Atelocollagen-based hydrogel loaded with Cotinus coggygria’s extract for treatment of type 2 diabetic wounds

Abstract Diabetes, a chronic metabolic disease, causes complications such as chronic wounds which are difficult to cure. New treatments have been investigated to accelerate the wound healing. In this study, a novel wound dressing from fibroblast-laden atelocollagen-based hydrogel with Cotinus coggygria’s extract was developed for diabetic wound healing. The antimicrobial activity of C.coggygria’s hexane (H), dichloromethane (DCM), dichloromethane:methanol (DCM-M), methanol (M), distilled water (DW) and traditional (T) extracts against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Candida albicans and their cytotoxic effects on fibroblasts were determined. While fibroblast growth was significantly (p˂0.05) promoted with the DCM (121.41 ± 1.04 %), M (109.40 ± 5.89 %) and DW (121.83 ± 6.37 %) extracts at their lowest concentrations, 2000µg/mL DCM and 7.8µg/mL T extracts had both non-cytotoxic and antifungal effects. The atelocollagen-based hydrogel was produced by thermal-crosslinking and its pore size (38.75 ± 7.67 µm), water content (96.63 ± 0.24 %) and swelling ratio (27.21 ± 4.08 %) were found to be suitable for a wound-dressing. A significant increase in DNA amount (28.27 ± 1.41 %) was observed in the plain hydrogel inoculated with fibroblasts, after 9-day incubation, and the hydrogel had an extensively interconnected cellular network. The hydrogels containing DW and T extracts were applied to wounds generated in the in vitro 3D type-2-diabetic human skin model (DHSM). Although the incubation period was not sufficient for closure of the wounds in both treatments, the hydrogel with T extract stimulated more fibroblast migration. In the fibroblast-laden version of the hydrogel with T extract, no wound closure was observed but more keratinocytes migrated to the wound region. These positive outcomes underline the potential of the developed wound dressing as a powerful alternative in improvement of diabetic wound healing in clinical practice.