@article{nordberg_huebner_schuchard_mellor_shirwaiker_loboa_spang_2021, title={The evaluation of a multiphasic 3D-bioplotted scaffold seeded with adipose derived stem cells to repair osteochondral defects in a porcine model}, volume={6}, ISSN={["1552-4981"]}, DOI={10.1002/jbm.b.34886}, abstractNote={Abstract}, journal={JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS}, author={Nordberg, Rachel C. and Huebner, Pedro and Schuchard, Karl G. and Mellor, Liliana F. and Shirwaiker, Rohan A. and Loboa, Elizabeth G. and Spang, Jeffery T.}, year={2021}, month={Jun} }
 @article{sheets_ewend_mohiti-asli_tuin_loboa_aboody_hingtgen_2020, title={Developing Implantable Scaffolds to Enhance Neural Stem Cell Therapy for Post-Operative Glioblastoma}, volume={28}, ISSN={["1525-0024"]}, DOI={10.1016/j.ymthe.2020.02.008}, abstractNote={Pre-clinical and clinical studies have shown that engineered tumoricidal neural stem cells (tNSCs) are a promising treatment strategy for the aggressive brain cancer glioblastoma (GBM). Yet, stabilizing human tNSCs within the surgical cavity following GBM resection is a significant challenge. As a critical step toward advancing engineered human NSC therapy for GBM, we used a preclinical variant of the clinically utilized NSC line HB1.F3.CD and mouse models of human GBM resection/recurrence to identify a polymeric scaffold capable of maximizing the transplant, persistence, and tumor kill of NSC therapy for post-surgical GBM. Using kinetic bioluminescence imaging, we found that tNSCs delivered into the mouse surgical cavity wall by direct injection persisted only 3 days. We found that delivery of tNSCs into the cavity on nanofibrous electrospun poly-l-lactic acid scaffolds extended tNSC persistence to 8 days. Modifications to fiber surface coating, diameter, and morphology of the scaffold failed to significantly extend tNSC persistence in the cavity. In contrast, tNSCs delivered into the post-operative cavity on gelatin matrices (GEMs) persisted 8-fold longer as compared to direct injection. GEMs remained permissive to tumor-tropic homing, as tNSCs migrated off the scaffolds and into invasive tumor foci both in vitro and in vivo. To mirror envisioned human brain tumor trials, we engineered tNSCs to express the prodrug/enzyme thymidine kinase (tNSCstk) and transplanted the therapeutic cells in the post-operative cavity of mice bearing resected orthotopic patient-derived GBM xenografts. Following administration of the prodrug ganciclovir, residual tumor volumes in mice receiving GEM/tNSCs were reduced by 10-fold at day 35, and median survival was extended from 31 to 46 days. Taken together, these data begin to define design parameters for effective scaffold/tNSC composites and suggest a new approach to maximizing the efficacy of tNSC therapy in human patient trials. Pre-clinical and clinical studies have shown that engineered tumoricidal neural stem cells (tNSCs) are a promising treatment strategy for the aggressive brain cancer glioblastoma (GBM). Yet, stabilizing human tNSCs within the surgical cavity following GBM resection is a significant challenge. As a critical step toward advancing engineered human NSC therapy for GBM, we used a preclinical variant of the clinically utilized NSC line HB1.F3.CD and mouse models of human GBM resection/recurrence to identify a polymeric scaffold capable of maximizing the transplant, persistence, and tumor kill of NSC therapy for post-surgical GBM. Using kinetic bioluminescence imaging, we found that tNSCs delivered into the mouse surgical cavity wall by direct injection persisted only 3 days. We found that delivery of tNSCs into the cavity on nanofibrous electrospun poly-l-lactic acid scaffolds extended tNSC persistence to 8 days. Modifications to fiber surface coating, diameter, and morphology of the scaffold failed to significantly extend tNSC persistence in the cavity. In contrast, tNSCs delivered into the post-operative cavity on gelatin matrices (GEMs) persisted 8-fold longer as compared to direct injection. GEMs remained permissive to tumor-tropic homing, as tNSCs migrated off the scaffolds and into invasive tumor foci both in vitro and in vivo. To mirror envisioned human brain tumor trials, we engineered tNSCs to express the prodrug/enzyme thymidine kinase (tNSCstk) and transplanted the therapeutic cells in the post-operative cavity of mice bearing resected orthotopic patient-derived GBM xenografts. Following administration of the prodrug ganciclovir, residual tumor volumes in mice receiving GEM/tNSCs were reduced by 10-fold at day 35, and median survival was extended from 31 to 46 days. Taken together, these data begin to define design parameters for effective scaffold/tNSC composites and suggest a new approach to maximizing the efficacy of tNSC therapy in human patient trials.}, number={4}, journal={MOLECULAR THERAPY}, author={Sheets, Kevin T. and Ewend, Matthew G. and Mohiti-Asli, Mahsa and Tuin, Stephen A. and Loboa, Elizabeth G. and Aboody, Karen S. and Hingtgen, Shawn D.}, year={2020}, month={Apr}, pages={1056–1067} }
 @article{mellor_nordberg_huebner_mohiti-asli_taylor_efird_oxford_spang_shirwaiker_loboa_2020, title={Investigation of multiphasic 3D-bioplotted scaffolds for site-specific chondrogenic and osteogenic differentiation of human adipose-derived stem cells for osteochondral tissue engineering applications}, volume={108}, ISSN={["1552-4981"]}, DOI={10.1002/jbm.b.34542}, abstractNote={Abstract}, number={5}, journal={JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS}, author={Mellor, Liliana F. and Nordberg, Rachel C. and Huebner, Pedro and Mohiti-Asli, Mahsa and Taylor, Michael A. and Efird, William and Oxford, Julia T. and Spang, Jeffrey T. and Shirwaiker, Rohan A. and Loboa, Elizabeth G.}, year={2020}, month={Jul}, pages={2017–2030} }
 @article{watson_nordberg_loboa_kullman_2019, title={Evidence for Aryl hydrocarbon Receptor-Mediated Inhibition of Osteoblast Differentiation in Human Mesenchymal Stem Cells}, volume={167}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfy225}, abstractNote={Multipotent mesenchymal stem cells (MSCs) maintain the ability to differentiate into adipogenic, chondrogenic, or osteogenic cell lineages. There is increasing concern that exposure to environmental agents such as aryl hydrocarbon receptor (AhR) ligands, may perturb the osteogenic pathways responsible for normal bone formation. The objective of the current study was to evaluate the potential of the prototypic AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to disrupt osteogenic differentiation of human bone-derived MSCs (hBMSCs) in vitro. Primary hBMSCs from three donors were exposed to 10 nM TCDD and differentiation was interrogated using select histological, biochemical, and transcriptional markers of osteogenesis. Exposure to 10 nM TCDD resulted in an overall consistent attenuation of alkaline phosphatase (ALP) activity and matrix mineralization at terminal stages of differentiation in primary hBMSCs. At the transcriptional level, the transcriptional regulator DLX5 and additional osteogenic markers (ALP, OPN, and IBSP) displayed attenuated expression; conversely, FGF9 and FGF18 were consistently upregulated in each donor. Expression of stem cell potency markers SOX2, NANOG, and SALL4 decreased in the osteogenic controls, whereas expression in TCDD-treated cells resembled that of undifferentiated cells. Coexposure with the AhR antagonist GNF351 blocked TCDD-mediated attenuation of matrix mineralization, and either fully or partially rescued expression of genes associated with osteogenic regulation, extracellular matrix, and/or maintenance of multipotency. Thus, experimental evidence from this study suggests that AhR transactivation likely attenuates osteoblast differentiation in multipotent hBMSCs. This study also underscores the use of primary human MSCs to evaluate osteoinductive or osteotoxic potential of chemical and pharmacologic agents in vitro.}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Watson, AtLee T. D. and Nordberg, Rachel C. and Loboa, Elizabeth G. and Kullman, Seth W.}, year={2019}, month={Jan}, pages={145–156} }
 @article{cai_pourdeyhimi_loboa_2019, title={Industrial-scale fabrication of an osteogenic and antibacterial PLA/silver-loaded calcium phosphate composite with significantly reduced cytotoxicity}, volume={107}, ISSN={["1552-4981"]}, DOI={10.1002/jbm.b.34185}, abstractNote={Abstract}, number={4}, journal={JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS}, author={Cai, Shaobo and Pourdeyhimi, Behnam and Loboa, Elizabeth G.}, year={2019}, month={May}, pages={900–910} }
 @article{bodle_hamouda_cai_williams_bernacki_loboa_2019, title={Primary Cilia Exhibit Mechanosensitivity to Cyclic Tensile Strain and Lineage-Dependent Expression in Adipose-Derived Stem Cells}, volume={9}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-019-43351-y}, abstractNote={Abstract}, journal={SCIENTIFIC REPORTS}, author={Bodle, Josephine and Hamouda, Mehdi S. and Cai, Shaobo and Williams, Ramey B. and Bernacki, Susan H. and Loboa, Elizabeth G.}, year={2019}, month={May} }
 @article{nordberg_bodle_loboa_2018, title={Mechanical Stimulation of Adipose-Derived Stem Cells for Functional Tissue Engineering of the Musculoskeletal System via Cyclic Hydrostatic Pressure, Simulated Microgravity, and Cyclic Tensile Strain}, volume={1773}, ISBN={["978-1-4939-7797-0"]}, ISSN={["1940-6029"]}, DOI={10.1007/978-1-4939-7799-4_18}, abstractNote={It is critical that human adipose stem cell (hASC) tissue-engineering therapies possess appropriate mechanical properties in order to restore function of the load bearing tissues of the musculoskeletal system. In an effort to elucidate the hASC response to mechanical stimulation and develop mechanically robust tissue engineered constructs, recent research has utilized a variety of mechanical loading paradigms including cyclic tensile strain, cyclic hydrostatic pressure, and mechanical unloading in simulated microgravity. This chapter describes methods for applying these mechanical stimuli to hASC to direct differentiation for functional tissue engineering of the musculoskeletal system.}, journal={ADIPOSE-DERIVED STEM CELLS: METHODS AND PROTOCOLS, 2ND EDITION}, author={Nordberg, Rachel C. and Bodle, Josie C. and Loboa, Elizabeth G.}, year={2018}, pages={215–230} }
 @article{mohiti-asli_risselada_jacob_pourdeyhimi_loboa_2017, title={Creation and Evaluation of New Porcine Model for Investigation of Treatments of Surgical Site Infection}, volume={23}, ISSN={["1937-3392"]}, DOI={10.1089/ten.tec.2017.0024}, abstractNote={Surgical site infection (SSI) is the most common cause of surgical failure, increasing the risks of postoperative mortality and morbidity. Recently, it has been reported that the use of antimicrobial dressings at the incision site help with prevention of SSI. Despite the increased body of research on the development of different types of antimicrobial dressings for this application, to our knowledge, nobody has reported a reliable large animal model to evaluate the efficacy of developed materials in a preclinical SSI model. In this study, we developed a porcine full-thickness incision model to investigate SSI caused by methicillin-resistant Staphylococcus aureus (MRSA), the leading cause of SSI in the United States. Using this model, we then evaluated the efficacy of our newly developed silver releasing nanofibrous dressings for preventing and inhibiting MRSA infection. Our results confirmed the ease and practicality of a new porcine model as an in vivo platform for evaluation of biomaterials for SSI. Using this model, we found that our silver releasing scaffolds significantly reduced bacterial growth in wounds inoculated with MRSA relative to nontreated controls and to wounds treated with the gold standard, silver sulfadiazine, without causing inflammation at the wound site. Findings from this study confirm the potential of our silver-releasing nanofibrous scaffolds for treatment/prevention of SSI, and introduce a new porcine model for in vivo evaluation of additional SSI treatment approaches.}, number={11}, journal={TISSUE ENGINEERING PART C-METHODS}, author={Mohiti-Asli, Mahsa and Risselada, Marije and Jacob, Megan and Pourdeyhimi, Behnam and Loboa, Elizabeth G.}, year={2017}, month={Nov}, pages={795–803} }
 @article{mehendale_mellor_taylor_loboa_shirwaiker_2017, title={Effects of 3D-bioplotted polycaprolactone scaffold geometry on human adipose-derived stem cell viability and proliferation}, volume={23}, ISSN={["1758-7670"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85019575149&partnerID=MN8TOARS}, DOI={10.1108/rpj-03-2016-0035}, abstractNote={
Purpose
This study aims to investigate the effect of three-dimensional (3D)- bioplotted polycaprolactone (PCL) scaffold geometry on the biological and mechanical characteristics of human adipose-derived stem cell (hASC) seeded constructs.
