Fibronectin Adsorption on Electrospun Synthetic Vascular Grafts Attracts Endothelial Progenitor Cells and Promotes Endothelialization in Dynamic In Vitro Culture
Ruben Daum,
Dmitri Visser,
Constanze Wild,
Larysa Kutuzova,
Maria Schneider,
Günter Lorenz,
Martin Weiss,
Svenja Hinderer,
Ulrich A. Stock,
Martina Seifert,
Katja Schenke-Layland
Affiliations
Ruben Daum
NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany
Dmitri Visser
NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany
Constanze Wild
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
Larysa Kutuzova
Applied Chemistry, University of Reutlingen, 72762 Reutlingen, Germany
Maria Schneider
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
Günter Lorenz
Applied Chemistry, University of Reutlingen, 72762 Reutlingen, Germany
Martin Weiss
NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany
Svenja Hinderer
NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany
Ulrich A. Stock
Department of Cardiothoracic Surgery, Royal Brompton and Harefield Foundation Trust, Harefield Hospital Hill End Rd, Harefiled UB9 6JH, UK
Martina Seifert
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
Katja Schenke-Layland
NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany
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.
