stem cell bio-ink and its possible use in 3d printed kidneys

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Disclaimer — This paper partially fulfills a writing requirement for first year (freshman) engineering students at the
University of Pittsburgh Swanson School of Engineering. This paper is a student, not a professional, paper. This paper is
based on publicly available information and may not be provide complete analyses of all relevant data. If this paper is used
for any purpose other than these authors’ partial fulfillment of a writing requirement for first year (freshman) engineering
students at the University of Pittsburgh Swanson School of Engineering, the user does so at his or her own risk.
STEM CELL BIO-INK AND ITS POSSIBLE USE IN 3D PRINTED KIDNEYS
Julia Saams, jks55@pitt.edu, Bursic 2pm, Meara Sedlak, mms201@pitt.edu, Bursic 2pm
Revised Proposal — The topic of 3D printed organs is not a
new technology, nor is it a simple, straightforward task.
Within 3D printing organs, many aspects of the process must
be created, tested and advanced to create a functional organ.
Some major problems that arise involve vascularization,
structure, and materials. Without a successful and sturdy bioink as printing material, the 3D printed organ would not be
viable off the printer. Within biomaterials, our focus is the
use of various stem cells from the human body and the
methods involved with these cells in order to create bio-ink.
With this stem cell bio-ink, we will specifically focus on its
use in 3D printed kidneys. Progress in this research on 3D
printed organs has the potential to change the current system
and state of organ transplants internationally.
Stem cells are unique in their nonspecialized nature;
however, they can, through a process called differentiation,
become specialized, taking on the form and function of the
chosen cell and serve as a prime source for bio-ink. They are
able to produce enough cells to print the tissue while also
able to become the specific cells needed for said tissue, such
as the nephron in the kidneys [1]. The cells are then able to
adhere to each other in the bio-ink, fusing and forming the
tissue [2]. With advances in integrating vascular and
filtration structures, entire fully functional organs may be
able to be printed and used for not just drug testing, but fullscale transplantation.
The progress and research in stem cell bio-ink and its use
in 3D printed kidneys is a topic that is important to not only
engineers, but to all people around the world. As the demand
for organs and death by organ failure steadily increases, the
amount of organs available for transplants has held constant.
Currently, 133,765 people are on the organ donation waiting
list [3], but only a small number will receive the transplant
they need. Organ donations from others require in-depth
health screenings for transplantation. These screenings are
conducted in order to ensure that the organ will not be
rejected from the patient’s body. With 3D printed organs
from stem cell bio-ink, however, the organ would run a
minimalized risk because it is made from the patient’s own
cells. With continued research and advancements in the area
of stem cell bio-ink, as well as advancements in 3D printing
all organs, but specifically kidneys, the number of organ
transplants needed will significantly decrease and could
possibly eliminate the need for organ donations altogether.
University of Pittsburgh Swanson School of Engineering 1
January 29, 2016
The approval of this technology, once it has proven
successful, would drastically change the face of medicine.
Lastly, research in 3D printed organs affects everyone
because in their life they are likely to need an organ
transplant or know someone that needs an organ transplant.
In order for our paper to be well organized, we intend to
use the following plan as a guideline when writing. First, we
will introduce the types of stem cells. Along with basic
descriptions about these stem cells, we will discuss how they
are transformed into bio-ink. If applicable, depending on
sources, we will compare how the different types of stem cells
hold up as bio-ink and which will be the best biomaterial.
After this, we will describe how bio-ink is made from stem
cells, explaining the different processes. Then, we will go into
detail about the printing of organs using this bio-ink. For
example, we could cover what materials the printer needs to
ensure that the organ will be viable. Finally, we will discuss
the printing with bio-ink in relation to advances in research
with 3D printed kidneys
REFERENCES
[1] R. Morizane, A. Lam, B. Freedman, S. Kishi, et al. (09
June 2015). “Nephron organoids derived from human
pluripotent stem cells model kidney development and injury.”
Nature
Biotechnology.
(Online
Journal).
http://www.nature.com/nbt/journal/v33/n11/full/nbt.3392.htm
l#affil-auth
[2] A. Faulkner-Jones, S. Greenhough, J. King, et al. (4
February 2013). “Development of a valve-based cell printer
for the formation of human embryonic stem cell spheroid
aggregates.” Biofabrication. (Article). Vol. 5, Number 1.
http://iopscience.iop.org/article/10.1088/17585082/5/1/015013/meta
[3] (25 September 2015). “Waiting List: Overall by Organ.”
Organ Procurement & Transplantation Network: Data
Reports.
(Online
Report).
http://optn.transplant.hrsa.gov/converge/latestData/rptData.as
p
ANNOTATED BIBLIOGRAPHY
Julia Saams
Meara Sedlak
(February 2004). “Biomedical Engineering Society Code of
Ethics.”
BMES.
(Code).
http://bmes.org/files/2004%20Approved%20%20Code%20of
%20Ethics(2).pdf
This code, from the Biomedical Engineering Society, lays
out the ethics that bioengineers are expected to follow in their
career. It discusses obligations in a professional, research or
training field in order to insure that morals are upheld. This
code of ethics will be useful information when discussing the
ethics involved with stem cell bio-ink technology in
bioengineering as well as 3D printed kidneys.
