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Vascular scaffolds with enhanced antioxidant activity inhibit graft calcification
Biomaterials ( IF 12.8 ) Pub Date : 2017-08-14 , DOI: 10.1016/j.biomaterials.2017.08.014
Bin Jiang , Rachel Suen , Jiao-Jing Wang , Zheng J. Zhang , Jason A. Wertheim , Guillermo A. Ameer

There is a need for off-the-shelf, small-diameter vascular grafts that are safe and exhibit high long-term patency. Decellularized tissues can potentially be used as vascular grafts; however, thrombogenic and unpredictable remodeling properties such as intimal hyperplasia and calcification are concerns that hinder their clinical use. The objective of this study was to investigate the long-term function and remodeling of extracellular matrix (ECM)-based vascular grafts composited with antioxidant poly(1, 8-octamethylene-citrate-co-cysteine) (POCC) with or without immobilized heparin. Rat aortas were decellularized to create the following vascular grafts: 1) ECM hybridized with POCC (Poly-ECM), 2) Poly-ECM subsequently functionalized with heparin (Poly-ECM-Hep), and 3) non-modified vascular ECM. Grafts were evaluated as interposition grafts in the abdominal aorta of adult rats at three months. All grafts displayed antioxidant activity, were patent, and exhibited minimal intramural cell infiltration with varying degrees of calcification. Areas of calcification co-localized with osteochondrogenic differentiation of vascular smooth muscle cells, lipid peroxidation, oxidized DNA damage, and cell apoptosis, suggesting an important role for oxidative stress in the calcification of grafts. The extent of calcification within grafts was inversely proportional to their antioxidant activity: Poly-ECM-Hep > ECM > Poly-ECM. The incorporation of antioxidants into vascular grafts may be a viable strategy to inhibit degenerative changes.

中文翻译:

具有增强的抗氧化活性的血管支架抑制移植物钙化

需要现成的,小直径的血管移植物,这些移植物是安全的并且表现出高的长期开放性。去细胞的组织可以潜在地用作血管移植物。然而,血栓形成和不可预测的重塑特性(如内膜增生和钙化)成为阻碍其临床应用的担忧。这项研究的目的是研究具有或不具有固定化肝素的抗氧化剂聚(1,8-八亚甲基柠檬酸酯-co-半胱氨酸)(POCC)复合抗氧化剂的基于细胞外基质(ECM)的血管移植物的长期功能和重塑。大鼠主动脉脱细胞以产生以下血管移植物:1)与POCC(Poly-ECM)杂交的ECM,2)随后被肝素(Poly-ECM-Hep)功能化的Poly-ECM,和3)未修饰的血管ECM。在三个月时将移植物评估为成年大鼠腹主动脉中的介入移植物。所有移植物均显示出抗氧化活性,具有专利性,并且在不同钙化程度下,壁内细胞浸润最少。钙化区域与血管平滑肌细胞的成骨细胞分化,脂质过氧化,氧化的DNA损伤和细胞凋亡共存,提示氧化应激在移植物钙化中起重要作用。移植物中的钙化程度与其抗氧化活性成反比:Poly-ECM-Hep> ECM> Poly-ECM。将抗氧化剂掺入血管移植物中可能是抑制退行性变化的可行策略。并表现出最小的壁内细胞浸润和不同程度的钙化。钙化区域与血管平滑肌细胞的成骨细胞分化,脂质过氧化,氧化的DNA损伤和细胞凋亡共存,提示氧化应激在移植物钙化中起重要作用。移植物中的钙化程度与其抗氧化活性成反比:Poly-ECM-Hep> ECM> Poly-ECM。将抗氧化剂掺入血管移植物中可能是抑制退行性变化的可行策略。并表现出最小的壁内细胞浸润和不同程度的钙化。钙化区域与血管平滑肌细胞的成骨细胞分化,脂质过氧化,氧化的DNA损伤和细胞凋亡共存,提示氧化应激在移植物钙化中起重要作用。移植物中的钙化程度与其抗氧化活性成反比:Poly-ECM-Hep> ECM> Poly-ECM。将抗氧化剂掺入血管移植物中可能是抑制退行性变化的可行策略。提示氧化应激在移植钙化中的重要作用。移植物中的钙化程度与其抗氧化活性成反比:Poly-ECM-Hep> ECM> Poly-ECM。将抗氧化剂掺入血管移植物中可能是抑制退行性变化的可行策略。提示氧化应激在移植钙化中的重要作用。移植物中的钙化程度与其抗氧化活性成反比:Poly-ECM-Hep> ECM> Poly-ECM。将抗氧化剂掺入血管移植物中可能是抑制退行性变化的可行策略。
更新日期:2017-08-17
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