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A Comprehensive Review of the Blood Vessel Tissue Engineering Market

Nicolas A. Etcheverry
UCLA Graduate Division of Bioengineering
Keywords: tissue engineering, blood vessels, vascular graft, cardiovascular disease,

ABSTRACT. With cardiovascular disease resulting in such a large
percentage of death worldwide, the push for tissue engineered
vascular grafts has led to a surge in pre-clinical and clinical studies to accelerate the production of these devices. While traditional non-biological grafts do serve as treatment options at the
moment, the future is bright for development of tissue engineered blood vessels, and research scientists are continuing to
push for this as a viable treatment option in the future.

through. Fenestrated capillaries have larger openings ranging from
30 to 40 μm in diameter, and red and white blood cells can pass
through.

HEALTHY TISSUE
A functioning cardiovascular system is composed of the heart,
arteries, veins, and capillaries. This system serves to deliver oxygen
to all the tissues and organs throughout the body. Oxygen initially
moves from the lungs and into the heart for systemic delivery. Arteries deliver the oxygen to the smaller diameter capillaries for
blood absorption, and veins transfer deoxygenated blood back to
the heart. Deoxygenated blood is pumped back into the lungs for
oxygenation.

FIGURE 2: Blood Vessel Anatomy

With regards to size of the different blood vessels, arteries and
arterioles (smaller arteries) range from 10 μm to 4 cm in thickness.
Veins and venules (smaller veins) range from 10 μm to 3 cm in
thickness. The pressure ranges for arteries and veins are 80 to 120
mmHg and 10 to 15 mmHg, respectively. Metarterioles connect arterioles and venules together in order to bypass the capillaries and
reduce the blood pressure in the capillaries.
DISEASED TISSUE

FIGURE 1: Cardiovascular System Anatomy

When looking at the anatomy of the blood vessels, distinct structural tissue organization can be visualized. Blood vessels are made
up of three tissue layers: the tunica intima, the tunica media, and
the tunica externa. The tunica intima is made up of one layer of
endothelial cells, and it is supported by the internal elastic lamina.
The tunica media is made up of smooth muscle cells and elastic tissue, and the tunica externa is composed of fibroblasts, collagen,
and nerves. Capillaries, which is where most the oxygen and nutrient absorption occurs, is only made up of endothelial cells. Three
types of capillaries are seen biologically: continuous, fenestrated,
and sinusoidal. Continuous capillaries have uninterrupted endothelial cell linings, and only small molecules like water and ions can
pass through. Fenestrated capillaries have pores 60 to 80 nm in diameter, and proteins as well as small molecules can diffuse

Most blood vessel related diseases can be attributed to the accumulation of calcium and fatty materials like cholesterol on the
interior of blood vessel walls. This build-up of plaque is called atherosclerosis, and it leads to many cardiovascular problems. Atherosclerosis reduces the elasticity of blood vessel walls, and it hardens the arteries. Because the fatty deposits block the flow of blood,
less blood travels through, and blood pressure increases. Inflammatory responses can also occur as macrophages and white blood
cells accumulate on the plaque, further increasing the blood flow
blockage. The progression of atherosclerosis is a slow process that
typically occurs over the course of four decades. Plaque accumulation can be attributed to dietary and lifestyle factors, and the side
effects aren’t very prevalent until the atherosclerosis has progressed to a more dangerous stage.
Atherosclerosis leads to many other blood vessel complications
that include aneurysms and hypertension. An aneurysm is the
weakening of a blood vessel wall, and it leads to a balloon-like bulge
developing in the artery. As the aneurysm increases in size, so does
its risk of rupturing. Rupturing leads to bleeding, hypovolemic
shock, and rapid death. Hypertension is defined as having an abnormally high blood pressure, and it is associated with a shortened

life expectancy. It is a silent killer because it is difficult to know how
high ones blood pressure is without daily cuff-based measurements. Persistent hypertension can lead to peripheral artery disease, chronic kidney disease, myocardial infarction, stroke, and aneurysms.

nearly half of all deaths in Europe at 48% [20] . Cardiovascular disease is also the leading cause of death for women in all countries
in Europe and the main cause of death for men in all the countries
excluding France, the Netherlands, and Spain. Smoking plays a big
role in this disease because of the 1.2 million people killed due to
smoking, and 450,000 people within this group died of CVD as a
result of smoking [20] . Overall, CVD costs the European Union an
estimated 192 billion euros a year, which is astronomically high.
57% is due to health care costs, 21% is due to productivity losses,
and 22% is due to informal care of people with CVD [20]. The main
forms of death from CVD are coronary heart disease and stroke,
which is similar to the US. Coronary heart disease is the most common cause of death in Europe, and it accounts for 1.92 million
deaths in Europe per year. One in six men die from the disease, and
one in seven women die from it as well. Stroke is the second most
common cause death in Europe accounting for 1.2 million deaths,
and one in six women as well as one in ten men die from the disease.

