Unwavering Pathobiology of Volumetric Muscle Loss Injury

TLDR

Volumetric muscle loss from extremity trauma causes chronic functional deficits, and while acellular ECM scaffolds have shown promise in some animal and clinical studies, other pre‑clinical reports have failed to demonstrate regenerative benefits. The study aimed to reconcile the conflicting evidence regarding ECM‑mediated regeneration in VML. Using a porcine VML model, the authors assessed muscle regeneration and functional recovery with unbiased analyses to evaluate ECM's capacity to drive remodeling. They found that VML triggers a strong inflammatory and fibrotic response leading to extensive fibrous tissue and persistent functional deficits, and ECM treatment did not improve these outcomes.

Abstract

Volumetric muscle loss (VML) resulting from extremity trauma presents chronic and persistent functional deficits which ultimately manifest disability. Acellular biological scaffolds, or decellularized extracellular matrices (ECMs), embody an ideal treatment platform due to their current clinical use for soft tissue repair, off-the-shelf availability, and zero autogenous donor tissue burden. ECMs have been reported to promote functional skeletal muscle tissue remodeling in small and large animal models of VML injury, and this conclusion was reached in a recent clinical trial that enrolled 13 patients. However, numerous other pre-clinical reports have not observed ECM-mediated skeletal muscle regeneration. The current study was designed to reconcile these discrepancies. The capacity of ECMs to orchestrate functional muscle tissue remodeling was interrogated in a porcine VML injury model using unbiased assessments of muscle tissue regeneration and functional recovery. Here, we show that VML injury incites an overwhelming inflammatory and fibrotic response that leads to expansive fibrous tissue deposition and chronic functional deficits, which ECM repair does not augment.