Movable typing of full‐lumen personalized Vein‐Chips to model cerebral venous sinus thrombosis

Author:

Zhao Yunduo Charles123,Zhang Yingqi123,Nasser Arian13ORCID,Hong Tianbo1,Wang Zihao13,Sun Allan1234,Moldovan Laura124,Edwards Leon S567,Passam Freda2389,Butcher Ken S10,Ang Timothy11,Ju Lining Arnold1234ORCID

Affiliation:

1. School of Biomedical Engineering University of Sydney Darlington New South Wales Australia

2. Charles Perkins Centre University of Sydney Camperdown New South Wales Australia

3. The University of Sydney Nano Institute (Sydney Nano), University of Sydney Camperdown New South Wales Australia

4. Heart Research Institute Camperdown New South Wales Australia

5. Department of Neurosciences Gosford Hospital North Gosford New South Wales Australia

6. Sydney Brain Centre Ingham Institute for Applied Medical Research Liverpool New South Wales Australia

7. South Western Sydney Clinical School University of New South Wales Liverpool New South Wales Australia

8. Department of Haematology Royal Prince Alfred Hospital Camperdown New South Wales Australia

9. Central Clinical School Faculty of Medicine and Health University of Sydney Camperdown New South Wales Australia

10. Prince of Wales Clinical School Prince of Wales Hospital Randwick New South Wales Australia

11. Departments of Interventional Neuroradiology Neurology Royal Prince Alfred Hospital Camperdown New South Wales Australia

Abstract

AbstractCerebral venous sinus thrombosis (CVST) is a type of stroke associated with COVID‐19 vaccine‐induced immune thrombotic thrombocytopenia. The precise etiology of CVST often remains elusive due to the highly heterogeneous nature of its governing mechanisms, specifically, Virchow's triad that involves altered blood flow, endothelial dysfunction, and hypercoagulability, which varies substantially amongst individuals. Existing diagnostic and monitoring approaches lack the capability to reflect the combination of these patient‐specific thrombotic determinants. In response to this challenge, we introduce a Vein‐Chip platform that recapitulates the CVST vascular anatomy from magnetic resonance venography and the associated hemodynamic flow profile using the “Chinese Movable Type‐like” soft stereolithography technique. The resultant full‐lumen personalized Vein‐Chips, functionalized with endothelial cells, enable in‐vitro thrombosis assays that can elucidate distinct thrombogenic scenarios between normal vascular conditions and those of endothelial dysfunction. The former displayed minimal platelet aggregation and negligible fibrin deposition, while the latter presented significant fibrin extrusion from platelet aggregations. The low‐cost movable typing technique further enhances the potential for commercialization and broader utilization of personalized Vein‐Chips in surgical labs and at‐home monitoring. Future research and development in this direction will pave the way for improved management and prevention of CVST, ultimately benefiting both patients and healthcare systems.

Funder

Ramaciotti Foundations

Publisher

Wiley

Subject

General Medicine,General Chemistry

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