Bioinspired electrospun decellularized extracellular matrix scaffolds promote muscle regeneration in a rat skeletal muscle defect model.

Volumetric muscle loss is a debilitating injury that can leave patients with long-lasting or permanent structural and functional deficits. With clinical treatments failing to address these shortcomings, there is a great need for tissue-engineered therapies to promote skeletal muscle regeneration. In this study, we aim to assess the potential for electrospun decellularized skeletal muscle extracellular matrix (dECM) to promote skeletal muscle regeneration in a rat partial thickness tibialis anterior defect model. Aligned electrospun scaffolds with varying degrees of crosslinking density were implanted into the defect site and compared to an empty defect control. After 8 weeks, muscles were harvested, weighed, and cellular and morphological analyses were performed via histology and immunohistochemistry. Cell infiltration, angiogenesis, and myogenesis were observed in the defect site in both dECM groups. However, favorable mechanical properties and slower degradation kinetics resulted in greater support of tissue remodeling in the more crosslinked scaffolds and preservation of existing myofiber area in both dECM groups compared to the empty defect control. More sustained release of pro-regenerative degradation products also promoted greater myofiber formation in the defect site. This study allowed for a greater understanding of how electrospun skeletal muscle scaffolds interact with existing skeletal muscle and can inform their potential as a therapy in a wide variety of soft tissue applications.