Contrasting biofunctionalization strategies for the enhanced endothelialization of biodegradable vascular grafts.

Contrasting biofunctionalization strategies for the enhanced endothelialization of biodegradable vascular grafts.
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DOI:
10.1021/bm501853s
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发表时间:
2015-02-09
期刊:
影响因子:
6.2
通讯作者:
Fisher, J. P.
Fisher, J. P.
中科院分区:
化学2区
文献类型:
--
作者:
Melchiorri, A. J.;Hibino, N.;Yi, T.;Lee, Y. U.;Sugiura, T.;Tara, S.;Shinoka, T.;Breuer, C.;Fisher, J. P.

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生物可降解血管移植物的表面改性是改善组织工程血管移植物(TEVG)原位内皮化和预防当前合成移植物相关主要并发症的重要策略。改善内皮化的重要策略包括通过TEVG的生物功能化增加内皮细胞动员和增加内皮细胞捕获。本研究的目的是评估两种生物功能化策略,以改善可生物降解聚酯血管移植物的内皮化。这些技术包括将肝素交联到移植物表面,以抑制血管内皮生长因子(VEGF)或抗CD34抗体(抗CD34Ab)。为此,肝素、VEGF和抗CD34Ab附着和定量测定证实了修饰策略的有效性。在体外和体内将这些组上的细胞附着和增殖与未修饰的移植物进行比较。为了评估体内移植物功能,将移植物作为下腔静脉间置导管植入小鼠体内。根据显微镜技术、组织学结果和eNOS表达,改良的血管移植物在体内显示内皮细胞附着和活性增加。改良移植物的内腔直径也比对照组保持得更好。总的来说,虽然两种功能化的移植物都优于未修饰的对照,但与加载VEGF的移植物相比,用抗CD34 Ab修饰的移植物似乎产生了最大的改善结果。
Surface modification of biodegradable vascular grafts is an important strategy to improve the in situ endothelialization of tissue engineered vascular grafts (TEVGs) and prevent major complications associated with current synthetic grafts. Important strategies for improving endothelialization include increasing endothelial cell mobilization and increased endothelial cell capture through biofunctionalization of TEVGs. The objective of this study was to assess two biofunctionalization strategies for improving endothelialization of biodegradable polyester vascular grafts. These techniques consisted of cross-linking heparin to graft surfaces to immobilize vascular endothelial growth factor (VEGF) or antibodies against CD34 (anti-CD34Ab). To this end, heparin, VEGF, and anti-CD34Ab attachment and quantification assays confirmed the efficacy of the modification strategy. Cell attachment and proliferation on these groups were compared to unmodified grafts in vitro and in vivo. To assess in vivo graft functionality, the grafts were implanted as inferior vena cava interpositional conduits in mice. Modified vascular grafts displayed increased endothelial cell attachment and activity in vivo, according to microscopy techniques, histological results, and eNOS expression. Inner lumen diameter of the modified grafts was also better maintained than controls. Overall, while both functionalized grafts outperformed the unmodified control, grafts modified with anti-CD34Ab appeared to yield the most improved results compared to VEGF-loaded grafts.
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