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.

中文翻译：

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人血清白蛋白和 NTPDase CD39 之间的重组融合构建体允许医疗器械的抗炎和抗血栓形成涂层

直接接触血液的医疗器械通常用于治疗心血管疾病。然而，这些装置与导致愈合延迟、异物排斥或装置相关血栓形成的炎症反应有关。我们开发了一种新型重组融合蛋白，作为一种新的生物相容性涂层策略，用于直接接触血液的医疗器械。我们将人血清白蛋白 (HSA) 与外核苷三磷酸二磷酸水解酶-1 (CD39) 进行基因融合，CD39 是一种有前途的抗血栓形成和抗炎药物候选物。HSA-CD39 融合蛋白在降解 ATP 和 ADP、主要促炎试剂和血小板激动剂方面具有很强的功能。它们的酶促特性导致 AMP 的产生，AMP 会被 CD73 进一步降解为腺苷，一种抗炎和抗血小板试剂。HSA-CD39 在冻干、包衣和包衣材料储存长达 8 周后起作用。HSA-CD39 涂层即使在灭菌后也显示出有前途和稳定的功能，并且不会阻碍原代人内皮细胞的内皮化。当涂在镍钛诺支架或聚氯乙烯管上时，它显示出高水平的血液相容性和减少的血细胞粘附。总之，我们开发了一种结合 HSA 和 CD39 的新重组融合蛋白，并证明它具有减少血栓形成和炎症并发症的潜力，这些并发症通常与直接接触血液的医疗器械有关。HSA-CD39 涂层即使在灭菌后也显示出有前途和稳定的功能，并且不会阻碍原代人内皮细胞的内皮化。当涂在镍钛诺支架或聚氯乙烯管上时，它显示出高水平的血液相容性和减少的血细胞粘附。总之，我们开发了一种结合 HSA 和 CD39 的新重组融合蛋白，并证明它具有减少血栓形成和炎症并发症的潜力，这些并发症通常与直接接触血液的医疗器械有关。HSA-CD39 涂层即使在灭菌后也显示出有前途和稳定的功能，并且不会阻碍原代人内皮细胞的内皮化。当涂在镍钛诺支架或聚氯乙烯管上时，它显示出高水平的血液相容性和减少的血细胞粘附。总之，我们开发了一种结合 HSA 和 CD39 的新重组融合蛋白，并证明它具有减少血栓形成和炎症并发症的潜力，这些并发症通常与直接接触血液的医疗器械有关。