REVIEW ARTICLE

Artificial blood vessel: The Holy Grail of

peripheral vascular surgery
John D. Kakisis,a,b Christos D. Liapis,b Christopher Breuer,a and Bauer E. Sumpio,a New Haven, Conn;
and Athens, Greece

Artificial blood vessels composed of viable tissue represent the ideal vascular graft. Compliance, lack of thrombogenicity,
and resistance to infections as well as the ability to heal, remodel, contract, and secrete normal blood vessel products are
theoretical advantages of such grafts. Three basic elements are generally required for the construction of an artificial
vessel: a structural scaffold, made either of collagen or a biodegradable polymer; vascular cells, and a nurturing
environment. Mechanical properties of the artificial vessels are enhanced by bioreactors that mimic the in vivo
environment of the vascular cells by producing pulsatile flow. Alternative approaches include the production of
fibrocollagenous tubes within the recipient’s own body (subcutaneous tissue or peritoneal cavity) and the construction of
an artificial vessel from acellular native tissues, such as decellularized small intestine submucosa, ureter, and allogeneic or
xenogeneic arteries. This review details the most recent developments on vascular tissue engineering, summarizes the
results of initial experiments on animals and humans, and outlines the current status and the challenges for the future.
( J Vasc Surg 2005;41:349-54.)

There is a tremendous impetus in the vascular commu-
nity to develop synthetic small-diameter grafts that have
high long-term patency rates. “Off the shelf” availability in
various diameters and lengths, uncomplicated storage or
preparation requirements, and ease of handling are the
main advantages of such grafts; their inherent thromboge-
nicity and compliance mismatch are the main drawbacks.
Synthetic grafts have been associated with excellent long-
term results in treating the pathology of large-diameter
arteries where the flow is high and the resistance is low. The
patency rates have been disappointing when they are used
to replace small-diameter (⬍6 mm) arteries such as the
coronary and the infragenicular vessels.1-3
One strategy to overcome these limitations applies
tissue engineering techniques to construct biologic substi-
tutes of diseased native vessels. These artificial blood vessels
should ideally be composed of viable tissue, able to contract
in response to hemodynamic forces and chemical stimuli,
and secrete normal blood vessel products. Artificial blood
vessels should also allow complete healing without any
immunologic reaction, remodeling according to the needs
From the Department of Vascular Surgery,a Yale University School of
Medicine, and the 2nd Department of Propedeutic Surgery,b Athens
University Medical School, Laiko Hospital.
Competition of interest: none.
Additional material for this article may be found online at
www.mosby.com/jvs.
Reprint requests: Bauer E. Sumpio, MD, PhD, Chief, Vascular Surgery, Yale
University School of Medicine, 333 Cedar Street, New Haven, CT
06510.
0741-5214/$30.00
Copyright © 2005 by The Society for Vascular Surgery.
doi:10.1016/j.jvs.2004.12.026
of the environment, and even have the ability to grow when
placed in children. Compliance, lack of thrombogenicity,
and resistance to infections are theoretical advantages of
such grafts, and burst strength and “off the shelf” availabil-
ity are additional desirable goals.4
This review summarizes recent developments in vascu-
lar tissue engineering and the initial in vivo studies. A
Medline search of the English-language literature was per-
formed using the key words artificial vessels, tissue engineer-
ing, and vascular grafts. Reference lists from all relevant
articles were reviewed to identify additional studies.
Construction of an artificial vessel. Three basic ele-
ments are generally required for the construction of an
artificial vessel: a structural scaffold, cells, and a nurturing
environment (Table).5-13 The scaffold provides a tempo-
rary skeleton to support the growing tissue and provides the
desired shape until the cells produce their own extracellular
matrix (ECM). Most scaffolds are based on collagen matri-
ces and biodegradable polymers. Another strategy is to use
a tubular mandrel as a supporting device in vitro and
remove it prior to implantation of the graft into the host.14
Autologous or allogeneic smooth muscle cells (SMCs),
fibroblasts, and endothelial cells (ECs) can then be seeded
on the scaffold and cultured until a cellularized vessel with
optimal mechanical properties is created. Bioreactors that
mimic the in vivo environment of the vascular cells by
producing pulsatile flow are being evaluated and may be
useful in this process.12,15,16
Artificial vessels based on collagen scaffolds.
