An injectable hyaluronic acid–silanol hydrogel containing arginine and puerarin for immune modulation and enhanced diabetic wound healing

Diabetic wound healing is a significant complication of diabetes mellitus, characterized by prolonged healing times, heightened infection risks, and potential amputations, necessitating innovative therapeutic approaches. This study aims to evaluate the efficacy of a novel injectable hydrogel, AP@HA-Si InjGel, which combines hyaluronic acid, silanol, and bioactive compounds to promote wound healing in diabetic patients. Utilizing a combination of in vitro assays, diabetic mouse models, and advanced techniques such as single-cell RNA sequencing, we demonstrated that AP@HA-Si InjGel significantly accelerates wound closure, enhances collagen deposition, and modulates macrophage polarization towards a pro-healing M2 phenotype while suppressing the inflammatory M1 phenotype. The hydrogel exhibited excellent biocompatibility with over 90 % cell viability and significant antioxidant properties, reducing reactive oxygen species accumulation. Histological analysis confirmed that AP@HA-Si InjGel promoted neovascularization and improved extracellular matrix remodeling, thereby enhancing tissue regeneration. Furthermore, single-cell RNA sequencing revealed distinct macrophage subtypes, with an increased proportion of M2 macrophages and a favorable differentiation trajectory towards enhanced wound healing. Overall, these findings highlight the therapeutic potential of AP@HA-Si InjGel as a comprehensive strategy for diabetic wound management, warranting further exploration in clinical settings to address the growing challenge of impaired wound healing in diabetic patients. • Developed an arginine-based injectable hydrogel for diabetic wound healing. •Hydrogel promotes M2 macrophage polarization and reduces M1 inflammation. •Single-cell RNA-seq identifies Cd209d + macrophages linked to tissue repair. •Hydrogel enhances angiogenesis, fibroblast activation, and collagen remodeling. •Offers a multifunctional strategy integrating immune and vascular modulation.