WO1995001190A1

WO1995001190A1 - Improved cardiovascular patch materials and method for producing same

Info

Publication number: WO1995001190A1
Application number: PCT/US1993/007563
Authority: WO
Inventors: Thane L. Kranzler; Norman Joseph Sharber; Terry Alan Hubbard
Original assignee: W.L. Gore & Associates, Inc.
Priority date: 1993-06-29
Filing date: 1993-08-11
Publication date: 1995-01-12
Also published as: AU4997493A

Abstract

The present invention is a cardiovascular patch and graft material which is resistant to fluid loss through suture seam holes or similar openings and method for forming and using such material. The patch of the present invention employs a porous polytetrafluoroethylene (PTFE) membrane and elastomeric biocompatible material which is injected under a pressure differential to impregnate interior pores of the membrane. The amount of elastomer on the surfaces of the PTFE membrane is minimalized so as to avoid limitations and complications which have been inherent in previous attempts to create bleed-resistant vascular patches and grafts.

Description

IMPROVED CARDIOVASCULAR PATCH MATERIALS AND METHOD FOR PRODUCING SAME

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to apparatus and method for sealing blood vessels and certain organs. More particularly, the present invention is a cardiac and cardiovascular patch, and method for producing and using same, which is resistant to leakage through suture holes.

2. Description of Rel ted Art

Artificial graft, patch, and tube materials are commonly employed today to seal openings in blood vessels and certain organs, such as the heart. As used herein, the term "cardiovascular patch" is intended to encompass any such material, regardless of shape, which is applied over a cut, tear, or other opening in a blood vessel or similar organ.

Cardiovascular patches generally comprise a membrane of bioco patible material which is sewn or otherwise adhered over an opening in the blood vessel. As so employed, the patches prevent leakage through the opening and can be used either as a temporary or permanent seal, and/or in conjunction with promoting healing of natural tissue. Depending upon the demands of particular applications, patches can be made from either resorbable or non- resorbable material. In the field of tubular grafts, examples of patents disclosing both resorbable and non-resorbable materials include United States Patents 4,416,028 issued November 22, 1983 to Eriksson et al . and 4,652,264 issued March 24, 1987, to Dumican. One of the difficulties in producing such grafts is that it is often desirable to provide a graft which is porous or at least somewhat permeable to provide a more biocompatible surface and to permit tissue in-growth, yet is impervious to fluid penetration. One example of such a patch is taught in United States Patent 4,743,252 issued May 10, 1988 to Martin, Jr. et al . This graft employs an impervious membrane, such as silicone rubber, formed between two or more layers of porous material. Unfortunately, this construction is believed to be deficient in a number of respects, such as being too resistant to gas passage through the patch material and being too limited in possible applications. One of the more successful biocompatible materials used today in a wide variety of biomedical applications is polytetrafluoroethylene (PTFE), and particularly expanded PTFE (ePTFE), such as that made in accordance with the teachings of United States Patents 3,953,566 issued April 27, 1976, to Gore, 3,962,153, issued June 8, 1976, to Gore, and 4,187,390 issued February 5, 1980, to Gore. This exceptionally inert and biocompatible material can be formed to have relatively high tensile strength. Moreover, ePTFE membranes provide a unique micro-porous structure which is waterproof (i.e. resisting liquid penetration) while remaining quite permeable to water vapor (i.e. allowing air and liquid vapor to pass through). It has been recognized that these properties both promote healing and avoid many serious problems, such as serous fluid transudate.

As such, ePTFE membrane and fibers are used in many different areas of bio edicine, including as grafts, sutures, vascular patches, prosthetic vessels, and are used to seal a variety of wounds or incisions in medical, dental and veterinary procedures.

With PTFE serving as an effective barrier to liquid body fluid penetration, a growing area of concern has become the seepage of liquid around PTFE material, and especially through seam holes created by suturing PTFE material in place. As is known, it is common for a surgical needle to be of a slightly greater diameter than the diameter of the suture, establishing a slight gap through which fluid can pass. Additionally, the stresses imposed by sutures tend to strain the PTFE material and enlarge any seam opening therethrough. As a result, there has developed an increased interest in finding some way to decrease or eliminate these problems.

