Novel Vascular Graft Grown Within Recipient’s Own
Peritoneal Cavity
Julie H. Campbell, Johnny L. Efendy, Gordon R. Campbell
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Abstract—A method by which to overcome the clinical symptoms of atherosclerosis is the insertion of a graft to bypass
an artery blocked or impeded by plaque. However, there may be insufficient autologous mammary artery for multiple
or repeat bypass, saphenous vein may have varicose degenerative alterations that can lead to aneurysm in high-pressure
sites, and small-caliber synthetic grafts are prone to thrombus induction and occlusion. Therefore, the aim of the present
study was to develop an artificial blood conduit of any required length and diameter from the cells of the host for
autologous transplantation. Silastic tubing, of variable length and diameter, was inserted into the peritoneal cavity of rats
or rabbits. By 2 weeks, it had become covered by several layers of myofibroblasts, collagen matrix, and a single layer
of mesothelium. The Silastic tubing was removed from the harvested implants, and the tube of living tissue was everted
such that it now resembled a blood vessel with an inner lining of nonthrombotic mesothelial cells (the “intima”), with
a “media” of smooth muscle–like cells (myofibroblasts), collagen, and elastin, and with an outer collagenous
“adventitia.” The tube of tissue (10 to 20 mm long) was successfully grafted by end-to-end anastomoses into the severed
carotid artery or abdominal aorta of the same animal in which they were grown. The transplant remained patent for at
least 4 months and developed structures resembling elastic lamellae. The myofibroblasts gained a higher volume fraction
of myofilaments and became responsive to contractile agonists, similar to the vessel into which they had been grafted.
It is suggested that these nonthrombogenic tubes of living tissue, grown in the peritoneal cavity of the host, may be
developed as autologous coronary artery bypass grafts or as arteriovenous access fistulae for hemodialysis patients.
(Circ Res. 1999;85:1173-1178.)
Key Words: artificial artery n autologous transplant n tissue engineering
A
they show a high incidence of rejection, deterioration, and
complications. Similarly, the use of dialdehyde starch–tanned
bovine xenografts has been generally abandoned because of a
high incidence of aneurysm formation and poor resistance to
infection.
For these reasons and because autologous grafts are not
always available, synthetic vascular prostheses such as Dacron fabric grafts and expanded polytetrafluoroethylene have
been developed. Although they perform reasonably satisfactorily in high-flow low-resistance conditions, these materials
are not suitable for small-caliber arterial reconstructions
because they are foreign bodies and because blood coagulation can occur on the luminal surface, resulting in occlusion.
One innovation designed to improve their patency is the
coating of the lumen of the graft with endothelial cells.2
Although flow through the graft is improved and thrombogenesis is reduced, graft failure due to occlusion by cell
overgrowth can still occur. Gene therapy has been used to
address this overgrowth, but retrovirally transduced cells on
the graft are not able to withstand the stresses encountered by
the flow of blood and are sheared off. Also, the procedure for
therosclerosis is the principal cause of coronary occlusion, stroke, aortic aneurysm, and gangrene of the
extremities and, as a single disease, is the major cause of
mortality and morbidity in the United States, Europe, and
other western nations. Atherosclerotic lesions are the result of
an inflammatory response and damage of the arterial wall
complicated by excessive lipid deposition.1 A method by
which to overcome the clinical symptoms of atherosclerosis
is the insertion of bypass grafts around an artery blocked or
impeded by plaques. The most common vascular graft material in use today is saphenous vein or mammary artery from
the patient him/herself (autografts). Both are flexible, viable,
nonthrombogenic, and compatible. However, although the
mammary artery seldom develops atherosclerosis, it may not
always be the proper size or length, and saphenous vein may
have varicose degenerative alterations that can lead to aneurysm formation when transplanted to a high-pressure arterial
site. Furthermore, the nonthrombogenic surface of endothelial cells of saphenous veins is often damaged during graft
preparation. Venous and arterial allografts have also been
tried but have generally been abandoned clinically because
Received May 3, 1999; accepted September 8, 1999.
From the Centre for Research in Vascular Biology, Department of Anatomical Sciences, The University of Queensland, Brisbane, Queensland,
Australia.
Correspondence to Dr Julie Campbell, Centre for Research in Vascular Biology, Department of Anatomical Sciences, The University of Queensland,
Brisbane, Queensland, 4072 Australia. E-mail [email protected]
© 1999 American Heart Association, Inc.
