Recent advances in electroactive biomaterials and electrical stimulation for skeletal muscle regeneration: materials, strategies, and mechanistic insights.

Skeletal muscle tissue plays a crucial role in strength generation, body movement, posture maintenance, and the protection of internal organs. Volumetric muscle loss not only causes significant physical and psychological distress and disability for patients, but also poses a serious societal challenge due to the substantial financial burden it places on healthcare systems. Currently, available treatment methods for muscle tissue injury have inherent limitations. Tissue engineering has emerged as a promising therapeutic strategy to address this issue. Bioelectric activity has been widely recognized for their important role in maintaining skeletal muscle homeostasis and promoting regeneration. Electroactive biomaterial-enabled electrical stimulation (ES) has been shown to effectively regulate various biological processes and is expected to serve as an external intervention to accelerate skeletal muscle repair. In this review, we summarize the forms of electroactive biomaterials utilized in skeletal muscle tissue regeneration in recent years, and compare the performance advantages and limitations of various materials. Furthermore, ES strategies based on these electroactive materials and their specific applications in promoting skeletal muscle regeneration are systematically reviewed, including endogenous ES, exogenous ES, piezoelectric stimulation, magnetoelectric stimulation, and triboelectric stimulation. The mechanisms are analyzed at three levels: regulation of cellular behavior, tissue reconstruction, and vascular-nerve integration. Finally, we outline the future application prospects of ES-based therapeutic strategies and highlight potential challenges that may arise in clinical translation.