and predation behaviours, may prevent animals from achieving maximal force capacity from their muscles during spring-loading. Here, we ask whether animals that have limited time for elastic energy storage operate with springs that are tuned to submaximal force production. To answer this question, we used a dynamic model of a muscle–spring system undergoing a fixed-end contraction, with parameters from a time-limited spring-loader (bullfrog: Lithobates catesbeiana ) and a non-time-limited spring-loader (grasshopper: Schistocerca gregaria ). We found that when muscles have less time to contract, stored elastic energy is maximized with lower spring stiffness (quantified as spring constant). The spring stiffness measured in bullfrog tendons permitted less elastic energy storage than was predicted by a modelled, maximal muscle contraction. However, when muscle contractions were modelled using biologically relevant loading times for bullfrog jumps (50 ms), tendon stiffness actually maximized elastic energy storage. In contrast, grasshoppers, which are not time limited, exhibited spring stiffness that maximized elastic energy storage when modelled with a maximal muscle contraction. These findings demonstrate the significance of evolutionary variation in tendon and apodeme properties to realistic jumping contexts as well as the importance of considering the effect of muscle dynamics and behavioural constraints on energy storage in muscle–spring systems. DA - 2016/9/14/ PY - 2016/9/14/ DO - 10.1098/rspb.2016.1561 VL - 283 IS - 1838 SP - SN - 1471-2954 KW - muscle-spring interaction KW - elastic energy storage KW - muscle dynamics KW - time-limited loading KW - fixed-end contraction KW - spring stiffness ER - TY - JOUR TI - Maternal smoking impacts key biological pathways in newborns through epigenetic modification in Utero AU - Rotroff, D. M. AU - Joubert, B. R. AU - Marvel, S. W. AU - Haberg, S. E. AU - Wu, M. C. AU - Nilsen, R. M. AU - Ueland, P. M. AU - Nystad, W. AU - London, S. J. AU - Motsinger-Reif, A. T2 - BMC Genomics DA - 2016/// PY - 2016/// VL - 17 ER - TY - JOUR TI - Engineered Nanoplatelets for Enhanced Treatment of Multiple Myeloma and Thrombus AU - Hu, Quanyin AU - Qian, Chenggen AU - Sun, Wujin AU - Wang, Jinqiang AU - Chen, Zhaowei AU - Bomba, Hunter N. AU - Xin, Hongliang AU - Shen, Qundong AU - Gu, Zhen T2 - ADVANCED MATERIALS AB - A platelet-membrane-coated biomimetic nanocarrier, which can sequentially target the bone microenvironment and myeloma cells to enhance the drug availability at the myeloma site and decrease off-target effects, is developed for inhibiting multiple myeloma growth and simultaneously eradicating thrombus complication. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. DA - 2016/11/16/ PY - 2016/11/16/ DO - 10.1002/adma.201603463 VL - 28 IS - 43 SP - 9573-+ SN - 1521-4095 ER - TY - JOUR TI - Biological evaluation of ultrananocrystalline and nanocrystalline diamond coatings AU - Skoog, Shelby A. AU - Kumar, Girish AU - Zheng, Jiwen AU - Sumant, Anirudha V. AU - Goering, Peter L. AU - Narayan, Roger J. T2 - JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE DA - 2016/12// PY - 2016/12// DO - 10.1007/s10856-016-5798-y VL - 27 IS - 12 SP - SN - 1573-4838 ER - TY - JOUR TI - intracellular trafficking network of protein nanocapsules: endocytosis, exocytosis and autophagy AU - Zhang, J. X. AU - Zhang, X. D. AU - Liu, G. AU - Chang, D. F. AU - Liang, X. AU - Zhu, X. B. AU - Tao, W. AU - Mei, L. T2 - Theranostics DA - 2016/// PY - 2016/// VL - 6 IS - 12 SP - 2099-2113 ER - TY - CONF TI - The application of acoustic angiography to assess the progression of angiogenesis in a spontaneous mouse model of breast cancer AU - Shelton, Sarah E. AU - Dayton, Paul A. AU - Aylward, Stephen R. AU - Foster, F. Stuart T2 - 2016 IEEE International Ultrasonics Symposium (IUS) AB - Acoustic angiography is a method for contrast enhanced ultrasound imaging that provides sufficient contrast and resolution to visualize microvasculature non-invasively. A dual-frequency transducer is used to transmit at low frequency and receive high frequency (superharmonic) echoes originating from intravascular microbubbles. Analysis of these images in healthy and tumor-bearing mice revealed that tumors possess quantifiably different vascular structure than healthy control animals, through measurements of vascular density and 2 metrics of tortuosity. Furthermore, tortuosity is correlated to proximity to the tumor margin, and distal tissue surrounding tumor regions has an intermediate level of tortuosity between that of tumor and control tissue. Overall, these results indicate that acoustic angiography images can reveal microvasculature in sufficient detail for vascular morphology to be used as a biomarker for cancer imaging. C2 - 2016/9// C3 - 2016 IEEE International Ultrasonics Symposium (IUS) DA - 2016/9// DO - 10.1109/ultsym.2016.7728697 PB - IEEE UR - http://dx.doi.org/10.1109/ultsym.2016.7728697 ER - TY - JOUR TI - Synergistic Transcutaneous Immunotherapy Enhances Antitumor Immune Responses through Delivery of Checkpoint Inhibitors AU - Ye, Yanqi AU - Wang, Jinqiang AU - Hu, Quanyin AU - Hochu, Gabrielle M. AU - Xin, Hongliang AU - Wang, Chao AU - Gu, Zhen T2 - ACS NANO AB - Despite the promising efficacy of immunoregulation in cancer therapy, the clinical benefit has been restricted by inefficient infiltration of lymphocytes in the evolution of immune evasion. Also, immune-related adverse events have often occurred due to the off-target binding of therapeutics to normal tissues after systematic treatment. In light of this, we have developed a synergistic immunotherapy strategy that locally targets the immunoinhibitory receptor programmed cell death protein 1 (PD1) and immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) for the treatment of melanoma through a microneedle-based transcutaneous delivery approach. The embedded immunotherapeutic nanocapsule loaded with anti-PD1 antibody (aPD1) is assembled from hyaluronic acid modified with 1-methyl-dl-tryptophan (1-MT), an inhibitor of IDO. This formulation method based on the combination strategy of "drug A in carriers formed by incorporation of drug B" facilitates the loading capacity of therapeutics. Moreover, the resulting delivery device elicits the sustained release and enhances retention of checkpoint inhibitors in the tumor microenvironment. Using a B16F10 mouse melanoma model, we demonstrate that this synergistic treatment has achieved potent antitumor efficacy, which is accompanied by enhanced effective T cell immunity as well as reduced immunosuppression in the local site. DA - 2016/9// PY - 2016/9// DO - 10.1021/acsnano.6b04989 VL - 10 IS - 9 SP - 8956-8963 SN - 1936-086X KW - drug delivery KW - immunotherapy KW - anti-PD1 KW - IDO KW - microneedle ER - TY - JOUR TI - Strong Bioinspired Polymer Hydrogel with Tunable Stiffness and Toughness for Mimicking the Extracellular Matrix AU - Su, Teng AU - Liu, Yi AU - He, Hongjian AU - Li, Jia AU - Lv, Yanan AU - Zhang, Lili AU - Sun, Yao AU - Hu, Chunpu T2 - ACS MACRO LETTERS AB - Inspired by the delicate architecture of hyaline articular cartilage, we report on a biomimetic polymer hydrogel that incorporates strong intermolecular hydrogen bonding between urethane–urethane linkages as well as urethane–ester linkages. The resultant hydrogel, containing ≈75% water, can endure a compressive stress up to 56 MPa with a strain of 98%, and exhibit tunable compressive modulus (0.19–1.38 MPa), as well as toughness (3629–28290 J m–2) within a wide range. The tensile strength and elastic modulus reach as high as 0.56 and 5.5 MPa, respectively. The high stiffness and toughness enable the gel to withstand cyclic compressive loadings without fracturing. Moreover, our hydrogel mimics the extracellular matrices of cartilage and bone tissues and provides biochemical and physical cues that support the three-dimensional proliferation of chondrocytes and osteogenic differentiation of preosteoblasts. DA - 2016/11// PY - 2016/11// DO - 10.1021/acsmacrolett.6b00702 VL - 5 IS - 11 SP - 1217-1221 SN - 2161-1653 ER - TY - CONF TI - Reverberation clutter and sources of image degradation in transcostal imaging AU - Pinton, G. AB - The generation of an ultrasound image of human tissue is based on the complex physics of acoustic wave propagation: diffraction, reflection, scattering, frequency dependent attenuation, and nonlinearity. One approach to simulating ultrasound images is to make approximations that can reduce the physics to systems that have a low computational cost. Here a maximalist approach is taken and the full three dimensional wave physics is simulated with finite differences. The objective of this paper is to integrate the Fullwave nonlinear acoustic simulation tool with acoustical maps derived from the National Library of Medicine's Visible Human to generate highly realistic simulations of transcostal imaging. These images and the acoustical field throughout the imaging volume are used to determine the relative importance of nonlinearity, phase aberration, reverberation clutter, and beam shape in image degradation. C2 - 2016/// C3 - 2016 ieee international ultrasonics symposium (ius) DA - 2016/// DO - 10.1109/ultsym.2016.7728711 ER - TY - CONF TI - On the quantitative potential of viscoelastic response (VisR) ultrasound using matrix array transducers: In silico demonstration AU - Hossain, M. M. AU - Moore, C. AU - Gallippi, C. AB - VisR ultrasound is an acoustic radiation force (ARF)-based imaging method that fits induced displacements to a 1D mass-spring-damper (MSD) model to estimate the ratio of viscous to elastic moduli, τ, in viscoelastic materials. A source of error in VisR τ estimation is complex and interrelated 3D system inertia. We hypothesize that error due to system inertia may be reduced by minimizing the volumetric extent of the employed ARF excitations, i.e. by reducing elevational and lateral F/#s using a matrix array transducer. This hypothesis was tested in silico using finite element method (FEM) models and Field II simulating homogeneous viscoelastic materials and viscoelastic materials with inclusions. In homogeneous viscoelastic materials, decreasing the elevational F/# from 5.0 to 0.75 yielded 62.5%, 96.7%, and 223.69% decreases in the median percent error in VisR τ estimates in materials with Young's modulus of 10, 50, and 100 kPa, respectively. In viscoelastic materials with inclusions, the elevational F/0.75 focal configuration better delineated inclusion borders in comparison to F/5.0, and measured contrast was closer to the true contrast. The CNRs achieved using elevational F/0.75 was 1.25 – 5.0 times higher than those from F/5.0. These results show that as the volumetric extent of ARF excitations decreases by reducing the elevational F/#, VisR τ estimates more closely approximate the true material τ. These results suggest that error in quantitative VisR τ estimates would be reduced by using a transducer capable of elevational focusing. C2 - 2016/// C3 - 2016 ieee international ultrasonics symposium (ius) DA - 2016/// DO - 10.1109/ultsym.2016.7728878 ER - TY - CONF TI - Molecular acoustic angiography: Comparison of contrast-to-tissue ratio with multi-pulse techniques and imaging multiple targeted microbubbles AU - Shelton, Sarah E. AU - Lindsey, Brooks D. AU - Dayton, Paul A. AU - Foster, F. Stuart T2 - 2016 IEEE International Ultrasonics Symposium (IUS) AB - Acoustic angiography is a high resolution (~100 μm) approach that utilizes the superharmonic signal produced by microbubbles, which we have recently extended for molecular imaging. These molecular images can also be overlaid onto images of microvascular anatomy in order to assess relationships between vascular morphology and targeting distribution. In this work we compare the contrast-to-tissue ratio (CTR) between superharmonic and multi-pulse molecular imaging and present images of microbubbles targeted to different biomarkers expressed by the vascular endothelial cells. Combing molecular and microvascular information about developing tumors could provide vital information for treatment planning, monitoring, and for ensuring clean margins in surgical resection. C2 - 2016/9// C3 - 2016 IEEE International Ultrasonics Symposium (IUS) DA - 2016/9// DO - 10.1109/ultsym.2016.7728703 PB - IEEE UR - http://dx.doi.org/10.1109/ultsym.2016.7728703 ER - TY - CONF TI - Laser-generated-focused ultrasound transducers for microbubble-mediated, dual-excitation sonothrombolysis AU - Kim, J. AU - Chang, W. Y. AU - Lindsey, B. D. AU - Dayton, P. A. AU - Dai, X. M. AU - Stavas, J. M. AU - Jiang, X. N. AB - A laser-generated-focused ultrasound (LGFU) transducer generates high-pressure (up to 20 MPa), high-frequency (>10 MHz) shock waves with a tight focal spot. In this work, we aim to demonstrate the feasibility of using LGFU transducers for sonothrombolysis in vitro. A carbon black LGFU transducer was designed, fabricated and characterized. The prototyped LGFU was applied with in-vitro thrombolysis tests involving microbubble contrast agent (MCA). A conventional piezo ultrasound transducer was used as a secondary excitation source to enhance the cavitation effect by dual-frequency excitation. The in vitro test results showed that microbubble-mediated LGFU treatment can yield the lytic rate of approximately 2 mg/min, suggesting that LGFU transducers may be useful in precision high lytic rate sonothrombolysis. C2 - 2016/// C3 - 2016 ieee international ultrasonics symposium (ius) DA - 2016/// DO - 10.1109/ultsym.2016.7728473 ER - TY - CONF TI - Large coherent apertures: Improvements in deep abdominal imaging and fundamental limits imposed by clutter AU - Bottenus, N. AU - Pinton, G. AU - Trahey, G. AB - Reverberation and aberration clutter can significantly degrade the ability to image deep abdominal structures in clinical practice. Despite increased hardware complexity and computing power, modern ultrasound arrays are still commonly limited to a length of several centimeters. We hypothesize that using a larger active aperture will improve image quality even in the presence of clutter. We use a simulated abdominal wall model to study the impact of an extended aperture and analyze both the point spread function and lesion imaging performance over a range of aperture sizes from 1 cm to 10 cm. Simulations demonstrate improved image quality as described by resolution and lesion detectability with growing aperture size up to the full extent of the 10 cm aperture. Although clutter degrades the overall imaging performance, it does not appear to impose a limit on the gains that can be made with increasing array size. C2 - 2016/// C3 - 2016 ieee international ultrasonics symposium (ius) DA - 2016/// DO - 10.1109/ultsym.2016.7728849 ER - TY - JOUR TI - Intracellular delivery and ultrasonic activation of folate receptor-targeted phase-change contrast agents in breast cancer cells in vitro AU - Marshalek, Joseph P. AU - Sheeran, Paul S. AU - Ingram, Pier AU - Dayton, Paul A. AU - Witte, Russell S. AU - Matsunaga, Terry O. T2 - JOURNAL OF CONTROLLED RELEASE AB - Breast cancer is a diverse and complex disease that remains one of the leading causes of death among women. Novel, outside-of-the-box imaging and treatment methods are needed to supplement currently available technologies. In this study, we present evidence for the intracellular delivery and ultrasound-stimulated activation of folate receptor (FR)-targeted phase-change contrast agents (PCCAs) in MDA-MB-231 and MCF-7 breast cancer cells in vitro. PCCAs are lipid-coated, perfluorocarbon-filled particles formulated as nanoscale liquid droplets capable of vaporization into gaseous microbubbles for imaging or therapy. Cells were incubated with 1:1 decafluorobutane (DFB)/octafluoropropane (OFP) PCCAs for 1h, imaged via confocal microscopy, exposed to ultrasound (9MHz, MI=1.0 or 1.5), and imaged again after insonation. FR-targeted PCCAs were observed intracellularly in both cell lines, but uptake was significantly greater (p<0.001) in MDA-MB-231 cells (93.0% internalization at MI=1.0, 79.5% at MI=1.5) than MCF-7 cells (42.4% internalization at MI=1.0, 35.7% at MI=1.5). Folate incorporation increased the frequency of intracellular PCCA detection 45-fold for MDA-MB-231 cells and 7-fold for MCF-7 cells, relative to untargeted PCCAs. Intracellularly activated PCCAs ranged from 500nm to 6μm (IQR=800nm-1.5μm) with a mean diameter of 1.15±0.59 (SD) microns. The work presented herein demonstrates the feasibility of PCCA intracellular delivery and activation using breast cancer cells, illuminating a new platform toward intracellular imaging or therapeutic delivery with ultrasound. DA - 2016/12/10/ PY - 2016/12/10/ DO - 10.1016/j.jconrel.2016.09.010 VL - 243 SP - 69-77 SN - 1873-4995 KW - Ultrasound KW - Phase-change contrast agent KW - Microbubble KW - Nanodroplet KW - Perfluorocarbon KW - Decafluorobutane KW - Octafluoropropane KW - Folate receptor KW - Breast cancer ER - TY - JOUR TI - Facilitating Teamwork in Adolescent and Young Adult Oncology AU - Johnson, Rebecca H. AU - Macpherson, Catherine Fiona AU - Smith, Ashley W. AU - Block, Rebecca G. AU - Keyton, Joann T2 - JOURNAL OF ONCOLOGY PRACTICE AB - A case of a young adult patient in the days immediately after a cancer diagnosis illustrates the critical importance of three interrelated core coordinating mechanisms-closed-loop communication, shared mental models, and mutual trust-of teamwork in an adolescent and young adult multidisciplinary oncology team. The case illustrates both the opportunities to increase team member coordination and the problems that can occur when coordination breaks down. A model for teamwork is presented, which highlights the relationships among these coordinating mechanisms and demonstrates how balance among them works to optimize team function and patient care. Implications for clinical practice and research suggested by the case are presented. DA - 2016/11// PY - 2016/11// DO - 10.1200/jop.2016.013870 VL - 12 IS - 11 SP - 1067-+ SN - 1935-469X ER - TY - CONF TI - Cross-sectional comparison of in vivo viscoelastic response (VisR) ultrasound in lower limb muscles of boys with and without Duchenne muscular dystrophy AU - Moore, C. J. AU - Selzo, M. R. AU - Caughey, M. C. AU - Meyer, D. O. AU - Emmett, R. AU - Howard, J. F. AU - Chopra, M. AU - Gallippi, C. M. AB - Duchenne muscular dystrophy (DMD) is a genetic disorder that causes progressive muscle degeneration involving necrosis and inflammation, with subsequent replacement of muscle fibers by fibrosis and fatty tissue. These compositional changes underlie mechanical property alterations in affected muscles, which may be assessed using Viscoelastic Response (VisR) ultrasound. We hypothesize that VisR will delineate differences in the viscoelastic properties of lower limb skeletal muscles in boys with versus without DMD. VisR imaging was performed in the vastus intermedius (VI), rectus femoris (RF), sartorius (SM) and gastrocnemius (GM) muscles of seven boys (4 DMD, 3 control) aged 7.9 – 10.4 years. Parametric images of relative elasticity (RE) and relative viscosity (RV) were rendered. From the parametric images, percent muscle area with relatively high RE or RV value was calculated and compared (Wilcoxon rank-sum) between DMD and control on a per-muscle basis. In the VI, RF and SM, percent muscle with relatively high RV was larger (VI: 17.7% v. 13.1% RF: 98.9% v. 93.7%, SM: 43.2% v. 40.6% p < 0.05) in DMD than control muscles. In the VI, percent muscle with relatively high RE was larger (32.8% v. 29.5%, p < 0.05) in DMD muscles. No significant differences were observed in the GM between DMD and control. VisR results were consistent with temporally-matched functional testing using a hand-held dynamometer, which showed 40.5% to 70.0% lower force output in DMD RF, VL and SM - and only 21.8% lower force output in DMD GM - relative to the corresponding control muscles. These results suggest that VisR imaging is relevant to delineating viscoelastic property alterations that are associated with dystrophic muscle degeneration in boys with DMD, in vivo. C2 - 2016/// C3 - 2016 ieee international ultrasonics symposium (ius) DA - 2016/// DO - 10.1109/ultsym.2016.7728722 ER - TY - CONF TI - Carotid plaque characterization with ARFI imaging: Blinded reader study AU - Czernuszewicz, T. J. AU - Homeister, J. W. AU - Caughey, M. C. AU - Huang, B. Y. AU - Lee, E. R. AU - Zamora, C. A. AU - Farber, M. A. AU - Fulton, J. J. AU - Ford, P. F. AU - Marston, W. A. AU - Vallabhaneni, R. AU - Nichols, T. C. AU - Gallippi, C. M. AB - Stroke is commonly caused by thromboembolic events originating from vulnerable atherosclerotic plaque in the carotid vasculature. The purpose of this study was to evaluate the ability of acoustic radiation force impulse (ARFI) imaging, a noninvasive elastography imaging technique, to assess the composition of carotid artery plaques using histologic examination as the gold standard. Twenty-five patients undergoing carotid endarterectomy (CEA) were enrolled and imaged with ARFI. After surgery, extracted specimens were histologically processed and matched to the ultrasound imaging plane. Parametric 2D ARFI images of peak displacement (PD) were evaluated by three radiologists blinded to the histology result. Receiver operating characteristic (ROC) curve analysis was performed, and area under the ROC curve (AUC) was taken as a metric of performance for detecting plaque features such as necrotic core (NC), intraplaque hemorrhage (IPH), collagen (COL), and calcium (CAL). Additionally, linear regression was performed on fibrous cap (FC) thickness measurements. Areas of plaque with NC and IPH were observed to have substantially increased ARFI PD (2× to 4×) compared to areas of plaque with COL or CAL. Median AUC for detecting soft plaque features (NC/IPH) was 0.887 (range: 0.867 - 0.924) and stiff plaque features (COL/CAL) was 0.859 (range: 0.771 - 0.929). FC thickness measured by two of the three radiologists matched closely with histology (reader 1: R 2 = 0.64; reader 2: R 2 = 0.89). This study suggests that ARFI is capable of distinguishing soft from stiff compositional elements of atherosclerotic plaques and may be relevant to improving plaque risk assessment. C2 - 2016/// C3 - 2016 ieee international ultrasonics symposium (ius) DA - 2016/// DO - 10.1109/ultsym.2016.7728873 ER - TY - CONF TI - Adaptive windowing in mechanically-steered intravascular ultrasound imaging: Ex vivo and in vivo studies with contrast enhancement