摘要
Cerebral 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.
基金
National Health and Medical Research Council(NHMRC)of Australia,Grant/Award Numbers:APP2003904,GNT2022247
NSW Cardiovascular Capacity Building Program,Grant/Award Number:Early-Mid Career Researcher Grant
MRFF Cardiovascular Health Mission Grants,Grant/Award Numbers:APP2016165,APP2023977
Ramaciotti Foundations,Grant/Award Number:2020HIG76
National Heart Foundation,Grant/Award Numbers:106979,106879
Office of Global and Research Engagement,Grant/Award Number:International Sustainable Development Goal Program
Sydney Nano Research Schemes,Grant/Award Number:Grand Challenge
National Heart Foundation Future Leader Fellow Level 2,Grant/Award Number:105863
Snow Medical Research Foundation Fellow,Grant/Award Number:2022SF176
New South Wales Government。