Acellular Scaffolds for Muscle Regeneration: Advances and Challenges.

Significance: Volumetric muscle loss is defined as composite loss of muscle mass. Severe injuries result in permanent functional impairment. Treatment options are limited. Tissue engineering techniques utilizing scaffolds offer promise as a potential therapy. Recent Advances: Emerging strategies, including bioactive molecules and growth factors in biocompatible scaffolds, may promote muscle regeneration following severe injury. In this context, scaffolds can act as a drug-delivery device, provide guidance to cells as a supporting matrix, and slowly release growth factors to promote healing. Critical Issues: Scaffolds engraftment and ability to promote tissue regeneration in injured beds remain limited. Tuning and optimizing scaffold fiber diameter, alignment, cellular cues, growth factor delivery, and porosity will be important in reconstituting functional skeletal muscle following loss. Future Directions: Our mechanistic understanding of interactions between biomimetic scaffolds and host tissue is still evolving, and future research can identify factors to promote tissue regeneration.