Method of replacing a body part with expanded porous polytetrafluoroethylene

Abstract

This invention provides an artificial vascular prosthesis suitable for implantation to replace damaged, stenosed, defective, or occluded veins or arteries. The prosthesis comprises a tube of expanded, porous polytetrafluoroethylene possessing a microstructure consisting of nodes interconnected by fibrils. The suitable range of fibrile length for such a prosthesis is 5-1000 microns, with the preferred range being 20-100 microns.

Description

This invention relates to artificial veins and arteries, and more particularly to artificial veins and arteries comprised of porous, expanded, high strength polytetrafluoroethylene.

The present day demand for viable substitutes for human veins and arteries, especially in small caliber replacements, is approaching critical proportions. In the very early days, the search for manufactured or synthetic materials which could be used for arterial and venous substitutes led to solid-wall glass tubes, and then progressed through various plastic materials and fabrics constructed of synthetic textile fibers.

In the early 1950's, the advantages to be gained through use of porous flexible plastic tubes over solid-walled tubes were discovered. Following this, a number of synthetic fibrous materials were woven or sewn into tubular configurations, and used as porous arterial prostheses. Such constructions performed satisfactorily for limited periods of time.

Over the past two decades, many different types of synthetic fibrous textile materials have been employed in various types of artificial vein and/or artery constructions. Basic animal experimentation has been conducted on growing pigs, adult dogs, sheep and to more limited extents in humans. The basic healing pattern in all is similar.

None of these synthetic fibrous prostheses have been entirely successful. For total success, an artificial arterial prosthesis must provide an open pathway for blood to pass along its entire length and additionally it must not generate embolization to the distal arterial bed. All prior synthetic polymeric materials exhibit varying degrees of surface thrombogenicity due to activation of plasma coagulation factors leading to fibrin formation.

As a result of a considerable volume of trial and testing of synthetic vascular prostheses, the characteristics of an "ideal" construction have been set forth*, namely:

"(1) absence of toxicity, allergenic potential or other overtly adverse chemical reaction; the biological reactivity of the material per se, over the range of that from Teflon to glass is not a limiting factor in the biological healing of the synthetic vascular prosthesis; (2) the prosthesis should be durable without significant deterioration of the synthetic yarn upon prolonged implantation. Nylon Orlon and Ivalon are disqualified on this account; Dacron, Vinyon-N and Teflon qualify. Dacron is preferable because of its superior mechanical handling properties during fabrication and at implantation; (3) the biological healing porosity should be of the order of 10,000 milliliters of water per minute per sq. cm. fabric at a pressure head of 120 mm Hg. It should be pointed out that no commercially available prosthesis today meets this specification because the limit of safe implantation from the viewpoint of hemorrhage is in the vicinity of 5000 ml. of water per min. per sq. cm., at a pressure head of 120 mm. Hg; (4) ideally, the material should have a low implant porosity to enable the administration of heparin to other anticoagulant: less than 50 cc. per min. per sq. sm. at a pressure head of 120 mm Hg; (5) there should be desirable handling properties which facilitate implantation which, therefore, becomes safer: (a) conformability ("scrunchability") for ease of performance of anastomosis: (b) linear elasticity is desirable; crimping in our experience is preferable to elastic yarn because with graft shortening the latter is more likely to affect adversely the porosity; (c) the fabrication should have good pliability and good twist characteristics for traversing flexion creases and subcutaneous and subfascial tunnels without significant mechanical kinking."

An object of this invention is to provide the most nearly ideal vascular prosthesis yet known. To accomplish this objective, a vascular prosthesis is disclosed comprising a tube of expanded, porous polytetrafluoroethylene possessing a microstructure as seen under at least 800X magnification consisting of nodes interconnected by fibrils. The length of the fibrils for a vascular prosthesis in accordance with this invention ranges from 5-1000 microns.

It is a wholly surprising discovery that when such a tube is used as an artificial vascular prosthetic, as the healing process proceeds, tissue grows into and through the pores between the fibrils of the tube forming a vascular replacement consisting of a building scaffold or skeleton of the synthetic material which becomes completely surrounded by and filled with new tissue. The spaces between the fibrils may be very small, perhaps less than 1 micron. However, the fibroblast cells appear to push aside the fibrils as they penetrate the porous structure, and finally corpuscular blood circulation develops into and throughout the tissue that has invaded the fibrillar structure of the prosthetic. Thus, the open space between the fibrils, which may constitute 80-90% of the bulk volume of the prosthetic material, is completely filled by natural living tissue. It is a wholly surprising discovery and contrary to prior art teachings that, during the healing process and without prior pre-clotting, such a tube which can be 80-90% porous will contain blood at arterial pressures. After healing, blood passage is through what is effectively a new-tissue tube, the blood coming in contact with the new-tissue inner surface (intima) of the tube. Also surprisingly, even prior to healing, this construction of synthetic-scaffold/new-tissue prosthetic appears to be the most non-thrombogenic vascular replacement yet known, as shown by the examples which follow.

