Design, development, in-vitro and in-vivo evaluation of polylactic acid-based multifunctional nanofibrous patches for efficient healing of diabetic wounds

Impaired healing of diabetic ulcers is one of the major complications of diabetic patients due to high susceptibility to microbial infections, impaired lymphianogenesis, edema, and consequently impairing proper healing. This could even lead to much worse complications that include severe gangrene, trauma and finally limb amputation. Therefore, this study aims to develop a multilayered durable nanofibrous wound patch loaded with three promising drugs (phenytoin, sildenafil citrate and simvastatin) each in a separate layer to target a different wound healing phase. Polylactic acid was used for the preparation of the nanofibrous matrix of the wound patch, where each drug was incorporated in a separate layer during the preparation process. Drugs release profiles were studied over 3 weeks. Results showed that both phenytoin and simvastatin were released within 14 days while sildenafil continued till 21 days. Both physicochemical and mechanical characteristics of the patches were fully assessed as well as their biodegradability, swellability, breathability and porosity. Results showed that incorporation of drugs preserved the physicochemical and mechanical properties as well as porosity of the developed nanofibers. In addition, patches were evaluated for their biocompatibility and cell adhesion capability before being tested through in-vivo diabetic wound rat model induced by alloxan for three weeks. In vivo results showed that the patches were successful in inducing proper wound healing in diabetic rat model with overcoming the above-mentioned obstacles within 3 weeks. This was confirmed through assessing wound closure as well as from histopathological studies that showed complete healing with proper cell regeneration and arrangement without forming scars.