Incubating Artificial Organs

David Rew

2/12/1

Independant Research G/T

Dr. Melissa Kiehl

Abstract

Many people suffer daily because of organ failures; organ failures impair one's quality of

life and can prevent people from living their full lives. Due to this people have to wait for
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someone to donate a functional organ so they can lead a semi normal lifestyle after they have

been treated with a replaced organ. As easy as this sounds, many people often have to wait

months and years before hearing back from a hospital telling them that they have an available

organ that can be used for the surgery. With such long wait times many patients end up dying

before they receive an organ. This may seem wrong but people are just relying on others to pass

away so that their organs can be used to save another person. By implementing 3D printed organ

technology into the medical field, one is expected to wait around a week before given a 3d

printed organ which is around 20x faster that it takes to receive a traditional organ. The purpose

of this study is to answer the problem of waiting for organs by conducting research on the

different methods to 3D printing, the incubation process, the role of stem cells, and using organs

for pharmaceutical purposes. Labs and scientist have conducted many studies and labs involving

3D printing organs and also managed to create various types of living tissue with 3D printing

technology. Although there is the technology to physically create various types of organs, there is

still much research that is needed before 3d printed organs can be implemented into hospitals.

Introduction

Humans are composed of many types of organs that all specialize in different functions.

Tissues are biological functioning materials that animals or plants are made from, which consist

of many specialized cells. Cells are the smallest unit of functionality for an organism and they
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are used to create tissues based on the cell structure. There are several types of tissues that

compose the human body: Epithelial, connective, muscular, and nervous tissue. Epithelial tissue

functions to cover/line body surfaces or cavities, and surround glands(Epithelial Tissue, 2013).

Muscular tissue acts to maintain posture, move the body, contract organs, and stabilize joints.

Without these tissues the body would not be able to move, breathe, or pump blood throughout

the body because various types of muscle tissue will be programed to undergo these

movements(Structure and Functions, n.d.). Connective tissue is one of the most important

tissues as it is commonly used; this tissue is used to protect, support, and transport tissues within

the body. Connective tissue has many different types of characteristics which allow it to be so

versatile in functioning the body, one of the types of connective tissue is bone which is used to

store calcium and provide support and protection for the body. Finally the last type of tissue is

nervous tissue which primarily works to receive stimulus, and control the body through

voluntary or involuntary networks.

Review of Literature

3D printing is a versatile process that allows users to create various types of artificial

structures that can be used for a variety of purposes. Like 3D printing, organ printing takes the

same basic principle of creating structures by applying a special hydrogel that will be used in

creating artificial organs. Whenever cellular tissue is damaged the body undergoes mitosis which
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is a process that uses stem cells to replicate the specific tissue that was damaged from the injury,

if mitosis was non existent, organisms would not be able to heal from a cut or wounds, which

would cause various types of infections and the transmission of diseases.

Organ printing will use the basic concept of replicating cells to create functioning cell

tissue that will be used to form the artificial organ and 3D printing which uses a nozzle to

extrude malleable material onto a scaffold which will hold the material so that multiple layer of a

material can be constructed to create the desired object. Stem cells will be used as the base of

creating the tissue of organs because they have the ability to undergo mitosis, which is a process

that creates cells that specialize in a specific task. Many people face organ failures later in life

and will have to undergo intensive therapy or surgery to improve their lifestyle. This paper will

discuss the benefits to 3D printing and how it can positively impact society on a global scale.

Bio-ink is the material used to create the base structure of an 3D printed organ(Arslan,

2016). The bio-ink is primarily named as a hydrogel because of its 99% composition of water

with the remaining one percent composed of cells; its properties allow for the cell to function

properly and combine with other cells to form complex levels of tissue. The bio-ink is created by

adding cells created through cell replication of a stem cell into the hydraulic gel scaffold, which

will be holding the newly created cells. Since the stem cells that are created the functioning unit

of the cells that will be used in the creating the tissue, the stem cells themselves will not be

functioning of the tissues. Although the hydrogel is only composed of a small proportion of cells,

this ratio allows the ink to develop and undergo mitosis to form more cells inside of the gel.

Once the hydrogel is formed, scientists place the gel into a machine that will extrude it through a

tiny nozzle, which will follow a process called bio fabrication- the formation of the organ with

many continuous layers of bio-ink and bio-paper. Once the organs structure has been finalized it
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will be taken to a incubating chamber where the cells inside of the organ will sit and incubate

while the gel is being slowly washed away to unfold the finished product.

