TGFβ1-Loaded Extracellular Matrix Hydrogels Promote Skeletal Muscle Stem Cell Regeneration via m6A-Mediated Integrin–ERK Signaling

Skeletal muscle stem cells (SkMSCs) play a crucial role in muscle regeneration and hold great potential for regenerative therapies. We developed a decellularized extracellular matrix (ECM) hydrogel that mimics the native muscle microenvironment, preserving its bioactive components. When loaded with TGFβ1, the hydrogel significantly boosted SkMSC proliferation and differentiation by activating ERK signaling. Mechanistically, TGFβ1 promoted m6A methylation of integrin mRNA, resulting in ERK phosphorylation. Moreover, ECM hydrogels and TGFβ1 synergistically enhanced SkMSC proliferation, differentiation, and muscle function through m6A-modulated integrin in Sprague-Dawley rats. These findings unveil a novel m6A-mediated pathway linking biochemical and mechanical signals to SkMSC fate, offering a promising biomaterial-based strategy for treating muscle diseases.