Methacrylic acid-based hydrogels enhance skeletal muscle regeneration after volumetric muscle loss in mice

Volumetric muscle loss (VML) impairs the regenerative ability of skeletal muscle resulting in scar tissue formation and loss of function. Current treatments are of limited efficacy as they do not fully restore function, i.e., force generation. Regenerative biomaterials, such as those containing methacrylic-acid (MAA), are proposed as a novel approach to enhancing muscle regeneration without added cells, growth factors or drugs. Here, the regenerative effects of two hydrogels were investigated: MAA-poly(ethylene glycol) (MAA-PEG) and MAAcollagen. These hydrogels were used to treat VML injuries in murine tibialis anterior muscles. The MAAcollagen hydrogel significantly increased regenerating muscle fiber size and muscle force production. While both hydrogels increased vascularization, only the MAA-collagen hydrogel increased apparent muscle innervation. The MAA-collagen hydrogel also significantly reduced a pro-inflammatory macrophage (MHCII+CD206-) population. Furthermore, the hydrogels had distinct gene expression profiles indicating that their regenerative abilities were carrier dependent. Overall, this study suggests MAA-collagen as a cell-free and drug-free approach to enhancing skeletal muscle regeneration after traumatic injury.

Automated summary

The study demonstrates that MAA-collagen hydrogel significantly enhances skeletal muscle regeneration after traumatic injury, increasing muscle fiber size and force production while reducing pro-inflammatory macrophages. The regenerative effects of the hydrogels are carrier-dependent with distinct gene expression profiles.