Conference Session B13
Paper #78
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COLLAGEN-GLYCOSAMINOGLYCANS HEART VALVE: A BREAKING BIOMATERIAL APPLICATION ON ORGAN TRANSPLANTATION
Zixie Liang, [email protected], Mena Lora, 3:00, Muyun Zhao, [email protected], Mahboobin, 4:00
Abstract —This paper discusses the viability of using
collagen-glycosaminoglycans (CG) to synthesize artificial
heart valves for transplantation and its possible future
development. A collagen-glycosaminoglycans heart valve is
an artificial structure developed using biomaterial and
tissue engineering to mimic the structure of human heart
valve.
It
contains
collagen
as
scaffold
and
glycosaminoglycans to increase the stability and flexibility
of the structure. These two materials originally exist in
human heart valves. An artificial heart valve made with
these materials can be easily accepted by human body.
The collagen-glycosaminoglycans heart valve is a
revolutionary invention in the history of heart valve
transplantation. Today, major sources of heart valves
include mechanical prosthesis, homografts which come from
matched human donors, and xenografts, which come from
other animal species. Patients using these artificial heart
valves often suffer under rejection reaction, bloodtransmitted disease and ethical crisis. CG heart valves will
successfully solve these problems. By using off-the-shelf CG
heart valves, doctors can do transplant surgery
instantaneously without wasting time looking for donors.
Laboratory-synthesized CG heart valves are free of bloodtransmitted disease, and also eliminate the moral dilemma of
xenografts. Furthermore, these CG heart valves can be
personalized based on patient’s unique genetics. Studies
have shown that due to the growth of population’s age and
cardiac diseases, more people will require heart valve
transplant in the future. Developing CG heart valves would
be extremely helpful to meet the requirement of growing
number of patients. Therefore future research is necessary.
Key Words -- Artificial heart valve, Biomaterial, Collagen
Glycosaminoglycans, Tissue engineering, Valvular disease.
AN OVERVIEW OF COLLAGENGLYCOSAMINOGLYCANS ARTIFICIAL
HEART VALVE
University of Pittsburgh Swanson School of Engineering 1
Submission Date:3/31/2017
Heart valve disease, accounts for 17.3 million deaths
per year, is one of the leading causes of human death. About
2150 Americans die each day from these diseases, which is
one of 40 seconds.[1] The most effective method to heart
valve disease is the transplantation surgery, however, current
heart valve resources used for transplantation, including
mechanical and biological heart valves, failed to meet
patients’ demands. Although both mechanical and biological
heart valve resources were developed and have saved
millions of people’s lives in the past 40 years, the
deficiencies and potential risks are still problems that
patients and doctors face every day [2][3]. Improvement of
artificial heart valves therefore becomes crucial. The
biological synthetic material Collagen-glycosaminoglycans
(CG) brought new excitement to the area of heart valve
transplantation. Collagen
and
glycosaminoglycans are
matters originally exist in human heart valves. A CG
artificial heart valve, manufactured with cell seeding
technique and minimally-invasive implantation of stem cells,
is a more reliable and effective artificial heart valve
comparing to existing substitutes used in heart valve
transplant surgeries. It shows low antigenicity, and can be
easily accepted by human body. Furthermore, lab
synthesized CG heart valves also resolves ethical issues
raised by living tissue transplantations. According to the
sustainable development goals published by the United
Nations Development Programme, a sustainable medical
device should be safe, effective, affordable and will promote
the well-being of all patients. CG heart valve, with its
advanced, convenient and reliable properties, shows its
sustainability. However, like all new technologies, CG heart
valve has its own deficiencies. One predicted problem is the
mechanical deficiency of bioprosthetic heart valve
degeneration; the other is the difficulty to balance between
cost and utility, between engineering and marketing. The
properties of CG heart valves applying on human body
require further research.
Zixie Liang
Muyun Zhao
INCREASING DEMAND OF HEART
VALVES
A heart valve transplant surgery involves replacing the
patient’s heart valve with an artificial substitute, a medical
device designed to mimic the physical and biological
properties of the natural human heart valve respectively. The
2 major substitutes are mechanical and biologic heart valves.