Circulation Research is available at http://www.circresaha.org
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obtaining endothelial cells from the patient is invasive, and
the cells are hard to propagate in vitro. Attempts have been
made to use skin granulation tissue as a vascular graft (the
Sparks mandril prosthesis3). This process involves the placement of a plastic/glass rod under the skin. With time,
cylindrical granulation tissue is formed, the rod is removed,
and the tissue is tanned to remove all cellular components,
leaving only a skeletonized collagen framework. However,
findings of a low bursting strength led to the addition of
external and internal synthetic grafts (such as Dacron) to the
skeletonized tube, but these grafts were still found to have
high rates of complication and low percentages of patency,4
and their usage is limited. Therefore, despite considerable
experimental and clinical research, none of the biological and
synthetic grafts produced thus far is an ideal substitute for an
artery.
We describe here a “designer” artery, produced in the
peritoneal cavity from cells of the same animal into which it
is grafted. These arterial substitutes are composed of living
myofibroblasts and the matrix they have produced, and they
are antigenically acceptable and strong, respond to agonists
and antagonists similar to blood vessels of the host, and are
lined by living, nonthrombogenic, mesothelial (endotheliumlike) cells.
Materials and Methods
Tubing Implantation and Harvest and Autologous
Tissue Transplantation
Thirty male adult Wistar rats (250 to 350 g) and 20 New Zealand
White rabbits (aged 3 to 4 months) were anesthetized with 2.5%
halothane (Fluothane; Laser Animal Health, Queensland, Australia)
(vol/vol O2). A small incision was made in the shaved abdominal
wall, and four 10-mm (for rat) or four 20-mm (for rabbit) lengths of
Silastic tubing with outer diameter of 3 mm (rat) and 5 mm (rabbit)
were placed inside the peritoneal cavity of each animal.
Two weeks after insertion of the tubing, the rats were premedicated with atropine (0.25 mg/kg body wt administered intraperitoneally) and anesthetized with 1% halothane. The 4 implants were
harvested from the peritoneal cavity of each rat, and any implants
that had adhered to the wall or bowel were discarded. Of the
free-floating implants, the one with the thickest capsule was selected
for autologous transplantation, and the others were used for histology
or Western analysis (see below). With the aid of an operating
microscope, 2 vascular clamps were placed on the area above and
below the transplant site in the abdominal aorta, which was then
resected. The elastic recoil left a gap of 5 to 10 mm between the cut
ends. The Silastic tubing was removed from the implant selected for
autologous transplantation, and at the same time, the tissue capsule
was gently everted such that the mesothelial layer now lined its
inside surface (Figure 1). The tube of living tissue was then trimmed
and aligned with the gap ready for suturing. Two stay sutures (9-0
silk) were placed at each anastomosis to orient the graft and the
artery and to facilitate the placing of other sutures. The mid
anastomotic site was sutured with 10-0 (22-mm) Ethilon suture
material and with round and nontraumatic needles (Ethicon, Inc).
Suturing was first performed at the distal anastomosis, followed by
the proximal anastomosis. A total of 8 interrupted sutures were
placed at each end: one each was placed at the dorsal, ventral,
medial, and lateral aspect of the anastomosis, and 4 more (Ethilon
9-0) interrupted sutures were then placed to fill the intervals between
them. The use of stay sutures was important, because they prevent
accidental suturing of the front and back wall of the same vessel. The
grafts were not preclotted, nor were heparin or spasmolytics
administered.
Figure 1. Diagrams of myofibroblast capsule (a), covered with a
layer of mesothelium, formed around Silastic tubing in the peritoneal cavity; tube of the living myofibroblast capsule after
removal of Silastic tubing (b); and eversion of myofibroblast
capsule such that mesothelium now lines the lumen (c).
Similarly, 2 weeks after insertion of 4 pieces of Silastic tubing into
their peritoneal cavities, 20 rabbits were preanesthetized with 1 mL
Saffan (IV, Gloxovet) injected into their marginal ear veins, and
continuous anesthesia was achieved with 2.5% halothane. The 4
grafts were harvested from each animal, the thickest free-floating
capsule was set aside for autologous transplantation into the right
carotid artery, and the others were fixed for histology. To expose the
right carotid artery, a midline incision (approximately in line with the
trachea) was made, the surrounding connective tissue was bluntly
dissected, and the submandibular glands were clamped and retracted
to one side. The transplantation procedure was similar to that in the
rat, except a 10-mm segment of artery was removed. After elastic
recoil, this left a gap of '20 mm between the cut ends into which the
trimmed everted tube of tissue (with Silastic tubing discarded) was
sutured.
