Artificial Heart

ARTIFICIAL HEART
A PROMISING APPROACH IN ARTIFICIAL ORGANS

Liliana Agostinho, 65109 and Joana Paulo, 72455
Master in Biomedical Engineering, 4th year, 2nd semester 2012

ABSTRACT
The emerging need of finding solutions on the medicine field appeals for high
technology intervention. The artificial organs’ development makes use of that
technology, not only using biomechanical techniques but also, and more recently,
cellular and tissue engineering allied to nanotechnology, to improve biocompability.
This paper makes an overview about what has been done in the field and focus the
particular case of the heart as an artificial organ, the different equipment and a future
perspective.

I. INTRODUCTION annual need for organ replacement therapies
increases by about 10 percent each year.
One of the greatest advancements in the The first approaches to artificial organs
world of medicine has been the ability to only used synthetic components; however,
create artificial organs that are able to restore we can now talk in “biohybrid” organs, which
the proper function of a patient’s body. By combine synthetic and biologic components,
definition, an artificial organ is “a man – made often incorporating multiple technologies
device that is implanted into the human body to involving sensors, new biomaterials, and
replace one or many functions of a natural innovative delivery systems. [3]
organ, which usually are related to life support”. The history of artificial organs started in
The main reasons for developing these devices 1885, when Frey & Gruber build and use the
include: first artificial heart–lung apparatus for organ
o Life support to prevent imminent death perfusion studies. Their device relies on a
while awaiting a transplant; thin film of blood and included heating and
o Dramatic improvement of the patient's cooling chambers, manometers, and
ability for self – care; sampling outlets, which permits monitoring
o Improvement of the patient's ability to of temperature, pressure, and blood gases
interact socially; during perfusion. [4] Since that time, little
o Esthetic restoration after cancer surgery or steps were taken towards the current
accident. [1,2] variability available.
The first case is the most critical and the one The most obvious example may be the
that provides greater challenges for medical dialysis machine, which although it implies a
and engineer community. Nowadays, the continuous power supply, it completely
average life expectancy is high due to better replaces the kidney’s function. There are
healthcare, fact coupled with shortage of already other artificial options for the brain,
organ donors, so organ assistance and ear, eye, heart, limbs, liver, lungs, pancreas,
substitution devices will play a larger role in bladder, ovaries, uterus and trachea.
managing patients with end-stage disease by There’s a huge expectation that artificial
providing a bridge to recovery or a organs would be superior to ordinary donor
transplant. For example, in the U.S. alone, the organs in several ways. They can be made to

ARTIFICIAL HEART, A PROMISING APPROACH IN ARTIFICIAL ORGANS

order more quickly than a donor organ can improved for providing an effective long-term
often be found; in a regenerative medicine treatment or cure of type 1 diabetes. [10, 11]
domain, it’s possible to construct an organ
being grown from a patient's own cells, so
there’s no need for immunosuppressant
drugs to prevent rejection.

II. STATE OF THE ART

The development of an artificial
implantable pancreas for treatment of diabetes
occurs since 1998 and is based on three
Figure 1: The Bioartificial Pancreas using Islet Sheet technology.
fundamental components: a blood glucose
monitor, an insulin pump and a control system. On July 2011, in Sweden, an artificial
The goals of this device are the prevention or trachea, fully synthetic, tissue – engineered,
delay of chronic complications of diabetes, as was successfully transplanted into a late –
well as less patient inconvenience and stage tracheal cancer patient. The organ was
discomfort than with multiple glucose self- created entirely in the lab, using a scaffold
tests and insulin injection. [5] The glucose built out of a porous polymer, and tissue
sensor consists on an immobilized enzyme and grown from the patient's own stem cells
an interface to an electrochemical transducer. inside a bioreactor designed to protect the
The main problem to overcome is the organ and promote cell growth. [12]
progressive loss of function and lack of
reliability of the sensor, caused by tissue
reactions, such as inflammation, fibrosis and
loss of vasculature, harming time precision. [6]
Now there are two available models for
glucose sensors, MiniMed CGMS and
GlucoWatch. [7] The pump itself is placed
internally and injects continuously insulin on
peritoneal cavity. Figure 2: Artificial trachea after two days of cell growth, just
before being implanted into the patient.
According to a CNN publication (March
2012), this device is currently on a trial phase The first artificial organ for substituting
and getting good results. [8] liver function was the Extracorporeal Liver
Another type of approach is the Assist Device (ELAD®), a bedside system that
bioengineering one. A tissue containing islets treats blood plasma, metabolizing toxins and
of Langerhans is implanted, which would synthesizing proteins just like a real liver
secrete the amount of insulin, amylin and does. This device is used to extend patients’
glucanon needed and deficient because of the lives until a liver transplant becomes
islets and beta cells destroyed by the disease. available, and it’s being explored if it can
They can be cells collected from animals or relieve the burden on the patient’s liver
designed from stem cells, and they are enough so that it can regenerate itself. [13]
encapsulated to block the immune response On October 2006, it was noticed the world’s
and eliminate the requirement of first bioartificial liver has been grown from
immunosuppressive drugs. [9]
stem cells by British scientists. The result liver
Microencapsulation techniques are being was the size of a coin but the same technique

