Near-infrared and pH dual-responsive chitosan/epigallocatechin gallate/hollow CuS hydrogel reprograms ROS dynamics for infected wound healing

Abstract

Bacterial-infected wounds pose a clinical challenge requiring innovative strategies integrating precise antibacterial action and microenvironment reprogramming. To address this, a multifunctional H-CuS NPs@epigallocatechin gallate (EGCG)/chitosan (CS)/3-formylphenylboronic acid (3-FPBA) hydrogel (H-CuS@EGCG HY) was engineered. This hydrogel exhibits injectability, self-healing, tissue adhesion, and pH-responsive behavior. During the initial phase of wound infection (weakly acidic microenvironment), this network undergoes controlled dissociation, enabling on-demand localized release of EGCG and Cu^1+/2+. Under near-infrared (NIR) irradiation, the photothermal effect of H-CuS NPs promotes mild heating, which enhances EGCG/Cu^1+/2+ release and penetration. The released Cu^1+/2+ further catalyzes •OH generation from H₂O₂ via Fenton reaction, synergizing with EGCG and photothermal therapy to improve antibacterial efficacy. Additionally, EGCG scavenges excess radicals, reducing oxidative stress and inflammation, while Cu^1+/2+ supports angiogenesis via VEGF regulation-collectively reprogramming the wound microenvironment. In vitro tests showed broad-spectrum antimicrobial activity with a 99 % eradication rate. In S. aureus-infected mouse models, compared to the control group, the H-CuS@EGCG HY + NIR group significantly reduced the levels of inflammatory cytokines (TNF-α), promoted the expression of CD31 and CD206, and effectively modulated the wound microenvironment, ultimately resulting in complete wound closure (100 %) by day 13, accompanied by full epidermal regeneration and minimal scarring. This study provides a promising strategy for the treatment of clinical wounds.