A lipoic acid supramolecular polymer-based hydrogel with self-regulating ROS, reduced blood sugar, and antibacterial ability for improved diabetic wound healing

Diabetic wound healing poses a significant challenge, and there is a growing need to develop a comprehensive treatment approach in this field of research. Recently, natural lipoic acid has garnered considerable attention because it can polymerize through dynamic disulfide bonds. Here, we developed an alpha-lipoic acid (LA) supramolecular polymer-based hydrogel (BI-AuLA) with gold nanostars (AuNSs), in which the bovine insulin (BI) improved diabetic wound healing. The LA supramolecular polymer plays a crucial role in restoring the damaged redox microenvironment by effectively regulating the balance between reactive oxygen species and glutathione. Additionally, the photothermal properties of AuNSs enable BI-AuLA to exhibit outstanding antibacterial activity against a range of bacteria when subjected to near-infrared (NIR) irradiation. Furthermore, BI-AuLA facilitates the sustained release of BI, thereby regulating local high glucose levels in the wound. Significantly, in the diabetes mellitus skin defect model, BI-AuLA induces intensive blood vessel formation and promotes uniform collagen arrangement, thereby facilitating effective wound healing. This groundbreaking supramolecular polymer-based hydrogel represents a highly embodied and tremendously encouraging strategy for addressing the challenges posed by extensive tissue damage resulting from diabetes.