}, number={3}, journal={RAPID PROTOTYPING JOURNAL}, author={Mehendale, Saahil V. and Mellor, Liliana F. and Taylor, Michael A. and Loboa, Elizabeth G. and Shirwaiker, Rohan A.}, year={2017}, pages={534–542} }
 @article{nordberg_zhang_griffith_frank_starly_loboa_2017, title={Electrical Cell-Substrate Impedance Spectroscopy Can Monitor Age-Grouped Human Adipose Stem Cell Variability During Osteogenic Differentiation}, volume={6}, ISSN={["2157-6580"]}, DOI={10.5966/sctm.2015-0404}, abstractNote={Abstract}, number={2}, journal={STEM CELLS TRANSLATIONAL MEDICINE}, author={Nordberg, Rachel C. and Zhang, Jianlei and Griffith, Emily H. and Frank, Matthew W. and Starly, Binil and Loboa, Elizabeth G.}, year={2017}, month={Feb}, pages={502–511} }
 @article{mohiti-asli_saha_murphy_gracz_pourdeyhimi_atala_loboa_2017, title={Ibuprofen loaded PLA nanofibrous scaffolds increase proliferation of human skin cells in vitro and promote healing of full thickness incision wounds in vivo}, volume={105}, ISSN={["1552-4981"]}, DOI={10.1002/jbm.b.33520}, abstractNote={Abstract}, number={2}, journal={JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS}, author={Mohiti-Asli, M. and Saha, S. and Murphy, S. V. and Gracz, H. and Pourdeyhimi, B. and Atala, A. and Loboa, E. G.}, year={2017}, month={Feb}, pages={327–339} }
 @article{huang_kim_kim_bakshi_williams_matthieu_loboa_shung_zhou_jiang_2016, title={A Novel Ultrasound Technique for Non-Invasive Assessment of Cell Differentiation}, volume={16}, ISSN={["1558-1748"]}, DOI={10.1109/jsen.2015.2477340}, abstractNote={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.}, number={1}, journal={IEEE SENSORS JOURNAL}, author={Huang, Wenbin and Kim, Jinwook and Kim, Kyngrim and Bakshi, Saurabh and Williams, John and Matthieu, Pattie and Loboa, Elizabeth and Shung, Koping Kirk and Zhou, Qifa and Jiang, Xiaoning}, year={2016}, month={Jan}, pages={61–68} }
 @article{wall_dyment_bodle_volmer_loboa_cederlund_fox_banes_2016, title={Cell signaling in tenocytes: Response to load and ligands in health and disease}, volume={920}, journal={Metabolic influences on risk for tendon disorders}, author={Wall, M. E. and Dyment, N. A. and Bodle, J. and Volmer, J. and Loboa, E. and Cederlund, A. and Fox, A. M. and Banes, A. J.}, year={2016}, pages={79–95} }
 @misc{bodle_loboa_2016, title={Concise Review: Primary Cilia: Control Centers for Stem Cell Lineage Specification and Potential Targets for Cell-Based Therapies}, volume={34}, ISSN={["1549-4918"]}, DOI={10.1002/stem.2341}, abstractNote={Abstract}, number={6}, journal={STEM CELLS}, author={Bodle, Josephine C. and Loboa, Elizabeth G.}, year={2016}, month={Jun}, pages={1445–1454} }
 @article{tuin_pourdeyhimi_loboa_2016, title={Creating tissues from textiles: scalable nonwoven manufacturing techniques for fabrication of tissue engineering scaffolds}, volume={11}, ISSN={["1748-605X"]}, DOI={10.1088/1748-6041/11/1/015017}, abstractNote={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.}, number={1}, journal={BIOMEDICAL MATERIALS}, author={Tuin, S. A. and Pourdeyhimi, B. and Loboa, E. G.}, year={2016}, month={Feb} }
 @article{bago_pegna_okolie_mohiti-asli_loboa_hingtgen_2016, title={Electrospun nanofibrous scaffolds increase the efficacy of stem cell-mediated therapy of surgically resected glioblastoma}, volume={90}, ISSN={["1878-5905"]}, DOI={10.1016/j.biomaterials.2016.03.008}, abstractNote={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.}, journal={BIOMATERIALS}, author={Bago, Juli R. and Pegna, Guillaume J. and Okolie, Onyi and Mohiti-Asli, Mahsa and Loboa, Elizabeth G. and Hingtgen, Shawn D.}, year={2016}, month={Jun}, pages={116–125} }
 @article{mohiti-asli_molina_diteepeng_pourdeyhimi_loboa_2016, title={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}, volume={22}, ISSN={["1937-335X"]}, DOI={10.1089/ten.tea.2016.0063}, abstractNote={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.}, number={21-22}, journal={TISSUE ENGINEERING PART A}, author={Mohiti-Asli, Mahsa and Molina, Casey and Diteepeng, Thamonwan and Pourdeyhimi, Behnam and Loboa, Elizabeth G.}, year={2016}, month={Nov}, pages={1258–1263} }
 @article{tuin_pourdeyhimi_loboa_2016, title={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}, volume={36}, ISSN={["1878-7568"]}, DOI={10.1016/j.actbio.2016.03.025}, abstractNote={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.}, journal={ACTA BIOMATERIALIA}, author={Tuin, Stephen A. and Pourdeyhimi, Behnam and Loboa, Elizabeth G.}, year={2016}, month={May}, pages={220–230} }
 @article{johnson_macpherson_smith_block_keyton_2016, title={Facilitating Teamwork in Adolescent and Young Adult Oncology}, volume={12}, ISSN={["1935-469X"]}, DOI={10.1200/jop.2016.013870}, abstractNote={ 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. }, number={11}, journal={JOURNAL OF ONCOLOGY PRACTICE}, author={Johnson, Rebecca H. and Macpherson, Catherine Fiona and Smith, Ashley W. and Block, Rebecca G. and Keyton, Joann}, year={2016}, month={Nov}, pages={1067-+} }
 @article{steward_cole_ligler_loboa_2016, title={Mechanical and Vascular Cues Synergistically Enhance Osteogenesis in Human Mesenchymal Stem Cells}, volume={22}, ISSN={["1937-335X"]}, DOI={10.1089/ten.tea.2015.0533}, abstractNote={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.}, number={15-16}, journal={TISSUE ENGINEERING PART A}, author={Steward, Andrew J. and Cole, Jacqueline H. and Ligler, Frances S. and Loboa, Elizabeth G.}, year={2016}, month={Aug}, pages={997–1005} }
 @article{neupane_jin_mellor_loboa_ligler_wang_2015, title={Continuous-wave stimulated emission depletion microscope for imaging actin cytoskeleton in fixed and live cells}, volume={15}, number={9}, journal={Sensors (Basel, Switzerland)}, author={Neupane, B. and Jin, T. and Mellor, L. F. and Loboa, E. G. and Ligler, F. S. and Wang, G. F.}, year={2015}, pages={24178–24190} }
 @article{mellor_mohiti-asli_williams_kannan_dent_guilak_loboa_2015, title={Extracellular Calcium Modulates Chondrogenic and Osteogenic Differentiation of Human Adipose-Derived Stem Cells: A Novel Approach for Osteochondral Tissue Engineering Using a Single Stem Cell Source}, volume={21}, ISSN={["1937-335X"]}, DOI={10.1089/ten.tea.2014.0572}, abstractNote={We have previously shown that elevating extracellular calcium from a concentration of 1.8 to 8 mM accelerates and increases human adipose-derived stem cell (hASC) osteogenic differentiation and cell-mediated calcium accretion, even in the absence of any other soluble osteogenic factors in the culture medium. However, the effects of elevated calcium on hASC chondrogenic differentiation have not been reported. The goal of this study was to determine the effects of varied calcium concentrations on chondrogenic differentiation of hASC. We hypothesized that exposure to elevated extracellular calcium (8 mM concentration) in a chondrogenic differentiation medium (CDM) would inhibit chondrogenesis of hASC when compared to basal calcium (1.8 mM concentration) controls. We further hypothesized that a full osteochondral construct could be engineered by controlling local release of calcium to induce site-specific chondrogenesis and osteogenesis using only hASC as the cell source. Human ASC was cultured as micromass pellets in CDM containing transforming growth factor-β1 and bone morphogenetic protein 6 for 28 days at extracellular calcium concentrations of either 1.8 mM (basal) or 8 mM (elevated). Our findings indicated that elevated calcium induced osteogenesis and inhibited chondrogenesis in hASC. Based on these findings, stacked polylactic acid nanofibrous scaffolds containing either 0% or 20% tricalcium phosphate (TCP) nanoparticles were electrospun and tested for site-specific chondrogenesis and osteogenesis. Histological assays confirmed that human ASC differentiated locally to generate calcified tissue in layers containing 20% TCP, and cartilage in the layers with no TCP when cultured in CDM. This is the first study to report the effects of elevated calcium on chondrogenic differentiation of hASC, and to develop osteochondral nanofibrous scaffolds using a single cell source and controlled calcium release to induce site-specific differentiation. This approach holds great promise for osteochondral tissue engineering using a single cell source (hASC) and single scaffold.}, number={17-18}, journal={TISSUE ENGINEERING PART A}, author={Mellor, Liliana F. and Mohiti-Asli, Mahsa and Williams, John and Kannan, Arthi and Dent, Morgan R. and Guilak, Farshid and Loboa, Elizabeth G.}, year={2015}, month={Sep}, pages={2323–2333} }
 @misc{wolf_dearth_sonnenberg_loboa_badylak_2015, title={Naturally derived and synthetic scaffolds for skeletal muscle reconstruction}, volume={84}, ISSN={["1872-8294"]}, DOI={10.1016/j.addr.2014.08.011}, abstractNote={Skeletal muscle tissue has an inherent capacity for regeneration following injury. However, severe trauma, such as volumetric muscle loss, overwhelms these natural muscle repair mechanisms prompting the search for a tissue engineering/regenerative medicine approach to promote functional skeletal muscle restoration. A desirable approach involves a bioscaffold that simultaneously acts as an inductive microenvironment and as a cell/drug delivery vehicle to encourage muscle ingrowth. Both biologically active, naturally derived materials (such as extracellular matrix) and carefully engineered synthetic polymers have been developed to provide such a muscle regenerative environment. Next generation naturally derived/synthetic “hybrid materials” would combine the advantageous properties of these materials to create an optimal platform for cell/drug delivery and possess inherent bioactive properties. Advances in scaffolds using muscle tissue engineering are reviewed herein.}, journal={ADVANCED DRUG DELIVERY REVIEWS}, author={Wolf, Matthew T. and Dearth, Christopher L. and Sonnenberg, Sonya B. and Loboa, Elizabeth G. and Badylak, Stephen F.}, year={2015}, month={Apr}, pages={208–221} }
 @article{nordberg_loboa_2015, title={Our Fat Future: Translating Adipose Stem Cell Therapy}, volume={4}, ISSN={["2157-6580"]}, DOI={10.5966/sctm.2015-0071}, abstractNote={Abstract}, number={9}, journal={STEM CELLS TRANSLATIONAL MEDICINE}, author={Nordberg, Rachel C. and Loboa, Elizabeth G.}, year={2015}, month={Sep}, pages={974–979} }
 @article{haslauer_avery_pourdeyhimi_loboa_2015, title={Translating textiles to tissue engineering: Creation and evaluation of microporous, biocompatible, degradable scaffolds using industry relevant manufacturing approaches and human adipose derived stem cells}, volume={103}, ISSN={["1552-4981"]}, DOI={10.1002/jbm.b.33291}, abstractNote={Abstract}, number={5}, journal={JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS}, author={Haslauer, Carla M. and Avery, Matthew R. and Pourdeyhimi, Behnam and Loboa, Elizabeth G.}, year={2015}, month={Jul}, pages={1050–1058} }
 @article{bodle_teeter_hluck_hardin_bernacki_loboa_2014, title={Age-Related Effects on the Potency of Human Adipose-Derived Stem Cells: Creation and Evaluation of Superlots and Implications for Musculoskeletal Tissue Engineering Applications}, volume={20}, ISSN={1937-3384 1937-3392}, url={http://dx.doi.org/10.1089/ten.TEC.2013.0683}, DOI={10.1089/ten.tec.2013.0683}, abstractNote={Human adipose-derived stem cells (hASC) are now a prevalent source of adult stem cells for studies in tissue engineering and regenerative medicine. However, researchers utilizing hASC in their investigations often encounter high levels of donor-to-donor variability in hASC differentiation potential. Because of this, conducting studies with this primary cell type can require extensive resources to generate statistically significant data. We present a method to generate pooled donor cell populations, termed "superlots," containing cell populations derived from four to five age-clustered donors. The goal of generating these superlots was to 1) increase experimental throughput, 2) to utilize assay resources more efficiently, and 3) to begin to establish global hASC differentiation behaviors that may be associated with donor age. With our superlot approach, we have validated that pooled donor cell populations exhibit proliferative activity representing the combined behavior of each individual donor cell line. Further, the superlots also exhibit differentiation levels roughly approximating the average combined differentiation levels of each individual donor cell line. We established that high donor-to-donor variability exists between the pre-, peri-, and postmenopausal age groupings and that proliferation and differentiation characteristics can vary widely, independent of age. Interestingly, we did observe that cell lines derived from postmenopausal donors demonstrated a relatively high proclivity for osteogenic differentiation and a relatively lowered proclivity for adipogenic differentiation as compared with cells derived from pre- and perimenopausal donors. In general, superlots effectively represented the average differentiation behavior of each of their contributing cell populations and could provide a powerful tool for increasing experimental throughput to more efficiently utilize resources when studying hASC differentiation.}, number={12}, journal={Tissue Engineering Part C: Methods}, publisher={Mary Ann Liebert Inc}, author={Bodle, Josephine C. and Teeter, Stephanie D. and Hluck, Brandon H. and Hardin, Joseph W. and Bernacki, Susan H. and Loboa, Elizabeth G.}, year={2014}, month={Dec}, pages={972–983} }
