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

Abstract

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.

SARS-CoV-2 Papain-like Protease Responsive ZnO/Daclatasvir-Loaded Chitosan/Gelatin Nanofibers as Smart Antimicrobial Medical Textiles: In Silico, In Vitro and Cell Studies

“…Each solution was fed separately into a 5 mL syringe and then electrospun into their corresponding nanofibrous matrices using NANON–O1A (Mecc, Fukuoka, Japan), according to the previously mentioned method [ 2 , 9 , 10 , 35 ]. The optimum parameters were 1 mL/h feed rate, 19 KeV applied voltage, 15 cm distance between syringe and collector, room temperature, and 35% humidity.…”

“…Furthermore, patients with an impaired immune system, including diabetic and cancer patients, suffer from a high risk of microbial and viral infection complications, which in turn, can end up causing trauma and gangrene. Unfortunately, such complications may result in limb amputation or even death [ 2 , 3 , 4 ].…”

Innovative Functional Biomaterials as Therapeutic Wound Dressings for Chronic Diabetic Foot Ulcers

“…PLA is an aliphatic polyester that is easily obtained in an eco-friendly way through the condensation of lactic acid, followed by the ring-opening polymerization of cyclic lactides [ 68 , 118 , 136 , 137 ]. Its good biocompatibility, biodegradability, and relatively high mechanical properties make PLA an appealing material for biomedical applications [ 68 , 118 , 119 ]. In addition, it has been associated with enhanced cell proliferation and growth factor signaling due to its inherent characteristics that make it similar to natural collagen fibers in the extracellular matrix [ 119 ].…”

“…Its good biocompatibility, biodegradability, and relatively high mechanical properties make PLA an appealing material for biomedical applications [ 68 , 118 , 119 ]. In addition, it has been associated with enhanced cell proliferation and growth factor signaling due to its inherent characteristics that make it similar to natural collagen fibers in the extracellular matrix [ 119 ]. A limitation to the clinical use of PLA is its low hydrophilicity, which can be mitigated by combining it with other materials or loading it with bioactive agents [ 118 ].…”

“…In addition, developed nanofiber membranes exhibited antibacterial activity against S. aureus , further highlighting their potential as attractive wound dressings for diabetic wound healing [ 118 ]. Other authors designed multilayered nanofibrous PLA patches for the loading of phenytoin (PHN), sildenafil citrate (SILD), and simvastatin (SIM) with anti-inflammatory, angiogenic, and lymphangiogenic properties, respectively [ 119 ]. Loaded patches kept their physicochemical and mechanical properties, as well as biocompatibility and cell adhesion capacity, in human dermal fibroblasts [ 119 ].…”