血管生成
伤口愈合
新生血管
细胞外基质
炎症
巨噬细胞极化
材料科学
脚手架
癌症研究
血管内皮生长因子
肉芽组织
真皮
生物医学工程
细胞生物学
医学
化学
病理
免疫学
巨噬细胞
体外
生物
生物化学
血管内皮生长因子受体
作者
Yanke Hu,Yahui Xiong,Yujie Zhu,Fei Zhou,Xiaogang Liu,Shuying Chen,Zhanpeng Li,Shaohai Qi,Lei Chen
标识
DOI:10.1021/acsami.3c04733
摘要
Morbid dermal templates, microangiopathy, and abnormal inflammation are the three most critical reasons for the scarred healing and the high recurrence rate of diabetic wounds. In this present study, a combination of a methacrylated decellularized extracellular matrix (ECMMA, aka EM)-based hydrogel system loaded with copper-epigallocatechin gallate (Cu-EGCG) capsules is proposed to fabricate bio-printed dermal scaffolds for diabetic wound treatment. Copper ions act as a bioactive element for promoting angiogenesis, and EGCG can inhibit inflammation on the wound site. In addition to the above activities, EM/Cu-EGCG (E/C) dermal scaffolds can also provide optimized templates and nutrient exchange space for guiding the orderly deposition and remodeling of ECM. In vitro experiments have shown that the E/C hydrogel can promote angiogenesis and inhibit the polarization of macrophages to the M1 pro-inflammatory phenotype. In the full-thickness skin defect model of diabetic rats, the E/C dermal scaffold combined with split-thickness skin graft transplantation can alleviate pathological scarring via promoting angiogenesis and driving macrophage polarization to the anti-inflammatory M2 phenotype. These may be attributed to the scaffold-actuated expression of angiogenesis-related genes in the HIF-1α/vascular endothelial growth factor pathway and decreased expression of inflammation-related genes in the TNF-α/NF-κB/MMP9 pathway. The results of this study show that the E/C dermal scaffold could serve as a promising artificial dermal analogue for solving the problems of delayed wound healing and reulceration of diabetic wounds.
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