Atelocollagen-based hydrogel loaded withCotinus coggygriaextract for treatment of type 2 diabetic wounds.

Candan Yilmaz Ozdogan, Halime Kenar, Huseyin Uzuner, Aynur Karadenizli
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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 withCotinus coggygriaextract was developed for diabetic wound healing. The antimicrobial activity ofC. coggygriahexane (H), dichloromethane (DCM), dichloromethane:methanol (DCM-M), methanol (M), distilled water (DW) and traditional (T) extracts againstStaphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalisandCandida 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-1DCM and 7.8 μg ml-1T 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 anin vitro3D 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.

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载cotinus coggygria提取物的胶原蛋白水凝胶用于治疗2型糖尿病伤口。
糖尿病是一种慢性代谢性疾病,会导致难以治愈的慢性伤口等并发症。已经研究了新的治疗方法来加速伤口愈合。在这项研究中,我们开发了一种新型的伤口敷料,该敷料是由含有成纤维细胞的间胶原蛋白水凝胶和Cotinus coggygria提取物制成的,用于糖尿病伤口愈合。测定了coggygria的己烷(H)、二氯甲烷(DCM)、二氯甲烷甲醇(DCM-M)、甲醇(M)、蒸馏水(DW)和传统提取物(T)对金黄色葡萄球菌、大肠杆菌、铜绿假单胞菌、粪肠球菌、白色念珠菌的抑菌活性及其对成纤维细胞的细胞毒作用。DCM(121.41±1.04%)、M(109.40±5.89%)和DW(121.83±6.37%)提取物的最低浓度均能显著促进成纤维细胞生长(p小于0.05),而2000µg/mL DCM和7.8µg/mL T提取物均具有非细胞毒和抗真菌作用。采用热交联法制备的胶原蛋白基水凝胶,其孔径(38.75±7.67µm)、含水量(96.63±0.24%)和溶胀率(27.21±4.08%)适合创面敷料。培养9天后,成纤维细胞接种的水凝胶中DNA含量显著增加(28.27±1.41%),水凝胶具有广泛连接的细胞网络。将含有DW和T提取物的水凝胶应用于体外3D 2型糖尿病人皮肤模型(DHSM)创面。虽然两种处理的潜伏期都不足以愈合伤口,但含有T提取物的水凝胶刺激了更多的成纤维细胞迁移。在含有T提取物的成纤维细胞的水凝胶中,没有观察到伤口愈合,但更多的角化细胞迁移到伤口区域。这些积极的结果强调了开发的伤口敷料作为改善糖尿病伤口愈合的有力替代方案在临床实践中的潜力。
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