Hwang Yongsung, Seo Timothy, Hariri Sara, Choi Chulmin, Varghese Shyni
Department of Bioengineering, University of California, San Diego, CA 92521, USA.
Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan-si, Chungcheongnam-do 31151, Korea.
Polymers (Basel). 2017 Nov 5;9(11):580. doi: 10.3390/polym9110580.
Biomaterials varying in physical properties, chemical composition and biofunctionalities can be used as powerful tools to regulate skeletal muscle-specific cellular behaviors, including myogenic differentiation of progenitor cells. Biomaterials with defined topographical cues (e.g., patterned substrates) can mediate cellular alignment of progenitor cells and improve myogenic differentiation. In this study, we employed soft lithography techniques to create substrates with microtopographical cues and used these substrates to study the effect of matrix topographical cues on myogenic differentiation of human embryonic stem cell (hESC)-derived mesodermal progenitor cells expressing platelet-derived growth factor receptor alpha (PDGFRA). Our results show that the majority (>80%) of PDGFRA+ cells on micropatterned polydimethylsiloxane (PDMS) substrates were aligned along the direction of the microgrooves and underwent robust myogenic differentiation compared to those on non-patterned surfaces. Matrix topography-mediated alignment of the mononucleated cells promoted their fusion resulting in mainly (~86%⁻93%) multinucleated myotube formation. Furthermore, when implanted, the cells on the micropatterned substrates showed enhanced in vivo survival (>5⁻7 times) and engraftment (>4⁻6 times) in cardiotoxin-injured tibialis anterior (TA) muscles of NOD/SCID mice compared to cells cultured on corresponding non-patterned substrates.
物理性质、化学成分和生物功能各异的生物材料可作为强大工具，用于调节骨骼肌特异性细胞行为，包括祖细胞的肌源性分化。具有特定拓扑线索（如图案化基底）的生物材料可介导祖细胞的细胞排列，并改善肌源性分化。在本研究中，我们采用软光刻技术制备具有微观拓扑线索的基底，并利用这些基底研究基质拓扑线索对表达血小板衍生生长因子受体α（PDGFRA）的人胚胎干细胞（hESC）来源的中胚层祖细胞肌源性分化的影响。我们的结果表明，与非图案化表面上的细胞相比，微图案化聚二甲基硅氧烷（PDMS）基底上的大多数（>80%）PDGFRA+细胞沿微槽方向排列，并经历了强大的肌源性分化。基质拓扑介导的单核细胞排列促进了它们的融合，主要导致（~86%⁻93%）多核肌管形成。此外，当植入时，与在相应非图案化基底上培养的细胞相比，微图案化基底上的细胞在NOD/SCID小鼠的心肌毒素损伤的胫前肌（TA）中显示出体内存活率提高（>5⁻7倍）和植入率提高（>4⁻6倍）。