FIGURE 3: Atherosclerosis within an artery

STATISTICS AND MARKET SIZE
Cardiovascular related diseases are the leading cause of death
worldwide, and the magnitude of this statistic greatly emphasizes
the need for tissue engineered vascular grafts. In 2008, 30% of all
global death was attributed to cardiovascular disease. According to
the Center for Disease Control, the breakdown of deaths from cardiovascular diseases can be split up accordingly: 52% as a result of
coronary heart disease, 17% as a result of stroke, 7% due to heart
failure, 6% for high blood pressure, and 4% for disease of the arteries. In the United States, 452,000 people died from coronary heart
disease, and 150,000 people died from strokes in 2003 [30]. These
were the first and third ranked leading causes of death in the US,
respectively. While the causes of death vary for different cardiovascular related illnesses, the cause of the disease can be attributed to atherosclerosis and hypertension leading to blockage of
arteries and higher blood pressure. It was approximated in 2007
that 15.8 million Americans had coronary artery disease, and that
1234 Americans die of coronary artery disease every year [3].
Awareness of the disease is growing, and as a result, the CVD death
rate is slowly declining. Medical improvements are still required to
push for a more dramatic decrease in death though, and hopefully,
tissue engineered vascular products will help with this. More than
81 million Americans have some form of CVD, and the costs of CVD
in 2007 amounted to a total of 431.8 billion dollars [30]. Treating
CVD accounted for 17% of the overall US health expenditures, and
the cost is expected to increase to 818 billion dollars in 2030.
According to the 2008 European Cardiovascular Disease Statistics, which was published by the British Heart Foundation and the
Department of Public Health at Oxford, cardiovascular disease
causes over 4.3 million deaths in Europe per year accounting for

FIGURE 4: Geographic distribution of Cardiovascular Market

Once again, cardiovascular disease is the leading cause of death in
the world, and the Worldwide Health Organization estimates that
24 million people will die from cardiovascular related illnesses. Due
to the high costs and large amounts of deaths associated with CVD,
the market size for medical products treating these diseases is very
large. In 2003, the cardiovascular market was estimated at 84.9 billion dollars, and the global cardiovascular market recorded sales of
170 billion dollars in 2010 [8]. The market is expected to grow to
187 billion dollars by 2016, and this consistent increase has allowed
for many companies to compete with a wide array of vascular products [8]. The market is definitely large enough to initially support
niche regenerative medicine focused companies as they attempt
to make tissue engineered vascular grafts the norm for current surgical procedures. Many cellular containing tissue engineered blood
vessels are beginning to enter clinical trials, and the market share
for these products could increase in the next few y
PRODUCTS ON THE MARKET: TRADITIONAL DEVICES
Cordis, a United States based medical company owned by Johnson
and Johnson, focuses on developing stents, catheters and guide
wires for many cardiovascular related diseases. One of its main
products is the CYPHER drug eluting stent. After angioplasty is performed, which involves inserting an inflatable balloon via guide
wire to compress the built up plaque on the artery wall, the stent
is inserted to prevent the artery from closing in on itself. The
CYPHER stent is composed of a stainless steel VELOCITY stent with

a thin coating of sirolimus on its surface in order to prevent overgrowth of normal tissue as the healing process occurs after coronary stent implantation. This is currently the most widely used drug
eluting stent, and it has benefitted more than 3 million people.
While this stent does not fit all of the categories required for it to
be considered a tissue engineering product, tissue engineered
grafts will have to compete with the safer mechanical properties
and consistent drug release of this FDA approved product.

products. Its medical division has developed a wide variety of synthetic grafts for vascular applications. Their products include the
Gore-TEX StretchVascular Graft, the Gore-TEX Bifurcated Stretch
Vascular Graft, the GORE Propaten Vascular Graft, and many others. Gore-TEX vascular products have met the challenges of vascular procedures for 30 years, and these grafts do not require preclotting, resist dilation, and resist infection spreading. Thrombosis
is not an issue with their products, and their different models allow
for a different sizes, stretching capability, and structure configuration for different medical procedures.

