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Claims  |
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What is claimed is:
1. A flexible, hardened segment of a mammalian umbilical cord vessel in a
shape other than that in which it occurs in nature, for use as a
prosthesis in mammals, said segment having vanishingly low antigenicity
and thrombogenicity.
2. The segment as defined in claim 1 wherein said segment is a portion of a
vein.
3. The segment as defined in claim 1 wherein said segment is a portion of
an artery.
4. The segment as defined in claim 1 wherein said segment is sterile.
5. The segment as defined in claim 1 wherein said segment has a shape such
that it can be manipulated into essentially planar form without wrinkling.
6. The segment as defined in claim 1 wherein said segment is tubular in
form.
7. The segment as defined in claim 6 wherein said tubular segment is free
of the valves of Hoboken.
8. The segment as defined in claim 1 wherein the thickness dimension of
said segment is essentially uniform.
9. The segment as defined in claim 1, wherein said mammalian umbilical cord
is a human umbilical cord.
10. A process for preparing a prosthesis for use in surgery comprising the
steps of
a. separating and removing at least one of the principal blood vessels from
a mammalian umbilical cord;
b. hardening said blood vessel by means of a reagent;
c. shaping said vessel.
11. The process as defined in claim 10 further comprising the step of
passing a cleansing liquid through said vessel to remove blood therefrom.
12. The process as defined in claim 11, wherein said cleansing liquid is
selected from the group consisting of hydrogen peroxide, Ringer's lactate
solution, sterile saline solution and water.
13. The process as defined in claim 10 wherein the separation of said
vessel from said umbilical cord is carried out mechanically.
14. The process as defined in claim 10 wherein a mandrel is inserted into
said vessel as a means of shaping same.
15. The process as defined in claim 10 wherein said vessel is shaped
subsequent to removal of same from said umbilical cord and said shaping
step comprises the substeps of inserting said vessel in an essentially
tubular mold, distending said vessel against the wall of said tubular
mold, and hardening said vessel so that it retains the shape of said
tubular mold.
16. The process as defined in claim 10, wherein said shaping is carried out
by hardening said vessel while mounted on a mandrel inserted therein.
17. The process as defined in claim 16 wherein said mandrel has an axis and
is of circular cross-section throughout, and further comprising the steps
of mounting said mandrel in a rotatable chuck, the axis of said chuck
coinciding with the axis of said mandrel, rotating said chuck and said
mandrel, and applying a cutting tool against the exterior of said vessel
to shape the exterior thereof.
18. The process as defined in claim 10 wherein said vessel is shaped by
hardening same while on a mandrel, and further comprising the steps of
mounting said mandrel in a chuck for rotation, and cutting away the
remainder of said umbilical cord by means of a cutting tool while rotating
said vessel on said mandrel.
19. The process as defined in claim 10 wherein said vessel is mounted on a
mandrel prior to hardening, and further comprising the steps of freezing
said umbilical cord including said vessel on said mandrel, mounting said
mandrel in a rotatable chuck and removing the remainder of said umbilical
cord from said vessel by means of a cutting tool while rotating said
mandrel.
20. The process as defined in claim 10, wherein said hardening is effected
by bringing said vessel in contact with a solution of an aldehyde.
21. The process as defined in claim 20, wherein said aldehyde is selected
from the group consisting of glutaraldehyde, dialdehyde starch, glyoxal
and formaldehyde.
22. The process as defined in claim 20, wherein said vessel is hardened by
bringing same in contact with a solution of glutaraldehyde at a
concentration of from 0.15% to 0.6% by weight for a period of about 15 to
about 45 minutes.
23. The process as defined in claim 20 wherein said vessel is hardened by
bringing same in contact with a solution of dialdehyde starch at a
concentration between about 0.5 and 2.0% by weight.
24. The process as defined in claim 10, further comprising the step of
slitting said hardened vessel axially so that said vessel may be
manipulated into essentially flat shape, and, optionally, cut into
segments.
25. The process as defined in claim 20, further comprising the steps of
washing the aldehyde-treated vessel with water, normal saline or dilute
sodium bicarbonate to remove aldehyde, and then with a suitable reagent
for the purpose of eliminating residual aldehyde.
26. the process as defined in claim 25 wherein said reagent is selected
from the group consisting of amino acids, alkali salts of aminoacids,
amines, hydroxylamines, peracids, peroxides and alkali hydrochlorite.
