Provisional Treatment of Volumetric Muscle Loss With Insulin-like Growth Factor 1 Releasing Muscle Void Fillers

INTRODUCTION: Volumetric muscle loss (VML) resulting from severe extremity injuries in combat remains a significant clinical challenge, particularly in austere environments. Current research emphasizes the development and evaluation of definitive treatments, largely neglecting acute stabilization strategies. To address this unmet need, this study investigated the efficacy of delivering insulin-like growth factor 1 long arginine 3 (IGF1-LR3) via a synthetic in situ forming hydrogel muscle void filler (MVF) to enhance muscle recovery after VML.

METHODS: Adult male Lewis rats underwent VML surgery, followed by implantation of a polyethylene glycol-acrylate MVF containing either soluble or poly(lactic-co-glycolic acid) (PLGA)-encapsulated IGF1-LR3 at a low (28 μg) or high (280 μg) dose, or no IGF1-LR3 (control). Neuromuscular function was assessed via isometric torque measurements. Muscle tissue was analyzed using wheat germ agglutinin and picrosirius red staining for fiber size, count, and fibrosis. Statistical analysis was performed using ANOVA with Holm-Šídák post hoc testing.

RESULTS: High-dose PLGA-encapsulated IGF1-LR3 resulted in increased muscle weight compared to the control group at 28 d post implantation. However, no differences were observed in specific torque or maximum torque production between any experimental groups. Histological analysis revealed no changes in muscle fibrosis or fiber size or count of IGF1-LR3 compared to controls.

CONCLUSIONS: The addition of IGF1-LR3 in an MVF did not enhance neuromuscular function or muscle fiber hypertrophy. Further studies are needed to optimize IGF1-LR3 delivery or alternative hypertrophy-inducing soluble factors.