Bioprinting and The Despairing Reach Out For Its Future Scientists

Gavin P. Enderlin


Introduction

Human beings have struggled with a vast variety of health problems such as injuries, diseases, and disorders. Many of these health problems, which do not yet have an effective cure, ultimately lead to fatal outcomes. Unfortunately, a majority of the diseases and disorders are obtained at a young age, typically at birth. During the early ages of mankind, these infants who were imminently born with these health problems had little to no hope for a treatment due to the lack of medical technology their society was in possession of. Although there has been an obvious increase in technology since the early stages of human life, many of the newborns today undergo health problems that our society has yet to find a cure for, causing these infants’ health problems to conclude to devastating possibilities.

The two unfortunate newborn babies, Kaylee Vitelli and Lillian O’Connor, shown in the pictures below, who were born with rare and harmful organ conditions demonstrate how horrid the possibilities can turn out to be.

Kaylee Vitelli (above)

Because Kaylee’s condition was far worse, due to the fact that she also was diagnosed with joubert syndrome, a rare brain disorder, and the possibility of her surviving was much slimmer than Lillian’s, the despairing decision was made to cut the life support of the newborn baby Kaylee in order to help save the life of the other newborn, Lillian O’Connor. Of course, along with this option, also came with an immense amount of painstaking decisions that would be made by the parents involving the loss of their daughter’s precious life so that another infant can continue on with theirs.

However, with the decision of donating the heart of a currently living baby to another, there were obvious ethical problems that stood with it. For instance, one cannot take the life of one to aid the life of another. There is also the problem that Kaylee’s heart will simply go to the next infant in line who needs a heart transplant. However, with the resolution of this procedure, it is possible that the weak new born receiving the transplant may not even survive the surgery, ending in the death of both infants. The ethical debate is especially true for a baby who does not have the ability to speak out to others whether he or she decides to keep his or her own life.

Lillian O’Connor (right)

After the decision was settled, as well as the doctors agreed to continue with the surgery of a heart transplant from Kaylee to Lillian, Kaylee’s parents decided to cut her life support and keep her in the waiting room until possible death, while the other newborn, Lillian, fortunately waited while being aided by life support. However, after Kaylee struggled to survive without life support for more than an hour, the parents had to place her right back where she began, striving for survival and staying dependent on the life support and doctors. Due to this choice that was made, both newborn babies were forced to sit in this terrible condition, waiting for either an unknown infant’s heart to be donated or for one of the two newborn babies to pass away so the other could have the possibility of surviving. The horrible crisis that Kaylee Vitelli and Lillian O’Connor were put through could have been avoided if a cure to their illness had been known.

There have been many attempts in the past to recreate and transplant synthetic organs and tissue to patients in need, such as Kaylee and Lillian. However, these cures are not able to give hope to many patients due to the inability to create a complex tissue like a synthetic heart. Although there are not current cures for patients in the need of tissue transplantation, there are a few studies in this field that are increasing their possibility of becoming a real world application. One of these studies is the use of Bioprinting. This is a technique that involves creating any synthetic tissue and transplanting it to any disabled human in need.

The process of bioprinting a human kidney

Many, if not all, of the troubles that are involved in the need for tissue and organ transplants that the disabled face worldwide can be solved through the implementation of bioprinting. However, this proposal is constrained by the lacking quantity of contributors who are involved in the research. It is crucial that future scientists and engineers of this research help aid the progression of the program for future success of applications in real world scenarios.

The History That Led To Bioprinting

Before any medical usage was focused on tissue and limb transplantation, victims of injuries or infections would simply live with the condition they were in and hope the pain would cease and the chances of fatality would fade away. According to Wilson Bennett, a graduate in mechanical engineering, since the treatment of lost tissue has started, approximately within the year of 484 B.C., there has been a great incline in the advancement of technology for treating these injuries or diseases throughout history. However, the vast majority of these solutions in the past did not include replacing the lost flesh or limbs with new usable tissue. These past techniques were predominantly used to stop infections or bleeding before the injury becomes fatal, if it had not by this time become so serious that the patient could not be saved.

