Researchers develop new method to 3D bioprint functional organoids

China3D printingOn October 2nd, researchers from the Federal Institute of Technology in Lausanne (EPFL) in Switzerland have developed a method of printing centimeter-scale tissues with high physiological relevance. The appearance and function of the tissues are almost similar to their full-size living bodies. Engineered micro-tissues can allow scientists to study biological processes and even test new treatments in ways that were not possible before, thereby opening up new avenues for drug development, diagnosis and regenerative medicine.

In a study published in the journal Nature Materials in September 2020, researchers reported on the design of a customized extrusion-mode bioprinting device that consists of a microscope and a fine nozzle that can be pumped through a syringe pump. And a device for depositing cells. This method is called Bio-Printing Auxiliary Tissue (BATE), which uses organoid-forming stem cells as a building block, which can be deposited directly into an extracellular matrix that helps spontaneous self-organization. By moving the microscope stage and continuously monitoring the process through the microscope lens, the researchers were able to deposit intestinal stem cell lines about a few centimeters in length into the gel.

So far, researchers have been able to design organoids similar to the brain, stomach, kidneys, lungs and liver, thus promoting the development of new treatment strategies and the development of personalized medicine. However, EPFL reports that traditional methods of growing organoids result in the assembly of stem cells into hollow spheres ranging in size from micrometers to millimeters.
In addition, according to Matthias Lütolf, a professor at the EPFL Institute of Bioengineering and lead author of the study, this method is “non-physiological” because many organs (such as the intestine or airway) are tubular and larger.In order to develop and normal human organs, Lütolf and his team turned to biological3D printing.

Although scientists have produced laboratory organoids for decades, advances in the field of biotechnology (such as tissue engineering, biomaterials, and biomanufacturing) have accelerated the research of organoids, thereby promoting the development of complex biological systems.
“Bioprinting is very compelling because it allows you to deposit cells anywhere in 3D space, so you can consider arranging cells into organ-like structures, such as tubes. Using traditional organoid growth methods, you can Grow stomach organoids or intestinal organoids-and with bioprinting, you can combine different cell types and arrange them in different ways.
In addition, what makes the newly developed method different from other methods of growing organoids is that it combines3D printingThe flexibility and precision of stem cells and the ability of stem cells to grow and organize themselves. “

The BATE bioprinting method uses spontaneous, self-organizing building blocks to create large-scale tissues. Image courtesy of EPFL.

The researchers also found that relying on microscope-based bioprinting reduces the need for in-depth expertise in hydrogel rheology and bio-ink formulations because it provides direct user feedback to visually control and regulate the printing process in real time, thereby Promotes the optimization of printouts. The versatility of BATE is also reflected in its ability to control the sequential deposition of supportive cells in space and time, because the integration of a bioprinter into an automatic microscope can track the appearance of tissue in real time, and if necessary, you can return to the scientists to describe Pinpoint specific locations of other cell types.
“In other bioprinting methods, you can’t see what’s going on. The beauty of using a microscope is that you can always see what you are doing, and you can see what the cells are doing.”

The study showed that once the stem cells are seeded, the cells begin to grow and interact with each other to form a continuous tubular tissue that mimics many of the anatomical and functional features of a conventional intestine. Similar results were obtained with primary mouse colon and gastric stem cells and human colon stem cells, indicating that BATE may be widely applicable to organoids derived from epithelial stem cells.

BATE is used in intestinal tissue engineering. Robust control of cell density and tissue geometry can be achieved directly in an environment that allows multi-cell self-organization. Image courtesy of EPFL.

The intestines grown in the laboratory can be up to three centimeters in size and consist of crypt-shaped pockets with stem cells. They contain the same specialized absorption and secretion cells as the whole intestine. The secretory cells of the mini-gut can also secrete antimicrobial molecules in response to specific stimuli.According to China3D printingNetwork understandingUsing traditional organoid growth methods, researchers can grow stomach organoids or intestinal organoids, and through bioprinting, they can combine different cell types and arrange them in different ways. In particular, BATE can print multiple pixel types sequentially to form complex geometric shapes and pixel type arrangements with good spatial resolution.

In this study, researchers were able to show how the concept of organoid fusion can use the same components to produce relatively large tissues, and how to simulate tissue boundaries by using components from related organs. In addition, the authors believe that, compared with other existing bioprinting technologies, their original cell printing method can guide tissue morphogenesis at different scales and has many advantages.

Picture of the nozzle to be installed on the microscope. Image courtesy of EPFL.
Research results show that BATE enables fragile cells (such as primary stem cells) to be directly organized into complex geometric shapes in the most effective 3D culture substrate (such as the matrix used in research). Since the microstructure of the final construct is produced by the cells in the subsequent remodeling and self-organization process, it also reduces printing time and geometric complexity.Although this research provides new tools for engineering self-organizing tissues and mimicking organ boundaries, Lutov believes that it has a long way to go for applications in regenerative medicine (including replacement of human tissues and organs). But he pointed out that the newly developed method can be used to build tissue models of human diseases (including cancer) and to test the effects of drug candidates on specific cell types in tissues.

China3D printingNet compile article!

(Editor in charge: admin)