There are three ways to 3D print an organ: micro extrusion printing, ink jet printing, laser

assisted printing and stereolithography (Yi,et al) . Micro-extrusion printing is one of the most

common methods to 3D printing organs because its methods are effective and simple; this is the

main method of printing that this paper will focus on. Micro-extrusion printing uses a nozzle and

piston to set the bio-ink onto a synthetic material used as an adhesive to each layer of the bio-ink

to create the organ. By using this method of inking, one can expect to see few errors and

problems within the finished product due to the printers flexibility with nozzle sizes, dispensing

force, and printing speed. Inkjet printing uses a selected volume of cells that is set inside of a 3D

printer which will go through an piezoelectric actualizer, which will vaporize a specific volume

of cells, in order to expose the cell and separate the cells into tiny droplets that will be extruded

out of a high precision nozzle to create the bio ink. By using this method, scientist are able to

separate a large volume of cells into tiny droplets within a short amount of time, but this

accelerated rate of separation causes membrane of some cells to be damaged due to the

actualizers high frequency waves. Laser assisted printing is one of the most precise types of 3D

printing due to its high precision laser. The laser assisted printer uses a strip of cells that are laid

on a surface, called the ribbon. Then a computer is programed to fire at the ribbon at the selected

spots so the target portions of the ribbon will turn into cell droplets which will fall onto a layer of

hydrogel that is directly beneath the ribbon to create the organ structure(Yi,et al, 2017).

Printed organs can be used to improve or save lives in the emergency room. The U.S.

Department of Health & Human Services claims that 118,578 people need a lifesaving organ
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transplant and only around 33,597 organ transplants performed so far in 2016 (Organ

Procurement and Transplantation Network, n.d.) this means that less than a third of the

population is receiving critical organs transplants in the U.S. The organs that are being created

will be produced from the cells of the patient receiving it, this prevents the body from rejecting

the 3D organ because the immune system will recognize the protein fibers surrounding it.

Although people donate their organs, they might not be in perfect condition, this causes many

patients who wait for organs to undergo another transplant after their previous one. Since patient

will be going under anesthesia during the operation, frequent exposure of the anesthetic can lead

to memory loss or serious side effect for the patient; this is to be taken account of so that doctors

can take the minimum measure to help the patient without performing too many surgeries.

In the future, 3D printing will be seen as a frequent practice to help patients recover from

damaged or dysfunctional organs. There will be a greater need for surgical technicians and

surgeons going into the medical field because organ transplantation will become a frequent

operation if 3D printing organs are implemented into hospitals. Medical major students will have

an easier time to get into medical school because of the demand for more students,which may

cause more schools to offer programs that are directly related to health/ biological sciences.

Students that are hoping to enter the medical field will be able to see living organs instead

of plastic models. Being able to see real organs has many advantages to potential medical

students; they will be more comfortable when dealing with a organ and recognizing specific

characteristics of it such as texture, size color, and weight, which are incomparable when

working with plastic models. Most medical students are not able to see major organs in the

human body until they reach medical school because they are a scarce item and the tissue

composing the organ will degrade if left outside of its preservation containers for a long periods
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of time. Students will be able to study the structures of organs more comfortably without having

to worry about damaging the precious organ when handling it.

Almost all pharmaceutical companies rely on animal testing to see if their products work.

Each year, more than 100 million animalsincluding mice, rats, frogs, dogs, cats, rabbits,

hamsters, guinea pigs, monkeys, fish, and birds are killed in U.S. laboratories for drug, food, and

cosmetics testing( Experiments on Animals, n.d.). Animal testing is a way that companies can

test their products without having to put human health at risk.

By introducing artificially created organs into the pharmaceutical industry, companies

will not have to rely on animals to figure out the effects of newly created drugs. Scientist will be

able to create chips that contain cell tissue, these will be able to replicate the functions of a living

organ. With these tissue based chips, companies will be able to create chips that are linked

together to create living systems of humans by connecting the chips, so that companies can see

the effects of another organ system if one of the other systems is affected by the drug. Many of

the human systems are intertwined with each other so some systems will not be able to function

without the presence of the other for an example the muscular system will not be able to move if

the skeletal system is not present because there will be base structure for the muscle to attach to.

Another example would be the the digestive system and the excretory system because if the

excretory system was not present then all of the digested food with no nutrients would remain in

our body which would make body bloat up and be unsuitable for daily tasks.

3D printed organs originate from human cell which can accurately diagnose the effects

of a pharmaceutical product when tested. When a drug is introduced inside the body, we can used

chips that contain living human tissue to see how the tissue will react to it, by using chips
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scientist will be able avoid any ethical concerns about animal testing and provide more detailed

results when describing the potential effects the drug will have. In addition to having more

accurate results computers will be able to track the specific problem of the chip without having

to set up various test, which can take up a lot of time. Pharmaceutical companies will have more

assurance when distributing out their product because it has been tested on tissue that is nearly

identical to the prescribed person, due to these highly accurate human tissue chips, there should

be no harm done to the patient if taken as prescribed.

