Smart Antibiofilm Platforms Based on Synthetic Antimicrobial Peptides-Engineered Hydrogels

Chronic wounds and implanted medical devices remain highly vulnerable to biofilm-associated infections, which resist conventional antibiotics and immune clearance. Synthetic antimicrobial peptides (AMPs) have emerged as promising alternatives, offering tunable sequences, short lengths for cost-effective synthesis, and functional modifications that enhance stability and antibiofilm potency. Hydrogels provide an optimal delivery matrix by enabling localized AMP release, maintaining a moist wound environment, and supporting stimuli-responsive or sustained therapeutic action. This review highlights recent advances in peptide engineering strategies-including rational sequence design, chemical modifications, and self-assembling nanostructures-alongside hydrogel integration approaches ranging from physical entrapment to covalent tethering and infection-triggered release systems. Mechanistic insights into antibiofilm activity are discussed, supported by in vitro, ex vivo, and in vivo evaluation models. Beyond antimicrobial efficacy, multifunctional AMP-hydrogel systems can deliver complementary benefits such as hemostasis, anti-inflammation, or enzymatic biofilm dispersal, further accelerating tissue repair. Despite significant progress, translational challenges remain, including peptide stability, manufacturing costs, regulatory hurdles, and host safety. Future directions point toward AI-driven peptide design, programmable hydrogels, and point-of-care integration to realize safe, effective, and multifunctional AMP-hydrogel therapies for chronic wound management and biofilm eradication.