FIGURE 5: CYPHER Drug Eluting Stent

Medtronic, another US medical company, also has a drug eluting
stent out on the market, and their device is called the ENDEAVOR.
The stent is composed of a thin cobalt alloy, and it releases the
drug, zotarolimus, which is an immunosuppressant. This prevents
an inflammatory response, and improves clinical outcomes of the
stent. The ENDEAVOR received better inflammation scores compared to the CYPHER at 180 days leading to improved vessel healing. The ENDEAVOR also showed a significant 37% relative risk reduction versus the CYPHER. Both of these drug-eluting stents are
in direct competition with one another and are on the forefront for
treating coronary heart disease surgically. These traditional, safer
products should take up a large portion of the cardiovascular disease market due to their standard features, but recent developments in the tissue engineering field should be pushing for larger
market percentages in the future. These drug eluting stents are not
a long term solution because many arteries can close up again over
time, so cardiac vascular grafts are the next logical predecessor.
ATRIUM is a biomedical company that develops vascular grafts
which are sold in the US as well as in Europe. The company has a
wide array of polytetrafluoroethylene (PTFE) based vascular grafts
which serve as a synthetic replacement for damaged arteries. Their
PTFE product line is comprised of the Advanta SST, the Advanta
VXT, and the Advanta VS. All of these variations of the PTFE vascular graft boast high quality construction, mechanical strength, a
contact minimizing transfer sleeve, and diameter markings. The
Advanta SST allows for vein-like pulsing and handling, and the Advanta VXT contains 60 micrometer pores for fibroblast infiltration.
The thin wall PTFE design conforms well to host blood vessels and
creates a leak proof anastomosis based connection. Clinical studies
have confirmed that these grafts are not likely to become infected
or develop complications like hematoma and seroma formation.
Gore Innovative Technologies relies on its scientific application
of the Gore-TEX (PTFE) to produce fabric, industrial, and medical

FIGURE 6: Gore-TEX Vascular PTFE Graft

Gore and ATRIUM take up another significant percentage of the
cardiovascular disease market. These traditional PTFE grafts are
flexible, reliable, and known to work well for patients suffering
from atherosclerosis in their arteries. Advances in the development
of extracellular matrix proteins and cell isolation have pushed towards more natural and biological grafts, but the tissue engineering companies will also have to compete with these standardized
non-biologic vascular grafts.
PRODUCTS ON THE MARKET: TISSUE ENGINEERED DEVICES
Artegraft has chosen to take a more biologically natural approach by developing a bovine collagen vascular graft. This graft
consists of a fibrous matrix that is tightly woven, cross-linked, and
flexible. It is supposed to be used distal to the aorta for procedures
like arterial bypass and segmental arterial replacement. This scaffold is great for cellular incorporation, which cannot be said for the
above mentioned synthetic grafts. Artegrafts product portfolio is
solely limited to this one device, so its long term stability within the
vascular graft market is questionable. It appears to be a much
smaller company relative to Gore and ATRIUM, so it could be
bought out by another company or fail attempting to compete with
the larger companies. It appears to be targeting more of a niche
market with its collagen scaffold for cell seeded vascular grafts, and
an increase in use of tissue engineered products for invasive surgical procedures would help the company in the long run.
Bio Nova, a leading biosynthetic manufacturer, specializes in collagen based medical devices. This company is located in Australia,
and it has obtained patents in the US, the EU, Australia, and China.
It produces its biomimetic collagen structures by placing a polyester tube inside a sheep. The collagen protein collects on the matrix,

allowing for the creation of a collagen based vascular graft. Their
leading product is the Omniflow II, which has recently passed clinical trials. The Omniflow II consists of collagen on a polyester mesh
endoskeleton, and the mesh provides mechanical strength and durability while the collagen enhances biocompatibility. The Omniflow II has a high radial elasticity, a non-antigenic hemocompatible
surface, as well as a no tissue in growth within the lumen. The Omniflow II has a much lower infection rate compared to other synthetic grafts (PTFE based grafts fall under the synthetic category).
The Omniflow II also had a higher state of being unobstructed or
patency compared to other synthetic grafts as well. The Omniflow
II is similar to Artegraft in that it incorporates biological components into its vascular graft, and the Omniflow has been used by
surgeons in over 20,000 clinical cases worldwide. The use of collagen to create more biomimetic vascular grafts will lead the way for
grafts containing cellular components as well as extracellular matrix proteins.

results in a graft that is the most biomimetic out of all of the previous products listed. This advancement will soon become the norm
and standard solution for vascular grafting, and the improvement
of these cellular grafts should lead to better results and a larger
market share assuming clinical trials go well. Cytograft has clinical
trials ongoing in Europe and South America regarding using the
graft as an access tube for hemodialysis. Another clinical trial is set
to begin involving the use of the graft as a lower limb bypass for
patients suffering from critical limb ischemia.

