An Australian-developed artery-on-a-chip could improve prediction of stroke risk by revealing which carotid plaques are most likely to generate dangerous clots.
An Australian-led team has developed a patient-specific artery-on-a-chip that recreates the unique anatomy and blood flow of an individual’s carotid artery, offering a potential new way to identify patients at greatest risk of ischaemic stroke before disaster strikes.
Published in Cell Biomaterials, the proof-of-concept study describes a “physical twin” that combines three-dimensional reconstructions of patients’ carotid arteries with living human cells and flowing blood to model how clots form and break away under real-world conditions.
The technology aims to tackle one of the biggest challenges in stroke prevention: predicting which patients with carotid artery disease will go on to suffer a stroke and which will remain stable.
Current clinical practice relies heavily on the degree of carotid artery narrowing to guide treatment decisions, but this approach has long been recognised as imperfect. Some patients with only moderate narrowing experience devastating strokes, while others with severe stenosis remain symptom-free for years.
Senior author Professor Lining Arnold Ju, from The University of Sydney, said the project was born from that clinical gap.
“We know that even patients at ‘low risk’ can suffer from severe or fatal strokes,” Professor Ju said.
“We wanted to find a better way to predict this risk.”
While clinicians can measure plaque size and the degree of vessel narrowing using imaging, those anatomical features alone provide only a partial picture of stroke risk.
The researchers hypothesised that subtle differences in the three-dimensional geometry of each patient’s artery and the resulting blood flow patterns may play a much greater role in determining whether a clot remains attached or embolises.
To test the theory, they reconstructed carotid arteries from six patients with varying degrees of atherosclerotic disease. Using advanced imaging and computational fluid dynamics, they recreated each patient’s artery as a microfluidic device that reproduced the vessel’s exact shape and blood flow characteristics.
The platform was lined with human endothelial cells to better mimic the biological behaviour of blood vessels.
After creating a controlled laser injury to expose the underlying collagen, the researchers perfused blood through the devices and observed how clots formed, grew, and detached.
Despite similar levels of carotid narrowing, the physical twins demonstrated markedly different patterns of blood flow and clot behaviour.
Some artery geometries generated highly disturbed flow, promoting unstable thrombi that were more likely to embolise. Others produced comparatively stable clot formation despite equivalent degrees of stenosis.
The researchers said the findings suggested that the shape of the artery and the complex local forces generated by blood flow may be stronger determinants of embolic stroke risk than the percentage narrowing currently used in routine assessment.
“Our work recreates precise, patient-specific carotid artery geometries,” Professor Ju said.
“The physical twin also uses cells that more closely mimic the dynamics of blood flow in these structures.”
First author Dr Yunduo Charles Zhao, from the Heart Research Institute in Sydney, said the work had been motivated by personal experience after his grandmother died from a stroke while he was completing his PhD.
“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,” Dr Zhao said.
Current management often involves balancing the risks of carotid endarterectomy or stenting against the possibility of future stroke, particularly in patients without symptoms.
Better methods of identifying unstable plaques could help determine who stands to benefit most from intervention while avoiding unnecessary procedures in lower-risk patients.
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The platform may also provide a realistic environment for testing new anti-thrombotic therapies before they enter clinical trials.
Although the study involved only six patient-derived artery models, the researchers said it demonstrates the feasibility of creating functional physical twins capable of capturing clinically relevant differences between individuals that conventional imaging cannot reveal.
The researchers are currently recruiting stroke patients for a clinical trial to evaluate how this technology can directly benefit underserved stroke patients.
Beyond stroke, they believe the approach could have wider applications across cardiovascular medicine.
By replicating patient-specific blood vessels and flow patterns, they said similar platforms could be adapted to investigate peripheral artery disease, deep-vein thrombosis, and aneurysms, where local haemodynamics also influenced disease progression and clinical outcomes.
While substantial validation would be needed before artery-on-a-chip technology became part of routine clinical care, the researchers said their study represented another step towards precision cardiovascular medicine, in which treatment decisions were informed not only by imaging findings but by realistic laboratory models of how disease behaved within each individual patient.