Heart beats along with human life about 2.5 billion
times, providing oxygenated blood to the entire body to
support our lives. While heart valve plays an important role
of human life, nearly 20,000 children worldwide are born
each year with congenital heart defects, many of which
require a heart valve replacement. [4] For those who were
born in good health, living in the modern world with
accelerating life pace and increasing working pressure make
it easily to have valvular disease due to irregular diet and
living habit. Meanwhile, aging is another fact that would
degrade heart function, which lead to valvular diseases.
According to the prediction from the Heart Valve
Engineering Magazine, as the world population increasing
from 6.4 to 8.9 billion inhabitants in 2050, the annual
number of patients requiring heart valve replacement is
estimated to triple from approximately 290,000 in 2003, to
over 850,000 by 2050 due to the growth of population’s age
and cardiac disease in both developed and developing
countries[5]. Methods on enhancing the survival and quality
of life of the large number of valvular disease patients
therefore become a crucial topic in the medical and
engineering field.
How Do Human Heart Valves Work
FIGURE 1 [2]
Sample of How a Healthy Heart Valve Works.
HEART VALVE TRANSPLANTATION
SUGERY
In general, a human heart valve contains two major
components: the leaflets and the chordae tendinae. The
leaflets are leaf-like parts that separate the atrium and
ventricles of the heart. The leaflets open to allow blood flow
in one direction, and close to block blood flowing in the
opposite direction. This structure enables blood to cycle in
the correct way. The chordae tendinae are cord-like structure
that contains mainly collagen. They act as scaffolds to hold
the leaflets in place.
Solution to valvular disease nowadays is to take heart
valve replacement surgery, which is removing the
damaged valve from a patient’s heart, and sewing a new
valve into place. A scientific research revealed the benefits
of heart valve replacement surgery on heart disease patients
by a comparison research, comparing the survival time of
old men around age 60 who had severe aortic stenosis but
didn’t take surgical treatments, with the survival time of
those who took heart valve replacements. Result showed that
old men with the replacement surgery usually prolonged
their life expectancy to 13 years while the old men without
surgery could only live for approximately 4 years. This
research proved that heart valve replacement surgery indeed
is beneficial to relieving heart disease. As the heart valve
replacement technology developed and this surgery method
advertised, more and more patients would like to take this
surgery to reduce their discomfort due to heart disease and to
prolong their lives. Only In 2016, more than 180,000
patients suffering from heart disease recovered by
transplanting artificial heart valve worldwide.
Mechanical Heart Valve
FIGURE 2 [5]
Sample of Mechanical Heart Valve
TYPES OF HEART VALVE SUBSTITUTES
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Zixie Liang
Muyun Zhao
Mechanical valve is designed to mimic the leaflets
function of a natural, healthy heart valve, which open and
close with each heartbeat, permitting proper blood flow
through the heart. It is composed of carbon, metallic and
polymeric materials, providing a significant product lifespan of greater than 20 years. From the first heart valve
replacing surgery casted by Dr. Charles A. Hufnagel in
1952, mechanical heart valve used for replacement surgery
has developed from the first simple ball-in-cage structure,
into various forms like cage valves, tilted disk valves,
bileaflet valves.
Biological Heart Valve
FIGURE 4 [7]
Sample of 3 Main Types of Mechanical Heart Valves:
Caged Ball, Tilting Disk and Bileaflet Valve
Mechanical artificial heart valves are designed based
on 3 main structure types: caged ball, tilting disk and
bileaflet valve. Even though these devices have saved
millions of patient’s lives in the past 60 years, all 3 types of
mechanical artificial heart valves have defects due to their
structures. The caged-ball design experiences high stresses
at the walls that can damage cells, as well as flow separation
due to high-velocity reverse flow surrounded by stagnant
flow. Tilting-disc valves have flow separation behind the
valve struts and disc as the result of a combination of high
velocity and stagnant flows. The bileaflet models have high
stresses during forward and leakage flows as well as
adjacent stagnant flow in the hinge area. The high shear
stress, stagnation, and flow separation of these three
structures can easily cause thrombosis, which is the process
of blood clots forming in a blood vessel. Clots lodge in the
valve flaps or hinges can block or obstruct blood flow, and
those who break off form into an embolism (traveling clot)
may move through the bloodstream, lodging into a vessel
and may eventually lead to problems like heart
attack or stroke. Patients with any mechanical heart valve
are therefore required to take blood thinning medication like
Plavix, which costs $200 per month, for a lifetime to prevent
clots from forming. This would end up with a huge amount
of maintenance fee for mechanical heart valves.