Weinberg and Bell5 were the first to report the in vitro
construction of a vessel; its multilayer structure resembled
that of an artery. Collagen and bovine aortic SMCs were
349
 JOURNAL OF VASCULAR SURGERY
350 Kakisis et al February 2005

Methods for preparing an artificial vessel and initial results

Mechanical
Author Scaffold Cells properties Implantation site Patency

Natural (collagen)
Weinberg and Bell,5 1986 Collagen Bovine aortic SMC, Poor, necessitating a Not tested
EC and Dacron mesh
fibroblasts
L’Heureux et al,6 1993 Type I and III Human umbilical Poor Not tested
collagen vein SMC and
EC
Human skin
fibroblasts
Hirai et al,7,8 1994 Type I collagen Canine jugular Poor, necessitating a Canine posterior vena 65% at 6
SMC and EC Dacron mesh cava months
Synthetic
(biodegradable
polymer)
Shum-Tim et al,9 1999 PGA-PHA Ovine carotid Good Ovine infrarenal aorta 100% at 5
SMC, EC and months
fibroblasts
Niklason et al,10 1999 PGA Bovine aortic SMC Good Swine saphenous artery 100% at 4
and EC weeks
11
Watanabe et al, 2001 PGA-CL/LA Canine femoral vein Moderate Canine inferior vena 100% at 13
SMC and cava months
fibroblasts
Hoerstrup et al,12 2001 PGA-P4HB Ovine carotid Good Not tested
fibroblasts and
EC
Hoerstrup et al,13 2002 PGA-P4HB Human umbilical Good Not tested
cord cells
None
L’Heureux et al,14 1998 Human umbilical Good Canine femoral artery 50% at 7 days
vein SMC and
EC
Human skin
fibroblasts
SMC, Smooth muscle cells; EC, endothelial cells; PGA, polyglycolic acid; PHA, polyhydroxyalkanoate; CL, caprolactone; LA, lactic acid; P4HB, poly-4-
hydroxybutyrate.

casted together in culture medium to create an annular
mold (Fig 1, online only). The inner surface of the graft was
seeded with bovine ECs and the outer with bovine adven-
titial fibroblasts. A Dacron mesh was embedded into the
wall to enhance the mechanical strength of the model.
Models made without the mesh dilated and ruptured at
very low intraluminal pressures (⬍10 mm Hg). A model
with one mesh had a burst strength of 40 to 70 mm Hg,
whereas three layers of collagen lattice alternating with two
meshes provided a burst strength of 120 to 180 mm Hg.
The absence of elastin, the longitudinal (instead of
circular) orientation of the SMCs, and the low densities of
the SMCs and collagen accounted for the poor mechanical
properties of the model. However, well differentiated
SMCs and functional endothelium, which could produce
von Willebrand’s factor and prostacyclin, made this blood
vessel model attractive and sparked further research into the
tissue engineering of blood vessels.
A similar technique used by Hirai et al7,8 yielded similar
results. Hybrid medial tissue was prepared by pouring a
cold solution of canine jugular SMCs and type I collagen
into a tubular glass mold. The luminal surface was seeded
with jugular ECs and the resulting graft was implanted in
canine vena cava. Despite the low venous pressures, the
graft ruptured within a few days of implantation. Subse-
quent grafts were wrapped with a Dacron mesh to prevent
tearing, and the patency rate of the wrapped grafts was 64%
at 6 months. Complete remodeling could be documented
by a monolayer of longitudinally oriented ECs on the
luminal surface, circumferentially oriented SMCs of the
contractile phenotype at the subendothelial layer, ingrown
fibroblasts throughout the vessel wall, meshes of collagen
fibrils in the intercellular space, and sheet-like elastic lamel-
lae in the subendothelial layer.
The poor mechanical strength of collagen-based artifi-
cial vessels has been partially attributed to the longitudinal
orientation of the SMCs before implantation. Several strat-
egies have been used to stimulate reorientation of the
SMCs in a circumferential direction. L’Heureux et al6
hypothesized that SMC orientation is directly influenced
by tensions that oppose cell contraction. In this context,
circumferential forces induced during the maturation of the
artificial vessel are favorable, whereas longitudinal forces are
not. To minimize longitudinal forces, the adherence of
JOURNAL OF VASCULAR SURGERY
Volume 41, Number 2
media to the glass mandrel was repeatedly broken up by
tapping the tube on a hard surface at least once a day. This
allowed free longitudinal contraction of the media. The
radial forces remained, stimulating reorientation of the
SMCs in a circumferential fashion.
