Domestic researchers have created a three-dimensional (3D) model of the human blood-brain barrier (BBB) that can elucidate the pathological mechanisms of neurodegenerative diseases like Alzheimer's. This model can replicate the complex process of neuroinflammation, which is a cause of neurodegenerative diseases, potentially offering a new breakthrough in disease research and drug development.
A joint research team led by Professor Jina Jang of Pohang University of Science and Technology (POSTECH) from the Department of Mechanical Engineering, Department of Bioengineering, Department of IT Convergence Engineering, and the Graduate School of Convergence, along with Professor Sunha Baek from the Department of Neurosurgery at Seoul National University Hospital, has successfully implemented a 3D model that accurately mimics the human blood-brain barrier (Blood-Brain Barrier, BBB) in the laboratory. This research was published in December of last year in the international academic journal Biomaterials Research.
Neurodegenerative diseases are conditions in which the functions of the brain and nervous system gradually weaken due to aging, including Alzheimer's, Parkinson's disease, and amyotrophic lateral sclerosis. One of the major causes of these diseases, chronic neuroinflammation, arises from the complex interactions between the blood-brain barrier and nerve cells, with the BBB playing a key role in this process. However, existing research models of the BBB have limitations in studying neurodegenerative diseases as they failed to replicate the complex 3D structures of blood vessels.
To overcome this, the research team developed a bio-ink specialized for blood vessels using decellularized extracellular matrix (CBVdECM1) derived from pig brain and blood vessels. Decellularized extracellular matrix refers to the tissue that remains after cells have been removed from the biological tissue. They then precisely replicated the anatomical structure and function of the human BBB using 3D bioprinting technology to create tube-shaped vascular models.
The most significant feature of this model is that cells form a double-layer structure autonomously without external stimulation. By mixing 'brain microvascular endothelial cells' and 'pericytes' in the CBVdECM1 bio-ink and printing them, the endothelial cells formed the inner wall of the blood vessel while the pericytes created the surrounding layer, producing a double-layer structure similar to actual blood vessels.
Using this developed model, the researchers were able to clearly reproduce the arrangement and organization process of 'tight junction proteins,' which were not observable in existing 2D models. They also successfully observed changes in the permeability of the BBB and inflammatory responses after treating inflammatory substances (TNF-α, IL-1β). The research team noted, "We effectively mimicked the pathological mechanisms of neuroinflammation, and this findings provide new insights into the roles of BBB damage and inflammation in neurodegenerative diseases."
Professor Jina Jang stated, "In the future, we plan to add cells such as astrocytes, neurons, and immune cells to implement more precise inflammatory responses and permeability, and to expand it as a patient-customized disease model." Professor Sunha Baek conveyed the significance of the research, saying, "We have developed an important platform to explore the pathological mechanisms of neuroinflammation and establish new treatment strategies."
Reference materials
Biomaterials Research (2024), DOI: https://doi.org/10.34133/bmr.0115