Researchers from Brazil have recently discovered a 3D bioprinting technique through which they can develop a functioning haptic mini-liver. They have improvised on the already existing procedure of 3D printing by artificially creating clump of cells using biomaterials.
The newly created organoid is capable of performing all the main functionality of a full-sized liver such as storing vitamins, building vital proteins, secreting bile and other typical functions. The research was performed by the scientists at the Human Genome and Stem Cell Research Center (HUG-CELL). The University of São Paulo (USP) hosted the research and the funding was provided by FAPESP.
This innovation makes possible the cultivation of a working miniature liver in only 90 days and shortly may lead to the development of alternative organ transplantation.
Many other studies have also been done on bioengineering techniques for the production of tissue but this is the first time where scientists have figured out a way to develop an organ that functions longer than reported by previously conducted studies.
Mayana Zatz, director of HUG-CELL and last author of the article published in Biofabrication says,
“More stages have yet to be achieved until we obtain a complete organ, but we’re on the right track to highly promising results. In the very near future, instead of waiting for an organ transplant, it may be possible to take cells from the patient and reprogram them to make a new liver in the laboratory. Another important advantage is zero probability of rejection, given that the cells come from the patient.”
The key part of the study that makes it differ from other lies in their new technique, the cells were included in the bio-ink used to produce tissue in the 3-D printer. Earlier the cells were generated individually due to which they tend to lose their functionality and didn’t last long.
“Instead of printing individualized cells, we developed a method of grouping them before printing. These ‘clumps’ of cells, or spheroids, are what constitute the tissue and maintain its functionality much longer,” said Ernesto Goulart, a postdoctoral fellow in USP’s Institute of Biosciences and first author of the article.
The clump of cells or spheroids formation process in this research thereby avoided the problem of the gradual loss of contact among cells and hence loss of tissue functionality.
Goulart told Agência FAPESP, “We started the differentiation process with the cells already grouped together. They were cultured in agitation, and groups formed spontaneously.”
The 90-day development process of the liver is segmented into three stages differentiation, printing, and maturation. Firstly, the extracted blood cells are reprogrammed to the point of pluripotency characteristic of stem cells, becoming induced pluripotent stem cells (iPSCs). This method was discovered by Japnese scientist Shinya Yamanaka, the 2012 Nobel Prize winner.
The next step comprises the induction of liver cells into differentiation. The spheroids, consisting of these cells are then mixed with a hydrogel-like fluid to develop the bio-ink that can be used to create liver organoids. It is then printed out, the structure produced matures in a specific culture for 18 days.
“The printing process entails the deposition of spheroids along three axes, which is necessary for the material to gain volume and give the tissue proper support,” Goulart said. “The gel-like bioink is crosslinked to make the structures more rigid so that they can be manipulated and even sutured.”
Another key benefit of this study is the zero probability of organ rejection as the cells are extracted from the patient. The research is currently limited to the production of mini livers but according to the scientists, this can be scaled up easily but with investments and interest.