Fibronectin Adsorption on Electrospun Synthetic Vascular Grafts Attracts Endothelial Progenitor Cells and Promotes Endothelialization in Dynamic In Vitro Culture
Fibronectin Adsorption on Electrospun Synthetic Vascular Grafts Attracts Endothelial Progenitor Cells and Promotes Endothelialization in Dynamic In Vitro Culture
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DOI：
10.3390/cells9030778
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发表时间：
2020-03-01
期刊：
影响因子：
6
通讯作者：
Schenke-Layland, Katja
中科院分区：
文献类型：
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作者：
Daum, Ruben;Visser, Dmitri;Schenke-Layland, Katja
适当的机械性能和快速的内皮化是保证植入物长期功能的关键。我们使用新开发的生物稳定性聚氨酯弹性体（TPCU）来设计具有良好力学性能的电纺丝血管支架（e -模量：4.8 +/- 0.6 MPa，破裂压力：3326 +/- 78 mmHg），并用纤维连接蛋白（FN）和装饰素（DCN）进行生物功能化。除了轻微的多态核细胞活化迹象外，未包被的和生物功能化的TPCU支架都没有引起严重的不良免疫反应。体外通过吸引内皮集落形成细胞（ecfc）模拟生物功能支架的体内内皮祖细胞归巢潜能。虽然DCN涂层与FN （FN + DCN）结合时确实能吸引ecfc，但在没有FN的情况下，DCN涂层的TPCU支架显示出细胞排斥作用。采用组织工程方法，将电纺丝和生物功能管状移植物与原代分离的血管内皮细胞在定制的生物反应器中动态培养，目的是设计一种先进的治疗药物产品。FN和FN + DCN功能化均支持融合和功能性内皮层的形成。
Appropriate mechanical properties and fast endothelialization of synthetic grafts are key to ensure long-term functionality of implants. We used a newly developed biostable polyurethane elastomer (TPCU) to engineer electrospun vascular scaffolds with promising mechanical properties (E-modulus: 4.8 +/- 0.6 MPa, burst pressure: 3326 +/- 78 mmHg), which were biofunctionalized with fibronectin (FN) and decorin (DCN). Neither uncoated nor biofunctionalized TPCU scaffolds induced major adverse immune responses except for minor signs of polymorph nuclear cell activation. The in vivo endothelial progenitor cell homing potential of the biofunctionalized scaffolds was simulated in vitro by attracting endothelial colony-forming cells (ECFCs). Although DCN coating did attract ECFCs in combination with FN (FN + DCN), DCN-coated TPCU scaffolds showed a cell-repellent effect in the absence of FN. In a tissue-engineering approach, the electrospun and biofunctionalized tubular grafts were cultured with primary-isolated vascular endothelial cells in a custom-made bioreactor under dynamic conditions with the aim to engineer an advanced therapy medicinal product. Both FN and FN + DCN functionalization supported the formation of a confluent and functional endothelial layer.