MOF-reinforced NIR-responsive composite hydrogel with photothermal antibacterial and antioxidant activities for diabetic wound healing

Abstract

Chronic diabetic wounds are marked by recurrent infection, persistent ROS and prolonged inflammation. Herein, we report a MOF-reinforced NIR-responsive composite hydrogel (CEPN) that features a dual-cross-linked network assembled from carboxymethyl chitosan (CMCS), polydopamine (PDA), epigallocatechin gallate (EGCG) and L-Cys@Cu MOF nanofibers. The CEPN composite hydrogel is fabricated via a facile one-pot procedure and undergoes rapid in situ gelation (within 50 s) at room temperature while exhibiting robust tissue adhesion (adhesive strength up to 32.2 kPa). The composite hydrogel integrates on-demand photothermal sterilization, broad-spectrum antioxidant capacity and enhanced mechanical robustness. Moreover, it efficiently scavenges reactive oxygen species (ROS) including O₂˙⁻, H₂O₂, ˙OH, and neutralizes the synthetic radicals DPPH˙ and ABTS˙⁺. Upon near-infrared (NIR) irradiation, the composite hydrogel rapidly generates localized hyperthermia, reaching 60 °C within 8 min, and exhibits excellent bactericidal efficacy. This effect is particularly enhanced against Gram-negative E. coli, while under NIR irradiation, S. aureus is also effectively eliminated, achieving complete bacterial eradication for both strains. In vitro and in vivo studies confirm that the composite hydrogel is highly biocompatible and also promotes cell migration and angiogenesis. In a diabetic mouse wound model, the composite hydrogel significantly reduces the wound area, accelerates tissue regeneration, and achieves ∼87% wound closure by day 11. Overall, this multifunctional composite hydrogel offers a simple, safe and effective treatment strategy for chronic diabetic wounds.