27. The process as defined in claim 25 wherein said reagent is an alkali
salt of L-glutamic acid.
28. The process as defined in claim 10 further comprising the step of
soaking said vessel in ethanol prior to hardening same, the purpose being
to produce a stiffer product.
29. The process as defined in claim 10, further comprising the step of
soaking said umbilical cord in a solution of hyaluronidase prior to
shaping said vessel, the purpose being removal of a portion of the
Wharton's jelly from said cord, and thereby to facilitate separation of
said vessel from said cord.
30. The process as defined in claim 10, further comprising the step of
storing said shaped vessel in a member selected from the group consisting
of a dilute solution of aldehyde and a 40-50% aqueous alcohol solution
containing 1% by weight of propylene oxide, in perparation for use of said
shaped vessel in a surgical procedure.
31. The process as defined in claim 30, wherein said aldehyde solution is a
dilute glutaraldehyde solution.
32. The process as defined in claim 10, wherein said umbilical cord is that
of a human.
33. The process as defined in claim 10, wherein said shaped vessel has a
form such that it is manually deformable into an essentially flat strip,
and further comprising the step of binding a suitably-sized strip of said
vessel about an eye as part of a surgical procedure for holding a detached
retina against the inner wall of the eyeball, the strip being fastened
about the eyeball so as to compress it sufficiently to generate a selected
internal pressure above atmospheric.
34. The process as defined in claim 10, wherein a suitably shaped segment
of said vessel is surgically attached to the interior of the pericardium
of the heart to form a lining thereof.
35. The process as defined in claim 10, wherein said shaped vessel is cut
to form a segment suitably shaped for use as a patch over an opening in a
bowel.
36. The process as defined in claim 16, wherein said vessel is cut to form
a patch for use as a reinforcement over a gap in a bowel, vessel or other
organ which has been sewn together and said patch is so used.
37. The process as defined in claim 10, wherein said shaped vessel is cut
into a strip and said strip is sewn over an anastamosis as a reinforcement
and to prevent leakage therethrough.
38. The process as defined in claim 10, wherein said shaped vessel is used
as a replacement for at least a part of an artery, a vein, a bile duct or
a ureter.
39. The process as defined in claim 10, wherein said shaped vessel is used
to form an artificial conduit between the bladder and the exterior of a
patient.
40. The process as defined in claim 10 wherein said vessel is used as a
patch to bridge or reinforce a defect in a urinary bladder.
41. The process as defined in claim 10, wherein said shaped vessel is used
for surgical repair of an esophagus.
42. The process as defined in claim 10, wherein said shaped vessel is used
as a patch over a surface trauma.
43. The process as defined in claim 42 wherein said trauma is a burn.
44. The process as defined in claim 42, wherein said trauma is a wound.
45. The process as defined in claim 42, wherein said trauma is infected.
46. The process as defined in claim 10, wherein said shaped vessel is used
as filler material in plastic surgery.
47. The process as defined in claim 10, wherein said vessel is a vein.
48. The process as defined in claim 10, wherein said vessel is an artery.
49. The process as defined in claim 10, wherein said mammal is a human.
50. The process as defined in claim 10, wherein said shaped vessel is used
as a covering for artificial, implanted organs and parts thereof.
51. The process as defined in claim 50, wherein said organ is a heart
valve.
52. The process as defined in claim 50, wherein said organ is a pacemaker.
53. The process as defined in claim 10, wherein said hardening process is
carried out at elevated temperature to accelerate said process.
54. The process as defined in claim 10, further comprising the step of
treating said vessel with a solution for essentially eliminating any
residual carbonyl groups, said step being carried out at elevated
temperature.
55. The process as defined in claim 10, wherein said vessel is treated with
said reagent for up to 6 days and further comprising treating said vessel
with a reactant for essentially eliminating all of said reagent from said
vessel. |
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Claims |
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Description |
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BACKGROUND OF THE INVENTION
With the improvement in diagnostic techniques as well as surgical
techniques, the need for flexible materials which may be implanted in the
body has grown rapidly. Thus, vascular prostheses are needed for
replacement of diseased or traumatized vessels including aneurysms,
patches are needed for covering relatively large openings in intestines or
other organs such as may be caused by bullet wounds, patches are needed
for reinforcing defective sections of intestines or esophagus and
coverings are needed for implanted organs such as heart valves and
pacemakers. A particularly pertinent example arises in the repair of
detached retinas. At the present time, so-called eye-slings are fashioned
from silicone plastic or fascia lata. In the procedure, the sling is sewn
to the eyeball in such a fashion that it compresses the eyeball, the
compression generally being such as to increase the internal pressure by
some 30 mm of Hg. However, these materials may erode the eye or lead to
infection since they are foreign bodies. Also, the use of facia lata
involves a second operation since this material must be taken from the
patient.
