A research team in South Korea has developed a 3D-bioprinted, in-vitro model of stenotic brain blood vessels in an effort to offer new insights into endothelial inflammation and personalised treatment strategies for cerebrovascular diseases like atherosclerosis and stroke.
According to the researchers, while such diseases represent a major global health concern, in-vivo study of vascular stenosis—a common feature of these diseases whereby the narrowing of blood vessels can disrupt normal blood flow and contribute to chronic vessel-wall inflammation—is challenging due to the complexity and variability of living systems. Additionally, traditional in-vitro models often fall short of effectively replicating the structural, mechanical and biological intricacies of the human cerebrovascular environment.
The researchers believe that, as such, there is a need for more physiologically relevant models in order to study how abnormal flow patterns drive endothelial dysfunction and inflammation.
In light of this, a collaborative team led by Byoung Soo Kim and Min-Ju Choi (both Pusan National University, Busan, South Korea), along with Dong-Woo Cho and Wonbin Park (both Pohang University of Science and Technology, Pohang, South Korea), developed a 3D-bioprinted, in-vitro model of stenotic brain blood vessels. Their study has been published online in the journal Advanced Functional Materials.
“We used a novel, embedded, coaxial bioprinting technique to rapidly fabricate perfusable vascular conduits with controlled luminal narrowing,” Kim explained. “Our bioink—a hybrid of porcine aorta-derived decellularised extracellular matrix [ECM], collagen, and alginate—offered both mechanical strength and essential biological cues to support endothelial cell attachment and function.”
The researchers further state that the bioprinted vessels encapsulated human endothelial cells, including umbilical vein and brain microvascular cells, and were exposed to flow conditions simulating both normal and stenotic blood vessels. The model successfully replicated in-vivo blood flow conditions and stenotic geometries associated with cerebrovascular diseases. Computational fluid dynamics simulations and tracer bead experiments confirmed that stenotic regions produced disturbed flow patterns characteristic of atherosclerotic vessels. In addition, endothelialised vessels showed continuous coverage and expressed all junction proteins, including CD31, VE-cadherin, and ZO-1. The vessels also maintained barrier integrity through selective permeability. Disturbed flow conditions triggered significant upregulation of inflammatory markers while the vessels retained characteristics of a mature endothelial barrier as well.
“This 3D bioprinting technology marks a significant advancement in cerebrovascular disease modelling by enabling anatomically accurate and physiologically relevant vessels,” Kim added.
Using a reinforced ECM-based bioink and coaxial bioprinting, the model replicates stenotic vessel geometry and flow dynamics, providing a realistic platform to study flow-induced endothelial inflammation. Its compatibility with multiple endothelial cell types broadens its utility in disease modelling and personalised medicine, according to the researchers—and, by bridging the gap between simplistic in-vitro systems and complex in-vivo models, this platform may reduce reliance on animal testing, and enhance drug screening and toxicity assessments.
They also note that future refinements—such as incorporating brain-specific ECM, co-culturing vascular support cells, and using patient-derived cells—could further enhance physiological accuracy and enable patient-specific modelling. Integration with organ-on-a-chip platforms and artificial intelligence (AI)-driven analytics may allow real-time monitoring of endothelial responses to therapies too, the researchers posit.
