Development of Inherently Antibacterial, Biodegradable, and Biologically Active Chitosan/Pseudo-Protein Hybrid Hydrogels as Biofunctional Wound Dressings

Developing a new family of hydrogel-based wound dressings that could have a dual biofunctionality of antibacterial and biological responses is highly desirable. In this study, an inherently effective antibacterial and biodegradable hydrogel dressing without the need for impregnated antibiotics was designed, synthesized, characterized, and examined for its effect on macrophages, which initiated inflammatory activity and activated both NO and TNF-α production for the purpose of achieving a better and faster wound healing. The purposes of this research was to develop a novel family of cationic biodegradable hydrogels based on arginine-based poly(ester urea urethane) (Arg-PEUU) and glycidyl methacrylate-modified chitosan (CS-GMA) that has both inherent antibacterial and bioactive functionality as a wound healing dressing for accelerated healing of contaminated or infected wounds. These hybrid hydrogels present a well-defined three-dimensional microporous network structure and have a high water absorption ability, and their biodegradation is effectively accelerated in the presence of lysozymes. The hemolytic activity test, MTT assay, and live/dead assay of these hybrid hydrogels indicated that they had no cytotoxicity toward red blood cells, NIH-3T3 fibroblast cells, and human vascular endothelial cells, thus corroborating their cytocompatibility. Furthermore, these hybrid hydrogels could elevate the release of both produced NO and TNF-α by stimulating and activating RAW 264.7 macrophages, augmenting their antibacterial biological response. The antibacterial assay of these hybrid hydrogels demonstrated their excellent antibacterial activity without the need for impregnated antibacterial agents. Taken together, this new family of biodegradable, antibacterial, and biologically responsive hybrid hydrogels exhibits great potential as biofunctional antibacterial wound dressing candidates for wound healing.