Patient-Specific Carotid Artery-on-a-Chip Platform Maps Shear-Dependent Stroke Risk

Article Impact Level: HIGH
Data Quality: STRONG
Summary of  Cell Biomaterials https://doi.org/10.1016/j.celbio.2026.100541 
Dr. Yunduo Charles Zhao  et al.

Points

University of Sydney researchers developed a patient-specific carotid artery-on-a-chip microfluidic platform to model individual thrombosis and stroke risk.
Reconstructing carotid geometries from six patients demonstrated that three-dimensional vascular shape and local flow dynamics influence clot behavior more than luminal narrowing alone.
Biomechanical testing revealed high-shear zones rely on von Willebrand factor A1 domain platelet capture while low-shear zones promote fragile embolizing thrombi.
Findings confirm that integrating computational fluid dynamics with humanized endothelium allows precise mapping of patient-specific biomechanical phenotypes to targeted therapies.
Clinical trials are evaluating the microfluidic physical twin system to guide personalized antithrombotic selection for stroke and other cardiovascular conditions.

Summary

This study evaluated the feasibility of utilizing a patient-specific carotid artery-on-a-chip “physical twin” platform to predict ischemic stroke risk and thrombus embolization dynamics. Conventional clinical practice relies heavily on anatomical degree of stenosis to assess stroke risk; however, patients with similar lesion severity exhibit markedly variable rates of embolization. The research sought to determine if integrating individualized carotid vessel geometry with humanized thrombogenic matrices and arterial endothelial cells under flow could better resolve patient-specific mechanobiology and shear-dependent clotting mechanisms.

Using microfluidics paired with computational fluid dynamics, the study reconstructed 3D carotid arterial geometries from six patients displaying varying degrees of vascular disease. Hemodynamic simulations and laser-induced collagen injury models revealed that local flow disturbances governed thrombus formation more than simple luminal narrowing. In high-shear regions, platelet capture was driven by von Willebrand factor (VWF) A1 domain interactions. Conversely, low-shear, disturbed-flow regions produced unstable thrombi prone to fragmentation and embolization, highlighting a spatial reorganization of adhesive mechanisms dictated by biomechanical forces.

Clinical utility was further demonstrated by connecting patient-specific vascular geometry to drug response profiles. The findings indicate that microfluidic “physical twins” serve as functional testbeds to identify biomechanical phenotypes, offering a more precise strategy for tailoring antithrombotic therapy than traditional anatomical criteria. Ongoing clinical trials aim to evaluate this platform in stroke cohorts, with potential applications extending to peripheral artery disease, deep-vein thrombosis, and vascular aneurysms.

Link to the article: https://www.cell.com/cell-biomaterials/fulltext/S3050-5623(26)00197-2?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS3050562326001972%3Fshowall%3Dtrue

References

Zhao, Y. C., Liu, Y., Wang, Z., Louis, N. E. L. R., Yap, N. A., Nasser, A., Sun, A., Chen, Y. C., Dupuy, A., Obeng, E. M., Kavurma, M. M., Butcher, K. S., Xu, X., You, J., Passam, F., Ang, T., & Ju, L. A. (2026). Patient-specific carotid artery-on-a-chip “physical twin” dissects complex flow-dependent VWF mechanopresentation. Cell Biomaterials, 100541. https://doi.org/10.1016/j.celbio.2026.100541