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INNOVATIONS IN BIOENGINEERING: ARTIFICIAL ORGANS

Jason Zheng ([email protected])

WHAT’S AHEAD? failure will only become more common. For example, every single day, roughly 20 individuals will lose their With thorough and thoughtful lives waiting for a transplant [2]. Additionally, only consideration, I’ve decided that bioengineering is the about half of US adults are signed up as donors right career path for me. I find bioengineering so [2]. A single individual can donate multiple organs for intriguing because it is a constant growing field with these patients, but many refuse to do so. The lack of research opportunities available in areas such as organ donors has caused many preventable deaths, and bioinstrumentation, biomechanics, bioimaging, and medical researchers and professionals are trying their . In order to advance healthcare, best to come up with solutions to this problem. In hopes bioengineers must make use of their scientific of saving these lives, researchers have turned to the knowledge and ingenuity in order to develop solutions laboratory in search for these extra organs. The growth to major problems that are being faced in the healthcare and advances within the design and development of world. The focus for this paper will be on the sector of artificial organs have increased greatly in the last few regenerative medicine within bioengineering, years due to this goal of enhancing the organ transplant particularly with artificial organs. I will then further process. discuss this topic with an in-depth analysis on the 3D printed by examining its development and function What Are Artificial Organs? within the field of medicine alongside specific examples. Despite the ethical issues involved with the development of artificial organs, this particular field of study has received immense support and financial WHAT’S REGENERATIVE MEDICINE? backing. As the name suggests, artificial organs are made to match the function of our natural organs Over the last few decades, many innovations in through [3]. Many medical healthcare have emerged. From leadless pacemakers to professionals are against this research due to the fact that needle-free insulin injectors, these new forms of these “organs” are not naturally-occurring and can be technology have helped to improve the lives of millions potentially harmful to humans. Others, however, are of people around the world. Not only that, the lifespan heavily in favor of this newly refined medical of humans has slowly increased as well. With all these innovation. Researchers at the McGowan Institute stated medical breakthroughs, the field of regenerative that, “Artificial organs can sustain patients during their medicine seems to stand out above the rest. According long wait for donor organs and sometimes eliminate the to the McGowan Institute for Regenerative Medicine at need for transplantation altogether” [4]. As their claim the University of Pittsburgh, “Regenerative medicine is suggests, artificial organs have the ability to not only a new way of treating injuries and diseases that uses save thousands of lives each year in the US but also specially-grown tissues and cells (including stem cells), reduce the complications faced by the patients who are laboratory-made compounds, and artificial organs [1]. placed on the transplant waitlist. For the scope of this paper, I will focus on the artificial organs aspect of this field. What Do I Think?

Why Artificial Organs? With all that I’ve read about artificial organs, I definitely feel confident that this form of technology Annually, organ failure is one of the leading causes will become a cornerstone in the future of the healthcare of death within the United States. With the rapid world. If I was on the transplant waitlist, I wouldn’t want increases of obesity and other diet-based diseases, organ to wait around for an organ that I might not even end up University of Pittsburgh, Swanson School of Engineering 1 10.31.2017

