Antimicrobial peptide hydrogels: synthesis, ROS regulation mechanism, and multimodal therapeutic applications in drug delivery systems

Antimicrobial peptides (AMPs) are a unique class of bioactive compounds with applications in antimicrobial therapy, anti-inflammatory regulation, and drug delivery. As antibiotic resistance escalates globally, AMPs have emerged as one of the most promising alternatives to conventional antibiotics. Nevertheless, their clinical utility is limited by pH-dependent instability and enzymatic degradation in vivo. Hydrogels, as versatile polymers, offer solutions through their tunable biological properties. Recent advances at the material-biomedical interface have spurred innovative strategies to engineer AMP hydrogels, overcoming intrinsic limitations. This review presents a comprehensive analysis and discussion of various synthetic approaches to antimicrobial peptide hydrogels, with particular emphasis on mechanisms involving the modulation of reactive oxygen species. Additionally, the current state of antimicrobial peptide hydrogels is explored within antifungal therapy, wound healing, cancer treatment, bioimaging, nucleic acid delivery, immunomodulation, and surgical implants. Finally, we offer a concise perspective on the future trajectory of antimicrobial peptide hydrogel research. We aim to provide a theoretical framework for ongoing studies in this domain and inspire innovative avenues for future investigations.