 @article{charoenpanich_wall_tucker_andrews_lalush_dirschl_loboa_2014, title={Cyclic Tensile Strain Enhances Osteogenesis and Angiogenesis in Mesenchymal Stem Cells from Osteoporotic Donors}, volume={20}, ISSN={["1937-335X"]}, DOI={10.1089/ten.tea.2013.0006}, abstractNote={We have shown that the uniaxial cyclic tensile strain of magnitude 10% promotes and enhances osteogenesis of human mesenchymal stem cells (hMSC) and human adipose-derived stem cells (hASC) from normal, nonosteoporotic donors. In the present study, MSC from osteoporotic donors were analyzed for changes in mRNA expression in response to 10% uniaxial tensile strain to identify potential mechanisms underlying the use of this mechanical loading paradigm for prevention and treatment of osteoporosis. Human MSC isolated from three female, postmenopausal osteoporotic donors were analyzed for their responses to mechanical loading using microarray analysis of over 47,000 gene probes. Human MSC were seeded in three-dimensional collagen type I constructs to mimic the organic extracellular matrix of bone and 10% uniaxial cyclic tensile strain was applied to promote osteogenesis. Seventy-nine genes were shown to be regulated within hMSC from osteoporotic donors in response to 10% cyclic tensile strain. Upregulation of six genes were further confirmed with real-time RT-PCR: jun D proto-oncogene (JUND) and plasminogen activator, urokinase receptor (PLAUR), two genes identified as potential key molecules from network analysis; phosphoinositide-3-kinase, catalytic, delta polypeptide (PIK3CD) and wingless-type MMTV integration site family, member 5B (WNT5B), two genes with known importance in bone biology; and, PDZ and LIM domain 4 (PDLIM4) and vascular endothelial growth factor A (VEGFA), two genes that we have previously shown are significantly regulated in hASC in response to this mechanical stimulus. Function analysis indicated that 10% cyclic tensile strain induced expression of genes associated with cell movement, cell proliferation, and tissue development, including development in musculoskeletal and cardiovascular systems. Our results demonstrate that hMSC from aged, osteoporotic donors are capable of enhanced osteogenic differentiation in response to 10% cyclic tensile strain with significant increases in the expression of genes associated with enhanced cell proliferation, musculoskeletal development, and angiogenesis. Surprisingly, cyclic tensile strain of magnitude 10% not only enhanced osteogenesis in hMSC from osteoporotic donors, but also enhanced expression of angiogenic factors. Better understanding and methodologies to promote osteogenesis in hMSC from elderly, osteoporotic donors may greatly facilitate achieving long-term success in bone regeneration and functional bone tissue engineering for this ever-growing patient population.}, number={1-2}, journal={TISSUE ENGINEERING PART A}, author={Charoenpanich, Adisri and Wall, Michelle E. and Tucker, Charles J. and Andrews, Danica M. K. and Lalush, David S. and Dirschl, Douglas R. and Loboa, Elizabeth G.}, year={2014}, month={Jan}, pages={67–78} }
 @misc{tuin_pourdeyhimi_loboa_2014, title={Interconnected, microporous hollow fibers for tissue engineering: Commercially relevant, industry standard scale-up manufacturing}, volume={102}, ISSN={["1552-4965"]}, DOI={10.1002/jbm.a.35002}, abstractNote={Abstract}, number={9}, journal={JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A}, author={Tuin, Stephen A. and Pourdeyhimi, Behnam and Loboa, Elizabeth G.}, year={2014}, month={Sep}, pages={3311–3323} }
 @article{mohiti-asli_pourdeyhimi_loboa_2014, title={Novel, silver-ion-releasing nanofibrous scaffolds exhibit excellent antibacterial efficacy without the use of silver nanoparticles}, volume={10}, ISSN={["1878-7568"]}, DOI={10.1016/j.actbio.2013.12.024}, abstractNote={Nanofibers, with their morphological similarities to the extracellular matrix of skin, hold great potential for skin tissue engineering. Over the last decade, silver nanoparticles have been extensively investigated in wound-healing applications for their ability to provide antimicrobial benefits to nanofibrous scaffolds. However, the use of silver nanoparticles has raised concerns as these particles can penetrate into the stratum corneum of skin, or even diffuse into the cellular plasma membrane. We present and evaluate a new silver ion release polymeric coating that we have found can be applied to biocompatible, biodegradable poly(l-lactic acid) nanofibrous scaffolds. Using this compound, custom antimicrobial silver-ion-releasing nanofibers were created. The presence of a uniform, continuous silver coating on the nanofibrous scaffolds was verified by XPS analysis. The antimicrobial efficacy of the antimicrobial scaffolds against Staphylococcus aureus and Escherichia coli bacteria was determined via industry-standard AATCC protocols. Cytotoxicity analyses of the antimicrobial scaffolds toward human epidermal keratinocytes and human dermal fibroblasts were performed via quantitative analyses of cell viability and proliferation. Our results indicated that the custom antimicrobial scaffolds exhibited excellent antimicrobial properties while also maintaining human skin cell viability and proliferation for silver ion concentrations below 62.5μgml(-1) within the coating solution. This is the first study to show that silver ions can be effectively delivered with nanofibrous scaffolds without the use of silver nanoparticles.}, number={5}, journal={ACTA BIOMATERIALIA}, author={Mohiti-Asli, Mahsa and Pourdeyhimi, Behnam and Loboa, Elizabeth G.}, year={2014}, month={May}, pages={2096–2104} }
 @article{mathieu_bodle_loboa_2014, title={Primary cilium mechanotransduction of tensile strain in 3D culture: Finite element analyses of strain amplification caused by tensile strain applied to a primary cilium embedded in a collagen matrix}, volume={47}, ISSN={["1873-2380"]}, DOI={10.1016/j.jbiomech.2014.04.004}, abstractNote={Human adipose-derived stem cells (hASC) exhibit multilineage differentiation potential with lineage specification that is dictated by both the chemical and mechanical stimuli to which they are exposed. We have previously shown that 10% cyclic tensile strain increases hASC osteogenesis and cell-mediated calcium accretion. We have also recently shown that primary cilia are present on hASC and that chemically-induced lineage specification of hASC concurrently results in length and conformation changes of the primary cilia. Further, we have observed cilia length changes in hASC cultured within a collagen I gel in response to 10% cyclic tensile strain. We therefore hypothesize that primary cilia may play a key mechanotransduction role for hASC exposed to tensile strain. The goal of this study was to use finite element analysis (FEA) to determine strains occurring within the ciliary membrane in response to 10% tensile strain applied parallel, or perpendicular, to cilia orientation. To elucidate the mechanical environment experienced by the cilium, several lengths were modeled and evaluated based on cilia lengths measured on hASC grown under varied culture conditions. Principal tensile strains in both hASC and ciliary membranes were calculated using FEA, and the magnitude and location of maximum principal tensile strain determined. We found that maximum principal tensile strain was concentrated at the base of the cilium. In the linear elastic model, applying strain perpendicular to the cilium resulted in maximum strains within the ciliary membrane from 150% to 200%, while applying strain parallel to the cilium resulted in much higher strains, approximately 400%. In the hyperelastic model, applying strain perpendicular to the cilium resulted in maximum strains within the ciliary membrane around 30%, while applying strain parallel to the cilium resulted in much higher strains ranging from 50% to 70%. Interestingly, FEA results indicated that primary cilium length was not directly related to ciliary membrane strain. Rather, it appears that cilium orientation may be more important than cilium length in determining sensitivity of hASC to tensile strain. This is the first study to model the effects of tensile strain on the primary cilium and provides newfound insight into the potential role of the primary cilium as a mechanosensor, particularly in tensile strain and potentially a multitude of other mechanical stimuli beyond fluid shear.}, number={9}, journal={JOURNAL OF BIOMECHANICS}, author={Mathieu, Pattie S. and Bodle, Josephine C. and Loboa, Elizabeth G.}, year={2014}, month={Jun}, pages={2211–2217} }
 @article{mohiti-asli_pourdeyhimi_loboa_2014, title={Skin Tissue Engineering for the Infected Wound Site: Biodegradable PLA Nanofibers and a Novel Approach for Silver Ion Release Evaluated in a 3D Coculture System of Keratinocytes and Staphylococcus aureus}, volume={20}, ISSN={["1937-3392"]}, DOI={10.1089/ten.tec.2013.0458}, abstractNote={Wound infection presents a challenging and growing problem. With the increased prevalence and growth of multidrug-resistant bacteria, there is a mounting need to reduce and eliminate wound infections using methodologies that limit the ability of bacteria to evolve into further drug-resistant strains. A well-known strategy for combating bacterial infection and preventing wound sepsis is through the delivery of silver ions to the wound site. High surface area silver nanoparticles (AgNPs) allowing extensive silver ion release have therefore been explored in different wound dressings and/or skin substitutes. However, it has been recently shown that AgNPs can penetrate into the stratum corneum of skin or diffuse into the cellular plasma membrane, and may interfere with a variety of cellular mechanisms. The goal of this study was to introduce and evaluate a new type of high surface area metallic silver in the form of highly porous silver microparticles (AgMPs). Polylactic acid (PLA) nanofibers were successfully loaded with either highly porous AgMPs or AgNPs and the antimicrobial efficacy and cytotoxicity of the two silver-based wound dressings were assessed and compared. To better mimic the physiological environment in vivo where both human cells and bacteria are present, a novel coculture system combining human epidermal keratinocytes and Staphylococcus aureus bacteria was designed to simultaneously evaluate human skin cell cytotoxicity with antimicrobial efficacy in a three-dimensional environment. We found that highly porous AgMPs could be successfully incorporated in nanofibrous wound dressings, and exhibited comparable antimicrobial efficacy and cytotoxicity to AgNPs. Further, PLA nanofibers containing highly porous AgMPs exhibited steady silver ion release, at a greater rate of release, than nanofibers containing AgNPs. The replacement of AgNPs with the newly introduced AgMPs overcomes concerns regarding the use of nanoparticles and holds great promise as skin substitutes or wound dressings for infected wound sites.}, number={10}, journal={TISSUE ENGINEERING PART C-METHODS}, author={Mohiti-Asli, Mahsa and Pourdeyhimi, Behnam and Loboa, Elizabeth G.}, year={2014}, month={Oct}, pages={790–797} }
 @article{lim_mccullen_piedrahita_loboa_olby_2013, title={Alternating Current Electric Fields of Varying Frequencies: Effects on Proliferation and Differentiation of Porcine Neural Progenitor Cells}, volume={15}, ISSN={2152-4971 2152-4998}, url={http://dx.doi.org/10.1089/cell.2013.0001}, DOI={10.1089/cell.2013.0001}, abstractNote={Application of sinusoidal electric fields (EFs) has been observed to affect cellular processes, including alignment, proliferation, and differentiation. In the present study, we applied low-frequency alternating current (AC) EFs to porcine neural progenitor cells (pNPCs) and investigated the effects on cell patterning, proliferation, and differentiation. pNPCs were grown directly on interdigitated electrodes (IDEs) localizing the EFs to a region accessible visually for fluorescence-based assays. Cultures of pNPCs were exposed to EFs (1 V/cm) of 1 Hz, 10 Hz, and 50 Hz for 3, 7, and 14 days and compared to control cultures. Immunocytochemistry was performed to evaluate the expression of neural markers. pNPCs grew uniformly with no evidence of alignment to the EFs and no change in cell numbers when compared with controls. Nestin expression was shown in all groups at 3 and 7 days, but not at 14 days. NG2 expression was low in all groups. Co-expression of glial fibrillary acidic protein (GFAP) and TUJ1 was significantly higher in the cultures exposed to 10- and 50-Hz EFs than the controls. In summary, sinusoidal AC EFs via IDEs did not alter the alignment and proliferation of pNPCs, but higher frequency stimulation appeared to delay differentiation into mature astrocytes.}, number={5}, journal={Cellular Reprogramming}, publisher={Mary Ann Liebert Inc}, author={Lim, Ji-Hey and McCullen, Seth D. and Piedrahita, Jorge A. and Loboa, Elizabeth G. and Olby, Natasha J.}, year={2013}, month={Oct}, pages={405–412} }
