The toolbox available to researchers on the hunt for new Alzheimer’s treatments has a potential new addition – a 3D model which accurately mimicks the blood-brain barrier (BBB).
Neurodegenerative diseases, including Alzheimer’s, Parkinson’s, 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, researchers have developed a cerebrovascular-specific bioink using “decellularised extracellular matrix” (CBVdECM), derived from porcine brain and blood vessels.
Additionally, they 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 organisation 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.
The research was led by researchers in South Korea, at Pohang University of Science and Technology (POSTECH) and Seoul National University Hospital.
Professor Sun Ha Paek of Seoul National University Hospital, said: “This study provides a crucial platform for investigating the pathological mechanisms of neuroinflammation and developing novel therapeutic strategies.
“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.”