Considerable success has been achieved in the use of synthetic vascular
grafts for replacement of defective arteries and veins. However, admirable
as have been the results achieved with such synthetic materials, they have
severe limitations. There is a substantial failure rate due to infection
supervening and there may be biologic failure or degradation by fibrin
layering, intimal or sub-intimal hyperplasia, and aneurysm formation.
Perhaps the most important of the limitations is that grafts smaller than
about 5 mm in inside diameter almost invariably become blocked by clots
which form therein and clotting difficulties arise in certain bodily
locations even with vascular grafts having inside diameters as great as 10
mm. Moreover, a delicate balance must be struck in the porosity of the
synthetic graft since the wall thereof must be sufficiently porous to
permit ingrowth and deposition of fibrin so that eventually the wall is
covered with scar tissue both internally and externally and yet not be so
porous that hemorrhage occurs. This makes it necessary to pre-clot the
graft prior to use.
Such grafts are made, in general, either of polyester (Dacron) and Teflon.
Fabrics woven or knitted of these polymers have also been useful as
patches or reinforcements. However, the range of usefulness is restricted.
As is obvious, the necessity for pre-clotting is a substantial
disadvantage as is the fact that they occasionally cause inflammation. As
aforenoted, a major disadvantage is the fact that they cannot reliably be
used in the form of vessels having an inside diameter smaller than 5 mm.
This precludes the possibility of replacement of coronary vessels as well
as the minute vessels in fingers. Also, they do not give full
reinforcement until they are completely overgrown with scar tissue.
Arterial homografts (human arteries) were used to restore continuity but
limited supply, limited range of sizes and development of aneurysms and
arterial sclerosis necessitated the search for better substitutes. In view
of the difficulties encountered with the various types of artificially
constructed grafts, these difficulties including: (1) infection which may
lead to hemorrhage, sepsis and death; (2) thrombogenicity of the inner
lining of the graft so that the graft is predisposed to clotting which may
result in total occlusion of the graft and distal embolism of the clot;
(3) the rigidity of fabric grafts which may result in twisting and kinking
especially where a joint is crossed such twisting and kinking leading to
graft occlusion, these must be considered as having serious deficiencies.
In the attempt to avoid artificial grafts, a variety of new techniques have
been developed. These include "cleaning out" an artery such as by
carbodissection, dilating arteries, development of bovine heterografts,
and creating collagen tubes by inserting a mandrel within the recipient
for later use of a graft.
It is known that homografts have been used for vascular grafting with
considerable success. Commonly, the saphenous vein has been used in cases
where the patient is the donor (an autograft) and where another human is a
donor (allograft). These vessels require no treatment before implantation;
however, they present problems of unavailability, disparity in size,
nonuniform caliber, presence of valves and varicies, and the need for
additional authorization in the case of allografts. The removal of the
saphenous vein to be used for vascular grafting in the same patient
involves keeping the patient on the table for a substantially longer time.
Moreover, the operation is quite delicate and frequently is a failure.
Finally, where rejection is a problem and the patient needs further
grafting after the patient's own saphenous veins have been removed, repair
by this method becomes impossible.
For these reasons as well as others which will appear it would be highly
desirable to provide a new material for use as replacement and
reinforcement for vessels and other organs of the body which would be free
of the problems of clotting, thrombogenicity and antigenicity. Moreover,
as will be disclosed herein, the new material proposed as a source for
repair and replacement of vessels and other organs of the body can be
prepared in a variety of forms which will give rise to new techniques of
great usefulness.
SUMMARY OF THE INVENTION
Umbilical cords contain both primitive veins and arteries. Surprisingly,
these veins and arteries have vanishingly low antigenicity and
thrombogenicity when hardened as disclosed herein, properties which are
extremely desirable in a material to be used for implantation into
patients. The steps involved in preparing such veins and arteries for use
in implantation are exemplified by the processing of the human umbilical
cord which contains one vein and two arteries. However, the umbilical
cords of other mammals can be similarly treated and used.
