Dual-layered metal nanorod-integrated carboxymethyl chitosan and hyaluronic acid hydrogels for accelerated wound healing via ROS scavenging, antibacterial activity, and macrophage reprogramming.

Wound healing is a sophisticated biological process, with the excessive accumulation of reactive oxygen species (ROS) and persistent inflammation emerging as principal challenges in the healing of infected wounds. The aggregation of ROS within the microenvironment can polarize macrophages towards a pro-inflammatory M1 phenotype (M1-Mφ), exacerbating inflammation and impeding the healing process. To address this issue, our study has engineered a ROS-degrading hydrogel integrated with bilayered metal nanorods (CMOHN). This hydrogel is synthesized through a Schiff base reaction using carboxymethyl chitosan (CMCS) and oxidized hyaluronic acid (HA), exhibiting pH-responsive characteristics. Gold nanorods (AuNRs) are synthesized via a seed-mediated growth method, and silver shell are deposited on their surface to form the bilayered metal nanorods, thereby endowing the hydrogel with photothermal antibacterial and ROS-scavenging capabilities. In vitro validation has demonstrated that the CMOHN possesses excellent self-healing, water absorption, bactericidal, antioxidant, and hemostatic properties. In vivo experiments have elucidated that the CMOHN facilitates the transition of macrophages from the pro-inflammatory M1-Mφ to the anti-inflammatory M2 phenotype by scavenging ROS, modulating the inflammatory microenvironment, and accelerating vascular and nerve regeneration, thereby promoting wound healing. The experiments indicate that CMOHN exhibits significant antibacterial, ROS-scavenging, and macrophage-modulating capabilities, which promote the healing of infected wounds and offer a novel therapeutic strategy for clinical applications.