The material of this invention is expanded, porous polytetrafluoroethylene. Although for some applications low strength material may be used, it is preferred that the material possess a matrix tensile strength in at least one direction exceeding 7300 psi. By definition, the tensile strength of a material is the maximum tensile stress, expressed in force per unit cross sectional area of the specimen, which the specimen will withstand without breaking (see, for example, The American Society for Testing and Materials. "1970 Annual Book of ASTM Standards-Part 24 ," at pg. 41). The true cross sectional area of solid material within a porous specimen is equivalent to the cross sectional area of the porous specimen multiplied by the fraction of solid material within that cross section. This fraction is equivalent to the ratio of the apparent specific gravity of the porous specimen divided by the specific gravity of the solid material which makes up the porous matrix. Thus, to compute matrix tensile strength of a porous specimen, one divides the maximum force required to break the sample by the cross sectional area of the porous sample, and then multiplies this quantity by the ratio of the specific gravity of the solid material divided by the apparent specific gravity of the porous specimen. Equivalently, the matrix tensile strength is obtained by multiplying the tensile strength computed according to the above definition by the ratio of the specific gravities of the solid material to the porous specimen.

The microstructure of this material as seen under 800X or greater magnification consists of nodes interconnected by fibrils. A schematic diagram of this material as it typically appears under microscopic examination is shown in FIG. 1. In FIG. 1, the porous material 10 is seen to comprise nodes 11 interconnected by fibrils 12. The length of the fibrils 12 in accordance with this invention exceeds about 5 microns. In tubular form and in use as a vascular prosthetic, the length of the fibrils 12 exceeds about 5 microns but is less than about 1000 microns.

The material of this invention is manufactured by stretching extruded, unsintered polytetrafluoroethylene, after removal of liquid lubricants used in the conventional extrusion of this polymer. Expanded, porous polytetrafluoroethylene (PTFE) is a relatively new material. Its preferred form is the subject of pending patent application U.S. application Ser. No. 376,188, assigned to W. L. Gore & Associates, Inc., Newark, Delaware. This material is marketed by Gore under the trademark GORE-TEX expanded fluorocarbon material. It is strong, highly porous, flexible, conformable, and possesses the inertness properties inherent to PTFE. It is chemically and biologically inert to almost all known substances. As such, the porous PTFE used in this invention possesses (before tissue invasion) nearly all of the desirable properties of the "ideal" prosthetic, whose properties were described hereinabove. However, these properties are also possessed by woven TEFLON and DACRON prostheses, which have been used extensively in the past as artificial veins and arteries. After tissue has invaded the structure of this invention, it functions as a natural part of the body. This is entirely different from prior art devices.

In accordance with the present invention, it was discovered that porous, expanded PTFE gave unexpectedly beneficial results when used as an artificial vascular prosthetic when the fiber (fibril) length in such devices was between 5 and 1000 microns. Within this range and during the healing process, fibroblastic and capillary ingrowth into the prosthetic occur, with uniform neointimal development over the grafts and suture line surfaces.

Below about 5 micron fibril length, tissue ingrowth does not occur and the advantages of this invention are lost.

Above about 1000 micron fibril length, mechanical disadvantages can occur in suturing the vascular graft to the host tube, and blood leakage can become a problem. This upper limiting range of fibril length is difficult to define quantitatively, however, and depends to some extent upon the skill of the surgeon administering the graft. Blood leakage can also occur in vascular devices which have long fibrils (exceeding 1000 microns) caused by the driving force of the internal blood pressure. In the range of 5 to 1000 micron fibril length, however, the prosthetics of this invention both contain the blood and simultaneously allow tissue ingrowth.

The preferred range of fibril length for the artificial vascular prosthetics of this invention is about 20-100 microns. This preferred range is evident from the examples which follow, which are given for illustration purposes and are not limitative.

EXAMPLE 1

Two series of experiments were conducted using dogs for the animal model and using the two carotid arteries and two femoral arteries for the segmental replacement sites. In both experimental series, all grafts were expanded, porous PTFE tubes, 4 cm in length and 4 mm in diameter. The wall thickness (20-32 mils), density (0.25-0.34 g/cc), and fibril length (5-100 microns) were varied. No heparin was administered. Harvesting ranged from 2 weeks to 4 months. The size of the animal was controlled to insure a reasonable match in size between the natural vessel and the prosthetic graft. The results of these two series of experiments are as follows:

The first series involved 64 implantations of which approximately 36 grafts have been harvested and submitted for histogical studies. The remaining are in living animals with palpable pulses over the grafts. Eight of the harvested grafts were occluded, four of which were possibly due to technical errors in surgery recorded at the time of implantation. This provides for an expected patency rate of 87.5% for the entire series. Histological examinations of patent grafts demonstrated fibroblastic ingrowth, capillary formation, and the development of uniform, smooth neointima throughout the lengths of the grafts, as well as over the suture line.

The second series of experiments involved the implantation of 107 grafts of which 51 have been harvested over time periods ranging from 2 weeks to 4 months. Of these 51, 12 were occluded, yielding a 76.4% patency rate. The remaining 56 grafts are presently in living dogs with palpable pulses over the grafts yielding an expected patency rate for the entire series of about 88%. In these two series, all grafts with a fibril length ranging from 5 to 20 microns yielded a 100% patency rate. Histological examination of all patent grafts has shown transmural fibroblastic and capillary ingrowth with uniform neointimal development over the grafts and suture line surfaces.