Animal testing can be expensive to the buyer because the quantity of animals needed to

perform the test. When performing an experiment there should be a large amount of samples

being taken to ensure that the whole population of a species is being represented, by doing this

scientist can reduce variance within our data and improve accuracy and precision. Animals that

are sent for testing consume resources, space, and drugs that are being tested, which is expensive

since the researcher has to purchase cages or a space for the animals to live without being

harmed, and food/water for the animal to live. Since the animals being tested are not in their

natural environment, they may show the symptoms being in a different environment which may

be seen as a potential effect of a drug for example a mouse will be more precuasious in the cage

than in the forest.

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Research Methods and Data Collection

The research design that this paper follows was created through meta analysis; this

gathers multiple research papers, gathers data on all the papers and then compare and contrast

each articles to find similar themes and opposing viewpoints. All data used to produce this paper

was collected using descriptive online resources that can be found using the web. During data

collection multiple websites and articles were gathered by conducting scholarly searches. Once

these data sources were located, all of them were evaluated for quantity of information, quality

of information, and when the sources were produced. Upon looking at seven different sources,

four of them were picked based on the rubric stated above. After deciding the sources that would

be used for data collection, these sources were used to gather various types of information based

on the common topic of 3D printing. The first source used case studies and observational data to

describe how organ chips are used to determine the effects of a certain drug on living tissue. The
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second source used a descriptive study that described the different methods of 3D printing and

how each type has its advantages when producing a certain type of tissue. The third source used

an prospective observational study and it discussed how 3D printing has a strong potential to

become a common fabrication technique in medicine as it enables fabrication of modular and

patient-specific scaffolds and devices, and tissue models, with high structural complexity and

design flexibility. The last source used an observational study and used case reports to collect

data on the different methods and applications to 3d printing. The data was analysis by using a

simple chart with four columns composed of the four articles, and seven rows that specify

different methods to how the data in the article was collected, results, and subtopics. By using a

table the data from each source was able to be analyzed for similarities and differences between

the author's arguments, while do so many similar topics arose from the different papers which

allowed some arguments to be stronger than others.

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Results and Data Analysis

The purpose of this paper was created to answer the following questions: Can 3D printed

organs be used to provide for those who are suffering from organ dysfunctionalities?, can organ

be used to accurately diagnose the effects of certain drugs on the human anatomy?, and how can

bioprinters be used to create functional 3D printed organs? This paper determines if 3D printing

is a viable and efficient way to reduce mortality rates all around the world. The information that

was collected addressed the applications to 3D printing, printing on chips, using 3D printed

tissue to screen drugs, and using 3D printed organs for transplants. The collected data is

displayed as a chart that compares similar sub topics that were present within each of the

sources. During data collection, the sources showed various methods to 3d print and explained

how different methods best suit the organ that they are producing. The data also shows that

tissues/organs are being used in lab today to screen drugs and show the effects of a drug on the

human body. Bio ink is also a common topic in the sources because there are different bio inks

that are more effective in binding together cells and producing a scaffold like environment for
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the cells to live inside. A presentation, and a website has been created using the data from the

sources; these products explained the science behind 3D printing organs and explains how the

science can be used to create complex organs. The powerpoint presentation was an important

step to display a overview of the research that has been conducted, and summarizes the

importance of the papers main question. The main purpose of the product of the research is

proving the hypothesis: 3D printers can be used to reduce mortality rates all around the world.

The knowledge in this paper is shared through the final product consisting of a website and a

brochure, both of these products will be used to present the final research product.

Discussion and Conclusion

3D printing is an important topic that cannot be ignored because of its usefulness towards

modern day medication. In today's society there is no way to cure cancer, treat cardiovascular

disease, dysfunctional organ, blindness, nerve damage and third degree burns. With 3D printed

technology our bodies can become like robots since the parts to our body can be easily created

and replaced as the new organ. Many people hate aging because the organs in the body start to

lose function and responsiveness to stimuli, with 3D printing, organs can be produced so they

replicate the organ when the patient was at their peak condition. Although this study can had seen

various 3D printing successes for patients that were suffering from a fatal condition, 3D printing

must not be used on the public until more research has been conducted to completely certify that

