Surface modification of decellularized bovine carotid arteries with human vascular cells significantly reduces their thrombogenicity
Abstract 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...
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oai:doaj.org-article:7ce4d23ac43f4b2180b8285fc3714eff2021-11-28T12:42:10ZSurface modification of decellularized bovine carotid arteries with human vascular cells significantly reduces their thrombogenicity10.1186/s13036-021-00277-21754-1611https://doaj.org/article/7ce4d23ac43f4b2180b8285fc3714eff2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13036-021-00277-2https://doaj.org/toc/1754-1611Abstract 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.Eriselda KeshiPeter TangMarie WeinhartHannah EverwienSimon MoosburnerNicolai SeiffertMichael LommelUlrich KertzscherBrigitta GlobkeAnja Reutzel-SelkeBenjamin StrückerJohann PratschkeIgor Maximillian SauerNils HaepKarl Herbert HillebrandtBMCarticleDecellularizationRecellularizationBypassVascular graftBiology (General)QH301-705.5ENJournal of Biological Engineering, Vol 15, Iss 1, Pp 1-20 (2021) |
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Decellularization Recellularization Bypass Vascular graft Biology (General) QH301-705.5 |
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Decellularization Recellularization Bypass Vascular graft Biology (General) QH301-705.5 Eriselda Keshi Peter Tang Marie Weinhart Hannah Everwien Simon Moosburner Nicolai Seiffert Michael Lommel Ulrich Kertzscher Brigitta Globke Anja Reutzel-Selke Benjamin Strücker Johann Pratschke Igor Maximillian Sauer Nils Haep Karl Herbert Hillebrandt Surface modification of decellularized bovine carotid arteries with human vascular cells significantly reduces their thrombogenicity |
description |
Abstract 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. |
format |
article |
author |
Eriselda Keshi Peter Tang Marie Weinhart Hannah Everwien Simon Moosburner Nicolai Seiffert Michael Lommel Ulrich Kertzscher Brigitta Globke Anja Reutzel-Selke Benjamin Strücker Johann Pratschke Igor Maximillian Sauer Nils Haep Karl Herbert Hillebrandt |
author_facet |
Eriselda Keshi Peter Tang Marie Weinhart Hannah Everwien Simon Moosburner Nicolai Seiffert Michael Lommel Ulrich Kertzscher Brigitta Globke Anja Reutzel-Selke Benjamin Strücker Johann Pratschke Igor Maximillian Sauer Nils Haep Karl Herbert Hillebrandt |
author_sort |
Eriselda Keshi |
title |
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_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_sort |
surface modification of decellularized bovine carotid arteries with human vascular cells significantly reduces their thrombogenicity |
publisher |
BMC |
publishDate |
2021 |
url |
https://doaj.org/article/7ce4d23ac43f4b2180b8285fc3714eff |
work_keys_str_mv |
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