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An in vitro 3D diabetic human skin model from diabetic primary cells
Biomedical Materials ( IF 4 ) Pub Date : 2020-12-17 , DOI: 10.1088/1748-605x/abc1b1
Candan Yilmaz Ozdogan 1 , Halime Kenar , Kivanc Emre Davun , Deniz Yucel , Emek Doger , Sahin Alagoz
Affiliation  

Diabetes mellitus, a complex metabolic disorder, leads to many health complications like kidney failure, diabetic heart disease, stroke, and foot ulcers. Treatment approaches of diabetes and identification of the mechanisms underlying diabetic complications of the skin have gained importance due to continued rapid increase in the diabetes incidence. A thick and pre-vascularized in vitro 3D type 2 diabetic human skin model (DHSM) was developed in this study. The methacrylated gelatin (GelMA) hydrogel was produced by photocrosslinking and its pore size (54.85 8.58 μm), compressive modulus (4.53 0.67 kPa) and swelling ratio (17.5 2.2%) were found to be suitable for skin tissue engineering. 8% GelMA hydrogel effectively supported the viability, spreading and proliferation of human dermal fibroblasts. By isolating dermal fibroblasts, human umbilical vein endothelial cells and keratinocytes from type 2 diabetic patients, an in vitro 3D type 2 DHSM, 12 mm in width and 1.86 mm thick, was constructed. The skin model consisted of a continuous basal epidermal layer and a dermal layer with blood capillary-like structures, ideal for evaluating the effects of anti-diabetic drugs and wound healing materials and factors. The functionality of the DHSM was showed by applying a therapeutic hydrogel into its central wound; especially fibroblast migration to the wound site was evident in 9 d. We have demonstrated that DHSM is a biologically relevant model with sensitivity and predictability in evaluating the diabetic wound healing potential of a therapeutic material.



中文翻译:

来自糖尿病原代细胞的体外 3D 糖尿病人体皮肤模型

糖尿病是一种复杂的代谢紊乱,会导致许多健康并发症,如肾衰竭、糖尿病性心脏病、中风和足部溃疡。由于糖尿病发病率持续快速增加,糖尿病的治疗方法和糖尿病皮肤并发症潜在机制的鉴定变得越来越重要。一个厚的和预血管化的体外本研究开发了 3D 2 型糖尿病人体皮肤模型 (DHSM)。通过光交联制备甲基丙烯酸化明胶 (GelMA) 水凝胶,发现其孔径 (54.85 ± 8.58 μm)、压缩模量 (4.53 ± 0.67 kPa) 和溶胀比 (17.5 ± 2.2%) 适用于皮肤组织工程。8% GelMA 水凝胶有效支持人真皮成纤维细胞的活力、扩散和增殖。通过分离 2 型糖尿病患者的真皮成纤维细胞、人脐静脉内皮细胞和角质形成细胞,体外构建了宽度为 12 毫米、厚度为 1.86 毫米的 3D 类型 2 DHSM。皮肤模型由连续的基底表皮层和具有毛细血管样结构的真皮层组成,非常适合评估抗糖尿病药物和伤口愈合材料和因子的效果。DHSM 的功能通过将治疗性水凝胶应用于其中央伤口来显示;特别是成纤维细胞向伤口部位的迁移在 9 d 时很明显。我们已经证明,DHSM 是一种生物学相关模型,在评估治疗材料的糖尿病伤口愈合潜力方面具有敏感性和可预测性。

更新日期:2020-12-17
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