The most pronounced technique used in the past was simply amputation of the tissue. This involved the removal of limbs due to the highly probably case of the tissue becoming infected or rapidly causing the person’s injury to become fatal. Although this method ceased the infection or injury from becoming more serious, if successful, it did not directly aid the patient in receiving a new limb or tissue to use.

An amputee who has lost the ability to swim as well as before the amputation

Instead, the patient would be forced to live his or her life without the ability to utilize a new way of using what they no longer have. For example, the swimmer within the picture to the left may of survived an injury, but the amputation did not offer the ability to swim as well as before the surgery. This problem, amputees losing their ability to use lost limbs, has been a problem that has not yet been effectively solved for a great amount of time now.

However, a large percentage of patients do not even survive amputation, especially in early ages of mankind. Although it was probable that the procedures done at this time were operated by well trained professionals, if the surgery was not needed the instant injury occurred to stop blood loss or disease and had to be done by someone untrained, it was likely that the technology at the time was not suitable enough to treat a patient with an amputated limb. After the procedure it was highly foreseeable that the patient would die due to blood loss or the exposure to contamination after the surgery. With amputation being as dangerous as it is today, one can easily imagine how much worse it would have been during much more early years. In fact, according to National Center for Biotechnology Information, NCBI, a well trusted national data recorder for biomedical and genomic documentation, even in modern times the percentage of patients not surviving this method of treatment one year after the surgery is at a range of an incredible nine to sixteen percent. Although this number of fatalities may not seem high, the death of merely one or two out of ten is an unsettling ratio.

Although amputation can lead to the end of treatment, there are techniques used in the past that are even used today to give aid in the receiving new forms of amputated arms or lost tissue in general. One of these techniques used in the past, as well as one of the most effective, is the use of prosthetics. Through the years, prosthetics has come a long way in advancement for allowing patients to gain the access to a new usable, but non-synthetic, limb. However, as the Medical Center of Orthotics and Prosthetics, a leading prosthetic company, mentions, even modern prosthetics can cause common issues such as discomfort, irritation, instability, and limb pain. Due to the use of inorganic material, it is very difficult to solve these problems because the prosthetic limb will almost never feel natural to the user. Although this technique usually does a good job of insuring that the patient receives the ability of use to the lost limb or tissue, it has always been missing a key factor throughout its upcoming, the real look of an organic limb and the ability to feel ones surroundings with it. With the desire of replacing patients’ lost tissue or limbs with a strongly related substitute, scientists began researching possible techniques in which this application could be used.

Thus, the beginning of tissue transplantation research was created. The research of tissue transplantation has led to many successful applications of technology in the use of treating damaged flesh and limbs. Many enthusiasts, such as prospective scientists or researchers, may wonder what tissue engineering exactly is. As Professor Chua Kai Chee, an experienced PhD of Nanyang Technological University who has conducted a well structured research group in the field of tissue engineering, and his assistant, Wai Yee Yeong, explains in one of their recently published books,Bioprinting: Principles and Applications, tissue engineering “is an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function” (Chua, 2015, p.5) With advanced implementation of this technique, the damaged tissue of people worldwide can be either rehabilitated or remade to give the individual the usage of the previous section of their body.

In fact, this technique is already in progress of becoming a real world practice. This practice is possible by the use of a number of cells, including stem cells, which are used as the building block of growing new tissue to replace the previous tissue that was damaged. (Chua, 2014, p.6) New variants of these cells are constantly either being identified or designed. These newly found cells are being put to use in multiple experiments as well. One of the experiments Chua stated in his book, utilized by the pediatric orthopedic surgeon W. Green, involved “generat[ing] cartilage using a chondrocyte [cartilage cell] culture technique. The chondrocytes were seeded onto bone spicules and implanted in nude mice” (Chua, 2015, p.7). The purpose of this experiment was to discover a new method of growing cartilage by coaxing cells to connect to the bones of mice. The general concept of this procedure is shown through the picture below. Once the desired variants of stem cells were aquired, each varient was placed in specific areas of the bone to seed and grow new tissue.

Although great attempts were made towards the primary intention of this experiment, growing cartilage, it turned out to be a failure. However, the concept was thought to be useful and was recorded for further use.

