Injectable polyethylene glycol/methacrylated polylysine double cross-linked hydrogel releases neuropeptides for infected wound healing

Wound infections caused by microorganisms often give rise to extensive inflammation and vascular damage that compromise the wound healing process. Designing approaches to more effectively controlling wound infections and accelerating this healing process are urgently needed. This study was designed with the goal of synthesizing an injectable, double cross-linked hydrogel suitable for use when treating infected wounds. After initially synthesizing methacrylated polylysine (PLMA) through polylysine grafting with methacrylic anhydride, CGRP and PLMA were incorporated into a PEG hydrogel network through reactions between NHS-activated carboxyl esters and amino groups (NH₂). PLMA was also employed to enhance the self-crosslinking activity, culminating in the production of PEG/PLMA/CGRP double cross-linked hydrogels. After injection these hydrogels were capable of undergoing rapid molding such that they were able to conform to the irregularly shaped wound contours. This PEG/PLMA/CGRP formulation was capable of mimicking nerve ending-mediated CGRP secretion to control wound healing, while also exhibiting robust antioxidant, anti-inflammatory, and pro-angiogenic properties. In addition, PEG/PLMA/CGRP hydrogels in vitro showed robust resistance to S. aureus and E. coli. In a rat model of S. aureus-mediated wound infection, this hydrogel markedly promoted wound healing. PEG/PLMA/CGRP hydrogels are thus an effective tool for use in the context of infected wound healing.