U.S. patent number 3,700,380 [Application Number 05/077,289] was granted by the patent office on 1972-10-24 for surface or lining compatible with blood or other tissue.
This patent grant is currently assigned to Tecna Corporation. Invention is credited to Sotiris Kitrilakis.
United States Patent |
3,700,380 |
Kitrilakis |
October 24, 1972 |
SURFACE OR LINING COMPATIBLE WITH BLOOD OR OTHER TISSUE
Abstract
A surface or lining containing microcavities for anchoring
pseudointimal growth within blood handling prostheses such as
vascular grafts, heart assist pumps, artificial hearts,
extracorporeal devices, and the like to form a thin, stable
autologous lining. The surface is also compatible with other living
tissue and promotes tissue adhesion to percutaneous leads,
catheters, cannulae, etc., which inhibits bacterial penetration and
consequent infection. A method of forming a lining or surface
containing microcavities.
Inventors: |
Kitrilakis; Sotiris (Berkeley,
CA) |
Assignee: |
Tecna Corporation (Berkeley,
CA)
|
Family
ID: |
22137199 |
Appl.
No.: |
05/077,289 |
Filed: |
October 1, 1970 |
Current U.S.
Class: |
623/3.29; 264/49;
264/293 |
Current CPC
Class: |
C08J
9/26 (20130101); A61M 39/0247 (20130101); A61F
2/0077 (20130101); A61F 2/06 (20130101) |
Current International
Class: |
A61F
2/00 (20060101); A61F 2/06 (20060101); A61M
1/00 (20060101); C08J 9/00 (20060101); C08J
9/26 (20060101); A61f 001/00 () |
Field of
Search: |
;128/334R,334C,348,35R,92 ;3/1,DIG.1,13 ;161/117,164 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Ersek et al.- Trans. Amer. Soc. Artif. Inter. Orgs. Vol. XV- June
1969- pp. 267-271.
|
Primary Examiner: Truluck; Dalton L.
Claims
I claim:
1. A prosthetic device having a tissue or blood-compatible flexible
surface adapted to receive ingrowth of living cells from an
interfacing region of tissue or blood, said surface including a
plurality of adjacent substantially discrete pockets defined by
walls which extend into said surface, said pockets having openings
which face outwardly in the direction of said region of tissue or
blood to provide means to accommodate a number of living cells, the
walls of said pockets extending inwardly to a depth in the range of
.002 to .020 inches to provide anchoring but not of such shape or
size as to prevent essentially normal transfer of nutrients to said
living cells in said pockets from said adjacent area of tissue or
blood.
2. A prosthetic device as in claim 1 in which said prosthetic
device is a hollow blood handling device with said surface in
contact with the blood whereby blood cells entering into said
pockets are nourished from the blood adjacent said surface.
3. A prosthetic device as in claim 1 in which the entire device is
flexible.
4. A prosthetic device as in claim 1 wherein said device is rigid
and the surface is part of a layer applied to the device.
5. A prosthetic device as in claim 3 wherein the surface is part of
a layer applied to the flexible device.
6. A prosthetic device as in claim 1 wherein said device is an
elongated device with said surface on the outside adapted to
penetrate the skin and receive ingrowth of cells.
7. A prosthetic device as in claim 1 wherein the size and shape of
said pockets have a predetermined distribution.
Description
BACKGROUND OF THE INVENTION
This invention relates generally to surfaces and linings compatible
with blood or other living tissue and to a method of making the
same, and more particularly to a lining for blood-carrying
prostheses and tissue-adhering surfaces for implanted devices.
The majority of blood-handling devices (catheters, blood pumps,
hemodializers, blood oxygenators) have historically been fabricated
from materials (e.g., silicone rubber, polypropylene,
polytetrafluoroethylene) which are made very smooth and inert to
avoid blood damage and thrombus formation. Such materials or
surfaces are classified as antithrombogenic substances. Much effort
has been devoted in the past and is currently being expended to
develop improved, satisfactory antithrombogenic surfaces but with
only limited success. The effective prevention of all thrombus
formation, thrombo-emboli, and blood trauma in devices formed of
such materials has not been realized. Other materials (hydrogels,
anionic cellulose) produce less complications, but have physical
properties which are inadequate for many applications.
On the other hand some success has been achieved with the use of
porous materials (primarily Dacron and Teflon) fabricated as woven
or knitted tubes and used as arterial grafts (replacement segments
of blood vessels) in patients with vascular disease or aortic
aneurisms. These prostheses develop a relatively thin pseudointimal
lining over a period of weeks which remains stable and satisfactory
for an indefinite period in many patients. The lining is formed by
the ingrowth of tissue through the porous material and the
deposition of fibrin and cellular material from the blood. It
covers these grafts in a few days with a biologic lining which is
blood-compatible and prevents significant blood trauma and thrombus
or thrombo-embolic formation.