With the future application of W. Greens past experiment, the impulse of generating tissue was later applied to other ideas of the tissue engineering development. In fact, a couple years later two scientists, Iannas Yannas of MIT and John Burke of Massachusetts General Hospital, organized an experiment that involved skin generation using the scaffolding of Green’s past work. This skin generation was utilized by the use of keratinocytes, skin cells that produce keratin, and fibroblasts, a cell that produces collagen and fiber, on protein scaffolds (Chua, 2015, p.7). Essentially, this experiment used stem cells of different tissue variants to regenerate burnt wounds of the skin from the basic scaffold of the wound. Because Greens experiment gave Yannas’s and Burkes a starting point, their test ended in great success.

Because of this medical breakthrough of tissue regeneration, the previous experiment led to new ideas and improvements. An example of one of these improvements, by E. Bell, a participant in the development of grafting skins cells to treat wounds, included “transferring sheets of keratinocytes onto burn wounds” (Chua, 2015, p.7). One can see the progression in the advancement of techniques over time from the completion of experiment to experiment. These three improvements, the use of cells, using keratin, collagen, and fiber, and using sheets of cells to help fabricate together to create new tissue, all aided in the advancement that led to the more recent research in bioprinting, the previously mentioned medical breakthrough in the field of tissue engineering.

Many skeptical scientists, such as a few expert researchers of bioprinting including Dr. Dan Thomas and Dominic Eggbeer, may feel that the research project is too complex to actually bring to use as a product in the world within a roughly short time frame. These two researchers both are convinced that bioprinting is more than a decade, if it ever becomes successful, away from being able to create a functional organ. However, tissue engineering is already advancing past being simply theories and the thought of it being too complex to become a reality. In fact, just recently a team at Massachusetts General Hospital, as well as a team of researchers from Massachusetts Institute of Technology, commonly known as MIT, has conducted an experiment to create the first lab grown limb.

They also released a time-lapse of the test through a video to share with the general public. The forearm was created from growing stem cells from a deceased rat onto the skeletal portion of an isolated rat arm. After the completion of its growth, the research team was able to cause the muscle fibers to react with electrical stimulation, concluding the success of responsive tissue. They were even able to surgically attach the limb to a living rat and found that blood circulation between the forearm and the rat is completely possible. This experiment alone shows how positively inclined the advancement of tissue engineering has become.

The advancement of the research of bioprinting was also discussed through the interview with Prof. Chua. He expressed that although bioprinting is currently within the early stages, scientists are hoping to be able to create a human heart within ten years. Although it may take ten years to create a human heart, the time it would take to create a more simple tissue, such as a nose, that can be surgically attached to a human would not be as far away in time. On top of these advancements, with this scientific revelation started in 2008, and is now able to create a real synthetic limb, there is no telling what promises lie ahead in the next decade or two.

With the conclusion that scientists can create a synthetic limb and surgically attach it to a specimen with the allowance of tissue responsiveness and blood circulation, as well as the possibility of creating human tissue within a decade, any scientist would have a hard time opposing the argument that the ability to 3D print synthetic tissue is a well pronounced achievement in comparison to the amount of time it will take to reach this goal. With the practicability of this program saving countless lives roughly within a decade, the great positive qualities of this achievement compared to the amount of time it may take to reach this goal is well worth the wait. However, because there is so much more to bioprinting that needs to be researched, the increase in contributing scientists is crucial to the progression of the program.

Because bioprinting is a generally recent study, it is understandable to believe that not many prospective scientists perusing a degree to aid this program are well educated of what bioprinting exactly is. Clearly through simply reading the name, one can assume it is the printing of biomaterials. However, that is nearly all one can interpret from the word. As Lijie Zhang and John Fisher, professors in the field of Biomedical Engineering, explain in their published book 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine, “3D bioprinting is the process of automated deposition of biological molecules on a substrate to form a 3D heterogeneous functional structure with data derived from a digital model” (Zhang, 2015, p.58). With the use of this technique, the operator of a 3D bioprinter can print virtually any form of tissue he or she desires to create. Because bioprinting has led to so many specific propositions, there are multiple techniques that have been created to satisfy each of the tissue regeneration projects.

