Advances in extracellular matrix-mimetic hydrogels for muscle repair and regeneration: Biomimetic design, preparation, mechanisms and tissue engineering applications

Abstract

Extracellular matrix (ECM)-mimetic hydrogels have attracted increasing attention in muscle tissue engineering because they can partially reproduce the biochemical and biophysical features of native regenerative niches. In contrast to conventional hydrogels that mainly serve as passive structural supports, emerging ECM-mimetic hydrogels are being designed to actively regulate multiple stages of tissue repair, including inflammatory remodeling, stem-cell activation, angiogenesis, and neuromuscular integration. Strategies such as decellularized matrix incorporation, anisotropic structural engineering, electroactive modification, and spatiotemporally controlled factor delivery have all shown great potential for improving regenerative outcomes in skeletal, cardiac, and smooth muscle tissues. Simultaneously, growing evidence suggests that successful regeneration depends not only on biochemical signaling, but also on dynamic interactions between cells and the surrounding matrix, particularly mechanotransduction, immune regulation, and adaptive remodeling processes. In this review, we summarize current advances in ECM-mimetic hydrogels from the perspectives of biomimetic design, regenerative mechanisms, and translational applications. We further discuss several unresolved challenges, including insufficient neurovascular integration, limited long-term matrix adaptability, and the lack of standardized functional evaluation systems. Finally, we highlight emerging directions involving bioelectronics, intelligent responsive biomaterials, and multi-omics-guided design strategies, which will be helpful in advancing the development of next-generation regenerative platforms for functional muscle reconstruction. The revised framework further distinguishes mature and provisional ECM targets, compares application-specific material selection, and maps commercially available or clinically advanced ECM-related products to their translational status.