A Keratin and Polyacrylamide Dual Network Hydrogel Based on Dynamic Coordination between Polydopamine and Mg2+ for Infected Wound Repair

Abstract Exogenous bacterial infection severely impairs skin wound repair and creates a complex therapeutic challenge that requires simultaneous infection control, oxidative stress regulation, and tissue regeneration. In this study, a PAM/HK/PDANP-Mg2+ multifunctional hydrogel (HPPM) was developed as a cascade therapeutic dressing for infected wounds. In this system, polyacrylamide (PAM) provided a flexible covalently cross-linked framework. Hydrolyzed keratin (HK) offered bioactive and cytocompatible interfaces. Polydopamine nanoparticles (PDANPs) endowed the hydrogel with adhesiveness, photothermal antibacterial activity, and radical scavenging capacity. Coordination between Mg2+ and PDA, together with intermolecular hydrogen bonding, contributed to reversible physical cross-linking within the PAM framework. The optimized HPPM (0.012) hydrogel exhibited a porous structure, high swelling ratio (∼1277%), strong adhesion properties (31.00 kPa), and large tensile elongation (∼560%). Under 808 nm near-infrared (NIR) irradiation, HPPM achieved mild photothermal heating and over 99% antibacterial efficiency against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). It also showed favorable antioxidant activity, cytocompatibility, and pro-migratory effects. In an S. aureus-infected rat wound model, HPPM (0.012) + NIR accelerated wound closure, reduced inflammation, enhanced collagen deposition and re-epithelialization, and regulated IL-10/TNF-α expression. These results suggest that HPPM promotes infected wound healing through dynamic coordination-driven cascade remodeling of the infected wound microenvironment.