Session C1
Paper 6171
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
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THE IMPORTANCE OF FREEFORM REVERSIBLE EMBEDDING OF
SUSPENDED HYDROGELS (FRESH) IN SCAFFOLD DESIGN
Kevin Berry, kmb274@pitt.edu, Bursic 2:00, Jim Howell, jkh48@pitt.edu, Mahboobin 10:00
Revised Proposal — Traditional 3D printers normally
printed on demand which demonstrates how important
FRESH is to the scientific community.
We will continue to consult the work Hinton and Jallerat,
the inventors of FRESH in order to familiarize ourselves with
the research currently going on at Carnegie Mellon
University. Beyond academic journals, we plan to utilize
proper video sources like “TED talks” in order to satisfy the
information needed about the ethics and the future of
bioprinting. To start, we will describe current pitfalls of the
industry. Following, we will explain how FRESH overcomes
these issues through its functionality, and finally conclude
with an exploration of ethics.
use plastics or wax for their printing materials. Bioprinting
specialist Young-Joon Seol explains, “What’s different here
is that we have the capability to print something that’s alive.”
[1]. Bioprinting has three fundamental approaches which are
biomimicry, autonomous self-assembly, and mini-tissue
building blocks [2]. Biomimicry consists of making exact
copies of biological parts and systems using scaffolds [2].This
approach requires the replication to be accurate on the
microscale which is done by using electrohydrodynamic
processes which achieve the nano and micro sized fibers [3].
These scaffolds have been at the heart of biomedical research
due to their complexity. Unfortunately, bioprinting brings up
ethical issues such as stem cells or human enhancement [6].
This paper will describe, explain, and analyze the new
FRESH system including the ethical issues involved and
explore how the invention of FRESH dramatically increases
the potential for bioprinted hearts and other complex organs
in the bioprinting field.
Soft biomaterials are notoriously difficult for tissue
engineers to work with in three dimensions because objects
made out of those materials tend to collapse under their own
weight [4]. In other words, the biological objects being
printed by the bioprinter were limited by both size and
complexity so objects like the human heart were out of reach.
However, the newly developed system of using freeform
reversible embedding of suspended hydrogels (FRESH)
allows scaffolds made out of soft biomaterials to support their
own weight. The soft hydrogel scaffold is embedded in a
thermoreversible support bath composed of gelatin
microparticles that behave as a rigid body at low shear
stresses but flow as a viscous fluid at higher shear stresses
[5]. “This is all done in a sterile, aqueous, buffered
environment compatible with cells, which means cells can be
extruded out of the printer nozzle with the hydrogel and
maintain viability” [5].
When FRESH is applied to bioprinting scaffolds the
barrier of size and complexity has finally been overcome and
the potential for bioprinted hearts has increased greatly.
FRESH could be the first step in unlocking a future where
specific organs, like the human heart, for specific patients are
University of Pittsburgh Swanson School of Engineering
1-29-16
REFERENCES
[1] M. Shaer. (May 2015). “Soon, Your Doctor Could Print a
Human Organ On Demand.” Smithsonian. (Online article)
Vol.
46,
no.
2
http://www.smithsonianmag.com/innovation/soon-doctorprint-human-organ-on-demand-180954951/
[2] A. Atala, S. Murphy. (2014). “3D Bioprinting of Tissues
and Organs.” Nature Biotechnology. (Online article) DOI:
10.1038/nbt.2958. Vol. 32 Issue 8, pp. 773-785.
[3] G. Kim, M. Kim. (2015). “Electrohydrodynamic Direct
Printing of PCL/Collagen Fibrous Scaffolds with a Core/Shell
Structure for Tissue Engineering Applications.” Chemical
Engineering
Journal.
(Online
article)
DOI:
10.1016/j.cej.2015.05.047. Vol. 279, pp. 317-326.
[4] F. Collins. (November 2015). “Building a Better Scaffold
for 3D Bioprinting.” National Institutes of Health. (Online
article) http://directorsblog.nih.gov/2015/11/03/building-abetter-scaffold-for-3d-bioprinting/
[5] T. Hinton, Q. Jallerat (October 2015). “ThreeDimensional Printing of Complex Biological Structure by
Freeform Reversible Embedding of Suspended Hydrogels.”
Science
Advances.
(Online
article)
DOI:
10.1126./sciadv.1500758.
Vol.
1,
no.
9
http://advances.sciencemag.org/content/advances/1/9/e1500
758.full.pdf
[6] s. Dodds. (February 2015). “3D Printing Raises Ethical
Issues in Medicine.”
ABC Science. (Online article)
1
Kevin Berry
Jim Howell
http://www.abc.net.au/science/articles/2015/02/11/4161675.
htm
used to begin our exploration of ethics and issues with
bioprinting.
T. Hinton, Q. Jallerat (October 2015). “Three-Dimensional
Printing of Complex Biological Structure by Freeform
Reversible Embedding of Suspended Hydrogels.” Science
Advances. (Online article) DOI: 10.1126./sciadv.1500758.
Vol.
1,
no.
