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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

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posted on 14.10.2021, 05:37 by MK Abraham, E Jost, JD Hohmann, AK Searle, V Bongcaron, Y Song, HP Wendel, Karlheinz PeterKarlheinz Peter, S Krajewski, Xiaowei WangXiaowei Wang
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.

Funding

This work was funded by the Australian National Health and Medical Research Council (NHMRC) and in part by the Victorian Government Operational Infrastructure Support Program. M.-K.A. was supported by the German Research Association (Deutsche Forschungsgemeinschaft); E.J. was supported by the Promotionskolleg des interdisziplinaren Zentrums fur Klinische Forschung (IZKF); A.S.K. was supported by the National Heart Foundation (NHF) Australian Indigenous Scholarship; K.P. was supported by a National Health and Medical Research Council Investigator Fellowship; S.K. was supported by the Margarete von Wrangell-Habilitationsstipendium des Minis- teriums fur Wissenschaft, Forschung und Kunst Baden-Wurttemberg; and X.W. was supported by an NHF Future Leader Fellowship with the Paul Korner Innovation Award and a Baker Fellowship.

History

Publication Date

18/09/2021

Journal

Pharmaceutics

Volume

13

Issue

9

Article Number

1504

Pagination

18p.

Publisher

MDPI

ISSN

1999-4923

Rights Statement

© 2021 by the authors. 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/).

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