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Modern Organ Replication Methods
Investigating the Development of Artificial Organs for Transplants
______________________________________________________________________________
Joy Rebustes, Undergraduate Mechanical Engineering Student, Northeastern University
Abstract
There is a constant shortage of donated organs for transplant patients. The waiting list has
significantly grown since 1989. Science and engineering are researching ways to eradicate this
problem by creating artificial organs. Three primary methods are discussed in this paper: organ
scaffolds, fully mechanical organ replacements and cell printed organs. Several factors are taken
into account, such as feasibility, organ development time, ease of development, compatibility
with the human body, and length of life. Out of these factors, the organ development time is most
important: there is a wide demand that must be met for patients. While each method has its own
advantages, cell printing is seen to have the most potential for creating a fully functional artificial
organ.
Keywords
3D Printing: Method of creating 3D parts using a computer generated image and printing that
image using a 3D printer
Computer-Aided Design (CAD): Designing a part or assembly using software programs such as
AutoCAD or Solidworks
Scaffold: A part that acts as a ‘skeleton’ for cells to rapidly grow on
Decellurization: Removing the living cells from tissue in order to achieve a collagen/elastic
‘skeleton’ for which to rapidly grow cells on
I. Introduction
Each day, about 18 people in the United States die while waiting for an organ transplant.
There is a constant shortage of donors, especially for children from the ages of 1 to 17. [1] While
there has been a positive trend in people signing up to be organ donors, there is still a giant gap
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between these transplants and waiting list. A transplant candidate can wait from only a few days,
to many years, depending on availability and level of the sickness of patient. The chart below
from the U.S. Department of Health and Human Services demonstrates this[1]:
Figure 1: Organ Transplant Chart[1]
While there has been a slight increase in donors and transplants, the waiting list has skyrocketed
since 1989. One way that doctors have tried to expedite the process is by attempting to make
these organs more adaptable to any patient. This method is called decellurization, where the host
cells are removed to create a collagen structure base. This base is then injected with stem cells
taken from the patient in need and developed into a fully functioning live organ. This method is
more than regular whole organ transplant because there is significantly lower chance of a
negative reaction in the recipient[2]. On the other hand, this method still requires donors and
therefore a long waiting list.
The system needs to be improved. For every organ that becomes available, hundreds of
thousands of people are waiting to receive it. Science and engineering have been working hard
trying to close the gap using technology instead of depending on organ donations. By relying on
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technology, patients will be able to have needed organs much quicker and the organ trafficking
in the black market may even be drastically reduced.
II. Presented Methods
A. Artificial Scaffolding
One of these new alternatives includes creating artificial scaffold. A scaffold is a skeleton
structure on which cells may grow, similar to the organ decellurization method. The challenge
with artificial scaffolding is creating a 3D structure out of materials that the human body will not
reject. Two methods of creating these scaffolds are being investigated: 3D printing and 3D
bioplotting, each with their own advantages.
1. 3D Printed Scaffolds
There are several kinds of 3D printers in the world, however the most common one used
for biomedical applications is a powder based machine. First, a computer generated image of a
3D object is formed using a Computer Aided Design (CAD) program, and then inputted into the
printer. The manufacturing process begins with a layer of powder. This powder is bonded
together with a solvent dispensed by an inkjet print head, creating a very thin slice of the object.
By binding fused powder layers numerous times, a 3D object can be achieved. When the object
is completed, it requires post treatment in order to remove the extra powder and supports
required to uphold the shape of the object. 3D printing allows a variety of shapes that are able to
be acquired.
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The effectiveness of this method can be seen with the
successful replication of a human heart. Using a CT and MRI
scan, several views of a patient’s heart with a congenital
defect was taken. A 3D
model was formed using
CAD and
recreated
in
physical form using 3D
Figure 2: CAD rendering of a heart [3]
printing (as seen in Figure
2). An elastomer and adhesive is alternatively poured and
integrated into the heart using a vacuum machine. Then the
model can be bent to break the original scaffold, leaving a
Figure 3: 3D Printed Heart
with elastomer[3]
completely smooth, slightly elastic heart (Figure 3). In these figures, the arrow points to the
congenital defect in this particular patient, depicting the accuracy of the printed heart. The heart
was proven to be able to slight expansion and compression to mimic a beating heart, using an
inflated balloon[3].
While this achievement looked at this particular patient’s congenital defect, it shows a
promising start to replicating a real heart. Instead of an elastomer, a cell matrix containing living
cells of the patient and other substances to promote growth would be applied on the skeleton
instead. If the 3D printing method is mastered, the need to wait for available organs might be
over. However, there are other better ways to create an artificial scaffold.
2. Bioplotted Scaffolds
Bioplotting is also “printed” layer by layer using a CAD model, however the dispenser
distributes a viscous plotting material into a liquid medium. The densities of these two
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substances are the same to remove the need of temporary supports in the 3D printing. Bioplotting
allows for a wider variety of materials for models, and can make similar structures to 3D
printing. The post treatment time for bioplotted structures is also significantly less, allowing for
overall less time to get an organ to a patient: crucial for those who are very sick and waiting. In a
particular study creating two structures
of the same shape and size, the 3D
printed object needed almost 20 hours
compared to the bioplotted object,
which required only 30 minutes.
When tested, the cell growth on
each of the scaffolds was about the
same rate, which points researchers to
lean toward bioplotting as the superior
method
for
organ
scaffolding.
However, it is a newer technology that
Figure 4: Magnified view of 3D printed scaffold (top)
and a 3D bioplotted similar scaffold (bottom) [4]
requires more research. There are more 3D printers available than bioplotters, which makes it
harder for a wider spread of researchers to work with this new machine.