In a word, mechanical heart valves are short of
minimizing the extent of blood damage and decreasing the
complexity of heart valve post operation. Its expense and
inconvenience make it an unsustainable medical product.
FIGURE 3 [5]
Sample of Biological Heart Valve
Other than mechanical heart valves, biological heart
valve is another existing type of artificial heart valve,
focusing on the mimicking the material properties of the
natural heart. Biological heart valve can be separated in to 2
categories. Homografts are heart valve tissues from matched
human donors, and xenografts are tissues from other animal
species. Most commonly used xenograft comes from either
porcine (pig) or bovine (cow) cardiac tissue.
DRAWBACKS OF CURRENT ARTIFICIAL
HEART VALVES
Although artificial prostheses for diseased heart valves
have been around for several decades, these substitutes are
still imperfect to replace the original healthy heart valves
due to hearts complex nature.
Defects of Mechanical Heart Valves
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Zixie Liang
Muyun Zhao
patients, so they have exact same material as the natural
heart valves. Homografts can prevent rejection reaction
effectively, and are much easier for people to accept
mentally. However, resources are limited due to the small
donor pool. The strict storage and transport restrictions also
made homografts even harder to access for most of patients.
Additionally, the upper age limit at 60 was set based on the
age-related degeneration of the tissue. Given the limitations
of the donor source, the time waiting for proper homografts
could be taken over the years.
Defects of Biological Heart Valves
While all mechanical prostheses have an absolute
requirement for anticoagulant treatment, suitable biological
heart valves can increase the blood flow, which avoid the
hazards of anticoagulation, and therefore eliminate the
trouble of taking lifetime anticoagulants therapy. However,
biological heart valves also have their own weaknesses.
Xenografts
Overall
Swine are generally considered the best sources of
biological heart valves for clinical xenotransplantation.
However, concerns on safety of xenotransplantation have
risen currently due to a research on clinical trial of swine’s
heart valve. In this research, number of potential viral
pathogens was identified on swine, including porcine
endogenous retrovirus (PERV), porcine cytomegalovirus
(PCMV), and porcine lymphotropic herpesvirus (PLHV),
which made any transplanted organ becomes a potential
source of virus [5]. Although no direct studies indicate the
absolute risk for transmission of such infections from pig to
human, people would not want to take this risk gambling
their own life.
At the same time, the potential conflict between
religious beliefs and the use of pig hearts is another issue
caused by xenotransplantation. For example, there is a
biblical prohibition against eating and touching swine for
Jewish in Leviticus: “And the swine–although it has true
hoofs, with the hoofs cleft through, it does not chew the cud:
it is impure for you. You shall not eat of their flesh or touch
their carcasses; they are impure for Me.” [6].
In order to investigate the views of major religions and
cultural groups regarding the use of allogeneic for soft tissue
repair, a group of researchers contacted representatives from
6 major religions, including Judaism, Islam, Buddhism,
Hinduism, Scientology, and Christianity, distributing
standardized questionnaires to the religious and cultural
authorities to obtain their views on the acceptability of
bovine-, or porcine-derived biological grafts. It turns out that
although dietary restrictions among Jews and Muslims do
not translate to tissue implantation restriction, and most of
other religions allow the use of xenogeneic tissue (the only
exception is the Hindus categorically, prohibiting any use of
animal products.), people with religious beliefs still consider
impure of having a pig’s heart beating inside their body.
The safety hazard and the moral dilemma of Xenograft make
it an unsustainable medical product [7].
Besides the defects of biological heart valves
mentioned above, the major weakness of biological heart
valves overall is their limitation on lifespan. Xenograft or
homograft valve can only last for average 15 years, and
nearly 65% of patients under age 60 who receive a
biological heart valve need reoperation(s) after 15 years.
(Tissue-engineered heart valves. Filová E, Straka F,
Mirejovský T, Masín J, Bacáková L Physiol Res. 2009; 58
Suppl 2:S141-58.) Other studies indicate even shorter life
spans for these valves, with patients needing a new
replacement in less than 10 years. (Heart valve tissue
engineering. Neuenschwander S, Hoerstrup SP Transpl
Immunol. 2004 Apr; 12(3-4):359-65.) These data indicate
that younger patients would have to suffer several reopenheart surgeries in their lifetime to maintain the function of
their heart valves. However, the re-open heart surgeries
would not only increase the infectious risks, but also would
burden patient’s family with the large amount of cost per
surgery. According to the data from the American Heart
Association report, valve replacement surgery typically costs
from about $80,000 to $200,000 or more. Additional Costs
would also be charged for necessary dental work done to
prevent oral bacteria from causing an infection in the new
valve. The heavy cost to maintain a biological heart valve
and the inconvenience of re-open heart surgery make the
biological heart valve an unsustainable medical product.
