Sreyas Ravi
Disclaimer—This paper partially fulfills a writing requirement for first year (freshman) engineering students at the University of Pittsburgh Swanson School of Engineering. This paper is a student, not a professional, paper. This paper is based on publicly available information and may not provide complete analyses of all relevant data. If this paper is used for any purpose other than these authors’ partial fulfillment of a writing requirement for first year (freshman) engineering students at the University of Pittsburgh Swanson School of Engineering, the user does so at his or her own risk.
3-D BIO-PRINTING:
ADDING A NEW DIMENSION TO TISSUE ENGINEERING
Sreyas Ravi ()
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Sreyas Ravi
ORGAN FAILURE: AN INTRODUCTION TO THE DARK MARKET OF
MEDICAL CRISES
Regardless of other medical issues in recent news, there is always a constant need for organs across the world. As reported by CNN statistics, “some 18 people die in the United States each day waiting in vain for transplants because of a shortage of organs” [1]. However, the circulation of organs is at a standstill due to the complications of matching patients with corresponding donations. Although stem cells have provided insight into how to staunch this global crisis, there has been a push by many bioengineers to automate the current stem cell procedures. In response to demand, bioengineers have constructed “bio-printers” such as Organovo in hopes of minimizing patients’ waiting times. Although there are many critics of the ethics, prices, and ramifications behind furthering stem cell technology and bio-printing, I firmly stand as a proponent of this new field of regenerative medicine because I believe that curing desperate patients outweighs the reservations of a few skeptics. As a bioengineer interested in tissue engineering, I am excited to discover what lies in store for this field, and hope to one day contribute to its advancement.
A HISTOLOGICAL HINDRANCE
A century ago, the average life expectancy in the United States was 54.2 years old, an age that many people today easily exceed while maintaining good physical and mental condition. Today, as reported by the CDC,modern medicine has pushed national life expectancy to 78.8 years old. Despite this improvement, organs still eventually fail due to natural aging. Whether it is to address cardiac irregularities or kidney failure, searching for a match between a donor and a patient is a long, tedious process that is not guaranteed. If a patient is fortunate enough to be matched, they still risk having their body reject the donor’s tissues. However, if a patient is given organs that are reconstructed from the patient’s own cells, then the he or shewill be significantly less likely to get sick post-surgery.
Constructing an organ from scratch poses many challenges to engineers. The human body is composed of hundreds of trillions of cells, of which most are specialized to perform specific tasks. Biologically, organs are complex structures made up of several matrices of tissue, making it seemingly impossible to redesign an organ on a macroscopic level. Although researchers and engineers havepreviously constructed artificial organs with metal components, Dr. Richard Schaub, an Artificial Heart bioengineer and University of Pittsburgh professor, states, “it is difficult to find materials or alloys that are compatible with the human body that are better than substances from the body itself to spur regeneration and restore functionality” [2]. An additional challenge that biological material faces, however, is surviving the surgical process, adding another layer of complexity to an already difficult task.Despite the challenges, utilizing the resources from the human body is still a worthwhile endeavor. Searching throughout the body, engineers can discover and harvest their building blocks for the next wave of regenerative medicine: stem cells.
STEM CELLS
BORN BUILDERS: WHY ARE STEM CELLS CRUCIAL TO REGENERATIVE MEDICINE?
To create a zygote, a sperm cell fuses with an egg to that undergoes cell replication to form a larger cell body called an embryo. At this point of mammalian development, embryonic cells have the unique property of being pluripotent, meaning they can differentiate and become any type of cell. Per several views gathered by the Library of Congress, “researchers believe that, because they are pluripotent, and easy to grow, they have the best potential for replacing damaged or lost tissue or body parts” [3]. After birth, humans continue to have these cells throughout their bodiesin the forms of bone marrow, liver tissue, and blood. They serve as templates for cell manufacturing that bioengineers can use externally.
Stem cell researchers typically use stem cells of zygotes from in vitro fertilization facilitiesthey best replicate the pluripotence needed to grow organs. However, scientists can also collect, research, and modify stem cells through harvesting them from the blood and bone marrow. Using a catheter to collect stem cells in blood or a long needle to extract small amounts of bone marrow from the body, scientists grow the cells in cell cultures streaked with nutrients to keep the cells alive and replicating. Once cells form multiple layers of tissues, these tissues are layered and molded to craft anatomical meshes and structures which are experimented on to test functionality and structural integrity.
IMPLICATIONS OF STEM CELL TECHNOLOGY
Stem cell technology has provided significant breakthroughs in the field of regenerative medicine. The most popular use of stem cells has been cell-based therapy. According to the National Institutes of Health, “today, donated organs and tissues are often used to replace ailing or destroyed tissue, but the need for transplantable tissues and organs far outweighs the available supply. Stem cells…offer the possibility of a renewable source of replacement cells and tissues to treat diseases” [4]. This means that patients in need of tissues and organswould not have to wait months or even years for a life-saving match and organ donation. They can receive treatment almost immediately after diagnosis using their own cells.
