@article{roosa_muhamed_young_nellenbach_daniele_ligler_brown_2021, title={Synthesis of sonicated fibrin nanoparticles that modulate fibrin clot polymerization and enhance angiogenic responses}, volume={204}, ISSN={["1873-4367"]}, DOI={10.1016/j.colsurfb.2021.111805}, abstractNote={Chronic wounds can occur when the healing process is disrupted and the wound remains in a prolonged inflammatory stage that leads to severe tissue damage and poor healing outcomes. Clinically used treatments, such as high density, FDA-approved fibrin sealants, do not provide an optimal environment for native cell proliferation and subsequent tissue regeneration. Therefore, new treatments outside the confines of these conventional fibrin bulk gel therapies are required. We have previously developed flowable, low-density fibrin nanoparticles that, when coupled to keratinocyte growth factor, promote cell migration and epithelial wound closure in vivo. Here, we report a new high throughput method for generating the fibrin nanoparticles using probe sonication, which is less time intensive than the previously reported microfluidic method, and investigate the ability of the sonicated fibrin nanoparticles (SFBN) to promote clot formation and cell migration in vitro. The SFBNs can form a fibrin gel when combined with fibrinogen in the absence of exogenous thrombin, and the polymerization rate and fiber density in these fibrin clots is tunable based on SFBN concentration. Furthermore, fibrin gels made with SFBNs support cell migration in an in vitro angiogenic sprouting assay, which is relevant for wound healing. In this report, we show that SFBNs may be a promising wound healing therapy that can be easily produced and delivered in a flowable formulation.}, journal={COLLOIDS AND SURFACES B-BIOINTERFACES}, author={Roosa, Colleen A. and Muhamed, Ismaeel and Young, Ashlyn T. and Nellenbach, Kimberly and Daniele, Michael A. and Ligler, Frances S. and Brown, Ashley C.}, year={2021}, month={Aug} } @article{schneible_young_daniele_menegatti_2020, title={Chitosan Hydrogels for Synergistic Delivery of Chemotherapeutics to Triple Negative Breast Cancer Cells and Spheroids}, volume={37}, ISBN={1573-904X}, DOI={10.1007/s11095-020-02864-2}, abstractNote={This study aimed to develop a hydrogel system for treating aggressive triple negative breast cancer (TNBC) via kinetically-controlled delivery of the synergistic drug pair doxorubicin (DOX) and gemcitabine (GEM). A 2D assay was adopted to evaluate therapeutic efficacy by determining combination index (CI), and a 3D assay using cancer spheroids was implemented to assess the potential for translation in vivo. The release of DOX and GEM from an acetylated-chitosan (ACS, degree of acetylation χAc = 40 ± 5%) was characterized to identify a combined drug loading that affords release kinetics and dose that are therapeutically synergistic. The selected DOX/GEM-ACS formulation was evaluated in vitro with 2-D and 3-D models of TNBC to determine the combination index (CI) and the tumor volume reduction, respectively. Therapeutically desired release dosages and kinetics of GEM and DOX were achieved. When evaluated with a 2-D model of TNBC, the hydrogel afforded a CI of 0.14, indicating a stronger synergism than concurrent administration of DOX and GEM (CI = 0.23). Finally, the therapeutic hydrogel accomplished a notable volume reduction of the cancer spheroids (up to 30%), whereas the corresponding dosages of free drugs only reduced growth rate. The ACS hydrogel delivery system accomplishes drug release kinetics and molar ratio that affords strong therapeutically synergism. These results, in combination with the choice of ACS as affordable and highly abundant source material, provide a strong pre-clinical demonstration of the potential of the proposed system for complementing surgical resection of aggressive solid tumors.}, number={7}, journal={PHARMACEUTICAL RESEARCH}, author={Schneible, John D. and Young, Ashlyn T. and Daniele, M. A. and Menegatti, S.