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A Recombinant Fusion Construct between Human Serum Albumin and NTPDase CD39 Allows Anti-Inflammatory and Anti-Thrombotic Coating of Medical Devices

Medical devices directly exposed to blood are commonly used to treat cardiovascular diseases. However, these devices are associated with inflammatory reactions leading to delayed healing, rejection of foreign material or device-associated thrombus formation. We developed a novel recombinant fusion p...

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Autores principales: Abraham, Meike-Kristin, Jost, Elena, Hohmann, Jan David, Searle, Amy Kate, Bongcaron, Viktoria, Song, Yuyang, Wendel, Hans Peter, Peter, Karlheinz, Krajewski, Stefanie, Wang, Xiaowei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466136/
https://www.ncbi.nlm.nih.gov/pubmed/34575580
http://dx.doi.org/10.3390/pharmaceutics13091504
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author Abraham, Meike-Kristin
Jost, Elena
Hohmann, Jan David
Searle, Amy Kate
Bongcaron, Viktoria
Song, Yuyang
Wendel, Hans Peter
Peter, Karlheinz
Krajewski, Stefanie
Wang, Xiaowei
author_facet Abraham, Meike-Kristin
Jost, Elena
Hohmann, Jan David
Searle, Amy Kate
Bongcaron, Viktoria
Song, Yuyang
Wendel, Hans Peter
Peter, Karlheinz
Krajewski, Stefanie
Wang, Xiaowei
author_sort Abraham, Meike-Kristin
collection PubMed
description Medical devices directly exposed to blood are commonly used to treat cardiovascular diseases. However, these devices are associated with inflammatory reactions leading to delayed healing, rejection of foreign material or device-associated thrombus formation. We developed a novel recombinant fusion protein as a new biocompatible coating strategy for medical devices with direct blood contact. We genetically fused human serum albumin (HSA) with ectonucleoside triphosphate diphosphohydrolase-1 (CD39), a promising anti-thrombotic and anti-inflammatory drug candidate. The HSA-CD39 fusion protein is highly functional in degrading ATP and ADP, major pro-inflammatory reagents and platelet agonists. Their enzymatic properties result in the generation of AMP, which is further degraded by CD73 to adenosine, an anti-inflammatory and anti-platelet reagent. HSA-CD39 is functional after lyophilisation, coating and storage of coated materials for up to 8 weeks. HSA-CD39 coating shows promising and stable functionality even after sterilisation and does not hinder endothelialisation of primary human endothelial cells. It shows a high level of haemocompatibility and diminished blood cell adhesion when coated on nitinol stents or polyvinylchloride tubes. In conclusion, we developed a new recombinant fusion protein combining HSA and CD39, and demonstrated that it has potential to reduce thrombotic and inflammatory complications often associated with medical devices directly exposed to blood.
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spelling pubmed-84661362021-09-27 A Recombinant Fusion Construct between Human Serum Albumin and NTPDase CD39 Allows Anti-Inflammatory and Anti-Thrombotic Coating of Medical Devices Abraham, Meike-Kristin Jost, Elena Hohmann, Jan David Searle, Amy Kate Bongcaron, Viktoria Song, Yuyang Wendel, Hans Peter Peter, Karlheinz Krajewski, Stefanie Wang, Xiaowei Pharmaceutics Article Medical devices directly exposed to blood are commonly used to treat cardiovascular diseases. However, these devices are associated with inflammatory reactions leading to delayed healing, rejection of foreign material or device-associated thrombus formation. We developed a novel recombinant fusion protein as a new biocompatible coating strategy for medical devices with direct blood contact. We genetically fused human serum albumin (HSA) with ectonucleoside triphosphate diphosphohydrolase-1 (CD39), a promising anti-thrombotic and anti-inflammatory drug candidate. The HSA-CD39 fusion protein is highly functional in degrading ATP and ADP, major pro-inflammatory reagents and platelet agonists. Their enzymatic properties result in the generation of AMP, which is further degraded by CD73 to adenosine, an anti-inflammatory and anti-platelet reagent. HSA-CD39 is functional after lyophilisation, coating and storage of coated materials for up to 8 weeks. HSA-CD39 coating shows promising and stable functionality even after sterilisation and does not hinder endothelialisation of primary human endothelial cells. It shows a high level of haemocompatibility and diminished blood cell adhesion when coated on nitinol stents or polyvinylchloride tubes. In conclusion, we developed a new recombinant fusion protein combining HSA and CD39, and demonstrated that it has potential to reduce thrombotic and inflammatory complications often associated with medical devices directly exposed to blood. MDPI 2021-09-18 /pmc/articles/PMC8466136/ /pubmed/34575580 http://dx.doi.org/10.3390/pharmaceutics13091504 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Abraham, Meike-Kristin
Jost, Elena
Hohmann, Jan David
Searle, Amy Kate
Bongcaron, Viktoria
Song, Yuyang
Wendel, Hans Peter
Peter, Karlheinz
Krajewski, Stefanie
Wang, Xiaowei
A Recombinant Fusion Construct between Human Serum Albumin and NTPDase CD39 Allows Anti-Inflammatory and Anti-Thrombotic Coating of Medical Devices
title A Recombinant Fusion Construct between Human Serum Albumin and NTPDase CD39 Allows Anti-Inflammatory and Anti-Thrombotic Coating of Medical Devices
title_full A Recombinant Fusion Construct between Human Serum Albumin and NTPDase CD39 Allows Anti-Inflammatory and Anti-Thrombotic Coating of Medical Devices
title_fullStr A Recombinant Fusion Construct between Human Serum Albumin and NTPDase CD39 Allows Anti-Inflammatory and Anti-Thrombotic Coating of Medical Devices
title_full_unstemmed A Recombinant Fusion Construct between Human Serum Albumin and NTPDase CD39 Allows Anti-Inflammatory and Anti-Thrombotic Coating of Medical Devices
title_short A Recombinant Fusion Construct between Human Serum Albumin and NTPDase CD39 Allows Anti-Inflammatory and Anti-Thrombotic Coating of Medical Devices
title_sort recombinant fusion construct between human serum albumin and ntpdase cd39 allows anti-inflammatory and anti-thrombotic coating of medical devices
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466136/
https://www.ncbi.nlm.nih.gov/pubmed/34575580
http://dx.doi.org/10.3390/pharmaceutics13091504
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