ENGR0011 Vidic 2:00 Group R01 REGENERATIVE ENGINEERING: BUILDING THE SCAFFOLDING OF TOMORROW Rachel Lukas (rel43@pitt.edu) PREAMBLE Often, freshman engineering students enter college as undergraduates without any awareness of what it truly means to be an engineer. They often see the profession as being simple and straight forward, an easy way to make money. However, engineering is much more substantial than that. In this paper I will divulge into the specifics of a branch of bioengineering that is of great importance to me personally. Furthermore, I will explain the significance of ethics in this engineering field along with why an assignment such as this is vital for undergraduate freshmen to take on. body using the patient’s own cells and implant the organ back into the patient. The development of bioengineered organs not only minimizes the need for conventional organ transplants, but also allows regenerative engineers and doctors to increase the survival rates of patients with a fabricated organ after transplant surgery. Implanting an engineered organ greatly reduces the possibility of a patient’s body rejecting the organ since it is composed of the patient’s cells rather than foreign cells [2]. WHAT COULD YOU POSSIBLY GROW FROM HUMAN CELLS? Bioengineered Bladders THE DOOR TO A NEW WORLD OF MEDICINE OPENS How to resolve a growing crisis Today, there is a growing international medical emergency, one that affects individuals in every country in the world. This crisis is the growing global scarcity of donor organs for those who are in need of a transplant. In fact, “more than 100,000 people are waiting for organ transplants in the U.S. alone; every day eighteen of them die” [1]. Even in the event where a donor organ can be obtained, the receiving patient still runs the risk of their body rejecting newly implanted tissues or organ. It is because of this that scientists are developing innovative alternatives to traditional organ and tissue replacements through a new branch of medical science called regenerative engineering. WHAT IS IT AND WHY IS IT IMPORTANT? Regenerative engineering includes a broad range of disciplines ranging from creating living, usable tissues to the repair of damaged parts of the body, to allowing organs to heal themselves in ways that once seemed to be impossible. Perhaps most significantly, regenerative engineering allows scientists to develop full-functioning organs outside of the In 2006 an experiment was conducted on children and young adults who were affected by spina bifida, a birth defect that causes bladders to function poorly, often leading to a host of medical issues including kidney failure [3]. In the experiment, bioengineered bladders crafted from the patients’ natural bladder cells were implanted into these patients. The laboratory-grown bladders were created by placing the patients’ cells, obtained from a biopsy of their bladders, onto a scaffold. This scaffold was a biomaterial created from a deceased bladder whose original cells were “washed” away, leaving only the basic skeleton of the bladder behind. Next, the patients’ bladder cells were placed onto the scaffold which acted as a bridge for the cells so they could adhere to it and multiply. After a month of growing the cells on the scaffold, the new bladder structure was incubated in an oven-like device that mimicked the human body’s natural conditions, thirty-seven degrees centigrade with ninety-five percent oxygen. The bladder then remained in incubation for a few weeks until the tissues matured [4]. Then, the bladder was transplanted into the patients’ body where nerves and blood vessels naturally grew into place, allowing the bioengineered bladder to function as if it were natural [3]. The results of the experiment were highly successful with none of the patients experiencing a rejection of the new bladder [4]. The success of the bioengineered The University of Pittsburgh, Swanson School of Engineering October 6, 2012 1 Rachel Lukas bladders opened the doors to the development of other types of tissues. Can these printers make any other tissues? Additionally, Atala and his team have modified a desktop inkjet printer to produce structures that can immediately be implanted into a patient upon completion. This printer works like an elevator, creating one layer of cells at a time to produce a three dimensional, bioengineered scaffold. For example, Atala and his team have successfully developed a method of printing bone segments that have been implanted into several patients [4]. In viewing X-ray images of the bioengineered bone, the tissues have been fully regenerated to the point where it is difficult to determine where there was natural bone and where it was biologically engineered. Furthermore, Atala and his team have been developing technology that can directly attach cells to injured patients at the site of an injury. Essentially, a flatbed scanner goes over a patient’s laceration and develops a summary of the tissues that are in need of repair. Subsequently, a printer then takes that information and creates the necessary tissues, layer by layer, directly onto the patient’s wound [4]. Once this technology is fully developed, it would hasten the healing process and recovery times of severe wounds in emergency situations and decrease the need for intensive surgery to repair damage caused by serious injuries. Reconstructing an Esophagus Regenerative engineers are