- Nov 10, 2025
- 2 min read
UNIST Professor Kang Hyun-wook’s team develops a spheroid production method combining cell culture and 3D printing
Easy, precise mimicry of human tissue… published in Advanced Functional Materials
November 27, 2020
A high-precision printing technique has been developed that can deposit “cell spheroids” — spherical clusters of cells — exactly where desired. Because cell spheroids, which are cultured in spherical form, more closely resemble human tissue structure than cells grown in two-dimensional culture, they are attracting attention as test-beds for understanding cancer metastasis and verifying drug efficacy.
The biomedical engineering team at UNIST (President Lee Yong-hun), led by Professor Kang Hyun-wook, has developed a “3D Bio-Dot Printing” technology that prints stem cell or cancer cell spheroids with high precision. This technique merges the method of culturing cells to form spherical clusters with 3D bio-printing of a bio-ink containing cells, basically combining two approaches.
This technology achieves precision so that the distance between cell spheroids can be controlled to the level of several micrometres (μm, 10⁻⁶ m). Because of that, it is possible to accurately mimic the paracrine interactions (untouched pairwise communications) between real human cells. Furthermore, regardless of the type of cells used, the advantages of 3D bio-printing—such as three-dimensional stacking and computer-aided precision bio-machining (CAD/CAM)—can still be employed. For that reason, it is expected to accelerate development of tissue models that more closely resemble human organs.
The 3D Bio-Dot Printing developed by the team works by placing individual spherical “dots” of bio-ink containing the cells into a mixed hydrogel that surrounds them. The mixed hydrogel around the bio-ink acts as a “mould” to gather the cells into a spherical cluster. This is because the crosslinker inside the bio-ink solidifies the contact surface into a spherical shape. In addition, the bio-ink contains a sacrificial material that dissolves away as the cells grow, so that the cells cluster together and mature inside the spherical mould.
The first author, Researcher Jeon Seung-gyu, explained: “Unlike previous spheroid 3D printing methods, there is no need for a separate spheroid culture step, and the spheroids can be formed directly at the desired location.”
In experiments, the research team successfully produced spheroids of cancer cells, pancreatic islet beta-cells (which secrete insulin), and liver cells. In particular, the liver-cell spheroids showed superior performance and longevity compared with those cultured by conventional spheroid methods. The team also carried out experiments investigating the inter-spheroid interactions among different types of cells. Using the developed bio-dot printing technique, they created models such as cancer invading fibroblasts and models showing interaction between vascular endothelial cells and liver-cell spheroids.
Professor Kang said: “Because the developed bio-dot printing process can be applied to various cell types—liver cells, pancreatic islet beta-cells, cancer cells, etc.—we expect that it will be helpful for ongoing projects such as cancer invasion models, liver-disease treatment patches, and stem-cell-spheroid-based xenograft organ development.”
This research was supported by the Ministry of Science and ICT and the Ministry of Education. The relevant work was published online on 22 September in the international materials journal Advanced Functional Materials.
