U.S. patent number 3,914,802 [Application Number 05/472,677] was granted by the patent office on 1975-10-28 for non-thrombogenic prosthetic material.
This patent grant is currently assigned to Michael Ebert. Invention is credited to Franklin G. Reick.
United States Patent |
3,914,802 |
Reick |
October 28, 1975 |
**Please see images for:
( Certificate of Correction ) ** |
Non-thrombogenic prosthetic material
Abstract
A non-thrombogenic material possessing mechanical, chemical,
biological and electrical properties that render the material
acceptable for a broad range of prosthetic applications. The
material is provided with a hydrophilic inner lining formed
primarily of a sintered network of colloidal silica bonded onto a
thin layer of oxygen-diffusing elastomeric material, reinforced by
a porous fabric backing. The silica imparts a net negative charge
to the lining which repels negatively-charged blood platelets in
contact therewith. The silica network acts as a matrix to promote
the growth of neo-intima.
Inventors: |
Reick; Franklin G. (Westwood,
NJ) |
Assignee: |
Ebert; Michael (Mamaroneck,
NY)
|
Family
ID: |
23876498 |
Appl.
No.: |
05/472,677 |
Filed: |
May 23, 1974 |
Current U.S.
Class: |
623/1.43;
623/1.49; 128/DIG.21 |
Current CPC
Class: |
A61L
33/027 (20130101); A61F 2/06 (20130101); Y10S
128/21 (20130101) |
Current International
Class: |
A61F
2/06 (20060101); A61L 33/02 (20060101); A61L
33/00 (20060101); A61F 001/24 () |
Field of
Search: |
;3/1,DIG.1-3,1.4,1.7
;128/334R,1R,1D,DIG.21 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
"Artificial Organs" by Howard J. Sanders, Chemical &
Engineering News, April 5, 1971, p. 49 relied upon under heading
Polypropylene fibers. .
"An External Velour Surface for Porous Arterial Prosthesis" by
Lester R. Sauvage et al., Surgery, Vol. 70, No. 6, pp. 940-953,
Dec. 1971. .
"The Coating of Intravascular Plastic Protheses with Colloidal
Graphite" by V. L. Gott et al., Surgery, Vol. 50, No. 2, Aug. 1961,
pp. 382-389..
|
Primary Examiner: Frinks; Ronald L.
Claims
I claim:
1. A non-thrombogenic prosthetic material comprising:
A. an elastomeric layer capable of oxygen-diffusion, the outer face
of the layer being bonded to a fabric backing acting to reinforce
the layer, the interstices of the fabric permitting cellular
diffusion to lock the material in place after implantation, and
B. a lining bonded to the inner face of said layer and formed
primarily of colloidal, negatively-charged silica particles to
repel negatively-charged blood platelets in contact therewith, said
particles being sintered to define a three-dimensional
micro-lattice acting as a matrix to promote the growth of
neo-intima.
2. A prosthetic material as set forth in claim 1, wherein said
elastomeric material is silicone rubber.
3. A prosthetic material as set forth in claim 1, wherein said
elastomeric material is urethane rubber.
4. A prosthetic material as set forth in claim 1, wherein said
fabric is formed of woven polyester yarns.
5. A prosthetic material as set forth in claim 3, wherein said
yarns are formed of polyethylene terephthalate.
6. A prosthetic material as set forth in claim 1, wherein said
material is in tubular form and said fabric backing is constituted
by a sleeve bonded to a tubular layer of elastomeric material whose
inner face has said lining bonded thereto.
7. A prosthetic material as set forth in claim 1, wherein said
lining further includes positively-charged fumed alumina particles
in a ratio to said negatively charged particles to provide a
desired net negative charge.
8. A prosthetic material as set forth in claim 1, wherein said
lining further includes colloidal graphite to render the lining
semi-conductive.
9. A prosthetic material as set forth in claim 1, wherein said
elastomeric layer has a thickness in the range of 0.0005 to 0.005
inches.
10. A material as set forth in claim 1 wherein said particles are
hydrophilic.
11. A material as set forth in claim 10 further including
hydrophobic particles in a ratio relative to said hydrophilic
particles to impart a desired wetting characteristic to said
material.
Description
BACKGROUND OF THE INVENTION
This invention relates generally to prosthetic materials, and more
particularly to prosthetic tubing adapted to replace veins and
arteries.