2


can be employed to grow full-size livers. circulates arterial blood, arriving from the
Fifteen years from that time, it was predicted lungs, where it has been oxygenated.
these livers can be implanted into patients. [14, Each half can be then cloven in two
15] chambers, the atrium and the ventricle. The
HepaLife, a company in Boston, announced ventricles are separated from the atria by
on 2008 the latest positive results of tests of its atrioventricular (AV) holes, where are placed
PICM-19 cells inside the bioreactor that would, valves that avoid blood reflux. There are the
if it becomes a real product, function as an mitral valve and tricuspid valve, on the left
external liver. This device reduces levels of and right side, respectively. These are
toxic ammonia by 75% in fewer than 24 hours. included on the blood pathway through the
[16] heart, together with the aortic and pulmonary
valves.

Figure 4: Anterior view of the human heart.

The cardiac cycle has two phases: systemic
Figure 3: HepaLife’s device structure. circulation, which begins at a contraction of
the left ventricle, pumping the blood out to the
III. HEART body through the aorta, and ends when it
returns to the heart (right atrium) via superior
1. Anatomy and Physiology
and inferior vena cava; pulmonary circulation,
The heart is a muscular organ, located on starting on the right ventricle, then the blood
the chest, which pumps the blood flows to the lungs where many gas exchange
continuously around the body through the occurs, and it arrives through the pulmonary
cardiac cycle. Its mass is between 250 and veins to the heart again (left atrium).
350 grams and it is about the size of a fist. It
is surrounded by the lungs and protected by 2. Pathology
the ribs and sternum. It’s constituted by a For the heart to fulfill its demanding task,
contractile mass, called the myocardium, apart from a proper blood supply, it needs a
coated inside by a thin membrane, the good functioning of the heart muscle. The
endocardium, and outside by a double – cardiac insufficiency (weakness of the heart
walled sac, the pericardium. muscle) designates a disease in which the
It is divided by the interatrioventricular heart muscle is weakened to such an extent
septum in two functionally separate and that it is no longer capable of pumping the
anatomically distinct units, right and left: on blood sufficiently powerful or adequately fast
the first, only circulates venous blood returned through the blood vessels. In such a case, part
from the peripheral organs; on the second of the blood accumulates upstream of the

3


heart, and we refer to it as a cardiac IV. EVOLUTION: FROM VALVES TO TOTAL
insufficiency or a heart weakness. The cause ARTIFICIAL HEART
for a cardiac insufficiency is to be found in an
acute or gradual injury of the heart muscle due 1. History and Advances of Artificial Heart
to, among others: Valves