 @article{saldutti_beyer_breslin_brown_chapin_campion_enright_faustman_foster_hartung_et al._2013, title={In vitro testicular toxicity models: Opportunities for advancement via biomedical engineering techniques}, volume={30}, number={3}, journal={Altex-alternatives to Animal Experimentation}, author={Saldutti, L. P. and Beyer, B. K. and Breslin, W. and Brown, T. R. and Chapin, R. E. and Campion, S. and Enright, B. and Faustman, E. and Foster, P. M. D. and Hartung, T. and et al.}, year={2013}, pages={353–377} }
 @article{bodle_rubenstein_phillips_bernacki_qi_banes_loboa_2013, title={Primary Cilia: The Chemical Antenna Regulating Human Adipose-Derived Stem Cell Osteogenesis}, volume={8}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0062554}, abstractNote={Adipose-derived stem cells (ASC) are multipotent stem cells that show great potential as a cell source for osteogenic tissue replacements and it is critical to understand the underlying mechanisms of lineage specification. Here we explore the role of primary cilia in human ASC (hASC) differentiation. This study focuses on the chemosensitivity of the primary cilium and the action of its associated proteins: polycystin-1 (PC1), polycystin-2 (PC2) and intraflagellar transport protein-88 (IFT88), in hASC osteogenesis. To elucidate cilia-mediated mechanisms of hASC differentiation, siRNA knockdown of PC1, PC2 and IFT88 was performed to disrupt cilia-associated protein function. Immunostaining of the primary cilium structure indicated phenotypic-dependent changes in cilia morphology. hASC cultured in osteogenic differentiation media yielded cilia of a more elongated conformation than those cultured in expansion media, indicating cilia-sensitivity to the chemical environment and a relationship between the cilium structure and phenotypic determination. Abrogation of PC1, PC2 and IFT88 effected changes in both hASC proliferation and differentiation activity, as measured through proliferative activity, expression of osteogenic gene markers, calcium accretion and endogenous alkaline phosphatase activity. Results indicated that IFT88 may be an early mediator of the hASC differentiation process with its knockdown increasing hASC proliferation and decreasing Runx2, alkaline phosphatase and BMP-2 mRNA expression. PC1 and PC2 knockdown affected later osteogenic gene and end-product expression. PC1 knockdown resulted in downregulation of alkaline phosphatase and osteocalcin gene expression, diminished calcium accretion and reduced alkaline phosphatase enzymatic activity. Taken together our results indicate that the structure of the primary cilium is intimately associated with the process of hASC osteogenic differentiation and that its associated proteins are critical players in this process. Elucidating the dynamic role of the primary cilium and its associated proteins will help advance the application of hASC in generating autologous tissue engineered therapies in critical defect bone injuries.}, number={5}, journal={PLOS ONE}, author={Bodle, Josephine C. and Rubenstein, Candace D. and Phillips, Michelle E. and Bernacki, Susan H. and Qi, Jie and Banes, Albert J. and Loboa, Elizabeth G.}, year={2013}, month={May} }
 @article{pedersen_loboa_labean_2013, title={Sensitization of Transforming Growth Factor-beta Signaling by Multiple Peptides Patterned on DNA Nanostructures}, volume={14}, ISSN={["1526-4602"]}, DOI={10.1021/bm4011722}, abstractNote={We report sensitization of a cellular signaling pathway by addition of functionalized DNA nanostructures. Signaling by transforming growth factor β (TGFβ) has been shown to be dependent on receptor clustering. By patterning a DNA nanostructure with closely spaced peptides that bind to TGFβ receptor, we observe increased sensitivity of NMuMG cells to TGFβ ligand. This is evidenced by translocation of secondary messenger proteins to the nucleus and stimulation of an inducible luciferase reporter at lower concentrations of TGFβ ligand. We believe this represents an important initial step toward realization of DNA as a self-assembling and biologically compatible material for use in tissue engineering and drug delivery.}, number={12}, journal={BIOMACROMOLECULES}, author={Pedersen, Ronnie O. and Loboa, Elizabeth G. and LaBean, Thomas H.}, year={2013}, month={Dec}, pages={4157–4160} }
 @article{puetzer_williams_gillies_bernacki_loboa_2013, title={The Effects of Cyclic Hydrostatic Pressure on Chondrogenesis and Viability of Human Adipose- and Bone Marrow-Derived Mesenchymal Stem Cells in Three-Dimensional Agarose Constructs}, volume={19}, ISSN={["1937-3341"]}, DOI={10.1089/ten.tea.2012.0015}, abstractNote={This study investigates the effects of cyclic hydrostatic pressure (CHP) on chondrogenic differentiation of human adipose-derived stem cells (hASCs) in three-dimensional (3-D) agarose constructs maintained in a complete growth medium without soluble chondrogenic inducing factors. hASCs were seeded in 2% agarose hydrogels and exposed to 7.5 MPa CHP for 4 h per day at a frequency of 1 Hz for up to 21 days. On days 0, 7, 14, and 21, the expression levels of collagen II, Sox9, aggrecan, and cartilage oligomeric matrix protein (COMP) were examined by real-time reverse transcriptase-polymerase chain reaction analysis. Gene expression analysis found collagen II mRNA expression in only the CHP-loaded construct at day 14 and at no other time during the study. CHP-loaded hASCs exhibited upregulated mRNA expression of Sox9, aggrecan, and COMP at day 7 relative to unloaded controls, suggesting that CHP initiated chondrogenic differentiation of hASCs in a manner similar to human bone marrow-derived mesenchymal stem cells (hMSC). By day 14, however, loaded hASC constructs exhibited significantly lower mRNA expression of the chondrogenic markers than unloaded controls. Additionally, by day 21, the samples exhibited little measurable mRNA expression at all, suggesting a decreased viability. Histological analysis validated the lack of mRNA expression at day 21 for both the loaded and unloaded control samples with a visible decrease in the cell number and change in morphology. A comparative study with hASCs and hMSCs further examined long-term cell viability in 3-D agarose constructs of both cell types. Decreased cell metabolic activity was observed throughout the 21-day experimental period in both the CHP-loaded and control constructs of both hMSCs and hASCs, suggesting a decrease in cell metabolic activity, alluding to a decrease in cell viability. This suggests that a 2% agarose hydrogel may not optimally support hASC or hMSC viability in a complete growth medium in the absence of soluble chondrogenic inducing factors over long culture durations. This is the first study to examine the ability of mechanical stimuli alone, in the absence of chondrogenic factors transforming growth factor beta (TGF-β)3, TGF-β1 and/or bone morphogenetic protein 6 (BMP6) to induce hASC chondrogenic differentiation. The findings of this study suggest that CHP initiates hASC chondrogenic differentiation, even in the absence of soluble chondrogenic inductive factors, confirming the importance of considering both mechanical stimuli and appropriate 3-D culture for cartilage tissue engineering using hASCs.}, number={1-2}, journal={TISSUE ENGINEERING PART A}, author={Puetzer, Jennifer and Williams, John and Gillies, Allison and Bernacki, Susan and Loboa, Elizabeth G.}, year={2013}, month={Jan}, pages={299–306} }
 @article{mathieu_loboa_2012, title={Cytoskeletal and Focal Adhesion Influences on Mesenchymal Stem Cell Shape, Mechanical Properties, and Differentiation Down Osteogenic, Adipogenic, and Chondrogenic Pathways}, volume={18}, ISSN={["1937-3376"]}, DOI={10.1089/ten.teb.2012.0014}, abstractNote={Mesenchymal stem cells (MSCs) hold great potential for regenerative medicine and tissue-engineering applications. They have multipotent differentiation capabilities and have been shown to differentiate down various lineages, including osteoblasts, adipocytes, chondrocytes, myocytes, and possibly neurons. The majority of approaches to control the MSC fate have been via the use of chemical factors in the form of growth factors within the culture medium. More recently, it has been understood that mechanical forces play a significant role in regulating MSC fate. We and others have shown that mechanical stimuli can control MSC lineage specification. The cytoskeleton is known to play a large role in mechanotransduction, and a growing number of studies are showing that it can also contribute to MSC differentiation. This review analyzes the significant contribution of actin and integrin distribution, and the smaller role of microtubules, in regulating MSC fate. Osteogenic differentiation is more prevalent in MSCs with a stiff, spread actin cytoskeleton and greater numbers of focal adhesions. Both adipogenic differentiation and chondrogenic differentiation are encouraged when MSCs have a spherical morphology associated with a dispersed actin cytoskeleton with few focal adhesions. Different mechanical stimuli can be implemented to alter these cytoskeletal patterns and encourage MSC differentiation to the desired lineage.}, number={6}, journal={TISSUE ENGINEERING PART B-REVIEWS}, author={Mathieu, Pattie S. and Loboa, Elizabeth G.}, year={2012}, month={Dec}, pages={436–444} }
 @article{asli_pourdeyhimi_loboa_2012, title={Release Profiles of Tricalcium Phosphate Nanoparticles from Poly(L-lactic acid) Electrospun Scaffolds with Single Component, Core-Sheath, or Porous Fiber Morphologies: Effects on hASC Viability and Osteogenic Differentiation}, volume={12}, ISSN={["1616-5195"]}, DOI={10.1002/mabi.201100470}, abstractNote={Abstract}, number={7}, journal={MACROMOLECULAR BIOSCIENCE}, author={Asli, Mahsa Mohiti and Pourdeyhimi, Behnam and Loboa, Elizabeth G.}, year={2012}, month={Jul}, pages={893–900} }
 @article{samberg_loboa_oldenburg_monteiro-riviere_2012, title={Silver nanoparticles do not influence stem cell differentiation but cause minimal toxicity}, volume={7}, ISSN={["1748-6963"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84868143959&partnerID=MN8TOARS}, DOI={10.2217/nnm.12.18}, abstractNote={ Aims: To evaluate the toxicity and cellular uptake of both undifferentiated and differentiated human adipose-derived stem cells (hASCs) exposed to silver nanoparticles (Ag-NPs), and to assess their effect on hASC differentiation. Materials & methods: hASC were exposed to 10- or 20-nm Ag-NPs at concentrations of 0.1, 1.0, 10.0, 50.0 and 100.0 µg/ml either before or after differentiation down the adipogenic or osteogenic pathways. Results: Exposure of hASC to either 10- or 20-nm Ag-NPs resulted in no significant cytotoxicity to hASC, and minimal dose-dependent toxicity to adipogenic and osteogenic cells at 10 µg/ml. Each of the hASC, adipogenic and osteogenic cells showed cellular uptake of both 10- and 20-nm Ag-NPs, without causing significant ultrastructural alterations. Exposure to 10- or 20-nm Ag-NPs did not influence the differentiation of the cells, and at antimicrobial concentrations of Ag-NPs resulted in a minimal decrease in viability. Conclusion: The biocompatibility of Ag-NPs with both undifferentiated and differentiated hASC establishes their suitability for incorporation into tissue-engineered graft scaffolds, for the prevention of bacterial contamination upon implantation. }, number={8}, journal={NANOMEDICINE}, author={Samberg, Meghan E. and Loboa, Elizabeth G. and Oldenburg, Steven J. and Monteiro-Riviere, Nancy A.}, year={2012}, month={Aug}, pages={1197–1209} }
 @article{bodle_hanson_loboa_2011, title={Adipose-Derived Stem Cells in Functional Bone Tissue Engineering: Lessons from Bone Mechanobiology}, volume={17}, ISSN={["1937-3376"]}, DOI={10.1089/ten.teb.2010.0738}, abstractNote={This review aims to highlight the current and significant work in the use of adipose-derived stem cells (ASC) in functional bone tissue engineering framed through the bone mechanobiology perspective. Over a century of work on the principles of bone mechanosensitivity is now being applied to our understanding of bone development. We are just beginning to harness that potential using stem cells in bone tissue engineering. ASC are the primary focus of this review due to their abundance and relative ease of accessibility for autologous procedures. This article outlines the current knowledge base in bone mechanobiology to investigate how the knowledge from this area has been applied to the various stem cell-based approaches to engineering bone tissue constructs. Specific emphasis is placed on the use of human ASC for this application.}, number={3}, journal={TISSUE ENGINEERING PART B-REVIEWS}, author={Bodle, Josephine C. and Hanson, Ariel D. and Loboa, Elizabeth G.}, year={2011}, month={Jun}, pages={195–211} }