A mandrel is passed through the vein to straighten the cord and serve as a
support during the subsequent dissection of the arteries and extraneous
tissue therefrom. The mandrel is removed and the vein is flushed clean of
residual blood. The arteries may also be flushed. If start of the chemical
treatment is to be postponed for longer than 1-2 hours, the vessels may be
refrigerated at about 4.degree. C for up to several weeks or freeze dried.
If the dissection is to be postponed after recovery of the umbilical cord
it may also be stored under refrigeration.
The vessels are irrigated for several minutes with an aldehyde solution
after which they may also be placed on mandrels. Each vessel is placed in
a hardening solution on its mandrel, the hardening solution also
containing an aldehyde. The vessel shrinks down onto the mandrel taking
the shape of the mandrel. Glutaraldehyde and dialdehyde starch are
effective as hardening agents as are formaldehyde and glyoxal. However,
glutaraldehyde is preferred.
It is desirable that the vessel be treated at this point to remove residual
aldehyde. In addition to conventional rinsing, the vessel may be treated
with a reagent which reacts with aldehyde, suitable reagents being
amino-acids, salts thereof, hydroxylamine, peroxides, peracids and
hypochlorites. The preferred reagent is sodium L-glutamate. The vessel can
then be removed from the mandrel, treated to remove residual hardener and
stored in a dilute aldehyde solution in preparation for use.
In preparation for implantation, the selected vessel is rinsed with a
sterile liquid such as water, saline etc. Any residual aldehyde on the
vessel is preferably removed prior to use. This can be effected by use of
the reagents described above. The pH of the reagents should be adjusted to
about 7.5 to 8.5. The adjustment can be made conveniently with NaHCO.sub.3
or a phosphate buffer.
A mandrel inserted in a vein or an artery can be used for shaping either
type of vessel and simultaneously eliminating the valves of Hoboken from
the arteries. Alternatively, the vein or artery can be placed inside a
mold, conveniently of aluminum, and distended by the use of a pressurized
fluid until the vessel takes the shape of the interior of the mold. A
hardening solution is used to fix the vessel in the shape either of the
mandrel or of the mold. The product, although hardened, is sufficiently
flexible so that it can be slit and laid out flat and cut into segments.
In this way, sections can be used as strips or as patches for a variety of
purposes. Also, by controlling the degree of hardening the material can be
shaped on a lathe to give a product of uniform wall thickness.
Dropping the temperature of a vessel increases its rigidity. In fact, it
may be frozen as a means of preserving it during storage. Using the term
"frozen" to indicate a drop in temperature sufficient to render the vessel
stiff enough for shaping on a lathe, the cord with a mandrel through the
vein can be mounted in a lathe and then rotated so that all elements other
than the vein can be cut away quickly. This facilitates obtaining the vein
when it is only the vein which is desired this being generally due to the
fact that it is greater in diameter than are the arteries.
The Wharton's jelly which is one of the constituents of the cord can be
partially removed from the cord prior to dissection thereof by soaking the
cord in a solution of hyaluronidase.
A stiffer product can be obtained by soaking the vessels in alcohol prior
to treating with a hardening agent.
In general, the vessels will not be used in exactly the form resulting from
treatment of the umbilical cord described above. Usually, it will be
necessary to trim the vessel to a shorter length, or to slit it, open it
up so that it can be made to lie flat and then cut to length so that it
can be used as a patch. The term "segments" will henceforth be used to
indicate entire vessels, portions of vessels, vessels in tubular form or
patches taken from vessels.
Segments may be used for replacement of non-pulsatile tubular members in
the body such as bile ducts and ureters. Other uses are as a retinal eye
sling, a patch for reinforcement of a section of the intestine, a skin
graft, a reinforcement for an artery or a vein, a patch to bridge defect
or to augment a portion of a urinary bladder and to create an artificial
conduit between the bladder and the skin. Strips formed by slitting a vein
or artery and opening same up, can be used for covering the join between
two sections of a bowel or a vein or an artery, such a join being an
anastamosis. A patch can also be used to cover a gash which has been sewn
together. It will reinforce the join and prevent leaks and other
disruptions. It can also be used on the esophagus.
Accordingly, an object of the present invention is a method of hardening
vessels from umbilical cords, segments of which are to be used as implants
in or grafts on patients.
Another object of the present invention is a method of shaping vessels from
umbilical cords.
A further object of the present invention is a method of preparing segments
of umbilical cords which are non-antigenic and non-thrombogenic.
An important object of the present invention is the provision of umbilical
cord segments which may be stored in preparation for surgical use.