EXAMPLE 2

Thirty-two grafts constructed from expanded, porous PTFE were substituted in one carotid artery in each of 32 sheep. The internal diameter of the grafts varied from 3 mm to 5.6 mm, with the graft lengths varying from 8 cm to 12 cm. The variables of wall thickness (20, 32, and 62 mils), density (0.22 to 0.34 g/cc), and fibril length (3 to 150 microns) were controlled. Heparin was administered during surgery. However, anticoagulants were not used during the post-operative period. Thus far, grafts have been harvested at 3 weeks, 6 weeks, 3 months, and 6 months. All these grafts were patent. The remaining grafts have palpable pulses over the grafts and are therefore patent.

Histological examination demonstrated that grafts with fibril length ranging from 20 to 150 microns contain fibroblastic and capillary ingrowth as well as neointimal development throughout the graft's lumen. Grafts with less than about 7 microns fibril length displayed an absence of fibroblastic and capillary ingrowth with no neointimal development over the graft's internal surface.

EXAMPLE 3

Grafts of expanded, porous PTFE were interposed in the carotid artery, femoral artery and femoral vein of mongrel dogs. The graft internal diameters ranged from 2.8 mm to 3.3 mm and were all 4 cm in length, with wall thickness of 32 mils, density ranging from 0.21 to 0.35 g/cc and a fibril length ranging from 25 to 1000 microns. Of the 36 grafts implanted, 18 have been harvested, 3 each at intervals of 1 month over a period of 6 months. Of these, none were occluded, yielding a 100% patency rate. Of the remaining 18 grafts, all are in living dogs with palpable pulses over the grafts indicating patency. Therefore the expected patency rate for the entire series is 100%. Histological findings confirm both fibroblastic and capillary ingrowth with thin, uniform neointimal development.

EXAMPLE 4

In the past two decades a variety of prosthetics have been developed for the replacement of large diameter arteries, e.g. over about 10 mm inside diameter. These prosthetics have failed to develop the neointima required for both long-term patency and the 100% elimination of microemboli (composed of platlet aggregates) which leads to neurological and physiological complications when they dislodge into the blood stream. Also, these prior prosthetics have given poor results when utilized in the venous system where flow rates are extremely low.

In this series of experiments 12 grafts of expanded, porous PTFE were interposed in the abdominal aortas of 12 dogs. All were 7.5 mm in diameter and 10 cm in length. All grafts possessed a wall thickness of 20 mils and fibril lengths of 20 to 40 microns. Of the 12 implantations, 5 grafts were harvested between 3 and 6 weeks and submitted for histological study. The remaining are in living animals and indicate patency. The five harvested grafts were patent with no presence of intimal thickening in any of the grafts. Histological examination of the five patent grafts demonstrated fibroblastic ingrowth and capillary formation. The expected patency rate for the experiment is 100%.

It is apparent that the foregoing specific illustrations of the artificial vascular prostheses of the present invention are only illustrative of the scope of this invention. Medical research necessarily proceeds slowly and cautiously. Results on animal research wherein healing patterns are similar to those in humans clearly indicate the potential benefits to be achieved in human vascular replacements resulting from tissue ingrowth and capillary formation throughout the polymeric substructure of this invention, together with the absence of embolization and high degree of patency. Definitive clinical results are not yet available. However, it is the goal of, and clearly within the scope of my invention to provide an artificial vascular prosthetic suitable for implantation in humans, possessing the abovementioned beneficial characteristics and properties.

Also the fibril-node structure of these prosthetics are generally suitable for other than vascular applications. The tissue ingrowth has been shown to occur in skin grafts and in membranes implanted subcutaneoulsy. Such grafts need not contain blood under the driving force of arterial pressure, and therefore the upper limit of fibril length for such applications is greater than 1000 microns, and is limited only by mechanical considerations.

While my invention has been disclosed herein in connection with certain embodiments and structural and procedural details, it is clear that changes, modifications or equivalents can be used by those skilled in the art. Accordingly, such changes within the principles of my invention are intended to be included within the scope of the claims below.

Claims

What is claimed is:

1. The method of replacing a part of the body by a device comprising expanded, porous polytetrafluoroethylene possessing a microstructure consisting of nodes interconnected by fibrils, wherein the length of substantially all of said fibrils exceeds 5 microns.

2. The method of claim 1 for replacing a vascular conduit by a tube of expanded, porous polytetrafluoroethylene wherein the length of substantially all of said fibrils exceeds 5 microns.

3. The method of claim 2 wherein the length of substantially all of said fibrils falls within the range 5-1000 microns.

4. The method of claim 3 wherein the expanded, porous polytetrafluoroethylene possesses a matrix tensile strength in at least one direction exceeding 7,300 psi.

5. The method of claim 3 wherein said fibrils are about 20-100 microns in length.

6. The method of claim 4 wherein said fibrils are about 20-100 microns in length.