AU - Lindsey, B. D. AU - Dayton, P. A. AU - Jiang, X. N. AB - Intravascular ultrasound (IVUS) is utilized frequently in vascular diseases such as coronary artery disease and peripheral vascular disease. Many techniques-including but not limited to IVUS-seek to characterize plaques in coronary artery disease in order to determine which are likely to rupture. Biologists have recently identified the development of intra-plaque vasa vasorum, small vessels which supply the coronaries with oxygen and nutrients, as a potential indicator of plaque vulnerability. By imaging plaques with penetrating vasa vasorum, high resolution contrast-enhanced ultrasound imaging may allow identification of vulnerable plaques prior to rupture. Here we present processing techniques for improving spatial resolution and image contrast in mechanically steered ultrasound imaging based on minimum variance (MV) beamforming and the phase coherence factor (PCF). In tissue-mimicking phantom studies, PCF processing improved CTR by a mean of 4.2 dB, while combined MV and PCF processing improved spatial resolution by 41.7%. These processing strategies may improve image quality in both conventional B-mode IVUS and contrast-enhanced IVUS. C2 - 2016/// C3 - 2016 ieee international ultrasonics symposium (ius) DA - 2016/// DO - 10.1109/ultsym.2016.7728433 ER - TY - CONF TI - A dual-frequency endoscopic transducer for imaging vascular invasion in pancreatic cancer AU - Lindsey, B. D. AU - Dayton, P. A. AU - Kim, J. AU - Jiang, X. N. AB - Pancreatic adenocarcinoma is among the most deadly of cancers, with surgery being typically the only curative option. Tumor resectability is typically determined via endoscopic ultrasound imaging, however, many patients who may be eligible for resection are not offered surgery due to the difficulty in determining vascular or lymphatic invasion. Contrast-enhanced ultrasound imaging may address this problem. We describe the development of a single element dual-frequency transducer for rotational endoscopic imaging designed to operate at 4/20 MHz to image microbubble superharmonics. The ability of the developed transducer to image in a tissue mimicking phantom at depths from 1.0 cm (CTR = 21.6 dB) to 2.5 cm (CTR = 11.4 dB) is demonstrated. The completed 4-Fr transducer is also capable of imaging microbubbles in a 200 µm-diameter tube through the wall of a ∼1 cm-diameter porcine artery, suggesting such a device may be suitable for direct visualization of small vessels from within the lumen of larger vessels such as the portal vein. C2 - 2016/// C3 - 2016 ieee international ultrasonics symposium (ius) DA - 2016/// DO - 10.1109/ultsym.2016.7728435 ER - TY - CONF TI - A dual-frequency co-linear array for prostate acoustic angiography AU - Li, S. B. AU - Kim, J. AU - Wang, Z. C. AU - Jiang, X. N. AU - Kasoji, S. AU - Lindsey, B. AU - Dayton, P. A. AB - Approximately 80% of men who reach 80-years of age will have some form of prostate cancer. The challenge remains to differentiate indolent from aggressive disease. Based on recent research, acoustic angiography, a novel contrast enhanced ultrasound imaging technique, can provide high-resolution visualization of tissue microvasculature and has demonstrated the ability to differentiate vascular characteristics between healthy and tumor tissue. We hypothesize that transrectal acoustic angiography may enhance assessment of prostate cancer. In this paper, we describe the development of a dual layer co-linear array ultrasound transducer for transrectal acoustic angiography. The KLM model and Field II were used for the element design and acoustic field simulation, respectively. The probe consists of 64 transmit elements with a center frequency of 3 MHz and 128 receive elements with a center frequency of 15 MHz. The dimensions of the array are 18 mm in azimuth and 8 mm in elevation. The pitch is 280 μm for transmitting (TX) elements and 140 μm for receiving (RX) elements. Pulse-echo test of TX/RX elements were conducted and compared with the simulation results. Real-time contrast imaging was tested using a Verasonics system. Non-linear responses from microbubble contrast agents at a depth of 18 mm were clearly observed. The axial beam width (-6 dB) and CTR were calculated from the measured signals to be 400 μm and 20 dB, respectively. These results suggest that the prototype co-linear array is capable of performing dual-frequency superharmonic imaging of microbubbles for prostate cancer assessment. C2 - 2016/// C3 - 2016 ieee international ultrasonics symposium (ius) DA - 2016/// DO - 10.1109/ultsym.2016.7728718 ER - TY - JOUR TI - The Age-Associated Reduction in Propulsive Power Generation in Walking AU - Franz, Jason R. T2 - EXERCISE AND SPORT SCIENCES REVIEWS AB - Propulsive power generation during push-off in walking decreases with advancing age. A common explanation is an accommodation for sarcopenia and muscle weakness. Yet, muscle strengthening often yields disappointing outcomes for walking performance. We examine the hypothesis that declines in force or power generating capacity of propulsive leg muscles cannot fully explain the age-related reduction in propulsive power generation during walking. DA - 2016/10// PY - 2016/10// DO - 10.1249/jes.0000000000000086 VL - 44 IS - 4 SP - 129-136 SN - 1538-3008 KW - plantarflexor KW - biomechanics KW - gait KW - elderly KW - ankle KW - geriatrics KW - ultrasound ER - TY - JOUR TI - Single-Step Fabrication of Computationally Designed Microneedles by Continuous Liquid Interface Production AU - Johnson, Ashley R. AU - Caudill, Cassie L. AU - Tumbleston, John R. AU - Bloomquist, Cameron J. AU - Moga, Katherine A. AU - Ermoshkin, Alexander AU - Shirvanyants, David AU - Mecham, Sue J. AU - Luft, J. Christopher AU - DeSimone, Joseph M. T2 - PLOS ONE AB - Microneedles, arrays of micron-sized needles that painlessly puncture the skin, enable transdermal delivery of medications that are difficult to deliver using more traditional routes. Many important design parameters, such as microneedle size, shape, spacing, and composition, are known to influence efficacy, but are notoriously difficult to alter due to the complex nature of microfabrication techniques. Herein, we utilize a novel additive manufacturing ("3D printing") technique called Continuous Liquid Interface Production (CLIP) to rapidly prototype sharp microneedles with tuneable geometries (size, shape, aspect ratio, spacing). This technology allows for mold-independent, one-step manufacturing of microneedle arrays of virtually any design in less than 10 minutes per patch. Square pyramidal CLIP microneedles composed of trimethylolpropane triacrylate, polyacrylic acid and photopolymerizable derivatives of polyethylene glycol and polycaprolactone were fabricated to demonstrate the range of materials that can be utilized within this platform for encapsulating and controlling the release of therapeutics. These CLIP microneedles effectively pierced murine skin ex vivo and released the fluorescent drug surrogate rhodamine. DA - 2016/9/8/ PY - 2016/9/8/ DO - 10.1371/journal.pone.0162518 VL - 11 IS - 9 SP - SN - 1932-6203 ER - TY - JOUR TI - Mechanical and Vascular Cues Synergistically Enhance Osteogenesis in Human Mesenchymal Stem Cells AU - Steward, Andrew J. AU - Cole, Jacqueline H. AU - Ligler, Frances S. AU - Loboa, Elizabeth G. T2 - TISSUE ENGINEERING PART A AB - Development and maintenance of a vascular network are critical for bone growth and homeostasis; strategies that promote vascular function are critical for clinical success of tissue-engineered bone constructs. Co-culture of endothelial cells (ECs) with mesenchymal stem cells (MSCs) and exposure to 10% cyclic tensile strain have both been shown to regulate osteogenesis in isolation, but potential synergistic effects have yet to be explored. The objective of this study was to expose an MSC-EC co-culture to 10% cyclic tensile strain to examine the role of this mechanical stimulus on MSC-EC behavior. We hypothesized that paracrine signaling from ECs would stimulate osteogenesis of MSCs, and exposure to 10% cyclic tensile strain would enhance this anabolic signal. Human umbilical vein ECs and human bone marrow-derived MSCs were either monocultured or co-cultured at a 1:1 ratio in a mixed osteo/angiogenic medium, exposed to 10% cyclic tensile strain at 1 Hz for 4 h/day for 2 weeks, and biochemically and histologically analyzed for endothelial and osteogenic markers. While neither 10% cyclic tensile strain nor co-culture alone had a significant effect on osteogenesis, the concurrent application of strain to an MSC-EC co-culture resulted in a significant increase in calcium accretion and mineral deposition, suggesting that co-culture and strain synergistically enhance osteogenesis. Neither co-culture, 10% cyclic tensile strain, nor a combination of these stimuli affected endothelial markers, indicating that the endothelial phenotype remained stable, but unresponsive to the stimuli evaluated in this study. This study is the first to investigate the role of cyclic tensile strain on the complex interplay between ECs and MSCs in co-culture. The results of this study provide key insights into the synergistic effects of 10% cyclic tensile strain and co-culture on osteogenesis. Understanding mechanobiological factors affecting MSC-EC crosstalk will help enhance strategies for creating vascularized tissues in tissue engineering and regenerative medicine. DA - 2016/8// PY - 2016/8// DO - 10.1089/ten.tea.2015.0533 VL - 22 IS - 15-16 SP - 997-1005 SN - 1937-335X ER - TY - JOUR TI - Low-Power Wearable Systems for Continuous Monitoring of Environment and Health for Chronic Respiratory Disease AU - Dieffenderfer, James AU - Goodell, Henry AU - Mills, Steven AU - McKnight, Michael AU - Yao, Shanshan AU - Lin, Feiyan AU - Beppler, Eric AU - Bent, Brinnae AU - Lee, Bongmook AU - Misra, Veena AU - Zhu, Yong AU - Oralkan, Omer AU - Strohmaier, Jason AU - Muth, John AU - Peden, David AU - Bozkurt, Alper T2 - IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS AB - We present our efforts toward enabling a wearable sensor system that allows for the correlation of individual environmental exposures with physiologic and subsequent adverse health responses. This system will permit a better understanding of the impact of increased ozone levels and other pollutants on chronic asthma conditions. We discuss the inefficiency of existing commercial off-the-shelf components to achieve continuous monitoring and our system-level and nano-enabled efforts toward improving the wearability and power consumption. Our system consists of a wristband, a chest patch, and a handheld spirometer. We describe our preliminary efforts to achieve a submilliwatt system ultimately powered by the energy harvested from thermal radiation and motion of the body with the primary contributions being an ultralow-power ozone sensor, an volatile organic compounds sensor, spirometer, and the integration of these and other sensors in a multimodal sensing platform. The measured environmental parameters include ambient ozone concentration, temperature, and relative humidity. Our array of sensors also assesses heart rate via photoplethysmography and electrocardiography, respiratory rate via photoplethysmography, skin impedance, three-axis acceleration, wheezing via a microphone, and expiratory airflow. The sensors on the wristband, chest patch, and spirometer consume 0.83, 0.96, and 0.01 mW, respectively. The data from each sensor are continually streamed to a peripheral data aggregation device and are subsequently transferred to a dedicated server for cloud storage. Future work includes reducing the power consumption of the system-on-chip including radio to reduce the entirety of each described system in the submilliwatt range. DA - 2016/9// PY - 2016/9// DO - 10.1109/jbhi.2016.2573286 VL - 20 IS - 5 SP - SN - 2168-2208 KW - Environmental and physiological sensing KW - wearable asthma monitoring ER - TY - JOUR TI - Genetic predictors of cardiovascular mortality during intensive glycemic control in type 2 diabetes: Findings from the ACCORD clinical trial AU - Shah, H. S. AU - Gao, H. AU - Morieri, M. L. AU - Skupien, J. AU - Marvel, S. AU - Pare, G. AU - Mannino, G. C. AU - Buranasupkajorn, P. AU - Mendonca, C. AU - Hastings, T. AU - Marcovina, S. M. AU - Sigal, R. J. AU - Gerstein, H. C. AU - Wagner, M. J. AU - Motsinger-Reif, A. A. AU - Buse, J. B. AU - Kraft, P. T2 - Diabetes Care DA - 2016/// PY - 2016/// VL - 39 IS - 11 SP - 1915-1924 ER - TY - JOUR TI - Enhanced cellular infiltration of human adipose-derived stem cells in allograft menisci using a needle-punch method AU - Nordberg, Rachel C AU - Charoenpanich, Adisri AU - Vaughn, Christopher E AU - Griffith, Emily H AU - Fisher, Matthew B AU - Cole, Jacqueline H AU - Spang, Jeffrey T AU - Loboa, Elizabeth G T2 - Journal of orthopaedic surgery and research DA - 2016/// PY - 2016/// VL - 11 IS - 1 SP - 132 ER - TY - JOUR TI - On the Quantitative Potential of Viscoelastic Response (VisR) Ultrasound Using the One-Dimensional Mass-Spring-Damper Model AU - Selzo, Mallory R. AU - Moore, Christopher J. AU - Hossain, Md. Murad AU - Palmeri, Mark L. AU - Gallippi, Caterina M. T2 - IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL AB - Viscoelastic response (VisR) ultrasound is an acoustic radiation force (ARF)-based imaging method that fits induced displacements to a one-dimensional (1-D) mass-spring-damper (MSD) model to estimate the ratio of viscous to elastic moduli, τ, in viscoelastic materials. Error in VisR τ estimation arises from inertia and acoustic displacement underestimation. These error sources are herein evaluated using finite-element method (FEM) simulations, error correction methods are developed, and corrected VisR τ estimates are compared with true simulated τ values to assess VisR's relevance to quantifying viscoelasticity. With regard to inertia, adding a mass term in series with the Voigt model, to achieve the MSD model, accounts for inertia due to tissue mass when ideal point force excitations are used. However, when volumetric ARF excitations are applied, the induced complex system inertia is not described by the single-degree-of-freedom MSD model, causing VisR to overestimate τ. Regarding acoustic displacement underestimation, associated deformation of ARF-induced displacement profiles further distorts VisR τ estimates. However, median error in VisR τ is reduced to approximately -10% using empirically derived error correction functions applied to simulated viscoelastic materials with viscous and elastic properties representative of tissue. The feasibility of corrected VisR imaging is then demonstrated in vivo in the rectus femoris muscle of an adult with no known neuromuscular disorders. These results suggest VisR's potential relevance to quantifying viscoelastic properties clinically. DA - 2016/9// PY - 2016/9// DO - 10.1109/tuffc.2016.2539323 VL - 63 IS - 9 SP - 1276-1287 SN - 1525-8955 KW - Acoustic radiation force (ARF) KW - mass spring damper (MSD) KW - viscoelasticity KW - viscoelastic response (VisR) ultrasound ER - TY - JOUR TI - On the Feasibility of Quantifying Fibrous Cap Thickness With Acoustic Radiation Force Impulse (ARFI) Ultrasound AU - Czernuszewicz, Tomasz J. AU - Gallippi, Caterina M. T2 - IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL AB - Acute cerebrovascular accidents are associated with the rupture of vulnerable atherosclerotic plaques in the carotid arteries. Fibrous cap (FC) thickness has been shown to be an important predictor of plaque rupture but has been challenging to measure accurately with clinical noninvasive imaging modalities. The goals of this investigation were first, to evaluate the feasibility of using transcutaneous acoustic radiation force impulse (ARFI) ultrasound to quantify FC thickness and second, to optimize both imaging and motion-tracking parameters to support such measurements. FCs with varying thickness (0.1-1.0 mm) were simulated using a simple-layered geometry, and their mechanical response to an impulse of radiation force was solved using finite-element method (FEM) modeling. Ultrasound tracking of FEM displacements was performed in Field II utilizing three center frequencies (6, 9, and 12 MHz) and eight motion-tracking kernel lengths (0.5λ - 4λ). Additionally, FC thickness in two carotid plaques imaged in vivo was measured with ARFI and compared to matched histology. The results of this study demonstrate that 1) tracking pulse frequencies around 12 MHz are necessary to resolve caps around 0.2 mm; 2) large motion-tracking kernel sizes introduce bias into thickness measurements and overestimate the true cap thickness; and 3) color saturation settings on ARFI peak displacement images can impact thickness measurement accuracy substantially. DA - 2016/9// PY - 2016/9// DO - 10.1109/tuffc.2016.2535440 VL - 63 IS - 9 SP - 1262-1275 SN - 1525-8955 KW - Acoustic radiation force KW - acoustic radiation force impulse (ARFI) KW - atherosclerosis KW - fibrous cap (FC) KW - finite-element method (FEM) KW - resolution KW - vulnerable plaque ER - TY - JOUR TI - Immediate effect of vibratory stimuli on quadriceps function in healthy adults AU - Pamukoff, Derek N. AU - Pietrosimone, Brian AU - Lewek, Michael D. AU - Ryan, Eric D. AU - Weinhold, Paul S. AU - Lee, Dustin R. AU - Blackburn, J. Troy T2 - MUSCLE & NERVE AB - Introduction: The purpose of this study was to compare the effect of whole body vibration (WBV) and local muscle vibration (LMV) on quadriceps function. Methods: Sixty adults were randomized to WBV, LMV, or control groups. Quadriceps function [Hoffmann (H)-reflex, active motor threshold (AMT), motor evoked potential (MEP) and electromyographic amplitude, peak torque (PT), rate of torque development (RTD), and central activation ratio (CAR)] was assessed before and immediately after and 10 and 20 minutes after interventions. Results: WBV improved PT, CAR, AMT, EMG, and MEP amplitude, and EMG amplitude and CAR were greater than control after application. LMV improved EMG amplitude and AMT, and EMG amplitude was greater than control after application. AMT remained lower 10 and 20 minutes after WBV and LMV. No differences were noted between LMV and WBV. Vibration did not influence H-reflex or RTD. Conclusions: WBV and LMV increased quadriceps function and may be used to enhance the efficacy of strengthening protocols. Muscle Nerve 54: 469–478, 2016 DA - 2016/9// PY - 2016/9// DO - 10.1002/mus.25081 VL - 54 IS - 3 SP - 469-478 SN - 1097-4598 KW - cortical KW - Hoffmann reflex KW - muscle KW - neuron KW - quadriceps KW - strength ER - TY - JOUR TI - Development of a protease-resistant reporter to quantify BCR-ABL activity in intact cells AU - Proctor, Angela AU - Zigoneanu, Imola G. AU - Wang, Qunzhao AU - Sims, Christopher E. AU - Lawrence, David S. AU - Allbritton, Nancy L. T2 - ANALYST AB - A peptidase-resistant ABL kinase substrate was developed by identifying protease-susceptible bonds on an ABL substrate peptide and replacing flanking amino acids with non-native amino acids. After an iterative design process, the lead, or designed, peptide X-A possesses a six-fold longer life in a cytosolic lysate than that of the starting peptide. The catalytic efficiency (kcat/KM) of purified ABL kinase for the lead peptide (125 s-1 μM-1) is similar to that of the starting peptide (103 s-1 μM-1) demonstrating preservation of the peptide's ability to serve as a kinase substrate. When incubated in cytosolic lysates, the lead peptide is slowly degraded into 4 fragments over time. In contrast, when loaded into intact cells, the peptide is metabolized into 5 fragments, with only 2 of the fragments corresponding to those in the lysate. Thus the two environments possess differing peptidase activities, which must be accounted for when designing peptidase-resistant peptides. In both settings, the substrate is phosphorylated by BCR-ABL providing a readout of BCR-ABL activity. A small panel of tyrosine kinase inhibitors verified the substrate's specificity for BCR-ABL/ABL kinase activity in both lysates and cells in spite of the multitude of other kinases present. The designed peptide X-A acts as a long-lived BCR-ABL kinase reporter in the leukemic cells possessing the BCR-ABL mutation. DA - 2016/// PY - 2016/// DO - 10.1039/c6an01378c VL - 141 IS - 21 SP - 6008-6017 SN - 1364-5528 ER - TY - JOUR TI - An Integrated Chemical Cytometry Method: Shining a Light on Akt Activity in Single Cells AU - Mainz, Emilie R. AU - Wang, Qunzhao AU - Lawrence, David S. AU - Allbritton, Nancy L. T2 - ANGEWANDTE CHEMIE-INTERNATIONAL EDITION AB - Abstract Tools to evaluate oncogenic kinase activity in small clinical samples have the power to guide precision medicine in oncology. Existing platforms have demonstrated impressive insights into the activity of protein kinases, but these technologies are unsuitable for the study of kinase behavior in large numbers of primary human cells. To address these limitations, we developed an integrated analysis system that utilizes a light‐programmable, cell‐permeable reporter deliverable simultaneously to many cells. The reporter's ability to act as a substrate for Akt, a key oncogenic kinase, was masked by a 2‐4,5‐dimethoxy 2‐nitrobenzyl (DMNB) moiety. Upon exposure to ultraviolet light and release of the masking moiety, the substrate sequence enabled programmable reaction times within the cell cytoplasm. When coupled to automated single‐cell capillary electrophoresis, statistically significant numbers of primary human cells were readily evaluated for Akt activity. DA - 2016/10/10/ PY - 2016/10/10/ DO - 10.1002/anie.201606914 VL - 55 IS - 42 SP - 13095-13098 SN - 1521-3773 KW - biosensors KW - chemical cytometry KW - kinase activity probes KW - photochemistry KW - single-cell analysis ER - TY - JOUR TI - A multinuclear metal complex based dnase-mimetic artificial enzyme: Matrix cleavage for combating bacterial biofilms AU - Chen, Z. W. AU - Ji, H. W. AU - Liu, C. Q. AU - Bing, W. AU - Wang, Z. Z. AU - Qu, X. G. T2 - Angewandte Chemie [International Edition in English] DA - 2016/// PY - 2016/// VL - 55 IS - 36 SP - 10732-10736 ER - TY - JOUR TI - Review of Automated Microinjection Systems for Single Cells in the Embryogenesis Stage AU - Permana, Sofie AU - Grant, Edward AU - Walker, Glenn M. AU - Yoder, Jeffrey A. T2 - IEEE-ASME TRANSACTIONS ON MECHATRONICS AB - Modern genetics research has resulted in significant advances in cell in vitro microinjection systems. Such systems provide biological and