As advantageous as this technology is, stem cells pose several problems as well. As this technology is still in its infantile stage, constructing parts of the human body is a longand inefficient process requiring pinpoint precision. As the ultimate purpose of the stem cells is to be implanted into the body to perform crucial functions, they must be assembled meticulously. Human coordination alone is not capable of organizing and delivering cells at this level of precision. Nonetheless, emerging from stem cell technology, bio-printing promises to potentially revolutionize regenerative medicine by taking the cell-building process to new levels of innovation.
BIO-PRINTING: INNOVATION THROUGH AUTOMATION
FROM TOY TO LIFE-SAVER:
ORIGINS OF 3-D PRINTING
Inspired by the recreational activity, bio-printing offers a novel solution to an incessant world problem. Initially, 3-D printing was a niche manufacturing product that had more recreational purposes than industrial uses. According to the Economist, a business newspaper,“three-dimensional printers take several different materials from metal to plastic and even chocolate to create a piece of final structure from scratch” [5]. It is a versatile machine that is efficient at using resources and deft in constructing even the most intricate of patterns. Therefore, it made a perfect solution for the transplant crisis occurring in the medical world.
In 2000, Clemson University’s Thomas Boland converted a standard ink printer to print proteins, E. coli bacteria, and eventually larger rodent cells. Instead of using printer ink, Boland used a cluster cells dubbed “bio-ink” that could bond to one another. Inspired by these findings, other engineers propelled Boland’s research forward by attempting cell printing in three dimensions. As described by science journalist Steven Leckart, “[Boland’s researchers] disabled the paper-feed mechanisms in their inkjets and added an elevator-like platform controlled by stepper motors; the platform could move up or down along the z-axis. Labs could print one layer of cells, lower the platform, and print another layer” [6]. An early ancestor to the machines that exist today, the current technology is based off this original concept.
EVOLUTION OF BIO-PRINTING
As mentioned before, a huge step that helped advance bio-printing was the development of bio-ink. The current bio-ink formula capable of printing out tissues and organs has significantly evolved from Boland’s ink. Combining natural polymers from seaweed and synthetic polymers from medical industries, researchers create amixture that has the unique properties of changing from a liquid to a solid when heated and promoting cell growth by increasing structural support. When extracted cells grown from a culture outside the body are added to the polymers, it creates a cell paste. Using CT scans and MRI images, engineers create digital images that a needle dispenser follows to deposit cells on a cohesive gel. After a few hours of incubating the tissue molds, the three-dimensional biological structure is created. When the structure is placed in the body surgically, the biodegradable polymer harmlessly dissolves away as the body adjusts to it, leaving no sign of surgery.
THE FUTURE OF MEDICINE:
PRINTING OUT CURES
FOR PATIENTS
FRESH OFF THE PRINT:
BIO-PRINTING IS A VIABLE CURE
Although in its early stages, 3-D printing has already saved countless lives. For example, in 2013, doctors operated on six-week old infant Kaiba Giofriddo, who had a congenital, collapsed bronchial tube. At that time, Kaiba’s tracheobronchomalacia was incurable,giving him a grim life-expectancy. However, per medical records of the University of Michigan, “Kaiba made headlines after he became the first patient to receive a customized tracheal splint implant created from CT scans and an image-based computer model with a laser-based 3-D printer” [7]. Since the surgery, Kaiba has breathed normally, and his doctors are tracking his vitals to test the long-term effects of having 3-D-printed artificial organs in the body. Impressively, the engineers used biocompatible plastics that will dissolve as Kaiba grows older. In a few years, a CT scan of Kaiba’s respiratory system will showa normal set of bronchial tubes with no evidence of surgery. Moreover, due to the success with Kaiba, this procedure has been utilized several more times to save other infants’ lives.
Engineerscreating viable tissue substitutes for damaged areas of the body opens a frontier of many exciting possibilities. The bio-printer employed in Kaiba’s surgery was developed from technology from an upcoming company called Organovo. The San Diego-based company is helping normalize bio-printing as a more popular route for patients with tissue and organ problems to choose. As reported by the American Society of Mechanical Engineering, “Organovo has also built models of human kidneys, bone, cartilage, muscle, blood vessels and lung tissue, building tissue the way you assemble something with Legos, per Organovo CEO Keith Murphy” [8]. In terms of human operations, engineers and doctors have successfully implanted 3-D printed bladders, tracheas, and various cell meshes in the body. However, with successful organ trials on rodents and preliminary molds for humans, Organovo plans to create the first organs to use stem cells and 3-D bio-printing within the next few years.