In United States Patents 5,100,422 issued March 31, 1992, to Berguer et al. and 5,104,400 issued April 14, 1992, to Berguer et al . it is proposed to dip or spray coat the abluminal (i.e. outside) side of a blood vessel patch of PTFE with a layer of polyurethane, silicone, or similar elastomer. The purpose of this coating is to cause the elastomer to contract around the suture when sewn in place to limit seepage through the seam holes.

Unfortunately, the patches proposed by these patents have a number of serious drawbacks. First, since many of the benefits of ePTFE membrane are achieved by having the porous side of the PTFE serving as the luminal side (i.e. facing the interior of the blood vessel) of the graft, these patents emphasize that care must be taken to mark the coated side of the graft so that it will be applied abluminally. This orientational bias presents a host of problems to the user, who must negotiate the intricacies of a medical procedure while also making sure that the patch is correctly positioned. This problem is compounded when the patch is cut to relatively small dimensions. Further, as should be clear by review of the Berguer et al . patents, the marking procedure itself is relatively complicated—needlessly increasing the cost of producing the patches.

Second, the use of a polyurethane coating on one side of a PTFE membrane is also considered too limited to be widely employed. Among the believed deficiencies of these products are: in addition to being neither porous nor permeable, polyurethane cannot normally serve as a blood contact material since it is prone to break down; a polyurethane coating is believed to result in excessive suture drag; and such coatings are not resorbable and cannot provide leakage protection in resorbable products. Other patents proposing some form of elastomer coating include United States Patents 4,304,010 issued December 8, 1981, to Mano (a tubular prosthesis of PTFE with a porous rubber coating on its exterior surface); 4,321,711 issued march 30, 1982, to Mano (a tubular prosthesis of PTFE containing an anti-coagulant substance and again coated on its exterior surface with a porous elastomer); 4,878,907 issued November 7, 1989, to Okada et al . (a tubular prosthesis constructed from a porous elastomer such as polyurethane and coated on its interior surface with a hydrogel material to avoid thrombosis); 4,990,158 issued February 5, 1991, to Kaplan et al. (a tubular prosthesis employing a nonabsorbable elastic core yarn and an absorbable relatively inelastic sheath yarn); 5,061,276 issued October 29, 1991, to Tu et al.,(employing a coating of elastomer and a winding of elastomer fibers around a substrate of PTFE); 5,152,782 issued October 6, 1992, to Kowligi et al . (a non- porous tubular prosthesis with a porous PTFE interior and a dip or spray coated exterior of non-porous polyurethane); and WIPO Application WO 91/19520 published December 26, 1991 (a tubular prosthesis of PTFE dipped coated in polyurethane or similar elastomer).

Although many of the above patents attempt to address some of the same concerns, regrettably all of these devices suffer from one or more drawbacks, such as positional bias—with one of the sides including a material which is not suitable for blood contact, limited applications, difficulty in manufacture and/or handling, etc.

Accordingly, it is a primary purpose of the present invention to provide a cardiovascular patch material which includes most of the advantages of a porous PTFE grafts while being resistant to seepage of fluid through small openings therein, such as suture holes.

It is a further purpose of the present invention to provide such a patch material which is easily manipulated and positioned by a user, without concern of positional bias between surfaces of the material.

It is another purpose of the present invention to provide a patch material which has wide applications and can be formed with either resorbable or non-resorbable material. These and other purposes of the present invention will become evident from review of the following specification.

SUMMARY OF THE INVENTION

The present invention is a patch material for use in a variety of medical or similar procedures where bleeding should be minimized, and method for forming and using such material. The patch material of the present invention comprises a porous polytetrafluoroethylene (PTFE) and an elastic or reboundable biocompatible material, such as resorbable elastomer or hydrogel, (hereafter "elastomeric material") which is embedded within the porous structure of the PTFE. Excess elastomeric material is removed from the surfaces of the PTFE so as not to interfere with its function.

When an opening is formed in the patch, such as in a suture seam, the elastomeric material rebounds, swells, or both into the opening to reduce fluid loss therethrough. Since the elastomeric material is impregnated into the interior of the PTFE, limitations and possible complications from the presence of such material on the surface of the patch are significantly reduced.

