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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doaj-88777bf763c04488bacd0ea6dfaeca3d2021-09-26T00:57:14ZengMDPI AGPharmaceutics1999-49232021-09-01131504150410.3390/pharmaceutics13091504A Recombinant Fusion Construct between Human Serum Albumin and NTPDase CD39 Allows Anti-Inflammatory and Anti-Thrombotic Coating of Medical DevicesMeike-Kristin Abraham0Elena Jost1Jan David Hohmann2Amy Kate Searle3Viktoria Bongcaron4Yuyang Song5Hans Peter Wendel6Karlheinz Peter7Stefanie Krajewski8Xiaowei Wang9Clinical Research Laboratory, Department of Thoracic, Cardiac and Vascular Surgery, University Hospital Tübingen, 72076 Tübingen, GermanyClinical Research Laboratory, Department of Thoracic, Cardiac and Vascular Surgery, University Hospital Tübingen, 72076 Tübingen, GermanyAtherothrombosis and Vascular Biology, Baker Heart & Diabetes Institute, Melbourne, VIC 3004, AustraliaAtherothrombosis and Vascular Biology, Baker Heart & Diabetes Institute, Melbourne, VIC 3004, AustraliaAtherothrombosis and Vascular Biology, Baker Heart & Diabetes Institute, Melbourne, VIC 3004, AustraliaMolecular Imaging and Theranostics Laboratory, Baker Heart & Diabetes Institute, Melbourne, VIC 3004, AustraliaClinical Research Laboratory, Department of Thoracic, Cardiac and Vascular Surgery, University Hospital Tübingen, 72076 Tübingen, GermanyAtherothrombosis and Vascular Biology, Baker Heart & Diabetes Institute, Melbourne, VIC 3004, AustraliaClinical Research Laboratory, Department of Thoracic, Cardiac and Vascular Surgery, University Hospital Tübingen, 72076 Tübingen, GermanyMolecular Imaging and Theranostics Laboratory, Baker Heart & Diabetes Institute, Melbourne, VIC 3004, AustraliaMedical 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.https://www.mdpi.com/1999-4923/13/9/1504albuminanti-thromboticCD39coating of medical devicesstent coatingtherapeutic fusion protein |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Meike-Kristin Abraham Elena Jost Jan David Hohmann Amy Kate Searle Viktoria Bongcaron Yuyang Song Hans Peter Wendel Karlheinz Peter Stefanie Krajewski Xiaowei Wang |
spellingShingle |
Meike-Kristin Abraham Elena Jost Jan David Hohmann Amy Kate Searle Viktoria Bongcaron Yuyang Song Hans Peter Wendel Karlheinz Peter Stefanie Krajewski Xiaowei Wang A Recombinant Fusion Construct between Human Serum Albumin and NTPDase CD39 Allows Anti-Inflammatory and Anti-Thrombotic Coating of Medical Devices Pharmaceutics albumin anti-thrombotic CD39 coating of medical devices stent coating therapeutic fusion protein |
author_facet |
Meike-Kristin Abraham Elena Jost Jan David Hohmann Amy Kate Searle Viktoria Bongcaron Yuyang Song Hans Peter Wendel Karlheinz Peter Stefanie Krajewski Xiaowei Wang |
author_sort |
Meike-Kristin Abraham |
title |
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_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_sort |
recombinant fusion construct between human serum albumin and ntpdase cd39 allows anti-inflammatory and anti-thrombotic coating of medical devices |
publisher |
MDPI AG |
series |
Pharmaceutics |
issn |
1999-4923 |
publishDate |
2021-09-01 |
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. |
topic |
albumin anti-thrombotic CD39 coating of medical devices stent coating therapeutic fusion protein |
url |
https://www.mdpi.com/1999-4923/13/9/1504 |
work_keys_str_mv |
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