Antimicrobial peptide hydrogel delivery systems: Design strategies and functional expansion.

Antimicrobial peptides (AMPs), owing to their unique membrane-disrupting mechanism and low susceptibility to resistance, represent important candidate therapeutics for combating multidrug-resistant bacterial infections. However, their clinical application is constrained by issues such as poor in vivo stability, short half-life, low bioavailability, and potential toxicity. Hydrogels, as biocompatible delivery platforms, can effectively encapsulate, protect, and control the release of AMPs through their three-dimensional network structure, significantly improving their pharmacokinetic properties and therapeutic efficacy. This review outlines the principles underlying the construction of peptide-based hydrogels, hybrid material hydrogels, composite delivery systems, and stimulus-responsive hydrogels, with particular emphasis on how these design strategies specifically address the challenges associated with delivering AMPs. Building upon this foundation, we have conducted an in-depth analysis of characteristics and existing challenges of hydrogels containing AMPs through three key pathways, including synergistic antimicrobial action, microenvironment regulation, and optimisation of in vivo processes. The article concludes by outlining the immense potential of artificial intelligence technology in advancing the intelligent design and personalised treatment of hydrogels containing AMPs. It further examines the core challenges currently confronting clinical translation and explores future development directions. This work aims to provide theoretical reference and practical guidance for the research and development of next-generation high-performance hydrogel systems containing AMPs.