Bursic 3:00 R07 THE IMPACT AND RAMIFICATIONS OF LABORATORY GROWTH OF COMPLEX ORGANS VIA THREE-DIMENSIONAL PRINTING Jurrien Le ([email protected]) INTRODUCTION In the year 2014, the National Speech and Debate Association’s September-October Lincoln Douglas Debate resolution was announced to be the following: “Resolved: A just society ought to presume consent for organ procurement from the deceased.”[1] In the multitude of debates on that resolution and similarly relevant pieces of legislation in other debate events, the costs and benefits of organ donation were researched in meticulous detail. However, one issue went primarily unaddressed by the debate community: the root cause of the need for increasing organ procurement, and what could be done to alleviate or mitigate that issue. For a biomedical engineer, this lack of donor organs and organ tissue not only is an issue that would be dealt with in their field, but is also an issue that directly impacts their ability to conduct their own research. Thus, it has become imperative to begin by analyzing the impact of the low rate of organ donation in society, and explaining the current technologies available to deal with the issue, with a particular focus on one of the more promising means, which is lab growth of artificial organs via threedimensional printing. CURRENT IMPACT OF LACK OF DONOR ORGANS ON SOCIETY In modern society, the importance of human organs should not be taken for granted. Not only do organs serve critical roles regarding basic bodily function inside the human body, but also serve to fulfill vital functions in society outside of the human body. One of the most evident functions is the implantation of harvested organs into people seeking replacement organs in order to save their lives. Unfortunately, there lies a stark disparity in the number of people seeking organs, and the number of organs actually available for transplant. According to data provided by the Organ Procurement and Transplantation Network of the United States Department of Health and Human Services, there are currently over one hundred and twenty-thousand candidates on the organ donation waiting list in the United States[2]. Unfortunately, the number of donor organs available is a nowhere near adequate amount to deal with this backlog, with United Network for Organ Sharing data noting that only eleven thousand, seven hundred, and seventy-six donor organs have been recovered this year[3]. This lack of organs for those University of Pittsburgh, Swanson School of Engineering 1 Submission Date 11/1/2016 seeking organ transplant has tangible consequences, with approximately twenty-two people dying each day in the United States while awaiting an organ transplant[3]. Furthermore, the lack of available donor organs has further ramifications for the state and capability of scientific medical research and testing, many of which are thoroughly detrimental. Human organ tissue has tremendous value for companies engaging in biomedical research and drug testing, for the purposes of ascertaining the efficacy of specific treatments on diseases or disorder. Unfortunately, due to the current scarcity and scarcity-induced cost of human tissue, researchers have been forced to test treatments on animal cells, which prolongs the length and long term cost of testing, due to the differences between human cells and animal cells, as reported by the Washington Post[4]. Thus, increasing the availability of organ tissue to medical researchers would decrease the time taken for testing of promising drug treatments, and shorten the transition from laboratory to market for these disease treatments. Given the increasing prevalence of drug resistant viruses, as well as the rising cost of drug treatment in the United States, the importance of developing new drug treatments to circumvent developed drug resistance and driving down drug treatment prices via increased competition in the treatment market can not be understated. ANALYSIS OF LABORATORYMEDIATED ORGAN CREATION Aside from actually increasing the number of organ donors in the United States, one of the more viable and ethical solutions for increasing the availability of human organs and organ tissue for medical purposes is the artificial creation of organs and organ tissue in the lab. With the tremendous advancements in stem cell harvesting, creation, and modification techniques made in recent years, laboratory growth of organs has significantly increased in viability, and also serves to provide its own bevy of benefits compared to traditional donor-harvested organs. First, laboratory-created organs are grown with either the patient’s own cells, or with cells grown from stem cells that have been wiped of proteins that trigger immune responses. This means that with custom lab grown organs, the need for side effect prone immune-suppressing medication is obviated, Bursic 3:00 R07 along with the risks involved with immune system rejection of organs harvested from donors, as reported by ABC news[5]. The second notable benefit of lab grown organs is that such organs can be custom made to uniquely fit the physiology of the patient who receives such an organ[6]. Continued investment of time, research, and economic resources into furthering artificial organ creation is imperative, as artificial organ creation is what Professor Clare Blackburn of the MRC Center for Regenerative Medicine at the University of Edinburgh calls “one of the ‘holy grails’ in regenerative medicine”, and is a process that can help solve for the issues affecting those seeking organ transplants as well as those in the medical research community, providing significant benefits over the current status quo situation[7]. dimensional printing, organic biomaterial and living cells can also be used as material. The precision inherent with three-dimensional printing technology provides a multitude of benefits to the artificial organ creation process. First, threedimensional printing allows for the rapid and precise creation of complex organic scaffolding upon which organs and organ tissue can be grown effectively and efficiently into needed shapes and structures[9]. This would reduce the time and cost expenditure of growing organ tissue, which would notably increase the availability of useable human organ tissue to medical researchers. Furthermore, the precision of three