The patch of the present invention is formed by injected elastomeric material within the porous membrane under a pressure differential. Multiple patches can be formed by a variety of methods, including through use of pressure or vacuum motivated flow chamber apparatus disclosed herein.

The cardiovascular patch material of the present invention includes the advantages of a porous PTFE grafts while being resistant to leakage through suture holes and similar openings. Moreover, the patch material of the present invention is relatively easily manipulated and positioned by a user, without concern of positional bias between surfaces of the material.

DESCRIPTION OF THE DRAWINGS

The operation of the present invention should become apparent from the following description when considered in conjunction with the accompanying drawings, in which: Figure 1 is an elevational view of a cardiovascular patch of the present invention shown being attached to an opening in a blood vessel;

Figure 2 is a partially schematic elevational view of apparatus used to form the patch material of the present invention; Figure 3 is a front elevational view of a sample fixture employed in the apparatus of Figure 2;

Figure 4 is a cross-sectional view along line 4-4 of Figure 3; Figure 5 is a partially schematic elevational view of another embodiment of apparatus used to form the patch material of the present invention; Figure 6 is an exploded elevational view of a sample fixture element employed in the apparatus of Figure 5.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is an improved cardiovascular patch material for use in sealing openings in blood vessels and similar structures, such as cardiac tissue, and a method for producing and using the same.

Shown in Figure 1 is a cardiovascular patch 10 of the present invention being applied over an incision 12 in an artery 14. As is common in procedures of this type, the patch 10 is sewn into place using sutures 16, forming a series of seam holes 18 in the patch 10.

The patch material comprises a membrane of polytetrafluoroethylene (PTFE), and preferably a porous expanded PTFE (ePTFE) such as that taught in United States Patents 3,953,566 issued April 27, 1976, to Gore, and 4,187,390 issued February 5, 1980, to Gore. This material is commercially available from W. L. Gore & Associates, Inc., of Flagstaff, AZ, under the designation GORE-TEX* Cardiovascular Patch in different dimensions and in 0.4 and 0.6 mm thicknesses. As has been explained, this material has numerous properties which make it uniquely suited for medical applications, including being highly biocompatible and both waterproof and vapor permeable. These properties allow the membrane material to be mounted in direct contact with blood and other body fluids without causing thrombosis or other complications.

Since the ePTFE is especially resistant to liquid penetration, the primary area where body fluid seepage can occur is through the seam holes 18 or other openings formed in the patch 10. Previous attempts to correct this problem have usually centered around providing some form of elastomer coating, generally polyurethane or silicone, on the abluminal (i.e. outside) surface of the patch. Although this may help to limit the size of seam holes, it produces a positional bias in the patch material which requires it to be carefully handled and mounted with the elastomeric coating facing outwardly.

In order to resist seepage of liquid through the seam holes 18 in the present invention, an elastomeric material has been completely embedded within the porous ePTFE membrane. Preferably, the elastomeric material comprises a biocompatible material which will not cause complications if it is mounted in contact with blood or other body fluids.

A preferred resorbable polymer material comprises a mixture of L-lactide, glycolide, and epsilon-caprolactone. Although components of this mixture do not provide the necessary elastomeric properties alone, in combination these components provide a superior elastomer for use in the present invention. Preferably, the components are mixed as follows: a mixture of E-caprolactone and L-lactide in combination as taught by United States Patents 4,057,537 and 4,643,734 where the resulting product is elastic; E- caprolactone and DL-lactide in combination as described in United States Patents 4,045,418 and 4,643,734 where the resulting product is elastic; or E-caprolactone, L-lactide, and glycolide in combination as described in United States Patent 4,045,418. Suitable resorbable elastic material was acquired from Stolle Research & Development Corp., Cincinnati, OH, in response to the following requested properties: resorbable (degrading within a few weeks), elastic, tensile strength of 1,000 to 1,500 (although this parameter is not considered critical), and glass transition temperature of between 25 and 40°C (to soften slightly at body temperature).