 @article{haslauer_moghe_osborne_gupta_loboa_2011, title={Collagen-PCL Sheath-Core Bicomponent Electrospun Scaffolds Increase Osteogenic Differentiation and Calcium Accretion of Human Adipose-Derived Stem Cells}, volume={22}, ISSN={["1568-5624"]}, DOI={10.1163/092050610x521595}, abstractNote={Human adipose-derived stem cells (hASCs) are an abundant cell source capable of osteogenic differentiation, and have been investigated as an autologous stem cell source for bone tissue engineering applications. The objective of this study was to determine if the addition of a type-I collagen sheath to the surface of poly(ε-caprolactone) (PCL) nanofibers would enhance viability, proliferation and osteogenesis of hASCs. This is the first study to examine the differentiation behavior of hASCs on collagen–PCL sheath–core bicomponent nanofiber scaffolds developed using a co-axial electrospinning technique. The use of a sheath–core configuration ensured a uniform coating of collagen on the PCL nanofibers. PCL nanofiber scaffolds prepared using a conventional electrospinning technique served as controls. hASCs were seeded at a density of 20 000 cells/cm2 on 1 cm2 electrospun nanofiber (pure PCL or collagen–PCL sheath–core) sheets. Confocal microscopy and hASC proliferation data confirmed the presence of viable cells after 2 weeks in culture on all scaffolds. Greater cell spreading occurred on bicomponent collagen–PCL scaffolds at earlier time points. hASCs were osteogenically differentiated by addition of soluble osteogenic inductive factors. Calcium quantification indicated cell-mediated calcium accretion was approx. 5-times higher on bicomponent collagen–PCL sheath–core scaffolds compared to PCL controls, indicating collagen–PCL bicomponent scaffolds promoted greater hASC osteogenesis after two weeks of culture in osteogenic medium. This is the first study to examine the effects of collagen–PCL sheath–core composite nanofibers on hASC viability, proliferation and osteogenesis. The sheath–core composite fibers significantly increased calcium accretion of hASCs, indicating that collagen–PCL sheath–core bicomponent structures have potential for bone tissue engineering applications using hASCs.}, number={13}, journal={JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION}, author={Haslauer, Carla Maria and Moghe, Ajit K. and Osborne, Jason A. and Gupta, Bhupender S. and Loboa, Elizabeth G.}, year={2011}, pages={1695–1712} }
 @article{mahajan_alexander_seabolt_catrambone_mcclung_odle_pfeiler_loboa_stahl_2011, title={Dietary Calcium Restriction Affects Mesenchymal Stem Cell Activity and Bone Development in Neonatal Pigs}, volume={141}, ISSN={["1541-6100"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79951993863&partnerID=MN8TOARS}, DOI={10.3945/jn.110.131193}, abstractNote={The effects of dietary calcium (Ca) deficiency on skeletal integrity are well characterized in growing and mature mammals; however, less is known about Ca nutrition during the neonatal period. In this study, we examined the effects of neonatal Ca nutrition on bone integrity, endocrine hormones, and mesenchymal stem cell (MSC) activity. Neonatal pigs (24 ± 6 h of age) received either a Ca-adequate (1.2 g/100 g) or an ~40% Ca-deficient diet for 18 d. Ca deficiency reduced (P < 0.05) bone flexural strength and bone mineral density without major differences in plasma indicators of Ca status. There were no meaningful differences in plasma Ca, phosphate (PO(4)), parathyroid hormone, or 1,25-dihydroxycholecalciferol due to Ca nutrition throughout the study. Calcium deficiency also reduced (P < 0.05) the in vivo proliferation of MSC by ~50%. In vitro studies utilizing homologous sera demonstrated that MSC activity was affected (P < 0.05) by both the Ca status of the pig and the sera as well as by their interaction. The results indicate that neonatal Ca nutrition is crucial for bone integrity and suggest that early-life Ca restriction may have long-term effects on bone integrity via programming of MSC.}, number={3}, journal={JOURNAL OF NUTRITION}, author={Mahajan, Avanika and Alexander, Lindsey S. and Seabolt, Brynn S. and Catrambone, Daniel E. and McClung, James P. and Odle, Jack and Pfeiler, T. Wayne and Loboa, Elizabeth G. and Stahl, Chad H.}, year={2011}, month={Mar}, pages={373–379} }
 @article{mccullen_gittard_miller_pourdeyhimi_narayan_loboa_2011, title={Laser Ablation Imparts Controlled Micro-Scale Pores in Electrospun Scaffolds for Tissue Engineering Applications}, volume={39}, ISSN={0090-6964 1573-9686}, url={http://dx.doi.org/10.1007/S10439-011-0378-2}, DOI={10.1007/s10439-011-0378-2}, abstractNote={Electrospun scaffolds have been used extensively for tissue engineering applications due to the simple processing scheme and versatility. However, many additional benefits can be imparted to these materials via post-processing techniques. Specifically the addition of structured pores on the micro-scale can offer a method to enable patterned cell adhesion, enhanced diffusional properties, and/or guide vascular infiltration upon implantation in vivo. In this study, we laser ablated electrospun poly(L: -lactic acid) (PLA) scaffolds and assessed the ablation process and cellular interaction by examining human adipose-derived stem cell (hASC) viability and proliferation on laser micro-machined scaffolds. Laser ablated pores of 150, 300, and 600 μm diameter were micro-machined through electrospun PLA scaffolds. Laser ablation parameters were varied and it was determined that the aperture and z-travel direction of the laser linearly correlated with the ablated pore diameter. To assess cytocompatibility of the micro-machined scaffolds, hASCs were seeded on each scaffold and cell viability was assessed on day 7. Human ASCs were able to adhere around the micro-machined features. DNA content was quantified on all scaffolds and it was determined that hASCs were able to proliferate on all scaffolds. The process of laser ablation could impart many beneficial features to electrospun scaffolds by increasing mass transport and mimicking micro-scale features and assisting in patterning of cells around micro-machined features.}, number={12}, journal={Annals of Biomedical Engineering}, publisher={Springer Science and Business Media LLC}, author={McCullen, S. D. and Gittard, S. D. and Miller, P. R. and Pourdeyhimi, Behnam and Narayan, R. J. and Loboa, E. G.}, year={2011}, month={Aug}, pages={3021–3030} }
 @article{charoenpanich_wall_tucker_andrews_lalush_loboa_2011, title={Microarray Analysis of Human Adipose-Derived Stem Cells in Three-Dimensional Collagen Culture: Osteogenesis Inhibits Bone Morphogenic Protein and Wnt Signaling Pathways, and Cyclic Tensile Strain Causes Upregulation of Proinflammatory Cytokine Regulators and Angiogenic Factors}, volume={17}, ISSN={["1937-335X"]}, DOI={10.1089/ten.tea.2011.0107}, abstractNote={Human adipose-derived stem cells (hASC) have shown great potential for bone tissue engineering. However, the molecular mechanisms underlying this potential are not yet known, in particular the separate and combined effects of three-dimensional (3D) culture and mechanical loading on hASC osteogenesis. Mechanical stimuli play a pivotal role in bone formation, remodeling, and fracture repair. To further understand hASC osteogenic differentiation and response to mechanical stimuli, gene expression profiles of proliferating or osteogenically induced hASC in 3D collagen I culture in the presence and absence of 10% uniaxial cyclic tensile strain were examined using microarray analysis. About 847 genes and 95 canonical pathways were affected during osteogenesis of hASC in 3D culture. Pathway analysis indicated the potential roles of Wnt/β-catenin signaling, bone morphogenic protein (BMP) signaling, platelet-derived growth factor (PDGF) signaling, and insulin-like growth factor 1 (IGF-1) signaling in hASC during osteogenic differentiation. Application of 10% uniaxial cyclic tensile strain suggested synergistic effects of strain with osteogenic differentiation media on hASC osteogenesis as indicated by significantly increased calcium accretion of hASC. There was no significant further alteration in the four major pathways (Wnt/β-catenin, BMP, PDGF, and IGF-1). However, 184 transcripts were affected by 10% cyclic tensile strain. Function and network analysis of these transcripts suggested that 10% cyclic tensile strain may play a role during hASC osteogenic differentiation by upregulating two crucial factors in bone regeneration: (1) proinflammatory cytokine regulators interleukin 1 receptor antagonist and suppressor of cytokine signaling 3; (2) known angiogenic inductors fibroblast growth factor 2, matrix metalloproteinase 2, and vascular endothelial growth factor A. This is the first study to investigate the effects of both 3D culture and mechanical load on hASC osteogenic differentiation. A complete microarray analysis investigating both the separate effect of soluble osteogenic inductive factors and the combined effects of chemical and mechanical stimulation was performed on hASC undergoing osteogenic differentiation. We have identified specific genes and pathways associated with mechanical response and osteogenic potential of hASC, thus providing significant information toward improved understanding of our use of hASC for functional bone tissue engineering applications.}, number={21-22}, journal={TISSUE ENGINEERING PART A}, author={Charoenpanich, Adisri and Wall, Michelle E. and Tucker, Charles J. and Andrews, Danica M. K. and Lalush, David S. and Loboa, Elizabeth G.}, year={2011}, month={Nov}, pages={2615–2627} }
 @article{mccullen_mcquilling_grossfeld_lubischer_clarke_loboa_2010, title={Application of Low-Frequency Alternating Current Electric Fields Via Interdigitated Electrodes: Effects on Cellular Viability, Cytoplasmic Calcium, and Osteogenic Differentiation of Human Adipose-Derived Stem Cells}, volume={16}, ISSN={["1937-3392"]}, url={https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20367249/?tool=EBI}, DOI={10.1089/ten.tec.2009.0751}, abstractNote={Electric stimulation is known to initiate signaling pathways and provides a technique to enhance osteogenic differentiation of stem and/or progenitor cells. There are a variety of in vitro stimulation devices to apply electric fields to such cells. Herein, we describe and highlight the use of interdigitated electrodes to characterize signaling pathways and the effect of electric fields on the proliferation and osteogenic differentiation of human adipose-derived stem cells (hASCs). The advantage of the interdigitated electrode configuration is that cells can be easily imaged during short-term (acute) stimulation, and this identical configuration can be utilized for long-term (chronic) studies. Acute exposure of hASCs to alternating current (AC) sinusoidal electric fields of 1 Hz induced a dose-dependent increase in cytoplasmic calcium in response to electric field magnitude, as observed by fluorescence microscopy. hASCs that were chronically exposed to AC electric field treatment of 1 V/cm (4 h/day for 14 days, cultured in the osteogenic differentiation medium containing dexamethasone, ascorbic acid, and β-glycerol phosphate) displayed a significant increase in mineral deposition relative to unstimulated controls. This is the first study to evaluate the effects of sinusoidal AC electric fields on hASCs and to demonstrate that acute and chronic electric field exposure can significantly increase intracellular calcium signaling and the deposition of accreted calcium under osteogenic stimulation, respectively.}, number={6}, journal={TISSUE ENGINEERING PART C-METHODS}, author={McCullen, Seth D. and McQuilling, John P. and Grossfeld, Robert M. and Lubischer, Jane L. and Clarke, Laura I. and Loboa, Elizabeth G.}, year={2010}, month={Dec}, pages={1377–1386} }
 @article{mccullen_zhan_onorato_bernacki_loboa_2010, title={Effect of Varied Ionic Calcium on Human Adipose-Derived Stem Cell Mineralization}, volume={16}, ISSN={["1937-3341"]}, DOI={10.1089/ten.tea.2009.0691}, abstractNote={Human adipose-derived stem cells (hASCs) are a relatively abundant and accessible stem cell source with multilineage differentiation capability and have great potential for bone tissue engineering applications. The success of bone tissue engineering is intimately linked with the production of a mineralized matrix that mimics the natural mineral present within native bone. In this study, we examined the effects of ionic calcium levels of 1.8 (normal concentration in cell culture medium), 8, and 16 mM on hASCs seeded in both two-dimensional monolayer and three-dimensional electrospun scaffolds and cultured in either complete growth medium (CGM) or osteogenic differentiation medium (ODM). The impact of calcium supplementation on hASC viability, proliferation, and mineral deposition was determined. hASCs remained viable for all experimental treatments. hASC proliferation increased with the addition of 8 mM Ca(2+) CGM, but decreased for the 16 mM Ca(2+) CGM treatment. Materials deposited by hASCs were analyzed using four techniques: (1) histological staining with Alizarin Red S, (2) calcium quantification, (3) Fourier transform infrared spectroscopy, and (4) wide-angle X-ray diffraction. Mineral deposition was significantly enhanced under both growth and osteogenic medium conditions by increasing extracellular Ca(2+). The greatest mineral deposition occurred in the ODM 8 mM Ca(2+) treatment group. Fourier transform infrared spectroscopy analysis indicated that elevated calcium concentrations of 8 mM Ca(2+) significantly increased both PO(4) amount and PO(4) to protein ratio for ODM. X-ray diffraction indicated that mineral produced with elevated Ca(2+) in both CGM and ODM had a crystalline structure characteristic of hydroxyapatite. Ionic calcium should be considered a potent regulator in hASC mineralization and could serve as a potential treatment for inducing prompt ossification of hASC-seeded scaffolds for bone tissue engineering prior to implantation.}, number={6}, journal={TISSUE ENGINEERING PART A}, author={McCullen, Seth D. and Zhan, Jackie and Onorato, Maureen L. and Bernacki, Susan H. and Loboa, Elizabeth G.}, year={2010}, month={Jun}, pages={1971–1981} }
