Formulation-Dependent Antibacterial Performance: Design and Biomedical Applications

Over the past decade, antibacterial materials have become a promising strategy to address both antibiotic-resistant and biomaterial-associated infections in clinical settings. Despite substantial progress, a gap remains between promising antibacterial performance in vitro and limited therapeutic outcomes in vivo. Herein, we present a mechanistic framework for understanding formulation-dependent antibacterial performance across five representative formulation architectures: nanoparticle-based systems, nanofibrous scaffolds, hydrogel matrices, surface coatings, and vesicular or microencapsulated carriers. We impart how structural organization and delivery dynamics regulate antibacterial mechanisms such as contact-mediated killing, controlled therapeutic release, and reactive oxygen species (ROS) generation and discuss their context-dependent suitability for diverse infection scenarios; these include acute wound infections, biofilm-associated implant infections, and chronic infected wounds. Particular emphasis is placed on factors contributing to the frequent failure of high in vitro log reduction efficacy translating into clinical success, including protein corona formation, biological barrier penetration, and dynamic host-pathogen interactions. Finally, we propose a comparative formulation-selection framework based on infection type, tissue environment, and therapeutic objectives to guide the rational design of next-generation antibacterial materials. This perspective bridges the gap between material innovation and clinical translation by highlighting formulation architecture as a central determinant of antibacterial performance in biomedical applications.