For non-resorbable applications, it is preferred to employ a hydrogel. These materials comprise a broad class of polymers which are water insoluble but swell substantially when placed in water or biological liquids. These products are commonly employed in a variety of industries, and particularly in the medical industry where they are used in such diverse areas as suture coatings and contact lenses. Such gels and the method of making them are specifically described in a number of patents, including United States Patents 4,379,874 issued April 12, 1983, to Stoy, and

4,943,618 issued July 24, 1990, to Stoy et al., and are available from a number of sources, including Kingston Technologies of Dayton, NJ. For use in the present invention, suitable hydrogel materials include polyethylene oxide (PEO), hydrophilic polyurethane, and polyhydroxy ethyl methacrylate (pHEMA). Other possibly suitable hydrogels may include xanthum gum and polyvinyl alcohol (PVA). It should be noted that the intent of the present invention is to provide a material which will rebound, swell, or both to fill suture holes or similar openings in cardiovascular patch material. Although not all hydrogels are cross-linked for mechanical strength and may not have traditional "elastic" properties (and therefore are not preferred for use in the present invention), such hydrogels may still swell and function adequately to seal suture holes when used in accordance with the teachings of the present application. Accordingly, the term "elastomeric material" should be read to encompass any material which will provide the rebounding and/or swelling reaction described herein.

In order to form a superior seal, and to avoid the positional bias inherent in previous attempts to place elastic coatings on graft material, the ePTFE membrane of the present invention is impregnated with the elastomeric material so that the body fluids are shielded from the elastomeric material by the outer surfaces of the ePTFE membrane. This construction produces an exceptional elastic seal around sutures, significantly reducing bleeding through suture holes, while allowing the patch material to be handled in a manner similar to conventional PTFE cardiovascular patches.

Ideally, the porous PTFE is impregnated with elastomeric material by establishing a pressure differential, through vacuum and/or pressure, and injecting the elastomeric material within the pores of the membrane. One apparatus 20 for performing this procedure is illustrated in Figures 2 through 4.

The apparatus 20 shown in Figure 2 comprises a delivery syringe 22 filled with elastic polymer mounted in fluid communication with a sealed chamber 24 via first port 26. The opposite side of the sealed chamber 24 has a second port 28 mounted in fluid communication with a collection syringe 30. As is explained below, sheets of membrane material are mounted in series within the chamber 24 and are saturated with polymer when the polymer is transferred from the delivery syringe 22 through chamber 24 and into the collection syringe 30.

The transfer of polymer can be accomplished by any suitable means, including by pressurizing the delivery syringe 22 and/or forming a negative pressure in the chamber 24 or collection syringe 30. In the embodiment shown in Figure 2, the transfer of polymer is accomplished by providing an air cylinder 32, including an actuating arm 33, connected via an air regulator to an air compressor 34 or other means to provide syringe motivating force. By aligning the actuating arm 33 with a plunger 38 of the delivery syringe 22, polymer can be motivated into the chamber 24 under air pressure from the air cylinder 32. Positioning means 40 is provided to hold the delivery syringe 22 and the air cylinder 32 in aligned orientation.

The chamber 24 is shown in greater detail in Figures 3 and 4. The chamber 24 comprises two mated end plates 41a, 41b, ports 26 and 28, respectively, being provided therein. Aligned in series between the end plates 41a, 41b are multiple sheets of porous membrane 42a, 42b, 42c, 42d, 42e stacked parallel with each other. On either side of the sheets of porous membrane, in di ect communication with each of the ports 26, 28, are layers of filter material 44, 46. The filter material 44, 46 serves to disperse the polymer and provide an even flow of elastomer over the entire area of each of the sheets of porous membrane. One suitable filter material is a woven polypropylene fiber available from Spectrum Medical Industries, Inc., of Los Angeles, CA, under the trademark SPECTRA MESH Polypropylene PP (Order No. 146418).

Once all elements shown in Figure 4 are properly positioned, the end plates 41a, 41b are attached to one another by means of bolts 48 or similar means. The sheets of membrane 42 and the filter material 44, 46, are then firmly compressed together between the end plates 41a, 41b.

