Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1784573055922601984 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8466136 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT abrahammeikekristin arecombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT jostelena arecombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT hohmannjandavid arecombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT searleamykate arecombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT bongcaronviktoria arecombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT songyuyang arecombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT wendelhanspeter arecombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT peterkarlheinz arecombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT krajewskistefanie arecombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT wangxiaowei arecombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT abrahammeikekristin recombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT jostelena recombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT hohmannjandavid recombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT searleamykate recombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT bongcaronviktoria recombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT songyuyang recombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT wendelhanspeter recombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT peterkarlheinz recombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT krajewskistefanie recombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices AT wangxiaowei recombinantfusionconstructbetweenhumanserumalbuminandntpdasecd39allowsantiinflammatoryandantithromboticcoatingofmedicaldevices |