Radially Electrospun Fibrous Membrane Incorporated with Copper Peroxide Nanodots Capable of Self-Catalyzed Chemodynamic Therapy for Angiogenesis and Healing Acceleration of Diabetic Wounds.

Abstract

Vascular dysfunction severely hinders the healing process of diabetic wounds. Therefore, a radially structured fibrous membrane was fabricated through electrospinning by using a polycaprolactone (PCL) and polyvinylpyrrolidone (PVP) mixed solution containing copper peroxide nanoparticles (CPs) as the chemodynamic therapy (CDT) agents, aiming to simultaneously accelerate tissue regeneration and angiogenesis. The fabricated membrane allowed for the in situ H2O2 generation activated by the acidic diabetic microenvironment and the subsequent Fenton-type reactions to realize 99.4% elimination against Staphylococcus aureus. Besides, the released Cu2+ ions significantly enhanced the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in human umbilical vein endothelial cells (HUVECs), and they showed enhanced in vitro angiogenesis. Interestingly, the CP-embedded membrane also guided cell spreading and orientated migration of L929 fibroblasts along the fiber distribution through the radially aligned topology. The in vivo implantation indicated that the raidally structured membrane modified by CPs not only dramatically accelerated wound healing of diabetic Sprague-Dawley (SD) rats in 14 days but also promoted angiogenesis in wound sites. The combination of the in situ CDT with the radially structured morphology of the functional membrane is highly promising in applications to promote diabetic wound healing through anti-infection and revascularization.