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Bioprinting - Digital manufacture of cells onto a biological membrane
#1
Additive manufacturing or three dimensional (3D) printing has been the latest rage in the industry for a couple of years now. Its ability to bring an image to life is being explored by engineers and scientists all over the world. The basic technique behind additive manufacturing is that a printer connected to a computer or data source adds layer by layer to create the object desired. For example, if you wanted to create a 3D print out of a pen, you would first have to scan the pen and digitize its image. Then, software would convert the scanned and digitized image into a series of files which will acts as layers. Then the printer print out these files layer by layer which are then joined together by a heating coil to generate a three dimensional print out of the pen. This method is known as fused filament fabrication and is one among the wide variety of processes available for 3D printing.

Three dimensional printing has a lot of applications however; the most important among them is its use in the field of medicine. It is a widely known fact that when it comes to organ transplants, there aren’t nearly enough donors as there are patients. Almost three decades after its development, additive manufacturing is becoming affordable and therefore, accessible making them the best candidates for development of synthetic organs.

Biological printing or bioprinting as it is more famously known allows direct digital manufacture of cells onto a biological membrane. The bioprinter has an output that adds cells to a geometrically mapped biological membrane moving left to right, adding the cells where required. The printer moves slowly and steadily adding very thin layers of cells and after a couple of hours it generates an actual desired structure.
One of the pioneers in this field was scientist Makoto Nakamura who created the first successful bioprinter in 2002. He realized that the drops that are released by an inkjet printer are quite similar in size to an actual cell and set out to make a printer that could print biological materials. He succeeded in producing a bioprinter that prints out biotubing similar to a blood vessel. Almost a year later, Scientist Thomas Boland and his lab at the bioengineering department at Clemson University modified an inkjet printer to accommodate and dispense pre grown cells in scaffolds. Since scaffolds like hydro gels aren’t safe if inserted inside the body, Dr.Gabor Forgacs developed new technology that allowed cells to be printed without scaffolds. His lab has been able to successfully print cells in toroidal patterns and are currently working on tubular and cuboidal structures.

Another pioneer in the tissue engineering industry, Organovo created a bioprinter based on Forgacs technology. This printer, Novogen MMX bioprinter has two jets- one houses a hydrogel that acts as a temporary support for the cell, other houses a cartridge which contains the bioink. Cells in the bioink are pre-grown in form of spheroids and then added to the cartridge where they form the bioink. The jets add the bioink into the hydrogel and layer by layer a tissue is created. The naturally fused cells are left for incubation and growth in the growth medium and the hydrogel is removed.

In the first decade of its development, bioprinting has been able to produce blood vessels, cardiac tissue, nerve cells and lung tissue. Another giant in the industry, NovaCopy has successfully printed a 3D plastic prosthetic leg for a duck and hope to achieve similar success with biological materials. This would be a huge accomplishment and a great source of hope for the handicapped. It is extremely hard to find a good prosthetic arm or leg that perfectly matches an individual’s requirements perfectly.

In spite of the excitement in the industry regarding this new and promising form of regenerative medicine, scientists are asking individuals to hold on to their hearts and not to get carried away in the hype. Bioprinting is a new technology which still needs to be understood, perfected and made accessible. Scientists at various labs all over the world are still learning how to make living cells pass through a print head without killing them. It is said that the world is still looking at a decade or two before bioprinted organs become available for mass use. We also need to figure out how to reduce the time required to generate an actual organ (printing a liver now would take anywhere from 10 hours to more than a day). Despite the warnings and the long wait ahead, you CAN look forward to that day when long waits and exhausting donor lists will be a thing of the past.
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#2
Recent progress in bioprinting

The previous article gives an overview of the potential applications of bioprinting in medicine. The technique seems almost the stuff of science fiction but recent advances are bringing it ever closer to being a viable alternative in organ transplantation.

This technique may have applications in space as well as on earth. NASA has an interest in studying metabolism of drugs in space and planetary environments. Recent refinements in bioprinting processes are promising in this context. A study from Drexel University in Philadelphia exploited the convergence of solid freeform fabrication technology with microfabrication techniques to make a microscale in vitro device which housed a chamber containing bioprinted three-dimensional liver cell-encapsulated hydrogel-based tissue constructs. These biomimicked the cell’s natural environment and could be demonstrated to display liver cell-specific function. Importantly in terms of the drug metabolism element of the study, the system achieved the necessary dynamic perfusion of the three-dimensional microscale liver analogue.

In a more down-to-earth consideration of the application of bioprinting, a recent study from RWTH Aachen University Hospital in Germany addressed issues impeding use of bioprinting technologies in organ transplantation and regenerative medicine. These include poor material-printing device and substrate combinations, and the relatively small size of printed constructs. This group considered the use of hydrogels. They used stem cell-laden hydrogels and hypothesised that they could be bioprinted when submerged in perfluorotributylamine (C(12)F(27)N), a hydrophobic high-density fluid. They used human mesenchymal stem cells and MG-63 cells and manufactured various three-dimensional structures. They found that these structures remained stable for more than six months and that there were viable cells in the structures 24 h after the printing process, as well as after 21 days in culture. After 14 and 21 days proliferating, viable cells were present. Furthermore, the compressive strength values of the printed hydrogels increased as a consequence of cell proliferation and matrix production during two weeks in culture.

There are therefore many potential applications of bioprinting. Continuing studies are needed to help realise the promise of this technique.

Sources

CHANG, R. et al., 2010. Biofabrication of a three-dimensional liver micro-organ as an in vitro drug metabolism model. Biofabrication, 2(4), pp. 045004-045004

DUARTE CAMPOS, D.,F. et al., 2013. Three-dimensional printing of stem cell-laden hydrogels submerged in a hydrophobic high-density fluid. Biofabrication, 5(1), pp. 015003-015003
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