Once the apparatus 20 shown in Figures 2-4 is arranged in the manner described, polymer can then be driven through the chamber 24 and into the porous membranes 42. Elastomer polymer should be delivered under a pressure until the porous membrane material has become saturated with polymer. Depending on a number of parameters, including the type and quantity of membranes employed and the type of solution and the pressures applied, general pressure ranges can extend from 3 to 60 psi, with 10 to 50 psi, and particularly 20 to 40 psi, being preferred. Duration of treatment generally runs about 4 to 60 minutes or more, although, depending upon the patch material and the thickness of the elastomeric solution, treatment may span a few seconds to 24 hours. Acceptable solutions for resorbable elastomers include a 1 to 15-20% solids weight solution of resorbable elastomer, with 1 to 5% being preferred, dissolved in a solvent such as acetone, ethyl acetate, or methylene chloride. Acceptable solutions for hydrogels include a 1 to 15-20% solution of hydrogel, with 7.5 to 12.5% being preferred, dissolved in a solvent such as dimethyl sulfoxide or sodium thiocyanate in water.

For a series of approximately five sheets of ePTFE membrane of 0.4 mm thickness, a polymer of resorbable solution or hydrogel dissolved in a fairly free flowing solution is preferably introduced under a pressure of 20 to 40 psi over a period of up to about 1 to 2 hours.

Once saturation of the membranes 42 has been achieved, most if not all excess elastomeric polymer should be removed from the membrane. While certain elastomeric compounds can be placed in blood contact with limited problems, it is preferred that a minimal amount of residual elastomeric polymer remains on the surface of the membrane. Depending upon the elastomeric polymer used, this can be accomplished in a number of ways. For the resorbable polymers described above, generally no further processing is required. The membrane is merely removed from the apparatus once it is saturated and allowed to dry. Ideally, the membrane is stretched over a frame or similar device during the drying process to assure a flat and even surface. The volatile nature of this polymer in solution assures that minimal polymer remains on the surface of the membrane when drying is complete.

For certain hydrogels, additional processing may be required. For example, with a HYPAN^β hydrogel available from Kingston Technologies, Inc., of Dayton, OH, after saturation, excess hydrogel is wiped or scraped off the surface of the membrane using a straightedge or similar device. At this stage, while the patch is still moist, the patch may be cut and packaged in a moisture- tight package. Alternatively, and quite preferably, the wiped patch material is placed into a solution of water to coagulate the hydrogel and then placed in a aqueous solution of glycerol (e.g. 50% water, 50% glycerol) to plasticize the hydrogel. Once plasticized, the patch can then be thoroughly dried prior to use. A hydrogel of polyethylene oxide or pHEMA should be able to be merely dried without plasticizing. Again, it may be desirable to stretch the material during the drying process for ease in handling of the final product. Once prepared, the membranes can then be cut to appropriate sizes for use as a cardiovascular patch material. It has been found that when prepared in this way, the cardiovascular patch material of the present invention can be handled and will perform in a manner similar to conventional ePTFE cardiovascular patches. More importantly, the presence of the elastomer filler allows the patch material to form a quick seal around sutures 16 to minimize blood loss through suture holes 18.

Another embodiment of apparatus for use in the present invention is illustrated in Figures 5 and 6. This apparatus 50 also employs an air compressor 52, a pressure regulator 54, an air cylinder 56 and actuating arm 58, a delivery syringe 60 including a plunger arm 62, and a treatment chamber 64. The primary difference in this embodiment comprises the construction of the treatment chamber 64. As is shown in exploded orientation in Figure 6, chamber 64 comprises a cylindrical casing 66, a two-part test fixture, including a first part 68 having a passage 69 down its center and a second part 70 adapted to receive the first part 69 and terminating in a port 71, multiple sheets of porous membrane 72a, 72b, 72c, 72d, and a sealing ring 74 with an opening 75 therein corresponding in dimensions to port 71. A layer of silicone 76 or similar material is provided on the first part 68 of the test fixture to form a tight seal within the second part 70. As is shown, the porous membranes 72 are cut to appropriate sizes to between fit between port 71 and the opening 75 in ring 74.