A collagen gel containing human dermal fibroblasts
was added around the media-like structure to simulate an
adventitia; an endothelium was established by injecting a
solution of human umbilical vein ECs onto the inner lining
of the vessel. The structure of the complete model resem-
bled that of an artery, but it still was not able to withstand
intraluminal pressure at a physiological level.
An innovative technique was introduced by Kanda
et al16 to induce longitudinal orientation of the ECs, which
enhances their stability under flow shear stress, and circum-
ferential orientation of the SMCs, which is expected to
increase the mechanical strength of the artificial vessel and
improve its vasomotor reactivity. The investigators hypoth-
esized that by applying pulsatile flow on a collagen-based
artificial vessel, the ECs would orient parallel to the direc-
tion of flow and the SMCs would align parallel to the
direction of stretch (i.e., circumferentially). They utilized a
nondegradable polyurethane graft with a collagen gel em-
bedding canine SMCs. Autologous ECs were then seeded
onto the media equivalent to create the framework of an
intima, and the graft was subjected to pulsatile flow of
culture medium. After 10 days of stress loading, the ECs
aligned parallel to the longitudinal axis of the graft and the
SMCs were oriented in a circumferential direction.
In the initial experiments, the application of direct,
pulsatile flow on an immature artificial vessel necessitated
the use of a polyurethane scaffold. To avoid the use of a
scaffold, the investigators17 utilized an elastomeric silicon
tube in the bioreactor. A hybrid media tissue composed of
type I collagen gel and bovine aortic SMCs was constructed
around this tube, which was subsequently subjected to
periodic cyclic inflation. After 5 days of culture under these
conditions, both the SMCs and collagen fibers were aligned
circumferentially.
Another strategy for influencing reorientation of SMCs
within artificial grafts was developed by Tranquillo et al.18
A strong magnetic field was applied during collagen fibril-
logenesis, when the media equivalent was first created,
resulting in circumferential orientation of the collagen
fibrils within the collagen scaffold. The entrapped SMCs
were subsequently aligned along the circumferentially ori-
entated fibrils through cell contact guidance. The tech-
nique appears to be simple, reproducible, and effective,
resulting in media equivalents that are stiffer and more
viscous than the nonmagnetically orientated controls.
Berglund et al19 recently presented the concept of a
construct-sleeve hybrid graft composed of an outer colla-
gen layer containing neonatal human dermal fibroblasts
and an inner support sleeve fabricated from type I collagen
gel and cross-linked with glutaraldehyde, ultraviolet, or
dehydrothermal treatment. Although inferior to native ar-
teries, the hybrid grafts approached the mechanical prop-
erties that are considered necessary for implantation in
Kakisis et al 351
animals. It is expected that as the support sleeve will de-
grade, the cellular layer will gradually strengthen and even-
tually become the load-bearing component of the graft.
The in vivo performance of the graft remains to be tested,
however.
Artificial vessels based on biodegradable scaffolds.
Several biocompatible and biodegradable polymers have
been used as scaffolds for the construction of artificial
vessels. Polyglycolic acid (PGA)10,20,21 is most commonly
used. Its high porosity permits the diffusion of nutrients
upon implantation and subsequent neovascularization, and
it is easily handled and fabricated into different shapes.19
Unfortunately, PGA meshes are rapidly bioabsorbed
(within 6 to 8 weeks) and unable to withstand systemic
pressures. To improve the physical properties of PGA,
several copolymers have been produced by combining PGA
with polyhydroxyalkanoate (PHA),9 poly(lactic acid-co-
lysine),11 poly-4-hydroxybutyrate (P4HB),12,13 poly-L-
lactic acid (PLLA),21,22 or polyethylene glycol (PEG).23
These combinations not only define the mechanical char-
acteristics of the scaffold but also regulate the phenotype of
the cells grown on them through cellular interactions with
the scaffold material.21
Shum-Tim et al9 have seeded a PGA-PHA co-polymer
directly with a mixed population of ovine carotid ECs,
SMCs and fibroblasts. The PGA inner layer was used to
promote cell attachment and tissue formation, whereas the
outer PHA layer provided the necessary mechanical
strength with a longer degradation period of ⬎52 weeks.
The tissue-engineered grafts were used to replace infrarenal
aortic segments in seven lambs and all remained patent for
up to 5 months. Collagen and DNA content, as well as the
mechanical strain-stress curve, approached those of the
native aorta over time. Histology revealed elastic fibers in
the medial layer and endothelial-specific von Willebrand
factor on the luminal surface.
