Surface modification of decellularized bovine carotid arteries with human vascular cells significantly reduces their thrombogenicity

Journal of Biological Engineering

Marie Weinhart¹  Benjamin Strücker²  Hannah Everwien³  Anja Reutzel-Selke³  Nicolai Seiffert³  Peter Tang³  Simon Moosburner³  Eriselda Keshi³  Karl Herbert Hillebrandt⁴  Brigitta Globke⁴  Igor Maximillian Sauer⁵  Johann Pratschke⁵  Nils Haep⁶  Michael Lommel⁷  Ulrich Kertzscher⁷ 

[1] Cluster of Excellence Matters of Activity. Image Space Material funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC 2025 – 390648296, Berlin, Germany;Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany;Institute of Physical Chemistry and Electrochemistry, Leibniz Universität Hannover, Hanover, Germany;Department of General, Visceral and Transplant Surgery, Universitätsklinikum Münster, Münster, Germany;Department of Surgery, Campus Charité Mitte

[2]  Campus Virchow-Klinikum, Experimental Surgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany;Department of Surgery, Campus Charité Mitte

[3]  Campus Virchow-Klinikum, Experimental Surgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany;Berlin Institute of Health (BIH), Berlin, Germany;Department of Surgery, Campus Charité Mitte

[4]  Campus Virchow-Klinikum, Experimental Surgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany;Cluster of Excellence Matters of Activity. Image Space Material funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC 2025 – 390648296, Berlin, Germany;Department of Surgery, Campus Charité Mitte

[5]  Campus Virchow-Klinikum, Experimental Surgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany;Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA;Institute for Cardiovascular Computer-Assisted Medicine, Biofluid Mechanics Lab, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany;

关键词: Decellularization;    Recellularization;    Bypass;    Vascular graft;   

DOI  :  10.1186/s13036-021-00277-2

来源: Springer

【 摘 要 】

BackgroundSince autologous veins are unavailable when needed in more than 20% of cases in vascular surgery, the production of personalized biological vascular grafts for implantation has become crucial. Surface modification of decellularized xenogeneic grafts with vascular cells to achieve physiological luminal coverage and eventually thromboresistance is an important prerequisite for implantation. However, ex vivo thrombogenicity testing remains a neglected area in the field of tissue engineering of vascular grafts due to a multifold of reasons.MethodsAfter seeding decellularized bovine carotid arteries with human endothelial progenitor cells and umbilical cord-derived mesenchymal stem cells, luminal endothelial cell coverage (LECC) was correlated with glucose and lactate levels on the cell supernatant. Then a closed loop whole blood perfusion system was designed. Recellularized grafts with a LECC > 50% and decellularized vascular grafts were perfused with human whole blood for 2 h. Hemolysis and complete blood count evaluation was performed on an hourly basis, followed by histological and immunohistochemical analysis.ResultsWhile whole blood perfusion of decellularized grafts significantly reduced platelet counts, platelet depletion from blood resulting from binding to re-endothelialized grafts was insignificant (p = 0.7284). Moreover, macroscopic evaluation revealed thrombus formation only in the lumen of unseeded grafts and histological characterization revealed lack of CD41 positive platelets in recellularized grafts, thus confirming their thromboresistance.ConclusionIn the present study we were able to demonstrate the effect of surface modification of vascular grafts in their thromboresistance in an ex vivo whole blood perfusion system. To our knowledge, this is the first study to expose engineered vascular grafts to human whole blood, recirculating at high flow rates, immediately after seeding.

【 授权许可】

CC BY