Synergistic Effect of Anti‐Infection, Anti‐Inflammatory and Pro‐Angiogenic for Novel Nanozyme‐Reinforced Supramolecular Hydrogel in Diabetic Wound Healing

ABSTRACT A multifunctional supramolecular hydrogel (TF‐MOD) through the synergistic integration of thioctic acid (TA), Fe 3+ , and MnO 2 @dopamine (DA) nanozymes was developed for diabetic wounds. The TA‐based dynamic disulfide network offered remarkable injectability, tissue adhesion, and controllable degradation. The Fe 3+ coordination significantly improved mechanical stability through metal‐ligand interactions. The incorporated MnO 2 @DA nanozymes created a triple therapeutic synergy through cooperative antioxidant effects (MnO 2 ’s catalase‐like activity, TA's redox activity achieving 92.3% H 2 O 2 clearance), antimicrobial action (photothermal therapy with a 26.1°C temperature increase and TA's inherent antibacterial properties), and enhanced anti‐inflammatory effects combined with pro‐angiogenic effects mediated by the nanozymes. Through rheological analysis, lap‐shear testing, and injectability assessments, the establishment of a stable yet dynamic network structure exhibited remarkable self‐healing, injectability, and tissue adhesion. The TF‐MOD hydrogel was designed to promote diabetic wound healing by providing sustained antibacterial efficacy (16.1% residual MRSA biofilm), anti‐inflammatory activity, and pro‐angiogenic effects, thereby enhancing collagen deposition (68.2%) and reducing wound area (15.2% remaining on day 10) significantly. Additionally, the TF‐MOD hydrogel demonstrated dual therapeutic effects for both infected wounds (12.4% residual area, 67.8% collagen deposition) and incisional wounds (214.8 µm width). The TF‐MOD hydrogel served as a novel and versatile platform for diabetic wound therapy.