pH-Responsive Multinetwork Hydrogel with Antibacterial, Anti-Inflammatory, and Microenvironment-Modulating Properties for Enhanced Hemostasis and Wound Healing

Abstract

Hydrogel dressings have emerged as versatile platforms for wound management. However, effective treatment remains challenging due to complex wound environments involving hemorrhage, bacterial infection, and inflammation. Herei, a multifunctional pH-responsive hydrogel (PCOB 1) was developed via multinetwork cross-linking and freeze–thaw cycles using oxidized pullulan (OP), collagen, poly(vinyl alcohol) (PVA), and borax, and was impregnated with in situ stabilized silver nanoparticles (AgNPs). The incorporation of AgNPs endowed the hydrogel with pH-triggered antibacterial activity, achieving >99% killing of E. coli and S. aureus, efficient biofilm disruption, >90% ROS/RNS scavenging, and catalase-mimetic activity. The hydrogel demonstrated rapid gelation, self-healing, and hemostasis within 33.3 s. The hydrogel promoted macrophage polarization from M1 to M2, enhanced collagen deposition, re-epithelialization, and granulation tissue formation, achieving 98.5 ± 0.6% wound closure by day 14 in vivo. This study presents a multifunctional hydrogel with antibacterial, antioxidant, and anti-inflammatory properties for accelerated wound healing.