Woven dECM yarn scaffolds enable volumetric muscle loss regeneration via immunomodulation.

Volumetric muscle loss (VML) represents a significant unmet clinical need in current medical practice. Decellularized extracellular matrix (dECM) offers a promising clinical approach. However, its inherent architecture impedes adaptive topological guidance for rapid cellular infiltration, spatial organization, and coordinated immune response, limiting functional restoration. Here, we report a dECM yarn scaffold (YS) fabricated by 3D weaving of rotary-cut yarns, achieving precise structural control, full interconnectivity and high porosity. In murine VML models, YS significantly improved vascularization, innervation, muscle mass, and strength restoration. Single-nucleus RNA-sequencing identified decreased SPP1+ neutrophil infiltration alongside increased CD206+/IGF-1+ macrophages, whose enhanced IGF-1 secretion stimulated PAX7+ muscle cell growth via amplified IGF-1R signaling. The robust regenerative efficacy and translational potential of YS was further confirmed in a canine VML model. Our study shows that restructured dECM scaffolds address structural constraints to enable effective in situ muscle regeneration, while simultaneously establishing a novel scaffold platform for regenerative medicine.