A biomimetic chip that mimics the microenvironment of adipose tissue has been developed, which is expected to enable the identification of obesity-related diseases and the development of treatments.

UNIST (President Yong-Hoon Lee) announced on the 6th that Professor Tae-Eun Park's research team in the Department of Biomedical Engineering has developed a microphysiological system that mimics the physiological and pathological characteristics of human white adipose tissue.

Adipose tissue is a type of connective tissue in the body that is mostly composed of fat cells. Among them, white adipose tissue plays an important role in storing energy in the body and maintaining homeostasis, and is an endocrine organ that secretes various substances such as fatty acids and hormones.

Obesity, which is caused by excessive fat accumulation in white adipose tissue, is the disease with the highest mortality rate worldwide. In addition, obesity can cause various complications such as diabetes and cardiovascular disease, and is also related to the occurrence and worsening of some cancers.

As interest in obesity grows worldwide, models that can mimic the physiological and pathological characteristics of adipose tissue are being developed.

However, existing culture methods have had difficulties in differentiating into adipocytes containing single-sphere-shaped fat lumps and maintaining the functionality of the differentiated cells. Furthermore, there were limitations in mimicking the microenvironment of adipose tissue and reproducing its physiological and pathological characteristics.

The research team successfully developed an adipose tissue biomimetic chip that mimics the physiological and pathological characteristics of obese adipose tissue.

The developed biomimetic chip consists of an upper microchannel in which adipocytes are cultured three-dimensionally in a hydrogel structure based on extracellular matrix (ECM) separated from adipose tissue, and a lower microchannel in which adipose endothelial cells are co-cultured.

The extracellular matrix has a three-dimensional structure that fills the space between multiple cells in a tissue and is composed of molecules secreted and accumulated from cells.

In particular, the extracellular matrix of adipose tissue dynamically changes its composition and properties during the obesity process, directly and indirectly regulating the behavior of adipocytes.

First, the research team created a hydrogel made of an extracellular matrix using a technology that decellularizes normal and obese adipose tissue.

The formed hydrogel possessed tissue-specific physiological and pathological characteristics and could accurately mimic the unique microenvironment of normal and obese adipose tissue. It also helped maintain the function of cultured primary adipocytes for a long period of time.

The research team created biochips of obese and normal adipose tissue, respectively, and reproduced the dysfunction observed in vascular endothelial cells within obese adipose tissue.

Increased intra-adipose inflammatory response due to obesity activates vascular endothelial cells and increases the number of intra-adipose immune cells. These pathological features were observed through approximately twice the immune cell adhesion in the developed obese adipose tissue biochip.

The research team also conducted research on the link between obesity and cancer, which has not been clearly identified. Through the developed adipose tissue biochip, we confirmed that the mobility and tissue attachment of cancer cells increased approximately two-fold under obese conditions. This showed that direct interactions between obese adipose tissue and cancer cells can be easily visualized and quantified.

“Through this study, we were able to mimic the microenvironment of obese adipose tissue,” said first author Researcher Hee-Jung Yoon. “By utilizing a biomimetic chip, we can observe the activation, inflammation, and dysfunction of vascular endothelial cells due to obese tissue, as well as their interactions with other cells. This can be used to elucidate various disease mechanisms related to fat or develop obesity treatments.”

This study was published in the international academic journal in the field of biomaterials, Acta Biomaterialia, on January 29, 2023.