The effects of AT-RvD1 delivery on SPM metabolism, myeloid recruitment, and myogenesis in a murine model of Volumetric Muscle Loss injury

Abstract

Volumetric Muscle Loss injury (VML) is the partial ablation of skeletal muscle, usually on the extremities, sustained through traumatic or surgical means, such as motor vehicle accidents, military combat, or surgical resection. The frank loss of musculature characteristic of VML sufficiently disrupts or eliminates the wound’s endogenous repair mechanisms such that healing becomes virtually impossible 1,2. VML patients must deal with permanent functional impairments, chronic inflammation, and chronic pain 1. Current clinical strategies for VML treatment include muscle flap autografts and free tissue transfer that, while salvaging the injured limb, are often no better than amputation in terms of functional improvement and patient quality of life 3,4. Much research in the field has been focused on overcoming the challenges and deficits associated with this clinical gold-standard. Biomaterial strategies using decellularized extracellular matrix (ECM) derived from skeletal muscle, porcine small intestinal submucosa (SIS), and urinary bladder matrix (UBM) have been extensively studied, with multiple FDA-approved products available for clinical use 5–7. However, these studies continue to show that minimal levels of physiologically-relevant muscle fibers are regenerated in both human and animal trials of acellular matrices. Instead, regenerated tissue has been overwhelmingly composed of non-functional and non-contractile fibrotic and adipose tissue 6. Common between both the clinical gold standards and the acellular matrix strategies being studied is the over-looking of the inhospitable microenvironment caused by persistent inflammation that serves to activate fibrotic pathways of regeneration 1,7. Thus, the need for an alternative strategy that targets this pathological inflammation and results in better long-term functional outcomes for patients after severe extremity trauma is clear.