A Modular Bottlebrush Polymer Platform for Decoupled Antibacterial and Antifouling Strategies against Wound Infections

Abstract Surface-associated and device-related bacterial infections require materials that can both eliminate pathogens and prevent microbial colonization. However, antibacterial activity in solution and antifouling performance at interfaces are governed by distinct physicochemical principles, making their integration within a single material challenging. Here, we report a modular bottlebrush polymer (BBP) platform that decouples these functions through architectural design. A library of seven BBPs with monoblock and ABA triblock architectures was synthesized to independently control side-chain charge distribution and interfacial hydration. Multivalent cationic side chains promoted efficient bacterial killing in solution, whereas hydrated PEG or zwitterionic bottlebrush layers anchored by cationic termini formed stable antifouling coatings. In diabetic mice, the BBPs showed no evidence of local irritation, systemic toxicity, or impaired wound healing. In an infected wound model, bactericidal BBPs reduced bacterial burden, while antifouling BBPs suppressed local inflammation. Their combined application improved therapeutic outcomes, demonstrating the benefit of a functionally decoupled strategy. Collectively, these findings establish a generalizable architectural framework for designing multifunctional anti-infective materials.