}, year={2020} } @article{schneible_shi_young_ramesh_he_dowdey_dubnansky_libya_gao_santiso_et al._2020, title={Modified gaphene oxide (GO) particles in peptide hydrogels: a hybrid system enabling scheduled delivery of synergistic combinations of chemotherapeutics}, volume={8}, ISSN={["2050-7518"]}, DOI={10.1039/d0tb00064g}, abstractNote={Composite material enabling the delivery of synergistic combination of doxorubicin and gemcitabine against breast cancer with molar and kinetic precision.}, number={17}, journal={JOURNAL OF MATERIALS CHEMISTRY B}, author={Schneible, John D. and Shi, Kaihang and Young, Ashlyn T. and Ramesh, Srivatsan and He, Nanfei and Dowdey, Clay E. and Dubnansky, Jean Marie and Libya, Radina L. and Gao, Wei and Santiso, Erik and et al.}, year={2020}, month={May}, pages={3852–3868} } @article{yuen_pozdin_young_turner_giles_naciri_trammell_charles_stenger_daniele_2020, title={Perylene-diimide-based n-type semiconductors with enhanced air and temperature stable photoconductor and transistor properties}, volume={174}, ISSN={["1873-3743"]}, DOI={10.1016/j.dyepig.2019.108014}, abstractNote={We report the synthesis and characterization of highly air and temperature stable, solution-processed, n-type organic semiconductors: a perylene-diimide monomer and a perylene-diimide-based pendant polymer. When integrated into a transistor structure, both materials possess pure n-type transport with mobility as high as 10−5 cm2 V−1 s−1 for the polymer. The organic semiconductors exhibit good photoconductor properties, with photocurrent to dark current ratios of up to 103 for the monomer, despite its lower FET mobility. The differences in transistor and photoconductor properties suggest different applications for each material. Both materials can be processed in air, and their transport properties have good air stability, improving with annealing even up to 200 °C in air. It is notable that such air-stable photoconductivity and transport properties have rarely been reported for n-type organic semiconductors before, as most n-type organic semiconductors are not stable in air. Hence, these materials may have potential in a wide range of applications.}, journal={DYES AND PIGMENTS}, author={Yuen, Jonathan D. and Pozdin, Vladimir A. and Young, Ashlyn T. and Turner, Brendan L. and Giles, Ian D. and Naciri, Jawad and Trammell, Scott A. and Charles, Paul T. and Stenger, David A. and Daniele, Michael A.}, year={2020}, month={Mar} } @article{day_schneible_young_pozdin_driessche_gaffney_prodromou_freytes_fourches_daniele_et al._2020, title={Photoinduced reconfiguration to control the protein-binding affinity of azobenzene-cyclized peptides}, volume={8}, ISSN={["2050-7518"]}, DOI={10.1039/d0tb01189d}, abstractNote={Light-controlled switching of cell-binding activity of fluorescently-labeled peptides for on-demand cell labeling.}, number={33}, journal={JOURNAL OF MATERIALS CHEMISTRY B}, author={Day, Kevin and Schneible, John D. and Young, Ashlyn T. and Pozdin, Vladimir A. and Driessche, George and Gaffney, Lewis A. and Prodromou, Raphael and Freytes, Donald O. and Fourches, Denis and Daniele, Michael and et al.}, year={2020}, month={Sep}, pages={7413–7427} } @article{young_white_daniele_2020, title={Rheological Properties of Coordinated Physical Gelation and Chemical Crosslinking in Gelatin Methacryloyl (GelMA) Hydrogels}, volume={20}, ISSN={["1616-5195"]}, DOI={10.1002/mabi.202000183}, abstractNote={Abstract}, number={12}, journal={MACROMOLECULAR BIOSCIENCE}, author={Young, Ashlyn T. and White, Olivia C. and Daniele, Michael A.}, year={2020}, month={Dec} } @article{rivera_pozdin_young_erb_wisniewski_magness_daniele_2019, title={Integrated phosphorescence-based photonic biosensor (iPOB) for monitoring oxygen levels in 3D cell culture systems}, volume={123}, ISSN={["1873-4235"]}, DOI={10.1016/j.bios.2018.07.035}, abstractNote={Physiological processes, such as respiration, circulation, digestion, and many pathologies alter oxygen concentration in the blood and tissue. When designing culture systems to recapitulate the in vivo oxygen environment, it is important to integrate systems for monitoring and controlling oxygen concentration. Herein, we report the design and engineering of a system to remotely monitor and