Jo Seung Bin, Erdenebileg Uyanga, Dashnyam Khandmaa, Jin Guang-Zhen, Cha Jae-Ryung, El-Fiqi Ahmed, Knowles Jonathan C, Patel Kapil Dev, Lee Hae-Hyoung, Lee Jung-Hwan, Kim Hae-Won
Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea.
Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea.
J Tissue Eng. 2020 Jan 23;11:2041731419900424. doi: 10.1177/2041731419900424. eCollection 2020 Jan-Dec.
For skeletal muscle engineering, scaffolds that can stimulate myogenic differentiation of cells while possessing suitable mechanical properties (e.g. flexibility) are required. In particular, the elastic property of scaffolds is of importance which helps to resist and support the dynamic conditions of muscle tissue environment. Here, we developed highly flexible nanocomposite nanofibrous scaffolds made of polycarbonate diol and isosorbide-based polyurethane and hydrophilic nano-graphene oxide added at concentrations up to 8%. The nano-graphene oxide incorporation increased the hydrophilicity, elasticity, and stress relaxation capacity of the polyurethane-derived nanofibrous scaffolds. When cultured with C2C12 cells, the polyurethane-nano-graphene oxide nanofibers enhanced the initial adhesion and spreading of cells and further the proliferation. Furthermore, the polyurethane-nano-graphene oxide scaffolds significantly up-regulated the myogenic mRNA levels and myosin heavy chain expression. Of note, the cells on the flexible polyurethane-nano-graphene oxide nanofibrous scaffolds could be mechanically stretched to experience dynamic tensional force. Under the dynamic force condition, the cells expressed significantly higher myogenic differentiation markers at both gene and protein levels and exhibited more aligned myotubular formation. The currently developed polyurethane-nano-graphene oxide nanofibrous scaffolds, due to their nanofibrous morphology and high mechanical flexibility, along with the stimulating capacity for myogenic differentiation, are considered to be a potential matrix for future skeletal muscle engineering.
对于骨骼肌工程而言，需要能够刺激细胞进行肌源性分化同时具备合适机械性能（如柔韧性）的支架。特别地，支架的弹性特性很重要，它有助于抵抗和支撑肌肉组织环境的动态条件。在此，我们开发了由聚碳酸酯二醇和异山梨醇基聚氨酯制成并添加浓度高达8%的亲水性纳米氧化石墨烯的高柔韧性纳米复合纳米纤维支架。纳米氧化石墨烯的掺入提高了聚氨酯衍生纳米纤维支架的亲水性、弹性和应力松弛能力。当与C2C12细胞共培养时，聚氨酯 - 纳米氧化石墨烯纳米纤维增强了细胞的初始黏附与铺展，并进一步促进了细胞增殖。此外，聚氨酯 - 纳米氧化石墨烯支架显著上调了肌源性mRNA水平和肌球蛋白重链表达。值得注意的是，柔性聚氨酯 - 纳米氧化石墨烯纳米纤维支架上的细胞能够受到机械拉伸以经历动态张力。在动态力条件下，细胞在基因和蛋白质水平上均显著表达更高的肌源性分化标志物，并呈现出更多排列整齐的肌管形成。由于其纳米纤维形态、高机械柔韧性以及对肌源性分化的刺激能力，目前开发的聚氨酯 - 纳米氧化石墨烯纳米纤维支架被认为是未来骨骼肌工程的潜在基质。
