Synthetic Polymeric Antibacterial Hydrogel for Methicillin-Resistant <i>Staphylococcus aureus-</i>Infected Wound Healing: Nanoantimicrobial Self-Assembly, Drug- and Cytokine-Free Strategy

Abstract

Antibacterial hydrogels are attracting extensive attention in soft tissue repair and regeneration, including bacteria-infected-wound healing. The abuse of antibiotics leads to drug resistance. Recent developments have demonstrated that the delivery of inorganic bactericidal agents in hydrogels can drive the wound healing process; however, this approach is complicated by external light stimuli, cytotoxicity, nondegradability, and sophisticated fabrication. Herein, an inherent antibacterial, bioresorbable hydrogel was developed by the spontaneous self-aggregation of amphiphilic, oxadiazole-group-decorated quaternary ammonium salts (QAS)-conjugated poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCEC-QAS) micellar nanoantimicrobials for methicillin-resistant <i>Staphylococcus aureus</i> (MRSA)-infected cutaneous wound healing. The PCEC-QAS hydrogel showed a stable gel state within the temperature range of 5-50 °C and antibacterial efficacy against both Gram-negative and -positive bacteria <i>in vitro</i> and <i>in vivo</i>. Additionally, the PCEC-QAS hydrogel facilitated the cell spreading, proliferation, and migration without cytotoxicity. An <i>in vivo</i> degradation and skin defect healing study suggested the PCEC-QAS hydrogel was totally absorbed without local or systemic toxicity and could promote wound repair in the absence of drugs, cytokines, or cells. Significantly, this hydrogel accelerated the regeneration of a MRSA-infected full-thickness impaired skin wound by successfully reconstructing an intact and thick epidermis similar to normal mouse skin. Collectively, a self-assembling PCEC-QAS antibacterial hydrogel is a promising dressing material to promote skin regeneration and prevent bacterial infection without additional drugs, cells, light irradiation, or delivery systems, providing a simple but effective strategy for treating dermal wounds.