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.