Another important object of the present invention is the provision of
umbilical cord segments which may be used as eye slings and as skin
grafts.
A significant object of the present invention is a group of surgical
procedures using umbilical cord segments prepared in accordance with the
present invention.
A particularly important object of the present invention is the use of
umbilical cord segments for reinforcement of members joined by
anastamosis.
Still other objects and advantages of the invention will in part be obvious
and will in part be apparent from the specification.
The invention accordingly comprises the several steps and the relation of
one or more of such steps with respect to each of the others, and the
article possessing the features, properties, and the relation of elements,
which are exemplified in the following detailed disclosure, and the scope
of the invention will be indicated in the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
For a fuller understanding of the invention, reference is had to the
following description taken in connection with the accompanying drawings,
in which:
FIG. 1 is a view in perspective of an umbilical cord prior to treatment;
FIG. 2 is a sectional view of an umbilical cord vessel on a cylindrical
mandrel;
FIG. 3 is a view in partial section of an umbilical cord vessel pressed
against the interior of a mold hydraulically;
FIG. 4 is a sectional view of an umbilical cord vessel on a tapered
mandrel;
FIG. 5 is a view in perspective of a segment of an umbilical cord;
FIG. 6 is a side view of a vessel reinforced at a seam by a segment in the
shape of a patch;
FIG. 7 is a sectional view of an anastamosis reinforced by a segment in the
form of a strip; and
FIG. 8 is a view in perspective of an eyeball wherein the region of
attachment of a retina to the interior of an eyeball is reinforced by an
eye sling, the sling being formed of an umbilical cord vessel in
accordance with the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The vessels in umbilical cords of mammals and especially of humans when
considered for use in repair, reconstruction, replacement, reinforcement
and augmentation of vessels, organs and other members, both interior and
exterior of the body, are unique with respect to both origin and
morphology. Taking the human umbilical cord as representative, though it
is to be understood that the umbilical cords of all mammals may be used in
the fashions described herein, it is composed of a vein and two arteries
surrounded by a sticky jelly-like substance called Wharton's jelly, all
encased in the surrounding tissue. The umbilical cord may vary in length
from a few inches to over 3 feet in length and is highly flexible. Both
the arteries and the veins contained in the cord are suitable for use in
surgery as will be described.
Since hardened and shaped segments are superior to the untreated umbilical
cord vessels for use in surgical implantation, it is obviously of great
advantage to be able to have a supply of umbilical cord vessels in various
configurations ready for use as the physician requires. The freshly
dissected vessels can be stored after freeze-drying or under refrigeration
for limited periods; however, it is preferable that they be chemically
treated so that storage for indefinite periods becomes possible even when
facilities for refrigeration are lacking. In our copending Application
Ser. No. 543,462 filed Jan. 23, 1975, methods of treating the umbilical
cord chemically have been disclosed. However, the previous application was
directed primarily toward the use of umbilical cord vessels in vascular
surgery, such use requiring that the umbilical cord vessels withstand
pulsatile pressures. Synthetic mesh reinforcement of the cord vessels was
disclosed. The present invention is directed toward a wider spectrum of
uses in which the strength requirements are less severe. For convenience,
as aforenoted, the term "segments" will be used to designate portions of
cord vessels or entire cord vessels in a variety of shapes and forms other
than that in which it occurs in nature. Included will be vessels in
tubular form where the tubular form may be tapered or essentially
rectangular in cross-section, and portions of vessels which have been slit
so that they can be laid out flat.
A human umbilical cord is shown in FIG. 1, the cord containing through the
length thereof a vein 11, two arteries 12 and the aforementioned Wharton's
jelly 13. The first step in the preparation of vein segments in accordance
with the present invention is to pass a mandrel through the vein. The
arteries and excess tissue are dissected away from the vein. The mandrel
is removed and the vein is then flushed clean of residual blood, using any
of water, a dilute solution of hydrogen peroxide, Ringer's lactate
solution or sterile saline solution, Ringer's lactate solution being
preferred.
Since the cord is very flexible and, in fact, may be twisted as well,
passing the mandrel through the vein straightens out the cord and makes it
convenient to handle. The mandrel may be mounted for rotation in a
suitable fixture. The arteries are twisted and coiled around the vein and
dissection of the arteries from the cord is therefore a delicate task
which is facilitated by the use of the mandrel in the vein and mounting
for rotation.
