Lysozyme Fiber‐Inspired Versatile Supramolecular Hydrogel Against Drug‐Resistant Pathogens and Biofilm Formation

Abstract Multidrug‐resistant (MDR) bacterial infections pose a significant threat to human health, particularly when introduced by surgical contamination, resulting in early‐stage implant‐related biofilm infections and potential implant failure. Inspired by the structure and function of lysozyme fibers, a biomimetic supramolecular hydrogel is developed that mimics the lysozyme fiber architecture and encapsulates D‐tyrosine (D‐Tyr), integrating bactericidal and anti‐biofilm functions within a self‐assembled positively charged nanofibrous network. The peptide backbone with quaternary ammonium salt‐modified fibers disrupts bacterial cell membranes through direct contact, thereby damaging structural integrity, causing cytoplasmic leakage and killing bacteria; meanwhile, D‐Tyr's effective sustained release inhibits initial bacterial contamination and prevents subsequent biofilm formation. In vivo, experiments demonstrated that the hydrogel significantly accelerated the healing of Methicillin‐resistant Staphylococcus aureus (MRSA)‐infected skin abscesses and prevented implant‐related biofilm infections during the preliminary stages of implantation. By exploiting synergistic bactericidal and anti‐biofilm effects, this lysozyme fiber‐inspired hydrogel offers a promising strategy to combat MDR bacterial infections and prevent biofilm‐related implant complications.