In both rats and rabbits, after suturing was complete, the distal
clamp was released to allow the graft to fill with blood under low
pressure, and then the proximal clamp was released to allow blood
flow under full arterial pressure through the graft. Light external
pressure with Gelfoam (Upjohn, New South Wales, Australia)
sealant was required at the anastomoses to control initial leakage.
Hemostasis was achieved by '2 to 3 minutes after removal of the
clamps, but the graft was continuously monitored for 10 to 14
minutes in case of secondary bleeding. Patency was determined by
direct inspection. The wound was irrigated with saline solution and
closed with Dexon (Davis & Geck) 4-0 sutures. The animals had free
access to standard food and water. A graft was deemed successful at
the time of operation if it was fully dilated and pulsating and if a
femoral pulse was present. Unsuccessful grafts were limp and
flaccid, with no detectable pulse.
The 30 rats were randomly divided into 5 groups (n56 per group)
and euthanized at 1, 1.5, 2, 3, and 4 months after transplantation. The
20 rabbits were divided randomly into 4 groups (n55 per group) and
euthanized at 1, 2, 3, and 4 months after transplantation.
Tissue Analysis
Free-floating implants from the rat and rabbit not used for autologous
transplantation were processed for light microscopy, immunohistochemistry,5 and transmission electron microscopy.6 In addition, fresh
implants from the rat (n56) were used for organ bath experiments
(see below). Total protein was extracted from another 6 rat implants
and subjected to Western blot analysis7 using antibodies to cytoskeletal markers and contractile filaments. In both cases, rat aorta was
used as a control. Antibodies used for Western blotting were
a-smooth muscle actin (1-A4, mouse IgG2a, 42 kDa, Sigma Chemical Co), b-actin (AC-74, 44 kDa, Sigma), smooth muscle myosin
heavy chain (mouse IgG1, hSM-V, 204 and 202 kDa, Sigma),
vimentin (V9, mouse Ig G2a, 57 kDa, Sigma), and desmin (D33,
mouse IgG1, 250 kDa, Dako), as well as collagen I (C-1926, Sigma),
collagen IV (epitopes a1 and a2, Sigma), elastin (Sigma), and ED1
for macrophages (Dako). Densitometric analysis was performed on
the bands by use of image analysis software (Mocha, Jandel
Scientific), and values for each implant protein were expressed as a
Campbell et al
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Figure 2. a, Free-floating silicone tubing,
10 mm long, covered by a capsule of
granulation tissue harvested from the
peritoneal cavity of a rat 2 weeks after
implantation. b, Longitudinal section of a
tube of granulation tissue after 2 weeks of
growth in the peritoneal cavity of a rat
(hematoxylin and eosin stain). Arrow indicates side from which Silastic tubing has
been removed. Magnification 3300. c,
Electron micrograph of 2-week granulation tissue formed in the rat peritoneal
cavity. Arrowhead indicates a mesothelial
cell lining several layers of myofibroblasts.
Magnification 33500. d, Electron micrograph of myofibroblasts in the wall of a
2-week granulation tissue tube formed in
the rat peritoneal cavity. Note the collagen matrix between cells. Magnification
38000.
percentage of that expressed in the aorta. For light microscopy,
sections were stained with hematoxylin and eosin and with both
Weigert’s and Hart’s stains for elastin. For immunohistochemistry,
sections were stained with antibodies to a-smooth muscle actin,
smooth muscle myosin heavy chain, and von Willebrand factor
(Serotec) by use of the biotin/streptavidin system. Negative controls
were obtained by omitting the primary antibody or staining with an
irrelevant monoclonal antibody of the same isotype. The volume
fraction of myofilaments (Vvmyo) of cells of the “media” was
determined as previously described.6
Rats and rabbits at 1, 2, 3, and 4 months after transplantation were
euthanized with pentobarbital (Lethobarb, Provet Supplies) and
perfusion-fixed. Wall thickness of the transplants was measured, and
cell density was calculated by image analysis (modification of the
method of Kleinert et al2 ). Sections were taken for light microscopy,
electron microscopy, and immunohistochemistry of the tissue before
transplantation. Transplants taken from the rat group killed at 1.5
months were taken for standard organ bath experiments to determine
the response of the tissue to contracting and relaxing agents and were
compared with 2-week implants and normal rat aorta.
All statistical analyses were performed by use of the statistical
software package SIGMASTAT (Jandel Scientific).
