Engineering Metal-Organic Frameworks for Enhanced Antimicrobial Efficacy: Synthesis Methodologies, Mechanistic Perspectives, and Versatile Applications.

Bacterial contamination and the escalating crisis of antibiotic resistance represent pressing global public health threats, with approximately 4.95 million deaths linked to antimicrobial resistance (AMR) in 2019 and projections estimating up to 10 million annual fatalities by 2050. As third-generation antimicrobial materials, metal-organic frameworks (MOFs) have emerged as promising alternatives to conventional agents, leveraging their unique attributes such as high specific surface areas, tunable porosity, and controlled metal ion release kinetics. This review provides a systematic analysis of the foundational principles and core antibacterial mechanisms of MOFs, which include the sustained release of metal ions (e.g., Ag⁺, Cu²⁺, Zn²⁺), the generation of reactive oxygen species (ROS), and synergistic effects with encapsulated functional molecules. We highlight how these mechanisms underpin their efficacy across a range of applications. Rather than offering an exhaustive list of synthesis methods and metal compositions, this review focuses on clarifying structure-function relationships that enable MOF-based materials to outperform conventional antimicrobials. Their potential is particularly evident in several key areas: wound dressings and medical coatings that enhance tissue regeneration and prevent infections; targeted nanotherapeutics against drug-resistant bacteria; and functional coatings for food preservation and water disinfection. Despite existing challenges, including gaps in clinical translation, limited efficacy in complex multi-species infections, and incomplete mechanistic understanding, MOFs hold significant promise to revolutionize antimicrobial therapy. Through interdisciplinary optimization and advancements in translational research, MOFs are poised to drive a paradigm shift from "passive defense" to "active ecological regulation", offering a critical solution to mitigate the global AMR crisis.