medical practitioners with high volume cell throughput and statistically relevant data. This paper provides the reader with a comprehensive review of the major research technologies used in automated cell microinjection and of their individual subsystems. Microinjection subsystems reviewed include machine vision, nonvision sensors and user interface (input), cell modeling, piercing mechanisms and injection control loop (control), cell holder and manipulator, and microinjection (output). The interdisciplinary technologies reviewed for microinjection sensing, automation, and control include microfluidic actuation, optical field actuation (optical trapping and optical guidance), electrical field actuation (electrorotation, electrowetting, and dielectrophoresis), and ultrasonic vibration. The survey concludes that research into automated microinjection systems will focus on reducing the scale of microinjection systems and developing appropriate controllers. DA - 2016/10// PY - 2016/10// DO - 10.1109/tmech.2016.2574871 VL - 21 IS - 5 SP - 2391-2404 SN - 1941-014X KW - Automation KW - biological cells KW - control system KW - mechatronics KW - reviews ER - TY - JOUR TI - Nanosecond Time-Resolution Study of Gold Nanorod Rotation at the Liquid-Solid Interface AU - Neupane, Bhanu AU - Chen, Fang AU - Wei, Yanli AU - Fang, Ning AU - Ligler, Frances S. AU - Wang, Gufeng T2 - CHEMPHYSCHEM AB - Abstract Early studies showed that the adsorption of nanorods may start from a special “anchored” state, in which the nanorods lose translational motion but retain rotational freedom. Insight into how the anchored nanorods rotate should provide additional dimensions for understanding particle–surface interactions. Based on conventional time‐resolution studies, gold nanorods are thought to continuously rotate following initial interactions with negatively charged glass surfaces. However, this nanosecond time‐resolution study reveals that the apparent continuous rotation actually consists of numerous fast, intermittent rotations or transitions between a small number of weakly immobilized states, with the particle resting in the immobilized states most of the time. The actual rotation from one immobilized state to the other happens on a 1 ms timescale, that is, approximately 50 times slower than in the bulk solution. DA - 2016/7/18/ PY - 2016/7/18/ DO - 10.1002/cphc.201600174 VL - 17 IS - 14 SP - 2218-2224 SN - 1439-7641 KW - adsorption KW - fluctuation correlation spectroscopy KW - gold nanorods KW - rotation KW - surface plasmon resonance ER - TY - JOUR TI - Microvessel manifold for perfusion and media exchange in three-dimensional cell cultures AU - Roberts, Steven A. AU - DiVito, Kyle A. AU - Ligler, Frances S. AU - Adams, André A. AU - Daniele, Michael A. T2 - Biomicrofluidics AB - Integrating a perfusable microvasculature system in vitro is a substantial challenge for "on-chip" tissue models. We have developed an inclusive on-chip platform that is capable of maintaining laminar flow through porous biosynthetic microvessels. The biomimetic microfluidic device is able to deliver and generate a steady perfusion of media containing small-molecule nutrients, drugs, and gases in three-dimensional cell cultures, while replicating flow-induced mechanical stimuli. Here, we characterize the diffusion of small molecules from the perfusate, across the microvessel wall, and into the matrix of a 3D cell culture. DA - 2016/9// PY - 2016/9// DO - 10.1063/1.4963145 VL - 10 IS - 5 SP - 054109 J2 - Biomicrofluidics LA - en OP - SN - 1932-1058 UR - http://dx.doi.org/10.1063/1.4963145 DB - Crossref ER - TY - JOUR TI - Mechanical Force-Triggered Drug Delivery AU - Zhang, Yuqi AU - Yu, Jicheng AU - Bomba, Hunter N. AU - Zhu, Yong AU - Gu, Zhen T2 - CHEMICAL REVIEWS AB - Advanced drug delivery systems (DDS) enhance treatment efficacy of different therapeutics in a dosage, spatial, and/or temporal controlled manner. To date, numerous chemical- or physical-based stimuli-responsive formulations or devices for controlled drug release have been developed. Among them, the emerging mechanical force-based stimulus offers a convenient and robust controlled drug release platform and has attracted increasing attention. The relevant DDS can be activated to promote drug release by different types of mechanical stimuli, including compressive force, tensile force, and shear force as well as indirect formats, remotely triggered by ultrasound and magnetic field. In this review, we provide an overview of recent advances in mechanically activated DDS. The opportunities and challenges regarding clinical translations are also discussed. DA - 2016/10/12/ PY - 2016/10/12/ DO - 10.1021/acs.chemrev.6b00369 VL - 116 IS - 19 SP - 12536-12563 SN - 1520-6890 ER - TY - JOUR TI - Evaluation of Silver Ion-Releasing Scaffolds in a 3D Coculture System of MRSA and Human Adipose-Derived Stem Cells for Their Potential Use in Treatment or Prevention of Osteomyelitis AU - Mohiti-Asli, Mahsa AU - Molina, Casey AU - Diteepeng, Thamonwan AU - Pourdeyhimi, Behnam AU - Loboa, Elizabeth G. T2 - TISSUE ENGINEERING PART A AB - Bone infection, also called osteomyelitis, can result when bacteria invade a bone. Treatment of osteomyelitis usually requires surgical debridement and prolonged antimicrobial therapy. The rising incidence of infection with multidrug-resistant bacteria, in particular methicillin-resistant staphylococcus aureus (MRSA), however, limits the antimicrobial treatment options available. Silver is well known for its antimicrobial properties and is highly toxic to a wide range of microorganisms. We previously reported our development of biocompatible, biodegradable, nanofibrous scaffolds that released silver ions in a controlled manner. The objective of this study was to determine the efficacy of these scaffolds in treating or preventing osteomyelitis. To achieve this objective, antimicrobial efficacy was determined using a 3D coculture system of human adipose-derived stem cells (hASC) and MRSA. Human ASC were seeded on the scaffolds and induced to undergo osteogenic differentiation in both the absence and presence of MRSA. Our results indicated that the silver ion-releasing scaffolds not only inhibited biofilm formation, but also supported osteogenesis of hASC. Our findings suggest that these biocompatible, degradable, silver ion-releasing scaffolds can be used at an infection site to treat osteomyelitis and/or to coat bone implants as a preventative measure against infection postsurgery. DA - 2016/11// PY - 2016/11// DO - 10.1089/ten.tea.2016.0063 VL - 22 IS - 21-22 SP - 1258-1263 SN - 1937-335X KW - nanofiber KW - antimicrobial KW - coculture KW - osteomyelitis ER - TY - JOUR TI - An Integrated System for Superharmonic Contrast-Enhanced Ultrasound Imaging: Design and Intravascular Phantom Imaging Study AU - Li, Yang AU - Ma, Jianguo AU - Martin, K. Heath AU - Yu, Mingyue AU - Ma, Teng AU - Dayton, Paul A. AU - Jiang, Xiaoning AU - Shung, K. Kirk AU - Zhou, Qifa T2 - IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING AB - Objective: Superharmonic contrast-enhanced ultrasound imaging, also called acoustic angiography, has previously been used for the imaging of microvasculature. This approach excites microbubble contrast agents near their resonance frequency and receives echoes at nonoverlapping superharmonic bandwidths. No integrated system currently exists could fully support this application. To fulfill this need, an integrated dual-channel transmit/receive system for superharmonic imaging was designed, built, and characterized experimentally. Method: The system was uniquely designed for superharmonic imaging and high-resolution B-mode imaging. A complete ultrasound system including a pulse generator, a data acquisition unit, and a signal processing unit were integrated into a single package. The system was controlled by a field-programmable gate array, on which multiple user-defined modes were implemented. A 6-, 35-MHz dual-frequency dual-element intravascular ultrasound transducer was designed and used for imaging. Result: The system successfully obtained high-resolution B-mode images of coronary artery ex vivo with 45-dB dynamic range. The system was capable of acquiring in vitro superharmonic images of a vasa vasorum mimicking phantom with 30-dB contrast. It could detect a contrast agent filled tissue mimicking tube of 200 μm diameter. Conclusion: For the first time, high-resolution B-mode images and superharmonic images were obtained in an intravascular phantom, made possible by the dedicated integrated system proposed. The system greatly reduced the cost and complexity of the superharmonic imaging intended for preclinical study. Significant: The system showed promise for high-contrast intravascular microvascular imaging, which may have significant importance in assessment of the vasa vasorum associated with atherosclerotic plaques. DA - 2016/9// PY - 2016/9// DO - 10.1109/tbme.2015.2506639 VL - 63 IS - 9 SP - 1933-1943 SN - 1558-2531 KW - Acoustic angiography KW - biomedical electronics KW - field-programmable gate arrays (FPGA) KW - intravascular ultrasound (IVUS) KW - microbubble contrast agent (MCA) KW - ultrasonic imaging KW - ultrasonic transducer ER - TY - JOUR TI - Acoustic angiography: A new high frequency contrast ultrasound technique for biomedical imaging AU - Shelton, Sarah E. AU - Lindsey, Brooks D. AU - Gessner, Ryan AU - Lee, Yueh AU - Aylward, Stephen AU - Lee, Hyunggyun AU - Cherin, Emmanuel AU - Foster, F. Stuart AU - Dayton, Paul A. T2 - SENSING AND ANALYSIS TECHNOLOGIES FOR BIOMEDICAL AND COGNITIVE APPLICATIONS 2016 AB - Acoustic Angiography is a new approach to high-resolution contrast enhanced ultrasound imaging enabled by ultra-broadband transducer designs. The high frequency imaging technique provides signal separation from tissue which does not produce significant harmonics in the same frequency range, as well as high resolution. This approach enables imaging of microvasculature in-vivo with high resolution and signal to noise, producing images that resemble x-ray angiography. Data shows that acoustic angiography can provide important information about the presence of disease based on vascular patterns, and may enable a new paradigm in medical imaging. DA - 2016/// PY - 2016/// DO - 10.1117/12.2229179 VL - 9871 SP - SN - 1996-756X KW - Ultrasound KW - contrast agent KW - microbubble KW - microvasculature KW - angiogenesis KW - broadband KW - superharmonic KW - transducer KW - dual-frequency KW - acoustic angiography ER - TY - JOUR TI - A piezoelectric shear stress sensor AU - Kim, Taeyang AU - Saini, Aditya AU - Kim, Jinwook AU - Gopalarathnam, Ashok AU - Zhu, Yong AU - Palmieri, Frank L. AU - Wohl, Christopher J. AU - Jiang, Xiaoning T2 - SENSORS AND SMART STRUCTURES TECHNOLOGIES FOR CIVIL, MECHANICAL, AND AEROSPACE SYSTEMS 2016 AB - In this paper, a piezoelectric sensor with a floating element was developed for shear stress measurement. The piezoelectric sensor was designed to detect the pure shear stress, suppressing effects of normal stress components, by applying opposite poling vectors to the piezoelectric elements. The sensor was first calibrated in the lab by applying shear forces where it demonstrated high sensitivity to shear stress (91.3 ± 2.1 pC/Pa) due to the high piezoelectric coefficients of 0.67Pb(Mg1∕3Nb2∕3)O3-0.33PbTiO3 (PMN-33%PT, d31=-1330 pC/N). The sensor also exhibited negligible sensitivity to normal stress (less than 1.2 pC/Pa) because of the electromechanical symmetry of the device. The usable frequency range of the sensor is up to 800 Hz. DA - 2016/// PY - 2016/// DO - 10.1117/12.2219185 VL - 9803 SP - SN - 1996-756X KW - PMN-33% PT crystal KW - bimorph piezoelectric structures KW - floating element KW - electromechanical symmetry ER - TY - JOUR TI - Wideband acoustic activation and detection of droplet vaporization events using a capacitive micromachined ultrasonic transducer AU - Novell, Anthony AU - Arena, Christopher B. AU - Oralkan, Omer AU - Dayton, Paul A. T2 - JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA AB - An ongoing challenge exists in understanding and optimizing the acoustic droplet vaporization (ADV) process to enhance contrast agent effectiveness for biomedical applications. Acoustic signatures from vaporization events can be identified and differentiated from microbubble or tissue signals based on their frequency content. The present study exploited the wide bandwidth of a 128-element capacitive micromachined ultrasonic transducer (CMUT) array for activation (8 MHz) and real-time imaging (1 MHz) of ADV events from droplets circulating in a tube. Compared to a commercial piezoelectric probe, the CMUT array provides a substantial increase of the contrast-to-noise ratio. DA - 2016/6// PY - 2016/6// DO - 10.1121/1.4953580 VL - 139 IS - 6 SP - 3193-3198 SN - 1520-8524 ER - TY - JOUR TI - Whole-Body and Local Muscle Vibration Immediately Improve Quadriceps Function in Individuals With Anterior Cruciate Ligament Reconstruction AU - Pamukoff, Derek N. AU - Pietrosimone, Brian AU - Lewek, Michael D. AU - Ryan, Eric D. AU - Weinhold, Paul. S. AU - Lee, Dustin R. AU - Blackburn, J. Troy T2 - ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION AB - Objective To determine the immediate effects of a single session of whole-body vibration (WBV) and local muscle vibration (LMV) on quadriceps function in individuals with anterior cruciate ligament reconstruction (ACLR). Design Singe-blind, randomized crossover trial. Setting Research laboratory. Participants Population-based sample of individuals with ACLR (N=20; mean age ± SD, 21.1±1.2y; mean mass ± SD, 68.3±14.9kg; mean time ± SD since ACLR, 50.7±21.3mo; 14 women; 16 patellar tendon autografts, 3 hamstring autografts, 1 allograft). Interventions Participants performed isometric squats while being exposed to WBV, LMV, or no vibration (control). Interventions were delivered in a randomized order during separate visits separated by 1 week. Main Outcome Measures Quadriceps active motor threshold (AMT), motor-evoked potential (MEP) amplitude, Hoffmann reflex (H-reflex) amplitude, peak torque (PT), rate of torque development (RTD), electromyographic amplitude, and central activation ratio (CAR) were assessed before and immediately after a WBV, LMV, or control intervention. Results There was an increase in CAR (+4.9%, P=.001) and electromyographic amplitude (+16.2%, P=.002), and a reduction in AMT (–3.1%, P<.001) after WBV, and an increase in CAR (+2.7%, P=.001) and a reduction in AMT (–2.9%, P<.001) after LMV. No effect was observed after WBV or LMV in H-reflex, RTD, or MEP amplitude. AMT (–3.7%, P<.001), CAR (+5.7%, P=.005), PT (+.31Nm/kg, P=.004), and electromyographic amplitude (P=.002) in the WBV condition differed from the control condition postapplication. AMT (–3.0% P=.002), CAR (+3.6%, P=.005), and PT (+.30Nm/kg, P=.002) in the LMV condition differed from the control condition postapplication. No differences were observed between WBV and LMV postapplication in any measurement. Conclusions WBV and LMV acutely improved quadriceps function and could be useful modalities for restoring quadriceps strength in individuals with knee pathologies. DA - 2016/7// PY - 2016/7// DO - 10.1016/j.apmr.2016.01.021 VL - 97 IS - 7 SP - 1121-1129 SN - 1532-821X KW - Knee KW - Muscles KW - Osteoarthritis KW - Rehabilitation KW - Resistance training ER - TY - JOUR TI - Towards an Integrated Microneedle Total Analysis Chip for Protein Detection AU - Miller, Philip AU - Moorman, Matthew AU - Manginell, Ron AU - Ashlee, Carlee AU - Brener, Igal AU - Wheeler, David AU - Narayan, Roger AU - Polsky, Ronen T2 - ELECTROANALYSIS AB - Abstract Real‐time monitoring of an individual’s physiologic state without constant observation by a healthcare professional necessitates the construction of an autonomous remote diagnostic device that is capable of performing a wide range of diagnostic functions. For many applications, assessing the immediate physiologic state of an individual as he or she is continuously exposed to diverse environments would require complex dynamic chemical processing scenarios that are capable of real time readouts. We seek to answer these problems by combining in vivo microneedle platforms with multifunctional lab‐on‐chip electrode arrays that are capable of detecting a wide variety of relevant biomarkers. The results presented here provide an important proof‐of‐concept demonstration of integration of microneedles with a microchip platform containing fluidic channels and electrode transducers. As shown by immunoassay detection of myoglobin and troponin, such a device may be used to extract interstitial fluid and monitor biologically important molecules. DA - 2016/6// PY - 2016/6// DO - 10.1002/elan.201600063 VL - 28 IS - 6 SP - 1305-1310 SN - 1521-4109 KW - lab-on-chip KW - biosensor KW - immunoassay KW - microneedle KW - myoglobin KW - troponin ER - TY - JOUR TI - Single Cell Chemical Cytometry of Akt Activity in Rheumatoid Arthritis and Normal Fibroblast-like Synoviocytes in Response to Tumor Necrosis Factor alpha AU - Mainz, Emilie R. AU - Serafin, D. Stephen AU - Nguyen, Tuong T. AU - Tarrant, Teresa K. AU - Sims, Christopher E. AU - Allbritton, Nancy L. T2 - ANALYTICAL CHEMISTRY AB - The etiology of rheumatoid arthritis (RA) is poorly understood, and 30% of patients are unresponsive to established treatments targeting tumor necrosis factor α (TNFα). Akt kinase is implicated in TNFα signaling and may act as a barometer of patient responses to biologic therapies. Fluorescent peptide sensors and chemical cytometry were employed to directly measure Akt activity as well as proteolytic activity in individual fibroblast-like synoviocytes (FLS) from RA and normal subjects. The specificity of the peptide reporter was evaluated and shown to be a valid measure of Akt activity in single cells. The effect of TNFα treatment on Akt activity was highly heterogeneous between normal and RA subjects, which was not observable in bulk analyses. In 2 RA subjects, a bimodal distribution of Akt activity was observed, primarily due to a subpopulation (21.7%: RA Subject 5; 23.8%: RA Subject 6) of cells in which >60% of the reporter was phosphorylated. These subjects also possessed statistically elevated proteolytic cleavage of the reporter relative to normal subjects, suggesting heterogeneity in Akt and protease activity that may play a role in the RA-affected joint. We expect that chemical cytometry studies pairing peptide reporters with capillary electrophoresis will provide valuable data regarding aberrant kinase activity from small samples of clinical interest. DA - 2016/8/2/ PY - 2016/8/2/ DO - 10.1021/acs.analchem.6b01801 VL - 88 IS - 15 SP - 7786-7792 SN - 1520-6882 ER - TY - JOUR TI - Enhanced Antiglioblastoma Efficacy of Neovasculature and Glioma Cells Dual Targeted Nanoparticles AU - Lv, Lingyan AU - Jiang, Yan AU - Liu, Xin AU - Wang, Baoyan AU - Lv, Wei AU - Zhao, Yue AU - Shi, Huihui AU - Hu, Quanyin AU - Xin, Hongliang AU - Xu, Qunwei AU - Gu, Zhen T2 - MOLECULAR PHARMACEUTICS AB - Combining treatment of anticancer cells and antiangiogenesis is considered to be a potential targeted strategy for brain glioblastoma therapy. In this study, by utilizing the overexpression of Interleukin 13 receptor α2 (IL-13Rα2) on the glioma cells and heparan sulfate on neovascular endothelial cells, we developed a paclitaxel (PTX) loaded Pep-1 and CGKRK peptide-modified PEG-PLGA nanoparticle (PC-NP-PTX) for glioma cells and neovasculature dual-targeted chemotherapy to enhance the antiglioma efficacy. There were significant differences both on the enhancement of cellular uptake in HUVEC and C6 cells and on the improvement of in vitro antiglioma activity in the respect of proliferation, tumor spheroid growth, tube formation, and migration between PC-NP-PTX and Taxol and NP-PTX. As for C6 cells, the IC50 were 3.59 ± 0.056, 2.37 ± 0.044, 1.38 ± 0.028, 1.82 ± 0.035, and 1.00 ± 0.016 μg/mL of Taxol, NP-PTX, Pep-NP-PTX, CGKRK-NP-PTX, and PC-NP-PTX, and for HUVEC cells, the IC50 were 0.44 ± 0.006, 0.33 ± 0.005, 0.25 ± 0.005, 0.19 ± 0.004, and 0.16 ± 0.004 μg/mL of Taxol, NP-PTX, Pep-NP-PTX, CGKRK-NP-PTX, and PC-NP-PTX, respectively. In vivo distribution assays confirmed that PC-NP-PTX targeted and accumulated effectively at glioma site. PC-NP-PTX showed a longer median survival time of 61 days when compared with Taxol (22 days), NP-PTX (24 days), Pep-NP-PTX (32 days), and CGKRK-NP-PTX (34 days). The in vivo antiglioma efficacy and safety evaluation showed PC-NP-PTX significantly enhanced the antiglioma efficacy and displayed negligible acute toxicity. DA - 2016/10// PY - 2016/10// DO - 10.1021/acs.molpharmaceut.6b00523 VL - 13 IS - 10 SP - 3506-3517 SN - 1543-8384 KW - glioma KW - antineovasculature KW - dual-targeted nanoparticle KW - drug delivery KW - paclitaxel ER - TY - JOUR TI - Creating tissues from textiles: scalable nonwoven manufacturing techniques for fabrication of tissue engineering scaffolds AU - Tuin, S. A. AU - Pourdeyhimi, B. AU - Loboa, E. G. T2 - BIOMEDICAL MATERIALS AB - Electrospun nonwovens have been used extensively for tissue engineering applications due to their inherent similarities with respect to fibre size and morphology to that of native extracellular matrix (ECM). However, fabrication of large scaffold constructs is time consuming, may require harsh organic solvents, and often results in mechanical properties inferior to the tissue being treated. In order to translate nonwoven based tissue engineering scaffold strategies to clinical use, a high throughput, repeatable, scalable, and economic manufacturing process is needed. We suggest that nonwoven industry standard high throughput manufacturing techniques (meltblowing, spunbond, and carding) can meet this need. In this study, meltblown, spunbond and carded poly(lactic acid) (PLA) nonwovens were evaluated as tissue engineering scaffolds using human adipose derived stem cells (hASC) and compared to electrospun nonwovens. Scaffolds were seeded with hASC and viability, proliferation, and differentiation were evaluated over the course of 3 weeks. We found that nonwovens manufactured via these industry standard, commercially relevant manufacturing techniques were capable of supporting hASC attachment, proliferation, and both adipogenic and osteogenic differentiation of hASC, making them promising candidates for commercialization and translation of nonwoven scaffold based tissue engineering strategies. DA - 2016/2// PY - 2016/2// DO - 10.1088/1748-6041/11/1/015017 