Bioprinting: The Future Of Organ Donation And Transplant

According to the American Transplant, 116,000 people are currently on the waiting list for a lifesaving organ transplant. Liver failure, collapsed lung, kidney failure, etc. are just some medical cases that result in the need for organ transplantation. Few are lucky enough to receive a transplant within weeks, however for others it could take years and unfortunately some never receive them. Researchers have tried countless times to limit the number of organ transplant casualties and only a few have shown success. That was until 2003 when Thomas Boland of Clemson University patented the use of inkjet printing for cells making 3-D printed (also known as bioprinting) organs a possibility for transplantation. Since then bioprinting has been further developed to encompass the production of tissue and organ structures. Years later advancements in bioprinting are accelerating leading it closer and closer to becoming a more common procedure.

Here's how Tandon, a 35-year-old biomedical and electrical engineer, sees it working: “A doctor uses a CT scanner to image the damaged section of bone and takes a small sample of fatty tissue. The scans and the sample are sent to EpiBone, which extracts stem cells -- undifferentiated cells that can essentially be programmed to perform a wide array of functions.” The key to bioprinting are the stem cells gathered from fatty tissue. These cells are the biomechanics that out each cell of our body. Common shown through Tandon’s research the acquired cells are applied to either a custom cut model or are used a biomaterial (explained later on on). However, unlike bioprinted organs, EpiBone places their constructs into a specially designed bioreactor, only about the size of a can of soda, with a chamber cast in the shape of a 3-D-printed bone model. This is “to ensure that the company's proprietary growth ‘cocktail’ passing through the chamber seeds the bone tissue uniformly.” A cocktail is a solution of both the host’s stem cells and a polymer that is crosslinked allowing the cells to perform regrowth. What emerges, a few weeks later, is a replacement organ that not only fits the patient exactly but is made out of the patient's own cells. Research groups such as EpiBone are conducting incredible studies revolutionizing modern medicine. For example, Epibone has begun a study that implants newly grown cheekbones into 16 pigs at the Louisiana State University School of Veterinary Medicine. Though research may seem close, Tandon ensures that, “it will be some time before EpiBone is ready to move on to human beings.”

Currently, 3D organ structures have reacted more like human organs than the 2D tissue samples used beforehand. This information provides the medical industry with a huge potential booster for the implementation of bioprinted organs later on in the future. Thresholds are constantly being broken in bioprinting through conducting experiments and studies. Through research, biomedical engineers have discovered exceptional biomaterials for bioprinting and organ regeneration. Materials currently used in the field of regenerative medicine for repair and regeneration (including bioprinting) are based on naturally derived polymers including ,”(alginate, gelatin, collagen, chitosan, fibrin and hyaluronic acid, often isolated from animal or human tissues),” or synthetic molecules. The advantages of natural polymers for 3D bioprinting and other tissue engineering applications is their similarity to human ECM (Extracellular matrix), and their inherent bioactivity. The Extracellular matrix (ECM) is what holds the cells within the organ tissue together, our cells produce a group of extracellular molecules that provides structural and biochemical support to the surrounding cells. Because these cells are naturally made by the human body, natural polymers are the preferred biomaterials used in bioprinting.

Although natural polymers are prefered there are certain advantages to synthetic polymers. One is specific is that they can be configured with specific physical properties to suit particular applications. However, synthetic polymers, “possess the risk of the poor bio-acceptability but could also lead to the toxicity because of the toxic degradation.” Even so, synthetic polymers hydrogels are attractive to bioprinting due to their “hydrophilic, absorbent and manageable physical and chemical properties.”

