#South Korea #Pusan National University #Busan #3D bioprinting #Atherosclerosis

Discovering New Frontiers in Atherosclerosis Research

Atherosclerosis and related cerebrovascular diseases like stroke are significant global health challenges, often characterized by vascular stenosis—a narrowing of blood vessels that disrupts blood flow and contributes to chronic inflammation. Traditional research methods face limitations when studying these processes due to the complexities of living systems. To address these challenges, a team of researchers from Pusan National University, in collaboration with Pohang University of Science and Technology (POSTECH), has made noteworthy advancements in this field.

The Breakthrough Model

Published online in the journal Advanced Functional Materials, the groundbreaking study details the creation of a 3D-bioprinted in vitro model of stenotic brain blood vessels. This innovative project is spearheaded by Professor Byoung Soo Kim and researcher Min-Ju Choi from Pusan National University, alongside Professor Dong-Woo Cho and Dr. Wonbin Park from POSTECH. Professor Kim describes their methodology, stating, "We utilized a new coaxial bioprinting technique to quickly create vascular conduits that accurately simulate the narrowing seen in stenosis."

The specialized bioink used in this study comprises decellularized extracellular matrix derived from porcine aorta, collagen, and alginate, which collectively serves both mechanical strength and biological cues necessary for endothelial cell support. This formulation enabled the team to reproduce the intricate conditions of blood flow in both normal and stenotic vessels altogether.

How It Works

By encapsulating human endothelial cells, including those from umbilical veins and brain microvessels, the model effectively mirrored in vivo blood flow patterns and the geometrical conditions associated with conditions like atherosclerosis. Computational fluid dynamics simulations corroborated the findings, proving that the model recreated disturbed flow patterns characteristic of pathological vessels. Moreover, the endothelialized vessels exhibited complete coverage, maintained junction proteins such as CD31 and VE-cadherin, and showcased selective permeability, thus retaining the essential properties of a functional endothelial barrier.

Interestingly, these disturbed flow conditions led to a notable increase in inflammation markers while the vessels retained mature endothelial characteristics. Professor Kim emphasizes the significant transformation this bioprinting technology brings to cerebrovascular disease modeling, stating, "This advancement bridges the gap between overly simplistic in vitro studies and complex in vivo systems, enhancing drug screenings and toxicity assessments, while also reducing reliance on animal testing."

Future Prospects

Looking forward, the researchers are set to refine the model further. Plans include incorporating brain-specific extracellular matrices, co-culturing vascular support cells, and utilizing patient-derived cells to increase physiological accuracy. The integration with organ-on-a-chip platforms and AI-driven analytics promises real-time monitoring capabilities of endothelial responses to therapies, pushing the boundaries of current biomedical research.

In essence, this study establishes a robust foundation for future cerebrovascular tissue engineering, fueling hopes for breakthroughs in understanding and treating diseases such as stroke and atherosclerosis. The evolution of bioprinting technology could significantly accelerate therapeutic discovery and personalized medicine approaches, heralding a new era in vascular health research.

Reference: Embedded 3D-Coaxial Bioprinting of Stenotic Brain Vessels with a Mechanically Enhanced Extracellular Matrix Bioink for Investigating Hemodynamic Force-Induced Endothelial Responses, Advanced Functional Materials.