Antimicrobial and Anti-Inflammatory Co-Loaded Chitosan/Polyvinyl Alcohol Hydrogel for Synergistic Treatment of Diabetic Wounds

Abstract

To develop a chitosan/polyvinyl alcohol (CS/PVA) hydrogel co-loaded with polyhexamethylene biguanide (PHMB) and celecoxib (CEL) for synergistic treatment of diabetic foot ulcers (DFUs). Blank CS/PVA, CEL/CS/PVA, PHMB/CS/PVA, and CEL/PHMB/CS/PVA hydrogels were prepared by freeze-thaw cycles. Their microstructure, swelling, degradation, antibacterial activity, hemocompatibility, and fibroblast migration were evaluated in vitro. A full-thickness wound model in streptozotocin-induced type 1 diabetic mice was used to assess wound healing, inflammation, angiogenesis, macrophage polarization, and biosafety. All hydrogels showed comparable swelling. On Day 7, the degradation rates were 71.04%, 55.80%, 47.49%, and 25.42%, respectively, with CEL/PHMB/CS/PVA showing the lowest degradation rate. PHMB-containing hydrogels inhibited E. coli and S. aureus. All materials had hemolysis rates < 5%, and the composite group showed 1.74%. The 24 h migration rates were 30%, 37%, 48%, and 67%, with the composite group being highest (p < 0.001). In diabetic mice, the composite group achieved 68.89% wound healing on Day 7 and 94.44% on Day 14, versus 69.59% on Day 14 in the untreated diabetic group (p < 0.001). It also increased collagen deposition, reduced IL-1β and IL-6, and promoted CD31⁺ angiogenesis, α-SMA⁺ vascular maturation, and CD206⁺ M2 macrophage polarization, with no obvious systemic toxicity. The CEL/PHMB/CS/PVA composite hydrogel promotes the healing of diabetic wounds through the synergistic effects of PHMB's antibacterial action and CEL's anti-inflammatory action. The hydrogel demonstrates good biosafety and potential for clinical translation.