The effect of stromal cell-derived factor-1α/heparin coating of biodegradable vascular grafts on the recruitment of both endothelial and smooth muscle progenitor cells for accelerated regeneration.

The effect of stromal cell-derived factor-1α/heparin coating of biodegradable vascular grafts on the recruitment of both endothelial and smooth muscle progenitor cells for accelerated regeneration.
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DOI:
10.1016/j.biomaterials.2012.07.042
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发表时间:
2012-11
期刊:
影响因子:
14
通讯作者:
Li, Song
Li, Song
中科院分区:
工程技术1区
文献类型:
--
作者:
Yu, Jian;Wang, Aijun;Tang, Zhenyu;Henry, Jeffrey;Lee, Benjamin Li-Ping;Zhu, Yiqian;Yuan, Failei;Huang, Fengping;Li, Song

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小直径人工血管移植失败率高,组织工程血管受可扩展性的限制。在这里,我们设计了用于原位血管组织工程的生物活性材料,该材料招募了两种内源性祖细胞用于血管再生。将肝素结合到微纤维血管移植物上以抑制血栓形成反应,并将基质细胞衍生因子-1α (SDF-1α)固定在肝素上以募集内源性祖细胞。在静态和流动条件下,肝素结合的SDF-1α比吸附的SDF-1α更稳定。采用吻合法在大鼠体内植入微纤维移植物,观察其功能性能。肝素包被改善短期通畅,固定化SDF-1α进一步改善长期通畅。SDF-1α有效募集内皮祖细胞(EPCs)到移植物的管腔表面,使其分化为内皮细胞(ECs)并加速内皮化。更有趣的是,SDF-1α增加了平滑肌祖细胞(SMPCs)向移植物的募集,SMPCs在体内和体外分化为平滑肌细胞(SMCs)。同样,sdf -1α-固定的移植物具有明显更高的弹性模量。这项工作证明了同时募集内皮细胞和SMCs祖细胞用于原位血管再生的可行性。这种原位组织工程方法将在再生医学中有广泛的应用。
Small-diameter synthetic vascular grafts have high failure rate and tissue-engineered blood vessels are limited by the scalability. Here we engineered bioactive materials for in situ vascular tissue engineering, which recruits two types of endogenous progenitor cells for the regeneration of blood vessels. Heparin was conjugated to microfibrous vascular grafts to suppress thrombogenic responses, and stromal cell-derived factor-1α (SDF-1α) was immobilized onto heparin to recruit endogenous progenitor cells. Heparin-bound SDF-1α was more stable than adsorbed SDF-1α under both static and flow conditions. Microfibrous grafts were implanted in rats by anastomosis to test the functional performance. Heparin coating improved the short-term patency, and immobilized SDF-1α further improved the long-term patency. SDF-1α effectively recruited endothelial progenitor cells (EPCs) to the luminal surface of the grafts, which differentiated into endothelial cells (ECs) and accelerated endothelialization. More interestingly, SDF-1α increased the recruitment of smooth muscle progenitor cells (SMPCs) to the grafts, and SMPCs differentiated into smooth muscle cells (SMCs) in vivo and in vitro. Consistently, SDF-1α-immobilized grafts had significantly higher elastic modulus. This work demonstrates the feasibility of simultaneously recruiting progenitor cells of ECs and SMCs for in situ blood vessel regeneration. This in situ tissue engineering approach will have broad applications in regenerative medicine.
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