Watanabe et al11 created a hybrid polymer scaffolding
composed of a PGA sheet and a co-polymer consisting of
L-lactides and ⑀-caprolactone. The scaffold was seeded with
a mixed cell population obtained from the femoral veins of
mongrel dogs and, after 7 days of culture, implanted as an
interposition graft into the inferior vena cava of the same
dog. The graft remained patent for up to 13 months, with
no evidence of stenosis or dilatation. The scaffold was
completely degraded by 3 months, and the overall gross
appearance of the artificial vein was similar to that of the
native inferior vena cava.
Niklason et al10 used a PGA scaffold and a biomimetic
system similar to that described by Kanda et al.17 However,
instead of pulsatile flow at 60 beats per minute, the fre-
quency of cyclic stretch was set at 165 to mimic the fetal
environment in large mammals and, presumably, facilitate
in vitro vasculogenesis. Bovine aortic SMCs were seeded on
tubular biodegradable PGA scaffolds and placed around
highly distensible silicon tubes. After 8 weeks of pulsatile
stretch in the bioreactor, the silicon tubing was removed,
and the luminal surfaces of the grafts were seeded with
bovine aortic ECs. Continuous perfusion was instituted for

352 Kakisis et al
another 3 days, imposing shear stress to the endothelialized
vessel lumen. The resulting graft had a wall thickness and
collagen content comparable to native arteries and a rup-
ture strength of 2150 ⫾ 709 mm Hg, which is greater than
the 1680 ⫾ 307 mm Hg reported for native human saphe-
nous veins.
Engineered vessels showed measurable contractions to
pharmacologic agents such as serotonin, endothelin-1 and
prostaglandin F2a and contained well-differentiated SMCs,
as displayed by the expression of calponin and myosin heavy
chains. The initial experience with two of these grafts
implanted into the saphenous artery of miniature swine was
promising. They were patent for up to 4 weeks, in contrast
to two nonpulsed grafts that thrombosed.
Hoerstrup et al12 applied direct flow of culture medium
with a bioreactor through the vascular lumen, thereby
generating significant shear on the luminal surface and
pulsatile stretch to the vessel wall. A co-polymer of PGA-
P4HB was used as the scaffold material because its strength,
pliability, and thermoplastic characteristics allowed fabrica-
tion into almost any shape using a heat-welding technique.
Grafts were sequentially seeded with ovine vascular myofi-
broblasts and ECs and placed in the pulse duplicator system
for up to 4 weeks.
Increased cell mass and collagen content, well orga-
nized in a layered fashion, was achieved in the pulsed
vascular grafts, resulting in supraphysiologic burst pressures
and suture retention strength appropriate for surgical im-
plantation within 3 weeks of culture. The burst pressure
(262 ⫾ 26 mm Hg), however, was still significantly lower
than that obtained by Niklason et al10 at 8 weeks of culture.
In addition to ovine vascular cells, Hoerstrup et al13 also
demonstrated the feasibility of seeding the grafts with human
umbilical cord cells. These cells exhibit myofibroblast-like
characteristics and have the advantage of being readily avail-
able and easy to obtain, without necessitating the sacrifice of
intact donor vessels. In addition, the authors suggest that
individual cell pools could be created from a person’s own
umbilical cord for potential future use. This technique would
eliminate the need to harvest autologous cells and the prob-
lem of immunogenicity of heterogenic cells.
The first clinical application of an artificial vessel based on
a biodegradable scaffold was reported by Shin’oka et al in
2001.24 Cells isolated from a peripheral vein were seeded on a
polycaprolactone-polylactic acid co-polymer tube reinforced
with woven PGA. The graft was used for the reconstruction of
an occluded pulmonary artery in a 4-year-old girl. Seven
months after implantation, the patient was doing well, with no
evidence of graft occlusion or aneurysm formation.
An alternative approach to the use of synthetic biode-
gradable scaffolds is to implant an acellular native tissue and
let the body act as a bioreactor and cell source to seed the
acellular matrix. Several tissues, including skin, fascia, peri-
toneum, muscle, small intestine submucosa, and ureter,
have been used for this purpose with various outcomes.4 It
has been well-established, however, that the mechanical
properties of uncross-linked, cell-extracted tissues are re-
markably similar to those of fresh tissue.25 Therefore, it
JOURNAL OF VASCULAR SURGERY
February 2005
would be reasonable to expect that decellularized alloge-
neic or xenogeneic arteries would give the best biome-
chanical profile for vascular tissue engineering. Neverthe-
less, decellularized canine arteries did not appear to
perform well when implanted as interposition carotid or
coronary artery bypass grafts in dogs, with an early throm-
bosis rate of 20% to 56%.26,27
The thrombogenicity of decellularized xenogeneic ves-
sels is mainly due to the lack of EC lining of the luminal
surface of the vessel. Bader et al28 have tried to overcome
this problem by reseeding decellularized porcine aortas
with pre-expanded human ECs and myofibroblasts har-
vested from saphenous vein biopsy specimens. Apart from
demonstrating the feasibility of reseeding decellularized
vessels with vascular cells, these experiments also revealed
that the in vivo immune response was greatly reduced after
such processing. Ex vivo reseeding of decellularized vascu-
lar matrix scaffolds could therefore be the answer to throm-
bogenicity, immunologic rejection, and lack of healing,
which are the three main problems of cryopreserved or
glutaraldehyde-fixed grafts.
