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Kayla Mendel
WRIT 340
Illumin Article
File > Print > New Organ: 3D Printers Used for Printing New Organs and Body Tissues
Abstract
Additive manufacturing, otherwise known as three dimensional printing, is an emerging
technology with an incredible span of applications. Recently, engineers have expanded the span
of three dimensional printing to include “bioprinting,” the creation of biological structures such
as hearts and livers using a three dimensional printer. By replacing the three dimensional
printer’s “ink” with a mixture of cells and other materials, scientists can create real functioning
human tissue and organs. These structures can have significant medical applications. Scientists
are researching the possibility of using bioprinting to print new skin, liver, and heart organs.
There is still a significant amount of work to be done before bioprinting is used in hospitals, but
the potential benefits to healthcare are so marvelous that many companies are invested in
researching this incredible technology.
Introduction
Every day an average of 18 people die waiting for organ transplants, as there are not
enough organs donated [1]. To help solve this problem, engineers are developing a groundbreaking new technology that applies the concept of additive manufacturing, otherwise known as
three dimensional printing, to the discipline of biology. By using an “ink” made of real cells,
scientists are able to print incredible structures that function in similar ways to real human tissue.
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Eventually, these structures will likely be able to act as donor organs for patients in need of
transplants. This process of printing with cells has been termed “bioprinting.”
How 3D Printers Work
3D printing, a form of additive manufacturing, has long been used to create solid objects
from computer models. Solid objects include keys, chess pieces or even operational whistles.
The 3D computer models can be either a scan of a real object, or a design that an engineer
creates from scratch using a Computer-Aided Design application. This first step can be seen as
step one in Figure 1 [2]. 3D additive manufacturing differs from other manufacturing processes
such as machining in that it starts with nothing and builds up [2]. For example, a 3D printer
could print a seamless, hollow sphere, whereas it is impossible to accomplish this using drills or
other machining tools. 3D printers use different types of plastics and resins to create objects of
all different shapes and properties [2]. In order to create a set of instructions for the printer, the
computer breaks down a model of the object into thin two-dimensional layers or slices [2]. An
example of these types of slices can be seen in Figure 2 which demonstrates one way in which a
chess pawn can be broken down into these layers. This model is then sent to the printer, as seen
in step two of Figure 1. The printer then prints out these thin layers one at a time, building upon
one another, as seen in step three of Figure 1. This process continues, until all the layers of the
object have been printed [2]. The final product of this process is a solid object that looks just
like the computer model that was sent to the printer.
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Figure 1. This figure illustrates the three general steps taken to design and print a 3D object
using additive manufacturing. The first step is to create a computer model of the object using
software such as a CAD application. The second step is to send this model to the printer as a set
of instructions that it can interpret. The third step is for the printer to lay down successive layers,
building up the model to create the physical object. Modified from source [2].
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Figure 2 This figure shows the way in which computer software is able to scan an object and
create a model of the object constructed of layers, which can each be printed individually.
How Bioprinters Work
The Material
Though based on the same concept as 3D printing, bioprinting is unique in that instead of
using a traditional material such as plastic or resin, the printers actually use an “ink”, or bioink
consisting of a mixture of real cells and a material that acts as a biological glue to create the
desired object [3]. There are several options for which type of cells to use for the printing
material. Engineers can either select cells collected from the patient’s own tissues, or can use
stem cells created in a lab [3]. In addition to living cells, the mixture used for printing also
contains a scaffolding material, which acts as an adhesive to hold cells together and give them a
structure to grow on to form the desired organ or tissue [3]. This bioink forms the basis of the
printed biological structure, allowing cells to grow into the scaffolding. The output from the
printer can range from a small piece of tissue to an entire organ.
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Creating a Plan
Bioprinting requires a 3D computer model of the object being printed as well as specific
instructions that the printer can follow to create the organ or tissue. Scientists can create maps of
the existing organ by using MRI and CT scans [4]. These scans determine the exact size and
shape of the organ and can be used to generate a computer model of the tissue. It is extremely
important that the scan be as precise and accurate as possible so that the new organ being printed
matches the original as closely as possible [4]. Engineers then slice the model into thin, printable
layers which will tell the printer exactly where to place each drop of cell mixture in order to
produce the tissue [4].
Printing the Object
After the “ink” is prepared for printing and a precise set of computer instructions for the
3D printer is made, the process of printing proceeds the same way that a regular 3D printer
would. The new organ or tissue is printed by depositing small droplets of bioink one layer at a
time until the object is complete [5]. This process takes a period of several hours, depending on
the complexity of the object being printed [5]. After the printing is complete, the organ is
incubated to allow the cells to grow into the scaffolding material and start functioning as the
desired organ [5]. Incubation times vary for different organs, but it will usually take a few days.