Recently, in the past few years, non-porous or impermeable
prostheses such as arterial grafts and blood pumps have also been
fabricated with anchoring surfaces of a fibrous nature to promote
the formation of a pseudointimal lining. It has been observed that
fibrin cells from the blood are deposited on the anchoring surface,
forming small areas of pseudointima which gradually increase in
size. Such linings are compatible with blood to the extent that
blood trauma has been tolerable and thrombo-embolism has been
virtually eliminated in well-designed prostheses. However, in
devices having complex shapes as with blood pump valves or flexing
surfaces the biologic material may not deposit uniformly. Thicker
deposits occur in portions where excessive growth takes place.
These thicker deposits may die from lack of nourishment and detach
to form thromboemboli or may accumulate at the valves and interfere
with the valve function. The thick lining may also reduce blood
flow in the smaller passages. In prosthetic devices which have
flexing elements, the thick biologic deposits may prevent proper
flexure and eventually cause failure. These problems occur despite
the use of large quantities of anticoagulating drugs in an effort
to prevent the formation of a thicker layer. The anchoring
substrates found in prior art have comprised loose-knit Dacron
cloth backed with silicone rubber, or Nylon and Dacron velour
backed with silicone rubber. Another type of substrate which has
been used employs Dacron fibers embedded in a polyurethane adhesive
to form a flocked surface.
The methods of anchoring biologic materials in the prior art have
not been entirely satisfactory. Velour and flocking fibers from
relatively thick substrates and as a result the fibrin-cellular
lining is also thick since it continues to form and does not
stabilize until the fibers are essentially completely covered. A
much thinner but adherent anchoring surface or substrate is highly
desirable.
A very thin substrate results in a more rapid coverage by biologic
materials (cells and fibrin) which stabilizes early and which
differentiates or forms pseudointima much more quickly. A thin
pseudointimal lining which forms rapidly is desirable to shorten or
avoid the period of anticoagulant treatment. The underlying cells
nearest the prosthesis are adequately nourished from the blood
stream if the biologic lining is thin, and the shear and bending
(tensile and compressive) stresses in the lining are reduced. A
rapidly-developing pseudointima on a thin anchoring substrate would
considerably reduce the interim risks of blood trauma, thrombus
formation, and thromboemboli as well as the problem of potential
failure resulting from thick cellular deposits on critical surfaces
(e.g., pump bladder, valve shunt). Adherence to the biologic lining
is dependent on both surface chemical and surface mechanical
properties. The configuration is most critical, yet no presently
used surfaces are satisfactory in this respect; the knitted or
woven cloths or flocked surfaces cannot be made sufficiently thin
and still retain good adhesive characteristics. The woven, knitted,
or matted fibrous surfaces are extremely difficult to apply
uniformly to irregular surfaces such as the valves and tubing of
blood pumps. They are also difficult to apply satisfactorily to
flexing surfaces as in blood pumping chambers because their
indistensibility along the surface leads to shear and tensile
stresses which can cause the pump chambers to fail or the fibers to
separate from the chamber surface.
Percutaneous leads or prosthetic devices in contact with tissue
have a history similar to that for bloodcarrying devices. These
devices have until recently used smooth, inert flexible or rigid
surfaces in contact with tissues (skin, subcutaneous tissue, or
internal organs or tissue). One problem with this approach is that
adhesion of the tissue to the surface had been inadequate,
resulting in relative motion and a consequent substantial risk of
complete removal of percutaneous leads (catheters, cannulae) or
damage to internal organs. Another problem is the substantial risk
and incidence of infection with percutaneous leads by bacteria
penetrating the interface between tissue and lead into the patient,
with localized infections frequently followed by more serious
systemic infections if the local infections are not diagnosed or
adequately treated.
Recently various fibrous materials (e.g., Dacron velours, Teflon
felt) have been adhered to the percutaneous leads in an effort to
solve both of these problems. This has generally resulted in
improved adhesion and fixation, but only moderately decreased risks
of infection. The bacteria have been able to penetrate the
interface between the tissue and fibrous anchoring surface and also
the one between the lead and anchoring surface either because the
tissue has not been able to penetrate the fibrous layer and block
bacterial influx, or because tissue adhesion to the fibrous layer
and lead has been inadequate to prevent bacterial penetration. As
with the pseudointimal lining, a thin layer of tissue on the
prosthesis anchoring surface must be made to penetrate and adhere
to all exposed surface materials by proper surface treatment and by
the mechanical configuration of the surface. Existing surfaces are
generally either too thick, such as the flocking type, or do not
lend themselves to fabrication of complex shapes, such as the woven
fabric type.
