Regeneration of Organs

Hannah Warren was born with a missing trachea, a fatal condition with a survival rate lower than 1%. She was breathing with a tube inserted through her mouth, and wasn’t able to speak or eat normally. However, the use of 3D bioprinting proved to be a boon for her. She is now able to breathe normally without any tube in her mouth. “It was beautiful,” said Dr. Macchiarini, the regenerative medicine specialist who performed this groundbreaking surgery.

The bioengineered windpipe was instrumental in the success of the surgery that granted Hannah a renewed life. The bioengineered trachea is a half-inch diameter tube made using plastic fibers, bathed in in a solution containing Hannah’s own stem cells (which were taken from Hannah’s bone marrow) and incubated in a bioreactor. Because the trachea was made using Hannah’s own stem cells, there was no risk of immune rejection.

While 3D printing has revolutionized the manufacturing industry, 3D bioprinting has even greater implications in the field of medicine.

Stem cells are at the center of healthcare research due to their potential in regenerative medicine. Now, the advent of 3D bioprinting for regenerative medicine can help realize the potential of the stem cells.

In the last few decades, printing technology has expanded its horizons from 2D printing to 3D printing. 3D printing has enabled production of structures with complex geometries and has revolutionized the quick prototyping and manufacturing of consumer products like toys, jewellery, and electrical components. Chuck Hull described 3D printing for the first time in 1986, as a process in which thin layers of a material treated with ultraviolet light were sequentially printed in layers to form a solid 3D structure, a method named “sterolithography”.

While 3D printing has revolutionized the manufacturing industry, 3D bioprinting has even greater implications in the field of medicine. 3D bioprinting begins with manufacturing the resin molds of the 3D scaffolds from biological materials. The development of solvent-free, aqueous-based systems enables the direct printing of biological materials into 3D scaffolds that could be used for transplantation with or without seeded stem cells.

How does 3D bioprinting work? First, imaging data from CT scans, X-rays or MRI are used to determine the size and detailed geometry of a patient’s damaged organ or tissue. Then, three processes are carried out: artificial organ design, scaffold materials selection, and cell source selection.

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The overall approach for 3D Bioprinting. The first step involves imaging of the damaged tissue/organ to guide the design of the regenerated organ. The design approach, material and cell source are then determined followed by bioprinting and its application for research and clinical purposes.

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There are also three design approaches for 3D bioprinting: biomimicry, autonomous self-assembly, and mini-tissues.

Biomimicry involves manufacturing artificial tissues or organs by reproducing cellular and extracellular components present in the native tissue or organ. As a result, biomimicry requires extensive knowledge about the microenvironment of the specific tissues and organs, including the arrangement of various cell types, composition of the extracellular matrix (ECM), gradients of soluble and insoluble factors, and the nature of biological forces. This knowledge is crucial for in vitro manufacturing of living tissues and organs with the same size and geometry as native organs.

On the other hand, autonomous self-assembly utilizes embryonic organ development as a guide to replicate a specific organ/tissue in vitro. Early cellular components of a developing tissue produce ECM components and appropriate cell signals that lead to autonomous organization and patterning of the desired tissue. A solid understanding of the developmental mechanisms of embryonic organogenesis, as well as the ability to manipulate the environment to drive these embryonic mechanisms, is crucial to the success of this approach.

The mini-tissue approach is a combination of the biomimicry and autonomous self-assembly approaches. The mini-tissue approach entails creation of the small function unit of the tissue/organ (such as the nephron in the kidney) and using that in combination with biomimicry or autonomous self-assembly to drive the generation of the tissue or organ.

In addition to determining the design approach, selecting the scaffold material and cell source to construct the microelements of the tissue is a key aspect of 3D bioprinting. There are natural as well as synthetic scaffold materials available. Natural scaffold materials such as alginate, gelatin, collagen, chitosan, and fibrin — or synthetic molecules such as polyethylene glycol — are used for tissue generation. While natural polymers resemble the human ECM and mimic its biological activity, synthetic scaffolds can be tailored to have specific physical properties. Properties of a material that make it suitable for 3D bioprinting include printability, biocompatibility, degradation rate, non-toxicity of byproducts, and various structural and mechanical properties.

The cell source being used depends on the design approach determined. For biomimicry, differentiated cells are used because the organ is in its final shape during manufacture. On the other hand, self assembly requires the use of stem cells, which have self-renewal and differentiation potential. In addition to the cell source, the cell proliferation rate as well as the immune response are important to control.

Upon determining the design approach, scaffold material, and cell source, the tissue can be matured using a bioreactor and tested in vitro before implantation. 3D bioprinting is a great advancement for the field of regenerative medicine as it can serve as a tool to provide organs to patients in need of transplants. While the use of 3D bioprinting can have a significant impact in regenerative medicine, it also evokes several ethical concerns. First, there is a high cost associated with bioprinting technology and treatment that raises the question of who gets access to the treatment — should only those who can afford it get the treatment, or should others get the treatment as well? Additionally, it is not clear how safe the treatment is, especially because the treatments may be tailored on a patient-by-patient basis. Lastly, can 3D bioprinting be used for human enhancement — replacing organs with ones that are stronger or have a higher capacity? There are many ethical concerns and questions, but 3D bioprinting is a significant advancement that can prove to be very beneficial in medicine if ethical concerns are addressed.

Sources

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Fountain, Henry. “Groundbreaking Surgery for Girl Born without Windpipe.” NY Times. N.p., n.d. Web. 28 Nov. 2015. <http://www.nytimes.com/2013/04/30/science/groundbreaking-surgery-for-girl-born-without-windpipe.html?_r=1>.

Griggs, Brandon. “The Next Frontier in 3-D Printing: Human Organs.” CNN. N.p., n.d. Web. 28 Nov. 2015. <http://edition.cnn.com/2014/04/03/tech/innovation/3-d-printing-human-organs/>.

Murphy, Sean V., and Anthony Atala. “3D Bioprinting of Tissues and Organs.” Nature Biotechnology: n. pag. Nature. Web. 28 Nov. 2015. <http://www.nature.com/nbt/journal/v32/n8/full/nbt.2958.html>.

“Regenerative Medicine and 3D Bioprinting: Polymers Sow the Seed of Life.” Interplas. N.p., n.d. Web. 28 Nov. 2015. <http://www.medicalplasticsnews.com/technology/regerative-medicine-and-3d-bioprinting%3A-polymers-sow-the-seed-of-life/>.

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“Toddler Gets New Windpipe from Her Own Stem Cells.” CNN. N.p., n.d. Web. 28 Nov. 2015. <http://edition.cnn.com/2013/05/01/health/toddler-stem-cells-windpipe/>.

About The Author

Aastha is a sophomore at Princeton planning to major in Molecular Biology. She is interested in pursuing certificates in Global Health and Health Policy as well as Quantitative and Computational Biology. She is very interested in healthcare related areas and plans on going to medical school. She likes writing about science news and research going on. She is part of several science and health related publications on campus in various positions. She is involved in research projects in the Princeton science departments for 2 years. She also participated in several science competitions. She is also a volunteer at the UMCPP.