Mineralized double-network hydrogels for the controlled release and improved stability of antimicrobial peptides

Abstract

Antimicrobial peptides (AMPs) have attracted considerable attention in chronic wound management and the prevention of implant-associated infections due to their excellent bactericidal activity, low toxicity, and great biocompatibility. However, their poor stability and uncontrolled release often result in transient efficacy, necessitating frequent administration. Developing a delivery system that ensures both sustained release and mechanical stability is crucial for the clinical translation of AMPs. To address these challenges, in this study, a Ca/P mineralized double-network (DN) hydrogel was developed, which consisted of a physically crosslinked polyvinyl alcohol (PVA) and a previously designed AMP termed IK3, to achieve controlled AMP release. The findings demonstrated that mineralization enhanced the structural integrity of the DN hydrogel while acting as a diffusion-regulating barrier to enable controlled and sustained IK3 release. In vitro antibacterial assays revealed sustained and potent antibacterial activity, with the mineralized hydrogel retaining strong efficacy after two months in PBS and demonstrating excellent biocompatibility. Compared to unmineralized hydrogels, the mineralized DN hydrogel exhibited superior mechanical strength, prolonged antimicrobial efficacy, and a reduced initial burst release. This study presents a novel strategy for optimizing AMP delivery, offering a multifunctional platform with exceptional potential for chronic wound healing and implant-associated infection prevention.