Wounds healing activities of topical chitosan/ Zinc oxide nanocomposite membrane and local insulin injection in diabetic rats through activation of growth factors and suppression of matrix metalloproteinase expressions

Abstract

Diabetes mellitus causes impaired wound healing. In this study, the potential wound healing activities of topical chitosan/ Zinc oxide nanocomposite membrane and local insulin injection in diabetic rats were evaluated. Diabetes was induced by a single IP injection of Streptozotocin (STZ) at a dose of 50mg/kg b.wt. Forty-eight male rats were divided into Six groups. Group I: control wounded, non-treated, non-diabetic rats, Group II: wounded diabetic non-treated, Group III: Normal wounded rats treated with chitosan/ Zinc oxide nanocomposite membrane, Group IV: Diabetic wounded treated with chitosan/ Zinc oxide nanocomposite membrane rats, Group V: wounded diabetic rats treated with local insulin injection, Group VI: Wounded diabetic rats treated with chitosan/ Zinc oxide nanocomposite membrane and local insulin injection. After 14 days of wound treatment, rats were euthanized and the skin tissue was collected for (EGF), (PDGF), (MMP9) and miRNA 21 gene expression analysis. A significant down-regulation of EGF, PDGF and miRNA 21 with up-regulation in MMP 9 were observed in diabetic non treated wounds as compared with control wounded. Meanwhile, a significant increase of EGF, PDGF and miRNA 21 with decrease in MMP 9 gene expression was observed in insulin, Chitosan/ZnO membrane treatment alone or in combination in wounded diabetic rats. Conversely, MMP9 was significantly down regulated after different treatments. The finding indicated that topical Chitosan/ZnO nanocomposite membrane and insulin injection exhibited a great effect on the acceleration of diabetic wound healing via increasing proangiogenic effect, re-epithelialization, and remodeling of ECM .

Biodegradable Polymers in Veterinary Medicine—A Review

“…Due to the activation of interleukine-1 controlling the proliferation of fibroblasts and collagen synthesis, chitosan accelerates the angiogenesis process and migration of neutrophils. It also increases vasculogenesis, as shown in trials with rats and horses [ 39 , 50 , 52 , 56 , 67 , 77 ].…”

“…Chitosan attracts and activates cell growth factors when applied to wounds due to its electrostatic interactions with glycosaminoglycans [ 48 , 49 ]. It was shown to boost vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF-2) expression in animals by immunostaining and treatment with hydrocolloid sponges and chitosan-collagen sponges [ 50 , 52 , 53 ]. Moreover, chitosan hydrogels can serve as storage tanks for various proteins, including growth factors, which can be administered locally to enhance healing [ 53 , 54 , 55 ].…”