control oxygen concentration inside a device for 3D cell culture. We integrate a photonic oxygen biosensor into the 3D tissue scaffold and regulate oxygen concentration via the control of purging gas flow. The integrated phosphorescence-based oxygen biosensor employs the quenching of palladium-benzoporphyrin by molecular oxygen to transduce the local oxygen concentration in the 3D tissue scaffold. The system is validated by testing the effects of normoxic and hypoxic culture conditions on healthy and tumorigenic breast epithelial cells, MCF-10A cells and BT474 cells, respectively. Under hypoxic conditions, both cell types exhibited upregulation of downstream target genes for the hypoxia marker gene, hypoxia-inducible factor 1α (HIF1A). Lastly, by monitoring the real-time fluctuation of oxygen concentration, we illustrated the formation of hypoxic culture conditions due to limited diffusion of oxygen through 3D tissue scaffolds.}, journal={BIOSENSORS & BIOELECTRONICS}, author={Rivera, Kristina R. and Pozdin, Vladimir A. and Young, Ashlyn T. and Erb, Patrick D. and Wisniewski, Natalie A. and Magness, Scott T. and Daniele, Michael}, year={2019}, month={Jan}, pages={131–140} } @misc{young_rivera_erb_daniele_2019, title={Monitoring of Microphysiological Systems: Integrating Sensors and Real-Time Data Analysis toward Autonomous Decision-Making}, volume={4}, ISSN={["2379-3694"]}, DOI={10.1021/acssensors.8b01549}, abstractNote={Microphysiological systems replicate human organ function and are promising technologies for discovery of translatable biomarkers, pharmaceuticals, and regenerative therapies. Because microphysiological systems require complex microscale anatomical structures and heterogeneous cell populations, a major challenge remains to manufacture and operate these products with reproducible and standardized function. In this Perspective, three stages of microphysiological system monitoring, including process, development, and function, are assessed. The unique features and remaining technical challenges for the required sensors are discussed. Monitoring of microphysiological systems requires nondestructive, continuous biosensors and imaging techniques. With such tools, the extent of cellular and tissue development, as well as function, can be autonomously determined and optimized by correlating physical and chemical sensor outputs with markers of physiological performance. Ultimately, data fusion and analyses across process, development, and function monitors can be implemented to adopt microphysiological systems for broad research and commercial applications.}, number={6}, journal={ACS SENSORS}, author={Young, Ashlyn T. and Rivera, Kristina R. and Erb, Patrick D. and Daniele, Michael A.}, year={2019}, month={Jun}, pages={1454–1464} } @article{su_huang_ma_liang_dinh_chen_shen_allen_qiao_li_et al._2019, title={Platelet-Inspired Nanocells for Targeted Heart Repair After Ischemia/Reperfusion Injury}, volume={29}, ISSN={["1616-3028"]}, DOI={10.1002/adfm.201803567}, abstractNote={Abstract}, number={4}, journal={ADVANCED FUNCTIONAL MATERIALS}, author={Su, Teng and Huang, Ke and Ma, Hong and Liang, Hongxia and Dinh, Phuong-Uyen and Chen, Justin and Shen, Deliang and Allen, Tyler A. and Qiao, Li and Li, Zhenhua and et al.}, year={2019}, month={Jan} } @article{su_huang_daniele_hensley_young_tang_allen_vandergriff_erb_ligler_et al._2018, title={Cardiac Stem Cell Patch Integrated with Microengineered Blood Vessels Promotes Cardiomyocyte Proliferation and Neovascularization after Acute Myocardial Infarction}, volume={10}, ISSN={["1944-8252"]}, DOI={10.1021/acsami.8b13571}, abstractNote={Cardiac stem cell (CSC) therapy has shown preclinical and clinical evidence for ischemic heart repair but is limited by low cellular engraftment and survival after transplantation. Previous versions of the cardiac patch strategy improve stem cell engraftment and encourage repair of cardiac tissue. However, cardiac patches that can enhance cardiomyogenesis and angiogenesis at the injured site remain elusive. Therapies that target cardiomyocyte proliferation and new blood vessel formation hold great