FIGURE 8: Cytograft’s Cellular Vascular Graft

FIGURE 7: Bio Nova’s Omniflow II

With regards to the European market, the German based company MAQUET has taken a leading role in providing vascular grafts
on a worldwide scale. Its large portfolio of different vascular grafts
puts it in competition with bigger companies like Medtronic and
Cordis in the US. MAQUET provides a lot of the machinery and
equipment used in cardiovascular and general surgery, and its vascular grafts include several variations of the following models: Intergard and Hemashield. These grafts come in many different
shapes and sizes, and they are composed of flexible polyester tubes
with collagen and heparin coatings for cellular migration and
thrombosis prevention. The large company portfolio, not just in
vascular grafting, opens up the company’s options, but it does not
appear to be pursuing any further biological grafting techniques involving cells.
CLINICAL STUDIES
While the companies described above have more modest approaches to vascular grafting, Cytograft chooses to take a riskier,
more novel approach. The California based company has developed a technology to produce cellular vascular grafts made up of
the patient’s own cells by rolling fibroblast sheets around temporary support cylinders. The fibroblast sheets are created by culturing a small dermal biopsy from the patient, and the mature vessels
have the mechanical properties of natural blood vessels. The vessel
lumen is then lined with the patient’s own endothelial cells. This
tissue engineered blood vessel can be used for coronary bypass as
well as hemodialysis access. Cytograft applies tissue engineering
tactics to produce its vascular grafts, and its cellular incorporation

Humacyte is currently recruiting participants for a clinical trial
involving the use of its recently developed acellular biologic vascular graft. The purpose of the clinical trial is to evaluate the safety
and efficacy of the vascular prosthesis as an above the knee bypass
graft in patients with peripheral arterial disease. The clinical trial
began in October 2013, and it is expected to end in December
2015. The human acellular and tubular vascular graft is made up of
collagen and other extracellular matrix proteins, and after implantation, it is anticipated that the collagen matrix will be infiltrated
with host cells and remodeled by the host. This should result in a
vascular structure that is more similar to native vascular tissue, and
it should also improve longevity and reduce chances for infection.
This collagen vascular graft is derived from human tissue to further
prevent any immunogenic response, and the trials will be conducted in Poland, where recruitment is occurring at the moment.
Humacyte is also conducting another clinical trial titled: Safety and
Efficacy of a Vascular Prosthesis for Hemodialysis Access in Patients
with End-Stage Renal Disease. The same human acellular vascular
graft is being tested for a different purpose, and the locations of
the clinical trials are located in North Carolina, Texas, and Virginia.
The study should be completed in September 2015, and it is currently recruiting patients as well.
Tissue Genesis, a regenerative medicine company located in
Honolulu, is currently conducting the clinical trial titled: Feasibility
of the TGI Adipose-derived Stromal Cell (ASC)-Coated ePTFE vascular graft. This study wants to examine the effects of coating a synthetic graft with cells to more closely resemble native vessels and
reduce both thrombosis and stenosis. Tissue Genesis has developed the Tissue Genesis Icellator: Cell Isolation System that takes a
patient’s adipose tissue and isolates the regenerative stem cells in
an automated process, which can then be used for various cell
therapies. With regards to the clinical trial, the stem cell-based
coating from the adipose tissue is sodded onto the internal lumen
of the vascular graft to achieve the intended effects described
above. This single blind study plans to compare the safety and efficacy of the Gore PROPATEN graft, a heparin coated ePTFE vascular
graft, with the adipose stem cell coated ePTFE vascular graft de-