 @article{mccullen_haslauer_loboa_2010, title={Fiber-reinforced scaffolds for tissue engineering and regenerative medicine: use of traditional textile substrates to nanofibrous arrays}, volume={20}, ISSN={["1364-5501"]}, DOI={10.1039/c0jm01443e}, abstractNote={Regenerative medicine is a promising therapeutic strategy for the repair and replacement of diseased or injured tissues and organs. The main approach for this method is the fabrication and use of scaffold materials to act as a surrogate framework and promote cell-seeded populations to develop into a mature and functional tissue. Scaffold based strategies for regenerative medicine have focused on the use of three dimensional, biocompatible, biodegradable structures to provide an adequate template for ex vivo cell expansion and maturation, native tissue ingrowth, and restoration of the original tissue qualities with respect to the tissue's biochemical constituents, morphology, form, and function. To achieve this, the use of fiber and/or textile substrates have been used as either the underlying skeleton or reinforcing agents with or without three-dimensional matrices to provide scaffolds that exhibit suitable mechanical properties, high cellularity, and better mimicry of the natural tissue organization and its resulting composition. In this article we discuss (1) fiber reinforcement in natural tissues, (2) literature examples of fiber reinforcement in engineered tissues, and (3) strategies and next steps to expand this field. Fiber reinforcement continues to be an ideal strategy for tissue scaffolds that require mechanical reinforcement while providing high surface volume in a compliant form.}, number={40}, journal={JOURNAL OF MATERIALS CHEMISTRY}, author={McCullen, Seth D. and Haslauer, Carla M. and Loboa, Elizabeth G.}, year={2010}, pages={8776–8788} }
 @article{moody_haslauer_kirk_kannan_loboa_mccarty_2010, title={In Situ Monitoring of Adipogenesis with Human-Adipose-Derived Stem Cells Using Surface-Enhanced Raman Spectroscopy}, volume={64}, ISSN={["1943-3530"]}, DOI={10.1366/000370210793335106}, abstractNote={ Methods capable of nondestructively collecting high-quality, real-time chemical information from living human stem cells are of increasing importance given the escalating relevance of stem cells in therapeutic and regenerative medicines. Raman spectroscopy is one such technique that can nondestructively collect real-time chemical information. Living cells uptake gold nanoparticles and transport these particles through an endosomal pathway. Once inside the endosome, nanoparticles aggregate into clusters that give rise to large spectroscopic enhancements that can be used to elucidate local chemical environments through the use of surface-enhanced Raman spectroscopy. This report uses 40-nm colloidal gold nanoparticles to create volumes of surface-enhanced Raman scattering (SERS) within living human-adipose-derived adult stem cells enabling molecular information to be monitored. We exploit this method to spectroscopically observe chemical changes that occur during the adipogenic differentiation of human-adipose-derived stem cells over a period of 22 days. It is shown that intracellular SERS is able to detect the production of lipids as little as one day after the onset of adipogenesis and that a complex interplay between lipids, proteins, and chemical messengers can be observed shortly thereafter. After 22 days of differentiation, the cells show visible and spectroscopic indications of completed adipogenesis yet still share spectral features common to the progenitor stem cells. }, number={11}, journal={APPLIED SPECTROSCOPY}, author={Moody, Benjamin and Haslauer, Carla M. and Kirk, Elizabeth and Kannan, Arthi and Loboa, Elizabeth G. and McCarty, Gregory S.}, year={2010}, month={Nov}, pages={1227–1233} }
 @article{mccullen_miller_gittard_gorga_pourdeyhimi_narayan_loboa_2010, title={In situ collagen polymerization of layered cell-seeded electrospun scaffolds for bone tissue engineering applications}, volume={16}, DOI={10.1089/ten.tea.2009.0753}, number={5}, journal={Tissue Engineering. Part C, Methods}, author={McCullen, S. D. and Miller, P. R. and Gittard, S. D. and Gorga, Russell and POURDEYHIMI, BEHNAM and Narayan, R. J. and Loboa, E. G.}, year={2010}, pages={1095–1105} }
 @article{mccullen_haslauer_loboa_2010, title={Musculoskeletal mechanobiology: Interpretation by external force and engineered substratum}, volume={43}, ISSN={["1873-2380"]}, DOI={10.1016/j.jbiomech.2009.09.017}, abstractNote={Mechanobiology aims to discover how the mechanical environment affects the biological activity of cells and how cells’ ability to sense these mechanical cues is converted into elicited cellular responses. Musculoskeletal mechanobiology is of particular interest given the high mechanical loads that musculoskeletal tissues experience on a daily basis. How do cells within these mechanically active tissues interpret external loads imposed on their extracellular environment, and, how are cell–substrate interactions converted into biochemical signals? This review outlines many of the main mechanotransduction mechanisms known to date, and describes recent literature examining effects of both external forces and cell–substrate interactions on musculoskeletal cells. Whether via application of external forces and/or cell–substrate interactions, our understanding and regulation of musculoskeletal mechanobiology can benefit by expanding upon traditional models, and shedding new light through novel investigative approaches. Current and future work in this field is focused on identifying specific forces, stresses, and strains at the cellular and tissue level through both experimental and computational approaches, and analyzing the role of specific proteins through fluorescence-based investigations and knockdown models.}, number={1}, journal={JOURNAL OF BIOMECHANICS}, author={McCullen, Seth D. and Haslauer, Carla M. and Loboa, Elizabeth G.}, year={2010}, month={Jan}, pages={119–127} }
 @article{marvel_okrasinski_bernacki_loboa_dayton_2010, title={The Development and Validation of a LIPUS System With Preliminary Observations of Ultrasonic Effects on Human Adult Stem Cells}, volume={57}, ISSN={["1525-8955"]}, DOI={10.1109/tuffc.2010.1645}, abstractNote={To study the potential effects of low-intensity pulsed ultrasound (LIPUS) on cell response in vitro, the ability to alter LIPUS parameters is required. However, commercial LIPUS systems have very little control over parameter selection. In this study, a custom LIPUS system was designed and validated by exploring the effects of using different pulse repetition frequency (PRF) parameters on human adipose derived adult stem cells (hASCs) and bone marrow derived mesenchymal stem cells (hMSCs), two common stem cell sources for creating bone constructs in vitro. Changing the PRF was found to affect cellular response to LIPUS stimulation for both cell types. Proliferation of LIPUS-stimulated cells was found to decrease for hASCs by d 7 for all three groups compared with unstimulated control cells (P = 0.008, 0.011, 0.014 for 1 Hz, 100 Hz and 1 kHz PRF, respectively) and for hMSCs by d 14 (donor 1: P = 0.0005, 0.0002, 0.0003; donor 2: P = 0.0003, 0.0002, 0.0001; for PRFs of 1 Hz, 100 Hz, and 1 kHz, respectively). Additionally, LIPUS was shown to strongly accelerate osteogenic differentiation of hASCs based on amount of calcium accretion normalized by total DNA (P = 0.003, 0.001, 0.003, and 0.032 between control/100 Hz, control/1 kHz, 1 Hz/1 kHz, and 100 Hz/1 kHz pulse repetition frequencies, respectively). These findings promote the study of using LIPUS to induce osteogenic differentiation and further encourage the exploration of LIPUS parameter optimization. The custom LIPUS system was successfully designed to allow extreme parameter variation, specifically PRF, and encourages further studies.}, number={9}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Marvel, Skylar and Okrasinski, Stan and Bernacki, Susan H. and Loboa, Elizabeth and Dayton, Paul A.}, year={2010}, month={Sep}, pages={1977–1984} }
 @article{reed_han_andrady_caballero_jack_collins_saba_loboa_cairns_van aalst_2009, title={Composite Tissue Engineering on Polycaprolactone Nanofiber Scaffolds}, volume={62}, ISSN={0148-7043}, url={http://dx.doi.org/10.1097/sap.0b013e31818e48bf}, DOI={10.1097/sap.0b013e31818e48bf}, abstractNote={Tissue engineering has largely focused on single tissue-type reconstruction (such as bone); however, the basic unit of healing in any clinically relevant scenario is a compound tissue type (such as bone, periosteum, and skin). Nanofibers are submicron fibrils that mimic the extracellular matrix, promoting cellular adhesion, proliferation, and migration. Stem cell manipulation on nanofiber scaffolds holds significant promise for future tissue engineering. This work represents our initial efforts to create the building blocks for composite tissue reflecting the basic unit of healing. Polycaprolactone (PCL) nanofibers were electrospun using standard techniques. Human foreskin fibroblasts, murine keratinocytes, and periosteal cells (4-mm punch biopsy) harvested from children undergoing palate repair were grown in appropriate media on PCL nanofibers. Human fat-derived mesenchymal stem cells were osteoinduced on PCL nanofibers. Cell growth was assessed with fluorescent viability staining; cocultured cells were differentiated using antibodies to fibroblast- and keratinocyte-specific surface markers. Osteoinduction was assessed with Alizarin red S. PCL nanofiber scaffolds supported robust growth of fibroblasts, keratinocytes, and periosteal cells. Cocultured periosteal cells (with fibroblasts) and keratinocytes showed improved longevity of the keratinocytes, though growth of these cell types was randomly distributed throughout the scaffold. Robust osteoinduction was noted on PCL nanofibers. Composite tissue engineering using PCL nanofiber scaffolds is possible, though the major obstacles to the trilaminar construct are maintaining an appropriate interface between the tissue types and neovascularization of the composite structure.}, number={5}, journal={Annals of Plastic Surgery}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Reed, Courtney R. and Han, Li and Andrady, Anthony and Caballero, Montserrat and Jack, Megan C. and Collins, James B. and Saba, Salim C. and Loboa, Elizabeth G. and Cairns, Bruce A. and van Aalst, John A.}, year={2009}, month={May}, pages={505–512} }
 @inbook{mccullen_hanson_lucia_loboa_2009, title={Development and application of naturally renewable scaffold materials for bone tissue engineering}, DOI={10.1002/9781444307474.ch11}, booktitle={Nanotechnology of renewable materials}, author={McCullen, S. D. and Hanson, A. D. and Lucia, Lucian and Loboa, E. G.}, editor={L. A. Lucia and Rojas, O. J.Editors}, year={2009} }
 @article{mccullen_zhu_bernacki_narayan_pourdeyhimi_gorga_loboa_2009, title={Electrospun composite poly(L-lactic acid)/tricalcium phosphate scaffolds induce proliferation and osteogenic differentiation of human adipose-derived stem cells}, volume={4}, ISSN={["1748-605X"]}, DOI={10.1088/1748-6041/4/3/035002}, abstractNote={Development of tissue-engineered bone constructs has recently focused on the use of electrospun composite scaffolds seeded with stem cells from various source tissues. In this study, we fabricated electrospun composite scaffolds consisting of β-tricalcium phosphate (TCP) crystals and poly(L-lactic acid) (PLA) at varying loading levels of TCP (0, 5, 10, 20 wt%) and assessed the composite scaffolds' material properties and ability to induce proliferation and osteogenic differentiation of human adipose-derived stem cells (hASCs) in the presence of osteogenic differentiating medium. The electrospun scaffolds all exhibited a nonwoven structure with an interconnected porous network. With the addition of TCP, the fiber diameter increased with each treatment ranging from 503.39 ± 20.31 nm for 0 wt% TCP to 1267.36 ± 59.03 nm for 20 wt% TCP. Tensile properties of the composite scaffolds were assessed and the overall tensile strength of the neat scaffold (0 wt% TCP) was 847 ± 89.43 kPA; the addition of TCP significantly decreased this value to an average of 350.83 ± 38.57 kPa. As the electrospun composite scaffolds degraded in vitro, TCP was released into the medium with the largest release occurring within the first 6 days. Human ASCs were able to adhere, proliferate and osteogenically differentiate on all scaffold combinations. DNA content increased in a temporal manner for each scaffold over 18 days in culture although for the day 12 timepoint, the 10 wt% TCP scaffold induced the greatest hASC proliferation. Endogenous alkaline phosphatase activity was enhanced on the composite PLA/TCP scaffolds compared to the PLA control particularly by day 18. It was noted that at the highest TCP loading levels of 10 and 20 wt%, there was a dramatic increase in the amount of cell-mediated mineralization compared to the 5 wt% TCP and the neat PLA scaffold. This work suggests that local environment cues provided by the biochemical nature of the scaffold can accelerate the overall osteogenic differentiation of hASCs and encourage rapid ossification.}, number={3}, journal={BIOMEDICAL MATERIALS}, author={McCullen, S. D. and Zhu, Y. and Bernacki, S. H. and Narayan, R. J. and Pourdeyhimi, B. and Gorga, R. E. and Loboa, E. G.}, year={2009}, month={Jun} }
