practice, few studies are available that clearly demonstrate the clinical benefit of 3D-printed materials(youssef et al., 2015).

Transcription

1 3D Printing Kidney These days, scientists are working on various complex technologies such as regenerative medicine and tissue engineering in order to produce transplantable organ and repair damaged organs (Gao & Cui, 2016). In a recent TED Talk, Anthony Atala, practicing surgeon and a researcher in the area of regenerative medicine, demonstrated the application of 3D printing kidney by illustrating its potential application to the science of kidney regeneration. Organ printing, as a computer-aided, jet-based 3D tissue-engineering of living human organs, is being applied to address the need for tissues and organs suitable for transplantation (Murphy & Atala, 2014). In fact, 3D bio-printing technology could be considered as a powerful tool for building tissue and organ structures (Seol, Kang, Lee, Atala, & Yoo, 2014). Although the application of 3D printing kidney is in the early stages, there are more benefits in this method than its drawbacks. First of all, the increase of aging population and patients with end-stage organ failure have accelerated the need for replacement organs. Currently, in the USA, one name is added to the organ transplant waiting list every 15 minutes, while less than one-third of waiting patients can receive matched organs from donors, and many of them die before receiving the desired organ. Specifically, in the fields of urology and nephrology, the need for organ donors is continuously increasing as the number of patients with chronic renal failure rises. In the USA alone, over 100,000 patients are waiting for a kidney transplant. In 2013, 4500 Canadians were on a waiting list for a transplant. Of those, nearly 80% were waiting for a kidney. Unfortunately, the number of organ donors has remained static. As a result, seeking alternative solutions to treat these problems especially end-stage renal disease is an urgent need (Garcia-Dominguez, Vicente, Vera-Donoso, & Marco-Jimenez, 2017). Secondly, progress in kidney transplantation is limited by the need for immunosuppressive therapies and chronic immunosuppression following transplantation. The regenerative medicine approaches, especially 3D printing kidney, are promising tools aiming to improve the chance of kidney transplantation (Peloso et al., 2015). In fact, this technology would eliminate complications arising from immunosuppression and transplant rejection because it uses the patient's own cells which are compatible and not challenged by the immune system (Soliman, Feibus, & Baum, 2015). Regenerative medicine and manufactured organs represent a potentially inexhaustible source of transplantable grafts that would bypass the need for immunosuppressive drugs.

2 The other problems which the organ printing technology could ultimately reduce or eliminate are the shortage of transplantable organs and organ donors. 3D printing technology allows precise placement of cells, biomaterials and biomolecules in spatially predefined locations within confined three-dimensional structures, makes a precise simultaneous 3dimensional positioning of several cell types, enables creation tissue with a high level of cell density, and solves the problem of vascularization in thick tissue constructs (Mironov, Kasyanov, Drake, & Markwald, 2008) such as the kidney by producing a customized organ. Also, this technology has high digital control of speed, resolution, cell concentration, drop volume, and diameter of printed cells(ventola, 2014). Accordingly, this technology may solve the organ transplantation problems in the future. The 3D printing technology as a future alternative for organ transplantation, not only decreases the need of organ donors but also is economically and functionally superior to dialysis in treatment of end- stage renal disease. In the United States, a kidney transplant costs $80,000, followed by $13,000 annual costs for anti-rejection medication, with a total cost of approximately $260,000 for each patient requiring transplantation (Soliman et al., 2015). In Canada, the annual cost to administer dialysis is around $60k per patient (requiring three visits a week to the hospital for hemodialysis treatments lasting roughly four to five hours each) where comparatively, a kidney transplant costs roughly $23k per procedure followed by $6k in annual costs for anti-rejection medications. In fact, when compared with maintenance peritoneal or hemodialysis, renal transplantation dramatically improves patient survival, quality of life, and is cost-effective in terms of health care expenditures(orlando, Soker, Stratta, & Atala, 2013). Considering the financial costs of current therapy options, the technology of 3D printing kidney will reduce the long-term costs of treatment of end-stage renal disease. Meanwhile, 3D printers can print products as and when needed, and does not cost more than mass manufacturing, no expense on storage of goods is required. In addition, using 3D printing kidney technology in the future can improve survival rates of patients with the end-stage renal disease. The mortality rate of kidney diseases is between 50 and 80%, and available therapies are associated with a high morbidity and mortality (Mata-Miranda, Delgado-Macuil, Rojas-Lopez, Martinez-Flores, & Vazquez-Zapien, 2017). According to a United States Renal Data System report as of July 27, 2012, life expectancy from the time the dialysis is initiated is approximately eight years for patients between the ages of 40 and 44, and 4.5 years for