Variations in this procedure are possible. Where only the vein is desired,
the cord, mounted on the mandrel, may be frozen after which the mandrel
can be chucked in a lathe and all material other than the vein itself cut
away using an appropriate cutting tool. Furthermore, if desired, the vein
itself may be trimmed to constant thickness.
Another mode of handling the cord is to soak it in hyaluronidase solution
to reduce the content of Wharton's jelly prior to the dissection step.
After dissecting out the desired vessel or vessels and clearing of residual
blood, they are irrigated for several minutes with a hardening agent,
preferably 3 - 10 minutes. This step effects partial elimination of
Hoboken's valves from the arteries. The hardening agent found most
suitable is the class of aldehydes. Examples are formaldehyde, glyoxal,
dialdehyde starch and glutaraldehyde, with glutaraldehyde being the best
from the standpoints of elimination of any traces of antigenicity and
thrombogenicity and convenience, with a solution of dialdehyde starch
being next best. The concentration of the glutaraldehyde solution should
be between about 0.15% and 0.7%. The concentration of dialdehyde starch
should be between about 0.5 to 2.0% by weight. At lower concentrations the
glutaraldehyde solution does not render the material non-antigenic, while
at higher concentrations the reaction is too rapid and embrittles the wall
of the vessel.
After irrigating a vessel with a hardening solution, the vessel is slipped
onto a mandrel of appropriate shape. The vessel on the mandrel is then
placed in a tank (not shown) of hardening solution for about 15 to 45
minutes, during which time the vessel conforms to the shape of the
mandrel. A preferred solution for hardening the vessel is 0.5%
glutaraldehyde buffered with 1% sodium bicarbonate so that the pH of the
solution is between 7.5 and 8.5. The hardening agent causes the vessel to
conform to the shape of the mandrel and also increases the strength of the
vessel material. A vein 11 is shown on a cylindrical mandrel 15 in FIG. 2.
Another means of shaping a vessel is shown in FIG. 3 in which a vein 11 is
inserted in a tubular mold 18, end 19 of vein 11 being closed with stopper
21. The other end 22 of vein 11 is connected to hose 23 for introduction
of hardening solution 16 under moderate pressure. The pressure of the
hardening solution 16 forces vein 11 against the interior of mold 18 to
conform to said interior. This process results in a vessel having a
smoothed exterior.
The practice of shrinking a vein or artery onto a cylindrical mandrel 15 as
in FIG. 2 or a tapered mandrel 25 as in FIG. 4 has the advantage that any
internal irregularities such as the valves of Hoboken are eliminated, the
reference numeral 24 indicating a vessel segment where the vessel may be
either a vein or an artery.
The vein in the human umbilical cord is substantially larger than the
arteries. Consequently, where larger segments are desired, veins are used
in preference to arteries. Using either an internal mandrel or an external
mold, a vein can be distended out to about 1.0 cm internal diameter. The
diameter of a human umbilical cord artery can be distended up to about 5
mm and can be collapsed down to about 0.5 mm. Arteries of such small
diameter are particularly valuable for replacement of blood vessels in the
body. In this context, the umbilical cords of the larger mammals, while
not so readily available as those of humans, contain larger vessels so
that larger and thicker-walled vessels and patches become available
through use of vessels from such sources. Also, the small mammals provide
vessels of smaller diameter, such vessels being needed for specialized
applications such as in fingers and toes.
It should be noted that for use of segments treated in accordance with the
present invention in pulsatile blood vessels smaller than about 2 mm
internal diameter, reinforcement with artificial mesh is unnecessary. This
follows not only from the fact that tubes of smaller diameter can
withstand higher pressure, in general, but from the fact that in
collapsing the vessels, the wall thickness is increased. Soaking the
vessel in alcohol prior to the aldehyde treatment results in a stiffer
vessel.
After hardening the vessel, it is rinsed to remove most of the hardener. A
1% solution of NaHCO.sub.3 may be used. It is then desirable to treat the
vessel or segment for a period of 30 - 45 minutes with a reagent which
reacts with residual aldehyde. Suitable materials are amino acids, alkali
salts thereof and oxidizing agents in dilute form such as peroxides,
peracids and hypochlorites. The amino acids as sodium salts, and
preferably of L-sodium glutamate, L-sodium alanine, L-sodium phenylalanine
and L-cysteine are particularly suitable for this purpose because they are
antithrombogenic, the best of the above being the glutamate. The mechanism
is believed to depend on condensation of the amine group of the aminoacid
with the carbonyl group of aldehydes. This leaves the carboxyl group of
the condensate free to ionize and impart a negative charge to the surface
of the vessel. Negatively charged surfaces are known to be
antithrombogenic.