Artificial vessels without the use of a scaffold.
L’Heureux et al14 have investigated a novel technique for the
production of artificial vessels, based exclusively on cultured
human cells, without the use of a scaffold (Fig 2, online only).
Human umbilical vein SMCs and skin fibroblasts were cul-
tured for ⬃30 days, at which time both cell types had formed
cohesive cellular sheets composed of cells and ECM, which
could be manually peeled from the culture flasks.
The SMC sheet was then wrapped around a tubular
support to produce the media of the vessel. After 1 week of
media maturation, the fibroblast sheet was rolled around
the media to provide the adventitia. After a 7-week matu-
ration period, the mandrel was removed and human um-
bilical vein ECs were seeded in the lumen and allowed to
grow for another week.
The end product was a well-organized, three-layer wall
vessel resembling a human artery. The tissue-engineered
graft had burst strength of 2594 ⫾ 501 mm Hg and
demonstrated good handling and suturability characteris-
tics. It showed no signs of degradation, tearing, or dilata-
tion when implanted as an interposition femoral artery graft
in mongrel dogs. On the other hand, intramural blood
infiltration was observed between the vessel wall layers and
the patency rate was only 50% at 7 days of implantation.
Current status and future perspectives. The ability
to apply tissue engineering techniques to construct autol-
ogous vascular grafts for surgical reconstruction is now a
clinical reality. Shin’oka’s group24,29,30 have reported their
clinical experience using tissue-engineered vessels as venous
conduits for reoperative reconstructive cardiovascular sur-
gical procedures in ⬎40 children with varying forms of
congenital heart disease. They report ⬎95% patency at 1
year, without evidence of stenosis or aneurysm formation
despite the small caliber of these vessels in the setting of a
re-do surgical environment.
Although significant advances have already been made,
the construction of a synthetic graft with mechanical prop-
JOURNAL OF VASCULAR SURGERY
Volume 41, Number 2
erties identical to those of native arteries remains an elusive
goal. It should be emphasized, however, that a major
advantage of an artificial vessel is that it does not need to
have mechanical properties identical to those of a native
artery at implantation.31 Being composed of viable tissue
with the potential to remodel, repair, and grow, an artificial
vessel is theoretically able to completely adapt to local
hemodynamic conditions and acquire the structural and
mechanical characteristics of the vessel it replaces, whether
this is an artery or a vein.
Although some authors are optimistic enough to be-
lieve that we are only a decade away from United States
Food and Drug Administration (FDA) approval of a tissue-
engineered blood vessel substitute,32 certain problems
need to be addressed:
1. Grafts currently being investigated require an extended
period of preparation, usually 1 to 3 months, so they
cannot be used in emergency situations.
2. The prolonged duration of culture increases the risk of
infection and raises the cost in terms of manpower,
equipment, and materials needed.
3. Most of the biodegradable polymers currently in use as
scaffolds for the construction of artificial vessels already
have FDA approval. This could actually be a step back-
wards. We need a biopolymer appropriate for use as a
vascular conduit, not one that is off the shelf.
