From Infection Control to Tissue Regeneration: Mechanisms, Design Strategies, and Smart Advances in Antibacterial Hydrogels

Abstract

Bacterial infection, biofilm formation, and the associated oxidative stress and persistent inflammation represent major obstacles to wound healing, tissue engineering, and implantable medical devices. Owing to their highly hydrated three-dimensional networks, favorable tissue compatibility, and versatile capacity for functional loading, hydrogels have been widely investigated for the treatment of infected wounds. This review systematically summarizes the major antibacterial mechanisms of hydrogels, including cationic contact-killing, chemical antibacterial activity mediated by metal ions and reactive halogen species, nanozyme-catalyzed reactions and bidirectional regulation of reactive oxygen species, as well as photothermal synergistic antibacterial therapy. Key design strategies are also discussed, including natural polymer-based matrices, multiple dynamic crosslinking, stimuli-responsive controlled release, three-dimensional printing, and spatial compartmentalization. In addition, recent advances in infection-microenvironment regulation, wet-interface adaptation, temporally coordinated tissue repair, and integrated diagnosis and therapy are highlighted. The field is currently shifting from single-mode bacterial eradication toward multistage tissue repair and intelligent theranostics. However, major challenges remain, including balancing antibacterial efficacy with biosafety, achieving reproducible manufacturing and sterilization-compatible formulations, maintaining functional stability during storage, and improving the clinical relevance and standardization of preclinical evaluation. In addition, most smart systems still lack quantitative coupling among pathological signals, therapeutic dosage, and treatment outcomes. Future studies should therefore integrate mechanistic design with manufacturing reproducibility, clinically relevant validation, and quantitative feedback regulation, thereby advancing antibacterial hydrogels from multifunctional proof-of-concept systems toward precise, controllable, and clinically translatable therapeutic platforms.