Once these elements are arranged in this manner, bolts (not shown) or similar means are installed through appropriate bolt holes 78, 80, 82 and the elements are tightly compressed together. Treatment then proceeds in a manner similar to that described above.

It should be understood that the apparatus illustrated in the drawings and discussed above are suitable for relatively small scale batch preparation of patches of the present invention. For larger scale production, it is contemplated to employ means to produce saturated membrane on either a continuous basis or in large scale batch production, such as with multiple chambers arranged in parallel. To accomplish this, any form of system to deliver polymer through the membranes via a pressure differential may by suitable, including means to motivate polymer continuously under pressure from a polymer supply and/or means to draw polymer continuously from a polymer supply under vacuum.

The patch of the present invention can be applied to many different types of vascul r repairs and reconstructions. Among the suitable applications are: great vessel repair or enlargement, cardiac free wall replacement or repair, peripheral vessel repair for stenosis due to vascular disease or trauma, or repair of vascular trauma caused by such inflictions as cancer or misadventure. These conditions are represented by procedures such as: coarctation of the aorta, pulmonary stenosis, right ventricular outflow tract widening, ventricular aneurysmectony, post endarterectomy patch angioplasty, profundaplasty, and revision of arteriovenous access fistulas. The patch material may also be formed into a tube or other useful shapes for certain applications (e.g. as a tubular vascular graft).

In addition to sealing around suture holes, the present invention has numerous other possible applications. For example, the patch of the present invention is particularly useful for procedures requiring repeated insertions of a needle through the patch material, such as in dialysis treatments or similar administrations. Moreover, the patch of the present invention is far less prone to compromise due to accidental punctures during use. Without intending to limit the scope of the present invention, the composition and method of the present invention may be better understood in light of the following examples: EXAMPLE 1 A resorbable elastomeric material was specifically ordered from Stolle Research and Development Corp. of Cincinnati, OH, with the following properties: L-lactide/glycolide/epsilon-caprolactone ratio (by NMR) of 65.0:17.6:17.4; weight average molecular weight (Mw) of 545,152; number average molecular weight (Mn) of 139,045; inherent viscosity (dL/g) of 2.05; glass transition temperature (Tg) of 27.1°C; Tg after dissolution in methylene chloride and precipitation in heptane of 33.2; residual L-lactide of 1.55%; and residual E-caprolactone of 3.14%. The general construction of this type of resorbable elastic polymer is taught in a number of patents including United States Patents 4,045,418, 4,057,537, and

4,643,734. The polymer was dissolved in acetone to make 15% by weight and 3% by weight solutions.

Conventional 0.4mm Cardiovascular Patch material, available from W. L. Gore & Associates, Inc., Flagstaff, AZ, under the trademark GORE-TEX Cardiovascular Patch, was cut to about 3 inches square and placed in the flow chamber apparatus illustrated in Figures 2-4. A total of six pieces were prepared simultaneously, but the top and bottom pieces of the stack were discarded. Pure acetone was first driven through the material at 40 psi. Next, a 15% polymer solution was driven through the material at 40 psi over about 3 hours. The four samples were then stretched and allowed to dry on a 3" x 4" frame overnight. Additional samples were made using the same technique but with the 3% solution.

A sample and control of a standard untreated 0.4mm Cardiovascular Patch of the same size were then implanted in surgically created elliptical defects in one of eight test animals and released simultaneously. The amount of bleeding through the patch material was estimated using pre-weighed 3" x 3" gauze to absorb the leaked blood. Blood was collected until hemostatis was achieved or for 15 minutes. The blood loss for the experimental patch and the control patch is described by the blood flow of the two patches, defined as: (grams blood loss for the experimental

SUBSf ITUTE SHEET -13a- patch)/(grams blood loss for the control patch). The results are summarized below:

SUBSTITUTE SHEET 14

Time to Time to Blood

Hemostasis Hemostasis Loss

Animal # Test (min.) Control (min.) Ratio

1 (*) 7.3 4.1 3.55

2 (*) 8.1 11.5 1.95

3 (*) 6.0 11.0 0.28

4 (+) 6.0 8.0 2.83

5 (+) 15.0 >15.0 2.12

6 (+) 10.0 8.7 1.49

7 (+) 3.2 4.0 0.67

8 (+) >15.0 >15.0 0.49

* = Sample with a 15% polymer solution

+ = Sample with a 3% polymer solution

The first three implants with the 15% polymer solution show improvement as the experiment'progressed. The five implants with

3% polymer solution also show this trend. The continued improvements in the results is believed to be due in part to increasing familiarity with the handling characteristics of the new patch material, which tends to be somewhat stiffer than conventional patch material. It is anticipated that after additional implants with this material, even better results would be achieved.