Prosthesis refers to the surgical practice of replacing defective
or missing parts of the human body with artificial devices. As
noted in the articles on "Artificial Organs" (Parts 1 and 2) which
appear in the Apr. 5, 1971 issue of Chemical and Engineering News,
the main problem encountered in connection with artifical hearts
and other organs as well as in human implants such as finger joints
and in synthetic plastic tubing serving as blood vessels, is the
incompatibility of the prosthetic material with human blood.
In order to be compatible with blood, it is vital that the
prosthetic material not cause blood clotting or bring about the
destruction of red blood cells. The material must not alter blood
proteins, cause damage to blood platelets, or produce other
deleterious blood changes.
According to the above-identified articles, all presently available
synthetic material without exception, when immersed in blood for
substantial periods of time, cause blood clotting. They can also
damage red blood cells, blood platelets and blood proteins.
Although artificial materials in contact with blood can give rise
to many adverse reactions, of greatest medical concern is the
tendency of known materials to cause blood clots or thrombi. If the
material has a marked tendency to induce clotting, it is referred
to as highly thrombogenic.
The reason why a thrombogenic material is unacceptable is that
clots forming on the surface thereof may dislodge and be carried
along in the blood stream until they completely block a blood
vessel, thereby inducing a heart attack or a stroke. In those
instances where the clot remains at its formation site in a narrow
organ such as a blood vessel, it can dangerously constrict the
vessel.
The mere fact that a given material does not promote clotting does
not automatically render it acceptable for prosthetic applications,
in that the same material can also bring about destruction of red
blood cells or damage blood proteins. Or its mechanical properties
may be unsatisfactory. To be acceptable in all respects, a
prosthetic material must satisfy a large number of critical
requirements, for in addition to those already mentioned, the
material must not damage adjacent tissue, it must be free of
carcinogenic or toxic agents, and it must not induce allergic
reactions or interfere with the normal immunological mechanism of
the body.
One widely used prosthetic material is silicone rubber. This
material is employed for implants and for various types of tubing
to drain fluid from the brain, the chest cavity, the bladder and
other organs. Silicone rubber, because of its flexibility, softness
and other mechanical, biological and chemical properties, has
distinct advantages. But though relatively compatible with blood,
silicone rubber, under some circumstances, such as when the blood
is not flowing fast enough, can promote clotting. Moreover, this
material does not possess sufficient strength when continuously
flexed for protracted periods.
Also in common use as a prosthetic material are synthetic polymers,
such as "Dacron" polyester fiber. Woven into a tight fabric, Dacron
has found its greatest surgical use as artificial blood vessels and
as patches for arteries and other human organs. While Dacron has
good tensile and flexural strength and a high degree of
compatibility with tissue, it can cause blood clotting. This
tendency toward clotting is also characteristic of Teflon
(polytetrafluoroethylene).
It is generally agreed that the manner in which blood flows greatly
affects its tendency to clot. It has been found that clotting is
more likely to occur when the flow rate of blood is too slow or
even worse, becomes stagnant. Turbulent flow also promotes
clotting. Hence if the interface between the blood and the
prosthetic device is not smooth, turbulence is produced which may
give rise to clotting. In general, the problem of thrombosis is not
a serious problem in the grafting of medium and large sized
vessels. But heretofore it has been a major deterent to small
vessel venous repair where the hemodynamics are usually
unfavorable.
A significant factor which influences thrombogenicity is the
electrical charge appearing on the surface of the prosthetic
material. It is known that a negatively-charged or anionic
substance is less prone to induce clotting than one which is
positively-charged. The lining of natural blood vessels has a
negative charge which is as high as 5 m V. This negative charge
causes the lining to repel blood platelets and red blood cells
whose surfaces are negatively-charged.
The reason this charge repulsion is believed to inhibit blood
clotting is that it prevents the attachment of platelets to the
wall of the blood vessel. Such adhesion causes the platelet
membrane to rupture and triggers off an intricate chain of
enzyme-activated steps that lead ultimately to the conversion of
fibrinogen to fibrin. Fibrin is an insoluble protein that forms the
matrix of a blood clot made up chiefly of fibrin, platelets and red
blood cells.
In an attempt to impart a negative charge to the surface of a
prosthetic material in contact with blood so as to repel
negatively-charged blood platelets, treated polymers have been
developed, these being called electrets. The polymers, after being
heated to slightly below their melting point, are exposed to a
strong electrical field. When the polymer cools, one side has a
negative surface charge and the opposite side a positive charge.