3 those who are between 60 and 64 years of age. These figures are far surpassed by the increased survival rates following kidney transplantation which are 85%, 70%, and 44% after 5, 10, and 20 years, respectively(orlando et al., 2013). Kidney transplantation is limited by the shortage of donor organs, immune rejection and lifelong treatment with immunosuppressive, so new researches on developing therapeutic strategies such as 3D printing kidney as a substitute treatment for kidney transplantation can increase the survival rate of patients with end-stage renal diseases. Despite the 3D kidney printing advantages, as any new technology, there are various technological concerns which may impede the adoption of the technology. Although the field of 3D printing kidney has developed considerably over the past years; it still is in the developmental stages. To make this technology and organ creation more applicable to clinical medicine, it requires to the progress in complex software design and standardization of kidney bio-printing techniques (Soliman et al., 2015). Moreover, it should mention that it is not sufficient to produce only a structural replication of an organ, and the new organ must be able to perform all of its clinical functions before being transplanted into a patient. For example, if a bio-printed kidney is incapable of secreting erythropoietin, this organ is not fully functional to the patient. In consequence, complex structures containing cells of different types must be printed (Soliman et al., 2015). In addition, there are logistical problems regarding cell-sourcing including cell quantity, cryopreservation, storage and distribution remain before wide-spread adoption can occur. The other concern that scientists are facing using 3D kidney printing is ethical problem. Indeed, different approaches address ethical considerations of tissue engineering such as research ethics and patients safety. With significant advances in molecular and cell biology and nanotechnology, the need for safe and effective therapies will also create unique ethical situations in the future. Also, the use of animals in biomedical research has generated opposition from animal rights groups which has created new challenges to scientists and researchers. Many ethical concerns related to the use of biomaterials fabricated from artificial substances including metals, polymers, and ceramics are related to the safety and harmful effects these materials on the human body. However, the development of biomaterials that incorporate biological materials such as cells with more traditional, non-biological materials will likely mean that new ethical questions will arise. However, several studies have suggested that 3D printers may be a useful technology in urological

4 practice, few studies are available that clearly demonstrate the clinical benefit of 3D-printed materials(youssef et al., 2015). Furthermore, in some cases, 3D printing technology uses stem cells which has some moral concerns. The destruction of human embryos in stem-cell research amounts to the killing of human beings. For those who adhere to this view, extracting stem cells from a blastocyst is morally equivalent to yanking organs from a baby to save other people's lives because isolation of one type of stem cell involves the destruction of human embryos as the earliest stage of human life. In like manner, traditionalists claim that creating living material artificially to implant back into the human body is wrong because the use of human embryonic stem cells as well as therapeutic cloning is implemented to grow the new tissue. Opponents feel that it's not the role of biomedical engineers to play God. These challenging issues have resulted in picket lines, public protests, and opposition from religious organizations. However, there are some argue that stem cell research is unethical especially in the Islamic tradition, tradition permits it as long as such research is aimed at improving human health. In conclusion, the field of regenerative medicine and 3D kidney printing could be the technology of the future of transplantation especially for patients suffering from renal failure. To be exact, it has many advantages in comparison with traditional organ transplantation. This technology could ultimately revolutionize the field of nephrology, reducing or eliminating the need for kidney donation from living or deceased donors, and would eliminate complications arising from immune suppression and transplant rejection. However, some technological limitations such as complexity of printing software, design, and process; also, traditional beliefs and ethical standards are some limitations and challenges of bio-printing technology. Advance in the 3D kidney printing may seem small, but if it continues at current pace, the human may see printed kidney start to take the burden off donor lists. Cooperation among various disciplines will develop this technology and make it accessible more quickly for future clinical application. References: Gao, G., & Cui, X. (2016). Three-dimensional bioprinting in tissue engineering and regenerative medicine. Biotechnol Lett, 38(2), doi: /s

5 Garcia-Dominguez, X., Vicente, J. S., Vera-Donoso, C. D., & Marco-Jimenez, F. (2017). Current Bioengineering and Regenerative Strategies for the Generation of Kidney Grafts on Demand. Curr Urol Rep, 18(1), 2. doi: /s Mata-Miranda, M. M., Delgado-Macuil, R. J., Rojas-Lopez, M., Martinez-Flores, R., & Vazquez-Zapien, G. J. (2017). Potential Therapeutic Strategies of Regenerative Medicine for Renal Failure. Curr Stem Cell Res Ther. doi: / x Mironov, V., Kasyanov, V., Drake, C., & Markwald, R. R. (2008). Organ printing: promises and challenges. Regen Med, 3(1), doi: / Murphy, S. V., & Atala, A. (2014). 3D bioprinting of tissues and organs. Nat Biotechnol, 32(8), doi: /nbt.2958 Orlando, G., Soker, S., Stratta, R. J., & Atala, A. (2013). Will regenerative medicine replace transplantation? Cold Spring Harb Perspect Med, 3(8). doi: /cshperspect.a Peloso, A., Katari, R., Murphy, S. V., Zambon, J. P., DeFrancesco, A., Farney, A. C.,... Orlando, G. (2015). Prospect for kidney bioengineering: shortcomings of the status quo. Expert Opin Biol Ther, 15(4), doi: / Seol, Y. J., Kang, H. W., Lee, S. J., Atala, A., & Yoo, J. J. (2014). Bioprinting technology and its applications. Eur J Cardiothorac Surg, 46(3), doi: /ejcts/ezu148 Soliman, Y., Feibus, A. H., & Baum, N. (2015). 3D Printing and Its Urologic Applications. Rev Urol, 17(1), Ventola, C. L. (2014). Medical Applications for 3D Printing: Current and Projected Uses. P t, 39(10), Youssef, R. F., Spradling, K., Yoon, R., Dolan, B., Chamberlin, J., Okhunov, Z.,... Landman, J. (2015). Applications of three-dimensional printing technology in urological practice. BJU Int, 116(5), doi: /bju.13183