Bilayer Polycaprolactone (Mitomycin C)/Poly(L-Lactic Acid)/Gelatine (Dimethyloxalylglycine) Nanofibres for Diabetic Wound Repair

Abstract

Background: Diabetic skin wounds arise from chronic hyperglycaemia, peripheral neuropathy, microvascular dysfunction, and compromised immunity. Chronic ulcers are further complicated by infection and local ischaemia–hypoxia, which collectively impede tissue repair. Conventional interventions, including glycaemic control, anti-infective therapy, debridement, and wound dressings, can only partially relieve clinical symptoms. Since these strategies fail to reverse ischaemia–hypoxia or restore the reparative capacity of endogenous cells, ulcers often recur, healing outcomes remain unsatisfactory, and limb amputation may become unavoidable. To overcome these drawbacks, we fabricated a bilayer electrospun microfibre membrane for diabetic wound repair. Methods: An electrospun microfibre membrane with a bilayer structure was fabricated. The outer layer, composed of polycaprolactone (PCL), provided mechanical support and enabled sustained release of mitomycin C (MMC). The inner layer, formulated with a 7:3 ratio of poly-L-lactic acid (PLLA) to gelatine (Gel), was designed to match the mechanical properties of the wound bed and was loaded with dimethyloxalylglycine (DMOG). Antibacterial assays against Escherichia coli and Staphylococcus aureus, as well as proangiogenic evaluations in ischaemic tissues, were conducted to characterise this composite membrane. Results: The outer PCL layer provided mechanical support and enabled sustained MMC release, producing effective antibacterial effects against E. coli and S. aureus. The DMOG-incorporated inner PLLA/GEL layer displayed favourable mechanical compatibility with wound tissue and successfully promoted angiogenesis under ischaemic conditions. By remodelling the wound microenvironment, the biomaterial improved vascularisation and decreased the bacterial load, ultimately accelerating the repair of diabetic skin wounds. Conclusions: This bilayer electrospun membrane integrates antibacterial and pro-angiogenic functions, showing promising application potential for the treatment of diabetic skin wounds.