potential for the protection against acute myocardial infarction (MI). Here, we report a new strategy for creating a vascularized cardiac patch in a facile and modular fashion by leveraging microfluidic hydrodynamic focusing to construct the biomimetic microvessels (BMVs) that include human umbilical vein endothelial cells (HUVECs) lining the luminal surface and then encapsulating the BMVs in a fibrin gel spiked with human CSCs. We show that the endothelialized BMVs mimicked the natural architecture and function of capillaries and that the resultant vascularized cardiac patch (BMV-CSC patch) exhibited equivalent release of paracrine factors compared to those of coculture of genuine human CSCs and HUVECs after 7 days of in vitro culture. In a rat model of acute MI, the BMV-CSC patch therapy induced profound mitotic activities of cardiomyocytes in the peri-infarct region 4 weeks post-treatment. A significant increase in myocardial capillary density was noted in the infarcted hearts that received BMV-CSC patch treatment compared to the infarcted hearts treated with conventional CSC patches. The striking therapeutic benefits and the fast and facile fabrication of the BMV-CSC patch make it promising for practical applications. Our findings suggest that the BMV-CSC patch strategy may open up new possibilities for the treatment of ischemic heart injury.}, number={39}, journal={ACS APPLIED MATERIALS & INTERFACES}, author={Su, Teng and Huang, Ke and Daniele, Michael A. and Hensley, Michael Taylor and Young, Ashlyn T. and Tang, Junnan and Allen, Tyler A. and Vandergriff, Adam C. and Erb, Patrick D. and Ligler, Frances S. and et al.}, year={2018}, month={Oct}, pages={33088–33096} } @article{young_cornwell_daniele_2018, title={Neuro-nano interfaces: Utilizing nano-coatings and nanoparticles to enable next-generation electrophysiological recording, neural stimulation, and biochemical modulation}, volume={28}, number={12}, journal={Advanced Functional Materials}, author={Young, A. T. and Cornwell, N. and Daniele, M. A.}, year={2018} } @article{stover_fukuyama_young_daniele_oberley_crapo_baeumer_2016, title={Topically applied manganese-porphyrins BMX-001 and BMX-010 display a significant anti-inflammatory response in a mouse model of allergic dermatitis}, volume={308}, ISSN={["1432-069X"]}, DOI={10.1007/s00403-016-1693-0}, abstractNote={In this study, we topically administered two antioxidant compounds, the manganese-porphyrin-derivatives BMX-001 and BMX-010, in a mouse model of allergic dermatitis and compared the efficacy for reduction of itch and inflammation. In vitro effects of BMX-001 and BMX-010 on keratinocytes, bone marrow derived dendritic cells (BMDCs) and T-cells were initially analysed. For assessment of scratching behaviour, BMX-001 and BMX-010 (0.01 and 0.1 %) were topically applied 16 h and/or 1 h before compound 48/80 or toluene-2,4,-diisocyanate (TDI) challenge in a TDI induced mouse dermatitis model. Additionally, assessment of allergic skin inflammation was performed in a similar manner in the TDI model. Post-treatment ear thickness was measured 24 h after TDI challenge and compared to basal values. The mice were sacrificed and the ear auricle was removed for further analysis. In vitro, both BMX substances significantly inhibited cytokine production of keratinocytes as well as of BMDC and T-cell proliferation. Topical treatment with BMX cream resulted in a significant decrease in scratching behaviour in the compound 48/80 model, but not in the TDI model. Mice treated with BMX-001 and BMX-010 showed a moderate dose dependent decrease in ear thickness, and interestingly, the concentration of the cytokines IL-1β and IL-4 in inflamed skin was reduced by 80–90 % by all treatment options. These first results suggest the potential benefit of a BMX-001 and BMX-010 cream for the treatment of allergic-inflammatory skin diseases.}, number={10}, journal={ARCHIVES OF DERMATOLOGICAL RESEARCH}, author={Stover, Kelsey and Fukuyama, Tomoki and Young, Ashlyn T. and Daniele, Michael A. and Oberley, Rebecca and Crapo, James D. and Baeumer, Wolfgang}, year={2016}, month={Dec}, pages={711–721} }