The difficulty with electrets is that they are not only costly and
difficult to fabricate, but their electrical charge may decay,
disappear or even reverse itself.
SUMMARY OF THE INVENTION
In view of the foregoing, it is an object of this invention to
provide a non-thrombogenic material possessing mechanical,
chemical, biological and electrical properties that render the
material acceptable for the full range of prosthetic
applications.
More particularly, it is an object of this invention to provide a
prosthetic tubing whose inner lining has a permanent negative
charge to prevent the formation of deleterious blood clots, the
structure of the lining encouraging the formation of self-renewing
living tissue (neo-intima or pseudo-intima) which is highly
compatible with the flowing blood in contact therewith.
Also an object of the invention is to provide a method for
fabricating small bore flexible tubing which is non-thrombogenic
and has other excellent prosthetic properties.
It is still another object of this invention to provide a technique
for forming an inner lining on a prosthetic material whose net
electrical charge may be preset to conform to blood
requirements.
Briefly stated, these objects are attained in a prosthetic material
having an inner surface or lining formed primarily by a fine layer
of sintered colloidal silica bonded to a thin film of elastomeric
material, such as silicone rubber, reinforced by a porous fabric
backing formed of synthetic yarn such as Dacron.
The porous fabric backing is conducive to external cellular
diffusion to lock the prosthetic material in place after
implantation. The lining has a net negative charge which repels
negatively-charged blood platelets, the lining surface being
micro-reticulated to provide a matrix encouraging the growth of
living tissue. The thin silicone rubber layer permits oxygen to
diffuse readily therethrough so that the support cells remain
healthy.
OUTLINE OF DRAWINGS
For a better understanding of the invention as well as other
objects and further features thereof, reference is made to the
following detailed description to be read in conjunction with the
accompanying drawing, wherein:
FIG. 1 schematically illustrates the structure of a prosthetic
material in accordance with the invention;
FIG. 2 shows the mandrel on which the material is fabricated,
and
FIG. 3 is a highly magnified view of the lattice network formed by
the sintered silica particles in the inner lining of the prosthetic
material.
DESCRIPTION OF THE INVENTION
A prosthetic tubing or other device in accordance with the
invention is constituted by an inner layer of a non-thrombogenic
substance which is bonded to and lines the face of a thin layer of
oxygen-diffusing elastomeric material such as silicone or urethane
rubber, the elastomeric layer being reinforced by a woven fabric
backing made of synthetic plastic yarns of high-strength and
acceptable chemical and biological properties. The resultant
structure is similar in some respects to that of a fire hose in
that the thin layer of rubber is externally-supported by an
exceptionally strong fabric to provide a high-strength,
burst-resistant tubing. This prosthetic tubing may be sutured,
glued or otherwise connected to a vein or artery stub.
Various surgical techniques for grafting prosthetic tubing to small
vessel stumps and for implanting prosthetic devices are disclosed
in the following references:
1. Jacobson and Suarez, Surgical Forum, 11,243 (1960)
2. MaCaffrey, Australian and New Zealand Journal of Surgery, 37,398
(1968)
3. Salmon, British Journal of Surgery, 55 (1), 58 (1968)
4. Strauch & Murray, Plastic & Reconstructive Surgery, 40
(4) 325 (1967)
5. Bellman, Acta Chir. Scand., 128,509 (1964)
The fabric backing is preferably woven of Dacron yarn, a polyester
fiber made from polyethylene terephthalate. The porous Dacron
permits diffusion to lock it into place after implantation. It is
soft and flexible and easily inflated by blood pressure. Dacron is
not adversely affected by aging or body fluids. Also suitable as a
backing is woven Lycra, made of a spandex fiber in the form of
continuous monofilaments.
As noted previously, blood platelets carry a negative charge, the
platelets being repelled by the negatively-charged surfaces of
healthy veins and arteries. This mutual repulsion prevents damage
to the extremely fragile platelets as they travel through an
elaborate venous network whose conduits are in various diameters.
Normal veins and arteries are extremely hydrophylic with respect to
blood plasma, the fluid wetting the vessel.