MATERIAL FOR ARTIFICIAL HEART
VALVE
The defects of previous artificial heart valves reflectes
the complexity of the nature heart valve evolved over time.
This complexity requires scientist and researchers to
understand native heart valve properties more completely
before creating the new living replacement heart
valve. Ideally, the creation of a viable heart valve
transplantation combines improved mechanical properties
with enhanced bioactivity promoting biomaterials.
Previously, designs of artificial heart valve were mainly
Homografts
Homografts are heart tissue harvested from brain dead
organ donors or from explanted heart of a heart transplant
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Zixie Liang
Muyun Zhao
focused on the mechanical properties of the natural heart
valves, but didn’t make a huge progress regarding to the
material. Additional insights into viable bio-material of
making artificial heart valve and how to combine this biomaterial with the mechanical properties of the heart valve
will enable researchers to make significant improvement in
the field of artificial heart valves.
The combination of collagen and glycosaminoglycan
was considered an ideal material in this application, as
collagen is the major extracellular component of the native
heart valve, while glycosaminoglycan providing necessary
fatigue resistance against the repeated shearing between the
different layers of the native heart valve [7]. In fact,
researchers in the Ireland have successfully synthesized a
cross-linked, multicomponent scaffold in a heart valve shape
made by collagen glycosaminoglycan material, and
examined the most suitable distribution of collagen and
glycosaminalglycans by simulating the environment in
human body. They fabricated the heart valve shaped CG
scaffold through freeze drying a CG slurry in a customize
mold, which can be personalized among different patients.
They first crosslinked the scaffolds physically by
dehydrothermal treatment at 105 Celsius for 24 hours, and
then crosslinked it chemically using (1-Ethyl-3-)3-dimethyl
aminopropyl carbodiimide (EDAC) in the presence of Nhydroxysuccinimide (NHS) solution. These processes
stiffened the scaffold while maintaining its elasticity.
Different
concentrations
of
both
collagen
and
glycosaminoglycans were also assessed to find the most
stable concentration of CG to work with. It turns out that
0.75% collagen with 0.044% glycosaminoglycan is the most
stable combination that can also maintain excellent cell
viability. In conclusion, A crosslinked, multicomponent
scaffold of collagen, GAG and fibrin can be characterized
for heart valve applications. And Fibrin gels reinforced with
a 0.75% collagen, 0.044% GAG scaffolds can resist VSMC
induced contraction significantly more than fibrin-only gels,
while allowing cell proliferation and maintaining excellent
cell viability. This sustainable improvement on material
showed the new possibility for heart valve tissue engineering.
FIGURE 5 [7]
Sample of the Heart Valve Shaped CG Material.
UTILIZE COLLAGEN
GLCOSAMINOGLCANS TO FORM
ARTIFICIAL HEART VALVES
Cell-seeding Technique
The biological and medical properties of collagen and
glycosaminoglycans (GAGs) illustrated above shows the
advantages of CG as a biomaterial, for these components are
naturally found in human heart valves and have the property
to resist stress and pressure, making them the ideal materials
for synthesizing artificial heart valves. The next step of
research needs to focus on the technique used to synthesize
CG material to mimic human heart valves under lab
condition. A paper published on the Tissue Engineering
magazine demonstrated an experiment to synthesize
glycosaminoglycans within a collagen gel scaffold by
seeding valvular cells onto collagen gel and applying
different stress and strain [8]. In a human heart valve, the
different compoennts, leaflets and chordae tendinae,
experience different pressure and stress when functioning.
