Immunotolerant Oligomer Scaffolds Promote Regenerative Remodeling and Improved Muscle Structure and Function After Volumetric Muscle Loss

Volumetric muscle loss (VML) overwhelms endogenous repair mechanisms, leading to defect contraction, fibrosis, and persistent aesthetic and functional deficits. Restorative biomaterials capable of re-establishing muscle structure and function represent promising strategies for treating severe injuries where conventional surgical repair is inadequate. Using a rat full-thickness VML model, we evaluated Oligomer, an engineered collagen polymeric biomaterial through spatial transcriptomic profiling. Spatial transcriptomic analyses defined a regenerative remodeling mechanism distinct from reparative or constructive remodeling, characterized by an immunotolerant environment that enabled infiltration of diverse progenitor populations, including pro-regenerative mesenchymal cells, pericytes, satellite cells, and endothelial and neural stem cells. This cellular niche supported coordinated activation of myogenic, vascular, and neural pathways, recapitulating key aspects of developmental myogenesis.