Jason Zheng receiving. With the development of these safe, fully- How Does A 3D Printed Liver Work? functioning artificial organs, I can be assured that my life won’t be in danger because there weren’t enough The 3D printed liver is designed to function like a resources to keep me alive. Not only that, the research natural liver within humans. Dr. Deb Nguyen from into this field will open up a better understanding into Organovo conducted a few experiments by creating stem cells and other fields of regenerative medicine, exVive3D from different patients’ stem cells [6]. which are all valuable components of bioengineering. According to her research, she found that the exVive3D livers were able to filter out toxins and maintain a WHAT’S AN EXAMPLE OF AN metabolic balance just like a normal liver [6]. These ARTIFICIAL ORGAN? results helped to further consolidate the legitimacy and safety of this new form of technology. The printed livers were able to function at such a high level because every As mentioned before, more and more Americans 3D printed liver was made using stem cells that were are in need of organ donors. According to extracted from the respective patients and grown Organdonor.gov, liver transplants are the second most individually in the lab. common form of organ transplants in 2016 [2]. Due to In another study, doctor Benjamin Sheperd this high demand for liver donors, my focus in this implanted parts of the exVive3D livers into mice with section will be on the discussion of artificial livers, impaired liver functions [7]. The results showed that the specifically 3D printed livers. Another reason for artificial tissue was able to bind to the weakened areas choosing the liver is because my mom had gone through of the mice’s livers and sustain normal functions for a many liver treatments to help maintain its function. By prolonged period of time [7]. This experiment just doing research into 3D livers, I’ll be able to educate shows how powerful the Organovo approach to 3D myself on something that is very personal to me and my printing really is. Not only were they able to produce a family. fully functioning liver from patients’ stem cells, but the exVive3D tissue was able to bind and restore functions How Is A 3D Printed Liver Made? of a damaged liver by having the artificial hepatocytes (liver cells) behave like naturally-occurring liver cells. For years now scientists have been developing 3D organs and many other types of human tissues. A big What Are My Thoughts? emphasis had been placed on organs such as the heart, lungs, and liver because of the critical roles that they Organovo really revolutionized the field of play when it comes to human survival. Organovo is one regenerative medicine by introducing a unique approach of the leading companies in making 3D printed livers to 3D printing organs. This type of research will only with their use of exVive3D tissues [5]. This approach is grow from now on, which means that bioengineers from unique and reliable, which is why they are more around the world will have the opportunity to dive into successful than other companies when it comes to 3D potentially new career paths. This is exciting for me printed livers. According to 3DPrint.com, “The because I am studying to become a bioengineer. Not exVive3D tissue consists of human stellate, endothelial, only will these breakthroughs push the boundaries of my and hepatocytes cell types, and are proven to be future career, but the exVive3D liver will assure that my functional for at least 42 days, enabling long term drug mom will receive proper treatment if her symptoms do interaction studies which far exceed those made possible return. with 2D liver cell samples” [6]. Based on this information, one can see that this specific form of 3D printed livers can be used to test long-term effects and HAS THE ORGANOVO 3D PRINTED potential issues that may be encountered when placed LIVERS BEEN USED ON HUMANS? inside humans. This aspect is especially important since many healthcare professionals argue that artificial In the last few years, Organovo have been organs aren’t safe. The Organovo method of 3D printing conducting many experiments in hopes of achieving the livers also involves extracting stem cells from the perfect artificial human liver. Despite the many patients themselves and converting them into the desired successes that they have found, the company is still cells that make up the exVive3D tissue [5]. This again conducting additional experiments in order to fully will guarantee the safety of future patients because the guarantee the safety of future transplants. According to usage of the patients’ own stem cells will greatly Michael David, the company’s vice president of decrease the chances of organ rejection. preclinical development, “Organovo’s approach is designed to overcome many of the challenges that cell therapies and conventional tissue engineering have

