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    Biological and Medical Applications of Materials and Interfaces

    Improving Hemocompatibility: How Can Smart Surfaces Direct Blood To Fight against Thrombi
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    • Fabian Obstals
      Fabian Obstals
      DWI − Leibniz-Institute for Interactive Materials e.V., Forckenbeckstraße 50, Aachen D-52074, Germany
      Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Forckenbeckstraße 50, Aachen D-52074, Germany
      More by Fabian Obstals
      Orcidhttp://orcid.org/0000-0001-8680-4410
    • Lena Witzdam
      Lena Witzdam
      DWI − Leibniz-Institute for Interactive Materials e.V., Forckenbeckstraße 50, Aachen D-52074, Germany
      Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Forckenbeckstraße 50, Aachen D-52074, Germany
      More by Lena Witzdam
      Orcidhttp://orcid.org/0000-0001-8388-6756
    • Manuela Garay-Sarmiento
      Manuela Garay-Sarmiento
      DWI − Leibniz-Institute for Interactive Materials e.V., Forckenbeckstraße 50, Aachen D-52074, Germany
      Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Forckenbeckstraße 50, Aachen D-52074, Germany
      More by Manuela Garay-Sarmiento
    • Nina Yu. Kostina
      Nina Yu. Kostina
      DWI − Leibniz-Institute for Interactive Materials e.V., Forckenbeckstraße 50, Aachen D-52074, Germany
      Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Forckenbeckstraße 50, Aachen D-52074, Germany
      More by Nina Yu. Kostina
    • Jonas Quandt
      Jonas Quandt
      DWI − Leibniz-Institute for Interactive Materials e.V., Forckenbeckstraße 50, Aachen D-52074, Germany
      Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Forckenbeckstraße 50, Aachen D-52074, Germany
      More by Jonas Quandt
      Orcidhttp://orcid.org/0000-0003-3806-3595
    • Rolf Rossaint
      Rolf Rossaint
      University Hospital Aachen, Pauwelsstraße 30, Aachen D-52074, Germany
      More by Rolf Rossaint
    • Smriti Singh
      Smriti Singh
      DWI − Leibniz-Institute for Interactive Materials e.V., Forckenbeckstraße 50, Aachen D-52074, Germany
      Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Forckenbeckstraße 50, Aachen D-52074, Germany
      More by Smriti Singh
      Orcidhttp://orcid.org/0000-0002-2164-9912
    • Oliver Grottke
      Oliver Grottke
      University Hospital Aachen, Pauwelsstraße 30, Aachen D-52074, Germany
      More by Oliver Grottke
    • Cesar Rodriguez-Emmenegger*
      Cesar Rodriguez-Emmenegger
      DWI − Leibniz-Institute for Interactive Materials e.V., Forckenbeckstraße 50, Aachen D-52074, Germany
      Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Forckenbeckstraße 50, Aachen D-52074, Germany
      *Email: [email protected]
      More by Cesar Rodriguez-Emmenegger
      Orcidhttp://orcid.org/0000-0003-0745-0840
    Other Access OptionsSupporting Information (6)

    ACS Applied Materials & Interfaces

    Cite this: ACS Appl. Mater. Interfaces 2021, 13, 10, 11696–11707
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsami.1c01079
    Published March 3, 2021
    Copyright © 2021 The Authors. Published by American Chemical Society
    Request reuse permissions

    Abstract

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    Nature utilizes endothelium as a blood interface that perfectly controls hemostasis, preventing the uncontrolled formation of thrombi. The management of positive and negative feedback that finely tunes thrombosis and fibrinolysis is essential for human life, especially for patients who undergo extracorporeal circulation (ECC) after a severe respiratory or cardiac failure. The exposure of blood to a surface different from healthy endothelium inevitably initiates coagulation, drastically increasing the mortality rate by thromboembolic complications. In the present study, an ultrathin antifouling fibrinolytic coating capable of disintegrating thrombi in a self-regulated manner is reported. The coating system is composed of a polymer brush layer that can prevent any unspecific interaction with blood. The brushes are functionalized with a tissue plasminogen activator (tPA) to establish localized fibrinolysis that solely and exclusively is active when it is required. This interactive switching between the dormant and active state is realized through an amplification mechanism that increases (positive feedback) or restores (negative feedback) the activity of tPA depending on whether a thrombus is detected and captured or not. Thus, only a low surface density of tPA is necessary to lyse real thrombi. Our work demonstrates the first report of a coating that self-regulates its fibrinolytic activity depending on the conditions of blood.