E. Pagès, M. Rémy, V. Kériquel, et al. (29 September 2015).
“Creation of Highly Defined Mesenchymal Stem Cell
Patterns in Three Dimensions by Laser-Assisted
Bioprinting.” Journal of Nanotechnology in Engineering and
Medicine. (Article). Vol. 6, Issue 2. DOI: 10.1115/1.4031217
This article, from an American Society of Mechanical
Engineers published, peer-reviewed journal, discusses the
success of a laser-assisted bioprinter (LAB) with stem cell
bio-ink. It discusses precision achieved with this printer and
its use in skin, cartilage, bone vasculature and kidneys and
the preparation of the bio-ink. This information will be useful
in our comparing of printing techniques and stem cell bioinks.
(25 September 2015). “Waiting List: Overall by Organ.”
Organ Procurement & Transplantation Network: Data
Reports.
(Online
Report).
http://optn.transplant.hrsa.gov/converge/latestData/rptData.as
p
This data, from the Organ Procurement and
Transplantation Network, a partnership that links
professionals to the transplantation network, puts number
values and statistics to claims made about organ
transplantation. It gives current numbers about those waiting
for transplants, divided up by organ, as well as yearly reports
about transplants needed and transplants received. The
information from this source will be useful to explain the
need for research in the field of 3D printing.
J. Ritz. (2012, May/June). “Magic from Human Regenerative
Technologies – Stem Cells.” Technology and Engineering
Teacher. (Article). Vol. 71, Issue 8, pp. 4-9.
http://web.b.ebscohost.com/ehost/detail/detail?sid=f20945dd9bea-4603-9a4b585d4de9a540%40sessionmgr111&vid=0&hid=102&bdata=
JkF1dGhUeXBlPWlwLHVpZCZzY29wZT1zaXRl#AN=749
71847&db=aph
Initially published in journal for technology and
engineering education, this article discusses the process of
differentiating stem cells and their applications in tissue
engineering, as well as the ethics behind it. It contributes to
our understanding on the role of stem cells in the normal
human body, and how this role can be developed for use in
manufacturing. Its discussion of the ethics involved in
obtaining stem cells is also helpful, in that it clarifies the
ethical issues we must face when working with stem cells.
A. Faulkner-Jones, S. Greenhough, J. King, et al. (4 February
2013). “Development of a valve-based cell printer for the
formation of human embryonic stem cell spheroid
aggregates.” Biofabrication. (Article). Vol. 5, Number 1.
http://iopscience.iop.org/article/10.1088/17585082/5/1/015013/meta
The research in this paper, from a professional journal
focusing on the use of biomaterials for manufacturing
biological systems, was concerned with engineering a printer
capable of printing stem cell bio-ink in aggregates in specific
patterns, while not overheating and damaging the cells or
printer. The progress made in this research will allow us to
expound on the actual application of the bio-ink in the
printing process.
C. Schubert, M. van Langeveld, L. Donoso. (28 November
2013). “Innovations in 3D printing: a 3D overview from
optics to organs.” British Journal of Ophthalmology. (Online
Article).
http://bjo.bmj.com/content/early/2013/11/28/bjophthalmol2013-304446.full
This overview of recent developments in additive
manufacturing, in a research article published in a
professional medical journal, discusses both the viability of
current bioprinting and the potential for continued advances
in manufacturing. Although it focuses primarily on optics, the
information provided on the growing industry behind 3D
printing and on the prospects of 3D printing organs gives us a
perspective on the future of the technology we’re researching.
R. Morizane, A. Lam, B. Freedman, S. Kishi, et al. (09 June
2015). “Nephron organoids derived from human pluripotent
stem cells model kidney development and injury.” Nature
Biotechnology.
(Online
Journal).
http://www.nature.com/nbt/journal/v33/n11/full/nbt.3392.htm
l#affil-auth
This research article, published in a peer-reviewed
biotechnology journal, lays out the process undertaken to
differentiate human pluripotent stem cells into nephron
structures, those cells found in the kidney. It outlines the
difficulties in developing functional nephron cells, and how
researchers have overcome these obstacles. This process is a
key part of producing the bio-ink for organ printing, and this
article provides us with the current methodology for doing so.
S. Wüst, M.E. Godla, R. Müller and S. Hofmann. (2014,
February). “Tunable hydrogel composite with two-step
processing in combination with innovative hardware upgrade
for cell-based three-dimensional bioprinting.” Acta
Biomaterialia. (Article). Vol. 10, No. 2, pp. 630-640. DOI:
10.1016/j.actbio.2013.10.016
This article, from a peer-reviewed scientific journal
published by Elsevier that covers biomaterial research,
discusses the process of cell encapsulation as well as the use
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Julia Saams
Meara Sedlak
of hydroxyapatite hydrogel with human mesenchymal stem
cells as printing material. The article explains how different
concentrations of hydroxyapatite affected multiple
characteristics of the hydrogel encapsulating the stem cells. It
goes on to discuss long-term success with the hydrogel and
the methods use to obtain this. Information from this source
will be useful to discuss different approaches with stem cells
in bio-ink.
T. Xu, W. Zhao, J. Zhu, M. Z. Albanna, J. J. Yoo, A. Atala.
(January 2013). “Complex heterogeneous tissue constructs
containing multiple cell types prepared by inkjet printing
technology.” Biomaterials. (Article). Vol. 34, Issue 1, pp.
130-139. DOI: 10.1016/j.biomaterials.2012.09.035
This article, published by Elvesier, is from a peerreviewed scientific journal that publishes information about
the physical, biological and chemical sciences. This article
discusses using multiple cell types in a single printing
structure in methods outside of the body and within the body.
Information from this article will be useful when discussing
the 3D printed kidney due to its multiple cell types as well as
methods for stem cell bio-ink.
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