• cardiovascular disease; The first mechanical prosthetic heart valve
• heart attack; was implanted in 1952. Over the years, 30
• high blood pressure; different mechanical designs have originated
• heart diseases that directly attack the worldwide. These valves have progressed from
heart muscle or the cardiac valves. simple caged ball valves, to modern bileaflet
valves.
If the symptoms occur all of a sudden and
The caged ball design is one of the early
rather quickly, we refer to it as an acute
mechanical heart valves that use a small ball
cardiac insufficiency. The chronic cardiac
that is held in place by a welded metal cage.
insufficiency, in contrast, often develops
The ball in cage design was modeled after ball
slowly and gradually, in most cases over a
valves used in industry to avoid backflow.
period of several months or years. [17]
Natural heart valves allow blood to flow
The weak heart muscle causes the patients
straight through the center of the valve. This
to feel symptoms that result from the fact
property is known as central flow, which keeps
that the heart is no longer capable of
the amount of work done by the heart to a
providing a sufficient blood supply for the
minimum. With non-central flow, the heart
body and blood accumulates upstream of the
must work harder to compensate for the
heart. Early symptoms of a cardiac
momentum lost due to the change of direction
insufficiency are:
of the fluid. Caged-ball valves completely block
• reduced physical fitness; central flow; therefore the blood requires more
• shortness of breath during hard physical energy to flow around the central ball. In
activity, when climbing stairs or addition, the ball may cause damage to blood
exercising; cells due to collision. Damaged blood cells
• water retention (edema) in ankles and release blood-clotting ingredients; hence the
back of the foot. patients are required to take lifelong
In the further course of the disease the water prescriptions of anticoagulants. [18]
retention may also affect other organs For a decade and a half, the caged ball valve
eventually resulting in a weight gain. In an was the best artificial valve design. In the mid-
advanced case of cardiac insufficiency the 1960s, new classes of prosthetic valves were
patient will feel breathlessness also under designed that used a tilting disc to better
slight physical stress or even when at rest. mimic the natural patterns of blood flow. The
We distinguish between different stages of tilting- disc valves have a polymer disc held in
cardiac insufficiency: [9] place by two welded struts. The disc floats
• low-level with the symptoms occurring between the two struts in such a way, as to
only under hardest physical stress; close when the blood begins to travel
• high-level with symptoms such as backward and then reopens when blood begins
shortness of breath already in a state of to travel forward again. The tilting-disc valves
rest; are vastly superior to the ball-cage design. The
titling-disc valves open at an angle of 60° and
The necessary treatment is determined by
close shut completely at a rate of 70
the stage of the cardiac insufficiency.
times/minute. This tilting pattern provides

4


improved central flow while still preventing designs have increasingly indicated time-
backflow. The tilting-disc valves reduce dependent (5 to 7 year) structural changes
mechanical damage to blood cells. This such as calcification and leaflet wear, leading
improved flow pattern reduced blood clotting to valve failure. Therefore tissue valves are
and infection. However, the only problem with rarely used in children and young adults at
this design was its tendency for the outlet present. [18, 19] On the other hand, mechanical
struts to fracture as a result of fatigue from the valves made with high strength
576 repeatedNair et al
Kalyani ramming of the struts by the disc. biocompatible material are durable and have
long-term functional capability. However,
mechanical valves are subject to thrombus
deposition and subsequent complications
resulting from emboli, and so patients with
implanted mechanical valves need to be on
long-term anticoagulant therapy. Currently,
mechanical valves are preferred except in
elderly patients or those who cannot be put
under anticoagulant therapy, like women
who may still wish to bear children, or
hemolytic patients.

