Fibronectin Adsorption on Electrospun Synthetic Vascular Grafts Attracts Endothelial Progenitor Cells and Promotes Endothelialization in Dynamic In Vitro Culture

被引:45
作者
Daum, Ruben [1 ]
Visser, Dmitri [1 ]
Wild, Constanze [2 ,3 ,4 ,5 ,6 ]
Kutuzova, Larysa [7 ]
Schneider, Maria [2 ,3 ,4 ,5 ,6 ]
Lorenz, Guenter [7 ]
Weiss, Martin [1 ,8 ]
Hinderer, Svenja [1 ]
Stock, Ulrich A. [9 ]
Seifert, Martina [2 ,3 ,4 ,5 ,6 ]
Schenke-Layland, Katja [1 ,8 ,10 ,11 ]
机构
[1] Univ Tubingen, NMI Nat & Med Sci Inst, D-72770 Reutlingen, Germany
[2] Charite Univ Med Berlin, Inst Med Immunol, D-13353 Berlin, Germany
[3] Charite Univ Med Berlin, BCRT, D-13353 Berlin, Germany
[4] Free Univ Berlin, D-13353 Berlin, Germany
[5] Humboldt Univ, D-13353 Berlin, Germany
[6] Berlin Inst Hlth, D-13353 Berlin, Germany
[7] Univ Reutlingen, Appl Chem, D-72762 Reutlingen, Germany
[8] Eberhard Karls Univ Tubingen, Res Inst Womens Hlth, Dept Womens Hlth, D-72076 Tubingen, Germany
[9] Royal Brompton & Harefield Fdn Trust, Dept Cardiothorac Surg, Harefield Hosp, Hill End Rd, Harefiled UB9 6JH, England
[10] Eberhard Karls Univ Tubingen, Cluster Excellence iFIT EXC 2180 Image Guided & F, D-72076 Tubingen, Germany
[11] Univ Calif Los Angeles, David Geffen Sch Med, Cardiovasc Res Labs, Dept Med Cardiol, Los Angeles, CA 90095 USA
关键词
vascular graft; endothelialization; tissue engineering; decorin; fibronectin; electrospinning; endothelial progenitor cells; bioreactor; biostable polyurethane; TO-MESENCHYMAL TRANSITION; GROWTH-FACTOR EXPRESSION; BASEMENT-MEMBRANE; EXTRACELLULAR-MATRIX; UP-REGULATION; MECHANICAL-PROPERTIES; FACTOR RECEPTORS; SHEAR-STRESS; STEM-CELLS; DECORIN;
D O I
10.3390/cells9030778
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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页数:29
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