The chordae tendinae only act as the support of the heart
valve therefore only experience stretch in one direction. The
leaflets, however, experience both stretch and pressure in
multiple direction when blood flow through them. The
different stress and pressure experienced by different parts
of the heart valve requires different tissue structure, and
therefore required different compositions of collagen and
GAGs. In order to mimic the structure and function of live
heart valves, CG heart valves also need to have different
ratio of collagen and GAGs in its artificial leaflets and
chordae tendinae. This experiment published on Tissue
Engineering magazine reveals the fact that when applied
different stress and pressure, the valvular cells seeded on
collagen gel is able to synthesize different types of GAGs,
therefore satisfying different structural needs of artificial
heart valve. According to the experiment, cells seeded in the
region where uniaxile (single-directional) stress is applied
secrets GAG dermatan 4-sulfate, which is the type of GAG
commonly found in chordae tendinae [8], thus making it a
good material for structural support. In contrast, cells seeded
in the region where multiaxile (multi-directional) stress and
pressure is applied secrets GAGs HA and chondroitin 6sulfate [8], which is commonly found on the leaflets that can
handle both stress and pressure from multiple directions. The
result of this experiment provides useful insight about the
technique used to generate different types of CG material for
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Zixie Liang
Muyun Zhao
specific parts of the artificial heart valve to mimic the
desired structure and function of human heart valve. In the
future bioengineers can apply this technique to synthesize
CG heart valves in labs that can be used for transplantation
surgery.
after transplantation [9]. Stem cells are unspecialized cells
commonly found in bone marrow and peripheral blood that
have the ability to rapidly divide and develop into any kind
of tissue cell. Tissue developed from stem cells will have the
same genetic as the donor of the stem cells. When
transplanted into human body, organs or tissues developed
with patient’s own stem cells can be easily accepted by the
immune system, thus minimizing the rejection reaction [9].
This minimal-invasive implantation of stem cells combined
with the cell-seeding technique mentioned in the previous
section will make a synthesized bioprosthetic heart valve
that causes minimal rejection reaction when transplanted. By
seeding stem cells in collagen gels under different stress and
pressure, these stem cells will develop into valvular cell and
secrete GAGs that mimic the leaflets and the chordae
tendinae. CG heart valves synthesized with stem cells will
be recognized by human body as its own organs instead of
foreign objects, therefore can be easily accepted by the
immune system and will not cause auto-immune diseases or
rejection reaction. Patients who received CG heart valve
transplantation will not need to take medications to relieve
rejection reaction. In this way, artificial heart valves
synthesized with seeding stem cells onto CG material will be
a more effective bioprosthetic heart valve for
transplantation.
FIGURE 6 [8]
Valvular-Cell-Seeded Collagen Gel Experiencing
Multi-Axial Stress
BENEFITS COMPARING TO CURRENT
HEART VALVE SUBSTITUTES
CG artificial heart valve, manufactured with cell
seeding technique and minimally-invasive implantation of
stem cells, is a more reliable artificial heart valve comparing
to existing substitutes used in heart valve transplant
surgeries. Comparing to mechanical heart valves and
bioprosthetic heart valves, a CG heart valves is a more
sustainable medical product. Its effectiveness, accessibility
and safety will greatly promote the well-being of patients
who are suffering from valvular diseases and thus improve
patients’ quality of life.
FIGURE 7 [8]
Valvular-Cell-Seeded Collagen Gel Experiencing
No Stress
Comparison with Mechanical Valves
CG heart valves have definite medical advantages
comparing to existing mechanical heart valves. Comparing
to current mechanical valve, which are made of metal and
plastic, CG material are biologically more similar to human
tissue. Unlike rigid mechanical valves, CG valves are made
of soft collagen that will not lyse blood cells when blood
flow through the leaflets. Patients receiving CG valves will
not be suffering under thrombus formation, which is blood
clotting caused by lysed blood cells collecting at narrow
Minimally-invasive Implantation of Stem Cells
Other than the structural design, CG material can also
be manipulated to mimic the genetics of patients. A preclinical research published by the Journal of the American
College of Cardiology has shown the possibility to combine
minimally-invasive implantation of autologous cells, also
known as stem cells, with tissue engineering to create
artificial heart valves that will decrease rejection reaction
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Zixie Liang
Muyun Zhao
regions of blood vessels [10]. Thus they can stay away from
life-long anticoagulants therapies that are fairly expensive.
Patients who need to take anticoagulant spend 3,000 dollars
every year on the medication. At the meantime they also
have to live with the life-threatening side effect of the
medication, which is excessive, non-stop bleeding when
injured [11]. In this sense, a CG artificial heart valve is a
much safer and cost-effective option comparing to a
mechanical heart valve. It saves the money from long-term
medication and reduces life-threatening side effects, thus
improving patients’ quality of life by making their lives less
painful and more enjoyable.