VL - 11 IS - 1 SP - SN - 1748-605X KW - human adipose derived stem cells KW - nonwoven tissue engineering scaffolds KW - scalable tissue engineering ER - TY - JOUR TI - Tumor microenvironment and intracellular signal-activated nanomaterials for anticancer drug delivery AU - Mo, Ran AU - Gu, Zhen T2 - MATERIALS TODAY AB - Cancer-associated stimuli-responsive nanosystems have been increasingly considered for the delivery of anticancer drugs, which primarily target the tumor microenvironment and/or intracellular elements to enhance intratumoral accumulation and promote drug release at the target site. The signals facilitating drug delivery include tumor and endocytic acidities, hypoxia, enzyme overexpression, as well as high levels of intracellular glutathione, reactive oxygen species, and adenosine-5′-triphosphate. This article reviews the current techniques and ongoing developments in anticancer drug delivery using these signals. In particular, the focus is placed on design strategies and methods of formulating novel nanoscaled materials. The merits and drawbacks of recent strategies, as well as potential future developments, are discussed. DA - 2016/6// PY - 2016/6// DO - 10.1016/j.mattod.2015.11.025 VL - 19 IS - 5 SP - 274-283 SN - 1873-4103 ER - TY - JOUR TI - Transformable DNA nanocarriers for plasma membrane targeted delivery of cytokine AU - Sun, Wujin AU - Ji, Wenyan AU - Hu, Quanyin AU - Yu, Jicheng AU - Wang, Chao AU - Qian, Chenggen AU - Hochu, Gabrielle AU - Gu, Zhen T2 - BIOMATERIALS AB - Direct delivery of cytokines using nanocarriers holds great promise for cancer therapy. However, the nanometric scale of the vehicles made them susceptible to size-dependent endocytosis, reducing the plasma membrane-associated apoptosis signaling. Herein, we report a tumor microenvironment-responsive and transformable nanocarrier for cell membrane targeted delivery of cytokine. This formulation is comprised of a phospholipase A2 (PLA2) degradable liposome as a shell, and complementary DNA nanostructures (designated as nanoclews) decorated with cytokines as the cores. Utilizing the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a model cytokine, we demonstrate that the TRAIL loaded DNA nanoclews are capable of transforming into nanofibers after PLA2 activation. The nanofibers with micro-scaled lengths efficiently present the loaded TRAIL to death receptors on the cancer cell membrane and amplified the apoptotic signaling with reduced TRAIL internalization. DA - 2016/7// PY - 2016/7// DO - 10.1016/j.biomaterials.2016.04.011 VL - 96 SP - 1-10 SN - 1878-5905 KW - Cancer KW - Protein delivery KW - DNA structures KW - Cytokine KW - Nanomedicine ER - TY - JOUR TI - Improving the analytical performance and versatility of paper spray mass spectrometry via paper microfluidics AU - Murray, Ian AU - Walker, Glenn AU - Bereman, Michael S. T2 - ANALYST AB - Paper-based microfluidic techniques were explored to increase paper spray mass spectrometry's performance and versatility. DA - 2016/// PY - 2016/// DO - 10.1039/c6an00649c VL - 141 IS - 13 SP - 4065-4073 SN - 1364-5528 ER - TY - JOUR TI - Imaging and simulation of Achilles tendon dynamics: Implications for walking performance in the elderly AU - Franz, Jason R. AU - Thelen, Darryl G. T2 - JOURNAL OF BIOMECHANICS AB - The Achilles tendon (AT) is a complex structure, consisting of distinct fascicle bundles arising from each triceps surae muscle that may act as mechanically independent structures. Advances in tissue imaging are rapidly accelerating our understanding of the complexities of functional Achilles tendon behavior, with potentially important implications for musculoskeletal injury and performance. In this overview of our recent contributions to these efforts, we present the results of complementary experimental and computational approaches to investigate AT behavior during walking and its potential relevance to reduced triceps surae mechanical performance due to aging. Our experimental evidence reveals that older tendons exhibit smaller differences in tissue deformations than young adults between regions of the AT presumed to arise from the gastrocnemius and soleus muscles. These observations are consistent with a reduced capacity for inter-fascicle sliding within the AT, which could have implications for the mechanical independence of the triceps surae muscles. More uniform AT deformations are also correlated with hallmark biomechanical features of elderly gait – namely, a loss of net ankle moment, power, and positive work during push-off. Simulating age-related reductions in the capacity for inter-fascicle sliding in the AT during walking predicts detriments in gastrocnemius muscle-tendon mechanical performance coupled with underlying shifts in fascicle kinematics during push-off. AT compliance, also suspected to vary due to age, systematically modulates those effects. By integrating in vivo imaging with computational modeling, we have gained theoretical insight into multi-scale biomechanical changes due to aging, hypotheses regarding their functional effects, and opportunities for experiments that validate or invalidate these assertions. DA - 2016/6/14/ PY - 2016/6/14/ DO - 10.1016/j.jbiomech.2016.04.032 VL - 49 IS - 9 SP - 1403-1410 SN - 1873-2380 KW - Ultrasound KW - Plantarflexor KW - Aging KW - Musculoskeletal modeling KW - Simulation KW - Biomechanics ER - TY - JOUR TI - Fibrin Network Changes in Neonates after Cardiopulmonary Bypass AU - Brown, Ashley C. AU - Hannan, Riley H. AU - Timmins, Lucas H. AU - Fernandez, Janet D. AU - Barker, Thomas H. AU - Guzzetta, Nina A. T2 - ANESTHESIOLOGY AB - Quantitative and qualitative differences in the hemostatic systems exist between neonates and adults, including the presence of "fetal" fibrinogen, a qualitatively dysfunctional form of fibrinogen that exists until 1 yr of age. The consequences of "fetal" fibrinogen on clot structure in neonates, particularly in the context of surgery-associated bleeding, have not been well characterized. Here, the authors examine the sequential changes in clotting components and resultant clot structure in a small sample of neonates undergoing cardiac surgery and cardiopulmonary bypass (CPB).Blood samples were collected from neonates (n = 10) before surgery, immediately after CPB, and after the transfusion of cryoprecipitate (i.e., adult fibrinogen component). Clots were formed from patient samples or purified neonatal and adult fibrinogen. Clot structure was analyzed using confocal microscopy.Clots formed from plasma obtained after CPB and after transfusion were more porous than baseline clots. Analysis of clots formed from purified neonatal and adult fibrinogen demonstrated that at equivalent fibrinogen concentrations, neonatal clots lack three-dimensional structure, whereas adult clots were denser with significant three-dimensional structure. Clots formed from a combination of purified neonatal and adult fibrinogen were less homogenous than those formed from either purified adult or neonatal fibrinogen.The results of this study confirm that significant differences exist in clot structure between neonates and adults and that neonatal and adult fibrinogen may not integrate well. These findings suggest that differential treatment strategies for neonates should be pursued to reduce the demonstrated morbidity of blood product transfusion. DA - 2016/5// PY - 2016/5// DO - 10.1097/aln.0000000000001058 VL - 124 IS - 5 SP - 1021-1031 SN - 1528-1175 ER - TY - JOUR TI - Fabrication of novel high surface area mushroom gilled fibers and their effects on human adipose derived stem cells under pulsatile fluid flow for tissue engineering. applications AU - Tuin, Stephen A. AU - Pourdeyhimi, Behnam AU - Loboa, Elizabeth G. T2 - ACTA BIOMATERIALIA AB - The fabrication and characterization of novel high surface area hollow gilled fiber tissue engineering scaffolds via industrially relevant, scalable, repeatable, high speed, and economical nonwoven carding technology is described. Scaffolds were validated as tissue engineering scaffolds using human adipose derived stem cells (hASC) exposed to pulsatile fluid flow (PFF). The effects of fiber morphology on the proliferation and viability of hASC, as well as effects of varied magnitudes of shear stress applied via PFF on the expression of the early osteogenic gene marker runt related transcription factor 2 (RUNX2) were evaluated. Gilled fiber scaffolds led to a significant increase in proliferation of hASC after seven days in static culture, and exhibited fewer dead cells compared to pure PLA round fiber controls. Further, hASC-seeded scaffolds exposed to 3 and 6dyn/cm(2) resulted in significantly increased mRNA expression of RUNX2 after one hour of PFF in the absence of soluble osteogenic induction factors. This is the first study to describe a method for the fabrication of high surface area gilled fibers and scaffolds. The scalable manufacturing process and potential fabrication across multiple nonwoven and woven platforms makes them promising candidates for a variety of applications that require high surface area fibrous materials.We report here for the first time the successful fabrication of novel high surface area gilled fiber scaffolds for tissue engineering applications. Gilled fibers led to a significant increase in proliferation of human adipose derived stem cells after one week in culture, and a greater number of viable cells compared to round fiber controls. Further, in the absence of osteogenic induction factors, gilled fibers led to significantly increased mRNA expression of an early marker for osteogenesis after exposure to pulsatile fluid flow. This is the first study to describe gilled fiber fabrication and their potential for tissue engineering applications. The repeatable, industrially scalable, and versatile fabrication process makes them promising candidates for a variety of scaffold-based tissue engineering applications. DA - 2016/5// PY - 2016/5// DO - 10.1016/j.actbio.2016.03.025 VL - 36 SP - 220-230 SN - 1878-7568 KW - Gilled high surface area fibers KW - Human adipose derived stem cells KW - Pulsatile fluid slow KW - Shear stress KW - Scalable tissue engineering scaffolds ER - TY - JOUR TI - Evaluation of silver-titanium implants activated by low intensity direct current for orthopedic infection control: An in vitro and in vivo study AU - Cavanaugh, Daniel L. AU - Tan, Zhuo AU - Norris, James P. AU - Hardee, Amelia AU - Weinhold, Paul S. AU - Dahners, Laurence E. AU - Orndorff, Paul E. AU - Shirwaiker, Rohan A. T2 - JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS AB - Silver is an alternative antimicrobial of interest for the prophylaxis of prosthetic infections and electrical activation is known to augment its oligodynamic efficacy. In this study, we evaluated the in vitro and in vivo efficacy of a silver (Ag)-titanium (Ti) implant activated by 30 µA direct current compared with three controls - passive Ag-Ti, active Ti-Ti, and passive Ti-Ti. We hypothesized that the experimental group would provide better resistance to pathogenic colonization on the implant. Modified Kirby-Bauer technique was used to evaluate in vitro efficacy of the four groups against five bacteria and one fungus. For in vivo evaluation, forty-eight rats were divided into four groups. The implant was secured in a wound cavity along the posterior margin of the femur. The wound was inoculated with 7.5 × 10(5) CFU of Staphylococcus aureus. Rats were euthanized 14 days postsurgery and quantitative cultures were performed on the implant segments and the wound cavity tissue. In vitro tests showed that the growth of all six pathogens was inhibited around the active Ag anodes of the experimental group. In vivo, none of the four groups were able to prevent wound infection, but the experimental group resulted in reduced colonization. The mean bacterial loads on Ti segments were significantly lower in the implants which also had an Ag segment (p = 0.0007), and this effect was more pronounced with electrical activation (p = 0.0377). The results demonstrate the antimicrobial potential of LIDC-activated Ag-Ti implants. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1023-1031, 2016. DA - 2016/7// PY - 2016/7// DO - 10.1002/jbm.b.33451 VL - 104 IS - 5 SP - 1023-1031 SN - 1552-4981 KW - prosthetic infection KW - oligodynamic silver KW - antimicrobial implant KW - electrical activation ER - TY - JOUR TI - Design and characterization of a microfabricated hydrogen clearance blood flow sensor AU - Walton, Lindsay R. AU - Edwards, Martin A. AU - McCarty, Gregory S. AU - Wightman, R. Mark T2 - JOURNAL OF NEUROSCIENCE METHODS AB - Modern cerebral blood flow (CBF) detection favors the use of either optical technologies that are limited to cortical brain regions, or expensive magnetic resonance. Decades ago, inhalation gas clearance was the choice method of quantifying CBF, but this suffered from poor temporal resolution. Electrolytic H2 clearance (EHC) generates and collects gas in situ at an electrode pair, which improves temporal resolution, but the probe size has prohibited meaningful subcortical use. We microfabricated EHC electrodes to an order of magnitude smaller than those existing, on the scale of 100 μm, to permit use deep within the brain. Novel EHC probes were fabricated. The devices offered exceptional signal-to-noise, achieved high collection efficiencies (40–50%) in vitro, and agreed with theoretical modeling. An in vitro chemical reaction model was used to confirm that our devices detected flow rates higher than those expected physiologically. Computational modeling that incorporated realistic noise levels demonstrated devices would be sensitive to physiological CBF rates. The reduced size of our arrays makes them suitable for subcortical EHC measurements, as opposed to the larger, existing EHC electrodes that would cause substantial tissue damage. Our array can collect multiple CBF measurements per minute, and can thus resolve physiological changes occurring on a shorter timescale than existing gas clearance measurements. We present and characterize microfabricated EHC electrodes and an accompanying theoretical model to interpret acquired data. Microfabrication allows for the high-throughput production of reproducible devices that are capable of monitoring deep brain CBF with sub-minute resolution. DA - 2016/7/15/ PY - 2016/7/15/ DO - 10.1016/j.jneumeth.2016.04.014 VL - 267 SP - 132-140 SN - 1872-678X KW - COMSOL Multiphysics KW - Electrolysis KW - Gas clearance KW - Photolithography KW - Platinum electrode ER - TY - JOUR TI - Alternate Metabolic Programs Define Regional Variation of Relevant Biological Features in Renal Cell Carcinoma Progression AU - Brooks, Samira A. AU - Khandani, Amir H. AU - Fielding, Julia R. AU - Lin, Weili AU - Sills, Tiffany AU - Lee, Yueh AU - Arreola, Alexandra AU - Milowsky, Mathew I. AU - Wallen, Eric M. AU - Woods, Michael E. AU - Smith, Angie B. AU - Nielsen, Mathew E. AU - Parker, Joel S. AU - Lalush, David S. AU - Rathmell, W. Kimryn T2 - CLINICAL CANCER RESEARCH AB - Clear cell renal cell carcinoma (ccRCC) has recently been redefined as a highly heterogeneous disease. In addition to genetic heterogeneity, the tumor displays risk variability for developing metastatic disease, therefore underscoring the urgent need for tissue-based prognostic strategies applicable to the clinical setting. We have recently employed the novel PET/magnetic resonance (MR) image modality to enrich our understanding of how tumor heterogeneity can relate to gene expression and tumor biology to assist in defining individualized treatment plans.ccRCC patients underwent PET/MR imaging, and these images subsequently used to identify areas of varied intensity for sampling. Samples from 8 patients were subjected to histologic, immunohistochemical, and microarray analysis.Tumor subsamples displayed a range of heterogeneity for common features of hypoxia-inducible factor expression and microvessel density, as well as for features closely linked to metabolic processes, such as GLUT1 and FBP1. In addition, gene signatures linked with disease risk (ccA and ccB) also demonstrated variable heterogeneity, with most tumors displaying a dominant panel of features across the sampled regions. Intriguingly, the ccA- and ccB-classified samples corresponded with metabolic features and functional imaging levels. These correlations further linked a variety of metabolic pathways (i.e., the pentose phosphate and mTOR pathways) with the more aggressive, and glucose avid ccB subtype.Higher tumor dependency on exogenous glucose accompanies the development of features associated with the poor risk ccB subgroup. Linking these panels of features may provide the opportunity to create functional maps to enable enhanced visualization of the heterogeneous biologic processes of an individual's disease. Clin Cancer Res; 22(12); 2950-9. ©2016 AACR. DA - 2016/6/15/ PY - 2016/6/15/ DO - 10.1158/1078-0432.ccr-15-2115 VL - 22 IS - 12 SP - 2950-2959 SN - 1557-3265 ER - TY - JOUR TI - ATP-Responsive and Near-Infrared-Emissive Nanocarriers for Anticancer Drug Delivery and Real-Time Imaging AU - Qian, Chenggen AU - Chen, Yulei AU - Zhu, Sha AU - Yu, Jicheng AU - Zhang, Lei AU - Feng, Peijian AU - Tang, Xin AU - Hu, Quanyin AU - Sun, Wujin AU - Lu, Yue AU - Xiao, Xuanzhong AU - Shen, Qun-Dong AU - Gu, Zhen T2 - THERANOSTICS AB - Stimuli-responsive and imaging-guided drug delivery systems hold vast promise for enhancement of therapeutic efficacy. Here we report an adenosine-5'-triphosphate (ATP)-responsive and near-infrared (NIR)-emissive conjugated polymer-based nanocarrier for the controlled release of anticancer drugs and real-time imaging. We demonstrate that the conjugated polymeric nanocarriers functionalized with phenylboronic acid tags on surface as binding sites for ATP could be converted to the water-soluble conjugated polyelectrolytes in an ATP-rich environment, which promotes the disassembly of the drug carrier and subsequent release of the cargo. In vivo studies validate that this formulation exhibits promising capability for inhibition of tumor growth. We also evaluate the metabolism process by monitoring the fluorescence signal of the conjugated polymer through the in vivo NIR imaging. DA - 2016/// PY - 2016/// DO - 10.7150/thno.14843 VL - 6 IS - 7 SP - 1053-1064 SN - 1838-7640 KW - drug delivery KW - nanomedicine KW - stimuli-responsive KW - ATP-responsive KW - theranostics KW - conjugated polymers ER - TY - JOUR TI - A genome-wide study of lipid response to fenofibrate in Caucasians: A combined analysis of the GOLDN and ACCORD studies AU - Irvin, M. R. AU - Rotroff, D. M. AU - Aslibekyan, S. AU - Zhi, D. G. AU - Hidalgo, B. AU - Motsinger-Reif, A. AU - Marvel, S. AU - Srinivasasainagendra, V. AU - Claas, S. A. AU - Buse, J. B. AU - Straka, R. J. AU - Ordovas, J. M. AU - Borecki, I. B. AU - Guo, X. Q. AU - Chen, I. Y. D. AU - Rotter, J. I. T2 - Pharmacogenetics and Genomics DA - 2016/// PY - 2016/// VL - 26 IS - 7 SP - 324-333 ER - TY - JOUR TI - The "Fingerprint" of Cancer Extends Beyond Solid Tumor Boundaries: Assessment With a Novel Ultrasound Imaging Approach AU - Rao, Sneha R. AU - Shelton, Sarah E. AU - Dayton, Paul A. T2 - IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING AB - Goal: Abnormalities of microvascular morphology have been associated with tumor angiogenesis for more than a decade, and are believed to be intimately related to both tumor malignancy and response to treatment. However, the study of these vascular changes in-vivo has been challenged due to the lack of imaging approaches which can assess the microvasculature in 3-D volumes noninvasively. Here, we use contrast-enhanced “acoustic angiography” ultrasound imaging to observe and quantify heterogeneity in vascular morphology around solid tumors. Methods: Acoustic angiography, a recent advance in contrast-enhanced ultrasound imaging, generates high-resolution microvascular images unlike anything possible with standard ultrasound imaging techniques. Acoustic angiography images of a genetically engineered mouse breast cancer model were acquired to develop an image acquisition and processing routine that isolated radially expanding regions of a 3-D image from the tumor boundary to the edge of the imaging field for assessment of vascular morphology of tumor and surrounding vessels. Results: Quantitative analysis of vessel tortuosity for the tissue surrounding tumors 3 to 7 mm in diameter revealed that tortuosity decreased in a region 6 to 10 mm from the tumor boundary, but was still significantly elevated when compared to control vasculature. Conclusion: Our analysis of angiogenesis-induced changes in the vasculature outside the tumor margin reveals that the extent of abnormal tortuosity extends significantly beyond the primary tumor mass. Significance: Visualization of abnormal vascular tortuosity may make acoustic angiography an invaluable tool for early tumor detection based on quantifying the vascular footprint of small tumors and a sensitive method for understanding changes in the vascular microenvironment during tumor progression. DA - 2016/5// PY - 2016/5// DO - 10.1109/tbme.2015.2479590 VL - 63 IS - 5 SP - 1082-1086 SN - 1558-2531 KW - Acoustic angiography KW - angiogenesis KW - spatial heterogeneity KW - tortuosity KW - ultrasound ER - TY - JOUR TI - Response of human macrophages to wound matrices in vitro AU - Witherel, Claire E. AU - Graney, Pamela L. AU - Freytes, Donald O. AU - Weingarten, Michael S. AU - Spiller, Kara L. T2 - WOUND REPAIR AND REGENERATION AB - Abstract Chronic wounds remain a major burden to the global healthcare system. Myriad wound matrices are commercially available but their mechanisms of action are poorly understood. Recent studies have shown that macrophages are highly influenced by their microenvironment, but it is not known how different biomaterials affect this interaction. Here, it was hypothesized that human macrophages respond differently to changes in biomaterial properties in vitro with respect to phenotype, including pro‐inflammatory M1, anti‐inflammatory M2a, known for facilitating extracellular matrix deposition and proliferation, and M2c, which has recently been associated with tissue remodeling. Using multiple donors, it was found that collagen scaffolds cross‐linked with 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide and N‐hydroxysuccinimide (EDC/NHS) promoted the least inflammatory phenotype in primary human macrophages compared with scaffolds