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3D BIO-PRINTING AND ENINGEERING
Daniel Funari ([email protected])
INTRODUCTION
Humans have always had a fascination
with enhancement. This is constantly shown in
popular culture, such as our obsession with
superheroes. While we may not ever be as
fantastical as superheroes, we are still constantly
trying to make our bodies better, whether
through exercise, surgery, or drugs. However, this
often proves to be futile. Despite our efforts, we
remain very delicate creatures. Our lives can be
abruptly changed by disease, limb loss, and organ
loss. Enormous amounts of people each day die
from organ failure. 119,000+ people are currently
on the organ transplant waiting list, 22 of whom
die each day while waiting for a transplant [1].
Often we are unable to appreciate something
until it is gone. Approximately 185,000
amputations occur in the United States each year,
and even more in the rest of the world [2] While
not life threatening, many times our conditions
are life changing, whether by loss of non-vital
organs, sight, hearing, skin, or limbs, countless
humans are left with their bodies incomplete.
3D-PRINTING
The advent of 3d printing has taken the
technological world by storm, and given light to
enormous amounts of potential. For a while, 3D
printing was only used for quick prototype
fabrication, with materials usually limited to
plastic resins and the like. Now, 3D printing is
being used on both an industrial level and a
consumer level. Printing materials are no longer
limited to plastics anymore either. Now different
types of 3d printers are able to print parts using
multiple types of plastics, metals, (such as
stainless steel, gold, titanium, silver, etc.) and
even ceramics. On the industrial level, such as in
University of Pittsburgh Swanson School of Engineering 1
Submission Date 011.01.2016
the aero space and automotive industry, 3D
printing allows many companies to fabricate
complex custom metal parts, often with complex
hollowed out cavities that wouldn’t be possible
with CNC or machining. 3D printing is often
referred to as “additive manufacturing”, where
material is added to make parts, opposed to
conventional methods such as CNC, where
material is taken away, much of which is not
recyclable. On a consumer level, affordable
desktop 3D printers are now widely available,
inspiring shared innovation and creativity
amongst individuals on an even larger scale [3].
3D PRINTING AND MEDICINE
3D printing also has many medical
applications. Because 3D printed objects are
designed and built on CAD programs, they can be
custom made with great ease to fit any system,
whether that be a machine or a human being. For
example, we can now print inexpensive plastic
prosthetics for amputees, or artificial hip, knee,
and facial replacements, which previously
would’ve cost thousands of dollars if they were
not 3D printed. 3D printing can also be applied to
smaller scales, such as an airway splint to fit the
trachea of an infants, made by researchers at the
university of Michigan Ann Arbor [4]. A team at
Harvard also found a way to print hollow tube
like structures that could be used for artificial
blood vessels, and another team at the Henry
Ford innovation Institute is printing artificial
heart valves [4]. Advances such as these could
prove to be an invaluable asset to surgeons and
doctors alike.
BIO-PRINTING
Daniel Funari
Now, with 120,000 people on the organ
transplant waiting list and only 30,000 donors
(and that gap is only getting bigger), and 185,000
people receiving amputations annually, wouldn’t
it be nice if we could supply organs on the same
scale that we can now supply 3D printed parts?
The newest and most exciting advance in the
world of 3D printing may be the answer:
bioprinting. Bioprinting is the construction of
organic constructs, usually organs or parts of
organs, by 3D printing with organic tissue. The
fundamental process is essentially the same as
typical 3D printing, where material is placed in
the x and y axis to form a single layer, and
subsequent layers are stacked up in the z
direction. However, because the material used
are living cells, certain steps must be taken to
ensure that the cells are able to retain the shape
they are placed in, and do not die. The first
example of bio printing was done at the Wake
Forest Institute for Regenerative medicine, using
a biofriendly scaffold structure to support the
printed cells, so that they may later grow and
interconnect with each other in an incubator. The
Printer prints layers of the scaffold material and
cells over each other until the structure is
complete. The cells are suspended or printed
with microgel, a gelatin enriched with vitamins
and proteins, in order to sustain the cells and
space them properly. The printed cells are usually
referred to as “bio ink”. The scaffold material is
usually made up of microgel, hydrogel (water
based gelatin), collagens (main structural protein
found in connective tissue), bio-compatible
plastic, or other biofriendly materials [5].
patients [5]. In order for the organ to not be
rejected, it has to be made from cells or stem cells
from the patient. Even then, there is still a risk of
rejection, because tissue from one part of the
body isn’t always accepted in other parts of the
body, as common surgical practice has shown [6].
