Abstract

Infectious wounds remain a formidable clinical challenge due to persistent bacterial colonization, uncontrolled inflammation, and impaired tissue regeneration. To address these issues, we developed a multifunctional immunoregulatory hydrogel by integrating curcumin (Cur) loaded polydopamine (PDA)-coated zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (Cur/ZIF/PDA) into a photo-cross-linkable hydrogel matrix derived from decellularized human amniotic membrane (dECMMA). This bioinspired hydrogel (dECMMA/ZIF/PDA) exhibited enhanced photothermal antibacterial activity, controlled drug release, and excellent biocompatibility. In vitro and in vivo studies demonstrated that the hydrogel not only efficiently eradicated bacteria but also promoted macrophage polarization toward an anti-inflammatory M2 phenotype, upregulated angiogenesis-related gene expression, and accelerated wound re-epithelialization and collagen remodeling. Notably, the synergistic action of photothermal therapy and immunomodulation significantly improved healing outcomes in a Staphylococcus aureus (S. aureus) infected wound model. This study presents a promising strategy for chronic wound management by leveraging naturally derived extracellular matrix components and multifunctional nanocarriers to orchestrate immune microenvironment remodeling and tissue regeneration.