cross‐linked with formaldehyde or glutaraldehyde. Importantly, gene expression analysis trends were largely conserved between donors, especially TNFa (M1), CCL22 (M2a), and MRC1 (M2a). Then the response of primary and THP1 monocyte‐derived macrophages to four commercially available wound matrices were compared—Integra Dermal Regeneration Template (Integra), PriMatrix Dermal Repair Scaffold (PriMatrix), AlloMend Acellular Dermal Matrix (AlloMend), and Oasis Wound Matrix (Oasis). Gene expression trends were different between primary and THP1 monocyte‐derived macrophages for all six genes analyzed in this study. Finally, the behavior of primary macrophages cultured onto the wound matrices over time was analyzed. Integra and Oasis caused down‐regulation of M2a markers CCL22 and TIMP3. PriMatrix caused up‐regulation of TNFa (M1) and CD163 (M2c) and down‐regulation of CCL22 and TIMP3 (both M2a). AlloMend caused up‐regulation in CD163 (M2c). Lastly, Oasis promoted the largest increase in the combinatorial M1/M2 score, defined as the sum of M1 genes divided by the sum of M2 genes. This preliminary study suggested that biomaterials influenced the wound microenvironment to affect macrophage phenotype. DA - 2016/// PY - 2016/// DO - 10.1111/wrr.12423 VL - 24 IS - 3 SP - 514-524 SN - 1524-475X ER - TY - JOUR TI - Point-of-care diagnostics for niche applications AU - Cummins, Brian M. AU - Ligler, Frances S. AU - Walker, Glenn M. T2 - Biotechnology Advances AB - Point-of-care or point-of-use diagnostics are analytical devices that provide clinically relevant information without the need for a core clinical laboratory. In this review we define point-of-care diagnostics as portable versions of assays performed in a traditional clinical chemistry laboratory. This review discusses five areas relevant to human and animal health where increased attention could produce significant impact: veterinary medicine, space travel, sports medicine, emergency medicine, and operating room efficiency. For each of these areas, clinical need, available commercial products, and ongoing research into new devices are highlighted. DA - 2016/5// PY - 2016/5// DO - 10.1016/j.biotechadv.2016.01.005 VL - 34 IS - 3 SP - 161-176 J2 - Biotechnology Advances LA - en OP - SN - 0734-9750 UR - http://dx.doi.org/10.1016/J.BIOTECHADV.2016.01.005 DB - Crossref KW - Point-of-care KW - Diagnostics KW - Space travel KW - Sports medicine KW - Veterinary KW - Emergency care KW - Operating room ER - TY - JOUR TI - Platelet-mimetic strategies for modulating the wound environment and inflammatory responses AU - Nandi, Seema AU - Brown, Ashley C. T2 - EXPERIMENTAL BIOLOGY AND MEDICINE AB - Platelets closely interface with the immune system to fight pathogens, target wound sites, and regulate tissue repair. Natural platelet levels within the body can be depleted for a variety of reasons, including excessive bleeding following traumatic injury, or diseases such as cancer and bacterial or viral infections. Platelet transfusions are commonly used to improve platelet count and hemostatic function in these cases, but transfusions can be complicated by the contamination risks and short storage life of donated platelets. Lyophilized platelets that can be freeze-dried and stored for longer periods of time and synthetic platelet-mimetic technologies that can enhance or replace the functions of natural platelets, while minimizing adverse immune responses have been explored as alternatives to transfusion. Synthetic platelets typically comprise nanoparticles surface-decorated with peptides or ligands to recreate specific biological characteristics of platelets, including targeting of wound and disease sites and facilitating platelet aggregation. Recent efforts in synthetic platelet design have additionally focused on matching platelet shape and mechanics to recreate the marginalization and clot contraction capabilities of natural platelets. The ability to specifically tune the properties of synthetic platelet-mimetic materials has shown utility in a variety of applications including hemostasis, drug delivery, and targeted delivery of cancer therapeutics. DA - 2016/5// PY - 2016/5// DO - 10.1177/1535370216647126 VL - 241 IS - 10 SP - 1138-1148 SN - 1535-3699 KW - Platelets KW - hemostasis KW - artificial platelets KW - platelet-mimetic KW - nanoparticles KW - bionanoscience ER - TY - JOUR TI - Numerical Simulation of Focused Shock Shear Waves in Soft Solids and a Two-Dimensional Nonlinear Homogeneous Model of the Brain AU - Giammarinaro, B. AU - Coulouvrat, F. AU - Pinton, G. T2 - JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME AB - Shear waves that propagate in soft solids, such as the brain, are strongly nonlinear and can develop into shock waves in less than one wavelength. We hypothesize that these shear shock waves could be responsible for certain types of traumatic brain injuries (TBI) and that the spherical geometry of the skull bone could focus shear waves deep in the brain, generating diffuse axonal injuries. Theoretical models and numerical methods that describe nonlinear polarized shear waves in soft solids such as the brain are presented. They include the cubic nonlinearities that are characteristic of soft solids and the specific types of nonclassical attenuation and dispersion observed in soft tissues and the brain. The numerical methods are validated with analytical solutions, where possible, and with self-similar scaling laws where no known solutions exist. Initial conditions based on a human head X-ray microtomography (CT) were used to simulate focused shear shock waves in the brain. Three regimes are investigated with shock wave formation distances of 2.54 m, 0.018 m, and 0.0064 m. We demonstrate that under realistic loading scenarios, with nonlinear properties consistent with measurements in the brain, and when the shock wave propagation distance and focal distance coincide, nonlinear propagation can easily overcome attenuation to generate shear shocks deep inside the brain. Due to these effects, the accelerations in the focal are larger by a factor of 15 compared to acceleration at the skull surface. These results suggest that shock wave focusing could be responsible for diffuse axonal injuries. DA - 2016/4// PY - 2016/4// DO - 10.1115/1.4032643 VL - 138 IS - 4 SP - SN - 1528-8951 ER - TY - JOUR TI - Nanoparticles and direct immunosuppression AU - Ngobili, Terrika A. AU - Daniele, Michael A. T2 - EXPERIMENTAL BIOLOGY AND MEDICINE AB - Targeting the immune system with nanomaterials is an intensely active area of research. Specifically, the capability to induce immunosuppression is a promising complement for drug delivery and regenerative medicine therapies. Many novel strategies for immunosuppression rely on nanoparticles as delivery vehicles for small-molecule immunosuppressive compounds. As a consequence, efforts in understanding the mechanisms in which nanoparticles directly interact with the immune system have been overshadowed. The immunological activity of nanoparticles is dependent on the physiochemical properties of the nanoparticles and its subsequent cellular internalization. As the underlying factors for these reactions are elucidated, more nanoparticles may be engineered and evaluated for inducing immunosuppression and complementing immunosuppressive drugs. This review will briefly summarize the state-of-the-art and developments in understanding how nanoparticles induce immunosuppressive responses, compare the inherent properties of nanomaterials which induce these immunological reactions, and comment on the potential for using nanomaterials to modulate and control the immune system. DA - 2016/5// PY - 2016/5// DO - 10.1177/1535370216650053 VL - 241 IS - 10 SP - 1064-1073 SN - 1535-3699 KW - Nanoparticles KW - immunosuppression KW - bionanoscience KW - nanotoxicology KW - immunotoxicity KW - anti-inflammatory ER - TY - JOUR TI - Muscle fatigue increases beta-band coherence between the firing times of simultaneously active motor units in the first dorsal interosseous muscle AU - McManus, Lara AU - Hu, Xiaogang AU - Rymer, William Z. AU - Suresh, Nina L. AU - Lowery, Madeleine M. T2 - JOURNAL OF NEUROPHYSIOLOGY AB - Synchronization between the firing times of simultaneously active motor units (MUs) is generally assumed to increase during fatiguing contractions. To date, however, estimates of MU synchronization have relied on indirect measures, derived from surface electromyographic (EMG) interference signals. This study used intramuscular coherence to investigate the correlation between MU discharges in the first dorsal interosseous muscle during and immediately following a submaximal fatiguing contraction, and after rest. Coherence between composite MU spike trains, derived from decomposed surface EMG, were examined in the delta (1–4 Hz), alpha (8–12 Hz), beta (15–30 Hz), and gamma (30–60 Hz) frequency band ranges. A significant increase in MU coherence was observed in the delta, alpha, and beta frequency bands postfatigue. In addition, wavelet coherence revealed a tendency for delta-, alpha-, and beta-band coherence to increase during the fatiguing contraction, with subjects exhibiting low initial coherence values displaying the greatest relative increase. This was accompanied by an increase in MU short-term synchronization and a decline in mean firing rate of the majority of MUs detected during the sustained contraction. A model of the motoneuron pool and surface EMG was used to investigate factors influencing the coherence estimate. Simulation results indicated that changes in motoneuron inhibition and firing rates alone could not directly account for increased beta-band coherence postfatigue. The observed increase is, therefore, more likely to arise from an increase in the strength of correlated inputs to MUs as the muscle fatigues. DA - 2016/6/1/ PY - 2016/6/1/ DO - 10.1152/jn.00097.2016 VL - 115 IS - 6 SP - 2830-2839 SN - 1522-1598 KW - motor unit coherence KW - isometric fatigue KW - intramuscular coherence KW - beta-band coherence KW - short-term synchronization ER - TY - JOUR TI - Microneedles Integrated with Pancreatic Cells and Synthetic Glucose-Signal Amplifiers for Smart Insulin Delivery AU - Ye, Yanqi AU - Yu, Jicheng AU - Wang, Chao AU - Nguyen, Nhu-Y AU - Walker, Glenn M. AU - Buse, John B. AU - Gu, Zhen T2 - Advanced Materials AB - An innovative microneedle (MN)-based cell therapy is developed for glucose-responsive regulation of the insulin secretion from exogenous pancreatic β-cells without implantation. One MN patch can quickly reduce the blood-sugar levels (BGLs) of chemically induced type-1 diabetic mice and stabilize BGLs at a reduced level for over 10 h. DA - 2016/3/1/ PY - 2016/3/1/ DO - 10.1002/ADMA.201506025 VL - 28 IS - 16 SP - 3115-3121 J2 - Adv. Mater. LA - en OP - SN - 0935-9648 UR - http://dx.doi.org/10.1002/ADMA.201506025 DB - Crossref ER - TY - JOUR TI - Light-Activated Hypoxia-Responsive Nanocarriers for Enhanced Anticancer Therapy AU - Qian, Chenggen AU - Yu, Jicheng AU - Chen, Yulei AU - Hu, Quanyin AU - Xiao, Xuanzhong AU - Sun, Wujin AU - Wang, Chao AU - Feng, Peijian AU - Shen, Qun-Dong AU - Gu, Zhen T2 - ADVANCED MATERIALS AB - A light-activated hypoxia-responsive conjugated polymer-based nanocarrier is developed for efficiently producing singlet oxygen ((1) O2 ) and inducing hypoxia to promote release of its cargoes in tumor cells, leading to enhanced antitumor efficacy. This dual-responsive nanocarrier provides an innovative design guideline for enhancing traditional photodynamic therapeutic efficacy integrated with a controlled drug-release modality. DA - 2016/5/4/ PY - 2016/5/4/ DO - 10.1002/adma.201505869 VL - 28 IS - 17 SP - 3313-3320 SN - 1521-4095 ER - TY - JOUR TI - Internalized compartments encapsulated nanogels for targeted drug delivery AU - Yu, Jicheng AU - Zhang, Yuqi AU - Sun, Wujin AU - Wang, Chao AU - Ranson, Davis AU - Ye, Yanqi AU - Weng, Yuyan AU - Gu, Zhen T2 - NANOSCALE AB - Drug delivery systems inspired by natural particulates hold great promise for targeted cancer therapy. An endosome formed by internalization of plasma membrane has a massive amount of membrane proteins and receptors on the surface, which is able to specifically target the homotypic cells. Herein, we describe a simple method to fabricate an internalized compartments encapsulated nanogel with endosome membrane components (EM-NG) from source cancer cells. Following intracellular uptake of methacrylated hyaluronic acid (m-HA) adsorbed SiO2/Fe3O4 nanoparticles encapsulating a crosslinker and a photoinitiator, EM-NG was readily prepared through in situ crosslinking initiated under UV irradiation after internalization. The resulting nanogels loaded with doxorubicin (DOX) displayed enhanced internalization efficiency to the source cells through a specific homotypic affinity in vitro. However, when treated with the non-source cells, the EM-NGs exhibited insignificant difference in therapeutic efficiency compared to a bare HA nanogel with DOX. This study illustrates the potential of utilizing an internalized compartments encapsulated formulation for targeted cancer therapy, and offers guidelines for developing a natural particulate-inspired drug delivery system. DA - 2016/// PY - 2016/// DO - 10.1039/c5nr08895j VL - 8 IS - 17 SP - 9178-9184 SN - 2040-3372 ER - TY - JOUR TI - Inkjet deposition of itraconazole onto poly(glycolic acid) microneedle arrays AU - Boehm, Ryan D. AU - Jaipan, Panupong AU - Skoog, Shelby A. AU - Stafslien, Shane AU - VanderWal, Lyndsi AU - Narayan, Roger J. T2 - BIOINTERPHASES AB - Poly(glycolic acid) microneedle arrays were fabricated using a drawing lithography process; these arrays were modified with a drug release agent and an antifungal agent by piezoelectric inkjet printing. Coatings containing poly(methyl vinyl ether-co-maleic anhydride), a water-soluble drug release layer, and itraconazole (an antifungal agent), were applied to the microneedles by piezoelectric inkjet printing. Microscopic evaluation of the microneedles indicated that the modified microneedles contained the piezoelectric inkjet printing-deposited agents and that the surface coatings were released in porcine skin. Energy dispersive x-ray spectrometry aided in confirmation that the piezoelectric inkjet printing-deposited agents were successfully applied to the desired target areas of the microneedle surface. Fourier transform infrared spectroscopy was used to confirm the presence of the component materials in the piezoelectric inkjet printing-deposited material. Itraconazole-modified microneedle arrays incubated with agar plates containing Candida albicans cultures showed zones of growth inhibition. DA - 2016/3// PY - 2016/3// DO - 10.1116/1.4941448 VL - 11 IS - 1 SP - SN - 1559-4106 ER - TY - JOUR TI - In vitro polarization of colonoids to create an intestinal stem cell compartment AU - Attayek, P. J. AU - Ahmad, A. A. AU - Wang, Y. L. AU - Williamson, I. AU - Sims, C. E. AU - Magness, S. T. AU - Allbritton, N. L. T2 - PLoS One DA - 2016/// PY - 2016/// VL - 11 IS - 4 ER - TY - JOUR TI - Hypoxia-Sensitive Materials for Biomedical Applications AU - Yu, Jicheng AU - Zhang, Yuqi AU - Hu, Xiuli AU - Wright, Grace AU - Gu, Zhen T2 - ANNALS OF BIOMEDICAL ENGINEERING DA - 2016/6// PY - 2016/6// DO - 10.1007/s10439-016-1578-6 VL - 44 IS - 6 SP - 1931-1945 SN - 1573-9686 KW - Hypoxia-responsive KW - Drug delivery KW - Bioimaging KW - Hypoxia inducible factor-1 KW - Bioreductive molecule ER - TY - JOUR TI - FEASIBILITY AND SAFETY OF CONTRAST-ENHANCED ULTRASOUND IN THE DISTAL LIMB OF SIX HORSES AU - Seiler, Gabriela S. AU - Campbell, Nigel AU - Nixon, Britton AU - Tsuruta, James K. AU - Dayton, Paul A. AU - Jennings, Samuel AU - Redding, W. Rich AU - Lustgarten, Meghann T2 - VETERINARY RADIOLOGY & ULTRASOUND AB - Vascular alterations play important roles in many orthopedic diseases such as osteoarthritis, tendonitis, and synovitis in both human and equine athletes. Understanding these alterations could enhance diagnosis, prognosis, and treatment. Contrast‐enhanced ultrasound (CEUS) could be a valuable method for evaluation of blood flow and perfusion of these processes in the equine distal limb, however no reports were found describing feasibility or safety of the technique. The goal of this prospective, experimental study was to describe the feasibility and safety of distal limb CEUS in a sample of six horses. For each horse, CEUS of the distal limb was performed after intravenous injections of 5 and 10 ml, as well as intra‐arterial injections of 0.5 and 1 ml contrast medium. Vital parameters were monitored and CEUS images were assessed qualitatively and quantitatively for degree of contrast enhancement. None of the horses had clinically significant changes in their vital parameters after contrast medium injection. One horse had a transient increase in respiratory rate, and several horses had mild increases of systolic blood pressure of short duration after intravenous, but not after intra‐arterial injections. Intra‐arterial injection was possible in all horses and resulted in significantly improved contrast enhancement both quantitatively ( P = 0.027) and qualitatively ( P = 0.019). Findings from this study indicated that CEUS is a feasible and safe diagnostic test for evaluation of the equine distal limb. Future studies are needed to assess the clinical utility of this test for horses with musculoskeletal diseases. DA - 2016/// PY - 2016/// DO - 10.1111/vru.12333 VL - 57 IS - 3 SP - 282-289 SN - 1740-8261 KW - contrast-enhanced KW - equine intra-arterial KW - ultrasound ER - TY - JOUR TI - Dual targeted nanocarrier for brain ischemic stroke treatment AU - Zhao, Yue AU - Jiang, Yan AU - Lv, Wei AU - Wang, Zhongyuan AU - Lv, Lingyan AU - Wang, Baoyan AU - Liu, Xin AU - Liu, Yang AU - Hu, Quanyin AU - Sun, Wujin AU - Xu, Qunwei AU - Xin, Hongliang AU - Gu, Zhen T2 - JOURNAL OF CONTROLLED RELEASE AB - Focal cerebral ischemia, known as stroke, causes serious long-term disabilities globally. Effective therapy for cerebral ischemia demands a carrier that can penetrate the blood-brain barrier (BBB) and subsequently target the ischemia area in brain. Here, we designed a novel neuroprotectant (ZL006) loaded dual targeted nanocarrier based on liposome (T7&SHp-P-LPs/ZL006) conjugated with T7 peptide (T7) and stroke homing peptide (SHp) for penetrating BBB and targeting ischemia area, respectively. Compared with non-targeting liposomes, T7&SHp-P-LPs/ZL006 could transport across BCEC cells and significantly enhance cellular uptake and reduce cells apoptosis of excitatory amino acid stimulated PC-12 cells. However, there was no significant difference in cellular uptake between SHp-modified and plain liposomes when PC-12 cells were incubated without excitatory amino acid. Besides, ex vivo fluorescent images indicated that DiR labeled T7&SHp-P-LPs could efficiently transport across BBB and mostly accumulated in ischemic region rather than normal cerebral hemisphere of MCAO rats. Furthermore, T7&SHp-P-LPs/ZL006 could enhance the ability of in vivo anti-ischemic stroke of MCAO rats. These results demonstrated that T7&SHp-P-LPs could be used as a safe and effective dual targeted nanocarrier for ischemic stroke treatment. DA - 2016/7/10/ PY - 2016/7/10/ DO - 10.1016/j.jconrel.2016.04.038 VL - 233 SP - 64-71 SN - 1873-4995 KW - Stroke KW - Stroke homing peptide KW - Dual-targeting liposomes KW - ZL006 KW - Neuroprotection ER - TY - JOUR TI - Concise Review: Primary Cilia: Control Centers for Stem Cell Lineage Specification and Potential Targets for Cell-Based Therapies AU - Bodle, Josephine C. AU - Loboa, Elizabeth G. T2 - STEM CELLS AB - Directing stem cell lineage commitment prevails as the holy grail of translational stem cell research, particularly to those interested in the application of mesenchymal stem cells and adipose-derived stem cells in tissue engineering. However, elucidating the mechanisms underlying their phenotypic specification persists as an active area of research. In recent studies, the primary cilium structure has been intimately associated with defining cell phenotype, maintaining stemness, as well as functioning in a chemo, electro, and mechanosensory capacity in progenitor and committed cell types. Many hypothesize that the primary cilium may indeed be another important player in defining and controlling cell phenotype, concomitant with lineage-dictated cytoskeletal dynamics. Many of the studies on the primary cilium have emerged from disparate areas of biological research, and crosstalk amongst these areas of research is just beginning. To date, there has not been a thorough review of how primary cilia fit into the current paradigm of stem cell differentiation and this review aims to summarize the current cilia work in this context. The goal of this review is to highlight the cilium's function and integrate this knowledge into the working knowledge of stem cell biologists and tissue engineers developing regenerative medicine technologies. Stem Cells 2016;34:1445-1454. DA - 2016/6// PY - 2016/6// DO - 10.1002/stem.2341 VL - 34 IS - 6 SP - 1445-1454 SN - 1549-4918 KW - Primary cilia KW - Tissue regeneration KW - Adipose stem cells KW - Bone marrow stromal cells KW - Cell biology KW - Stem cell-microenvironment interactions KW - Cellular therapy KW - Progenitor cells ER - TY - JOUR TI - Aggregate entropy scoring for quantifying activity across endpoints with irregular correlation structure AU - Zhang, Guozhu AU - Marvel, Skylar AU - Truong, Lisa AU - Tanguay, Robert L. AU - Reif, David M. T2 - REPRODUCTIVE TOXICOLOGY AB - Robust computational approaches are needed to characterize systems-level responses to chemical perturbations in environmental and clinical toxicology applications. Appropriate characterization of response presents a methodological challenge when dealing with diverse phenotypic endpoints measured using in vivo systems. In this article, we propose an information-theoretic method named Aggregate Entropy (AggE) and apply it to scoring multiplexed, phenotypic endpoints measured in developing zebrafish (Danio rerio) across a broad concentration-response profile for a diverse set of 1060 chemicals. AggE accurately identified chemicals with significant morphological effects, including single-endpoint effects and multi-endpoint responses that would have been missed by univariate methods, while avoiding putative false-positives that confound traditional methods due to irregular correlation structure. By testing AggE in a variety of high-dimensional real