Results
Formation of a Granulation Tissue Tube in the
Peritoneal Cavity
In both the rat and rabbit, an average of 2 of 4 pieces of
Silastic tubing implanted in the peritoneal cavity remained
free-floating and had become completely encased in a capsule
of granulation tissue by 2 weeks (Figure 2a). However, in 2
rats and 1 rabbit, all 4 harvested tubes had adhesions. These
were removed, discarded, and replaced by fresh tubing. After
2 weeks, 3 of the 4 new implants in each of the 3 animals
remained free-floating and by 2 weeks had developed a
capsule of granulation tissue. The tissue was removed from
the Silastic tubing of all free-floating implants by trimming
one end and then pealing it back over the tubing, a procedure
similar to taking off a sock (see Figure 1). This caused little
or no damage and, at the same time, everted the tube of living
tissue. The Silastic tubing functioned only as an irritant and
molding and was now discarded.
Light microscopy of the capsule from both the rat and
rabbit showed that close to where the Silastic tubing had been
was a layer of connective tissue covered by several layers of
cell-rich granulation tissue (Figure 2b). There was concentric
layering of collagen bundles, and the spindle-shaped cells
contained large amounts of synthetic organelles and abundant
focal/dense bodies in myofilament bundles (Figure 2c and
2d). Vvmyo in these cells of the rat tube was 35.761.6%
compared with 63.765.7% (P,0.05) for smooth muscle cells
in the aorta of the same animals (Table 1). Macrophages,
readily distinguished by their irregular shape and high vesicle
content, were commonly seen. The inside lining of the
everted tubes consisted of a single layer of cells that stained
positively for von Willebrand Factor,8 and transmission
electron microscopy confirmed their identification as mesothelial cells (Figure 2c). The hollow tubes of living tissue
thus resembled normal blood vessels, with an inner “endothelium” (mesothelium in this case), “media” of myofibroblasts, and a thin outer “adventitia” of connective tissue.
Western analysis showed that the rat granulation tissue
tube contained a similar content of a-smooth muscle and
desmin as the rat aorta, with less smooth muscle myosin
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TABLE 1. Vvmyo of Spindle-Shaped Cells in 2-Week Implant
Harvested From Peritoneal Cavity of Rat and at 3 Months After
Transplantation Into Rat Abdominal Aorta
Rat Tissue
2-wk peritoneal implant
Vvmyo, %
(n560 Cells)
35.761.6
3 mo after transplantation
58.761.4*
Aorta
63.765.7*
Values are mean6SD.
*P,0.1.
heavy chain and much greater levels of b-actin and vimentin
(Table 2). The levels of collagen types I and IV were similar
to levels in the aorta, but elastin levels were low.
Granulation Tissue Tube as Autologous Vascular
Graft (Artificial Artery)
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The potential usefulness of the granulation tissue– derived
tube as vascular graft material was demonstrated in both the
rat and rabbit. The rabbit had a 10-mm segment of its right
carotid artery removed and replaced with 20 mm of everted
granulation tissue lined with mesothelial cells grown for 2
weeks in the peritoneal cavity of the same animal. The rat had
its abdominal aorta cut, but no segment removed, and 10 mm
of autologous granulation tissue inserted at the cut ends. After
1, 2, 3, and 4 months after implant, the presence or absence
of a pulse through the transplant was evaluated, then the
proximal site of the vessel was clamped, and the graft was
perfusion-fixed followed by postdrop fixation.
One month after transplantation, grafts in all 6 rats of group
1 had a pulse and were patent. At 2 months, 4 of 6 grafts were
patent, and at 3 and 4 months, 3 of 6 grafts were patent,
giving an overall patency rate of 67%. None of the grafts had
been preclotted, nor had heparin or spasmolytics been administered to the animals at the time of transplantation because
we wished to test the antithrombotic benefits of the mesothelial lining. Nonpatent grafts had their lumens blocked by
incorporated thrombi and by a-smooth muscle actin–stained
cells. Signs of recanalization were sometimes seen. The
patent rat grafts possessed a normal intact wall and a strong
pulse. Mesothelium (or migrated endothelium), which stained
for von Willebrand factor,8 constituted the inner lining. The
TABLE 2. Comparison of Proteins in Rat Granulation Tissue
Tube, Formed in Peritoneal Cavity Over 2 Weeks, With Rat
Aorta by Densitometric Analysis of Western Blots
Antibodies
Myofibroblast Tube
Protein Relative to Aorta,
% Value6SD (n53)
a-Smooth muscle actin
10862
b-Actin
5606188
Smooth muscle myosin heavy chain
2361
Vimentin
9116337
Desmin
8668
Collagen type I
7663
Collagen type IV
9361
Elastin
961
average wall thickness of the graft increased from
0.1860.02 mm (pretransplant) to 0.2560.02 mm by 1 month,
after which no further change was observed. No significant
(P,0.1) increase in cell number was evident in the “media,”
with the increase in graft thickness being due to the large
amount of extracellular matrix, mainly collagen, that developed on the outer surface of the wall (Figure 3a). This
“adventitia” contained vasa vasorum as seen with antibodies
to a-smooth muscle actin (Figure 3b). Similar results were
found for rabbit granulation tissue tubes grafted into the
carotid artery, with an overall patency rate of 70% (14 of 20
at the different time points).