Another measure of suture line performance is the time to hemostasis. The experimental patches achieved hemostasis first in five of the seven cases in which hemostasis was achieved by either patch.

EXAMPLE 2

An elastomeric hydrogel material was obtained from Kingston Technologies, Inc., of Dayton, NJ, under the designation HYPAN HN68. This hydrogel is a hydrophilic polymer composed of hard and soft segments. The polymer was dissolved in dimethylsulfoxide (DMSO) to make a 7.5% by weight solution.

Standard 0.4 mm GORE-TEX Cardiovascular Patch material was cut into discs approximately 30 mm in diameter and placed in the flow chamber apparatus 50 similar to that illustrated in Figures 5 and 6. Samples for this experiment were filled with the hydrogel driven from a syringe by hand until the solution flowed through the 15

material. Subsequent experiments have demonstrated that about 30 psi driving pressure works well. Samples were then placed in water for about five minutes to coagulate the polymer. Next, samples were removed from the fixtures and excess polymer was removed from the samples surface using a sharp blade.

It should be noted that polymer may also be removed prior to coagulation. Additionally, it may be possible to remove the excess polymer through a chemical process.

Samples were then placed in water overnight. Next, samples were placed in a 50% water/50% glycerol solution for approximately eight hours. The glycerol plasticizes the hydrogel. Samples were then removed to dry overnight. Samples were cut to about 0.5 cm x 2.5 cm for implant.

A sample and control of a standard untreated 0.4mm Cardiovascular Patch of the same size were then implanted in surgically created elliptical defects in one of five test animals and released simultaneously. The amount of bleeding through the patch material was estimated using pre-weighed 3" x 3" gauze to absorb the leaked blood. Animals were maintained at an elevated activated coagulation time (ACT) through administration of heparin and Indomethacin. The blood loss for the experimental patch and the control patch is described by the blood flow ratio of the two patches, which is defined as follows: (grams blood loss for the experimental patch)/(grams blood loss for the control patch). The results are summarized below:

Time to Time to Blood

Hemostasis Hemostasis Loss

Animal # Test (min.) Control (min.) Ratio

1 >20.0 >20.0 0.71

2 17.6 >25.0 0.46

3 >20.0 >20.0 0.56

4 12.3 >22.0 0.44

5 5.0 >20.0 0.84

The average blood loss ratio for the HN68 material comparisons was x-0.50 (s-0.23). This indicates that the HN68 material reduced 16 suture line bleeding by about 50%. It should be noted that there is some inconsistency in the blood volume collection. Three of the platelet inhibited dogs achieved hemostasis with the experimental patch but not with the control patch. In each of these animals, the control patch blood was collected for a different length of time (20, 22, and 25 min.), but the improved suture line performance of the hydrogel filled patch was still apparent.

Another measure of suture line performance is the time to hemostasis. The experimental patches achieved hemostasis in 3 of 5 cases while the control patch did not achieve hemostasis in any of the comparisons.

It should be evident from the foregoing experimental results that the elastomer filled cardiovascular patch material of the present invention produces significantly improved performance with regard to suture line bleeding without the detrimental limitations of previous attempts to incorporate elastomeric material in cardiovascular patches.

While particular embodiments of the present invention have been illustrated and described herein, the present invention should not be limited to such illustrations and descriptions. It should be apparent that changes and modifications may be incorporated and embodied as part of the present invention within the scope of the following claims.

