Researchers develop a 3D-bioprinted in vitro model of stenotic brain blood vessels

Cerebrovascular diseases such as atherosclerosis and stroke remain a major cause of morbidity and mortality worldwide. A common feature of these diseases is vascular stenosis, i.e., the narrowing of blood vessels, which disrupts normal blood flow and contributes to chronic inflammation in the vessel wall. Endothelial cells lining the vasculature play a key role in sensing shear stress from blood flow and responding to disturbed hemodynamics by expressing pro-inflammatory molecules. However, studying this phenomenon in vivo is challenging due to the complexity and variability of living systems.

Traditional in vitro models, including static cultures and microfluidic devices, often fall short of replicating the structural, mechanical, and biological complexity of the human cerebrovascular environment. This emphasizes the need for a more physiologically relevant model to study how abnormal flow patterns drive endothelial dysfunction and inflammation.

To bridge this critical research gap, a collaborative team led by Professor Byoung Soo Kim and Researcher Min-Ju Choi from Pusan National University, along with Professor Dong-Woo Cho and Dr. Wonbin Park from Pohang University of Science and Technology (POSTECH), developed a 3D-bioprinted in vitro model of stenotic brain blood vessels. Their groundbreaking study was published online in the journal Advanced Functional Materials on June 24, 2025. "We used a novel embedded coaxial bioprinting technique to rapidly fabricate perfusable vascular conduits with controlled luminal narrowing," explains Prof. Kim. "Our bioink, a hybrid of porcine aorta-derived decellularized extracellular matrix (dECM), collagen, and alginate, offered both mechanical strength and essential biological cues to support endothelial cell attachment and function."

The bioprinted vessels encapsulated human endothelial cells, including umbilical vein (HUVECs) and brain microvascular cells (HBMECs), and were exposed to flow conditions simulating both normal and stenotic blood vessels. The model successfully fabricated in vivo blood flow conditions and mimicked stenotic geometries associated with cerebrovascular diseases. Computational fluid dynamics simulations and tracer bead experiments confirmed that stenotic regions produced disturbed flow patterns, characteristic of those seen in atherosclerotic vessels. The endothelialized vessels showed continuous coverage and expressed all junction proteins, including CD31, VE-cadherin, and ZO-1. The vessels also maintained barrier integrity by demonstrating selective permeability. Notably, under disturbed flow conditions, there was a significant upregulation of inflammatory markers, hallmarks of a mature endothelial barrier.

"This 3D bioprinting technology marks a significant advancement in cerebrovascular disease modeling by enabling anatomically accurate and physiologically relevant vessels," shares Prof. Kim. 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 modeling and personalized medicine. By bridging the gap between simplistic in vitro systems and complex in vivo models, this platform also reduces reliance on animal testing and enhances drug screening and toxicity assessments.

Future refinements such as incorporating brain-specific ECM, co-culturing vascular support cells, and using patient-derived cells could further enhance physiological accuracy and patient-specific modeling. Integration with organ-on-a-chip platforms and AI-driven analytics could also enable real-time monitoring of endothelial responses to therapies.

In conclusion, this study delivers a robust and versatile platform for cerebrovascular tissue engineering. As bioprinting technologies continue to evolve, they hold the potential to transform how we study and treat diseases like stroke and atherosclerosis, accelerating therapeutic discovery and the development of personalized interventions.