Although the preferred method of storage subsequent to hardening and
shaping of the vessel is a dilute solution of aldehyde, it is advantageous
to treat the vessel with an amino acid after hardening to eliminate
aldehyde as indicated. Although not known for certain, it appears the the
residual aldehyde groups are initially oriented so that they are readily
accessible for reaction with an amine group, whereas, after storage
unreacted aldehyde groups are oriented inwardly of the vessel or segment
wall and so inaccessible.
The preferred method of storage of segments is in a dilute solution of
aldehyde, 0.5% glutaraldehyde being preferred. Some further hardening of
the segment takes place over a period of 4-6 days. However, the extent of
hardening during storage is small and can readily be compensated for in
the principal hardening stage.
In preparation for implantation, after storage, the segment is rinsed, as
in sterile saline or 1% NaHCO.sub.3 solution. It is preferably treated
again with sodium L-glutamate or one of the other aforenoted compounds to
eliminate residual aldehyde.
An alternate method of storage is in a solution of 40-50% aqueous alcohol
containing about 1% of alcohol. Treatment of segments stored by this
method with reagent to remove aldehyde is, of course, unnecessary.
As will be recognized, a substantial number of variations on the procedures
outlines above are feasible. Thus, after flushing out the vein in the
umbilical cord, a mandrel, either tapered or straight, may be inserted
into the vein, the cord frozen, the mandrel placed in a chuck and all
elements other than the vein cut away on a lathe. In the process, the
exterior of the vein may be cut so that the wall thickness becomes uniform
or, tapered, if so desired. As would be expected, the vessel or segment
must be rendered sterile after subjection to such manipulation.
Conventional non-destructive techniques such as radiation, antibiotics and
elevated temperature are used.
Another variation is to slit the vein open and lay it out flat. The use of
a flat mandrel facilitates the formation of flat segments. The vessel may
then be cut into segments 20 of any desired size as shown in FIG. 5, such
segments to be used as reinforcements or patches. One use of such a patch
is shown in FIG. 6 wherein a vessel 26, which may be a portion of a bowel
which has been sewn together to form a seam 27, using sutures 28. This
repair of the vessel 26 can be reinforced by placing a segment 29 as a
patch over seam 27 and suturing the patch over vessel 26.
The function of such a patch is greater than mere reinforcement. As is well
known, in stitching together portions of walls of organs in the body, it
is necessary that the sutures not be pulled too tight and that the
stitches not be too close, else the blood supply to the wall of the organ
may be cut off in which case gangrene may supervene. As a result, using
standard techniques, there may be leakage through the suture line in the
wall. It is for this reason that drains are so commonly used. Reinforcing
the seam with a patch as shown in FIG. 6, greatly decreases if not
completely eliminates this danger.
Another version of the use of a segment prepared in accordance with the
present invention is shown in FIG. 7 which represents an anastamosis in a
bowel 31. In accordance with the usual surgical procedure, the two ends 32
and 33 of bowel 31 are turned inward and the ends are then sewn together
with suture 34. A segment 36 is then sewn around the join between bowel
ends 32 and 33, thereby eliminating or greatly reducing the danger of
seepage of bowel contents into the abdomen. Needless to say, although FIG.
7 shows only a single turn of segment about the bowel, two or more turns
about the bowel could also be taken.
The interiors of the vessels are somewhat rougher than the exteriors
thereof, even after shaping on a mandrel. This difference persists when
the vessel is opened up for forming a patch. The surgeon using such a
patch can use either face at his discretion for joining to an organ.
A plurality of segments may be used in certain applications such as for
lining the pericardium of the heart, or a heart valve, or for covering an
artificial implant such as a pacemaker. Segments may also be used in
plastic surgery as an inert reconstructive material.
Although the tensile strength of a hardened vessel is only moderate, it has
other characteristics which make it highly desirable for use surgically.
These are the aforenoted non-antigenicity and non-thrombogenicity as well
as characteristic flexibility, slipperyness and complete compatibility
with body organs and vessels.
