Multifunctional dynamic cerium-polypeptide hydrogel with antibacterial antioxidative anti-inflammatory for multidrug-resistant bacterial infected wound healing

Bacterial infection, especially multidrug-resistant (MDR) bacterial infection, is a great challenge in clinical wound repair, highlighting the urgent to develop antibacterial hydrogel dressing. In this work, a multifunctional cerium-polypeptide hydrogel (FEPC) with comprehensive antibacterial, antioxidant, anti-inflammatory and angiogenesis ability was developed for the treatment of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) infected wounds. The FEPC hydrogel was constructed using Ce³⁺ and antibacterial polypeptide co-crosslinked γ-polyglutamic acid (γ-PGA) through double dynamic electrostatic and coordination interaction. This unique dynamic architecture endowed FEPC with outstanding injectability and rapid self-healing capacity, ensuring conformal coverage of irregular wounds. <i>In vitro</i> experiments demonstrated that FEPC showed robust antibacterial activity, and could effectively eliminate reactive oxygen species (fixed terminology). Meanwhile, the FEPC hydrogel could downregulate the expression of pro-inflammatory cytokines and promote angiogenesis by upregulating the VEGF expression. Importantly, <i>in vivo</i> assessments using MRSA-infected full-thickness wounds showed that FEPC hydrogel could rapidly repair the MRSA infected wounds (54% wound repair rate on Day 3 for FEPC <i>vs</i> reported hydrogel below 40% rate) and promote epithelialization and hair follicle regeneration within 14 days. Histological analysis confirmed that FEPC hydrogel could significantly inhibit infection and excessive inflammation, as well as accelerate angiogenesis. This work suggests that cerium-polypeptide hydrogel is a perfect partner for treating MDR bacterial infected wounds, providing a viable solution for synergistically combat infection, oxidative stress and other related-disease treatments.