A few of the primary techniques used have been explained through an online interview with Professor Chua. He has clarified two common forms of bioprinting and the differences between the two: contact and non-contact printing. Essentially, contact-based printing directly applies material to the surface. Chua states contact based printing is predominantly used when “The contact mechanism created during deposition is necessary to direct the interfacial action of the deposited materials.” These materials are generally high viscosity and are able to deposition the material to the surface with ease. On the other hand, non-contact printing involves injecting the material at a very close proximity to the receiving substrate. For this technique, Chua explains it is generally used for lower viscosity materials, similar to inkjet or laser based printing. In the picture below, one can see the differences between non-contact printing, picture a, and contact printing, picture b. Picture a well illustrates the use of the material being distriubuited throughout the surfaces in close proximity to eachother. While on the other side, picture b demonstrates contact printing directly applying the material to the surface.

An example of non-contact printing (picture a) and contact printing (picture b)

In his previously mentioned book, Bioprinting: Principles and Applications, he also mentions non-contact printing is a method more suited for smaller scaled applications, such as printing microscopic tissue. Although this technique is great for smaller practices, when it comes to larger practices non-contact printing is not as useful as contact printing, due to the use of a larger apparatus that ejects the material to the surface.

Three Current Tissue Transplantation Techniques and Their Downsides

As previously stated, in the past there were multiple methods of treating defected tissue; such as amputating and prosthetics. However, these methods really only ceased the problem from formulating into a fatal scenario, if the patient survived the injury or surgery. These treatments had no real cure to treating tissue by recreating an organic substitute of what was lost. Fortunately with the passing of the years, more useful techniques have emerged that allow the transplantation of organic material. These three techniques, well explained in Chua’s book, used today include autografting, allografting, and xenografting. Although these three methods of tissue transplantation have been proven to be practical in different scenarios, each of them has a couple downfalls that restrict their usage.

The first technique clarified by Chua is autografting. This method involves transferring tissue, including anything from simply skin to a more complex tissue such as muscle or bone, from one area of the patient’s body and transplanting it to a different area. Because this method uses tissue from the same patient, there are little to no rejection issues with the body accepting the new tissue. However, the negative aspect of this technique involves the high cost, pain, and a loss of tissue from the area of the body it was harvested from. These negative features are all due to the fact that the tissue transplantation would ultimately involve two surgeries; one to harvest the tissue from one part of the body and another to transplant it to the needed area. This application is typically only used for the scenario in which there is a shortage of tissue form a donor.

However, for a situation where tissue donation is a possibility in the patient’s near future, a popular technique used is allografting. This method, as Prof. Chua explains, involves tissue transplantation from a donor and transferring it to the patient in need of the desired tissue. This tissue is often received from a deceased donor. Because of this, the receiver does not have to pay for the surgery for harvesting the tissue from the donor. Therefore, the cost of this is typically low since the patient is only paying for one surgery. Although this surgery is normally managed at a lower cost, there is currently a large problem of limited availability of tissue for donation. Due to the lack of donations available, many patients are forced to stand by in an exceptionally long waiting list. This commonly ends in the patient dying due to no donations being available. (Having trouble thinking of transition) also, where is the concrete support her.

Because of this lack of donatable tissue and human lives, there have been many attempts to solve it. One of these attempts, which has become a common practice today, is xenografting: the use of transplanting tissue from an animal to an injured patient. This technique effectively solves the problem of not being able to obtain enough tissue for transplantation. However, there are many problems that come along with it. One of these problems includes the high risk of disease transmission. Although the tissue can come from a clean animal raised in captivity, the transmission from animal to human often times is rejected by the body, ending in diseases and disorders for the patient. If the tissue came from another human, the makeup of the tissue would be similar and the patient can receive anti-rejection drugs to help the body accept the new tissue.

However, due to the animal tissue being so different from the patient, there is little to no solutions to this problem. Another complication includes the ethical concerns of the animal that is forced to go through the procedure. The tissue is typically received form a living and healthy animal. Many people of multiple societies today feel this is unfair to the animal that loses its life to aid a human. Currently this practice is not too common. However, it is a concern that it will grow and become a large disturbance to society.