and simulated datasets, we have characterized its performance and suggested implementation parameters that can guide its application across a wide range of experimental scenarios. DA - 2016/7// PY - 2016/7// DO - 10.1016/j.reprotox.2016.04.012 VL - 62 SP - 92-99 SN - 0890-6238 KW - Developmental neurotoxicology KW - Chemical biology KW - Morphology KW - Zebrafish KW - High throughput screening KW - ToxCast KW - Multiplexed assays ER - TY - JOUR TI - Adaptive windowing in contrast-enhanced intravascular ultrasound imaging AU - Lindsey, Brooks D. AU - Martin, K. Heath AU - Jiang, Xiaoning AU - Dayton, Paul A. T2 - ULTRASONICS AB - Intravascular ultrasound (IVUS) is one of the most commonly-used interventional imaging techniques and has seen recent innovations which attempt to characterize the risk posed by atherosclerotic plaques. One such development is the use of microbubble contrast agents to image vasa vasorum, fine vessels which supply oxygen and nutrients to the walls of coronary arteries and typically have diameters less than 200μm. The degree of vasa vasorum neovascularization within plaques is positively correlated with plaque vulnerability. Having recently presented a prototype dual-frequency transducer for contrast agent-specific intravascular imaging, here we describe signal processing approaches based on minimum variance (MV) beamforming and the phase coherence factor (PCF) for improving the spatial resolution and contrast-to-tissue ratio (CTR) in IVUS imaging. These approaches are examined through simulations, phantom studies, ex vivo studies in porcine arteries, and in vivo studies in chicken embryos. In phantom studies, PCF processing improved CTR by a mean of 4.2dB, while combined MV and PCF processing improved spatial resolution by 41.7%. Improvements of 2.2dB in CTR and 37.2% in resolution were observed in vivo. Applying these processing strategies can enhance image quality in conventional B-mode IVUS or in contrast-enhanced IVUS, where signal-to-noise ratio is relatively low and resolution is at a premium. DA - 2016/8// PY - 2016/8// DO - 10.1016/j.ultras.2016.04.022 VL - 70 SP - 123-135 SN - 1874-9968 KW - Intravascular ultrasound KW - Contrast-enhanced ultrasound KW - Adaptive beamforming KW - Phase coherence factor KW - High frequency ultrasound KW - Superharmonic ER - TY - JOUR TI - A Simple Model to Estimate Plantarflexor Muscle-Tendon Mechanics and Energetics During Walking With Elastic Ankle Exoskeletons AU - Sawicki, Gregory S. AU - Khan, Nabil S. T2 - IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING AB - A recent experiment demonstrated that when humans wear unpowered elastic ankle exoskeletons with intermediate spring stiffness, they can reduce their metabolic energy cost to walk by ∼7%. Springs that are too compliant or too stiff have little benefit. The purpose of this study was to use modeling and simulation to explore the muscle-level mechanisms for the "sweet spot" in stiffness during exoskeleton assisted walking.We developed a simple lumped uniarticular musculoskeletal model of the plantarflexors operating in parallel with an elastic "exo-tendon." Using an inverse approach with constrained kinematics and kinetics, we rapidly simulated human walking over a range of exoskeleton stiffness values and examined the underlying neuromechanics and energetics of the biological plantarflexors.Stiffer ankle exoskeleton springs resulted in larger decreases in plantarflexor muscle forces, activations, and metabolic energy consumption. However, in the process of unloading the compliant biological muscle-tendon unit, the muscle fascicles experienced larger excursions that negatively impacted series elastic element recoil that is characteristic of a tuned "catapult mechanism."The combination of disrupted muscle-tendon dynamics and the need to produce compensatory forces/moments to maintain overall net ankle moment invariance could explain the "sweet spot" in metabolic performance at intermediate ankle exoskeleton stiffness. Future work will aim to provide experimental evidence to support the model predictions presented here using ultrasound imaging of muscle-level dynamics during walking with elastic ankle exoskeletons.Engineers must account for the muscle-level effects of exoskeleton designs in order to achieve maximal performance objectives. DA - 2016/5// PY - 2016/5// DO - 10.1109/tbme.2015.2491224 VL - 63 IS - 5 SP - 914-923 SN - 1558-2531 KW - Ankle exoskeleton KW - computer simulation KW - elastic energy storage KW - energetics KW - Hill-type muscle model KW - human walking KW - metabolic cost KW - muscle-tendon dynamics KW - plantarflexors (PF) ER - TY - JOUR TI - A Novel Laser Ultrasound Transducer Using Candle Soot Carbon Nanoparticles AU - Huang, Wenbin AU - Chang, Wei-Yi AU - Kim, Jinwook AU - Li, Sibo AU - Huang, Shujin AU - Jiang, Xiaoning T2 - IEEE TRANSACTIONS ON NANOTECHNOLOGY AB - As a novel composite material for laser ultrasound transducer, candle soot nanoparticles polydimethylsiloxane (CSPs-PDMS) has been demonstrated to generate high frequency, broadband, and high-amplitude ultrasound waves. In this study, we investigated the mechanism of the high-optoacoustic conversion efficiency exhibited by the composite. A thermal-acoustic coupling model was proposed for analyzing the performance of the composite. The theoretical result matches well with the experimental observation. The acoustic beam profile was compared with Field II simulation results. The 4.41 × 10 -3 energy conversion coefficient and 21 MHz--6 dB frequency bandwidth of the composite suggest that CSPs-PDMS composites is promising for a broad range of ultrasound therapy and non-destructive testing applications. DA - 2016/5// PY - 2016/5// DO - 10.1109/tnano.2016.2536739 VL - 15 IS - 3 SP - 395-401 SN - 1941-0085 KW - Broadband ultrasound KW - candle soot KW - high frequency ultrasound KW - nano-particles composite KW - optoacoustic ER - TY - JOUR TI - Using Field Asymmetric Ion Mobility Spectrometry for Odor Assessment of Automobile Interior Components AU - Li, Juan AU - Gutierrez-Osuna, Ricardo AU - Hodges, Ryan D. AU - Luckey, Gail AU - Crowell, Joel AU - Schiffman, Susan S. AU - Nagle, H. Troy T2 - IEEE SENSORS JOURNAL AB - The of the quality of odors emitted from automobile cabin interiors is an important element for the design of vehicles that meet prospective customers' expectations. Extending our previous work on machine-versus-human odor assessment for intact automobile cabin interiors, in this paper, we evaluated odors generated from individual interior parts using a human panel and field asymmetric ion mobility spectrometry (FAIMS). We used image processing techniques to extract geometric features from FAIMS dispersion fields, and built the predictive models for three odor assessment parameters (intensity, irritation, and pleasantness) by means of partial least squares regression. The best feature set was chosen by backward sequential feature selection. Using k -fold cross validation, we achieved statistically significant correlation 0.95 between human panel measured and machine olfaction predicted odor assessment scores with a sample set of 48 interior automobile parts. These results, generated using the geometric image processing methods demonstrated herein, further support the feasibility of replacing a human panel by machine olfaction for the assessment of odor quality of interior automobile parts. DA - 2016/7/15/ PY - 2016/7/15/ DO - 10.1109/jsen.2016.2568209 VL - 16 IS - 14 SP - 5747-5756 SN - 1558-1748 KW - Automobile odor assessment KW - field asymmetric ion mobility spectrometry KW - machine olfaction KW - image processing KW - partial least squares regression KW - k-fold cross-validation ER - TY - JOUR TI - Targeted Transthoracic Acoustic Activation of Systemically Administered Nanodroplets to Detect Myocardial Perfusion Abnormalities AU - Porter, Thomas R. AU - Arena, Christopher AU - Sayyed, Samer AU - Lof, John AU - High, Robin R. AU - Xie, Feng AU - Dayton, Paul A. T2 - CIRCULATION-CARDIOVASCULAR IMAGING AB - Background— Liquid core nanodroplets containing condensed gaseous fluorocarbons can be vaporized at clinically relevant acoustic energies and have been hypothesized as an alternative ultrasound contrast agent instead of gas-core agents. The potential for targeted activation and imaging of these agents was tested with droplets formulated from liquid octafluoropropane (C3) and 1:1 mixtures of C3 with liquid decafluorobutane (C3C4). Methods and Results— In 8 pigs with recent myocardial infarction and variable degrees of reperfusion, transthoracic acoustic activation was attempted using 1.3 to 1.7 MHz low (0.2 mechanical index [MI]) or high MI (1.2 MI) imaging in real time (32–64 Hertz) or triggered 1:1 at end systole during a 20% C3 or C3C4 droplet infusion. Any perfusion defects observed were measured and correlated with delayed enhancement magnetic resonance imaging and postmortem staining. No myocardial contrast was produced with any imaging setting when using C3C4 droplets or C3 droplets during low MI real-time imaging. However, myocardial contrast was observed in all 8 pigs with C3 droplets when using triggered high MI imaging and in 5 of 6 pigs that had 1.7 MHz real time-high MI imaging. Although quantitative myocardial contrast was lower with real-time high MI imaging than 1:1 triggering, the correlation between real-time resting defect size and infarct size was good ( r =0.97; P <0.001), as was the correlation with number of transmural infarcted segments by delayed enhancement imaging. Conclusions— Targeted transthoracic acoustic activation of infused intravenous C3 nanodroplets is effective, resulting in echogenic and persistent microbubbles which provide real-time high MI visualization of perfusion defects. DA - 2016/1// PY - 2016/1// DO - 10.1161/circimaging.115.003770 VL - 9 IS - 1 SP - SN - 1942-0080 KW - acoustic activation KW - angiography KW - echocardiography KW - fluorocarbons KW - perfusion ER - TY - JOUR TI - Sigma receptor-mediated targeted delivery of anti-angiogenic multifunctional nanodrugs for combination tumor therapy AU - Li, Y. K. AU - Wu, Y. Y. AU - Huang, L. AU - Miao, L. AU - Zhou, J. P. AU - Satterlee, A. B. AU - Yao, J. T2 - Journal of Controlled Release DA - 2016/// PY - 2016/// VL - 228 SP - 107-119 ER - TY - JOUR TI - Relationship between maximum isometric joint moment and functional task performance in patients with brachial plexus injury: A pilot study AU - Crouch, Dustin L. AU - Santago, Anthony C., II AU - Plate, Johannes F. AU - Li, Zhongyu AU - Saul, Katherine R. T2 - GAIT & POSTURE AB - We evaluated whether subjects with brachial plexus injury (BPI) adapted their movements to reduce the mechanical demand on their impaired upper extremity. In 6 subjects with unilateral BPI with C5 and C6 involvement, we measured bilateral maximum isometric shoulder and elbow strength, and computed joint kinematics and net muscle-generated joint moments during 7 unimanual functional tasks. Compared to the unimpaired extremity, maximum strength in shoulder abduction, extension, and external rotation was 60% (p = 0.02), 49% (p = 0.02), and 75% (p = 0.02) lower, respectively, on the impaired side. Significant kinematic and kinetic differences were observed only when reaching to the back of the head. However, because of substantially reduced strength in their impaired upper extremities, subjects used a significantly higher percentage of their maximum strength during several tasks and along several directions of movement. The peak percentage of maximal strength subjects used across tasks was 32% (p = 0.03) and 29% (p = 0.03) more on their impaired side in shoulder extension and external rotation, respectively. Subjects had less reserve strength available for performing upper extremity tasks and, therefore, may be less adaptive to strength declines due to injury progression and normal aging. Quantitatively measuring maximal strength may help clinicians ensure that patients maintain sufficient upper extremity strength to preserve long-term functional ability. DA - 2016/2// PY - 2016/2// DO - 10.1016/j.gaitpost.2015.12.038 VL - 44 SP - 238-244 SN - 1879-2219 KW - Nerve KW - Shoulder KW - Simulation KW - Strength KW - Kinematics ER - TY - JOUR TI - Multi-Level Canonical Correlation Analysis for Standard-Dose PET Image Estimation AU - An, Le AU - Zhang, Pei AU - Adeli, Ehsan AU - Wang, Yan AU - Ma, Guangkai AU - Shi, Feng AU - Lalush, David S. AU - Lin, Weili AU - Shen, Dinggang T2 - IEEE TRANSACTIONS ON IMAGE PROCESSING AB - Positron emission tomography (PET) images are widely used in many clinical applications, such as tumor detection and brain disorder diagnosis. To obtain PET images of diagnostic quality, a sufficient amount of radioactive tracer has to be injected into a living body, which will inevitably increase the risk of radiation exposure. On the other hand, if the tracer dose is considerably reduced, the quality of the resulting images would be significantly degraded. It is of great interest to estimate a standard-dose PET (S-PET) image from a low-dose one in order to reduce the risk of radiation exposure and preserve image quality. This may be achieved through mapping both S-PET and low-dose PET data into a common space and then performing patch-based sparse representation. However, a one-size-fits-all common space built from all training patches is unlikely to be optimal for each target S-PET patch, which limits the estimation accuracy. In this paper, we propose a data-driven multi-level canonical correlation analysis scheme to solve this problem. In particular, a subset of training data that is most useful in estimating a target S-PET patch is identified in each level, and then used in the next level to update common space and improve estimation. In addition, we also use multi-modal magnetic resonance images to help improve the estimation with complementary information. Validations on phantom and real human brain data sets show that our method effectively estimates S-PET images and well preserves critical clinical quantification measures, such as standard uptake value. DA - 2016/7// PY - 2016/7// DO - 10.1109/tip.2016.2567072 VL - 25 IS - 7 SP - 3303-3315 SN - 1941-0042 KW - PET estimation KW - multi-level CCA KW - sparse representation KW - locality-constrained linear coding KW - multi-modal MRI ER - TY - JOUR TI - MOLECULAR ACOUSTIC ANGIOGRAPHY: A NEW TECHNIQUE FOR HIGH-RESOLUTION SUPERHARMONIC ULTRASOUND MOLECULAR IMAGING AU - Shelton, Sarah E. AU - Lindsey, Brooks D. AU - Tsuruta, James K. AU - Foster, F. Stuart AU - Dayton, Paul A. T2 - ULTRASOUND IN MEDICINE AND BIOLOGY AB - Ultrasound molecular imaging utilizes targeted microbubbles to bind to vascular targets such as integrins, selectins and other extracellular binding domains. After binding, these microbubbles are typically imaged using low pressures and multi-pulse imaging sequences. In this article, we present an alternative approach for molecular imaging using ultrasound that relies on superharmonic signals produced by microbubble contrast agents. Bound bubbles were insonified near resonance using a low frequency (4 MHz) element and superharmonic echoes were received at high frequencies (25-30 MHz). Although this approach was observed to produce declining image intensity during repeated imaging in both in vitro and in vivo experiments because of bubble destruction, the feasibility of superharmonic molecular imaging was demonstrated for transmit pressures, which are sufficiently high to induce shell disruption in bound microbubbles. This approach was validated using microbubbles targeted to the αvβ3 integrin in a rat fibrosarcoma model (n = 5) and combined with superharmonic images of free microbubbles to produce high-contrast, high-resolution 3-D volumes of both microvascular anatomy and molecular targeting. Image intensity over repeated scans and the effect of microbubble diameter were also assessed in vivo, indicating that larger microbubbles yield increased persistence in image intensity. Using ultrasound-based acoustic angiography images rather than conventional B-mode ultrasound to provide the underlying anatomic information facilitates anatomic localization of molecular markers. Quantitative analysis of relationships between microvasculature and targeting information indicated that most targeting occurred within 50 μm of a resolvable vessel (>100 μm diameter). The combined information provided by these scans may present new opportunities for analyzing relationships between microvascular anatomy and vascular targets, subject only to limitations of the current mechanically scanned system and microbubble persistence to repeated imaging at moderate mechanical indices. DA - 2016/3// PY - 2016/3// DO - 10.1016/j.ultrasmedbio.2015.10.015 VL - 42 IS - 3 SP - 769-781 SN - 1879-291X KW - Microbubble KW - Targeted imaging KW - Angiogenesis KW - Microvasculature KW - Biomarker ER - TY - JOUR TI - Iron oxide nanoparticles induce autophagosome accumulation through multiple mechanisms: Lysosome impairment, mitochondrial damage, and ER stress AU - Zhang, X. D. AU - Zhang, H. Q. AU - Liang, X. AU - Zhang, J. X. AU - Tao, W. AU - Zhu, X. B. AU - Chang, D. F. AU - Zeng, X. W. AU - Mei, L. T2 - Molecular Pharmaceutics DA - 2016/// PY - 2016/// VL - 13 IS - 7 SP - 2578-2587 ER - TY - JOUR TI - Influence of chondrodystrophy and brachycephaly on geometry of the humerus in dogs AU - Smith, Emily J. AU - Marcellin-Little, Denis J. AU - Harrysson, Ola L. A. AU - Griffith, Emily H. T2 - VETERINARY AND COMPARATIVE ORTHOPAEDICS AND TRAUMATOLOGY AB - To assess the geometry of canine humeri as seen on radiographs in chondrodystrophic dogs (CD) and brachycephalic dogs (BD) compared to non-chondrodystrophic dogs (NCD).Mediolateral (ML) and craniocaudal (CC) radiographs of skeletally mature humeri were used (CD [n = 5], BD [n = 9], NCD [n = 48]) to evaluate general dimensions (length, width, canal flare, cortical thickness), curvature (shaft, humeral head, and glenoid), and angulation (humeral head and condyle). Measurements from CD, BD, and NCD were compared.Mean humeral length was shorter in CD (108 mm) compared to BD (184 mm, p = 0.001) and NCD (183 mm, p <0.001). Craniocaudal cortical thickness at 70% of humeral length and ML cortical thickness at 30%, 50%, and 70% of humeral length were less in CD compared to BD and NCD. Humeral shaft curvature was greater in CD (9.9°) compared to BD (6.7°, p = 0.023). The ratio of glenoid radius of curvature / humeral length was greater for CD (11.1%) compared to NCD (9.7%, p = 0.013). The ratio of humeral width / humeral length was greater for BD (29.4%) compared to NCD (26.2%, p = 0.043). The ratio of glenoid length / humeral length was greater in CD (18.0%) than BD (16.4%, p = 0.048) and NCD (15.6%, p <0.001).Bone proportions and curvature in CD differ from BD and NCD. Differences are minor and unlikely to have clinical significance. DA - 2016/// PY - 2016/// DO - 10.3415/vcot-15-11-0181 VL - 29 IS - 3 SP - 220-226 SN - 2567-6911 KW - Dog KW - anatomy KW - humerus ER - TY - JOUR TI - High-throughput characterization of chemical-associated embryonic behavioral changes predicts teratogenic outcomes AU - Reif, David M. AU - Truong, Lisa AU - Mandrell, David AU - Marvel, Skylar AU - Zhang, Guozhu AU - Tanguay, Robert L. T2 - ARCHIVES OF TOXICOLOGY AB - New strategies are needed to address the data gap between the bioactivity of chemicals in the environment versus existing hazard information. We address whether a high-throughput screening (HTS) system using a vertebrate organism (embryonic zebrafish) can characterize chemical-elicited behavioral responses at an early, 24 hours post-fertilization (hpf) stage that predict teratogenic consequences at a later developmental stage. The system was used to generate full concentration-response behavioral profiles at 24 hpf across 1060 ToxCast™ chemicals. Detailed, morphological evaluation of all individuals was performed as experimental follow-up at 5 days post-fertilization (dpf). Chemicals eliciting behavioral responses were also mapped against external HTS in vitro results to identify specific molecular targets and neurosignalling pathways. We found that, as an integrative measure of normal development, significant alterations in movement highlighted active chemicals representing several modes of action. These early behavioral responses were predictive for 17 specific developmental abnormalities and mortality measured at 5 dpf, often at lower (i.e., more potent) concentrations than those at which morphological effects were observed. Therefore, this system can provide rapid characterization of chemical-elicited behavioral responses at an early developmental stage that are predictive of observable adverse effects later in life. DA - 2016/6// PY - 2016/6// DO - 10.1007/s00204-015-1554-1 VL - 90 IS - 6 SP - 1459-1470 SN - 1432-0738 KW - Developmental neurotoxicology KW - Alternative testing KW - Chemical biology KW - Behavior KW - Zebrafish KW - High-throughput screening KW - Bioinformatics KW - Data integration KW - ToxCast KW - Bioactivity ER - TY - JOUR TI - Enhanced Cancer Immunotherapy by Microneedle Patch-Assisted Delivery of Anti-PD1 Antibody AU - Wang, Chao AU - Ye, Yanqi AU - Hochu, Gabrielle M. AU - Sadeghifar, Hasan AU - Gu, Zhen T2 - NANO LETTERS AB - Despite recent advances in melanoma treatment through the use of anti-PD-1 (aPD1) immunotherapy, the efficacy of this method remains to be improved. Here we report an innovative self-degradable microneedle (MN) patch for the sustained delivery of aPD1 in a physiologically controllable manner. The microneedle is composed of biocompatible hyaluronic acid integrated with pH-sensitive dextran nanoparticles (NPs) that encapsulate aPD1 and glucose oxidase (GOx), which converts blood glucose to gluconic acid. The generation of acidic environment promotes the self-dissociation of NPs and subsequently results in the substantial release of aPD1. We find that a single administration of the MN patch induces robust immune responses in a B16F10 mouse melanoma model compared to MN without degradation trigger or intratumoral injection of free aPD1 with the same dose. Moreover, this administration strategy can integrate with other immunomodulators (such as anti-CTLA-4) to achieve combination therapy for enhancing antitumor efficacy. DA - 2016/4// PY - 2016/4// DO - 10.1021/acs.nanolett.5b05030 VL - 16 IS - 4 SP - 2334-2340 SN - 1530-6992 KW - Anti-PD-1 KW - cancer immunotherapy KW - microneedle patch KW - melanoma KW - drug