Engineered endothelium-mimicking antithrombotic surfaces via combination of nitric oxide-generation with fibrinolysis strategies

Thrombosis associated with implants can severely impact therapeutic outcomes and lead to increased morbidity and mortality. Thus, developing blood-contacting materials with superior anticoagulant properties is essential to prevent and mitigate device-related thrombosis. Herein, we propose a novel si...

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Main Authors: Wenxuan Wang, Qing Ma, Da Li, Wentai Zhang, Zhilu Yang, Wenjie Tian, Nan Huang
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-01-01
Series:Bioactive Materials
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X24003980
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author Wenxuan Wang
Qing Ma
Da Li
Wentai Zhang
Zhilu Yang
Wenjie Tian
Nan Huang
author_facet Wenxuan Wang
Qing Ma
Da Li
Wentai Zhang
Zhilu Yang
Wenjie Tian
Nan Huang
author_sort Wenxuan Wang
collection DOAJ
description Thrombosis associated with implants can severely impact therapeutic outcomes and lead to increased morbidity and mortality. Thus, developing blood-contacting materials with superior anticoagulant properties is essential to prevent and mitigate device-related thrombosis. Herein, we propose a novel single-molecule multi-functional strategy for creating blood-compatible surfaces. The synthesized azide-modified Cu-DOTA-(Lys)3 molecule, which possesses both NO release and fibrinolysis functions, was immobilized on material surfaces via click chemistry. Due to the specificity, rapidity, and completeness of click chemistry, the firmly grafted Cu-DOTA-(Lys)3 endows the modified material with excellent antithrombotic properties of vascular endothelium and thrombolytic properties of fibrinolytic system. This surface effectively prevented thrombus formation in both in vitro and in vivo experiments, owing to the synergistic effect of anticoagulation and thrombolysis. Moreover, the modified material maintained its functional efficacy after one month of PBS immersion, demonstrating excellent stability. Overall, this single-molecule multifunctional strategy may become a promising surface engineering technique for blood-contacting materials.
format Article
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institution OA Journals
issn 2452-199X
language English
publishDate 2025-01-01
publisher KeAi Communications Co., Ltd.
record_format Article
series Bioactive Materials
spelling doaj-art-3e7746c4f6c244008a893c11bfa48ce22025-08-20T02:22:34ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-01-014331932910.1016/j.bioactmat.2024.09.011Engineered endothelium-mimicking antithrombotic surfaces via combination of nitric oxide-generation with fibrinolysis strategiesWenxuan Wang0Qing Ma1Da Li2Wentai Zhang3Zhilu Yang4Wenjie Tian5Nan Huang6School of Materials Science and Engineering, Key Lab of Advanced Technology of Materials of Education Ministry, Southwest Jiaotong University, Chengdu, 610031, ChinaSchool of Materials Science and Engineering, Key Lab of Advanced Technology of Materials of Education Ministry, Southwest Jiaotong University, Chengdu, 610031, China; Dongguan Key Laboratory of Smart Biomaterials and Regenerative Medicine, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, 523059, ChinaSchool of Materials Science and Engineering, Key Lab of Advanced Technology of Materials of Education Ministry, Southwest Jiaotong University, Chengdu, 610031, ChinaDongguan Key Laboratory of Smart Biomaterials and Regenerative Medicine, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, 523059, ChinaDongguan Key Laboratory of Smart Biomaterials and Regenerative Medicine, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, 523059, China; Corresponding author.Cardiology Department, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China; Corresponding author.School of Materials Science and Engineering, Key Lab of Advanced Technology of Materials of Education Ministry, Southwest Jiaotong University, Chengdu, 610031, China; GuangZhou Nanchuang Mount Everest Company for Medical Science and Technology, Guangzhou, Guangdong, 510670, China; Corresponding author. School of Materials Science and Engineering, Key Lab of Advanced Technology of Materials of Education Ministry, Southwest Jiaotong University, Chengdu, 610031, China.Thrombosis associated with implants can severely impact therapeutic outcomes and lead to increased morbidity and mortality. Thus, developing blood-contacting materials with superior anticoagulant properties is essential to prevent and mitigate device-related thrombosis. Herein, we propose a novel single-molecule multi-functional strategy for creating blood-compatible surfaces. The synthesized azide-modified Cu-DOTA-(Lys)3 molecule, which possesses both NO release and fibrinolysis functions, was immobilized on material surfaces via click chemistry. Due to the specificity, rapidity, and completeness of click chemistry, the firmly grafted Cu-DOTA-(Lys)3 endows the modified material with excellent antithrombotic properties of vascular endothelium and thrombolytic properties of fibrinolytic system. This surface effectively prevented thrombus formation in both in vitro and in vivo experiments, owing to the synergistic effect of anticoagulation and thrombolysis. Moreover, the modified material maintained its functional efficacy after one month of PBS immersion, demonstrating excellent stability. Overall, this single-molecule multifunctional strategy may become a promising surface engineering technique for blood-contacting materials.http://www.sciencedirect.com/science/article/pii/S2452199X24003980Nitric oxideFibrinolysisEndothelium mimickingAntithrombosisSurface modification
spellingShingle Wenxuan Wang
Qing Ma
Da Li
Wentai Zhang
Zhilu Yang
Wenjie Tian
Nan Huang
Engineered endothelium-mimicking antithrombotic surfaces via combination of nitric oxide-generation with fibrinolysis strategies
Bioactive Materials
Nitric oxide
Fibrinolysis
Endothelium mimicking
Antithrombosis
Surface modification
title Engineered endothelium-mimicking antithrombotic surfaces via combination of nitric oxide-generation with fibrinolysis strategies
title_full Engineered endothelium-mimicking antithrombotic surfaces via combination of nitric oxide-generation with fibrinolysis strategies
title_fullStr Engineered endothelium-mimicking antithrombotic surfaces via combination of nitric oxide-generation with fibrinolysis strategies
title_full_unstemmed Engineered endothelium-mimicking antithrombotic surfaces via combination of nitric oxide-generation with fibrinolysis strategies
title_short Engineered endothelium-mimicking antithrombotic surfaces via combination of nitric oxide-generation with fibrinolysis strategies
title_sort engineered endothelium mimicking antithrombotic surfaces via combination of nitric oxide generation with fibrinolysis strategies
topic Nitric oxide
Fibrinolysis
Endothelium mimicking
Antithrombosis
Surface modification
url http://www.sciencedirect.com/science/article/pii/S2452199X24003980
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