The cells within the wall of the grafts in both the rat and
rabbit stained intensely for a-smooth muscle actin (Figure
3b) and smooth muscle myosin (Figure 3c). By 3 months, the
Vvmyo of the cells in the rat transplant had increased to
58.761.4%, which was not significantly different from
smooth muscle cells in the rat aorta near to the transplant site
(Table 1). Structures that resembled elastic lamellae and
stained with both Hart’s and Weigert’s elastic stain began to
appear in both rat and rabbit grafts by 1 month; at first they
were found only near the lumen and then throughout the
“media.”
To determine whether the graft responded to contractile
and relaxing agents, organ bath experiments were carried out
on grafts transplanted to the rat aorta for 6 weeks (n56); these
grafts were compared with rings of aorta from the same
animal. First, 1021 mol/L KCl was administered to determine
whether the transplanted graft had any contractile activity.
Rings from the aorta had an increase in contraction of 16 mN,
whereas the transplanted graft contracted to 3 mN (Figure
4a). Both contracted tissues relaxed in response to (1025
mol/L) acetylcholine. Both tissues were then exposed to the
contractile agonists 5-hydroxytryptamine (1029 to 1025
mol/L) and phenylephrine (1029 to 1024 mol/L). The transplant showed no contractile response to 5-hydroxytryptamine; however, it did respond to phenylephrine, with a
contractile response of 1.5 mN at 1025 mol/L compared with
a response of 15.5 mN exhibited by the aorta at the same
concentration (Figure 4b). Before grafting into the host
artery, the tubes of granulation at 2 weeks had no response to
contractile or relaxing agents (n56).
Discussion
It has previously been observed that small foreign bodies
(such as plastic disk, boiled liver, agar, gelatin, egg white,
filter membranes, and boiled blood clot) introduced into the
peritoneal cavity of the rat, rabbit, or mouse initiate an
inflammatory response, with the resultant granulation tissue
covered by a layer of mesothelium.9 –11 We speculated that if
a tube of tissue could be grown and then freed from the
molding and everted, this process might be used to develop an
autologous vascular substitute.
Indeed, it was shown that tubes of granulation tissue can be
grown within an animal’s own peritoneal cavity by using
moldings of Silastic tubing of different lengths and diameters.
These tubes of tissue possess a lining of mesothelial cells and
a living contractile wall composed of myofibroblasts with
tensile strength provided by collagen type I. The mesothelial
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Figure 3. a, Transverse section of a
10-mm tube of 2-week granulation tissue, 4 months after it had been grafted
by end-to-end anastomoses into the
abdominal aorta of the same rat (hematoxylin and eosin stain). Note the thickened “adventitia.” Magnification 330. b,
a-Smooth muscle actin staining (brown)
of myofibroblasts in a 20-mm tube of
2-week granulation tissue formed in the
rabbit peritoneal cavity 4 months after it
had been grafted by end-to-end anastomoses into the carotid artery of the same
animal. Note the small blood vessels in
“adventitia.” Magnification 3100. c, Wall
of 20-mm tube of 2-week granulation
tissue formed in the rabbit peritoneal
cavity 4 months after grafting by end-toend anastomoses into the carotid artery
of the same animal (stained with antibodies to smooth muscle myosin heavy
chain [brown]). Magnification 3150. d,
Wall of 10-mm tube of 2-week granulation tissue formed in the rat peritoneal
cavity 4 months after grafting by end-toend anastomoses into the abdominal
aorta of the same animal (stained with
Weigert’s elastic stain). Arrow indicates
elastic fibrils. Magnification 3300.