delivery ER - TY - JOUR TI - Electrospun nanofibrous scaffolds increase the efficacy of stem cell-mediated therapy of surgically resected glioblastoma AU - Bago, Juli R. AU - Pegna, Guillaume J. AU - Okolie, Onyi AU - Mohiti-Asli, Mahsa AU - Loboa, Elizabeth G. AU - Hingtgen, Shawn D. T2 - BIOMATERIALS AB - Engineered stem cell (SC)-based therapy holds enormous promise for treating the incurable brain cancer glioblastoma (GBM). Retaining the cytotoxic SCs in the surgical cavity after GBM resection is one of the greatest challenges to this approach. Here, we describe a biocompatible electrospun nanofibrous scaffold (bENS) implant capable of delivering and retaining tumor-homing cytotoxic stem cells that suppress recurrence of post-surgical GBM. As a new approach to GBM therapy, we created poly(l-lactic acid) (PLA) bENS bearing drug-releasing human mesenchymal stem cells (hMSCs). We discovered that bENS-based implant increased hMSC retention in the surgical cavity 5-fold and prolonged persistence 3-fold compared to standard direct injection using our mouse model of GBM surgical resection/recurrence. Time-lapse imaging showed cytotoxic hMSC/bENS treatment killed co-cultured human GBM cells, and allowed hMSCs to rapidly migrate off the scaffolds as they homed to GBMs. In vivo, bENS loaded with hMSCs releasing the anti-tumor protein TRAIL (bENSsTR) reduced the volume of established GBM xenografts 3-fold. Mimicking clinical GBM patient therapy, lining the post-operative GBM surgical cavity with bENSsTR implants inhibited the re-growth of residual GBM foci 2.3-fold and prolonged post-surgical median survival from 13.5 to 31 days in mice. These results suggest that nanofibrous-based SC therapies could be an innovative new approach to improve the outcomes of patients suffering from terminal brain cancer. DA - 2016/6// PY - 2016/6// DO - 10.1016/j.biomaterials.2016.03.008 VL - 90 SP - 116-125 SN - 1878-5905 KW - Cytotoxic stem cell KW - Electrospun nanofibrous scaffolds KW - Surgical resection KW - Cancer KW - Molecular imaging ER - TY - JOUR TI - Development of an Environment-Aware Locomotion Mode Recognition System for Powered Lower Limb Prostheses AU - Liu, Ming AU - Wang, Ding AU - Huang, He T2 - IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING AB - This paper aimed to develop and evaluate an environment-aware locomotion mode recognition system for volitional control of powered artificial legs. A portable terrain recognition (TR) module, consisting of an inertia measurement unit and a laser distance meter, was built to identify the type of terrain in front of the wearer while walking. A decision tree was used to classify the terrain types and provide either coarse or refined information about the walking environment. Then, the obtained environmental information was modeled as a priori probability and was integrated with a neuromuscular-mechanical-fusion-based locomotion mode (LM) recognition system. The designed TR module and environmental-aware LM recognition system was evaluated separately on able-bodied subjects and a transfemoral amputee online. The results showed that the TR module provided high quality environmental information: TR accuracy is above 98% and terrain transitions are detected over 500 ms before the time required to switch the prosthesis control mode. This enabled smooth locomotion mode transitions for the wearers. The obtained environmental information further improved the performance of LM recognition system, regardless of whether coarse or refined information was used. In addition, the environment-aware LM recognition system produced reliable online performance when the TR output was relatively noisy, which indicated the potential of this system to operate in unconstructed environment. This paper demonstrated that environmental information should be considered for operating wearable lower limb robotic devices, such as prosthetics and orthotics. DA - 2016/4// PY - 2016/4// DO - 10.1109/tnsre.2015.2420539 VL - 24 IS - 4 SP - 434-443 SN - 1558-0210 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84963864628&partnerID=MN8TOARS KW - A priori probability KW - locomotion mode recognition KW - prosthetics and orthotics KW - terrain recognition ER - TY - JOUR TI - Biological Response of Human Bone Marrow-Derived Mesenchymal Stem Cells to Commercial Tantalum Coatings with Microscale and Nanoscale Surface Topographies AU - Skoog, Shelby A. AU - Kumar, Girish AU - Goering, Peter L. AU - Williams, Brian AU - Stiglich, Jack AU - Narayan, Roger J. T2 - JOM DA - 2016/6// PY - 2016/6// DO - 10.1007/s11837-016-1934-x VL - 68 IS - 6 SP - 1672-1678 SN - 1543-1851 ER - TY - JOUR TI - Adding Stiffness to the Foot Modulates Soleus Force-Velocity Behaviour during Human Walking AU - Takahashi, Kota Z. AU - Gross, Michael T. AU - Werkhoven, Herman AU - Piazza, Stephen J. AU - Sawicki, Gregory S. T2 - SCIENTIFIC REPORTS AB - Abstract Previous studies of human locomotion indicate that foot and ankle structures can interact in complex ways. The structure of the foot defines the input and output lever arms that influences the force-generating capacity of the ankle plantar flexors during push-off. At the same time, deformation of the foot may dissipate some of the mechanical energy generated by the plantar flexors during push-off. We investigated this foot-ankle interplay during walking by adding stiffness to the foot through shoes and insoles and characterized the resulting changes in in vivo soleus muscle-tendon mechanics using ultrasonography. Added stiffness decreased energy dissipation at the foot (p < 0.001) and increased the gear ratio (i.e., ratio of ground reaction force and plantar flexor muscle lever arms) (p < 0.001). Added foot stiffness also altered soleus muscle behaviour, leading to greater peak force (p < 0.001) and reduced fascicle shortening speed (p < 0.001). Despite this shift in force-velocity behaviour, the whole-body metabolic cost during walking increased with added foot stiffness (p < 0.001). This increased metabolic cost is likely due to the added force demand on the plantar flexors, as walking on a more rigid foot/shoe surface compromises the plantar flexors’ mechanical advantage. DA - 2016/7/15/ PY - 2016/7/15/ DO - 10.1038/srep29870 VL - 6 SP - SN - 2045-2322 ER - TY - JOUR TI - A cyber expert system for auto-tuning powered prosthesis impedance control parameters AU - Huang, He AU - Crouch, D. L. AU - Liu, M. AU - Sawicki, G. S. AU - Wang, D. T2 - Annals of Biomedical Engineering DA - 2016/// PY - 2016/// DO - 10.1007/s10439-015-1464-7 VL - 44 IS - 5 SP - 1613–1624 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84944521097&partnerID=MN8TOARS ER - TY - JOUR TI - Versatile Protein Nanogels Prepared by In Situ Polymerization AU - Ye, Yanqi AU - Yu, Jicheng AU - Gu, Zhen T2 - MACROMOLECULAR CHEMISTRY AND PHYSICS AB - Proteins with unique structure and function have tremendous applications for cancer treatment, vaccination, diagnosis, regenerative medicine, and therapies for loss‐of‐function genetic diseases. A general method of loading and delivering active forms of proteins toward cells and tissues is highly desirable for remaining activity, enhancing stability, and avoiding potential immunogenicity of proteins. Nanogels with cross‐linked structure provide a versatile platform for storage and release of proteins. Herein, the recent advances in protein nanogels made by the in situ polymerization method, from preparation to application are summarized. A range of stimuli‐responsive formulations for on‐demand release, in a spatial, temporal, and dosage‐controlled manner, is highlighted. Future opportunities as well as challenges of protein nanogels are also discussed. image DA - 2016/2// PY - 2016/2// DO - 10.1002/macp.201500296 VL - 217 IS - 3 SP - 333-343 SN - 1521-3935 KW - drug delivery KW - in situ polymerization KW - nanogels KW - protein KW - stimuli-responsive ER - TY - JOUR TI - The proteasome controls presynaptic differentiation through modulation of an on-site pool of polyubiquitinated conjugates AU - Pinto, M. J. AU - Alves, P. L. AU - Martins, L. AU - Pedro, J. R. AU - Ryu, H. R. AU - Jeon, N. L. AU - Taylor, A. M. AU - Almeida, R. D. T2 - Journal of Cell Biology DA - 2016/// PY - 2016/// VL - 212 IS - 7 SP - 789-801 ER - TY - JOUR TI - Discovery of Q-phases and direct conversion of carbon into diamond and h-BN into c-BN AU - Narayan, J. AU - Bhaumik, A. AU - Narayan, R. T2 - Advanced Materials & Processes DA - 2016/// PY - 2016/// VL - 174 IS - 3 SP - 24-28 ER - TY - JOUR TI - Co-fabrication of chitosan and epoxy photoresist to form microwell arrays with permeable hydrogel bottoms AU - Ornoff, Douglas M. AU - Wang, Yuli AU - Proctor, Angela AU - Shah, Akash S. AU - Allbritton, Nancy L. T2 - BIOMATERIALS AB - Microfabrication technology offers the potential to create biological platforms with customizable patterns and surface chemistries, allowing precise control over the biochemical microenvironment to which a cell or group of cells is exposed. However, most microfabricated platforms grow cells on impermeable surfaces. This report describes the co-fabrication of a micropatterned epoxy photoresist film with a chitosan film to create a freestanding array of permeable, hydrogel-bottomed microwells. These films possess optical properties ideal for microscopy applications, and the chitosan layers are semi-permeable with a molecular exclusion of 9.9 ± 2.1 kDa. By seeding cells into the microwells, overlaying inert mineral oil, and supplying media via the bottom surface, this hybrid film permits cells to be physically isolated from one another but maintained in culture for at least 4 days. Arrays co-fabricated using these materials reduce both large-molecular-weight biochemical crosstalk between cells and mixing of different clonal populations, and will enable high-throughput studies of cellular heterogeneity with increased ability to customize dynamic interrogations compared to materials in currently available technologies. DA - 2016/1// PY - 2016/1// DO - 10.1016/j.biomaterials.2015.09.032 VL - 74 SP - 77-88 SN - 1878-5905 KW - Hydrogel KW - Microwell array KW - Chitosan KW - Microfabrication ER - TY - JOUR TI - Synthesis and comparative evaluation of novel Cu-64-labeled high affinity cell-specific peptides for positron emission tomography imaging of tumor vasculature AU - Merrill, Joseph R. AU - Krajewski, Krzysztof AU - Yuan, Hong AU - Frank, Jonathan E. AU - Lalush, David S. AU - Patterson, Cam AU - Veleva, Anka N. T2 - BIOMATERIALS AB - Tumor angiogenesis, the formation of new tumor blood supply, has been recognized as a hallmark of cancer and represents an important target for clinical management of various angiogenesis-dependent solid tumors. Previously, by screening a bacteriophage peptide library we have discovered the FHT-peptide sequence that binds specifically to bone marrow-derived tumor vasculature with high affinity. Here in an effort to determine the potential of the FHT-peptide for in vivo positron emission tomography (PET) imaging of aggressive tumor vasculature we studied four FHT-derivatives: NOTA-FHT, NOTA-(FHT)2, NOTA-PEG-FHT, and NOTA-PEG-(FHT)2. These peptide analogs were synthesized, labeled with the PET radionuclide (64)Cu, and characterized side-by-side with small animal PET and computed tomography imaging (microPET/CT) at 1 h, 4 h, and 24 h post injection in a subcutaneous Lewis lung carcinoma (LLC) tumor model. Because of its excellent in vivo kinetic properties and high tumor-to-background ratio, the (64)Cu-NOTA-FHT radiopeptide was selected for more detailed evaluation. Blocking studies with excess of unlabeled peptide showed specific and peptide mediated (64)Cu-NOTA-FHT tumor uptake. Biodistribution experiments in the same tumor model confirmed microPET/CT imaging results. Human radiation absorbed dose extrapolated from rodent biodistribution of (64)Cu-NOTA-FHT revealed favorable dosimetry profile. The findings from this investigation warrant further development of (64)Cu-NOTA-FHT as a potential targeted diagnostic radiopharmaceutical for PET imaging of aggressive tumor vasculature. DA - 2016/4// PY - 2016/4// DO - 10.1016/j.biomaterials.2016.01.031 VL - 84 SP - 241-249 SN - 1878-5905 KW - Molecular imaging KW - Tumor angiogenesis KW - Cu-64-labeled cell-specific peptides KW - Diagnostic PET radiopharmaceuticals KW - Radiation absorbed dose ER - TY - JOUR TI - Single-cell functional analysis of parathyroid adenomas reveals distinct classes of calcium sensing behaviour in primary hyperparathyroidism AU - Koh, James AU - Hogue, Joyce A. AU - Wang, Yuli AU - DiSalvo, Matthew AU - Allbritton, Nancy L. AU - Shi, Yuhong AU - Olson, John A., Jr. AU - Sosa, Julie A. T2 - JOURNAL OF CELLULAR AND MOLECULAR MEDICINE AB - Primary hyperparathyroidism (PHPT) is a common endocrine neoplastic disorder caused by a failure of calcium sensing secondary to tumour development in one or more of the parathyroid glands. Parathyroid adenomas are comprised of distinct cellular subpopulations of variable clonal status that exhibit differing degrees of calcium responsiveness. To gain a clearer understanding of the relationship among cellular identity, tumour composition and clinical biochemistry in PHPT, we developed a novel single cell platform for quantitative evaluation of calcium sensing behaviour in freshly resected human parathyroid tumour cells. Live-cell intracellular calcium flux was visualized through Fluo-4-AM epifluorescence, followed by in situ immunofluorescence detection of the calcium sensing receptor (CASR), a central component in the extracellular calcium signalling pathway. The reactivity of individual parathyroid tumour cells to extracellular calcium stimulus was highly variable, with discrete kinetic response patterns observed both between and among parathyroid tumour samples. CASR abundance was not an obligate determinant of calcium responsiveness. Calcium EC50 values from a series of parathyroid adenomas revealed that the tumours segregated into two distinct categories. One group manifested a mean EC50 of 2.40 mM (95% CI: 2.37-2.41), closely aligned to the established normal range. The second group was less responsive to calcium stimulus, with a mean EC50 of 3.61 mM (95% CI: 3.45-3.95). This binary distribution indicates the existence of a previously unappreciated biochemical sub-classification of PHPT tumours, possibly reflecting distinct etiological mechanisms. Recognition of quantitative differences in calcium sensing could have important implications for the clinical management of PHPT. DA - 2016/2// PY - 2016/2// DO - 10.1111/jcmm.12732 VL - 20 IS - 2 SP - 351-359 SN - 1582-4934 KW - hyperparathyroidism KW - parathyroid KW - adenoma KW - calcium KW - single-cell analysis ER - TY - JOUR TI - Predicting standard-dose PET image from low-dose PET and multimodal MR images using mapping-based sparse representation AU - Wang, Yan AU - Zhang, Pei AU - An, Le AU - Ma, Guangkai AU - Kang, Jiayin AU - Shi, Feng AU - Wu, Xi AU - Zhou, Jiliu AU - Lalush, David S AU - Lin, Weili AU - Shen, Dinggang T2 - Physics in Medicine and Biology AB - Positron emission tomography (PET) has been widely used in clinical diagnosis for diseases and disorders. To obtain high-quality PET images requires a standard-dose radionuclide (tracer) injection into the human body, which inevitably increases risk of radiation exposure. One possible solution to this problem is to predict the standard-dose PET image from its low-dose counterpart and its corresponding multimodal magnetic resonance (MR) images. Inspired by the success of patch-based sparse representation (SR) in super-resolution image reconstruction, we propose a mapping-based SR (m-SR) framework for standard-dose PET image prediction. Compared with the conventional patch-based SR, our method uses a mapping strategy to ensure that the sparse coefficients, estimated from the multimodal MR images and low-dose PET image, can be applied directly to the prediction of standard-dose PET image. As the mapping between multimodal MR images (or low-dose PET image) and standard-dose PET images can be particularly complex, one step of mapping is often insufficient. To this end, an incremental refinement framework is therefore proposed. Specifically, the predicted standard-dose PET image is further mapped to the target standard-dose PET image, and then the SR is performed again to predict a new standard-dose PET image. This procedure can be repeated for prediction refinement of the iterations. Also, a patch selection based dictionary construction method is further used to speed up the prediction process. The proposed method is validated on a human brain dataset. The experimental results show that our method can outperform benchmark methods in both qualitative and quantitative measures. DA - 2016/1/6/ PY - 2016/1/6/ DO - 10.1088/0031-9155/61/2/791 VL - 61 IS - 2 SP - 791-812 J2 - Phys. Med. Biol. OP - SN - 0031-9155 1361-6560 UR - http://dx.doi.org/10.1088/0031-9155/61/2/791 DB - Crossref KW - positron emission tomography (PET) KW - sparse representation KW - mapping-based sparse representation KW - incremental refinement KW - standard-dose PET prediction KW - multimodal MR images ER - TY - JOUR TI - Photo-Cross-Linked Scaffold with Kartogenin-Encapsulated Nanoparticles for Cartilage Regeneration AU - Shi, Dongquan AU - Xu, Xingquan AU - Ye, Yanqi AU - Song, Kai AU - Cheng, Yixiang AU - Di, Jin AU - Hu, Quanyin AU - Li, Jianxin AU - Ju, Huangxian AU - Jiang, Qing AU - Gu, Zhen T2 - ACS NANO AB - The regeneration of cartilage, an aneural and avascular tissue, is often compromised by its lack of innate abilities to mount a sufficient healing response. Kartogenin (KGN), a small molecular compound, can induce bone marrow-derived mesenchymal stem cells (BMSCs) into chondrocytes. The previous in vitro study showed that kartogenin also had a chondrogenesis effect on synovium derived mesenchymal stem cells (SMSCs). Herein, we present the effect of an ultraviolet-reactive, rapidly cross-linkable scaffold integrated with kartogenin-loaded nanoparticles using an innovational one-step technology. In vivo studies showed its potential role for cell homing, especially for recruiting the host’s endogenous cells, including BMSCs and SMSCs, without cell transplantation. Of note, the regenerated tissues were close to the natural hyaline cartilage based on the histological tests, specific markers analysis, and biomechanical tests. This innovative KGN release system makes the chondrogenesis efficient and persistent. DA - 2016/1// PY - 2016/1// DO - 10.1021/acsnano.5b06663 VL - 10 IS - 1 SP - 1292-1299 SN - 1936-086X KW - drug delivery KW - tissue engineering KW - hydrogel KW - regenerative medicine KW - nanoparticles ER - TY - JOUR TI - Elastic drug delivery: could treatments be triggered by patient movement? AU - Zhang, Yuqi AU - Yu, Jicheng AU - Zhu, Yong AU - Gu, Zhen T2 - NANOMEDICINE AB - NanomedicineVol. 11, No. 4 EditorialFree AccessElastic drug delivery: could treatments be triggered by patient movement?Yuqi Zhang, Jicheng Yu, Yong Zhu & Zhen GuYuqi Zhang Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill & North Carolina State University, Raleigh, NC 27695, USASearch for more papers by this author, Jicheng Yu Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill & North Carolina State University, Raleigh, NC 27695, USASearch for more papers by this author, Yong Zhu Department of Mechanical & Aerospace Engineering, North Carolina State University, Raleigh, NC 27695, USASearch for more papers by this author & Zhen Gu*Author for correspondence: E-mail Address: zgu@email.unc.edu Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill & North Carolina State University, Raleigh, NC 27695, USASearch for more papers by this authorPublished Online:19 Jan 2016https://doi.org/10.2217/nnm.15.197AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Keywords: drug deliverymechanical-responsivenanoparticlewearable devicesFirst draft submitted: 22 October 2015; Accepted for publication: 12 November 2015; Published online: 19 January 2016Nanoparticle-based drug delivery systems have drawn extensive attention for treating a broad range of diseases during the last few decades [1,2]. In order to enhance therapeutic efficacy, reduce side effects and prolong action time, vast efforts have been dedicated to the development of on-demand, precise drug release. In light of this, numerous stimuli-responsive designs have been exploited, including external triggers like mechanical force, temperature, light, ultrasound, electric current and magnetic field as well as internal factors like pH, redox, enzymes, ATP and hypoxia [3–8]. Compared with other stimuli-responsive designs, the macroscopic mechanical force-mediated approach, as one of the most promising strategies, possesses several advantages. It can be generated on-demand during the patients’ daily movement, such as tension in bone joints, tendons and muscles, or compression in cartilage and bones. Therefore, a self-administrated therapy can be readily achieved without requirement of additional instrumentations. In addition, in contrast to the inaccurate internal factors due to the complicated physiological environment, the degree of stretch or compression is more conveniently controlled by the patient themselves, leading to a precise dosage-, spatial- and temporal-controllable administration of drug release.Physical deformation of drug carriers supported on an elastomer substrate caused by stretch or compression is one of the most important strategies for mechanical force-triggered release. Mooney group designed a compression-responsive system for controlled release of growth factor [9]. Inspired by the natural extracellular matrices, they developed a hydrogel with reversible binding of drug as synthetic extracelluar matrices. The physical-loaded hydrogel could respond to repeated compression stimulus and as a result released free drug. Afterward, the matrices could be refilled by free drug during relaxation via dissociation of previously bound drug. Using VEGF as a model drug in in vivo studies, they demonstrated that the implanted hydrogels allowed an increase in VEGF concentration near implantation site as applying mechanical signals, subsequently leading to a local enhanced vascularization. In another case, Jeong group developed a strain-sensitive patch consisting of arrays of microcapsules onto a rubbery substrate for drug release [10]. When stretch was applied to the elastomer substrate, the volume of the stretchable microcapsules