ETHICAL CONCERNS FOR BIO-PRINTING
Although there are many benefits to using this technology, there are also many critics questioning the ethics of such surgeries. Primarily, researchers at Gartner, Inc., an information and advisory firm, believe that 3-D printing has future ramifications that will hurt the medical industry. They also worry about “complex ‘enhanced’ organs involving nonhuman cells corrupting the regenerative medicine field, skyrocketing prices so that only the wealthy can afford them” [9]. Furthermore, director of Gartner Pete Basiliere also pointed out the controversy of taking stem cells from zygotes that are preserved in in vitro facilities, questioning whether taking cells from embryonic life forms cruelly terminate them. Nevertheless, Murphy assures that Organovo and other 3-D printers use solely human stem cells in their projects that are still in their early stages. Since this is a new technology, there is still financial room to lower the price for patients once the technology is more established. Ethically, in vitro facilities house donations of which many are for the cause of research as well.
Most importantly, 3-D bio-printing canimprove people’srecoveries from injuries. As an athlete who has torn his ACL, I know that the patella tendon graft screwed into my knee is not the ideal replacement for the original ligament because it did not originally serve the same function. In fact, “the overall incidence rate of having to go through it again within 24 months is six times greater than someone who has never had an ACL tear”, according to researchers from the American Orthopedic Society of Sports Medicine, a leading orthopedic organization in the country [10]. So far, researchers have reconstructed a few knee ligaments, but their results are weak and die quickly outside the culture. With more time to investigate growing human muscles, ligaments, and tendons, orthopedic surgeons can potentially reduce the probability of injuries from recurring.
In dire situations when time is limited to a few days, this surgery can salvage hope for desperatepatients who need transplants Although the technology is still in early stages, once accomplished, doctors can balance the numbers of donors and patients by having 3-D printing as an option for patients. When my friend’s father was in the hospital for kidney failure, everyone in our community was tested for a possible match. Unfortunately, none of us could donate a kidney to him, and he went through peritoneal dialysis machine for weeks for his body to process fluids. Luckily, after three-month wait, he finally received a match and a transplant. Nevertheless, I can still remember how painful the situation was for my friend. For months, he had to go visit the hospital to see his father, and I remember how emotionally fragile he was in school. If anyone wished his father a speedy recovery, he would instantly frown and turn silent. No family should have to suffer through this. With pushes from Organovo, the wait can be eliminated, and the chances of a full recovery faster will promise to push the frontier of human longevity.
A NOBLE CAUSE FOR MY FUTURE
In fifty years, I cannot predict what my health will be like. Genetically, I may develop diabetes and heart problems passed down my paternal family tree. I may tear ligaments in my arthritic knees or lose cartilage due to stress upon my knee joints. Unfortunately, no matter how much I exercise, no matter how healthy I eat, no matter how many supplements I take, there is always a chance that my organs or tissue structures will fail. It is a daunting truth, one that is seemingly inescapable and inevitable. However, stem cell technology and, more specifically, three-dimensional printing, offers a safety blanket of medical care that can change the way we perceive age and disease. Printing tissues and organs, we can stabilize the circulation of organs globally. As an aspiring bioengineer, I hope to contribute to the field of regenerative medicine by studying stem cell technology and organ printing as a Pitt student. When I become a bioengineer, I will strive to accomplish regenerative medicine’s noble cause. Families will not lose loved ones to the dying hope of an organ and tissue match. A positive CT scan will not be an assumed death sentence. Technology will not limit engineers as they push further to an ideal world in which regenerative medicine can cure sicknesses of higher magnitude. Without question, with 3-D bio-printing, mankindis knocking on the door to a future in which we may not live eternal lives, but will uphold a lasting goal to save thousands of lives for generations to come.
SOURCES
[1] B. Griggs. “The Next Frontier in 3-D printing: Human Organs.” Cable News Network. 04.05.2014. Accessed 10.29.16.
[2] R. Schaub. Conversation regarding Artificial Organs. University of Pittsburgh Swanson School of Engineering. 10.20.16.
[3] A. Mandal. “What are Stem Cells?” News Medical Life Sciences. 12.23.2013. Accessed 10.29.16.
[4] “Stem Cell Information.” National Institutes of Health, U.S. Department of Health and Human Services.
Accessed 10.29.16.
[5] “Printing a bit of me.” The Economist. 05.08.2014. Accessed 10.30.16.
[6] S. Leckart. “How 3-D Printing Body Parts Will Revolutionize Medicine.” Popular Science, Bonnier Corporation Company. 08.06.2013. Accessed 10.29.2016.
[7] M. Fessenden. “3-D printed windpipe gives infant breath of life.” Nature, Macmillan Publishers Limited. 05.28.2013. Accessed 10.28.2016.
[8] M. Crawford. “Creating Valve Tissue Using 3-D Bio-Printing.” American Society of Mechanical Engineers. 05.01.2013. Accessed 10.27.2016.
[9] B. Griggs. “The Next Frontier in 3-D printing: Human Organs.” Cable News Network. 04.05.2014. Accessed 10.29.16.