There is a wide variety of surgical procedures in which cord segments can
be used to great advantage. It has already been mentioned that a segment
can be used to reinforce a seam and an anastamosis. It can also be used to
reinforce a weak portion or a defect in the wall of an organ such as an
urinary bladder. A segment can be shaped to form an artificial conduit
between the urinary bladder and the skin. A most important use is as a
retinal eye sling. The need for a sling arises in the surgical procedure
for repairing a detached retina. The way in which an eye sling is used is
shown in FIG. 8 wherein the reference numeral 47 generally indicates an
eyeball. The pupil 48 of the eyeball 47 is shown and the area where a
repair has been effected surgically is shown at 49. The region of repair
must be held under pressure until the retina attaches itself permanently
to the eyeball. For this purpose a sling 51 is wrapped around the eyeball
so that the eyeball is compressed against the retina in the interior
thereof. This generally requires that the internal pressure in the eyeball
be increased by about 30 mm of mercury.
Up to the present time retinal eye slings have been made of silicone
plastic or fascia lata. The former can erode the eyeball and precipitate
infection. Consequently, a certain fraction of such procedures fail and,
in such cases, blindness can result. Use of fascia lata, on the other
hand, necessitates a prior operation in order to obtain the material.
Substitution of a segment prepared in accordance with the present
invention eliminates these difficulties. The material is completely
compatible with the body and has no tendency to erode the eyeball.
Another important use for patches derived from umbilical cord vessels is in
connection with skin grafting. A patch can be placed in position over a
burned or traumatized area, even in the presence of infection. In many
cases even a dressing is not needed. The patch "takes" quickly. Healing,
including clearing of underlying infection, proceeds rapidly under the
patch and with no need for the usual change of surgical dressings. The
patch sloughs off when healing is sufficiently advanced. Of major
importance, these grafts will persist for several months while healing
proceeds.
The use of umbilical cord vessels, whether from humans or from other
mammals, as can be seen from the above, presents numerous advantages. The
supply is virtually unlimited and the treatment needed for rendering the
vessels appropriate for use in surgery is simple. Also, many variations
are possible in order to meet specific and varied needs. As a result,
sterile cord vessel segments can be produced in unlimited supply and at
relatively low cost. They can be stored indefinitely and in a variety of
shapes and thicknesses to meet virtually any need. Assuming they are
stored in dilute glutaraldehyde solution, they need only be rinsed in
sterile water or saline solution or dilute NaHCO.sub.3 preparatory to use.
If desired, they can be further rinsed in sodium-L-glutamate to eliminate
any residual aldehyde.
It has already been noted that a number of useful variations in the
chemical treatment of umbilical cord vessels, i.e., segments, are
possible. The following variations are based on the fact that although the
major hardening of the vessel in a hardening solution takes place in a
period of up to about 45 minutes, further hardening continues for 4-6 days
at room temperature when the vessel is stored in a solution of a hardening
agent. These variations may be categorized as follows:
1. Continue the initial hardening process for 4-6 days without interruption
for elimination of aldehyde.
1a. Keep the mandrel or mold in contact with the vessel for up to about 45
minutes.
1b. Keep the mandrel or mold in contact with the vessel for 4-6 days.
2. Raise the temperature of the hardening solution by up to about
60.degree. C and shorten the time of contact of the vessel with the
hardening solution correspondingly, the time of contact between solution
and vessel to be long enough for completion of the hardening process.
2a. Keep the mandrel or mold in contact with the vessel only until shaping
is complete.
2b. Keep the mandrel or mold in contact with the vessel until hardening is
complete.
3. Treat the hardened vessel or segment with an aldehyde-destroying reagent
for a period long enough to insure essentially complete elimination of
carbonyl groups from the vessel or segment.
3a. Carry out said treatment prior to storage and sterilize by conventional
means and store.
3a.1. Carry out said treatment at ambient temperature.
3a.2. Carry out said treatment at elevated temperature.
3b. Carry out said treatment subsequent to storage and sterilize by
conventional means.
3b.1. Carry out said treatment at ambient temperature.
3b.2. Carry out said treatment at elevated temperature.
It will thus be seen that the objects set forth above, among those made
apparent from the preceding description, are efficiently attained and,
since certain changes may be made in carrying out the above process and in
the article set forth without departing from the spirit and scope of the
invention, it is intended that all matter contained in the above
description and shown in the accompanying drawings shall be interpreted as
illustrative and not in a limiting sense.
It is also too be understood that the following claims are intended to
cover all of the generic and specific features of the invention herein
described, and all statements of the scope of the invention which, as a
matter of language, might be said to fall therebetween.
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