With the illustration below, one can easily see the differences between autografting, allografting, and xenografting. Due to the highly unlikely scenario a twin of another is in need of tissue transplantation, isografting is generally not used.

Although these techniques probed useful of replacing lost or defected tissue, the tissue used had to come from another living organism. Because of the passing of tissue from other organisms or itself, it only takes one valuable tissue and gives it to another. It is simply a take and receive method instead of only receiving.

Due to the problems within these methods, it is clear that the need for a technique that does not involve a take and receive method is still in existence. However, these problems, such as taking tissue from another organism as well as problems with the receiver’s body not accepting the transplant, can be resolved with the use of bioprinting. The use of simply printing new tissue and transplanting it to a patient will have very little problems that coexist with it. However, a strong concern for bioprinting is merely the high cost that it would entail. Many attentive followers of modern news, such as James Jeffery, a masters graduate in the field of journalism, believes that bioprinting would be far too expensive and will never reach realistic business pricing. He states that “bioprinting companies are scrambling for money to fund their utopian ambitions”. This is generally believed to be because although the companies are progressing, there is still no product out there in the market to bring in money to their business.

Although Jeffery’s concerns seem valid, through the interview with Prof. Chua he has also discussed the future of bioprinting in terms of cost that explain why the arguments against bioprinting could be too quickly judged. He has stated “As the technology is still at a very premature research and development stage, the costs involved are definitely on the high side. We are, however, hopeful that such organ transplant technologies will become affordable for the general public in the future. That said, it is difficult at this point of time to estimate the exact costing to perform a bioprinted organ transplant.” Although it is still difficult to predict the affordability in the future, like all new products that are presented to the world, it is predictable that the price will lower. Chua has also stated that with the ability to save countless lives it is highly possible to see that the government would allow benefits for the technology to aid in the affordability.

However, if the worst comes to reality and the price stays on the high side, with the ability to purchase surgery to save one’s life without waiting a long time for a tissue donation it is likely that almost anyone will spend the money to save their life. In conclusion to the concern of pricing, with the multiple predictions of bioprinting becoming more affordable, whether it be due to the technology being cheaper to produce tissue or government granting aid to patients, as well as the thought that money does not play a great role in terms of a person buying tissue to save their life, the concern of affordability is likely to not play a large role in whether a patient in need will purchase a bioprinted tissue or not due to the fact that the life of a human being is on the line.

Closing Thoughts On The Increasing Need For Bioprinting

With the population increasing, the number of people in the world who are in need of tissue transplants is vastly increasing. Also, recent medical advancements are also causing the supply of donatable organs to decrease due to the ability of curing tissue donators from their health conditions that cause them to decease. The decreasing of the supply to demand ratio is producing the urgency for our world we live in to be introduced to another form of tissue transplantation that allows a far greater supply of tissue. In fact, according to the American Transplant Foundation, a non-profit organization dedicated to increase the availability of donatable organs,states that “more than 123,000 people in the United States are currently on the waiting list for a lifesaving organ transplant” This great number of people is only in the United States. One can only imagine the immeasurable increase of people in need of organ transplant if the statistics showed the need worldwide. With the passing of time, these numbers are only going to increase. This emphasizes the urgent need for an improved tissue transplantation technique that has no constraint in the supply of donatable tissue even more.

With the prospective of bioprinting materializing in the future, it can solve many of the problems of tissue transplantation our society faces. This possible technique would eliminate the need to take tissue from one area of a patient or another organism in order to give it to another in need. There is also the possibility of this method being completed at a lower cost than some current solutions. Because of the tissue being created in a lab, there would be little to no rejection issues between the new tissue and the receiving organism. Most importantly, the greatest concern, the lack of donatable tissue will cease to exist due to the ability to simply print any variant of tissue desired. However, with the demand of this research increasing, the need for scientists and researchers willing to participate in its advancement increases as well. The contribution of future scientists and researchers is crucial for the progression of bioprinting becoming a reality to aid in eliminating the health concerns of innocent people in our society, such as Kaylee Vitelli and Lillian O’Connor, the previously mentioned infants who were forced to pass through the horrid situation of needing a life saving transplant with possibly no donatable organs available.