2 Jason Zheng struggled to address, including limited engraftment and significant migration of cells away from the liver” [8]. HOW WILL THE FUTURE LOOK? What Michael David was essentially saying is that, since the exVive3D printed livers are so much more advanced in terms of its design and function, a considerable Many medical professionals have said that the amount of time must be spent on testing such a complex study into artificial organs is pushing the boundaries of piece of technology. In addition to research within ethicality within the medical field. Organovo’s approach Organovo labs, the company had decided to is also seen as unethical because of the use of stem cells. commercialize their exVive3D tissues for further testing However, stem cells actually make the process safer for by other medical companies [8]. This is a huge step by future patients. Although the critics provide a strong the company because expanding the scope of the testing argument, there is no doubt that the development of will mean that the exVive3D livers are going to be used artificial organs is the only solution to help those in need by patients sooner than what many critics had of organ donors. Currently, thousands of people are anticipated. dying annually because there aren’t enough resources to go around. With the efforts made by institutions such as How Will These Livers Be Used? McGowan and Organovo, the future of healthcare seems to be promising. Not only will this new form of Organovo’s goal is not only to profit off of a major technology revolutionize the healthcare world due to its scientific breakthrough but also to save thousands of reliability, safety, and complexity, but it will also create lives each year. As mentioned earlier, liver transplants opportunities for future members of the medical are the second most common type of organ transplants community such as myself. in the US. With so many individuals on the transplant waitlist, it is Organovo’s ultimate goal to bring relief to SOURCES those who are suffering due to the lack of organ donors. Instead of waiting for a liver donor, many of these [1] “What Is Regenerative Medicine?” McGowan individuals in the future will receive liver transplants Institute for Regenerative Medicine. Accessed that make use of the exVive3D livers. This method may 10.26.2017. prove to be less dangerous because the artificial livers http://www.upmc.com/Services/regenerative- will be grown using the patients’ own stem cells, which medicine/education/Pages/default.aspx greatly reduces the chances for organ rejection. Not only [2] “Organ Donation Statistics.” U.S. Department of that, Organovo also found success in using “patches” of Health & Human Services. Accessed 10.26.2017. the exVive3D tissues to regenerate or restore functions https://www.organdonor.gov/statistics- of weakened livers. This is especially important because stories/statistics.html the exVive3D tissue could be used to develop 3D printed [3] “Artificial Organs.” McGowan Institute for organs other than the liver. According to the company’s Regenerative Medicine. Accessed 10.26.2017. CEO, Keith Murphy, the Organovo exVive3D livers http://www.upmc.com/Services/regenerative- will be made available to patients as soon as 2020 [9]. medicine/research/artificial-organs/Pages/default.aspx In just a few years, the medical world will witness [4] “Regenerative Medicine Research.” McGowan something that will transform . Institute for Regenerative Medicine. Accessed 10.26.2017. What’s My Take? http://www.upmc.com/Services/regenerative- medicine/research/Pages/default.aspx I personally feel that Organovo is doing the right [5] C. Scott. “University of California San Diego’s 3D thing by commercializing their product. Many medical Printed Liver Tissue May Be the Closest We’ve Gotten companies out there are competitive and race to be the to a Real Printed Liver.” Organovo. 02.09.2016. first ones to discover or invent something. Organovo Accessed 10.26.2017. knows that their main objective is to save millions of https://3dprint.com/118932/ucsan-diego-3d-printed- lives in the future and by commercializing the exVive3D liver/ tissue, the success of the healthcare world as a whole can [6] B. Krassenstein. “exVive3D 3D Printed Human be reached faster. The success of this liver is also Liver Tissue Now Commercially Available by exciting in the way that it could lead to the development Organovo.” Organovo. 11.18.2014. Accessed of other stable, artificial organs. I strongly believe that 10.26.2017. this type of research will benefit me when I graduate https://3dprint.com/25499/organovoexvive3d-liver/ with a degree in bioengineering because the success of [7] C. Scott. “Organovo’s 3D Printed Liver Tissue this project will open up many doors for engineers and Shows Extended Survival and Function in Animal Test researchers around the world. Subjects.” Organovo. 05.18.2017. Accessed

3 Jason Zheng

10.27.2017. https://3dprint.com/174905/organovo- liver-tissue-function/ [8] “Organovo Introduces 3D Bioprinted Human Liver as Leading Therapeutic Tissue in Preclinical Development.” Organovo. Accessed 10.27.2017. http://ir.organovo.com/phoenix.zhtml?c=254194&p=ir ol-newsArticle&ID=2209393 [9] L. Mearian. “3D-printed partial liver transplants targeted for 2020.” Organovo. 03.27.2017. Accessed 10.27.2017. https://www.computerworld.com/article/3184834/healt hcare-it/3d-printed-partial-liver-transplants-targeted- for-2020.html

ACKNOWLEDGEMENT

I would like to personally thank Mrs. Newborg and my writing instructor, Amanda Brant, for answering my questions via email during the course of this paper.

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