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), Fe3+, and MnO2@dopamine (DA) nanozymes was developed for diabetic wounds. The TA-based dynamic disulfide network offered remarkable injectability, tissue adhesion, and controllable degradation. The Fe3+ coordination significantly improved mechanical stability through metal-ligand interactions. The incorporated MnO2@DA nanozymes created a triple therapeutic synergy through cooperative antioxidant effects (MnO2's catalase-like activity, TA's redox activity achieving 92.3% H2O2 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.