Abstract
Most hospital-acquired infections originate from bacterial biofilms on implantable devices, where the extracellular polymeric substance (EPS) matrix protects microbes and promotes multidrug resistance (MDR). Preventing biofilm initiation, particularly bacterial adhesion and proliferation, offers an effective strategy to combat device-associated infections. However, developing biocompatible materials that combine antimicrobial and antiadhesive functions remains a challenge. Herein, we present a strategy to engineer antibiofilm hydrogels by incorporating antimicrobial peptoids (ampetoids) into a gelatin-based matrix with controlled supramolecular organization. By tuning the stoichiometric ratio between thiol-functionalized ampetoids and norbornene groups in the matrix, we controlled peptoid nanostructure within the hydrogel, where suppression of peptoid self-assembly proved critical for balancing antimicrobial activity, antiadhesive properties, and cytocompatibility. This molecular-level control enabled the hydrogels to inhibit biofilm formation by S. aureus and P. aeruginosa. These results highlight regulation of peptoid self-assembly within hydrogels as a promising approach for designing multifunctional antibiofilm coatings for contamination-prone medical devices.