layer is extremely important because it possesses fibrinolytic
and anticoagulant activity,12 and synthetic grafts seeded with
mesothelium are known to have a high patency rate similar to
grafts seeded with endothelium.13
We also showed that the artificial artery can be used
successfully as an autologous arterial transplant and remain
patent for at least 4 months, with constituent cells becoming
more smooth muscle—like, with a Vvmyo similar to smooth
muscle cells of the adjacent arterial wall. By 6 weeks after
transplantation, the cells have begun to respond to the
contractile agents phenylephrine and KCl and to relax in
Figure 4. a, Rat thoracic aorta (upper trace) and graft of 2-week
granulation tissue tube transplanted into rat abdominal aorta for
6 weeks (lower trace). Response to 1021 mol/L KCl (point A) and
1025 mol/L acetylcholine (point B). b, Rat thoracic aorta (upper
trace) and graft of 2-week granulation tissue tube transplanted
into rat abdominal aorta for 6 weeks (lower trace). Response to
increasing concentrations of phenylephrine is shown. Arrow
indicates 1029 mol/L phenylephrine (maximum concentration
1024 mol/L).
response to acetylcholine. However, we have not yet determined whether all the cells in the transplant come from the
original myofibroblasts or whether some are derived from the
transmural ingrowth of smooth muscle cells or “fallout”
hemopoietic cells, as has been reported for vascular and
synthetic grafts.14 Also, it is not known whether the mesothelium is sloughed off the grafts and replaced by local endothelium after their transplantation to high-pressure (rat abdominal aorta and rabbit carotid) arterial sites. The source of
the lining cells will be determined in future experiments by
staining sections with endothelium-specific antibodies
(ED31) throughout the length of the transplants over time.
Because the patency of the transplants reported in the present
study was high, even though they were not preclotted nor had
heparin or spasmolytics been administered to the animals, the
source of the lining cells was not considered essential
information for this initial study.
After the present study was complete, a report15 appeared
in Science (April) describing the in vitro development of
vascular grafts from cells isolated from biopsied pig carotid
artery or bovine aorta grown for 8 weeks on pulsed or
nonpulsed biodegradable polymer matrices. The engineered
grafts responded to contractile agonists at a magnitude of
'5% of control rabbit abdominal aorta. One pig had a pulsed
xenograft transplanted into the right saphenous artery; 3
others had autologous grafts (1 pulsed and 2 nonpulsed) into
the same site. The pulsed grafts remained patent for '4
weeks, whereas the nonpulsed grafts thrombosed after 3
weeks. There are several advantages of our grafts compared
with those described above: our grafts are developed entirely
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in vivo over only 2 weeks by the donor/host themselves; they
need no artificial mesh as part of the wall; and they develop
elastic lamellae and have a demonstrated patency for at least
4 months. Their grafts before transplantation had contractile
responses of '5% of control artery, whereas our tissue at 6
weeks after transplantation had a 10% to 20% response.
Although our results are preliminary and more extensive
experiments are required before such grafts can be used in
humans, we believe that this new type of graft material may
open new perspectives in the field of arterial reconstructive
surgery. These grafts may be developed to replace or bypass
pieces of diseased artery for coronary artery bypass, thus
avoiding the removal of saphenous vein (which is often
varicose in the elderly) or mammary artery for this purpose.
They may also be useful as readily replaceable arteriovenous
access fistulae for hemodialysis patients. The grafts are
biocompatible, have a nonthrombogenic surface, develop
elastic fibers, exhibit a pulse, and contract and relax in
response to exogenous agents, making them superior to
synthetic grafts. Because they are grown inside the subject’s
own body, there is no tissue rejection and limited graft
complication. By altering the diameter and/or length of tubing
used as a molding, grafts of different sizes can be produced.
The procedure also allows for multiple or repeat grafting,
because several tubes of tissue can be grown in the peritoneal
cavity at the same or a later time.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Acknowledgments
This study was supported in part by a grant from the National Health
and Medical Research Council of Australia and by a postgraduate
award (to Dr Efendy) from The University of Queensland. This study
is the subject of Australian Provisional Patent Application No.
PP5422/98, filed August 21, 1998, with extra data added December
22, 1998 (PP7859/98). We thank Dr Lindsay Brown for his expertise
with the organ bath experiments and Anita Thomas, Steve Stamatiou,
Nathalie Worth, and Nicole Smith for technical assistance.
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Circ Res. 1999;85:1173-1178
doi: 10.1161/01.RES.85.12.1173
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