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

BACKGROUND: Since 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 physiol...

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Autores principales: Keshi, Eriselda, Tang, Peter, Weinhart, Marie, Everwien, Hannah, Moosburner, Simon, Seiffert, Nicolai, Lommel, Michael, Kertzscher, Ulrich, Globke, Brigitta, Reutzel-Selke, Anja, Strücker, Benjamin, Pratschke, Johann, Sauer, Igor Maximillian, Haep, Nils, Hillebrandt, Karl Herbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611970/
https://www.ncbi.nlm.nih.gov/pubmed/34819102
http://dx.doi.org/10.1186/s13036-021-00277-2
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author Keshi, Eriselda
Tang, Peter
Weinhart, Marie
Everwien, Hannah
Moosburner, Simon
Seiffert, Nicolai
Lommel, Michael
Kertzscher, Ulrich
Globke, Brigitta
Reutzel-Selke, Anja
Strücker, Benjamin
Pratschke, Johann
Sauer, Igor Maximillian
Haep, Nils
Hillebrandt, Karl Herbert
author_facet Keshi, Eriselda
Tang, Peter
Weinhart, Marie
Everwien, Hannah
Moosburner, Simon
Seiffert, Nicolai
Lommel, Michael
Kertzscher, Ulrich
Globke, Brigitta
Reutzel-Selke, Anja
Strücker, Benjamin
Pratschke, Johann
Sauer, Igor Maximillian
Haep, Nils
Hillebrandt, Karl Herbert
author_sort Keshi, Eriselda
collection PubMed
description BACKGROUND: Since 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. METHODS: After 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. RESULTS: While 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. CONCLUSION: In 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13036-021-00277-2.
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spelling pubmed-86119702021-11-29 Surface modification of decellularized bovine carotid arteries with human vascular cells significantly reduces their thrombogenicity Keshi, Eriselda Tang, Peter Weinhart, Marie Everwien, Hannah Moosburner, Simon Seiffert, Nicolai Lommel, Michael Kertzscher, Ulrich Globke, Brigitta Reutzel-Selke, Anja Strücker, Benjamin Pratschke, Johann Sauer, Igor Maximillian Haep, Nils Hillebrandt, Karl Herbert J Biol Eng Research BACKGROUND: Since 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. METHODS: After 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. RESULTS: While 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. CONCLUSION: In 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13036-021-00277-2. BioMed Central 2021-11-24 /pmc/articles/PMC8611970/ /pubmed/34819102 http://dx.doi.org/10.1186/s13036-021-00277-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Keshi, Eriselda
Tang, Peter
Weinhart, Marie
Everwien, Hannah
Moosburner, Simon
Seiffert, Nicolai
Lommel, Michael
Kertzscher, Ulrich
Globke, Brigitta
Reutzel-Selke, Anja
Strücker, Benjamin
Pratschke, Johann
Sauer, Igor Maximillian
Haep, Nils
Hillebrandt, Karl Herbert
Surface modification of decellularized bovine carotid arteries with human vascular cells significantly reduces their thrombogenicity
title Surface modification of decellularized bovine carotid arteries with human vascular cells significantly reduces their thrombogenicity
title_full Surface modification of decellularized bovine carotid arteries with human vascular cells significantly reduces their thrombogenicity
title_fullStr Surface modification of decellularized bovine carotid arteries with human vascular cells significantly reduces their thrombogenicity
title_full_unstemmed Surface modification of decellularized bovine carotid arteries with human vascular cells significantly reduces their thrombogenicity
title_short Surface modification of decellularized bovine carotid arteries with human vascular cells significantly reduces their thrombogenicity
title_sort surface modification of decellularized bovine carotid arteries with human vascular cells significantly reduces their thrombogenicity
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611970/
https://www.ncbi.nlm.nih.gov/pubmed/34819102
http://dx.doi.org/10.1186/s13036-021-00277-2
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