Exogenous and endogenous nitric oxide eluting polylactic acid-based nanofibrous scaffolds for enhancing angiogenesis of diabetic wounds

Delayed wound healing is a major complication that diabetic patients suffer from due to high microbial infection susceptibility, high diabetic wound alkalinity, a low lymphangiogenesis rate, and a high inflammation rate, resulting in severe gangrene. Hence, this study aims to develop a multifunctional adhesive nanofibrous patch to promote the wound healing process. Phenytoin, sildenafil citrate, and/or nitric oxide-eluting nanoparticles were incorporated separately within the polylactic acid nanofibrous layer. Polylactic acid was fabricated in the form of highly porous nanofibrous matrices that resemble the natural structure of skin tissues in order to act as scaffolds that help cell migration and proliferation. A polylactic acid nanofibrous layer incorporating phenytoin was designed to stimulate fibroblast proliferation and inhibit inflammation. Another polylactic acid nanofibrous layer was loaded either with nitric oxide-eluting nanoparticles or sildenafil as a pro-angiogenic layer that can supply tissues with nitric oxide gas either exogenously or endogenously, respectively. The developed nanofibrous layers were in-vitro evaluated through different physicochemical, mechanical, and biological approaches. Finally, the efficiency of the prepared single multilayered patch was tested using an in-vivo alloxan-induced diabetic rats' model, which proved that the patches were able to release the incorporated cargos in a controlled manner, enhancing the wound healing process.