3D printing can be safely executed without any potential health risks associated with 3D printed

organs.
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MLA Works Cited

Arslan-Yildiz, A. (2016). PAPER Towards artificial tissue models: past, present, and

future of 3D bioprinting. Biofabrication, 8(1). http://dx.doi.org/10.1088/1758-

5090/8/1/014103

Experiments on Animals: Overview [Fact sheet]. (n.d.). Retrieved February 12, 2017,

from PETA website: http://www.peta.org/issues/animals-used-for-

experimentation/animals-used-experimentation-factsheets/animal-experiments-overview/

Epithelial Tissue. (2013, June 1). Retrieved March 5, 2017, from Anatomy & Physiology

a learning initiative website: http://anatomyandphysiologyi.com/epithelial-tissue/

Organ Procurement and Transplantation Network. (n.d.). Retrieved February 12, 2017,

from U.S. Department of Health & Human Services website:

https://optn.transplant.hrsa.gov/

Peckham, M. (2013, February 5). We Can Almost Print New Organs Using 3D Stem

Cells. Retrieved December 7, 2016, from Techland Time website:

http://techland.time.com/2013/02/05/we-can-almost-print-new-organs-using-3d-stem-

cells/
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Radenkovic, D., Solouk, A., & Seifalian, A. (2016). Personalized development of human

organs using 3D printing technology. Medical Hypotheses, 87, 30-33.

http://dx.doi.org/10.1016/j.mehy.2015.12.01

Structure and Functions of Muscular Tissue. (n.d.). Retrieved March 5, 2017, from

Ivyroses website: http://www.ivyroses.com/HumanBody/Tissue/Tissue_Muscular-

Tissue.php

Yi, H.-G., Lee, H., & Cho, D.-W. (2017). 3D Printing of Organs-On-Chips.

Bioengineering 2017, 4(1). http://dx.doi.org/10.3390/bioengineering401001

Appendices

Appendix A:

Citations for Appendix A:

Atricle #2:

Peng, J. (2016). The Future of Medicine: 3D-Printed Organs. Berkeley Scientific Journal,

21(1). Retrieved from http://escholarship.org/uc/item/5g53600j

Article # 4:

Ji, S., & Guvendiren, M. (2017). Recent Advances in Bioink Design for 3D Bioprinting

of Tissues and Organs. Biomimetic Fabrication for 3D Biology.

https://doi.org/10.3389/fbioe.2017.00023

Article #3:

Vermeulen, N., Haddow, G., Seymour, T., Faulkner-Jones, A., & Shu, W. (2015). 3D

bioprint me: A socio ethical view of bioprinting human organs and tissues. Global

Medical Ethics. http://dx.doi.org/10.1136/medethics-2015-103347

Article #1:
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Yi, H.-G., Lee, H., & Cho, D.-W. (2017). 3D Printing of Organs-On-Chips.

Bioengineering 2017, 4(1). http://dx.doi.org/10.3390/bioengineering4010010

Article #1 Article #2 Article #4 Article #3

Methods(How The researchers The study was The study was Study was
was the study conducted their conducted in a conducted a constructed by
conducted; who research by lab by Dr. group of researchers
were the creating various Anthony Atala, bioengineers Instructive
participants) types of organ director of the Biomaterials and
tissues Wake Forest Additive
Institute for Manufacturing
Regenerative (EBAM)
Medicine at Laboratory, Otto
Wake Forest H. York Newark,
University, NJ, USA

Results (what Although 3D 3d printing has Bio printing is Bio inks are
conclusions did printing is the many parts and the best way to certainly helpful
the researchers best method to techniques that fabricate organs in creating
draw ) biofabricate can be carried to but raises ethical organs but there
organs and increase concerns to the are different type
cellular efficiency with public of bio inks that
structures, it still each type of should be used
needs tissue structure in different types
improvement of printing
methods

Something from Different types of Many people Technology is Bio inks are the
your research organs benefit have to been steadily base base that
hypothesis from the types of checked before increases but it will ued to create
bioprinting they are able to is not fast the organ
methods that receive an organ enough
were used to
create them

Something from 3d printed Organs can be Artificial tissue Bio ibk will be
your research organs will used used to provide allows the created through
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hypothesis to save people's instant treatment effects of a virus a gelatin,

lives to patients non the human synthetic, and
suffering tissue without algae solution
diseased organs having to hurt which will
anyone. function as the
ECM

Something from Eliminates the The wait time for Human organs Call printing will
your research need to have a patient is from can be replaced become more
hypothesis organ donors 3 to 7 years with artificial popular over the
ones years

Conclusions/ 3D printing still The process of There are many There is no real
Limitations has a long way printing organs social and need to improve
to go. There still is not that simple economic accuracy for the
needs more and there are challenges machine
research to be different factors around 3D because of the
done on in determining a printing have designs
heterogeneous organs received less
structures and complexity when praise than they
increasing the creating it. should have
accuracy of the
ink droplets