NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany.
Institute of Medical Immunology and BIH Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany.
Cells. 2020 Mar 23;9(3):778. doi: 10.3390/cells9030778.
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.
合适的机械性能和快速的内皮化是确保植入物长期功能的关键。我们使用一种新开发的生物稳定型聚氨酯弹性体(TPCU)来设计具有良好机械性能的电纺血管支架(E-模量:4.8±0.6MPa,爆破压力:3326±78mmHg),并对其进行纤维连接蛋白(FN)和核心蛋白聚糖(DCN)的生物功能化。未涂层或未生物功能化的 TPCU 支架除了少数多形核细胞活化的迹象外,不会引起主要的免疫不良反应。通过吸引内皮祖细胞(ECFCs),在体外模拟生物功能化支架的体内内皮祖细胞归巢潜力。尽管 DCN 涂层与 FN 结合确实可以吸引 ECFCs(FN+DCN),但在没有 FN 的情况下,DCN 涂层的 TPCU 支架表现出细胞排斥效应。在组织工程方法中,将电纺和生物功能化的管状移植物在定制的生物反应器中与原代分离的血管内皮细胞一起进行培养,目的是构建先进的治疗药物产品。FN 和 FN+DCN 的功能化都支持形成一个连续的、功能齐全的内皮层。