 @article{sumanasinghe_pfeiler_monteiro-riviere_loboa_2009, title={Expression of Proinflammatory Cytokines by Human Mesenchymal Stem Cells in Response to Cyclic Tensile Strain}, volume={219}, ISSN={["1097-4652"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000263572000009&KeyUID=WOS:000263572000009}, DOI={10.1002/jcp.21653}, abstractNote={Abstract}, number={1}, journal={JOURNAL OF CELLULAR PHYSIOLOGY}, author={Sumanasinghe, Ruwan D. and Pfeiler, T. Wayne and Monteiro-Riviere, Nancy A. and Loboa, Elizabeth G.}, year={2009}, month={Apr}, pages={77–83} }
 @article{sumanasinghe_osborne_loboa_2009, title={Mesenchymal stem cell-seeded collagen matrices for bone repair: Effects of cyclic tensile strain, cell density, and media conditions on matrix contraction in vitro}, volume={88A}, ISSN={["1552-4965"]}, DOI={10.1002/jbm.a.31913}, abstractNote={Abstract}, number={3}, journal={JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A}, author={Sumanasinghe, Ruwan D. and Osborne, Jason A. and Loboa, Elizabeth G.}, year={2009}, month={Mar}, pages={778–786} }
 @article{hanson_marvel_bernacki_banes_aalst_loboa_2009, title={Osteogenic Effects of Rest Inserted and Continuous Cyclic Tensile Strain on hASC Lines with Disparate Osteodifferentiation Capabilities}, volume={37}, ISSN={["1573-9686"]}, DOI={10.1007/s10439-009-9648-7}, abstractNote={We investigated the effects of two types of cyclic tensile strain, continuous and rest inserted, on osteogenic differentiation of human adipose-derived adult stem cells (hASCs). The influence of these mechanical strains was tested on two hASC lines having different mineral deposition potential, with one cell line depositing approximately nine times as much calcium as the other hASC line after 14 days of culture in osteogenic medium on tissue culture plastic. Results showed that both continuous (10% strain, 1 Hz) and rest inserted cyclic tensile strain (10% strain, 1 Hz, 10 s rest after each cycle) regimens increased the amount and rate of calcium deposition for both high and low calcium depositing hASC lines as compared to unstrained controls. The response was similar for both types of tensile strain for a given cell line, however, cyclic tensile strain had a much stronger osteogenic effect on the high calcium depositing hASC line, suggesting that mechanical loading has a greater effect on cell lines that already have an innate ability to produce bone as compared to cell lines that do not. This is the first study to investigate the osteodifferentiation effects of cyclic tensile strain on hASCs and the first to show that both continuous (10%, 1 Hz) and rest inserted (10%, 1 Hz, 10 s rest) cyclic tensile strain accelerate hASC osteodifferentiation and increase calcium accretion.}, number={5}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Hanson, Ariel D. and Marvel, Skylar W. and Bernacki, Susan H. and Banes, Albert J. and Aalst, John and Loboa, Elizabeth G.}, year={2009}, month={May}, pages={955–965} }
 @article{van aalst_reed_han_andrady_hromadka_bernacki_kolappa_collins_loboa_2008, title={Cellular Incorporation Into Electrospun Nanofibers}, volume={60}, ISSN={0148-7043}, url={http://dx.doi.org/10.1097/sap.0b013e318168db3e}, DOI={10.1097/SAP.0b013e318168db3e}, abstractNote={Nanofibers are an emerging scaffold for tissue engineering. To date no one has reported cell incorporation into nanofibers. Human foreskin fibroblasts and human adipose-derived adult stem cells (hADAS) were grown to confluence, resuspended in phosphate-buffered saline, and then solubilized in polyvinyl alcohol (PVA). Nanofibers were created using an electrospinning technique across an electric potential of 20 kV. Cell interaction with nanofibers was assessed with optical microscopic imaging and scanning electron microscopy. PVA nanofibers with incorporated cells were then solubilized in phosphate-buffered saline; cell viability was assessed by trypan blue exclusion. Viable cells were allowed to proliferate. Chondrogenesis in fibroblasts was induced with TGF-&bgr;1. Both fibroblasts and hADAS survived the electrospinning process and were incorporated into PVA nanofibers. hADAS cell proliferation was negligible; however, fibroblasts proliferated and showed retained ability to undergo chondrogenesis. Cells can be incorporated into nanofibers, with maintained viability, proliferation, and function.}, number={5}, journal={Annals of Plastic Surgery}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={van Aalst, John A. and Reed, Courtney R. and Han, Li and Andrady, Tony and Hromadka, Michael and Bernacki, Susan and Kolappa, Kamalkumar and Collins, James B. and Loboa, Elizabeth G.}, year={2008}, month={May}, pages={577–583} }
 @article{rouse_haslauer_loboa_monteiro-riviere_2008, title={Cyclic tensile strain increases interactions between human epidermal keratinocytes and quantum dot nanoparticles}, volume={22}, ISSN={["0887-2333"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000254694500024&KeyUID=WOS:000254694500024}, DOI={10.1016/j.tiv.2007.10.010}, abstractNote={The effects of quantum dots (QD) on cell viability have gained increasing interest due to many recent developments utilizing QD for pharmaceutical and biomedical applications. The potential use of QD nanoparticles as diagnostic, imaging, and drug delivery agents has raised questions about their potential for cytotoxicity. The objective of this study was to investigate the effects of applied strain on QD uptake by human epidermal keratinocytes (HEK). It was hypothesized that introduction of a 10% average strain to cell cultures would increase QD uptake. HEK were seeded at a density of 150,000 cells/mL on collagen-coated Flexcell culture plates (Flexcell Intl.). QD were introduced at a concentration of 3 nM and a 10% average strain was applied to the cells. After 4 h of cyclic strain, the cells were examined for cell viability, QD uptake, and cytokine production. The results indicate that addition of strain results in an increase in cytokine production and QD uptake, resulting in irritation and a negative impact on cell viability. Application of physiological load conditions can increase cell membrane permeability, thereby increasing the concentration of QD nanoparticles in cells.}, number={2}, journal={TOXICOLOGY IN VITRO}, author={Rouse, Jillian G. and Haslauer, Carla M. and Loboa, Elizabeth G. and Monteiro-Riviere, Nancy A.}, year={2008}, month={Mar}, pages={491–497} }
 @article{pfeiler_sumanasinghe_loboa_2008, title={Finite element modeling of 3D human mesenchymal stem cell-seeded collagen matrices exposed to tensile strain}, volume={41}, ISSN={["1873-2380"]}, DOI={10.1016/j.jbiomech.2008.04.007}, abstractNote={The use of human mesenchymal stem cells (hMSCs) in tissue engineering is attractive due to their ability to extensively self-replicate and differentiate into a multitude of cell lineages. It has been experimentally established that hMSCs are influenced by chemical and mechanical signals. However, the combined chemical and mechanical in vitro culture conditions that lead to functional tissue require greater understanding. In this study, finite element models were created to evaluate the local loading conditions on bone marrow-derived hMSCs seeded in three-dimensional collagen matrices exposed to cyclic tensile strain. Mechanical property and geometry data used in the models were obtained experimentally from a previous study in our laboratory and from mechanical testing. Eight finite element models were created to simulate three-dimensional hMSC-seeded collagen matrices exposed to different levels of cyclic tensile strain (10% and 12%), culture media (complete growth and osteogenic differentiating), and durations of culture (7 and 14 days). Through finite element analysis, it was determined that globally applied uniaxial tensile strains of 10% and 12% resulted in local strains up to 18.3% and 21.8%, respectively. Model results were also compared to experimental studies in an attempt to explain observed differences between hMSC response to 10% and 12% cyclic tensile strain.}, number={10}, journal={JOURNAL OF BIOMECHANICS}, author={Pfeiler, T. Wayne and Sumanasinghe, Ruwan D. and Loboa, Elizabeth G.}, year={2008}, month={Jul}, pages={2289–2296} }
 @misc{bernacki_wall_loboa_2008, title={Isolation of human mesenchymal stem cells from bone and adipose tissue}, volume={86}, journal={Stem cell culture}, author={Bernacki, S. H. and Wall, M. E. and Loboa, E. G.}, year={2008}, pages={257–278} }
 @article{mccullen_stevens_roberts_clarke_bernacki_gorga_loboa_2007, title={Characterization of electrospun nanocomposite scaffolds and biocompatibility with adipose-derived human mesenchymal stem cells}, volume={2}, number={2}, journal={International Journal of Nanomedicine}, author={McCullen, S. D. and Stevens, D. R. and Roberts, W. A. and Clarke, L. I. and Bernacki, S. H. and Gorga, R. E. and Loboa, E. G.}, year={2007}, pages={253–263} }
 @article{finger_sargent_dulaney_bernacki_loboa_2007, title={Differential effects on messenger ribonucleic acid expression by bone marrow-derived human mesenchymal stem cells seeded in agarose constructs due to ramped and steady applications of cyclic hydrostatic pressure}, volume={13}, ISSN={["1076-3279"]}, DOI={10.1089/ten.2006.0290}, abstractNote={This study investigated the differential effects of ramped and steady applications of cyclic hydrostatic pressure (CHP) on chondrogenic differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs) in 3-dimensional culture in the absence of transforming growth factor-beta (TGF-beta). A custom hydrostatic pressure system was designed and manufactured. hMSCs were seeded in agarose and exposed to steady (7.5 MPa) or ramped (1 MPa to 7.5 MPa over a 14-day period) CHP for 4 h/d at f = 1 Hz for 14 days. Real-time reverse transcriptase polymerase chain reaction analysis was performed on days 0, 4, 9, and 14 to determine changes in messenger ribonucleic acid (mRNA) expression levels of Sox9, aggrecan, collagen I, and collagen II. Collagen II and aggrecan mRNA expression remained unchanged. Collagen I increased at day 4 in CHP specimens before decreasing to levels at or below same-day unloaded controls at days 9 and 14. On average, ramped and steady regimens of CHP increased Sox9, with the largest upregulation occurring at day 4 in response to steady pressure. These findings indicate that hydrostatic pressure may induce chondrogenesis in hMSC-seeded agarose constructs without TGF-beta, and that hMSCs are capable of withstanding high initial pressures that may initiate chondrogenesis faster than lower pressures.}, number={6}, journal={TISSUE ENGINEERING}, author={Finger, Allison R. and Sargent, Carolyn Y. and Dulaney, Katherine O. and Bernacki, Susan H. and Loboa, Elizabeth G.}, year={2007}, month={Jun}, pages={1151–1158} }
 @article{hanson_wall_pourdeyhimi_loboa_2007, title={Effects of oxygen plasma treatment on adipose-derived human mesenchymal stem cell adherence to poly(L-lactic acid) scaffolds}, volume={18}, ISSN={["1568-5624"]}, DOI={10.1163/156856207782246812}, abstractNote={Plasma treatment of substrate surfaces can be utilized to improve adhesion of cells to tissue-engineered scaffolds. The purpose of this study was to enhance cell adhesion to non-woven poly(L-lactic acid) (PLLA) scaffolds using oxygen plasma treatment to increase surface hydroxyl groups and thereby enhance substrate hydrophilicity. It was hypothesized that oxygen plasma treatment would increase the number of adipose-derived human mesenchymal stem cells (hMSCs) that adhered to melt-blown, non-woven PLLA scaffolds without affecting cell viability. The number of cells that adhered to the oxygen plasma-treated (10 min at 100 W) or untreated PLLA scaffolds was assessed at 2, 4, 8, 12, 24 and 48 h post-seeding via DNA analysis. Cell viability and morphology were also assessed at 2, 4, 8, 12 and 24 h post-seeding via a live/dead assay and hematoxylin staining, respectively. Oxygen plasma treatment decreased the contact angle of water from 75.6° to 58.2°, indicating an increase in the surface hydrophilicity of PLLA. The results of the DNA analysis indicated that there was an increased number of hMSCs on oxygen plasma treated scaffolds for two of the three donors. In addition, oxygen plasma treatment promoted a more even distribution of hMSCs throughout the scaffold and enhanced cell spreading at earlier time points without altering cell viability. This early induction of cell spreading and the uniform distribution of cells, in turn, may increase future proliferation and differentiation of hMSCs under conditions that simulate the microenvironment in vivo.}, number={11}, journal={JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION}, author={Hanson, Ariel D. and Wall, Michelle E. and Pourdeyhimi, Behnam and Loboa, Elizabeth G.}, year={2007}, month={Nov}, pages={1387–1400} }