SUMMARY OF THE INVENTION AND OBJECTS
In accordance with the present invention, there is provided a
lining or surface containing a plurality of microcavities or
pockets which is compatible with blood and living tissue and forms
a tenacious base or anchor for pseudointimal growth and tissue
ingrowth and yet provide normal metabolic processes to the cells.
The microcavities are formed by providing particles or fibers in
the base material and thereafter removing the particles or fibers
leaving microcavities.
It is an object of the present invention to provide a surface which
forms a thin substrate capable of tenacious anchoring of subsequent
cell deposition and ingrowth.
The foregoing and other objects will be more clearly apparent from
the following description when taken in connection with the
accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1A-1E show the steps of forming microcavities in a substrate
using fibrous material.
FIGS. 2A and 2B show the steps of forming a microcavity in a
substrate using granular particles.
FIG. 3 shows a regularly shaped enclosed volume having a surface
formed in accordance with the present invention.
FIGS. 4A-4E show the steps of another process for forming a surface
containing microcavities.
FIG. 5 shows an enlarged view of a portion of skin and subcutaneous
tissue together with a percutaneous lead device according to the
invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
In general, the surface or lining containing microcavities or
pockets in accordance with the present invention is formed by
applying fibrous, or particulate or granular material to the
surface which is to contain microcavities, while the surface is
soft, causing the surface to set up, cure or harden with the fibers
or granules partially or wholly incorporated therein, and
thereafter using a solvent which dissolves the fibers or particles
leaving a surface which contains microcavities at the location
where the fibers or particles were embedded. The size and shape of
the microcavities can be controlled by the selection of the size
and shape of the fibers, particles or granules. The density or
surface distribution of these pores or pockets can be controlled in
the manufacturing process by regulating the particle
distribution.
Referring particularly to FIG. 1, there are shown the steps of
forming a surface containing microcavities. In FIG. 1A there is
shown a substrate which forms the prosthetic device. A layer 12,
for example, silicon rubber, heat curing polyurethane or solvent
evaporation polyurethane is applied and adheres to the surface of a
substrate, FIG. 1B. The layer 12 is in its soft or tacky state but
can be hardened by a curing ambient depending upon the material
used. Fibers may be flocked or otherwise applied to the tacky
surface 12 as shown in FIG. 1C whereby the fibers are randomly
embedded in the layer 12. Thereafter, the layer 12 is hardened by
solvent evaporation, irradiation heating or the like, FIG. 1D.
Finally a solvent which serves to selectively etch or dissolve the
fibers leaving the layer 12 is applied. The fibers are dissolved
leaving a plurality of microcavities 14 in the layer or surface 12.
The surface is then sterilized as, for example, by washing and
autoclaving.
The materials used for the substrate, base material or layer,
fibers and solvents are not necessarily inert or tissue compatible.
By way of example, the substrate may be a metal or metal alloy such
as stainless steel, aluminum, ferrous-nickel, titanium, a rigid
plastic such as polypropylene, Teflon, Nylon and polycarbonate or
an elastomer such as silicon rubber, polyurethane and natural
rubber.
The adhesive layer 12 may be silicon rubber, polyurethane, or
solvent-evaporation polyurethane as previously described.
The fibers applied may be Nylon, Dacron or acetate. In the event
that Nylon or Dacron is employed, acetic acid may be employed for
selectively dissolving the Nylon or Dacron while the acetate may be
selectively dissolved by acetone or methyl ethyl ketone.
It will, of course, be apparent that the foregoing are merely
examples of suitable material for the substrate and for the
flocking fibers. The selection of the substrate as being either
rigid or an elastomer depends upon the use for which the prostheses
or implanted device is to be put. Furthermore, the layer is
selected whereby it is compatible with the blood or other living
cells with which it will be in intimate contact and for which it
will provide the base for growth of cells or depositions and
adhesion of organized cellular linings.
In FIG. 2 there is shown a method of forming microcavities by
employing particles or granules 16 rather than fibrous material 13.
For example, the particles 16 may be NaCl crystals of a selected
size or shape distribution. The embedded particles or granules may
be dissolved with distilled water leaving a plurality of
irregularly shaped microcavities 17. The layer is then
sterilized.
