Nanofiber Yarn/Hydrogel Core-Shell Scaffolds Mimicking Native Skeletal Muscle Tissue for Guiding 3D Myoblast Alignment, Elongation, and Differentiation

Designing scaffolds that can mimic native skeletal muscle tissue and induce 3D cellular alignment and elongated myotube formation remains an ongoing challenge for skeletal muscle tissue engineering. Herein, we present a simple technique to generate core shell composite scaffolds for mimicking native skeletal muscle structure, which comprise the aligned nanofiber yarn (NFY) core and the photocurable hydrogel shell. The aligned NFYs are prepared by the hybrid composition including poly(caprolactone), silk fibroin, and polyaniline via a developed dry wet electrospinning method. A series of core shell column and sheet composite scaffolds are ultimately obtained by encapsulating a piece and layers of aligned NFY cores within the hydrogel shell after photo-cross-linking. C2C12 myoblasts are seeded within the core shell scaffolds, and the good biocompatibility of these scaffolds and their ability to induce 3D cellular alignment and elongation are successfully demonstrated. Furthermore, the 3D elongated myotube formation within core shell scaffolds is also performed after long-term cultivation. These data suggest that these core shell scaffolds combine the aligned NFY core that guides the myoblast alignment and differentiation and the hydrogel shell that provides a suitable 3D environment for nutrition exchange and mechanical protection to perform a great practical application for skeletal muscle regeneration.

设计能够模拟天然骨骼肌组织并诱导三维细胞排列和细长肌管形成的支架，对于骨骼肌组织工程来说仍然是一个持续的挑战。在此，我们提出了一种简单的技术来制备核壳复合支架以模拟天然骨骼肌结构，该支架包含排列的纳米纤维纱（NFY）核和光固化水凝胶壳。通过一种改进的干湿电纺方法，由包括聚己内酯、丝素蛋白和聚苯胺的混合成分制备排列的NFY。经过光交联后，通过在水凝胶壳内封装一片和多层排列的NFY核，最终获得了一系列核壳柱状和片状复合支架。将C2C12成肌细胞接种在核壳支架内，成功证明了这些支架良好的生物相容性以及它们诱导三维细胞排列和伸长的能力。此外，经过长期培养后，在核壳支架内也实现了三维细长肌管的形成。这些数据表明，这些核壳支架结合了引导成肌细胞排列和分化的排列的NFY核以及为营养交换和机械保护提供合适三维环境的水凝胶壳，在骨骼肌再生方面具有很大的实际应用价值。