This process is demonstrated in Figure 3. The organ is then ready to serve its purpose, whether
that is for biomedical research or to serve as a donor organ.
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Figure 3. This image shows the way in which small droplets of bioink can be deposited layer by
layer to build a biological object in parts [A] and [B]. Parts [C] and [D] show how, after
incubation, the droplets of cells grow together to form functioning tissue. From source [5]
Why Use 3D Printers to Print Organs
Traditional transplants of donor organs have relatively high organ rejection rates
compared to the projected rejection rates of printed organs [5]. Additionally, transplant
recipients of donor organs are required to endure extensive anti-rejection treatments after
transplantation [5]. Organs can be printed with a patient’s own cells, which dramatically reduce
the risk of the body rejecting the new organ [5]. Bioprinting can build desperately needed donor
organs completely from scratch when donor organs are too hard to come by.
The field of tissue engineering is able to grow organs, but with different challenges than
are faced by bioprinting. Tissue engineering involves replacing human cells in an already
existing organ to help it grow and restore normal function [11]. This can be problematic in that
the layout of cells often becomes misaligned as the organ grows [11]. Bioprinting avoids this
potential problem by laying down each cell with extreme precision. Overall, bioprinting presents
itself as a great alternative to organ transplants.
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Bioprinting can also be used to heal wounded organs, such as skin burn wounds. The
possibility of printing new cells directly onto wounds has the potential to improve current
methods of healing organs in just a matter of minutes [6]. In these ways, engineers may be able
to solve problems that no other scientist or doctor has been able to solve.
Printing functional tissues and organs can also have applications in biomedical research,
allowing engineers to try out new drugs on real tissues without having to wait for donor tissues
to become available [5]. This may allow biomedical research to progress at faster rates than
otherwise possible.
Specific Applications of Bioprinting
Printing Skin Cells for Burn Victims
One particular medical problem that engineers are working towards solving with the 3D
printer is replacing the traditional skin graft. Instead of taking healthy skin from a patient and
grafting it to a wound, engineers are investigating methods of printing new skin directly onto
wounds, such as burn wounds [6]. Bioprinting as a means of treating skin wounds is the most
developed application of bioprinting. In fact, using 3D printers to print skin cells into wounds
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has already been successful in healing burn-like wounds in lab mice, [6] as shown in Figure 4.
Figure 4. This image presents an examination of the effect of printed skin into burn wounds on
mice. (A) shows printed mouse wound after one week, (B) shows same wound after two weeks,
and (C) shows the same wound, nearly healed, after three weeks. For comparison, (D) shows a
comparable burn wound left untreated after one week, (E) after two weeks, and (F) after three
weeks, still remaining unhealed. From source [12]
Engineers are able to print skin directly into a wound by following the same basic
principles as other forms of bioprinting. First, doctors need to take a scan of the wound in order
to create a 3D computer model. The computer can then analyze this model to create a plan of
how to fill the wound layer by layer with a cell “ink” similar to that used to create new organs
[6]. Finally, the printer can print directly into the wound in just a matter of minutes, filling it
with living cells that can grow and heal the wound over the course of a few weeks [6]. This has
the potential to help save lives in the field of battle by being able to immediately treat burn
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victims. It also has the potential to be implemented into general hospitals, giving patients more
painless procedures and shorter healing times for skin wounds.
Printing a Liver
While using bioprinting to heal skin wounds can be very complex, engineers are taking
on the even more challenging problem of printing a fully functioning human liver. So far,
engineers at Organovo, a 3D human tissues research group, have been successful in printing liver
cells that act just like real liver cells, producing cholesterol and some of the same enzymes that
real liver cells produce [7]. The two types of liver cells that this company has produced are
called hepatocytes and stellates [8]. By creating these liver cells, engineers are paving the way
towards being able to print a fully functional liver that can be transplanted into a patient’s body.
It takes about three hours to physically print the liver tissue, and an additional week for the tissue
to mature fully [13]. Additionally, scientists are able to use liver cells they can print to learn
about how diseases interact with human livers, and experiment with disease-fighting drugs to
work on creating cures for all kinds of diseases [8]. Current liver disease research uses only 2D
liver tissue, which is not optimal. The advancement towards bioprinting of new livers marks
great strides in biomedical technology.
Printing a New Heart
Like the liver, there is also a high demand for donor hearts [1]. However, the heart is far
more complex than the liver, making it more challenging to reproduce. Despite the challenge,
engineers have also been focusing on applying 3D printing to the creation of real functioning
hearts [9]. Scientists at the Cardiovascular Innovation Institute have been working towards
building “bioficial” hearts out of patients’ own cells [9]. By following the same process of
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bioprinting as used for printing other types of tissues, engineers have been able to recreate a
functioning heart from living cells. This process involves creating the pieces of the heart
individually through bioprinting, then assembling the pieces together to create a functioning
heart [13]. With more development, researchers predict that the whole assembly process will
take only a few hours with an incubation period of about a week [13].
