The development of 3D organ printing

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Abstract

Bio-printing will be examined as a future possibility to dramatically decrease the organ shortage and increase effectiveness of treatments for many organ malfunctions. Many researchers have been working towards creating the first functional organ using additive manufacturing, also known as 3D printing. The process of bio-printing is much more complicated compared to the simpler, influential 3D printer. 3D Bio-Printing Solutions based in Russia has successfully manufactured a thyroid gland for a mouse. However, the schedule to transplant the organ into the mouse is not until July 2015. The future of bio-printing, if successful, will give many people the ability to receive an organ transplant that they have been waiting on for so long. It will also have the ability to increase the effectiveness of drug testing. Instead of using animals or humans, pharmaceutical companies and other researchers can practice new medicines on printed organs in a timelier manner and without dealing with the possible negative ramifications on harming living things.

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Keywords: bio-printing, additive manufacturing, organ, 3D printing

3D Organ Printing

In 1984 Charles Hull invented the first 3D printer, which has proven to become continuously influential in the world of science. Recently, a new research field of bio-printing and bio-patterning has emerged from the use of Hull’s 3D invention. There are many possibilities bio-printing can create that I will discuss; these include, but are not limited to, various tissues, pieces of organs and transplant-ready organs.

The basics of 3D bio-printing are unique compared to traditional 3D printing. Also known as additive manufacturing, 3D printing generates an object by laying down multiple layers of material. The creation of a 3D printed object is formed using additive processes, hence the name additive manufacturing. Bio-printing involves stem cells which can serve as building material for all types of body tissues. Using an individual’s own stem cells will allow the body to accept the organ produced by additive manufacturing. Stem cells are extracted from fat tissue and used as the bio-ink for the tissues or organ being created. The cells are formed into an agglomeration of cells and then are layered onto hydrogel, a type of polymeric gel known to hold large amounts of water. When the hydrogel dissolves the final printed organ is put into a bio reactor to fully mature.

Since the Russian company, 3D Bio-Printing Solutions, launched in 2007 they have experimented with printing various kinds of tissues. Bits of lung, kidney and heart muscle were constructed during these experiments. Those various tissues were never integrated with living organisms, however, until recently. In 2014 the Russian scientists announced that they would successfully develop the first organ, a transplant-ready thyroid, by March 15, 2015. Laboratory head researcher, Vladimir Mironov, said that the team chose a thyroid due to its “simplicity”. To test the successfulness of the bio-printed organ, they used mice. By shutting off the thyroid with radioactive iodine the level of hormones in the mice would decrease, allowing the team to transplant the printed organ in hopes of getting the hormones back to normal.

On March 12, 2015 the first animal thyroid gland was printed and prepared to be transplanted into a mouse in order to further evaluate its abilities. The plan remains the same; the mouse will be purposely given an excess amount of iodine to cause hypothyroidism. After the printed organ is transplanted they will evaluate the conditions that arise. The information will not be released to the public until July of 2015.

Creating a fully functional thyroid for a mouse is a big step towards creating a thyroid for humans. Thyroid diseases are rarely fatal, however kidney complications kill millions. Even more severe, according to the American Cancer Association, 62,450 new cases of thyroid cancer and 1,950 deaths are predicted in the year of 2015. Hoping that the thyroid will be proven successful, Mironov has a goal of printing the first functional kidney within the next three years. The American Cancer Association estimates 61,560 new cases and 14,080 deaths this year. The ability to print a functional thyroid or kidney will greatly decrease the organ donor shortage and save many Americans each year who suffers from kidney cancer and other kidney-related diseases.

Russian researchers from 3D Bio-Printing Solutions also plan to construct a new magnetic version of 3D printers to be used in space. Currently the stem-cells organs are bio-printed with layers because of gravity. However, if the cells are put in space where gravity does not apply, they can form an organ with the help of a special magnetic field. Agreements have already been made, according to Mironov, for tests to be conducted on the International Space Station.

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More conclusive research within the US includes pieces of organs and miniaturized organs. A company called Organovo, based in San Diego is already selling pieces of liver tissues to researchers aiming to test experimental drugs for toxicity to liver cells. In hopes to eliminate human trials altogether, Organovo announced on April 1, 2015 that the world’s first 3D bio-printed fully cellular kidney tissue would be unveiled at theExperimental Biologyconference in Boston. The new technology will allow pharmaceutical companies to conduct biological research on kidneys without the use for human subjects, making the process quicker and safer. The Organovo researchers hope that this will pave the way for finding new ways to improve and cure kidney diseases. The liver tissue samples they have already created can survive up to 42 days in the lab; they assume that it is likely the kidney tissue will have a similar lasting period. Organovo's chief executive Keith Murphy is hoping that within five years his company will be prepared to begin clinical trials repairing damaged organs with bio-printed products.

In April 2015, Anthony Atala and his team at Wake Forest Institute for Regenerative Medicine in North Carolina used additive manufacturing to produce artificial miniature organs - a liver and heart. After Wake Forest researchers manufactured the organs they were placed on a two-inch chip for further testing and monitoring. While still on the chip, these miniature organ structures are examined by connecting them to a system of multiple sensors and fluid channels filled with a blood substitute. The blood substitute is continuously pumped through them not only to keep the cells alive, but to introduce new chemicals, pathogens or therapies into the system for examination. Using the sensors, the scientists will also be able to measure the temperature, oxygen levels, pH balance and other factors worth noting.

The Wake Forest Institute for Regenerative Medicine is working with others throughout the United States to develop miniaturized organs as part of aBody on a Chip Project. This project could greatly decrease the need for testing animals. Using animal or humans for testing drugs could take up to two or three years. Using the printed organs will reduce the time period to two or three months. Of course, these organs are not suitable for transplant as they measure four by four by one millimeter; this is about one-fourth the size of a dime. The miniaturized organs can be developed so that they behave similarly to their larger counterparts. This is ideal for testing new treatments and to examine the effects of new substances. Atala, like Organovo’s Murphy, believes that the next step in bio-printing will be printing strips of tissue for repairing damaged organs. According to many researchers, including Wake Forest's Anthony Atala, the technology for printing whole functional organs for the purpose of transplanting is still years away, however it is rapidly developing.

Medical researchers have been reproducing human cells in laboratories by hand for years; they have been able to create blood vessels, urine tubes, skin tissue and other living body parts. However, scientists are already making quite an impression in the biology field using the bio-printing machines to construct tiny strips of organ tissue such as liver, heart and kidney. A Virginia foundation that supports regenerative medicine researchprovided an incentive to accelerate the development. This incentive of a $1 million prize has been set asidefor the first organization to print a fully functioning liver. One early contender for the prize is the California-based company,Organovo. This is a rapidly developing study with a healthy competition to solve the dilemma of organ shortage and treatment research.

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