From antibiotic impasse to cellular breakthrough: Advances in cell-based and cell-inspired strategies against...

Antimicrobial resistance (AMR) has become a major global health threat, while conventional antibiotics remain limited by microbial dysbiosis, systemic toxicity, poor tissue penetration, biofilm protection, intracellular bacterial persistence, and physiological barriers. In response to these challenges, cell-based and cell-inspired anti-infective strategies have emerged as promising complementary approaches for treating refractory bacterial infections. This review classifies these strategies according to the therapeutic role of the cellular component. First, viable cells can serve as living medicines, using intrinsic or engineered functions such as inflammatory homing, pathogen recognition, phagocytosis, reactive oxygen and nitrogen species generation, antimicrobial peptide secretion, neutrophil extracellular trap formation, and infected-cell killing to enhance bacterial clearance. Second, cells can act as carriers for antimicrobial payloads, including antibiotics, photosensitizers, nanomedicines, and immunomodulators, thereby improving lesion targeting, barrier traversal, local retention, and controlled release. Third, in vivo host-cell modulation can restore or reprogram endogenous immune cells through gene delivery, immune regulation, intracellular infection control, or cell hitchhiking, enhancing host antibacterial defense without ex vivo cellular manufacturing. In addition, cell-derived and biomimetic platforms, including extracellular vesicles, membrane-coated nanoparticles, and artificial cells, can reproduce selected cellular functions such as targeting, immune evasion, toxin neutralization, pathogen capture, and chemical antibacterial activity. This review further discusses the therapeutic mechanisms of these strategies across infection-site targeting, pathogen eradication, immune regulation, and post-infectious tissue recovery. Although preclinical studies have shown encouraging results, current clinical evidence remains concentrated mainly in viable-cell interventions, and robust antibacterial efficacy has not yet been established for many emerging platforms. Key translational challenges include manufacturing scalability, cost-effectiveness, batch consistency, safety control, regulatory classification, and standardized potency assessment. Overall, cell-based and cell-inspired anti-infective strategies are unlikely to replace antibiotics, but they may become important complementary tools for combating persistent, recurrent, and drug-resistant bacterial infections.