Skeletal Muscle Regenerative Engineering.

Skeletal muscles have the intrinsic ability to regenerate after minor injury, but under certain circumstances such as severe trauma from accidents, chronic diseases or battlefield injuries the regeneration process is limited. Skeletal muscle regenerative engineering has emerged as a promising approach to address this clinical issue. The regenerative engineering approach involves the convergence of advanced materials science, stem cell science, physical forces, insights from developmental biology, and clinical translation. This article reviews recent studies showing the potential of the convergences of technologies involving biomaterials, stem cells and bioactive factors in concert with clinical translation, in promoting skeletal muscle regeneration. Several types of biomaterials such as electrospun nanofibers, hydrogels, patterned scaffolds, decellularized tissues, and conductive matrices are being investigated. Detailed discussions are given on how these biomaterials can interact with cells and modulate their behavior through physical, chemical and mechanical cues. In addition, the application of physical forces such as mechanical and electrical stimulation are reviewed as strategies that can further enhance muscle contractility and functionality. The review also discusses established animal models to evaluate regeneration in two clinically relevant muscle injuries; volumetric muscle loss (VML) and muscle atrophy upon rotator cuff injury. Regenerative engineering approaches using advanced biomaterials, cells, and physical forces, developmental cues along with insights from immunology, genetics and other aspects of clinical translation hold significant potential to develop promising strategies to support skeletal muscle regeneration.