2. Mechanical Heart Valve
Figure 1. Caged ball valves. (a) Hufnagel–Lucite valve, (b) Starr–Edwards, (c) Smeloff–Cutter,
Figure 5: Caged ball valves. (a) Hufnagel–Lucite valve, (b)
(d) McGovern–Cronie, (e) DeBakey–Surgitool and (f) Cross–Jones.
Starr–Edwards, (c) Smeloff–Cutter, (d) McGovern–Cronie, (e) Prosthetic Heart Valves are fabricated of
DeBakey–Surgitool and (f) Cross–Jones.
2. History of mechanical valve different biomaterials. Biomaterials are
The pioneering efforts of Dr. Charles Hufnagel, who made the first successful placement of a designed to fit the peculiar requirements of
totally mechanical valvular prosthesis, started the era of artificial heart valves 1979.
Bileaflet valves were introduced in [1,2]* . Hufnagel
achieved this feat in 1952, byswing aopen completely,ball occluder into the
The leaflets inserting Plexiglas cage containing a parallel blood flow through the specific chambers of
descending thoracic aorta. The first implant of a mitral valve replacement in its anatomic
position to the direction the Starr-Edwards prosthesis was put the clinical use [3].
took place in 1960, when of the blood flow. The the heart, with emphasis on producing more
A number of similar caged ball designs appeared subsequently; like the Magovern–Cromie,
DeBakey–Surgitool, Smeloff–Cutterwere not figure 1). valves. The
bileaflet valves prostheses (see ideal central flow and reducing blood clots. Some
Even though caged ball valves have proven to be durable, their centrally occluding design
bileaflet valve constitutes the majority of of these biomaterials are alumina, titanium,
results in a larger pressure drop across the valve and higher turbulent stresses, distal to the
valve. Their relatively large profile increases the possibility of interference with anatomical
modern valve designs. These valves are carbon, polyester and polyurethane.
structures after implantation. This led to the development of low-profile caged disc valves in
the mid-1960s. The Cross–Jones, Kay–Shiley and Beall caged-disc designs were introduced
distinguished mainly for providing the The mechanical properties of these
during 1965 to 1967 [4]. These valves were used exclusively in the atrio-ventricular position.
However, because of high complication rates, this model soon fell into disuse.flow
closest approximation to central biomaterials involve how a material responds
The next significant development was the introduction of tilting disc valves by Bjork–
Shiley in 1967 [4]. The in a naturalthis valve involves a [19]
achieved design concept of heart valve. free-floating disc, which in to the application of a force. The three
the open position tilts to an angle depending on the design of the disc-retaining struts. In
the open position it acts like an aerofoil, with the blood flowing over and around it, thus
fundamental types of forces that can be
minimising the flow disturbance. The original Bjork–Shiley prosthesis employed a Delrin applied are stretching (tension), bending, or
* References in this paper are not in journal format twisting. Materials respond to the forces by
deforming (changing shape). An elastic
response is reversible, while an inelastic
response is irreversible. In the elastic region,
Figure 6: Bileaflet valve models. (a) St. Jude Medical, (b) an elastic modulus relates the relative
Carbomedics and (c) Duramedics.
deformation a material undergoes to the
Biological tissue valves are made from stress that is applied. The transition between
porcine aortic valves or fabricated using elastic deformation and failure occurs at the
bovine pericardial tissue and suitably treated yield point (or stress) of the material. In
with gluteraldehyde to preserve them and to designing a component with the material, an
remove antigenic proteins. Clinical inelastic response is considered failure.
experiences with different tissue valve Failure can be plastic deformation or ductile

5


failure. It can also be breaking, including components (strut failure, poppet escape,
brittle failure or fracture. Mechanical ball variance);
properties of a material in the range of elastic  Reoperation for any other reason (e.g.:
behavior include its elastic modulus under hemolysis, noise, and incidental).
tension and shear stresses, its Poisson’s ratio, The performance of mechanical valves is
its resilience, and its flexural modulus. The in several ways related to valve design and
transition to failure is denoted by the yield structural mechanics. The design
stress or breaking strength of the material. configuration affects the load distribution
During the last fifty years of development, a and dynamics of the valve components,
set of material requirements for valves have which in conjunction with the material
evolved which can be summarized as [18] properties determine the durability and
below: successful performance of the valve. The flow
 Cause minimal trauma to blood elements engendered by the geometry of the
and the endothelial tissue of the components determines the extent of flow
cardiovascular structure surrounding the separation and high shear regions. The
valve; hinges in the bileaflet and tilting disc valves
 Show good resistance to mechanical and can produce regions of flow stagnation,
structural wear; which may cause localized thrombosis, which
 Minimize chances for platelet and may in turn restrict occluder movement. [18,
thrombus deposition; 19]

 Be non-degradable in the physiological Biochemical degradation and mechanical
environment; wear is often inter-related, since degradation
 Neither absorb blood constituents nor accelerates material removal from surface
release foreign substances into the blood; due to wear, which in turn accelerates the
 Have good processibility (especially rate of the biochemical reaction by
suitable for sterilization of the device by continually exposing new surface to the
appropriate means) and take good surface corroding media. The use of large surface
finish. areas of exposed metal in valves is often
Problems that interfere with the quoted as leading to thromboembolic
successful performance of valves can be complications. A cloth covering on the metal
grouped as below: can sharply reduce these complications, but
 Degradation of valve components; other problems associated with fabric wear
 Structural failure; or uncontrollable tissue proliferation that
 Clinical complications associated with the restricts flow can arise. The degradation of
valve. the silicon-rubber balls used in ball valves
Clinically, valve failure has been provides a good development in mechanical
considered to be present if any of the heart valve prosthesis example of
following events require reoperation and/or deterioration caused by biochemical
cause death: incompatibility and also leads to mechanical
 Anticoagulant-related hemorrhage (ACH); failure.
Under the conditions used, namely high
 Prosthetic valve occlusion (thrombosis or
flow rate, all of the materials are reasonably
tissue growth);
non-thrombogenic. Very small surface cracks
 Thromboembolism;
have been demonstrated to initiate thrombus
 Prosthetic valve endocarditis (PVE);
formation, presumably due to a small volume
 Hemodynamic prosthetic dysfunction,
of stagnant flow. In spite of desirable
including structural failure of prosthetic

