Atelocollagen-based hydrogel loaded with Cotinus coggygria 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 wound healing. In this study, a novel wound dressing from fibroblast-laden atelocollagen-based hydrogel with Cotinus coggygria extract was developed for diabetic wound healing. The antimicrobial activity of C. coggygria 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 and Candida albicans, as well as their cytotoxic effects on fibroblasts were determined. While fibroblast growth was significantly (p< 0.05) promoted with DCM (121.41 ± 1.04%), M (109.40 ± 5.89%) and DW (121.83 ± 6.37%) extracts at their lowest concentrations, 2000 μg ml⁻¹ DCM and 7.8 μg ml⁻¹ T extracts had both non-cytotoxic and antifungal effects. An 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 wound dressings. A significant increase in the deoxyribonucleic acid amount (28.27 ± 1.41%) was observed in the plain hydrogel loaded with fibroblasts after 9 d of incubation, and the hydrogel had an extensively interconnected cellular network. The hydrogels containing DW and T extracts were applied to wounds generated in an in vitro 3D type-2-diabetic human skin model. Although the incubation period was not sufficient for closure of the wounds in either of the 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 to improve diabetic wound healing in clinical practice.