The lining of a prosthetic material in accordance with the
invention makes it possible to alter the inner surface of the
prosthetic so that no discontinuity of any sort is introduced into
the system. That is to say, the electrical charge of the lining is
essentially equivalent to that encountered in the natural artery or
vein in which the prosthetic tubing is interposed, hence there is
no charge discontinuity therebetween; the lining has hydrophylic
properties comparable to that of natural venous tubing, hence there
is no wetting discontinuity; and the surface of the lining has
physical properties comparable to that of natural venous tubing,
hence there is no conductivity discontinuity.
The inner lining of the prosthetic tube is formed primarily of
dispersed Cab-O-Sil, (the trademark for colloidal silica particles
sintered together in chain-like formations), or particulate
material having equivalent properties. This product is formed in a
high temperature vapor phase flame hydrolysis process producing
extremely fine particles of a diameter of about 15 millimicrons.
One gram of Cab-O-Sil contains over 11 million billion particles
and covers an area of about 200 square meters.
A typical Cab-O-Sil surface contains covalently bonded hydroxyl and
siloxane groups. When Cab-O-Sil particles are dispersed in liquid
and allowed to stand, they develop, as shown in FIG. 3, a
loosely-woven lattice-like, three-dimensional network as a result
of hydrogen bonding between particles. Cab-O-Sil, in water (or
blood), as indicated in the descriptive booklet published by the
White Pigment Division of Godfrey L. Cabot, Inc. of Boston, Mass.,
is normally negatively-charged.
Thus, when a fine Cab-O-Sil coating is formed on the inner surface
of a prosthetic device, the resultant lining exhibits a negative
charge which repels negatively-charged blood platelets and prevents
the formation of blood clots. The lining is therefore inherently
non-thrombogenic. Nevertheless the lining is synthetic in nature,
whereas the best approach to making a foreign material fully
compatible with blood is to allow the material to become covered
with a layer of living tissue whereby the blood does not come in
direct contact with a foreign substance but with living tissue
similar to that of normal body organs. Such living tissue or
neo-intima causes little damage to blood cells and blood proteins,
and since neo-intima is self-renewing, it can repair itself.
A serious difficulty heretofore experienced in making a surface
non-thrombogenic by growing living tissue over it, is that if the
tissue layer continues to grow and becomes too thick, the tissue
cannot survive. The reason for this is that the cells in the
neo-intima depend on blood for nutrition, and unless the neo-intima
is extremely thin, blood cannot reach all of the cells.
The extraordinary advantage of the microscale three-dimensional
Cab-O-Sil network lining is that it affords a nearly ideal matrix
or scaffolding for growing a thin neo-intimal layer that remains
fully intact because it enables all of the cells to receive an
adequate supply of blood.
It is also to be noted that attempts have heretofore been made to
provide a growth matrix for a neo-intimal layer by means of a
gossamer-like polypropylene fiber web bonded to a substrate. In
this web arrangement, should the neo-intimal layer grow too thick
so that the blood is unable to reach the innermost cells, the
resultant death of these cells cause the neo-intima to come loose
from the web and to be sloughed off into the blood stream, as a
result of which the exposed underlying web may cause clotting. But
in the present invention, even should some of the neo-intima peel
off the lining network, the negative charge on the exposed area
would prevent the formation of blood clots.
Thus as shown in FIG. 1, the prosthetic material is constituted by
a thin, gossamer-like lining 10 of sintered silica particles in a
lattice-like formation which has a negative charge and is in
contact with the flowing blood 11, making possible the growth of a
thin layer of neo-intima. Lining 10 is firmly anchored on the face
of a silicone rubber film 12 which permits the diffusion of oxygen
therethrough, the film being bonded to the inner surface of a woven
Dacron fabric backing 13 whose interstices facilitate cell growth
and bonding of the material to the body tissue 14 in contact
therewith. When the sintered silica three-dimensional network comes
in contact with blood, minute blood clots form in the interstices
of the network and are held therein. In time, these minute clots
coalesce, and a layer of cells forms over them, so that eventually,
the clots are replaced by a layer of living tissue.
METHOD OF FABRICATION:
As illustrated in FIG. 2, the prosthetic tubing in accordance with
the invention is made from the inside out on a Teflon-coated
mandrel 15. Teflon which is the trademark for tetraflouroethylene
(TFE) flourocarbon polymers, has useful no-stick properties. We
shall now describe the sequence of steps to be carried out in
making prosthetic tubing.