signed by Tissue Genesis. The company hopes to address the clinical need for small diameter blood vessels (4 to 5 mm). Vascular surgery has been very successful in replacing atherosclerotic arteries
that are large in diameter, but as diameter decrease, patency decreases as well. Current treatments for damaged small diameter
veins involve the use of the saphenous vein bypass graft, and Tissue
Genesis wants to eliminate the need for this procedure with a
higher patency for its cell coated vascular graft. The clinical trial is
ongoing and will be completed by September 2015.
MAQUET, located in Germany, is a worldwide leader with regards to providing medical systems to doctors and hospitals. It is
the largest subsidiary of the GETINGE group, and it just recently
successfully completed a clinical trial in order to sell its FUSION vascular graft. The clinical trial was completed in July 2013, and
MAQUET is no marketing the graft to doctors in Europe. The clinical
trial was called Evaluation of FUSION Vascular Graft for Above Knee
Targets, and it involved implanting the graft to examine the safety
and efficacy at 30 days, 6 months, and 1 year. The FUSION graft is
made up of an inner and outer layer. The inner layer is comprised
of expanded polytetrafluoroethylene (ePTFE), and the outer layer
is made of a knit polyester textile, polyethylene terephthalate
(PET). The two layers are fused together with a polycarbonate-urethane adhesive, and the FUSION provides the easy handling of
ePTFE as well as the minimal suture hole bleeding seen in knit polyester grafts.

FIGURE 9: (A) Decellularized Vascular Graft; Immunofluorescent
detection of CD31 (B), CD144 (C), vWF (D) for characterization
of endothelial cells after recellularization

PRECLINICAL STUDIES
In order to develop an ideal tissue engineered vascular graft, the
graft must meet certain requirements. The graft must be biocompatible, have solid mechanical properties, and be easily processable. Two methods currently exist to develop tissue engineered vascular grafts. The first method involves using a bioreactor to create
physiological-like stimuli on cell seeded scaffolds for in vitro tissue
engineered vascular graft maturation before implantation. The
other method involves using the body as a bioreactor after implantation for scaffold/cellular maturation. A lot of emphasis has been
placed on scaffold selection in this tissue engineering field.

FIGURE 10: Depiction of Fibroblasts seeded on collagen and elastin scaffold

Decellularizing a tissue construct involves removing all the cellular components of the tissue while remaining the mechanical components of the extracellular matrix. This can be done through enzymatic of chemical digestion, and many different animal models
have been used in order to generate these biological scaffolds. One
thing to keep in mind is that the composition of the extracellular
matrix is related to the source, so the age and health of the animal
source as well as the harvesting process affects the mechanical and
immunological properties of the scaffold. Decellularizing tissue can
lead to loss of certain ECM components as well.
Even though this procedure is not perfect, many groups have
experimented with decellularized scaffolds for tissue engineered
vascular grafts. In 1999, Sullivan’s research group became one of
the first groups to do so. They successfully decellularized porcine
small intestinal submucosa, wrapped it around a 4 mm mandrel,
and coated collagen in the lumen. They cross-linked the collagen,
and these grafts showed good patency and physiological endothelialization [59]. Haverich’s group made a trypsin-based decellularized tissue from aortas, and they recellularized the constructs
within a bioreactor using human endothelial cells, and myofibroblasts. The immune response after implantation was decreased [1].
Mayer’s group decellularized iliac vessels using a chemical method,
and they seeded endothelial progenitor cells (isolated from sheep
blood) on the decellularized vessels [51]. The implanted constructs
remained patent after 130 days, and they even demonstrated contractile activity, which is important for blood flow. In 2003, Niklason’s group grew smooth muscle cells on a PGA tubular scaffold in
a bioreactor. As the PGA degraded, the excreted extracellular matrix took over. This construct was then decellularized and seeded
with autologous endothelial cells obtained from a biopsy [52,53].
Other methods of tissue engineered vascular graft development
involve using natural polymers as scaffolds. Natural polymers have
great biological properties, but their mechanical properties leave
more to be desired. Some examples of natural polymers used in
this field include fibrin, elastin, hyaluronan, and collagen. Fibrin, a
protein used in wound healing and clot formation, can be purified
from blood and used to generate scaffolds without immune responses being a factor. Elastin is an extracellular matrix protein that
provides elasticity and durability in many organs and tissues. It enhances attachment of endothelial cells and regulates the activity of
smooth muscle cells. Hyaluronan is a nonsulfated glycosaminoglycan which provides for a hydrophilic, nonadhesive, and biocompat-

ible scaffold. Finally, collagen, the major extracellular matrix protein, serves as great natural scaffold for tissue engineering. Mechanical support, biological compatibility, and a low antigenicity
are all covered by this protein.

group recently decided to electrospin silk fibroin with collagen type
I to allow for cell attachment and vascular graft creation [64].

