Antimicrobial hydrogels for oral infection management: From molecular design to clinical translation

Oral infections, including periodontitis, peri-implantitis, and endodontic lesions, remain persistent global health burdens exacerbated by antimicrobial resistance (AMR), limited biofilm eradication, and poor drug retention in complex oral microenvironments. Antimicrobial hydrogels have emerged as a transformative class of biomaterials, offering localized, sustained, and multifunctional therapeutic platforms to address these challenges. This review comprehensively delineates the mechanistic principles underlying antimicrobial hydrogel design, ranging from antifouling and contact-killing strategies to quorum-sensing disruption, enzymatic biofilm degradation, and stimuli-responsive drug release. We detail recent innovations in hydrogel formulations incorporating antibiotics, antimicrobial peptides, metal nanoparticles, and immunomodulators, tailored for dental applications. Specifically, injectable and adhesive hydrogel systems have demonstrated significant efficacy in periodontal regeneration, implant surface disinfection, and root canal therapy by integrating antibacterial, anti-inflammatory, antioxidative, and regenerative functions. Furthermore, advanced hydrogel coatings and nanocomposite-infused networks enable responsive and synergistic actions against polymicrobial biofilms while supporting host tissue repair. Despite encouraging preclinical outcomes, translational hurdles-including long-term stability, standardized delivery, and clinical scalability-remain critical barriers. By integrating antimicrobial efficacy with microenvironmental modulation, next-generation hydrogels represent a promising frontier for precision dentistry and biofilm-associated infection control. STATEMENT OF SIGNIFICANCE: The review addresses a critical global health challenge: oral infections such as periodontitis, peri-implantitis, and endodontic lesions, which are exacerbated by antimicrobial resistance, biofilm persistence, and complex oral microenvironments. We provide a comprehensive synthesis of the design principles and therapeutic strategies underpinning antimicrobial hydrogels, including antifouling surfaces, contact-killing mechanisms, quorum-sensing disruption, enzymatic biofilm degradation, and stimuli-responsive drug release. Furthermore, we highlight recent innovations in hydrogel systems incorporating antibiotics, antimicrobial peptides, metal nanoparticles, and immunomodulators, tailored for dental applications.