3D Model Accurately Mimics the Blood–Brain Barrier

A 3D model accurately mimicking the Blood-Brain Barrier (BBB) in a laboratory environment has been successfully developed by research teams led by Professor Jinah Jang from the Departments of Mechanical Engineering, Life Sciences, IT Convergence Engineering, and the Graduate School of Convergence at POSTECH, and Professor Sun Ha Paek from the Department of Neurosurgery at Seoul National University Hospital. This study was recently published in Biomaterials Research, an international academic journal on materials science.

Neurodegenerative diseases, including Alzheimer’s, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS), result from the progressive decline of brain and nervous system functions, primarily due to aging. Chronic neuroinflammation, a key driver of these disorders, arises from the intricate interactions between cerebral blood vessels and neural cells, where the BBB plays a pivotal regulatory role. However, existing BBB models have been unable to replicate the complex three-dimensional 3D structure of cerebral blood vessels, posing significant challenges for research and drug development.

To address these limitations, the research team developed a cerebrovascular-specific bioink using “decellularized extracellular matrix” (CBVdECM), derived from porcine brain and blood vessels. Additionally, the team applied 3D bioprinting technology to construct a tubular vascular model that precisely replicates the anatomical structure and function of the human BBB.

A key feature of this model is the spontaneous formation of a dual-layered structure without external stimuli. When “HBMEC (human brain microvascular endothelial cells)” and “HBVP (human brain vascular pericytes)” were incorporated into the CBVdECM bioink and printed, the endothelial cells self-assembled into the inner vascular wall, while pericytes formed a surrounding layer. This resulted in the creation of a dual-layered structure that closely resembles the architecture of actual blood vessels.

Further, the research team successfully replicated the arrangement and organization process of “tight junction proteins,” a component typically absent in conventional 2D models. Additionally, BBB permeability and inflammatory responses were observed following exposure to inflammation-inducing substances (TNF-α and IL-1β). This approach enabled the precise modeling of neuroinflammatory mechanisms, yielding critical insights into the role of BBB dysfunction and inflammation in the pathophysiology of neurodegenerative diseases.

Professor Sun Ha Paek of Seoul National University Hospital commented, “This study provides a crucial platform for investigating the pathological mechanisms of neuroinflammation and developing novel therapeutic strategies.” Professor Jinah Jang of POSTECH added, “We aim to integrate additional cell types, such as glial cells, neurons, and immune cells, to refine methods for quantifying inflammatory responses and permeability, while also expanding to patient-specific disease models.”

This research was supported by Ministry of Trade, Industry & Energy and the Korea Planning & Evaluation Institute of Industrial Technology’s Industrial Technology Alchemist Project, as well as the National Research Foundation of Korea’s University-Focused Research Institute Support Program.

Reference: Han H, Lee S, Gao G, Yi HG, Paek SH, Jang J. Cerebrovascular-specific extracellular matrix bioink promotes blood–brain barrier properties. Biomater Res. 2024;28:0115. doi: 10.34133/bmr.0115

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