    Copyright © 2021 The Authors. Published by American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsami.1c01079.

    • Additional data and figures including the grafting of polymer brushes, physicochemical characterization of the surface coating, antifouling measurements, immobilization of tPA on antifouling polymer brushes, feedback loop for the activation of plasminogen by tPA, amplification mechanism to digest fibrin, and static blood experiments (PDF)

    • Video S1. Digestion of a fibrin clot of PMP membranes with tPA-functionalized polymer brushes (MP4)

    • Video S2. No digestion of fibrin on polymer-brush-coated PMP membranes even after 8 h (MP4)

    • Video S3. No digestion of fibrin on bare PMP membranes even after 8 h 30 min (MP4)

    • Video S4. Lab bench video of the full digestion of a fibrin clot of PMP membranes with tPA-functionalized polymer brushes after 5 h compared to the control samples (MP4)

    • Video S5. Lab bench video of the full digestion of a second fibrin clot of PMP membranes with tPA-functionalized polymer brushes after 5 h compared to the control samples (MP4)

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    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

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    This article is cited by 23 publications.

    1. Duanqi Fan, Xiaoli Liu, Hong Chen. Endothelium-Mimicking Materials: A “Rising Star” for Antithrombosis. ACS Applied Materials & Interfaces 2024, 16 (40) , 53343-53371. https://doi.org/10.1021/acsami.4c12117
    2. Jenny Englert, Marc Palà, Lena Witzdam, Farahnaz Rayatdoost, Oliver Grottke, Gerard Lligadas, Cesar Rodriguez-Emmenegger. Green Solvent-Based Antifouling Polymer Brushes Demonstrate Excellent Hemocompatibility. Langmuir 2023, 39 (50) , 18476-18485. https://doi.org/10.1021/acs.langmuir.3c02765
    3. Chia-Hsuan Lin, Shyh-Chyang Luo. Zwitterionic Conducting Polymers: From Molecular Design, Surface Modification, and Interfacial Phenomenon to Biomedical Applications. Langmuir 2022, 38 (24) , 7383-7399. https://doi.org/10.1021/acs.langmuir.2c00448
    4. Feng Wang, Mengdi Liang, Bei Zhang, Weiqiang Li, Xianchen Huang, Xicheng Zhang, Kaili Chen, Gang Li. Advances in artificial blood vessels: Exploring materials, preparation, and functionality. Journal of Materials Science & Technology 2025, 219 , 225-256. https://doi.org/10.1016/j.jmst.2024.09.029
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    6. 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 2025, 43 , 319-329. https://doi.org/10.1016/j.bioactmat.2024.09.011
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    14. Kaijun Li, Jinyu Peng, Yuqi Liu, Fanjun Zhang, Dimeng Wu, Rifang Luo, Zongliang Du, Li Yang, Gongyan Liu, Yunbing Wang. Surface Engineering of Central Venous Catheters via Combination of Antibacterial Endothelium‐Mimicking Function and Fibrinolytic Activity for Combating Blood Stream Infection and Thrombosis. Advanced Healthcare Materials 2023, 12 (23) https://doi.org/10.1002/adhm.202300120
    15. Carlos Eduardo Neri-Cruz, Franciane Mouradian Emidio Teixeira, Julien E. Gautrot. A guide to functionalisation and bioconjugation strategies to surface-initiated polymer brushes. Chemical Communications 2023, 59 (49) , 7534-7558. https://doi.org/10.1039/D3CC01082A
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    17. David Coronel-Meneses, Calef Sánchez-Trasviña, Imma Ratera, Karla Mayolo-Deloisa. Strategies for surface coatings of implantable cardiac medical devices. Frontiers in Bioengineering and Biotechnology 2023, 11 https://doi.org/10.3389/fbioe.2023.1173260
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    20. Jonas Quandt, Manuela Garay‐Sarmiento, Lena Witzdam, Jenny Englert, Yannik Rutsch, Cornelia Stöcker, Fabian Obstals, Oliver Grottke, Cesar Rodriguez‐Emmenegger. Interactive Hemocompatible Nanocoating to Prevent Surface‐Induced Coagulation in Medical Devices. Advanced Materials Interfaces 2022, 9 (33) https://doi.org/10.1002/admi.202201055
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    ACS Applied Materials & Interfaces

    Cite this: ACS Appl. Mater. Interfaces 2021, 13, 10, 11696–11707
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsami.1c01079
    Published March 3, 2021
    Copyright © 2021 The Authors. Published by American Chemical Society
    Request reuse permissions

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