6


characteristics of the biomaterials used in the heart attack. “Stem cells help reduce cardiac
heart valves prosthesis, problems of infarction and improve ejection fraction,”
thromboembolic complications continue to reveals Totey. Also, stem cells can be injected
occur at the rate of 1 to 3% per patient year in patients with cardiac myopathy. “Cardiac
in these valves. The mechanical stresses myopathy is a condition, in which, the heart
induced by the flow of blood across the valve muscle gets inefficient. And therefore, the
prosthesis have been linked to blood damage pumping efficiency of the heart or ejection
and activation of formed elements (red blood fraction as it is called, decreases to the extent
cells, white blood cells and platelets) that the patient starts to feel breathless and
resulting in the deposition of thrombi in unable to function and heart failure occurs,”
regions of relative stasis in the vicinity of the explains Dr Ashok Seth, Chairman and Chief
valve. [20] Cardiologist, Max Heart & Vascular Institute,
The pressure distribution on the leaflets, Delhi. [21]
and impact forces between the leaflets and After a person gets a heart attack, the
guiding struts are also being experimentally cardiomyocites can die within 20 minutes
measured in order to understand the causes due to the occlusion of the artery. Once dead,
of strut failure. The flow through the the heart starts remodeling itself to maintain
clearance between the leaflet and the housing the normal cardiac output and to meet the
at the instant of the valve closure and in the demands of the body. Stem cells, if injected at
fully closed position, and the resulting wall the appropriate time, help in regenerating
shear stresses within the clearance are also the damaged muscles and healing the scarred
suggested as being responsible for clinically tissue, thereby, bringing the cardiac functions
significant hemolysis and thrombus to almost normal without causing
initiation. Further improvements in the remodeling.
design of the valves based on the closing
dynamics as well as improvements in
material may result in minimizing
thromboembolic complications as well as
occasional structural failure with implanted
mechanical valves. [18-20]

3. Heart Cloning
Existing methods of treatment are not Figure 7: Heart steam cells were injected in the "skeleton" of a
heart and placed it in an incubator. Days later, the new heart
quite effective in repairing damaged heart started beating.
muscle in end-stage cardiovascular diseases.
New research suggests that stem cells can Studies undertaken in small and big
regenerate into heart cells. Nandini animals have proved that when injected with
Patwardhan traces the significance of stem stem cells, they have the ability to home in on
cells in the cardiovascular segment. [13] the diseased muscles and then change
Stem cells can be used for any kind of lineage. But the question that arises is, how
myocardial infarction (heart attack) like do these cells multiply into the desired
acute myocardial infarction, chronic muscle cells? “For instance, when we inject
myocardial infarction and congestive heart stem cells into the heart, they know exactly
failure. However, it is advisable to treat where they have to home in, based on the
patients with myocardial infraction at the chemo attraction. The dead muscle gives out
earliest, preferably within 20-25 days of certain chemocytes, which attract stem cells