The biggest problem with printing
working human organs is the issue of
vasculature. Bone, skin, nerve tissue [7], and even
ovaries [8] have been functionally printed and
successfully transplanted into rats, but doing the
same for humans is a little different. Cells need
nutrients and oxygen to live, which in normal
organs is supplied by blood running through our
complex vasculature. In order to survive, cells
must be within 150 to 200 microns (the width of
a few human hairs) of the nearest capillary,
otherwise, the amount of oxygen and nutrients
will not be sufficient. Pre-existing vasculature has
the tendency to penetrate and spontaneously
grow into the newly added tissue, to an extent. In
the cases of 3D printed organs and tissues in rats,
the level of spontaneous vascularization is
sufficient due to the small size of rat organs and
tissues. However, in the case of humans, the size
of the organs is too great for such undirected
vascularization to supply enough blood to all the
cells [9].
BIO-PRINTING AT WAKEFOREST
A pioneer in the bioprinting world is the
Wake Forest Institute for Regenerative Medicine,
led by its director, Dr. Anthony Alata (and funded
by the Armed Forces Institute for Regenerative
Medicine). Dr. Alata and his team have been
developing bioprinting and printed tissues for
decades [10]. So far they have printed skin,
muscle, bone, cartilage, bladders, vaginas, heart
valves, ear scaffolds, and kidney prototypes.
Many of the previously mentioned printed parts
have been successfully placed into rats and mice.
The way the parts are made is by printing both
bio friendly scaffolding and cell enriched
hydrogel simultaneously, and then placing the
part in tissue growth encouraging liquid for an
extended period of time, until cell growth has
begun all throughout the scaffolding. The part is
then placed into the host, where the cells
continue to grow and vascularize until the part is
THE CHALLENGES
Because there are so many different types
of human tissues, and each organ can be made up
of multiple types of tissues, and have different
structures, bioprinting becomes much more
complicated. For each organ and tissue, intensive
research has to be done to be able to successfully
print that particular living tissue or organ. For
example, skin cells change depending on depth,
bladders are made up of different inner and outer
cell linings, and kidneys and livers are even more
complex. If these organs are successfully printed,
then there is the challenge of transplanting it into
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Daniel Funari
a functioning part of the body. Simpler tests
included transplanting an ear scaffold under the
skin of a rat (in order to receive vascularization),
where cartilage eventually fully developed and
the ear appeared as normal [11].
While many of the successes have been
through experimenting on mice, there are cases
of successes on humans other than simple tissue
grafts. The bladders printed at The Wake Forest
Lab were successfully transplanted into 7
patients with myelomeningocele, ages 4-19 in
2006 [9]. In another endeavor, 3D printed
vaginas were successfully implanted into 4
women with vaginal aplasia, using cells from the
existing vulva tissue [12].
Eventually, Atlata and his team hope to
print and successfully implement more
complicated organs, such as kidneys.
Development for printing a functional kidney is
already underway, as the wake forest team has
previously printed a kidney shaped prototype,
made up of living kidney tissue. However, the
prototype was without the intricate inner
structures, such as the fine networks of vessels
called glomeruli that allow the organ to filter
waste materials from the blood [9]. Kidneys are
made up of 3 different kinds of cells, and the
inner structures need proper vascularization in
order to survive. To solve the issue of blood,
Wake forest scientists made a newer 3D printer
called ITOP (Integrated Tissue-Organ Printer)
that prints biodegradable polymers (PCL) at
regular intervals, which creates very small
channels in the printed tissue, allowing for even
and thorough vascularization throughout the
tissue. The bio-ink used in ITOP is delivered
within a strong gel that helps the printed material
retain its shape during printing. After, the
scaffolding is washed away, leaving just the bio
printed tissue [11]. Using ITOP, the Wake Forest
team has printed muscle, bone (in the form of a
jaw bone), and cartilage (in the form of the
previously discussed ear).
Atlata and his team have also looked into
3D printing skin directly onto burn sites. The
have developed a skin printer that sprays the skin
tissue on the wounds, and depending on the
depth of the wound (gauged by a depth sensing
laser) different types of skin cells are sprayed
[13]. So far the printer has been used on pigs [14]
successfully, but it is still pre-clinical.