1. The first step in the manufacturing procedure is to cover the
mandrel with a release agent. Preferably, this agent has
non-thrombogenic properties, so that should any trace thereof
remain on the inner surface of the tubing, it will not impair the
non-thrombogenic characteristic of this surface. Suitable for this
purpose is Pluronic-F68. Pluronic is a trademark for polyoxyakylene
derivatives of propylene glycol. Also acceptable as a release agent
is Ethomid (polyethoxylated highmolecular-weight amides).
2. The second step is to spray a dispersion of Cab-O-Sil particles
over the release agent coating to form an extremely fine layer
thereover. The solvent for this dispersion is preferably hexane,
for this solvent does not interact with the release agent and does
wick up through the particles.
An ideal lining is one having a net negative charge comparable to
that found in a natural blood vessel and similarly hydrophylic. In
order to obtain these characteristics, it may be necessary to
intermingle the Cab-O-Sil particles with Alon, which is a
positively-charged fine-particle gamma alumina (also hydrophylic),
made by the flame hydrolysis of aluminum chloride. By varying the
ratio between the intermixed Alon and Cab-O-Sil particles, one may
obtain the desired net negative charge and the desired hydrophylic
lining characteristics. To adjust the hydrophylic properties, some
Silanox or other hydrophobic colloidal particles may be added to
the Cab-O-Sil particles.
It also may be desirable to add small amounts of colloidal graphite
to the mixture to impart semi-conductive electrical properties to
the lining. In effect, therefore, the surface in contact with the
blood can be "tuned" to attain optimum charge-carrying and wetting
properties.
3. The third step is to spray over the lining layer a thin layer of
silicone rubber to anchor the Cab-O-Sil particles therein without
however encapsulating the particles or fully covering the surface
thereof. Electrostatic spraying in a hexane solvent is preferred to
create a thin elastomeric film whose thickness lies in a range of
about 0.0005 to 0.005 inches, the film being readily diffused by
oxygen. As an alternative to silicone rubber, one may use Silastic
which has characteristics similar to unvulcanized rubber and
contains organo-silicon polymers. The silicone rubber layer, after
spraying, is permitted to air cure for about an hour.
4. The fourth step is to cover the silicone rubber layer on the
mandrel with a long sleeve of woven Dacron fabric. To facilitate
this operation, the sleeve is first wet down with water which acts
as a lubricant, after which the sleeve is gently pulled over the
mandrel. The sleeve is then smoothed down to squeeze out the water.
After the sleeve is fully dry, the sleeve is dipcoated in highly
dilute silicone rubber hexane solution (RTV) in order to bond the
Dacron fabric sleeve to the silicone rubber underlayer without
however filling and plugging the interstices of the fabric. It is
important to maintain porosity of the sleeve. The sleeve is now
permitted to air cure for several hours.
5. The fifth step involves removing the long prosthetic tube from
the mandrel 15. For this purpose, a ring 16 having a lateral water
inlet 17 is fitted over one end of the mandrel, the ring having a
hub extension 18 which is inserted under one end of the expansible
tube. By forcing water or other lubricating fluid through inlet 17,
the long tube is dilated, thereby making it possible to withdraw
the tube from the mandrel.
6. The sixth step involves the careful cleaning of the tube. This
is done with hot water under high pressure to produce a highly
turbulent stream which rinses loosely-bonded particles from the
tube lining and removes whatever release agents remain therein.
Finally, the tube is sterilized in preparation for use.
If desired, the inner lining may be coated with blood, a cell
dispersion, Heparin, Pluronic F68, hydrogel or any other material
heretofore used to enhance the performance characteristics of a
prosthetic tubing.
KNEE JOINT SUPPORT
The fire hose construction described herein is satisfactory under
body conditions where gentle deflection is encountered, for the
tube will remain cylindrical when inflated with blood. But in high
flex areas such as bone joints, there is a risk of creasing. This
is undesireable, for creasing introduces a flow discontinuity which
may promote the formation of clots.
If an area of high flex is anticipated, one may construct the
prosthetic tubing in the manner previously described on the
mandrel, and add to the long Dacron sleeve a shorter concentric
sleeve of woven Dacron felt at a position corresponding to the flex
area. This short sleeve may then be cemented in place. The sleeve
acts to resist creasing and to maintain a smooth blood flow through
the high flex area.
While there have been shown and described preferred embodiments of
the invention, it will be appreciated that many changes may be made
therein without departing from the essential spirit of
invention.
* * * * *