FIGURE 8 [12]
Table of Median Waiting Time for Heart Transplant
POTENTIAL PROBLEMS AND FUTURE
RESEARCH
Comparison with Bioprosthetic Valves
When comparing to existing bioprothetic valves, CG
valves still has its advantages. Current bioprosthetic tissue
valves are made of chemically treated human or animal
organs. For human tissue transplantation or homograft, the
time it takes to find a matched donor is incredibly long.
According to the national data collected by U.S. Department
of Health & Human Services, The median waiting time for a
heart transplantation surgery varies from 62 to 726 days.
This means a dying patient might need to wait for about two
years to get a matching organ that can save his or her life.
The supply of tissue valves from human donors cannot keep
up to the growing needs of the patients. When time means
life, this this process shows severe disadvantages [12]. CG
valves can be synthesized using valvular cells or stem cells
taken from the patients. This process will take less time and
save more lives. Comparing to waiting for organ donor, CG
heart valves have better accessibility. The other option,
tissue valves taken from animal species and treated
chemically tends to carry viruses and other blood transmitted
diseases [5]. It also causes severe rejection reaction when
transplanted into human body. CG heart valves, which are
synthesized in lab, are free of blood transmitted diseases. Its
biological properties matches with the genetics of human
body therefore will not evoke rejection reactions. Comparing
to current tissue valves, CG artificial heart valves offer a
more accessible and safer choice to patients, so that they can
receive transplant surgeries in a short amount of time and do
not have to worry about blood borne diseases or rejection
reaction. This will greatly promote patients’ well-being thus
making CG heart valve a more sustainable medical device.
Mechanical Issue: Bioprosthetic Heart Valve
Degeneration
Despite all the technical and ethical advantages, like all
new technologies, CG heart valve has its own deficiencies.
One predicted mechanical deficiency is the bioprosthetic
heart valve degeneration or fatigue, which means the “wearout” of bioprosthetic heart valves [13]. Unlike mechanical
heart valves that are made of metal, plastic and other
materials with long duration, heart valves made with
biomaterials last for at most ten years. A young patient who
receives a bioprosthetic heart valve transplant surgery will
need another operation after ten years. This adds great risk
and economic burden to this patient’s family [14]. Why do
bioprostetic heart valves fail? A study done on the
degeneration of bioprosthetic heart valves shows that the
fatigue of heart valves is mainly caused by the molecular
damage of cuspal collagen and loss of glycosaminoglycans
(GAGs) [13]. In a human heart, blood is pumped through
aortic valves at high speed. The mechanism of high speed
fluid flowing through the cusps, or tips, of the heart valve
will create increasing stress on the cusps. Under this highstress environment, type-I collagen molecules on the cusps
will be stretched and distorted. At the same time, GAGs
stored in the cusp will be removed constantly, causing a
decrease in the flexibility of heart valves [13]. These two
factors together will severely damage the tissue of cusps of
the heart valve, making it unable to block the unnecessary
blood flow back to the heart, therefore causing the fatigue of
a heart valve. In live heart valves, human body will keep
generating new collagen molecules and GAGs to replace the
damaged and lost ones. However, artificial heart valves
cannot regenerate like live heart valves do. Collagen and
GAGs are the main components of CG artificial heart valves.
When these two components are damaged and cannot be
regenerated, CG heart valves will have issue of degeneration.
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Zixie Liang
Muyun Zhao
This mechanical deficiency need to be fixed before CG
artificial heart valves can be put onto the market.
A potential solution to this problem is the integration of
stem cells into CG material. As mentioned before, stem cells
are unspecialized body cells that have the potential to
develop into any type of cell. Implantation of stem cell into
CG materials under specific stress conditions will trigger
these stem cells to develop into valvular cells. The
implantation of stem cells into CG heart valves can
minimize rejection reaction because the genetic of CG heart
valves containing stem cell will match the genetic of the
patient’s body. The immune system will recognize the CG
heart valve as a part of the body therefore won’t attack it.