also developing cures for esophageal injuries and congenital long-gap esophageal atresia, a birth defect where the esophagus does not connect to the stomach normally. These treatments are still in development, and have only been tested on laboratory rats; however, these experiments show a great deal of promise. In the rat tests, cells from the test subject were again transferred to a biomaterial scaffold where the esophageal cells were able to reproduce and form tissues. Then, the tissue was implanted back into the rats. After ten and sixteen weeks post-implantation of the bioengineered esophageal tissue, the test rats were sacrificed and dissected to view the progress of the inserted tissue. It was found that in both groups of rats, the esophagus was readily repairing itself with the help of the biomaterial scaffold [5]. This experiment shows potential in the fact that it was so successful in the rats, and it raises hopes that esophageal regeneration may soon be a viable treatment for human patients with esophageal damage and other defects. A MORE DIFFICULT TASK: VASCULAR ORGANS SO, WHAT DOES ALL OF THIS IMPLY? What Regenerative Growth Offers the Future “[Our lab uses] a desktop inkjet printer, but instead of using ink, we're using cells.” Regenerative growth bioengineering has opened the door to new therapies for damaged tissues and organs that were previously thought to be extremely daunting procedures, if not impossible ones. For example, bladders and esophageal tissues can be bioengineered outside of the body using the patient’s own cells. Additionally, vascular organs such as kidneys, which are more challenging to create, have been experimentally produced through the use of highly sophisticated cellular printers. Although only the bioengineered bladders have been implanted into human patients, the rest of the aforementioned technologies are not far behind. These other components of regenerative engineering each yield great optimism in one day being able to treat failures or complications associated with birth defects, diseases, physical damage from injuries, and cancer in many organs and tissues found throughout the human body. Vascular organs, those containing copious amounts of blood vessels, are more difficult to regenerate than hollow, sack-like organs such as the bladder [1]. However, Anthony Atala of the Wake Forest Institute for Regenerative Medicine in Winston-Salem, North Carolina has developed an ink-jet printer that can essentially produce copies of any bodily structure using cells. The printers that Atala and his team are developing use images from CT scanners or X-rays to obtain a blueprint for an organ, in this case the kidney. Using the CT scan, Atala and his team are able to obtain all of the volumetric characteristics of the patient’s kidney, and can then transfer the image into a computerized format that the printer can read. At that point, the printer starts moving through the organ, level by level, printing cells as it goes along. In this fashion, a new kidney can be developed for the patient, using their own cells, in about seven hours [4]. 2 Rachel Lukas regenerative engineering alone. Instead, the Biomedical Engineering Society has refined the NSPE canons in such a way that they are directly correlated with biomedical engineering. In turn, the BMES code of ethics can be more precisely applied to regenerative engineering than the NSPE standards alone. The BMES clearly states in their code’s preamble that “public health and welfare are paramount considerations” for biomedical engineers [8]. This is reflected in the very premise of regenerative engineering where the goal is to improve upon current treatments for congenital defects and injuries associated with the human body’s tissues and organs. More specifically, there are two principles in the BMES code that are extremely important for regenerative engineering. The first of these statements says that biomedical engineers must “use their knowledge, skills, and abilities to enhance the safety, health, and welfare of the public” [8]. Essentially, this is what regenerative engineers strive to accomplish. In developing artificial organs and tissues, regenerative engineers aim to universally improve the lives of patients through more efficient and successful transplants of organs. Furthermore, regenerative engineers are required to “consider the broader consequences of their work in regard to cost, availability, and delivery of healthcare” [8]. Anthony Atala and his team are a prime example of how regenerative engineers abide by these ethics. Their printers are being designed to operate in any emergency room, especially the flatbed cell printer that places the necessary cells directly onto a patient [4]. In improving this technology, more effective treatments for injuries will become more widely available. Although cost is still an issue, this can be minimized with further research and development of the printers in the future. A PERSONAL CONNECTION Several years ago, an event occurred that made me become determined to remedy the donor organ shortage. In 2007, one of my very close friends was diagnosed with a tumor on his right kidney; doctors said had to be removed as soon as possible for fear that it was a malignant, cancerous tumor. So, at the age of fifteen, my friend lost a kidney and was put on the waiting list for a donor one, on which his name remains to this day. Luckily, he