Claims

17

The invention claimed is: 1. A cardiovascular patch which comprises: a porous membrane of expanded polytetrafluoroethylene (PTFE) having top and bottom surfaces; an elastomeric biocompatible material thoroughly embedded within interior pores of the membrane with minimal elastomeric material present on either the top or bottom surfaces of the porous membrane; wherein when an opening is formed in the patch the elastomeric material within the membrane closes into the opening to resist leakage through the patch. 2. The patch of claim 1 wherein the elastomeric biocompatible material comprises a resorbable polymer. 3. The patch of claim 2 wherein the resorbable polymer comprises a mixture of L-lactide, glycolide, and epsilon- caprolactone. 4. The patch of claim 1 wherein the elastomeric biocompatible material comprises a hydrogel. 5. The patch of claim 4 wherein the hydrogel is selected from the group consisting of polyethylene oxide (PEO), xanthum gum, hydrophilic polyurethane, and polyhydroxy ethyl methacrylate (pHEMA). 6. The patch of claim 1 wherein the substrate is substantially free of biocompatible material on its top and bottom surfaces. 7. The patch of claim 2 wherein when an opening is formed in the patch material, the resorbable elastomer rebounds to seal the opening. 8. The patch of claim 4 wherein when an opening is formed in the patch material, the hydrogel swells to seal the opening. 9. The patch of claim 1 wherein the opening comprises a seam formed by a needle and sutures; and the elastomeric material closes around the sutures to resist bleeding through the suture seam. 10. The patch of claim 2 wherein the resorbable polymer comprises a mixture of L-lactide and epsilon-caprolactone. 18 11. A method of reducing leakage through a cardiovascul r patch applied to a surgical site, which comprises: providing a patch comprising a membrane of porous expanded polytetrafluoroethylene (PTFE) having top and bottom surfaces, and an elastomeric biocompatible material filling the pores within the PTFE with minimal elastomeric material on the top and bottom surfaces of the membrane; forming the patch into a shape to overlay the surgical site; applying sutures to seal the patch on the surgical site, the sutures forming openings within the patch when sewn in place: wherein the elastomeric biocompatible material within the patch seals around the sutures when they are sewn in place so as to assist in reducing fluid loss through the openings. 12. The method of claim 11 which further comprises: providing a biocompatible material selected from the group consisting of resorbable elastomer and hydrogel; and forming the patch by injecting the biocompatible material under a pressure differential within the membrane, saturating the pores within the membrane, and removing excess biocompatible material from the outside of the membrane. 13. A method of producing an improved cardiovascular patch which comprises: providing a porous patch membrane; providing an elastomeric biocompatible material; placing the vascular patch membrane within a flow chamber; injecting the elastomeric material into the flow chamber under a pressure differential so as to cause it to impregnate interior pores of the membrane. 14. The method of claim 13 wherein multiple patch membranes are stacked in the flow chamber, the flow of elastomeric material passing in series through the membrane material so stacked. 15. The method of claim 13 wherein the pressure differential is established by motivating the biocompatible material under compression. 16. The method of claim 13 which further comprises providing a biocompatible material comprising a 19 resorbable polymer; pre-treating the membrane with a first solvent; forming a mixture of the biocompatible material with a second solvent prior to injection into the membrane. 17. The method of claim 16 wherein the first and second solvents include acetone. 18. The method of claim 17 which further comprises forming the mixture of biocompatible material and solvent in proportion of at least 3% by weight of biocompatible material. 19. The method of claim 18 which further comprises drying the substrate under tension after injection of the biocompatible material. 20. The method of claim 13 which further comprises providing a biocompatible material comprising a hydrogel; placing the substrate in an aqueous solution following injection to coagulate the hydrogel; and removing excess hydrogel from the membrane's surface following coagulation. 21. The method of claim 20 which further comprises placing the membrane in a plasticizer solution following injection of the hydrogel to assist in plasticizing the hydrogel; and drying the membrane after plasticization of the hydrogel. 22. A cardiovascular patch which comprises: a porous membrane of polytetrafluoroethylene (PTFE) having top and bottom surfaces; a biocompatible hydrogel material thoroughly embedded within interior pores of the membrane with minimal hydrogel material present on either the top or bottom surfaces of the porous membrane; wherein when a opening is formed in the patch the hydrogel material within the membrane closes into the opening to resist leakage through the patch.