Furthermore, if the body recognizes the stem cells inside the
CG heart valves, this artificial heart valve made with
biomaterial will have the possibility to turn into part of the
body [15]. This means the body cells implanted in CG
material will regenerate when damaged by blood flow,
therefore resolving the issue of bioprosthetic heart valve
degeneration. An artificial heart valve that regenerates and
grow as a real organ do not need to be replaced over time,
thus reducing the risk of reoperation and the economic
burden on the patient. Further research is still necessary to
make it possible, but once this technical issue is resolved,
CG heart valve will greatly improve the patient’s quality of
life.
most people choose to offer the more reliable although more
expensive product in contrast with the cheaper but less
reliable product [16]. This conclusion is based on the
utilitarian theory and the rights of person. The utilitarian
theory states that in order to come to a conclusion about
what good and bad, people need to consider the party of
interest and possible outcome [16]. In this case, the party of
interest is patients who need heart valve transplant surgery,
which includes the wealthy and the poor. Possible outcome
is life and death of patients. A more reliable artificial heart
valve will save more lives, but its affordability will eliminate
the poor patients from accessing it. At this point the rights of
person need to be taken into consideration. If given all
patients the right to choose between these two products,
patients will obviously choose the more reliable product that
will save their lives. Therefore a bioengineer who also
values ethics will able to conclude that, the more reliable
although more expensive product, in this case the CG heart
valve, is a more ethical choice for patients. It should be put
onto market although future research to lower cost is
necessary.
A PROMISING MATERIAL WITH A
BRIGHT FUTURE
A large number of patients suffering under valvular
disease worldwide each year, and that number is still rapidly
increasing. Due to the large demand and deficiencies in
current existing heart valve substitutes, it is necessary to
develop a new artificial heart valve that is safer and can be
manufactured quickly to meet the increasing demand.
Collagen glycosaminoglycans, a new synthesized
biomaterial meets all the requirements above. Collagen and
glycosaminoglycans both exist in human heart valves;
therefore this material mimics human tissue and has low
antigenicity. CG material can be synthesized in labs using
cell-seeding technique combining with minimally-invasive
implantation of stem cells, enabling it to have a stable
structure and minimal rejection reaction. Comparing to
traditional mechanical valves and bioprosthetic tissue valves,
CG heart valve has the smallest side effect. It is a safe, clean
and ethical choice for transplantation surgery. However,
current model of CG heart valve still have some deficiency
such as low duration time due to loss of collagen and GAGs,
and difficulty to balance between cost and utility of this new
medical product. All in all, CG heart valve is a promising
product. It will greatly promote the well-being of patients
suffering under valvular disease by providing a more
accessible, more effective and safer choice of artificial heart
valve. Its accessibility, safety and effectiveness make it a
more sustainable and competitive medical product [17]. It
Ethical Concern: Balancing Cost and Utility
Another issue with CG artificial heart valves is the
ethical balance between engineering and marketing, between
cost and utility [16]. CG heart valve, being a new technology,
is going to cost several thousand dollars more than existing
artificial heart valves when it first comes to market.
Although it is more advanced, it will be less affordable
comparing to existing technology. From the engineering
point of view, CG heart valves are more advanced medically,
therefore is a safer choice for patients and will save more
lives. However, from the marketing point of view, the high
cost of this new technology will stop some patients from
pursuing it, making it not affordable to patients with
economic difficulty. With a smaller market, CG heart valves
will save fewer lives, thus making it a less sustainable
product. It is hard to maintain the ethical balance between
engineering and marketing. What will be better to the
patients? Will it be the more reliable but more expensive CG
heart valves, or the less reliable but more affordable artificial
heart valves that are currently on the market? A hypothetical
case study performed in a graduate bioengineering class
discussed the ethical balance between cost and utility of a
newly developed medical product. The graduate
bioengineering students voted on this case and the result is
8
Zixie Liang
Muyun Zhao
will save millions of lives in the future, although further
research is necessary before it can be put onto market.
http://www.heart.org/HEARTORG/Conditions/Arrhythmia/
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2.12.2008. Vol. 14, Issue 1, p93-101. 9p.
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Well-Being.” United Nations Development Programme.
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ACKNOWLEDGEMENT
We would like to thank the doctors and researchers
who devote themselves on heart valve replacement surgeries
and its development. We also want to thank the University
of Pittsburgh Swanson School of Engineering for offering us
an opportunity to investigate deeply into a certain
technology in our future field of study. We also greatly
appreciate the staffs in the library and writing center for
providing us with abundant links to resources and helping us
with this paper. Finally we would like to thank our peer
advisor for sharing her past experiences on constructing a
conference paper.
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