CONCLUSION
Imagine a world where 3D printing
organs became its own industry, with organs
being produced on enormous scales. Bio-printing
could very well be approaching that situation.
While Bio printing may seem like science fiction,
it is a very real technology that is being
developed right now. With a steady supply of
livers and kidneys being pumped out, the need
for donors would become nonexistent. The 22
people who die each day waiting for a transplant
would be saved, and the donor-transplant gap
would close rapidly. Perhaps one day skin
printers could be used to heal soldiers and burn
victims, or provide cosmetic applications with a
new way to approach facial reconstructive
surgery. Maybe one day we could even be able to
print entire limbs. Bio-printing is a technology
worth advancing in, and the prospects are getting
ever closer.
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Daniel Funari
http://www.thescientist.com/?articles.view/articleNo/37270/tit
le/Organs-on-Demand/
[10] Scott, Clare. "Wake Forest Researchers
ELECTRONIC/DIGITAL/ONLINE SOURCES
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http://www.organdonor.gov/statisticsstories/statistics.html
[2] "Amputee Coalition." Amputee Coalition.
Successfully Implant Living, Functional 3D
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N.p., n.d. Web. 31 Oct. 2016.
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[11] Dubnicoff, Todd. "Meet ITOP: A One Stop
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[3] "3D Printing Industry Examples and Case
Shop for 3D Printing Body Parts." The Stem
Cellar. N.p., 2016. Web. 31 Oct. 2016.
Studies." 3D Printer. N.p., n.d. Web. 31 Oct.
2016.
https://blog.cirm.ca.gov/2016/02/18/meet-itopa-one-stop-shop-for-3d-printing-body-parts/
[12] Lytton, Charlotte. "Lab-Created Vaginas,
http://www.javelin-tech.com/3dprinter/industry/
[4] Ledford, Heidi. “The printed organs coming to
a body near you”. Nature.com. Nature Publishing
Successfully Implanted in Four Women,
Function Normally." The Daily Beast.
Newsweek/Daily Beast, April 11 2016. Web. 31
Oct. 2016.
Group, April 15, 2015. Web. 31 Oct. 2016.
http://www.nature.com/news/the-printedorgans-coming-to-a-body-near-you-1.17320
[5] Harris, Willaims. "How 3-D Bioprinting
http://www.thedailybeast.com/articles/2014/04
/12/lab-created-vaginas-successfully-implantedin-four-women-function-normally.html
[13] "Printing Skin Cells on Burn Wounds." -
Works." HowStuffWorks. N.p., 17 Dec. 2013.
Web. 31 Oct. 2016.
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ern-technology/3-d-bioprinting.htm
[6] Gilpin, Lyndsey. "3D 'bioprinting': 10
Wake Forest School of Medicine. January 4
2014, 2016. Web. 31 Oct. 2016.
http://www.wakehealth.edu/Research/WFIRM/
Research/Military-Applications/Printing-SkinCells-On-Burn-Wounds.htm
[14] Shaer, Matthew. Smithsonian Magazine.
Things You Should Know about How It Works
- TechRepublic." TechRepublic. N.p., 15 Apr.
2015. Web. 31 Oct. 2016.
http://www.techrepublic.com/article/3dbioprinting-10-things-you-should-know-abouthow-it-works/
[7] Boggs, Will. "3D 'bioprinter' Produces Bone,
Smithsonian, May 2015. Web. 31 Oct. 2016.
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on-doctor-print-human-organ-on-demand180954951/?no-ist
Muscle, and Cartilage." Reuters. Thomson
Reuters, 16 Feb. 2016. Web. 31 Oct. 2016.
ACKNOWLEDGMENTS
http://www.reuters.com/article/us-healthbiotech-3d-printers-idUSKCN0VO28X
[8] Fan, Shelly. "New 3D Printed Ovaries Allow
I would like to acknowledge my Mom,
my floormate Jack, my floormate Daniel
Zunino, and Dr. Natasa Vidic
Infertile Mice to Give Birth." Singularity HUB.
N.p., 03 June 2016. Web. 31 Oct. 2016.
http://singularityhub.com/2016/04/10/this-3dprinted-prosthetic-ovary-restores-femalefertility-in-mice/
[9] Yandell, Kate. "Organs on Demand | The
Scientist Magazine®." N.p., Sep 1 2013. Web.
31 Oct. 2016.
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