Semi-Interpenetrating Hydrogel with Long-Term Intrinsic Antibacterial Properties Promotes Healing of Infected Wounds In Vivo.

Abstract

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-co-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 Staphylococcus aureus (MRSA) cultured on its surface without observable cytotoxicity in vitro. It observably shortened the healing process by 2 orders of magnitude of MRSA colonies compared with the control in the MRSA-infected full-thickness skin wound of rats in vivo 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.