Strategies for biofilm disruption: Mechanisms, polymeric networks, mixed infections, and emerging biomaterials.
Biofilms represent the predominant microbial lifestyle in clinical and environmental settings, where the extracellular polymeric substance (EPS) matrix provides structural integrity, metabolic cooperation, and pronounced antimicrobial tolerance. This matrix forms a dynamic macromolecular network of polysaccharides, proteins, extracellular DNA (eDNA), lipids, and associated ions that collectively regulate hydration, adhesion, diffusion resistance, and persistence. Across ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens and Candida albicans, conserved matrix components shape biofilm architecture, enabling nutrient sequestration, immune evasion, and chronic infection. Mechanistic advances in biofilm eradication highlight the roles of enzymatic depolymerization, antibiotic penetration dynamics, nanoparticle-mediated disruption, bacteriophage-encoded depolymerases, and antibody-guided targeting. Parallel progress in biofilm inhibition emphasizes quorum-sensing interference, adhesion blockade, surface engineering, vaccines, and immunomodulatory strategies that prevent early community establishment. Emerging approaches-including peptide nucleic acids, aptamers, CRISPR-based antimicrobials, and biofilm-responsive delivery systems-enable precise targeting of genetic and structural vulnerabilities. Together, these developments provide a mechanistic foundation for next-generation antibiofilm interventions and support translational strategies aimed at recalcitrant, persistent infections.