Kyushu University scientists successfully transplant 3D bioprinted liver buds into rats
Scientists from the Kyushu University in Japan have recently demonstrated the ability to implant their 3D bioprinted liver tissue into rats. The breakthrough could mark a step in the right direction for the development of implantable 3D printed liver tissue in humans.
The research project, which was recently published in the journal Scientific Reports, shows that cell-based therapies could be a viable alternative to orthotopic transplantation for treating liver disease. In other words, the researchers have shown that rather than transplant a whole new organ, 3D bioprinted tissue patches could be used to treat a patient’s native liver.
This vein of research, which is being explored by other academic groups and medical companies, is essentially looking for a solution to the long liver transplant waiting lists that exist, as well as to complications that arise from orthotopic organ transplants.
As the Kyushu University researchers explain in their study, “the novel transplantation of an in vitro-generated liver bud might have therapeutic potential.” The study also demonstrates ex vivo methods for growing a liver bud.
More specifically, the researchers have put forward a method through which liver buds—similar to a liver tissue patch—are grown in vivo (within the living organism). Perhaps most notable about the project is the innovative 3D bioprinting process used to build the liver tissue buds in the first place.
“This study demonstrates a method for rapidly fabricating scalable liver-like tissue by fusing hundreds of liver bud-like spheroids using a 3D bioprinter,” reads the study. “Its system to fix the shape of the 3D tissue with the needle-array system enabled the fabrication of elaborate geometry and the immediate execution of culture circulation after 3D printing—thereby avoiding an ischemic environment ex vivo.”
Let’s take a look at the novel process in more detail: rather than use a scaffold like structure to embed the liver cells in—which is a common bioprinting technique—the researchers instead opted for a needle-based approach.
This method consists of using a 3D bioprinting nozzle to deposit (or skewer) the liver cells (or spheroids) onto an array of needles. By repeating this process, the bioprinter effectively builds a 3D structure onto the needles based off of a predesigned 3D model.
Once the 3D structure is obtained, the spheroids fuse together and can be removed from the needle array, resulting in a scaffold-free bioprinted structure. After only a few days, the holes from the needles are grown over in culture, making for a solid bioprinted tissue form.
Perhaps most impressively, the researchers were able to successfully implant their bioprinted liver tissue buds onto rat livers. After testing many different methods of this process, the researchers finally found a 3D bioprinted tissue sample which began to graft to the rat liver seven days after the transplantation.
“In summary, our transplantation method has two major advantages: it does not involve any vascular obstructions and the presence of direct connection between the graft and the recipient’s liver parenchyma would facilitate greater graft growth,” said the researchers in their study.
The bioprinting method, for its part, offers the benefit of being able to produce 3D tissue samples in complex structures, as well as creating a solid scaffold-free shape which “enables the immediate execution of culture circulation after 3D printing—thereby avoiding an ischemic environment ex vivo—which supports the biofabrication of scalable tissue.”
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