Singapore researchers have developed a new 3D model to study vascular diseases

A Singapore team of Singaporean scientists and clinicians from Nanyang Technological University (NTU Singapore) and Tan Tock Seng Hospital (TTSH) has developed a three-dimensional (3D) model of a human arterial vessel wall

This chip is called the "arterial wall chip", and it will help to study atherosclerosis, that is, cholesterol and inflammatory cells form plaques on the blood vessel wall, causing blood vessel stenosis and blood flow contraction, which leads to cardiovascular disease

Cardiovascular diseases account for approximately 32% of deaths in the world, claiming approximately 17.

This 3D model is like a sandwich

The research team used this new microfluidic chip to simulate the cross-section of the artery wall and study the effect of oxidative stress on blood vessels

When free radicals and antioxidants are out of balance, the human body will produce oxidative stress

The study was published in the laboratory on a chip in the Wall Street Journal in June and found that oxidative stress increased and smooth muscle cells moved inward in the middle layer of the artery, leading to inflammation inside the endothelial cell layer of the artery (see Figure 1-Arterial Wall Structure)

In the process of atherosclerosis, the "bad cholesterol" or low-density lipoprotein (LDL) cholesterol and immune cells (white blood cells) in the endothelial layer will also increase, resulting in hardening of the blood vessels and plaque growth

This is the first time that the above effects have been observed in a 3D environment, because previous studies on atherosclerosis have been conducted using animal models or two-dimensional (2D) cell culture.

This discovery was made by an interdisciplinary team led by Assistant Professor Hou Hanwei from the School of Mechanical and Aerospace Engineering of Nanyang Technological University, and Rinkoo Dalan, a senior consultant in endocrinology at TTSH and associate professor of Lee Kong Chian School of Medicine

Professor Hou, the senior author of the study and associate professor at Nanyang Technological University's Lee Kong Chian School of Medicine, said: "Our new'on-the-chip' model can help clinicians better understand the basic biology and vascular dysfunction at the beginning of atherosclerosis.

As part of the research, the team tested two compounds, vitamin D and metformin (a common diabetes drug), and showed that they can help prevent smooth muscle cell migration and immune cell adhesion, two key processes involving atheroma Hardened

In the future, new drug compounds and molecules can also be tested on the arterial wall of the chip to evaluate their effectiveness in preventing the effects of oxidative stress or the reverse migration of smooth muscle cells

Professor Dalan of Assoc said that of all deaths caused by cardiovascular diseases, 58% occurred in Asia[3]: "Despite significant progress in treatment, the mortality and morbidity associated with atherosclerosis are still high.

Derek John Hausenloy, Professor of Cardiovascular and Metabolic Diseases Program at the National University of Singapore School of Medicine and Director of the National Heart Research Institute of Singapore, made an independent comment on the findings: "Cardiovascular disease is the leading cause of death and disability in Singapore and around the world
.
These diseases include cerebrovascular, coronary and peripheral arterial diseases, the main cause of which is atherosclerosis
.
The ability to model atherosclerosis using this new type of human arterial wall chip will help discover and verify the prevention of atherosclerosis A new treatment target for the formation of plaques, and improve the health of these patients
.
"

Finding the best hydrogel (or extracellular matrix) composition is the key to establishing this three-dimensional co-culture model containing multiple types of cells, so that both vascular smooth muscle cells and endothelial cells are kept in a "healthy" state and accurately represent Human artery wall
.

Assistant Professor Tay is also a faculty member in the School of Biological Sciences and an expert in the development of hydrogels.
He said: "This research emphasizes the importance of interdisciplinary methods to solve complex diseases
.
By combining different biological cells with the best cell culture Combining materials, it is now possible to reproduce and simulate the actual conditions in the blood vessels caused by atherosclerosis
.

"This is a positive step in the development of an in vitro preclinical platform that may gradually replace animal testing to better understand diseases and drug testing
.
"

The team now plans to conduct more experiments, use their new chip to further improve the model, and use it to study other vascular diseases, except for atherosclerosis in different stages of development
.

This innovation is consistent with the 2025 strategic plan of Nanyang Technological University.
Addressing the needs and challenges of healthy living and aging is one of the four major human challenges that Nanyang Technological University aims to solve
.

Original search:

DOI 10.
1039 / D1LC00131K

A novel human arterial wall-on-a-chip to study endothelial inflammation and vascular smooth muscle cell migration in early atherosclerosis