Engineered decellularized muscle extracellular matrix fabrics enable functional volumetric muscle loss repair.

Abstract

Volumetric muscle loss (VML) presents a significant clinical challenge, as existing biomaterials fail to recapitulate the anisotropic architecture and pro-regenerative niche that is essential for functional muscle restoration. Although decellularized extracellular matrix (dECM) is bioactive, its exhibits inherently dense structures with poor interconnectivity, that severely restrict cellular infiltration and tissue remodeling. To overcome this, we devised an innovative fabrication strategy involving fragmentation, film formation, fiber cutting, and weaving to engineer muscle-derived dECM (mdECM) into woven fiber scaffolds (mFS). This strategy transformed mdECM into tissue-specific "fabrics" with highly interconnected and guidable porosity, directly addressing the limitations of conventional dense mdECM scaffolds (mDS). The mFS dramatically enhanced cell migration in vitro and promoted rapid host-cell infiltration, and vascularization. In a rat VML model, mFS implantation drove aligned myofiber regeneration alongside synchronized vascularization and innervation, leading to significantly superior functional recovery compared to mDS. Single-cell omics reveals a novel mechanism by which lymphatic endothelial cells and regulatory T cells coordinate the inflammatory response to jointly promote muscle regeneration. This work establishes a facile and translatable mdECM tissue fabric platform that integrates the native bioactivity of mdECM with a rationally designed, regenerative-friendly microstructure, thereby providing a transformative strategy for functional reconstruction of complex muscle defects.