dimensional printing allows for the relatively rapid creation and precise placement of unique cells and blood vessel networks in complex organs, due to the fact that such cells and vessels are literally printed into the organ as part of the organ blueprint used in the printing process[10]. Thus, the viability of threedimensional printed organs compared to traditional lab grown organs would be significantly higher, due to the greater control that scientists would have over the structure of the organ. USE OF THREE-DIMENSIONAL PRINTING TECHNOLOGY IN ORGAN CREATION Unfortunately, there remains a prominent issue with existing artificial organ creation methods. Some commonly sought organs, such as the kidneys and liver, have significantly more complex structures, involving multiple types of cells and networks of blood vessels that are absolutely essential to the proper continued function of the organ in a human body. This inherent complexity makes it significantly more difficult for these organs to be created in a lab, where precision at the microscopic scale is needed for proper incorporation of these vessels and cells into a functioning organ, as noted by the BBC[8]. It is this issue that has been a primary inhibitor of the development of artificial complex organ laboratory creation, to which the inception and development of three-dimensional printing technology is one of the most viable and prominent solutions. At the most basic level, three-dimensional printing is virtually identical to conventional inkjet printing methods, in which an inkjet or extruder nozzle is used to deposit a layer of material onto a printing base, which can be a sheet of paper for conventional inkjet printing, or a different material, dependent on the item printed and material used in printing. Where three-dimensional printing methods differ from conventional printing methods is in the fact that a three-dimensional printer sprays or extrudes multiple micrometer-thin layers of material, building the desired object up layer by layer until the structure or object is formed. The materials used in three-dimensional printing vary, with the most common material used being multiple unique blends of plastic. However, due to the rapid progression of technological development in the realm of three- FUTURE PATH OF THREEDIMENSIONAL ORGAN PRINTING Given that the current state of three-dimensional printing of complex organs is still largely experimental and untested, the logical next step would be to print out and test the viability of three-dimensional printing of a complex organ. With further development, this technology could hypothetically bring about the end of the current organ shortage affecting the United States. The United States currently is a society where hundreds of thousands of people languish on a waiting list seeking an organ that they need for continued survival but don’t even know if they’ll live long enough to get, while scientists and researchers pay thousands to dollars for the organ tissue samples they need to effectively sustain their potentially lifesaving research. With threedimensional organ printing technology, that society could be a relic of the past. In this future which we strive for, patients seeking an organ transplant could have cells harvested, grown, and printed into a viable transplant organ in a matter of months, while remaining free from the risks of immune rejection and the need to take immunosuppressant drugs that have deleterious side effects. In this same future, scientific biomedical research continues to blossom and advance at a rapid pace, unhindered by the previously experienced costs of either having to purchase organ tissue at a high price, or work with the experimental complexity of testing with animal tissue. Instead, medical and pharmaceutical researchers will be able to print out and grow their own 2 Bursic 3:00 R07 organ tissue samples in a three-dimensional printer at relatively minimal cost, and begin conducting tests of lifesaving treatments immediately. As it stands, the potential of three-dimensional organ printing is truly massive, and it is a technology that should be invested in and further developed for today’s society, and the society of future generations. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC459793 3/ [10] Ventola, C. Lee. “Medical Applications for 3D Printing: Current and Projected Uses”. Pharmacy and Therapeutics Journal. 10/2014. Accessed 10/31/2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC418969 7/ SOURCES ACKNOWLEDGEMENTS [1] "Past Topics” National Speech and Debate Association. Accessed 10/31/2016. https://www.speechanddebate.org/topics/ I would like to acknowledge the Leland High School Speech and Debate team, without which I would not have been inspired to do research into organ procurement my junior year of high school. [2] “Waiting list candidates as of today” Organ Procurement and Transplantation Network. Accessed 10/31/2016. https://optn.transplant.hrsa.gov/data/ [3] “Data” United Network for Organ Sharing. Accessed 10/31/2016. https://www.unos.org/data/ [4] Paquette, Danielle. “Why drug companies need human tissue-especially liver” The Washington Post. 7/17/2015. Accessed 10/31/2016. https://www.washingtonpost.com/news/wonk/wp/2015/ 07/17/why-planned-parenthood-wont-stop-donatingfetal-organs/ [5] Noonan, Jessica. “Lab-Grown ‘Custom’ Organs May Be Future of Medicine”. ABC News. 6/25/2012. Accessed 10/31/2016. http://abcnews.go.com/Health/lab-grown-customorgans-future-medicine/story?id=16631764 [6] Locke, Susannah. “An organ shortage is killing people. Are lab-grown organs the answer?” Vox. 11/20/2014. Accessed 10/31/2016. http://www.vox.com/2014/11/20/7252365/lab-grownorgans [7] Centre for Regenerative Medicine. “Fully functional immune organ grown in mice from lab-created cells”. Centre for Regenerative Medicine. 8/24/2014. Accessed 10/31/2016. http://www.crm.ed.ac.uk/news/fullyfunctional-immune-organ-grown-mice-lab-created-cells [8] Yong, Ed. “Will we ever…grow synthetic organs in the lab?” BBC Future. 2/24/2012. Accessed 10/31/2016. http://www.bbc.com/future/story/20120223-will-weever-create-organs [9] A. Do, S. Geary, B. Khorsand, A. Salem. “3D Printing of Scaffolds for Tissue Regeneration Applications”. US National Library of Medicine. 6/10/2015. Accessed 10/31/2016. 3
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