The influence of RGD-bearing hydrogels on the re-expression of contractile vascular smooth muscle cell phenotype |
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| Authors: | Jeffrey A. Beamish Alexander Y. Fu Ae-jin Choi Nada A. Haq Kandice Kottke-Marchant Roger E. Marchant |
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| Affiliation: | 1. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA;2. Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH 44195, USA;1. Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO 80309, USA;2. Department of Industrial Engineering and Biotech Research Center, University of Trento, via Sommarive 9, 38123 Trento, Italy;1. Department of Chemical and Materials Engineering, National Central University, Jhongli, Taoyuan, Taiwan;2. Institute of Biomedical Engineering, National Central University, Jhongli, Taoyuan, Taiwan;3. R&D Center for Membrane Technology, Chung Yuan Christian University, Jhongli, Taoyuan, Taiwan;4. Center for Dynamical Biomarkers and Translational Medicine, Jhongli, Taoyuan, Taiwan;5. Department of Life Science, National Central University, Jhongli, Taoyuan, Taiwan;6. Department of Chemical Engineering, Chung Yuan Christian University, Jhongli, Taoyuan, Taiwan;1. University of California Los Angeles, Bioengineering Department, USA;2. University of California Los Angeles, Chemical and Biomolecular Engineering Department, USA;1. Department of Molecular Pharmacology and Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-Machi, Maebashi, Gunma 371-8511, Japan;2. Department of Bioresources, Mie University, Kamihama-Machuya 1515, Tsu, Mie 514-8507, Japan;3. Research Institute of Pharmaceutical Sciences, Musashino University, Nushitokyo, Tokyo 202-8585, Japan;4. Department of Health and Nutrition, Takasaki University of Health and Welfare, Takasaki, Japan;5. Department of Biochemistry, Gunma University Graduate School of Medicine, 3-39-22 Showa-Machi, Maebashi, Gunma 371-8511, Japan;6. Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan;1. Department of Biomedical Engineering, Rensselaer Polytechnic Institute, 110 8th Street Troy, NY, 12180, USA;2. Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, 110 8th Street Troy, NY, 12180, USA |
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| Abstract: | This study reports on the ability of poly(ethylene glycol) diacrylate (PEGDA) hydrogel scaffolds with pendant integrin-binding GRGDSP peptides (RGD-gels) to support the re-differentiation of cultured vascular smooth muscle cells (SMCs) toward a contractile phenotype. Human coronary artery SMCs were seeded on RGD-gels, hydrogels with other extracellular matrix derived peptides, fibronectin (FN) and laminin (LN). Differentiation was induced on RGD-gels with low serum medium containing soluble heparin, and the differentiation status was monitored by mRNA expression, protein expression, and intracellular protein organization of the contractile smooth muscle markers, smooth muscle α-actin, calponin, and SM-22α. RGD-gels supported a rapid induction (2.7- to 25-fold up-regulation) of SMC marker gene mRNA, with expression levels that were equivalent to FN and LN controls. Marker protein levels mirrored the changes in mRNA expression, with levels on RGD-gels indistinguishable from FN and LN controls. Furthermore, these markers co-localized in stress fibers within SMCs on RGD-gels suggesting the recapitulation of a contractile apparatus within the cells. These results indicate that SMCs cultured on RGD-bearing hydrogels can re-differentiate toward a contractile phenotype suggesting this material is an excellent candidate for further development as a bioactive scaffold that regulates SMC phenotype. |
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