Smart/stimuli-responsive metal-organic frameworks for on-demand antibacterial therapy in the oral cavity.

Abstract

Biofilm-associated oral infections, including dental caries, periodontitis, and peri-implantitis, remain fundamentally challenging to manage due to the highly dynamic oral microenvironment and the intrinsic tolerance of multispecies biofilms to conventional antimicrobial strategies. In this context, stimuli-responsive metal-organic frameworks (MOFs) have emerged not merely as drug carriers, but as programmable platforms capable of integrating environmental sensing, on-demand activation, and multimodal antibacterial action. This review critically re-examines smart MOF-based antibacterial systems through the lens of the oral microenvironment, highlighting how pH fluctuations, enzymatic activity, inflammatory redox stress, and biomechanical forces collectively govern MOF stability, activation, and therapeutic performance. We establish oral-specific design principles for stimuli-responsive MOFs, systematically analyze representative MOF families-including ZIFs, Zr-based frameworks, porphyrinic MOFs, and MIL-series materials-and delineate key activation mechanisms driven by pH, enzymes, redox cues, and light. Particular emphasis is placed on the integration of photodynamic therapy (PDT) with controlled antibiotic release, where MOFs enable spatially confined, synergistic disruption of biofilms while mitigating off-target toxicity and antimicrobial resistance. Beyond mechanistic insights, we critically evaluate preclinical evidence across in vitro, ex vivo, and animal models, and identify translational bottlenecks related to biosafety, ion release control, material reproducibility, and clinical deployment in the oral cavity. By bridging oral pathophysiology with materials engineering, this review provides a conceptual and practical framework for the rational design of next-generation, adaptive MOF systems, and offers guidance for prioritizing research directions with the greatest potential for clinical impact in precision antibacterial dentistry.