Antibacterial biomaterials: disruption of antibiotic tolerance for resistance prevention

Antimicrobial resistance (AMR) remains a critical global health challenge, exacerbated by antibiotic misuse that accelerates bacterial tolerance and undermines therapeutic efficacy. The lack of new antibiotics and the high cost of drug development further intensify the urgency for the development of alternative antimicrobial strategies. Emerging evidence suggests that biomaterials can disrupt the progression from antimicrobial tolerance (AMT) to AMR, offering a promising avenue to enhance treatment outcomes and suppress the rise of resistant strains. This review outlines the transition mechanisms from bacterial tolerance to resistance and explores how biomaterials can counter these adaptations. Using properties such as electrostatic interactions, ligand coordination, and vesicular disruption, biomaterials can inhibit bacterial growth and alter the metabolism, preventing AMT-to-AMR progression. They also initiate programmed cell death pathways and generate oxidative stress through photothermal, photodynamic, and chemodynamic therapies, and can also target bacterial DNA and protein synthesis. Additionally, biomaterials enhance immune responses including neutrophil activity and macrophage polarisation. Using biofilm and intracellular infection models, we show that biomaterials effectively prevent biofilm formation and target intracellular pathogens. Finally, we summarize infection mechanisms in organoid-based models, including immune and bacteria-organoid systems. In summary, this review highlights biomaterials as versatile agents with outstanding potential for future antimicrobial strategies. • Addressing the progression of antibiotic tolerance-to-resistance using biomaterial based strategies. • Strategies include bacterial targeting, regulation and disruption of bacterial activities and immunotherapy. • Treatment of biofilms and intracellular bacteria. • Highlighting advanced approaches such as bacterial-organoid models.