Acrylated Hyaluronic-Acid Based Hydrogel for the Treatment of Craniofacial Volumetric Muscle Loss

Current treatment options for craniofacial volumetric muscle loss (VML) have disadvantages and cannot fully restore normal function. Bio-inspired semisynthetic acrylated hyaluronic acid (AcHyA) hydrogel, which fills irregularly shaped defects, resembles an extracellular matrix, and induces a minimal inflammatory response, has shown promise in experimental studies of extremity VML. We therefore sought to study AcHyA hydrogel in the treatment of craniofacial VML. For this, we used a novel model of masseter VML in the rat. Following the creation of a 5 mm × 5 mm injury to the superficial masseter and administration of AcHyA to the wound, masseters were explanted between 2 and 16 weeks postoperatively and were analyzed for evidence of muscle regeneration including fibrosis, defect size, and fiber cross-sectional area (FCSA). At 8 and 16 weeks, masseters treated with AcHyA showed significantly less fibrosis than nonrepaired controls and a smaller decrease in defect size. The mean FCSA among fibers near the defect was significantly greater among hydrogel-repaired than control masseters at 8 weeks, 12 weeks, and 16 weeks. These results show that the hydrogel mitigates the fibrotic healing response and wound contracture. Our findings also suggest that hydrogel-based treatments have potential use as a treatment for the regeneration of craniofacial VML and demonstrate a system for evaluating subsequent iterations of materials in VML injuries. Impact Statement Craniofacial volumetric muscle loss (VML) is a debilitating condition for which current treatment options are unable to restore normal appearance, or function. Tissue engineering approaches, such as hydrogel implants, may be an effective strategy to fill the volumetric defects and promote de novo muscle regeneration. In this study, we describe a novel rodent model for the study of craniofacial VML and a hyaluronic acid-based hydrogel that can be used as a treatment for the regeneration of craniofacial VML.