Mussel-inspired adhesive macromolecule modified zinc oxide nanoparticles incorporated into polyethylene glycol hydrogels for enhancing infected wound healing.

Infected wounds remain a major clinical challenge due to bacterial invasion, which disrupts the natural healing cascade through excessive reactive oxygen species (ROS) generation, severe vascular damage, and persistent inflammation. Inspired by the catechol-rich adhesive domains of mussel foot proteins, we developed an extracellular matrix (ECM)-mimetic polyethylene glycol (PEG) hydrogel incorporating polydopamine (PDA)-functionalized zinc oxide nanoparticles (ZnONPs) for infected wound therapy. The amino acid-functionalized PEG hydrogel reproduces ECM-like properties to facilitate cell migration and efficient exudate management; however, its lack of intrinsic antimicrobial activity limits therapeutic efficacy. To address this limitation, ZnONPs were coated with mussel-inspired PDA, replicating the adhesive and redox-active features of marine-derived macromolecules. PDA surface modification via amidation enhances hydrogel-tissue adhesion and enables sustained release of bioactive Zn²⁺ ions. In vitro, PEG/PDA@ZnONPs hydrogels achieved inhibition rates of 95.1 ± 1.00 % against S. aureus and 95.30 ± 1.15 % against E. coli, and scavenged ∼79 % of DPPH radicals, indicating potent antimicrobial and antioxidant properties. In vivo, the hydrogel modulated macrophage polarization by suppressing the pro-inflammatory M1 phenotype (CD163) and promoting the reparative M2 phenotype (INOS) and enhancing pro-healing signals, leading to 95.1 % wound closure within 14 days compared to 64.8 % in controls. Collectively, these findings highlight PDA-modified ZnONPs-loaded PEG hydrogels as a promising platform for advanced wound management.