Semi-Interpenetrating Hydrogel with Long-Term Intrinsic Antibacterial Properties Promotes Healing of Infected Wounds <i>In Vivo</i>

Bacterial infections significantly deteriorate the process of wound healing. The wound dressings loaded with antimicrobials are widely used to reduce bacterial infections. However, release-based sterilization may increase the risk of drug resistance of bacteria and complicate translation. Thus, the development of long-term intrinsic antibacterial wound dressings is highly desirable. In this study, an intrinsic antibacterial hydrogel (PVA/PPG-HBPL) consisting of poly(vinyl alcohol) (PVA), poly(polyethylene glycol methyl ether methacrylate-<i>co</i>-glycidyl methacrylate) (PPG), and hyperbranched poly-l-lysine (HBPL) was designed and fabricated. The mechanical properties of the PVA/PPG-HBPL hydrogel were enhanced by hydrogen bonding and semi-interpenetrating networks. It also possessed a favorable ability to absorb the wound exudates. The release of antibacterial HBPL was significantly decreased by the methods of cyclic freeze-thawing and covalent cross-linking during hydrogel fabrication, enabling the PVA/PPG-HBPL hydrogel with intrinsic and long-term antibacterial performance. The PVA/PPG-HBPL hydrogel dressing killed 99.9% of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) cultured on its surface without observable cytotoxicity <i>in vitro</i>. It observably shortened the healing process by 2 orders of magnitude of <i>MRSA</i> colonies compared with the control in the MRSA-infected full-thickness skin wound of rats <i>in vivo</i> even after being soaked in phosphate-buffered saline (PBS) for 21 days (PBS was changed every 3 days). The antibacterial hydrogels could kill wound bacteria in a timely manner, significantly reduce inflammatory cell infiltration, and promote neovascularization and collagen deposition.