encapsulating cargoes decreased accordingly with the substrate, then pumping out the preloaded molecules. Under different degrees of mechanical stretching, the release rate and amount of cargoes could be adjusted. This patch has the potential to respond to body motions, even to the mechanical stretching of organs, muscles and tendons when it is implanted into body.We have recently developed a multipurpose wearable, tensile strain-triggered drug delivery device, which comprised of a stretchable elastomer and microgel depots containing drug-loaded nanoparticles [11]. The drugs can be continuously released from the nanoparticles and temporarily stored in the microgels. When applying a tensile strain, the drugs were released from micro-depots due to the enlarged surface area for diffusion and Poisson's ratio-induced compression toward the microgels. Therefore, a sustained drug release can be conveniently achieved by daily body motion, while a pulsatile release is able to be controlled through intentional administration. We demonstrated that this device could be simply attached to a finger joint, and stretched to trigger the drug release when the finger is flexed for multiple cycles, which allowed patients to control the dose and release timing of antibacterial drug on their own.Furthermore, we integrated this stretch-sensitive device with a microneedle array patch for on-demand transcutaneous insulin delivery [3], which allowed the blood glucose level of mice to decline quickly to a normoglycemic range within 0.5 h. Meanwhile, the obvious pulsatile and continuous reduction in blood glucose level were observed when applying a strain with an interval of 4 h. Based on this technology, the diabetic patients can easily maintain normoglycemia through simple joint movement instead of a traditional painful insulin injection. This skin-mountable device can be further extended for anti-inflammatory, anti-infective drug or painkiller delivery. More importantly, this facile strategy allows immediate medical treatment in emergency situation by patient's simple body movement.Besides the direct drug release via changing diffusion area or pumping out caused by physical deformation, tension or compression can also generate energy to change the physical properties of drug carriers. For example, Pioletti group exploited dissipation properties of hydrogel as an internal heat source to trigger the thermal-sensitive drug release instead of additional external heat source [12]. Self heating was quickly produced after 5 min cyclic mechanical loading. The increased temperature further caused the shrinkage of thermal-responsive nanoparticles entrapped in the hydrogel and subsequent drug release.In addition, mechanical stretch or compression is able to tune the molecular conformation and intermolecular interaction between host molecule and guest molecule, resulting in a force-triggered drug release [13,14]. Based on this phenomenon, Ariga group reported a mechanically controlled monolayer formed by a steroid cyclophane molecule with a cyclic core linked to four steroid moieties via the flexible L-lysine spacer [13]. The applied compression could lead to a cavity-forming conformation of the cyclophane. Therefore, the hydrophobic model drug was easily trapped in this hydrophobic cavity. In contrast, expansion of the monolayer could release the encapsulated drug through the molecular transformation from cavity to planarity. Similarly, they developed a mechanical stimulus-activated β-cyclodextrin (CyD)-crosslinked alginate gel [15]. As applying mild mechanical compression, the model drug ondansetron, the entrapped guest, could be released from the host CyD moieties, due to the change in inclusion ability of CyD. The host–guest interactions dominated by van der Waals interactions and hydrogen bonds in a gel matrix can be more easily broken than covalent bonds, which provide a convenient on-demand administration of medicines operated intentionally by the patient.The research and development of patients’ movement-controlled drug delivery systems hold promise in improving patients’ compliance by providing a self-directed and on-demand treatment. Nonetheless, there are still many remaining challenges for clinical development. For example, the current systems cannot precisely control the release dose of therapeutics. A fundamental study on the dynamic relationships between the phase transitions of materials and the relevant release profile should be closely investigated. Moreover, regarding the different movement extent and ability for different individuals, how to generate a personalized platform and consistently apply the mechanical trigger signal are difficult tasks ahead that need to be addressed. Integration of this device with other wearable modalities to monitor the real-time physiological signals (e.g., electrocardiograph, blood glucose levels or body temperature [16,17]) and motion signals [18,19] might be able to provide feedback to guide the precise, personalized drug delivery. Last but not least, good biocompatibility and biodegradability for materials is extremely important for further translation of the elastic drug delivery system. Tailoring materials mimicking the structures and composites of natural systems offer a promising strategy [5,20].Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.References1 Jiang T, Mo R, Bellotti A, Zhou J, Gu Z. Gel–liposome‐mediated co‐delivery of anticancer membrane‐associated proteins and small‐molecule drugs for enhanced therapeutic efficacy. Adv. Funct. Mater. 24(16), 2295–2304 (2014).Crossref, CAS, Google Scholar2 Sun W, Jiang T, Lu Y, Reiff M, Mo R, Gu Z. Cocoon-like self-degradable dna nanoclew for anticancer drug delivery. J. Am. Chem. Soc. 136(42), 14722–14725 (2014).Crossref, Medline, CAS, Google Scholar3 Yu J, Zhang Y, Ye Y et al. Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery. Proc. Natl Acad. Sci. USA 112(27), 8260–8265 (2015).Crossref, Medline, CAS, Google Scholar4 Mo R, Jiang T, Disanto R, Tai W, Gu Z. ATP-triggered anticancer drug delivery. Nat. Commun. 5, 3364 (2014).Crossref, Medline, Google Scholar5 Lu Y, Sun W, Gu Z. Stimuli-responsive nanomaterials for therapeutic protein delivery. J. Control. Release 194, 1–19 (2014).Crossref, Medline, CAS, Google Scholar6 Wu Z, Wu Y, He W, Lin X, Sun J, He Q. Self‐propelled polymer‐based multilayer nanorockets for transportation and drug release. Angew. Chem. Int. Ed. Engl. 52(27), 7000–7003 (2013).Crossref, Medline, CAS, Google Scholar7 Choi SW, Zhang Y, Xia Y. A temperature‐sensitive drug release system based on phase‐change materials. Angew. Chem. Int. Ed. Engl. 49(43), 7904–7908 (2010).Crossref, Medline, CAS, Google Scholar8 Zhang Y, Yin Q, Yin L, Ma L, Tang L, Cheng J. Chain‐shattering polymeric therapeutics with on‐demand drug‐release capability. Angew. Chem. Int. Ed. Engl. 52(25), 6435–6439 (2013).Crossref, Medline, CAS, Google Scholar9 Lee KY, Peters MC, Anderson KW, Mooney DJ. Controlled growth factor release from synthetic extracellular matrices. Nature 408(6815), 998–1000 (2000).Crossref, Medline, CAS, Google Scholar10 Hyun DC, Moon GD, Park CJ, Kim BS, Xia Y, Jeong U. Strain‐controlled release of molecules from arrayed microcapsules supported on an elastomer substrate. Angew. Chem. Int. Ed. Engl. 50(3), 724–727 (2011).Crossref, Medline, CAS, Google Scholar11 Di J, Yao S, Ye Y et al. Stretch-triggered drug delivery from wearable elastomer films containing therapeutic depots. ACS Nano 9(9), 9407–9415 (2015).Crossref, Medline, CAS, Google Scholar12 Moghadam MN, Kolesov V, Vogel A, Klok H-A, Pioletti DP. Controlled release from a mechanically-stimulated thermosensitive self-heating composite hydrogel. Biomaterials 35(1), 450–455 (2014).Crossref, Medline, CAS, Google Scholar13 Ariga K, Terasaka Y, Sakai D, Tsuji H, Kikuchi J-I. Piezoluminescence based on molecular recognition by dynamic cavity array of steroid cyclophanes at the air-water interface. J. Am. Chem. Soc. 122(32), 7835–7836 (2000).Crossref, CAS, Google Scholar14 Michinobu T, Shinoda S, Nakanishi T et al. Mechanical control of enantioselectivity of amino acid recognition by cholesterol-armed cyclen monolayer at the air-water interface. J. Am. Chem. Soc. 128(45), 14478–14479 (2006).Crossref, Medline, CAS, Google Scholar15 Izawa H, Kawakami K, Sumita M, Tateyama Y, Hill JP, Ariga K. β-Cyclodextrin-crosslinked alginate gel for patient-controlled drug delivery systems: regulation of host–guest interactions with mechanical stimuli. J. Mater. Chem. B 1(16), 2155–2161 (2013).Crossref, CAS, Google Scholar16 Myers AC, Huang H, Zhu Y. Wearable silver nanowire dry electrodes for electrophysiological sensing. RSC Adv. 5(15), 11627–11632 (2015).Crossref, CAS, Google Scholar17 Kim D-H, Lu N, Ma R et al. Epidermal electronics. Science 333(6044), 838–843 (2011).Crossref, Medline, CAS, Google Scholar18 Yao S, Zhu Y. Wearable multifunctional sensors using printed stretchable conductors made of silver nanowires. Nanoscale 6(4), 2345–2352 (2014).Crossref, Medline, CAS, Google Scholar19 Yao S, Zhu Y. Nanomaterial‐enabled stretchable conductors: strategies, materials and devices. Adv. Mater. 27(9), 1480–1511 (2015).Crossref, Medline, CAS, Google Scholar20 Mitragotri S, Anderson DG, Chen X et al. Accelerating the translation of nanomaterials in biomedicine. ACS Nano 9(7), 6644–6654 (2015).Crossref, Medline, CAS, Google ScholarFiguresReferencesRelatedDetailsCited ByExternal stimuli-responsive drug delivery systemsMechanical on-off gates for regulation of drug release in cutaneous or musculoskeletal tissue repairsMaterials Science and Engineering: C, Vol. 115Biomechano-Interactive Materials and Interfaces7 June 2018 | Advanced Materials, Vol. 30, No. 31Nanomaterial‐Enabled Wearable Sensors for Healthcare30 November 2017 | Advanced Healthcare Materials, Vol. 7, No. 1 Vol. 11, No. 4 Follow us on social media for the latest updates Metrics History Published online 19 January 2016 Published in print February 2016 Information© Future Medicine LtdKeywordsdrug deliverymechanical-responsivenanoparticlewearable devicesFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download DA - 2016/// PY - 2016/// DO - 10.2217/nnm.15.197 VL - 11 IS - 4 SP - 323-325 SN - 1748-6963 KW - drug delivery KW - mechanical-responsive KW - nanoparticle KW - wearable devices ER - TY - JOUR TI - Tumor Microenvironment-Mediated Construction and Deconstruction of Extracellular Drug-Delivery Depots AU - Hu, Quanyin AU - Sun, Wujin AU - Lu, Yue AU - Bomba, Hunter N. AU - Ye, Yanqi AU - Jiang, Tianyue AU - Isaacson, Ari J. AU - Gu, Zhen T2 - NANO LETTERS AB - Protein therapy has been considered the most direct and safe approach to treat cancer. Targeting delivery of extracellularly active protein without internalization barriers, such as membrane permeation and endosome escape, is efficient and holds vast promise for anticancer treatment. Herein, we describe a "transformable" core-shell based nanocarrier (designated CS-NG), which can enzymatically assemble into microsized extracellular depots at the tumor site with assistance of hyaluronidase (HAase), an overexpressed enzyme at the tumor microenvironment. Equipped with an acid-degradable modality, the resulting CS-NG can substantially release combinational anticancer drugs-tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) and antiangiogenic cilengitide toward the membrane of cancer cells and endothelial cells at the acidic tumor microenvironment, respectively. Enhanced cytotoxicity on MDA-MB-231 cells and improved antitumor efficacy were observed using CS-NG, which was attributed to the inhibition of cellular internalization and prolonged retention time in vivo. DA - 2016/2// PY - 2016/2// DO - 10.1021/acs.nanolett.5b04343 VL - 16 IS - 2 SP - 1118-1126 SN - 1530-6992 KW - Drug delivery KW - stimuli-responsive KW - tumor microenvironment KW - apoptosis KW - antiangiogenesis ER - TY - JOUR TI - Recent advances of cocktail chemotherapy by combination drug delivery systems AU - Hu, Quanyin AU - Sun, Wujin AU - Wang, Chao AU - Gu, Zhen T2 - ADVANCED DRUG DELIVERY REVIEWS AB - Combination chemotherapy is widely exploited for enhanced cancer treatment in the clinic. However, the traditional cocktail administration of combination regimens often suffers from varying pharmacokinetics among different drugs. The emergence of nanotechnology offers an unparalleled opportunity for developing advanced combination drug delivery strategies with the ability to encapsulate various drugs simultaneously and unify the pharmacokinetics of each drug. This review surveys the most recent advances in combination delivery of multiple small molecule chemotherapeutics using nanocarriers. The mechanisms underlying combination chemotherapy, including the synergistic, additive and potentiation effects, are also discussed with typical examples. We further highlight the sequential and site-specific co-delivery strategies, which provide new guidelines for development of programmable combination drug delivery systems. Clinical outlook and challenges are also discussed in the end. DA - 2016/3/1/ PY - 2016/3/1/ DO - 10.1016/j.addr.2015.10.022 VL - 98 SP - 19-34 SN - 1872-8294 KW - Chemotherapy KW - Combination KW - Cancer KW - Nanocarriers KW - Drug delivery ER - TY - JOUR TI - Rational Design of a Dephosphorylation-Resistant Reporter Enables Single-Cell Measurement of Tyrosine Kinase Activity AU - Turner, Abigail H. AU - Lebhae, Michael S. AU - Proctor, Angela AU - Wang, Qunzhao AU - Lawrence, David S. AU - Allbritton, Nancy L. T2 - ACS CHEMICAL BIOLOGY AB - Although peptide-based reporters of protein tyrosine kinase (PTK) activity have been used to study PTK enzymology in vitro, the application of these reporters to intracellular conditions is compromised by their dephosphorylation, preventing PTK activity measurements. Nonproteinogenic amino acids may be utilized to rationally design selective peptidic ligands by accessing greater chemical and structural diversity than is available using the native amino acids. We describe a peptidic reporter that, upon phosphorylation by the epidermal growth factor receptor (EGFR), is resistant to dephosphorylation both in vitro and in cellulo. The reporter contains a conformationally constrained phosphorylatable moiety (7-(S)-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) in the place of l-tyrosine and is efficiently phosphorylated in A431 epidermoid carcinoma cells. Dephosphorylation of the reporter occurs 3 orders of magnitude more slowly compared with that of the conventional tyrosine-containing reporter. DA - 2016/2// PY - 2016/2// DO - 10.1021/acschembio.5b00667 VL - 11 IS - 2 SP - 355-362 SN - 1554-8937 ER - TY - JOUR TI - Odor Assessment of Automobile Cabin Air With Field Asymmetric Ion Mobility Spectrometry and Photoionization Detection AU - Li, Juan AU - Hodges, Ryan D. AU - Gutierrez-Osuna, Ricardo AU - Luckey, Gail AU - Crowell, Joel AU - Schiffman, Susan S. AU - Nagle, H. Troy T2 - IEEE SENSORS JOURNAL AB - Odor quality in the cabin air of automobiles can be a significant factor in the decision to purchase a vehicle and the overall customer satisfaction with the vehicle over time. A current standard practice uses a human panel to rate the vehicle cabin odors on intensity, irritation, and pleasantness. However, human panels are expensive, time-consuming, and complicated to administer. To address this issue, we present a machine olfaction approach to assess odors inside automobiles. The approach uses a field asymmetric ion mobility spectrometer and a photoionization detector to measure volatile organic compounds, and a multivariate technique to map sensor data into human ratings. Validation on an experimental dataset of odors from ten different vehicles shows a correlation (0.67-0.84) between model predictions and ground truth from a trained human panel. These results support the feasibility of replacing human panel assessments by objective instrumental means for quality control tasks in the production process. DA - 2016/1/15/ PY - 2016/1/15/ DO - 10.1109/jsen.2015.2478853 VL - 16 IS - 2 SP - 409-417 SN - 1558-1748 KW - Air quality KW - machine olfaction KW - odor assessment KW - field asymmetric ion mobility spectrometry KW - photoionization detection KW - multidimensional scaling KW - linear regression ER - TY - JOUR TI - Microneedle-based sensors for medical diagnosis AU - Miller, Philip R. AU - Narayan, Roger J. AU - Polsky, Ronen T2 - JOURNAL OF MATERIALS CHEMISTRY B AB - The field of microneedle sensors is reviewed discussing current trends and future applications. DA - 2016/// PY - 2016/// DO - 10.1039/c5tb02421h VL - 4 IS - 8 SP - 1379-1383 SN - 2050-7518 ER - TY - JOUR TI - Effects of Mesenchymal Stem Cell and Growth Factor Delivery on Cartilage Repair in a Mini-Pig Model AU - Fisher, Matthew B. AU - Belkin, Nicole S. AU - Milby, Andrew H. AU - Henning, Elizabeth A. AU - Soeegaard, Nicole AU - Kim, Minwook AU - Pfeifer, Christian AU - Saxena, Vishal AU - Dodge, George R. AU - Burdick, Jason A. AU - Schaer, Thomas P. AU - Steinberg, David R. AU - Mauck, Robert L. T2 - CARTILAGE AB - Objective We have recently shown that mesenchymal stem cells (MSCs) embedded in a hyaluronic acid (HA) hydrogel and exposed to chondrogenic factors (transforming growth factor–β3 [TGF-β3]) produce a cartilage-like tissue in vitro. The current objective was to determine if these same factors could be combined immediately prior to implantation to induce a superior healing response in vivo relative to the hydrogel alone. Design Trochlear chondral defects were created in Yucatan mini-pigs (6 months old). Treatment groups included an HA hydrogel alone and hydrogels containing allogeneic MSCs, TGF-β3, or both. Six weeks after surgery, micro-computed tomography was used to quantitatively assess defect fill and subchondral bone remodeling. The quality of cartilage repair was assessed using the ICRS-II histological scoring system and immunohistochemistry for type II collagen. Results Treatment with TGF-β3 led to a marked increase in positive staining for collagen type II within defects ( P < 0.05), while delivery of MSCs did not ( P > 0.05). Neither condition had an impact on other histological semiquantitative scores ( P > 0.05), and inclusion of MSCs led to significantly less defect fill ( P < 0.05). For all measurements, no synergistic interaction was found between TGF-β3 and MSC treatment when they were delivered together ( P > 0.05). Conclusions At this early healing time point, treatment with TGF-β3 promoted the formation of collagen type II within the defect, while allogeneic MSCs had little benefit. Combination of TGF-β3 and MSCs at the time of surgery did not produce a synergistic effect. An in vitro precultured construct made of these components may be required to enhance in vivo repair in this model system. DA - 2016/4// PY - 2016/4// DO - 10.1177/1947603515623030 VL - 7 IS - 2 SP - 174-184 SN - 1947-6043 KW - cartilage KW - repair KW - mesenchymal stem cells KW - TGF-3 KW - animal models ER - TY - JOUR TI - Design, Fabrication, and Characterization of a Bifrequency Colinear Array AU - Wang, Zhuochen AU - Li, Sibo AU - Czernuszewicz, Tomasz J. AU - Gallippi, Caterina M. AU - Liu, Ruibin AU - Geng, Xuecang AU - Jiang, Xiaoning T2 - IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL AB - Ultrasound imaging with high resolution and large penetration depth has been increasingly adopted in medical diagnosis, surgery guidance, and treatment assessment. Conventional ultrasound works at a particular frequency, with a [Formula: see text] fractional bandwidth of [Formula: see text], limiting the imaging resolution or depth of field. In this paper, a bifrequency colinear array with resonant frequencies of 8 and 20 MHz was investigated to meet the requirements of resolution and penetration depth for a broad range of ultrasound imaging applications. Specifically, a 32-element bifrequency colinear array was designed and fabricated, followed by element characterization and real-time sectorial scan (S-scan) phantom imaging using a Verasonics system. The bifrequency colinear array was tested in four different modes by switching between low and high frequencies on transmit and receive. The four modes included the following: 1) transmit low, receive low; 2) transmit low, receive high; 3) transmit high, receive low; and 4) transmit high, receive high. After testing, the axial and lateral resolutions of all modes were calculated and compared. The results of this study suggest that bifrequency colinear arrays are potential aids for wideband fundamental imaging and harmonic/subharmonic imaging. DA - 2016/2// PY - 2016/2// DO - 10.1109/tuffc.2015.2506000 VL - 63 IS - 2 SP - 266-274 SN - 1525-8955 KW - Bifrequency ultrasound KW - colinear array KW - composite transducer ER - TY - JOUR TI - ATP-Responsive Drug Delivery Systems AU - Sun, Wujin AU - Gu, Zhen T2 - EXPERT OPINION ON DRUG DELIVERY AB - Advances in material science brought about a wide range of drug delivery systems, from traditional bulk controlled release formulations to modern nanotechnology based carriers, for improved drug ef... DA - 2016/3/3/ PY - 2016/3/3/ DO - 10.1517/17425247.2016.1140147 VL - 13 IS - 3 SP - 311-314 SN - 1744-7593 ER - TY - JOUR TI - A Novel Ultrasound Technique for Non-Invasive Assessment of Cell Differentiation AU - Huang, Wenbin AU - Kim, Jinwook AU - Kim, Kyngrim AU - Bakshi, Saurabh AU - Williams, John AU - Matthieu, Pattie AU - Loboa, Elizabeth AU - Shung, Koping Kirk AU - Zhou, Qifa AU - Jiang, Xiaoning T2 - IEEE SENSORS JOURNAL AB - A novel technique for the characterization of mammalian cells during cell culture was studied using a lead magnesium niobate-lead titanate single crystal piezoelectric resonator. Tests were conducted to observe changes in material properties of human adipose derived stem cells during both proliferation and osteogenic differentiation. The resonator electrical impedance was recorded as a function of the cell acoustic impedance, an indicator of cell viscoelasticity. Observed electrical impedance change (in percentage) from day 1 to day 14 for human adipose derived stem cells undergoing chemical-induced osteogenic differentiation was ~1.7× that observed for proliferating stem cells maintained in complete growth medium. DA - 2016/1// PY - 2016/1// DO - 10.1109/jsen.2015.2477340 VL - 16 IS - 1 SP - 61-68 SN - 1558-1748 KW - Lead magnesium niobate-lead titanate piezoelectric resonator KW - in-situ cell differentiation monitoring KW - electrical impedance measurement KW - osteogenic differentiation ER -