Incorporation of magnesium oxide nanoparticles into electrospun membranes improves pro-angiogenic activity and promotes diabetic wound healing

Highlights: • Incorporating MgO into electrospun membranes improves their moisture permeability without compromising their flexibility. • Incorporated MgO enhances the pro-angiogenic properties and degradation prolife of electrospun nanofiber membranes. • MgO-incorporated membrane alleviates inflammatory response and leads to accelerated diabetic wound healing of rats. Deficient angiogenesis is the major abnormality impairing the healing process of diabetic wounds. Electrospun nanofiber membranes have shown promise for wound dressing. A prerequisite for electrospun membranes to treating diabetic wounds is the capacity to promote angiogenesis of wounds. Current approaches are mainly focused on the use of pro-angiogenic growth factors to enhance the angiogenic properties of electrospun membranes. Despite improved angiogenesis, both the incorporation of growth factors into electrospun nanofibers and maintenance of its activity in the long term is of technical difficulty. We herein report an electrospun membrane made of polycaprolactone (PCL)/gelatin/magnesium oxide (MgO) nanoparticles (PCL/gelatin/MgO), which releases magnesium ions (Mg²⁺) to enhance angiogenesis. MgO-incorporated membranes promote the proliferation of human umbilical vein endothelial cells and upregulate vascular endothelial growth factor (VEGF) production in vitro. Subcutaneous implantation study in a rat model demonstrates that the MgO-incorporated membrane shows a faster degradation profile and elicits moderate immune responses that gradually resolve. Upon subcutaneous implantation, PCL/gelatin/MgO membranes allow robust blood vessel formation as early as one week after surgery, and the newly formed capillary networks enrich within the degrading membrane over time. PCL/gelatin/MgO membranes significantly accelerated diabetic wound healing by suppressing inflammatory responses, promoting angiogenesis, and boosting granulation formation. Taken together, these results are implicative to rationally designing magnesium-incorporated electrospun membranes with improved pro-angiogenic activity for treating diabetic wounds.