An Ion-Releasing Bioactive Glass Accelerates Skeletal Muscle Regeneration and Functional Recovery Following Acute Injury

Abstract

Bioactive glasses represent an emerging strategy for localized skeletal muscle repair. Here, we investigated whether an injectable borophosphate bioactive glass [cobalt oxide–time release ion matrix (CoO-TRIM)] can accelerate skeletal muscle regeneration and functional recovery following acute injury. Using a barium chloride (BaCl2) injury model, muscle function, myogenesis, angiogenesis, and inflammation were evaluated in mouse tibialis anterior (TA) and extensor digitorum longus (EDL) muscles at 8 and 14 days post-injury (dpi). Mice were randomly assigned to Untreated, Saline-treated, and CoO-TRIM-treated groups. CoO-TRIM accelerated the regenerative process, with increased myofiber size and restoration of TA contractile function to values not significantly different from Healthy muscle by 14 dpi compared to Injured Untreated and Saline-treated muscles. Vascular endothelial growth factor (VEGF) concentrations were elevated through 14 dpi following CoO-TRIM treatment and accompanied by enhanced muscle vascularity in both TA and EDL muscles. CoO-TRIM modulated the inflammatory response, with increased inflammatory signaling during active regeneration at 8 dpi, followed by an accelerated transition toward a pro-regenerative environment characterized by increased CD163+ M2 macrophages and sustained IL-10 signaling. In contrast, CoO-TRIM produced no detectable effects in healthy contralateral muscles. These findings support ion-releasing bioactive glass as a cell- and growth factor-free strategy for skeletal muscle repair.