Chitosan and polyvinyl alcohol-based bilayer electrospun nanofibrous membrane incorporated with astaxanthin promotes diabetic wound healing by addressing multiple factors

Delayed diabetic wound regeneration can be attributed to multiple underlying factors, including bacterial infection, endogenous reactive oxygen species (ROS), impaired angiogenesis and exaggerated inflammatory response. Here, a bilayer electrospun nanofibrous membrane (ENM) was fabricated through sequential electrospinning to accelerate diabetic wound healing by addressing aforementioned challenges. For the purpose, nano Zinc Oxide was mixed into chitosan as the bottom layer of ENM (CS/ZnO NPs), while astaxanthin (AST) was encapsulated in a composite nanofibrous membrane of polyvinyl alcohol, chitosan and Ti 3 C 2 T X MXene (PVA/CS/MXene) as the upper layer, thus preparing the bilayer CZ/PCM@AST ENM, which reflected the therapeutic properties of spatial structure distribution and time series on diabetic wounds. The bilayer CZ/PCM@AST ENM was verified to possess sufficient biocompatibility and effective antibacterial properties on E. coli and S. aureus . Furthermore, the ENM facilitated sustained AST release at inflammatory sites, effectively scavenging excessive ROS and inhibiting inflammatory responses, ultimately accelerating diabetic wound healing, as demonstrated through both in vitro and in vivo evaluations. In summary, the multi-effect combination strategy improved complicated pathological microenvironment of wound sites, thereby presenting a promising method in diabetic wound treatment. Scheme 1: Fabrication process of CZ/PCM@AST ENM by coaxial electrospinning and mechanism for the potential application of CZ/PCM@AST ENM in the microenvironment of diabetic wound healing. (Created with BioRender.com , with permission).