A caffeic acid-loaded hydrogel attenuates inflammation and accelerates infected wound healing

Infected wounds are often accompanied by persistent bacterial colonization, dysregulated inflammation, and aggravated oxidative stress, which worsen the local microenvironment and hinder tissue repair. Therefore, the development of bioactive dressings with antibacterial, antioxidant, and inflammation-regulating properties is of great importance. This study aimed to construct a caffeic acid-loaded double-network hydrogel and evaluate its potential for the treatment of infected wounds.

The porous structure, fluid absorption capacity, and release behavior of the hydrogel were characterized. Its cytocompatibility, hemocompatibility, antibacterial activity, antioxidant capacity, and regulatory effects on macrophages and fibroblasts were further evaluated in vitro. In addition, an infected full-thickness skin defect model was established to assess its therapeutic efficacy in vivo.

The hydrogel exhibited a favorable porous structure and fluid absorption capacity, and achieved sustained release of caffeic acid. It also showed good cytocompatibility and hemocompatibility, along with strong inhibitory effects against Staphylococcus aureus and Escherichia coli, and enhanced free radical scavenging activity. In addition, the hydrogel upregulated Arg-1 expression and downregulated iNOS expression in macrophages, promoting macrophage polarization toward the anti-inflammatory M2 phenotype, while also enhancing the expression of Col I and Col III in fibroblasts. In vivo, the hydrogel improved local infection status, accelerated wound healing, and enhanced re-epithelialization and collagen deposition.

These findings indicate that the caffeic acid-loaded double-network hydrogel not only reduces bacterial burden and oxidative stress in infected wounds, but also improves the local reparative microenvironment by regulating inflammation-related cell phenotypes and promoting extracellular matrix synthesis, thereby accelerating tissue regeneration. This study provides a new strategy for the design of bioactive dressings for infected wounds and also offers experimental evidence for local therapeutic approaches that integrate infection control with tissue repair.