9
http://advances.sciencemag.org/content/advances/1/9/e1500
758.full.pdf
This article, from the professional and peer reviewed journal
Science Advances, details the research on freeform reversible
embedding of suspended hydrogels (FRESH). The article
explains in great detail, how FRESH allows complex
scaffolds can now be designed without the fear of them
collapsing under their own weight. This is the main source of
our paper as it describes the technology that we are
presenting.
ANNOTATED BIBLIOGRAPHY
A. Atala, S. Murphy. (2014). “3D Bioprinting of Tissues and
Organs.” Nature Biotechnology. (Online article) DOI:
10.1038/nbt.2958. Vol. 32 Issue 8, pp. 773-785.
This article, from the professional and peer reviewed journal
Nature Biotechnology, intensively describes the multiple
approaches to bioprinting as well as describe how each type
of bioprinter operates in immense detail. The article describes
the positives and the negatives of each bioprinting approach
as well as each type of bioprinter. This detailed source will be
our main source for describing biomimicry and scaffolds in
technical detail.
C. V. Blitterswijk. (2008). Tissue Engineering. Burlington,
MA: Elsevier. (print book). pp. 685-703.
This textbook written and edited by a various number
professionals provides a broad perspective on tissue
engineering. Specifically, it provides perspectives regarding
the ethics of both tissue engineering and bioprinting. It
presents and defines concepts such as gradualism and
conceptualism as philosophies in ethics, and then it goes on
to connect them to the purposes of tissue engineering as a
whole. This source will be used in our discussion of ethics of
bioprinting.
G. Kim, M. Kim. (2015). “Electrohydrodynamic Direct
Printing of PCL/Collagen Fibrous Scaffolds with a Core/Shell
Structure for Tissue Engineering Applications.” Chemical
Engineering
Journal.
(Online
article)
DOI:
10.1016/j.cej.2015.05.047. Vol. 279, pp. 317-326.
This article, from the professional and peer reviewed
Chemical
Engineering
Journal,
details
how
electrohydrdodynamic process are used to build collagen
scaffolds of increasing complexity that achieve mechanically
stable and controllable micropore structures. The article then
details the experiments used to make the collagen scaffolds
and explores their results. This source will be used in order to
support other sources on scaffolds throughout our technical
description of bioprinting.
F. Collins. (November 2015). “Building a Better Scaffold for
3D Bioprinting.” National Institutes of Health. (Online
article) http://directorsblog.nih.gov/2015/11/03/building-abetter-scaffold-for-3d-bioprinting/
This article, posted by the National Institutes of Health which
is funded by the U.S. Department of Health and Human
Services, explores the disadvantages of current scaffold
designs and then introduces and summarizes the work of
Hinton and Jallerat on FRESH at Carnegie Mellon University
and then describes the next step in Hinton’s and Jallerat’s
research. This article will be used to supplement the
information on scaffold designs.
C. S. Kumar. (2006). Tissue, Cell, and Organ Engineering.
Baton Rouge, LA: Wiley-VCH. (print book). pp. 1-216.
This book, a collection of works from various authors,
focuses on the nano and micro levels of bioprinting. By
exploring the different methods of using biological scaffolds
to support printing and cellular signals to encourage selfadhesion and proliferation of cells, the work details the
actual mechanisms of biological printing. This source will be
used as a reference for many of the current practices of
biological printing and to explain how these practices work.
S. Dodds. (February 2015). “3D Printing Raises Ethical Issues
in Medicine.”
ABC Science. (Online article)
http://www.abc.net.au/science/articles/2015/02/11/4161675.
htm
This online article, posted by ABC Science and written by
Susan Dodds who is a co-author for the book 3D Bioprinting:
Printing Parts for Bodies, explores the ethical issues that
result from bioprinting. The article describes the possible
issues with the future of bioprinting like: justice and access,
safe treatments, and human enhancement. The article will be
H. Lipson & M. Kurman. (2013). Fabricated: The new
World of 3D Printing. Indianapolis, IN: Wiley. (print book).
pp. 214-218.
This book written by leading researchers on 3D printing,
explores many of the uses of 3D printers ranging from
carpentry to biological printing. The authors describe that
the future of bioprinting may result in a viable method of
producing organs for donation, prosthetics for amputees, or
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Kevin Berry
Jim Howell
plastics for cosmetics. Our use of this source will be to
describe the potential avenues the new FRESH system
especially for the production of organs.
M. Shaer. (May 2015). “Soon, Your Doctor Could Print a
Human Organ On Demand.” Smithsonian. (Online article)
Vol.
46,
no.
2
http://www.smithsonianmag.com/innovation/soon-doctorprint-human-organ-on-demand-180954951/
This article, from Smithsonian magazine, documents the
history of bioprinting and its proposed future through the eyes
of Dr. Anthony Atala, one of the leading researchers in
bioprinting. The article describes the basic details of
bioprinting and explains what bioprinting is currently capable
of by showing multiple examples such as ears and hear valves.
This article will be used to introduce our topic and represent
the current capabilities of bioprinting.
3