Weinberg and Bell made a vascular graft using smooth muscle
cells and collagen casted in a mold at 37∘C [10]. This was done in
1986, but the tissue engineered vascular graft failed to meet the
mechanical properties required for use after implantation. In 2000,
Nerem’s group improved the mechanical properties of the graft
mentioned above by using a silicone tube to create a mechanical
stimulus [16]. In 2005, Andreadis conducted a research study that
involved smooth muscle cells seeded within fibrin gels [17]. Endothelial cells were then seeded on the outer surface of the fibrin
graft. This tissue engineered graft showed good signs of patency 15
weeks after implantation into an animal model.
Preclinical research studies have also placed a great emphasis
on the use of synthetic polymers. Synthetic polymers have tunable
mechanical properties which are much better compared to their
natural counterparts. The ease of manufacturing these synthetic
scaffolds also adds on to their benefits when used for tissue engineering vascular grafts. Four types of synthetic materials are used
in tissue engineering. Polygylcolic acid (PGA) is a polyester that degrades very quickly in the body due to hydrolysis, and it emits carbon dioxide and water as it degrades. It only lasts 6 months within
the body [23, 15]. Polylactic acid (PLA) is another polyester that has
a slower degradation rate than PGA. Poly-ɛ-caprolactone (PCL) is
another polyester used for synthetic scaffolding, and it has a very
slow hydrolysis-based degradation, and it takes over a year for it to
fully degrade in vivo [23]. Polyglycerolsebacate (PGS) is an elastomer that degrades in 2 months after being placed in the body [66].
All of the above mentioned polymers are FDA approved and remain
a focus of emphasis for use as scaffolds for tissue engineering.

FIGURE 11: Schematic representation of the Triograft which is
currently undergoing pre-clinical studies

While a lot of improvements are being made pre-clinically, a
southern California company is leading the way with its novel three
layered design for a tissue engineered vascular graft. Their product
is called the Triograft, and it is made up of two synthetic scaffolds
to allow for different degradation times. The three scaffold layers
are listed in order from interior to exterior: PLA, PCL, PLA. All three
scaffolds are coated with both collagen and elastin to promote cell
attachment as well as flexibility. Once again going from interior to
exterior, endothelial cells are seeded on the PLA, smooth muscle
cells are seeded on the PCL, and fibroblasts are seeded on the outer
PLA. PCL has the slower degradation time compared to PLA in order
for it to serve as a mechanical support for the smooth muscle cells
over the course of a year. After the year, all of the synthetic scaffolds should be degraded allowing for the natural extracellular matrix to take over.

FIGURE 12: Cylindrical mandrel scaffold rolling technique used
to create the cellular Triograft
FIGURE 10: Mechanical stress of bovine aortic smooth muscles
as performed by Langer’s lab group

In 1999, Langer’s lab group created PGA scaffolds seeded with
bovine aortic smooth muscle cells. The scaffolds were cultured in
vitro with the cells under mechanical stress [39]. Endothelial cells
were eventuall seeded on the interior of the tubular structure using
a perfusion bioreactor. This tissue engineered vascular graft had
good mechanical strength, and it did not undergo too much inflammation after implantation in vivo. The current research has advanced to more complex systems in the late 2000s. One research
group developed two layered grafts made up of a fibrin hydrogel
and a fibrinogen layer [39]. Smooth muscle cells were seeded onto
the construct, and the group was able to show that the smooth
muscle cells distributed uniformly in the inner layer in order to
maintain the proper contractile properties. Another research

With regards to culturing, autologous endothelial cells, fibroblasts, and smooth cells (obtained from biopsy) are seeded onto
respective synthetic scaffolds containing collagen and elastin. Mechanical strain in both the x and y directions is placed on the scaffolds to promote cell elasticity and flexibility during cell culture. After desired cell confluence is reached, the seeded scaffold are
wrapped around a cylindrical mandrel and cultured via bioreactor.
The scaffolds are initially held together by biodegradable sutures
to form the tube-like structure. Afterwards the graft is moved to
another bioreactor which uses perfusion to supply media to the interior and convection to deliver media to the exterior portion of
the graft. Finally, the graft is coated with heparin to prevent thrombosis. This company is still performing pre-clinical studies, but it is
working to secure clinical trials in the near future.

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