has managed to cope with living with a single kidney; however, he will be held under close observation for the rest of his life to make sure that his other kidney preforms as it should. So, when I began to research possibilities for a future career, I came across the idea of regenerative bioengineering. Instantly I fell in love with it and all of the possibilities that regenerative growth could provide to the medical field. I have confidence that through developing regenerative technologies, thousands of people, like my friend, will be able to improve their standard of living by being able to have their bodies run at their full potential. Therefore, it is my belief regenerative medicine will open the gates to a flood of new information about healing in the years to come and must be thoroughly explored. ETHICS: WHO CARES? The Ethics Resource Center defines a code of ethics as “a central guide and reference for users in support of day-today decision making” that clearly and explicitly explains in detail how individuals must perform [6]. Equally, all engineers are legally and morally required to follow a specific code of ethics, regardless of their discipline or concentration. The National Society of Professional Engineers states in their code’s preamble that “engineers are expected to exhibit the highest standards of honesty and integrity” in their work [7]. The NSPE canons reflect these conditions and specifically exemplify how engineers are expected to perform. The NSPE code precisely outlines practices that are acceptable and unacceptable for engineers to undertake. Furthermore, the code focuses heavily on avoiding corrupt enterprises, fraud, or unlawful activities. Engineers are also required to give credit for work and research when it is due. Additionally, and most importantly, engineers are required to promote the “safety, health, and welfare of the public” [7]. Each section of the NSPE ethics can be applied to every engineering discipline in general. However, this code of ethics is far too broad to apply to WHY DO FRESHMEN NEED TO CARE? An assignment similar to this paper is an important one for freshman engineering students to undertake for multiple reasons. First, it required students like myself to research a current engineering topic that interested them. Individually, this made me realize the fact that I truly want to major in bioengineering so that I can one day become a regenerative engineer. This paper made me look into what technologies that regenerative engineers are developing, and inspired me to one day do the same. Furthermore, this assignment is crucial to incorporate in a freshman curriculum because it has students investigate the codes of ethics that govern engineers. Again from my own experience, I know that I had 3 Rachel Lukas a vague notion that a guideline of sorts existed for engineers, but I never really thought about them in depth. After researching the codes of ethics that apply to the different disciplines of engineering, I realized just how important they are to this profession. Every aspect of engineering, from how reports are compiled and presented to the experiments that bioengineers perform, are governed by a code of ethics. Having freshmen research these policies is crucial in creating well informed young engineers who are conscious of the world around them. Therefore, it is my belief that assignments such as this should be universally adopted in engineering schools beyond the Swanson School of Engineering at the University of Pittsburgh. ADDITIONAL SOURCES "Esophageal Atresia Symptoms, Treatment, Diagnosis." (2009). Atresia.info. http://www.atresia.info/esophagealatresia.htm. ACKNOWLWDGEMENTS I would first like to thank my dear acquaintance, Kyle Spies, for giving me the motivation and pressure to keep on task throughout the entire research process. Additionally, I would like to thank the librarians in the Swanson School of Engineering’s library who were extremely accommodating in helping me gather the necessary information for this paper from legitimate sources. REFERENCES [1] J. Glausiusz. (2011). "The Big Idea: Organ Regeneration." National Geographic. (Online article). http://ngm.nationalgeographic.com/2011/03/big-idea/organregeneration-text. p. 1-2 [2] R. Hunziker. (2012) "Regenerative Medicine." National Institutes of Health (Online article). http://report.nih.gov/NIHfactsheets/ViewFactSheet.aspx?csi d=62. p. 1 [3] R Lovett. (2006) "First Lab-Grown Organs Implanted in Humans." National Geographic. (Online article). http://news.nationalgeographic.com/news/2006/04/0404_06 0404_bladders.html. p. 1-2 [4] “Printing a Human Kidney.” TED Conferences LLC. (2011) (Video). http://www.ted.com/talks/anthony_atala_printing_a_human_ kidney.html. [5] J. Basu, K. Mihalko, R. Payne, et al. (2012). "Extension of Bladder-Based Organ Regeneration Platform for Tissue Engineering of Esophagus." Medical Hypotheses. 78.2 pp.231-34 http://www.sciencedirect.com/science/article/pii/S03069877 11005597. [6] “Why Have a Code of Conduct?” Ethics Resource Center. (2010) (Online Article) http://www.ethics.org/resource/why-have-code-conduct [6] “NSPE Code of Ethics for Engineers” National Society of Professional Engineers. (2012) (Online article) http://www.nspe.org/Ethics/CodeofEthics/index.html [7] “Biomedical Engineering Society Code of Ethics” Biomedical Engineering Society. (2012) (Online article) http://www.bmes.org/aws/BMES/pt/sp/ethics 4