In our everyday live the field of biogrowth research may lack in popularity however, major studies have been conducted since before the development of bioprinters. Biogrowth was the before stages leading up to the development of bioprinting. In its prototype stages, between 1999 and 2001, after a series of tests on dogs, Bioengineer Anthony Atala created custom-grown bladders that were transplanted into seven young patients suffering from spina bifida, a disorder that causes bladders to fail. By 2006, Atala announced that after close supervision the bioengineered bladders were working extraordinarily well. The marked history in bioprinting being that it was the first time a lab grown organ was successfully transplanted into a person. The possibilities are endless at this point. The skin-cell printer is one of several active projects developed by Atala that receives funding from the U.S. Department of Defense, The goal is to successfully create, “tissue regeneration initiatives for facial and genital injuries, both of which have been endemic among American soldiers injured in recent wars”. Anthony Atala has shown to be a remarkable export in the progression of bioengineering. In 2014 a group researchers led by Atala successfully implanted vaginas engineered using the patient's' own cells inteenagers suffering from are productive disorder called Mayer-Rokitansky-Küster-Hauser syndrome. Researchers have stated that, “the main advantage of 3D printing technologies in large hard tissue and organ engineering is their capability to produce complex 3D objects rapidly from a computer model with varying internal and external structures.”

Scientific and Economic Assumptions and Predictions for the Future of Bioprinting

The potential for the technology is never ending, and the industry is poised to boom even more over the next ten years. A report published by IDTechEx estimates that the global 3D printing market will reach $7 billion by 2025, with about half coming from 3D bioprinting. In the future, for example, Tandon says, EpiBone's technology could be used to treat anything from bone loss and broken femurs to complex facial fractures and genetic defects. Autologous grafts produced by computer-assisted manufacturing will be faster to implant and minimize donor site morbidity. The practical limitation in terms of graft size is the ability to create a vascular network. Once this limit is overcome, the production of “ready-to-implant” organs and autologous free flaps with a vascular pedicle will become possible. These innovative advancements in 3D bio-printing open up a new frontier for oncology research and could herald an era of progressive clinical cancer therapeutics.

These diverse applications illustrate the versatility and potential of bioprinting as a technology still in its infancy. In its infancy there is still much to be addressed through future research. Bioprinter technology and its compatibility with physiologically relevant materials and cells, Biomaterials ability to maintain complex combinations or gradients to achieve desired functional, Moreover, bioprinting remains a promising solution for addressing the growing international organ shortage. The ability to generate tissues for transplant on-demand with reduced immune response risk holds significant promise in the fabrication of artificial organs. Current limitations of Bioprinting and can they solved? In the simplest case of printing with a single material, each layer must be connected and mechanically supported as it is printed. When voids are introduced in one layer, subsequent layers that deposit material over the void may collapse causing a cascade of offset features and inaccurate geometries. One possible solution to this problem is to incorporate a sacrificial material, which is a method widely employed in the fabrication of suspended structures in MEMS. The lack of reliable methods to print pre-vascularized tissues is a hurdle that cannot be overlooked. This problem is not unique to bioprinting, but bioprinting is unique in its ability to create large tissues with high metabolic demands relatively quickly. Many of the small-scale tissues researchers currently print can survive through diffusion alone, but full-scale organs and large tissue constructs will require an embedded vasculature as well as mechanically robust conduits to connect to host arteries and veins.

Currently, the applications of bioprinting are not at its full potential. There are certain limitations that suppress the fundamental use of bioprinting and its implications to medicine. Bioprinting has its unique issues including, “the lack of reliable methods to print pre-vascularized tissues...a hurdle that cannot be overlooked” but bioprinting is unique in its ability to create large tissues with high metabolic demands relatively quickly. Presently, many of the small-scale tissues researchers print can survive through diffusion alone, but full-scale organs and large tissue constructs require an embedded vasculature as well as mechanically robust conduits to connect to host arteries and veins making it quite difficult. However, it can be done and researchers are attenuating the boundaries of bioprinting each day at a time making it a more accessible procedure for everyone.

Conclusion

Bioprinting is the procedure of the future, for now it requires further testing however, boundaries are being broken each day in the constant development and research brought together by the ideas of some the world’s best biomedical engineers. One day someone in need of a transplant will no longer wait in fear for a compatible match to pop up, it is speculated that in the future bioprinted organs will take as little as a week to grow and be specially prepared for the patient. Many of the challenges facing the 3D bioprinting field relate to specific technical, material and cellular aspects of the bioprinting process.

01 February 2021
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