Typically, the depth of the microactivities is between 0.002 and
0.020 inches. This provides a relatively thin pseudointima for
adequate diffusion of nutrients from the flowing blood, minimal
tissue stress during operation. In a blood pump this thin lining
will not interfere with proper pump valve function, and presents
minimal tissue or lining stress due to pumping chamber flexure.
The above described processes are particularly suitable for use in
devices which have irregular or enclosed surfaces. For example, in
FIG. 3 there is shown a sketch of a device including an enclosed
volume. The steps in forming such a device would be to form the
outer wall 21 of the device which, in essence, is the substrate,
applying an elastomer or other layer 22, embedding, then hardening
and then dissolving the particles to leave a plurality of
microcavities 23.
In FIG. 4 there is shown another process for forming a surface
including microcavities. A mold 26 is provided with a polymer
adhesive layer 27 which, in its soft condition, is flocked with
suitable flocking material such as fibers 28. The layer 27 is
thereafter set up or hardened and is prevented from adhering to the
mold by suitable mold release compound. When the layer is hardened,
the outer surface layer 29 is applied over the surface. Thereafter,
the molded object 29 is removed from the mold along with layer 27
and the embedded particles 28 which then, in turn, are dissolved
leaving a plurality of internal microcavities 31.
Thus, it is seen that there has been provided an improved surface
or lining and method of forming same with microcavities which are
controllably spaced and interconnected. Such cavities permit the
supply of nutrients from the adjacent cells or from the bloodstream
to penetrate easily through the lining and into the cavities to
nourish the cells within the cavities from many directions, for
example, three or more directions whereby to provide an improved
anchoring surface for use in prostheses or any type of device which
is in contact with blood.
The depth and size of the microcavities can be controlled by the
fiber length and size or the particle size and shape. The openings
are of uniform density but may be randomly angled with some holes
interconnecting below the surface. This structure provides good
adhesion to the non-cellular coagulum and fibrin-cellular
constituents which form the pseudoendothelium.
This type of formation of microcavities has several advantages.
Whereas in prior art methods the flocked fibers are not tightly
adhered to the surface and some may separate and form emboli or
nucleate thromboembolisms, the negative flock or cavities are an
integral part of the prostheses device. Good cellular interface
adhesion is obtained by pseudointimal growth or ingrowth of
internal tissue or skin and subcutaneous tissue. Therefore no
interface separation in the prostheses will occur. Furthermore,
good tissue adhesion in a percutaneous lead device provides an
interface sealed against bacterial infection. The microcavity
surface can be made extremely thin without the difficulties
encountered using the flock, woven, knitted, or other fiber
techniques, where very small diameter or very short fibers must be
used and which are difficult to work with.
The microcavity surface of the present invention is particularly
well suited as an external coating for percutaneous lead devices
such as tubes, shunts, cannulae insulated wire and various other
tubular or mass, energy, and information transport devices which
provide an external connection to a point beneath the skin. Such
lead devices are used as access to the circulating blood and as
linkages to implanted devices such as blood pumps. The skin and
subcutaneous tissue grows into the microcavities to provide a
tenacious adhesion with the exposed surface of the lead device.
This results in safety, appearance, and comfort for the patient and
also in the formation of the bacterial seal at the interface of the
tissue and microcavity surface which is extremely effective in the
prevention of infection caused by bacteria penetrating the body
along the interface.
Referring to FIG. 5, one embodiment of the percutaneous lead device
of the invention is illustrated in the form of a hollow lead tube
32 in an implanted position after penetration through skin 33 and
subcutaneous tissue 34. Tube 32 includes an outer wall containing a
plurality of microcavities 36 of the aforementioned type.
Microcavities 36 may either be incorporated directly into the outer
surface of tube 32 or may be applied in an adhesive layer. The lead
tube material is preferably flexible to reduce tissue shear and
tensile stresses caused by body movement or external binding of the
tube. Shear stresses may be further reduced by orienting the tube
generally parallel to the skin surface for a substantial extent in
the subcutaneous tissue.
Another application of the microcavity surface of the present
invention, not shown, is as an external lining on the surfaces of
implanted prostheses which encourages the formation of a thin
adherent tissue envelope. Although the tissue forming this envelope
has somewhat different characteristics than skin and subcutaneous
tissue, it grows into the lining in essentially the same manner.
The envelope prevents damage to surrounding organs and tissue, is
fully compatible with the body and body fluids, and substantially
lowers the risk of infection at the prosthesis surface by
preventing stagnant pockets of fluid at the interface. Such tissue
encapsulation also improves fixation and support of the prosthesis
and protects the same against damage.
* * * * *