This research has been so successful that researchers have already been able to implant
printed heart parts into mice [9]. This is a very difficult and complex process, as creating a new
heart requires replicating the complexity of blood vessels, valves, coronary vessels,
microcirculation, contractile cells, and work with the organ’s system of sending electrical signals
[9]. However, these are all challenges that engineers are tackling, with the prospect of improving
healthcare in the future.
Potential Problems and Challenges
The possibilities of bioprinting are seemingly endless, yet engineers are still tackling
several remaining barriers. The first major concern is that current bioprinters are not able to
create objects with the precision and detail necessary for replicating biological objects. Placing
cells in the exact same alignment as with the original organ requires printers to have very fine
precision, which engineers are working on achieving [10].
It will be very expensive to develop bioprinting to the point where it can be implemented
into medicine as there are still substantial amounts of research to be done. Millions of dollars
have already been spent developing the best technologies possible, but much work is still left to
be done, and will continue to cost companies millions more dollars. For example, the company
developing functional liver cells, Organovo, earned revenues of $1.2 million between 2010 and
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2012, but losses were much higher at $9.3 million for the same period of time [10]. Companies
remain optimistic and continue operations, but due to the long time scale of bioprinting projects
it will likely be decades before this work results in financial profits.
Impact on Society
Bioprinting has the potential to completely revolutionize medical care, especially
improving the area of organ transplants. Serious illness can affect anyone, leaving them in need
of a replacement organ [1]. The wait time to receive a donor organ can be extremely long and
many people will not receive the organs that they need [1]. This encourages the push towards
means of creating organs in other ways, namely bioprinting. Through techniques similar to the
3D printing of regular objects, engineers are able to print copies of functioning organs. While
these practices are new, they are becoming more reliable and advanced with time, and will likely
be seen in practice for organ transplantation within the next 10 years.
Sources
[1] Donate the Gift of Life [Online]. U.S. Department of Health and Human Services, Available:
http://www.organdonor.gov/index.html
[2] Darell, Richard (2012, December). 3D Printing Guide: How It All Works [Online], Bit
Rebels, Available: http://www.bitrebels.com/technology/printing-guide-3d-process-infographic/
[3] Oz, Mehmet and Roizen, Michael (2013, July 15). 3-D Printers are Creating Ears, but
Replacement Organs in Future: Drs. Oz and Roizen [Online], Available:
http://www.cleveland.com/healthfit/index.ssf/2013/07/3-d_printers_are_creating_ears.html
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[4] How Bioprinting Works [Online], The Washington Post, Available:
http://www.washingtonpost.com/wp-srv/special/science/how-bioprinting-works/
[5] Barnatt, Christopher (2013, May 4). Bioprinting [Online], Explaining the Future, Available:
http://www.explainingthefuture.com/bioprinting.html
[6] Printing Skin Cells on Burn Wounds [Online], Wake Forest School of Medicine, Available:
http://www.wakehealth.edu/Research/WFIRM/Research/Military-Applications/Printing-SkinCells-On-Burn-Wounds.htm
[7] CBC News (2013, June 7). Liver-like Cells Made With 3D Printer [Online], Available:
http://www.cbc.ca/news/business/liver-like-cells-made-with-3d-printer-1.1394194
[8] Yirka, Bob (2013, April 24). Organovo Announces Ability to Print 3D Human Liver Tissue
[Online], Medical Express, Available: http://medicalxpress.com/news/2013-04-organovo-ability3d-human-liver.html
[9] Ungar, Laura (2013, May 29). Researchers Closing in on Printing 3-D Hearts [Online],
USA Today, Available: http://www.usatoday.com/story/tech/2013/05/29/health-3d-printingorgan-transplant/2370079/
[10] Jeffery, James (2013, July 17). 3D Printing Human Organs – But Where’s the Money for
It? [Online], The Guardian, Available: http://www.theguardian.com/technology/2013/jul/17/3dprinting-organs-money
[11] Forgas, Norotte, and Marga (2013). Organ Engineering by Bioprinting [Online], Sense
Research Foundation, Available: http://www.sens.org/outreach/conferences/organ-engineeringbioprinting
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[12] Binder, Zhao, Park, Xu, Dice, Atala, and Yoo. In Situ Bioprinting of the Skin for Burns
[Online], Wake Forest Institute for Regenerative Medicine, Available:
https://ccc.amedd.army.mil/conferences/2009/posters/RM9.pdf
[13] Clark, Liat. Bioengineer: The Heart is One of the Easiest Organs to Bioprint, We’ll do it in
a Decade [Online], Wired, Available: http://www.wired.co.uk/news/archive/2013-11/21/3dprinted-whole-heart