Scientists in Australia have developed an artery-on-a-chip platform that can replicate a patient’s exact vascular structure to better assess their risk of ischemic stroke. Results published today in Cell Biomaterials show that differences in artery shape explain significant differences in stroke risk seen between patients with similar levels of artery narrowing.
“Our findings suggested that three-dimensional vascular shape and local flow disturbances matter far more than simple narrowing,” said Yunduo Charles Zhao, graduate student at the University of Sydney and the Heart Research Institute in Newtown, Australia. “We hope these tools will allow us to study drugs aimed at reducing the risk of stroke and to eventually provide personalized treatments for each patient based on their anatomy.”
Despite significant advances in imaging and management, stroke risk stratification is still very imprecise. Nearly 20% of patients receiving what is considered an optimal antiplatelet therapy continue to experience recurrent strokes, reflecting an incomplete understanding on how complex mechanical and biological factors determine whether clots grow, stabilize, or cause a stroke.
“This idea was born out of a critical clinical gap,” said Lining Arnold Ju, PhD, associate professor at the University of Sydney in Australia and senior author of the study. “We know that even patients at ‘low risk’ can suffer from severe or fatal strokes. We wanted to find a better way to predict this risk.”
Ju’s team used high-resolution 3D printing to create a “physical twin” that replicated the three-dimensional structure of the carotid artery from six patients who had previously experienced stroke of the carotid artery. To capture the full complexity of each patient’s unique physiology, the model also included the thrombogenic matrix and endothelium tissues, and simulated blood flow through the chip.
“Our work recreates precise, patient-specific carotid artery geometries,” said Ju. “The physical twin also uses cells that more closely mimic the dynamics of blood flow in these structures.”
Using computer simulations, the researchers modeled blood flow through each carotid artery, uncovering substantial differences in local blood flow despite similar degrees of narrowing. They then used a laser to create an injury in the physical twins and study how blood clots formed, revealing that subtle differences in an artery’s shape could lead to strikingly different clotting responses.
The researchers are currently recruiting patients with a stroke history for a clinical trial designed to evaluate the potential of this technology to improve diagnosis and treatment in underserved stroke patients. Down the line, the artery-on-a-chip physical twins could find applications in other cardiovascular conditions, such as peripheral artery disease, deep-vein thrombosis, and aneurysms.
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