Hydroxyethyl cellulose-guided self-assembled pH-independent antibacterial hydrogel for MRSA-infected wound therapy

Wound infections caused by bacterial invasion significantly impair tissue regeneration and prolong healing. While injectable hydrogels show promise for wound management, their clinical application is limited by pH sensitivity in infected wound microenvironments. In this study, we successfully developed a novel pH-independent antibacterial hydrogel (FHAg) via hydroxyethyl cellulose (HEC)-guided self-assembly of Fmoc-Glu-OMe and in situ synthesized silver nanoparticles (AgNPs). The HEC matrix provides a stable structural scaffold for the hydrogel, promotes π-π stacking self-assembly, and confers exceptional stability within a broad pH range (3.0–7.4), effectively overcoming the pH-sensitivity limitation of conventional hydrogels in acidic wound microenvironments. The hydrogel exhibited exceptional biocompatibility, potent antibacterial and antibiofilm activity in vitro. In vivo MRSA -infected rat wound model revealed two key advantages: 99.9% bacterial eradication efficacy and accelerated wound healing within 12 days. This pH-resilient hydrogel platform addresses critical challenges in infected wound care, showing strong potential for clinical translation.