3. Drawbacks of the Scaffolding Method
While there have been many promising developments with artificial scaffolding, there are
still drawbacks. The cellular growth on the scaffolds easily varies. To create a perfect, new
organ, the cells must grow uniformly throughout the skeleton. In addition, the natural variance of
cell types in different locations in organs is hard to recreate. Also, with rigid scaffolds,
contractile tissues, such as in the heart, will have much difficulty moving[5].
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B. Mechanical Organs
1.
BioLung and SynCardia
Instead of scaffolds, some have ventured to create fully mechanical organs, requiring no
injection of cells. The BioLung weighs less than a pound and is incorporated into a vest that the
patient wears. The BioLung is directly attached to the patient’s
cannulae, where gas exchange can occur with the lung’s bundles
of hollow fibers full of oxygen. A graphical depiction of the
BioLung may be seen in Figure 5. A completely mechanical
organ diminishes any need for organs or cells from either patient
Figure 5: Diagram of the BioLung [6]
temporary
stand-in
to
the
or donor. However, most mechanical organs serve as a
actual
transplant, such as the SynCardia heart
in Figure 6. As seen, it resembles a real
heart, but is still a long way from being
a permanent solution to heart problems.
Though it does save lives of patients
Figure 6: Diagram of the BioLung [6]
who need assistance until a real heart is available, it is far more preferable to have the true
transplant than multiple surgeries in the cardiac area[6].
2.
Drawbacks of Mechanical Organs
Will artificial organ replication ever be as functional as natural development? Currently,
this is too difficult to know. Natural contractile movement is often too difficult to replicate and
materials that will not be attacked by a body’s immune system are rare. All organs have specific
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placement of various cells, which has proved to be very difficult to develop in an artificial
scaffold, and fully mechanical organs do not have the longevity that living replicating cells do.
C. Cell Printing
Science has been able to create a new method incorporating both 3D printing and natural
cells with a layer by layer cell printing method. The printing material is called ‘bioink,’ a culture
medium of endothelial cells. The bioink is printed layer by layer into 3D gel to create dense,
functional, fused cell tubes.[5]
This method has been successful with
endothelial, smooth muscles, and stem cells.
Again, this method also requires CAD for a
3D model and transferring the data to the
organ printer. The bioink will vary depending
Figure 7: Cell Arrangement to Make 3D Parts [5]
on the tube being creating, from the type of cell, to the medium to control growth. However, this
method has only gone so far as to create tube shaped parts of the larger organs. Figure 7 shows
the current arrangement of cell growth. As seen, they are either cube shaped, which does not
appear naturally in human tissue, or tube shaped. Each part is printed layer by layer. While tube
shaped tissues do exist in the human body, the other various shapes still must be developed to
create fully functioning organs. Much more research is worth looking into for this technology: it
has the most potential to being a successful replacement for donors. When printing with cells,
there is no worry for finding human-friendly materials, requires no post treatment after printing,
can be adapted for each patient, while being less artificial than the products of other methods.
With time and more research, there will be a chance that donors will no longer be needed, and
more lives can be saved.
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III.
Conclusions
Overall, much research is still needed to create an efficient method to eradicate the gap
between transplant patients and donors. Fully mechanical organs only survive for a period of
time, and having multiple surgeries put patients at risk.
While printed scaffolds mimicking decellurized organs have been the primary focus of
research for tissue engineering, there are still too many factors that need to be overcome for it to
be successful. These includes finding materials that the human body will not reject, endurance of
the structure, and natural organ movement that must be adjusted for each new kind of organ. The
biggest challenge for scaffolding is especially natural organ movement due to its rigid skeleton.
Therefore, focusing on other methods, such as cell printing, would be the most logical path to
developing a fully artificial transplant organ.
Cell printing may be the future for artificial organ transplants. While tube shaped organ
parts are the only current development, the possibilities this method offers allow for a more
natural full organ. Cell printing eliminates the search for body-friendly materials, and using
naturally replicating cells removes the factor of breaking down like mechanical organs.
Popularity for this method should be spread in order to speed the process for full development.
This includes research on how to cell print beyond tubular organs. Once this setback is
overcome, any organ can be printed specifically for each patient. Thorough examinations must
be made to ensure the artificial organ is reasonably comparable to the natural organ in life-span
and function. However, once this method is accepted into the medical industry as a viable source
for organs rather than donations, many lives can be saved from the transplant waiting list.
IV.
Acknowledgements
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The Northeastern University Library Resources for access to references in this report, and
revisions from Michael Hurtado and Amy Black.
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References
[1] (2012). The Need is Real: Data. [Online]. Available: http://organdonor.gov/about/data.html.
[2] (2011, February 11). Organ Scaffolding. [Online]. Available:
http://www.cloneorgans.com/organ-scaffolding/34/.
[3] Markert, Mathias et al. “A Beating Heart Model 3D Printed from Specific Patient,” in 29th
Annual International Conference of the IEEE EMBS Cite Internationale, Lyon, France, 2007,
pp 4472-4475.
[4] Pfister, Andreas et al. “Biofunctional Rapid Prototyping for Tissue-Engineering
Applications: 3D Bioplotting versus 3D Printing,” Institut fur Makromolekulare Chemie and
Freiburger Materialforschungszentrum, Freiburg, Germany, Jun. 2003.
[5] Varghese, David et al. “Advances in tissue engineering: Cell Printing,” in The Journal of
Thoracic and Cardiovascular Surgery. Clemson, NC: 2005. pp.470-472.
[6] Mertz, Leslie, “From Artificial Kidneys to Artificial Hearts and Beyond,” IEEE Pulse. Pp 1420. May, 2012.