 @article{wall_bernacki_loboa_2007, title={Effects of serial passaging on the adipogenic and osteogenic differentiation potential of adipose-derived human mesenchymal stem cells}, volume={13}, ISSN={["1076-3279"]}, DOI={10.1089/ten.2006.0275}, abstractNote={Adipose-derived human mesenchymal stem cells (hMSCs) will be more valuable for tissue engineering applications if they can be extensively subcultured without loss of phenotype and multilineage differentiation ability. This study examined the effects of serial passaging on growth rate, gene expression, and differentiation potential of adipose-derived hMSCs. Differentiation was assessed by analyzing changes in messenger RNA (mRNA) expression of osteogenic and adipogenic marker genes and by determining production of calcium deposits and lipid vacuoles. Cells cultured in osteogenic medium for 2 weeks upregulated expression of alkaline phosphatase mRNA relative to cells in growth medium, and deposited calcium. Calcium deposition decreased in cells from passages 4 to 6 but returned to levels near or above those of primary cells by passage 10. Cells cultured in adipogenic medium upregulated expression of lipoprotein lipase and peroxisome proliferator activated receptor-gamma mRNA relative to cells in growth medium, and formed lipid vacuoles at all passages. By passage 8, however, cells in adipogenic medium also deposited calcium. Growth rate was stable through passage 5, then decreased. The results of this study indicate that adipose-derived hMSCs are capable of both adipogenic and osteogenic differentiation through 10 passages (34 population doublings) but that osteogenic differentiation may start to dominate at later passages.}, number={6}, journal={TISSUE ENGINEERING}, author={Wall, Michelle E. and Bernacki, Susan H. and Loboa, Elizabeth G.}, year={2007}, month={Jun}, pages={1291–1298} }
 @article{yan_gurumurth_wright_pfeiler_loboa_everett_2007, title={Genetic background influences fluoride's effects on osteoclastogenesis}, volume={41}, ISSN={["8756-3282"]}, DOI={10.1016/j.bone.2007.07.018}, abstractNote={Excessive fluoride (F) can lead to abnormal bone biology. Numerous studies have focused on the anabolic action of F yet little is known regarding any action on osteoclastogenesis. Little is known regarding the influence of an individual's genetic background on the responses of bone cells to F. Four-week old C57BL/6J (B6) and C3H/HeJ (C3H) female mice were treated with NaF in the drinking water (0 ppm, 50 ppm and 100 ppm F ion) for 3 weeks. Bone marrow cells were harvested for osteoclastogenesis and hematopoietic colony-forming cell assays. Sera were analyzed for biochemical and bone markers. Femurs, tibiae, and lumbar vertebrae were subjected to microCT analysis. Tibiae and femurs were subjected to histology and biomechanical testing, respectively. The results demonstrated new actions of F on osteoclastogenesis and hematopoietic cell differentiation. Strain-specific responses were observed. The anabolic action of F was favored in B6 mice exhibiting dose-dependent increases in serum ALP activity (p < 0.001); in proximal tibia trabecular and vertebral BMD (tibia at 50&100 ppm, p = 0.001; vertebrae at 50 and 100 ppm, p = 0.023&0.019, respectively); and decrease in intact PTH and sRANKL (p = 0.045 and p < 0.001, respectively). F treatment in B6 mice also resulted in increased numbers of CFU-GEMM colonies (p = 0.025). Strain-specific accumulations in bone [F] were observed. For C3H mice, dose-dependent increases were observed in osteoclast potential (p < 0.001), in situ trabecular osteoclast number (p = 0.007), hematopoietic colony forming units (CFU-GEMM: p < 0.001, CFU-GM: p = 0.006, CFU-M: p < 0.001), and serum markers for osteoclastogenesis (intact PTH: p = 0.004, RANKL: p = 0.022, TRAP5b: p < 0.001). A concordant decrease in serum OPG (p = 0.005) was also observed. Fluoride treatment had no significant effects on bone morphology, BMD, and serum PYD cross-links in C3H suggesting a lack of significant bone resorption. Mechanical properties were also unaltered in C3H. In conclusion, short term F treatment at physiological levels has strain-specific effects in mice. The expected anabolic effects were observed in B6 and novel actions hallmarked by enhanced osteoclastogenesis shifts in hematopoietic cell differentiation in the C3H strain.}, number={6}, journal={BONE}, author={Yan, Dong and Gurumurth, Aruna and Wright, Maggie and Pfeiler, T. Wayne and Loboa, Elizabeth G. and Everett, Eric T.}, year={2007}, month={Dec}, pages={1036–1044} }
 @article{wall_rachlin_otey_loboa_2007, title={Human adipose-derived adult stem cells upregulate palladin during osteogenesis and in response to cyclic tensile strain}, volume={293}, ISSN={["0363-6143"]}, DOI={10.1152/ajpcell.00065.2007}, abstractNote={ Cell morphology may be an important stimulus during differentiation of human adipose-derived adult stem (hADAS) cells, but there are limited studies that have investigated the role of the cytoskeleton or associated proteins in hADAS cells undergoing differentiation. Palladin is an actin-associated protein that plays an integral role in focal adhesion and cytoskeleton organization. In this study we show that palladin was expressed by hADAS cells and was modulated during osteogenic differentiation and in response to cyclic tensile strain. Human ADAS cells expressed the 90- and 140-kDa palladin isoforms and upregulated expression of both isoforms after culture in conditions that promoted osteogenesis. Palladin mRNA expression levels were also increased in hADAS cells subjected to cyclic tensile strain. Knockdown of the palladin gene during osteogenesis resulted in decreased actin stress fibers and decreased protein levels of Eps8, an epidermal growth factor receptor tyrosine kinase that colocalizes with actin. Silencing the palladin gene, however, did not affect hADAS cells' commitment down the osteogenic lineage. }, number={5}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY}, author={Wall, Michelle E. and Rachlin, Andrew and Otey, Carol A. and Loboa, Elizabeth G.}, year={2007}, month={Nov}, pages={C1532–C1538} }
 @article{pfeiler_lalush_loboa_2007, title={Semiautomated finite element mesh generation methods for a long bone}, volume={85}, ISSN={["1872-7565"]}, DOI={10.1016/j.cmpb.2006.10.009}, abstractNote={The objective of this work was to develop and test a semi-automated finite element mesh generation method using computed tomography (CT) image data of a canine radius. The present study employs a direct conversion from CT Hounsfield units to elastic moduli. Our method attempts to minimize user interaction and eliminate the need for mesh smoothing to produce a model suitable for finite element analysis. Validation of the computational model was conducted by loading the CT-imaged canine radius in four-point bending and using strain gages to record resultant strains that were then compared to strains calculated with the computational model. Geometry-based and uniform modulus voxel-based models were also constructed from the same imaging data set and compared. The nonuniform voxel-based model most accurately predicted the axial strain response of the sample bone (R(2)=0.9764).}, number={3}, journal={COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE}, author={Pfeiler, T. W. and Lalush, D. S. and Loboa, E. G.}, year={2007}, month={Mar}, pages={196–202} }
 @article{sumanasinghe_bernacki_loboa_2006, title={Osteogenic differentiation of human mesenchymal stem cells in collagen matrices: Effect of uniaxial cyclic tensile strain on bone morphogenetic protein (BMP-2) mRNA expression}, volume={12}, ISSN={["1076-3279"]}, DOI={10.1089/ten.2006.12.3459}, abstractNote={Human mesenchymal stem cells (hMSCs) differentiate down an osteogenic pathway with appropriate mechanical and/or chemical stimuli. This study describes the successful culture of hMSCs in 3D collagen matrices under mechanical strain. Bone marrow-derived hMSCs were seeded in linear 3D type I collagen matrices and subjected to 0%, 10%, or 12% uniaxial cyclic tensile strain at 1 Hz for 4 h/day for 7 or 14 days. Cell viability studies indicated that hMSCs remained viable throughout the culture period irrespective of the applied strain level. Real-time RT-PCR studies indicated a significant increase in BMP-2 mRNA expression levels in hMSCs strained at 10% compared to the same day unstrained controls after both 7 and 14 days. An increase in BMP-2 was also observed in hMSCs subjected to 12% strain, but the increase was significant only in the 14-day sample. This is the first report of the culture of bone marrow-derived hMSCs in 3D collagen matrices under cyclic strain, and the first demonstration that strain alone can induce osteogenic differentiation without the addition of osteogenic supplements. Induction of bone differentiation in 3D culture is a critical step in the creation of bioengineered bone constructs.}, number={12}, journal={TISSUE ENGINEERING}, author={Sumanasinghe, Ruwan D. and Bernacki, Susan H. and Loboa, Elizabeth G.}, year={2006}, month={Dec}, pages={3459–3465} }
 @article{loboa_fang_parker_warren_fong_longaker_carter_2005, title={Mechanobiology of mandibular distraction osteogenesis: finite element analyses with a rat model}, volume={23}, ISSN={["1554-527X"]}, DOI={10.1016/j.orthres.2004.09.010}, abstractNote={Three-dimensional finite element (FE) analyses were performed to characterize the local mechanical environment created within the tissue regenerate during mandibular distraction osteogenesis (DO) in a rat model. Finite element models were created from three-dimensional computed tomography image data of rat hemi-mandibles at four different time points during an optimal distraction osteogenesis protocol (i.e., most successful protocol for bone formation): end latency (post-operative day (POD) 5), distraction day 2 (POD 7), distraction day 5 (POD 10), and distraction day 8 (POD 13). A 0.25 mm distraction was simulated and the resulting hydrostatic stresses and maximum principal tensile strains were determined within the tissue regenerate. When compared to previous histological findings, finite element analyses showed that tensile strains up to 13% corresponded to regions of new bone formation and regions of periosteal hydrostatic pressure with magnitudes less than 17 kPa corresponded to locations of cartilage formation. Tensile strains within the center of the gap were much higher, leading us to conclude that tissue damage would occur there if the tissue was not compliant enough to withstand such high strains, and that this damage would trigger formation of new mesenchymal tissue. These data were consistent with histological evidence showing mesenchymal tissue present in the center of the gap throughout distraction. Finite element analyses performed at different time points during distraction were instrumental in determining the changes in hydrostatic stress and tensile strain fields throughout distraction, providing a mechanical environment rationale for the different levels of bone formation in end latency, and distraction day 2, 5, and 8 specimens.}, number={3}, journal={JOURNAL OF ORTHOPAEDIC RESEARCH}, author={Loboa, EG and Fang, TD and Parker, DW and Warren, SM and Fong, KD and Longaker, MT and Carter, DR}, year={2005}, month={May}, pages={663–670} }
 @article{loboa_fang_warren_lindsey_fong_longaker_carter_2004, title={Mechanobiology of mandibular distraction osteogenesis: experimental analyses with a rat model}, volume={34}, ISSN={["1873-2763"]}, DOI={10.1016/j.bone.2003.10.012}, abstractNote={We analyzed mechanobiological influences on successful distraction osteogenesis (DO). Mandibular distraction surgeries were performed on 15 adult male Sprague-Dawley rats. Animals underwent gradual distraction (GD), progressive lengthening by small increments (5-day latency followed by 0.25 mm distractions twice daily for 8 days followed by 28-day maturation period). Distracted hemimandibles were harvested on postoperative days (POD) 5, 7, 10, 13, and 41. Load-displacement curves were then recorded for ex vivo distractions of 0.25 mm and stresses determined. Histologically, new bone formation appeared in GD specimens on distraction day 2 (POD 7), filling 50-60% of the gap by distraction day 8 (POD 13), with nearly complete bony bridging at end maturation (POD 41). Average tensile strains imposed by each incremental distraction ranged from approximately 10% to 12.5% during distraction days 2-8 and were associated with bone apposition rates of about 260 microm/day. Because this GD protocol was previously determined to be optimal for DO, we conclude that strains within this range provide an excellent environment for de novo bone apposition. Distraction caused tissue damage in distraction day 2, 5, and 8 specimens as evidenced by distinct drops in the load/displacement curves. Taken together, our interpretation of these data is that daily distractions cause daily tissue damage which triggers new mesenchymal tissue formation.}, number={2}, journal={BONE}, author={Loboa, EG and Fang, TD and Warren, SM and Lindsey, DP and Fong, KD and Longaker, MT and Carter, DR}, year={2004}, month={Feb}, pages={336–343} }