Pusan National University unveils 3D-printed brain vessels to transform atherosclerosis research

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.

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Reference
DOI: https://doi.org/10.1002/adfm.202504276

About Pusan National University
Pusan National University, located in Busan, South Korea, was founded in 1946 and is now the No. 1 national university of South Korea in research and educational competency. The multi-campus university also has other smaller campuses in Yangsan, Miryang, and Ami. The university prides itself on the principles of truth, freedom, and service and has approximately 30,000 students, 1,200 professors, and 750 faculty members. The university comprises 14 colleges (schools) and one independent division, with 103 departments in all.

Website: https://www.pusan.ac.kr/eng/Main.do

About the author

Byoung Soo Kim is an Associate Professor in the Department of Biomedical Convergence Engineering at Pusan National University. His research spans 3D printing, cell and tissue mechanics, artificial organs, and biomimetic systems. He leads the 3D Printing and Biofabrication Lab, focusing on the development of functional biomaterials and in vitro disease models using bioprinting technology. He earned his PhD in Mechanical Engineering from POSTECH and completed postdoctoral training at the Catholic University of Korea-POSTECH Biomedical Engineering Research Institute at Seoul St. Mary’s Hospital. He also served as a visiting researcher at Northwestern University Feinberg School of Medicine.

Lab website address: https://sites.google.com/view/3pab-lab/welcome?authuser=0

ORCID id: 0000-0002-6693-0003