7


to go there and convert into that lineage,” end-stage heart failure. [22]
states Shah. “Before we ventured on to You may need a TAH for one of two reasons:
humans, we have seen this being proved  To keep you alive while you wait for a
through various experiments on small and heart transplant;
big animals,” he adds. Unfortunately, there is  If you're not eligible for a heart transplant,
no way to control multiplying stem cells into but you have end-stage heart failure in
different non-desirable tissues. “However, both ventricles.
there is not a single report which shows that The TAH is attached to your heart's upper
stem cells, after injection into particular chambers—the atria (AY-tree-uh). Between
organ, have developed into undesirable the TAH and the atria are mechanical valves
tissue or cells. That shows that stem cells that work like the heart's own valves. Valves
injection are quite safe,” reveals Totey. [21] control the flow of blood in the heart. (For
The process of injecting stem cells is not a more information, go to the Health Topics
very long drawn process. “We inject stem How the Heart Works article.)
cells by the intra-coronary method. This Currently, there are two types of TAH.
means, we inject them into the coronary They're known by their brand names: the
artery—the culprit artery of the patient. The CardioWest and the AbioCor. The main
muscle which is subtended by this artery, difference between these TAH’s is
which has been blocked, is our area of CardioWest is connected to an outside power
interest,” discloses Shah. source and AbioCor isn't.
A guiding catheter is put into the coronary CardioWest has tubes that, through holes
artery. Then a wire is sent over it into the in the abdomen, run from inside the chest to
culprit artery. A balloon is sent on the wire. an outside power source.
Once inside the artery, the balloon is inflated
to stop the blood supply for a couple of
minutes. A lumen is inserted, through which a
million stem cells, cultivated from the bone
marrow of the patient, are injected in the
artery. The stem cells reach the target area,
where they have to home in. The balloon is
inflated till the stem cells are injected so that
blood does not flow during the process. “We
keep the balloon inflated for two to three
minutes, inject the stem cells and deflate the
balloon. Again after three to four minutes, we Figure 8: A - shows the normal structure and location of the
heart. B - shows a CardioWest TAH. Tubes exit the body and
repeat the procedure till all the stem cells are
connect to a machine that powers and controls how the
injected,” explains Shah. “On an average we CardioWest TAH works.
inject 100 million stem cells. However, we
are doing it arbitrarily right now,” he adds. AbioCor is completely contained inside the
chest. A battery powers this TAH. The battery
4. Total Artificial Heart is charged through the skin with a special
A total artificial heart (TAH) is a device magnetic charger.
that replaces the two lower chambers of the Energy from the external charger reaches
heart. These chambers are called ventricles the internal battery through an energy
(VEN-trih-kuls). You may benefit from a TAH transfer device called transcutaneous energy
if both of your ventricles don't work due to transmission, or TET. [22]

8


An implanted TET device is connected to - will provide a substitute for natural organs.
the implanted battery. An external TET coil is There has been considerable
connected to the external charger. Also, an improvement in the durability and functional
implanted controller monitors and controls efficiency of mechanical heart valves. These
the pumping speed of the heart. improvements have been by gradual
incremental improvements coupled with a
few revolutionary advances like the
introduction of tilting disc/bileaflet valves.
Despite all these improvements,
complications (though their rates are very
low) continue to be associated with their use.
All current models of mechanical heart valves
need anti coagulation therapy to minimize
the risk of thrombosis and embolism.
Management of anticoagulation levels and
Figure 9: A - shows the normal structure and location of the bleeding are other concerns.
heart. B - shows an AbioCor TAH and the internal devices that Recent trends in the choice of materials
control how it works.
indicate a preference towards soft occluder
Therefore, a TAH usually extends life for materials. One team in Germany is working
months beyond what is expected with end- towards bileaflet valves with soft occluders.
stage heart failure. If you're waiting for a Medtronic– Hall also had announced that
heart transplant, a TAH can keep you alive they will be looking for a valve with soft
while you wait for a donor heart. It also can occluder in the near future. The advantages
improve your quality of life. However, a TAH of using soft occluder material are many.
is a very complex device. It's challenging for They absorb the impact forces generated
surgeons to implant, and it can cause during valve closure, there by reducing the
complications. [22] chance of suture dehiscence. The reduction
Currently, TAHs are used only in a small in the impact forces also reduces the load
number of people. Researchers are working that needs to be transferred to the
to make even better TAHs that will allow surrounding tissues through the suture ring,
people to live longer and have fewer reducing the irritation caused by the
complications. continuous movement at the cloth–metal
V. CONCLUSION interface. Another improvement caused by
the soft occluder is the reduction in the
Some devices - such as the left ventricular probability of occurrence of cavitation and
assist device and bioartificial liver - will cavitation damage. This has been reason-
provide assistance while new therapies ably established by various studies
incorporating stem cells, gene therapy, or conducted on Chitra heart valve, which
engineered tissues are employed to repair or showed that even at very high loading rates,
replace the damaged organ. Until these new the chance for cavitation in valves with soft
therapies can be developed and tested, occluders is minimum.
medical devices will play a crucial role in
facilitating organ recovery and, perhaps,
organ salvage through natural repair
mechanisms. Where organ recovery is not
possible, artificial organs - when fully refined

9


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Liebert Inc.; laboratorio-1316632 (last login in 22/05/2012);

[11] JL, Lee et al., A newly developed [22] SLEPIAN, M. et al., The Syncardia
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cell sheet engineering, Cell Transplant. 2008,
17(1-2):51-9;

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