Alternative types of cells are already being used in
animal models to eliminate the need for surgical harvest of
ECs from large veins or tissue microvessels of patients with
atherosclerosis.33 Endothelial progenitor cells (EPCs) pro-
vide a valuable cell source for cardiovascular tissue engi-
neering, because they are present in peripheral blood and
can differentiate into ECs with comparable antithrombo-
genic potential. Shirota et al34 have shown that the produc-
tion rate of endothelial-type nitric oxide synthase and 6-
keto-prostaglandin-F1-a by EPCs are approximately one
third and one half of mature ECs, respectively, whereas the
tissue-type plasminogen activator production rate of EPCs
is almost the same as that of ECs. Moreover, EPC-seeded
decellularized porcine iliac vessels implanted in sheep ex-
hibited high patency, rapid vascular wall regeneration, con-
tractile activity, and nitric oxide-induced vasodilation sim-
ilar to those of native carotid arteries.35
Apart from EPCs, smooth muscle progenitor cells (SPCs)
have also been identified in peripheral blood.36 Ex vivo expan-
sion of these cells has been achieved and may be exploited for
the construction of an artificial vessel in the lab. Even more
exciting is that in vivo recruitment of SPCs to an implanted
construct seems feasible, because these cells show increased
integrin ␣5␤1 expression, which allows them to attach to
fibronectin or other ␣5␤1 adhesive matrices.
Significant advancements in the properties of artificial
vessels can be expected in the foreseeable future with the
combination of tissue engineering and gene therapy. For
instance, the incorporation in the vessel wall of SMCs trans-
fected with the tropoelastin gene may result in increased
elastin synthesis and deposition,37 whereas transfection of
Kakisis et al 353
SMCs with the cyclic guanosine monophosphate-dependent
protein kinase gene may enhance the contractile characteris-
tics of the cells and, consequently, of the graft.38
In this context, Matsuda39 harvested fibroblasts from
skin tissue and transfected them with a triple-gene-encod-
ing adenovirus to express a tissue factor pathway inhibitor,
C-type natriuretic peptide, and vascular endothelial growth
factor. The transfected fibroblasts were incorporated into a
collagen gel wrapped with a polyurethane film, and the
construct was implanted into canine carotid arteries. The
grafts exhibited 100% patency at 1 month and 70% patency
at 3 months, whereas all of the nontransfected fibroblast-
inoculated grafts occluded ⱕ2 days after implantation.
Genetic and molecular engineering can also be applied to
scaffold technology to improve its mechanical and biologic
properties. Modification of chain length and location of cross-
link junctions in the polymer allow for the preparation of
materials with well-defined mechanical characteristics.40 The
application of nanofibrous technology to create scaffolds that
mimic the natural extracellular matrix enhances the ability to
achieve ingrowth of vascular cells,41 whereas incorporation of
adhesion peptides or growth factors will improve the capacity
of the scaffold to support the attachment of vascular cells and
their production of ECM.42-45
It should be noted, however, that the incorporation of
cell adhesion peptides in polymer scaffolds is a double-edge
sword. Several peptides, such as the RGDS (Arg-Gly-Asp-
Ser), KQAGDV (Lys-Gln-Ala-Gly-Asp-Val) and VAPG
(Val-Ala-Pro-Gly), have been shown to promote cell
attachment to collagen-based, PEG, or poly(lactic acid-co-
lysine) scaffolds and prevent cell wash-out after exposure to
shear.42-44 On the other hand, increased cell adhesion
results in decreased ECM protein synthesis by the cells.43
This may lead to graft failure because the mechanical integ-
rity of the tissue construct will depend entirely on the ECM
density after the degradation of the scaffold.
This problem may be overcome by tethering growth
factors to the scaffold. For example, as reported by Mann et
al,45 transforming growth factor-␤1 attached to a PGA scaf-
fold increases the production of ECM proteins by vascular
SMCs, thus counteracting the effects of adhesive ligands on
ECM production, but it does not increase SMC proliferation.
This is particularly important in artificial vessels, as prolifera-
tion of SMCs could lead to narrowing of the vessel lumen.
Drug-eluting scaffolds are another revolutionary devel-
opment in the fabrication of artificial vessels. Yoon et al46
have incorporated dexamethasone, a steroidal anti-inflam-
matory drug, into the polymer phase of a PLGA scaffold.
Dexamethasone was slowly released in a controlled manner
for over 30 days, leading to a drastic suppression in the
proliferation of lymphocytes and SMCs in vitro. Although not
yet tested in vivo, such scaffolds show promise for the preven-
tion of intimal hyperplasia.
In conclusion, initial results show that the construction
of an artificial vessel that combines desirable biologic and
mechanical characteristics is feasible. The incorporation of
recent advances in molecular and genetic engineering to
the already developed techniques is expected to aid in the

354 Kakisis et al
solution of the problems that have emerged. The clinical
imperative for better vascular grafts, the great scientific
challenge, and the large commercial opportunity for such a
graft guarantee that significant developments are to be
anticipated in this field in the near future.
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Submitted Oct 12, 2004; accepted Dec 6, 2004.
Additional material for this article may be found online
at www.mosby.com/jvs.