From Antimicrobial Biomaterials to Infection-Resilient Interfaces: Engineering the Host, Microbe, and Material Interface Against Drug-Resistant Biofilms

Drug-resistant biofilm infections remain a major challenge for medical devices and implants. Biofilm formation can reduce antimicrobial effectiveness through physiological heterogeneity, tolerance, persistence, and interactions with the host and biomaterial surface. Antimicrobial biomaterials have been developed to prevent colonization, detect infection, provide antimicrobial activity, control established biofilms, and support tissue recovery. However, their performance depends on the biological context in which they function. This review examines these strategies through interactions among the host, microbe, and material, using carbapenem-resistant Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus, and carbapenem-resistant Pseudomonas aeruginosa as selected biological stress-test examples for evaluating biomaterial performance. It also considers the limitations in current evaluation, including planktonic testing, biological conditioning, microbial adaptation, effects on non-target microorganisms, material stability, manufacturing, and clinical translation. Antimicrobial activity alone does not establish effective performance in infection. Material function must match the microbial state, host environment, and intended clinical use while maintaining host compatibility and function during use. We propose infection resilience as a design framework organized around Prevent, Detect, Respond, Resolve, and Regenerate. Infection resilience refers to coordinated material performance under changing microbial and host conditions rather than the number of functions incorporated into a material. This framework offers a practical basis for more biologically relevant evaluation and purposeful design of antimicrobial biomaterials for drug-resistant biofilm infections.