Intimal Lining And Pump With Vertically Drafted Webs

Abstract

An intimal lining and a circulatory assist device comprising a pump means with associated inlet and outlet valves and means for connecting said pump to a human arterial blood supply containing at least in the pump chamber a non-porous elastomeric substrate with an intimal lining consisting of a vertically expanded microfiber web of polypropylene fibers 10-50 microns deep and containing a substantial percentage of surface pores in the range 20-100 microns and in which the fibers have an average fiber diameter of about 0.05-1.0 micron.

Description

The present invention particularly relates to a product for producing vertically expanded fibrous webs suitable for making blood compatible intimal linings for circulatory assist devices. Such webs are designed to provide a substrate for infiltration by cells which will develop into a securely anchored living lining of healthy tissue (neointima) on the surface of a prosthesis to prevent thrombosis and other complications associated with blood/polymer interactions. Thus, such linings find use on the walls of artificial hearts and other circulatory assist devices within and without the body, such as arterial prostheses and linings for blood pumps. Such circulatory assist devices are fashioned from a pump means with associated inlet and outlet valves and means for connecting said pump to a human arterial blood supply containing at least in the pump chamber a non-porous elastomeric substrate with an intimal lining consisting of a vertically expanded microfiber web of polypropylene fibers 10-50 microns deep and containing a substantial percentage of surface pores in the range 20-100 microns and in which the fibers have an average fiber diameter of about 0.05 - 1.0 micron. The lining for circulatory assist devices of the present invention is a porous or fibrous surface rendered compatible with blood by permanent ingrowth of an intimately entrapped cellular layer which completely covers the artificial surface, thus replacing the blood/material interface with a blood/tissue interface. It is expected that such an intimal lining or neointima, for ideal maintenance conditions, should have a thickness of about 10-100 microns, and preferably 10-50 microns. Target values for fiber diameter of about 1 micron and fiber web thickness of about 10-50 microns have therefore been established.

The formation of the specialized webs of this invention is the culminating effort of a series of steps, a portion of which is in the prior art.

Step 1. Preparation of Ultrafine Plastic Fibers. A melt immiscible blend of a polyolefin and an ethylene-acrylic acid copolymer, e.g., 60 percent polypropylene/40 percent ethylene-acrylic acid copolymer, is subjected to longitudinal drafting after melt extrusion of the two incompatible thermoplastics. When the above mixture of immiscible polymers is mechanically worked in the molten state, the result is the formation of a melt containing insoluble polymer droplets which are on the order of 10 microns in diameter. On extrusion, these droplets become a composite of rod-like bundles of fibers of the component thermoplastics. After stretch or longitudinal orientation, the ethylene-acrylic acid copolymer portion is removed by a suitable solvent, leaving ultrafine polypropylene fibers having a diameter in the range 0.05 - 1.0 micron which are uniform in diameter and essentially circular in cross section. The ethylene-acrylic acid copolymer is removed from the tape by treatment in dilute aqueous base at 90.degree.-95.degree.C. The ethylene-acrylic copolymers contain at least 14 percent acrylic acid and generally in the range 20-50 percent acrylic acid. Additional alternatives to the process and the materials employable are described in Belgian Pat. No. 751,610 (Union Carbide, 1970).

A generalized teaching of co-extrusion of mutually immiscible thermoplastics followed by extraction or removal of one component is taught in U.S. Pat. No. 3,099,067 Merriam et al (Union Carbide).

Step 2. Formation of Thin Fiber Networks by Transverse Drafting. Transverse drafting is achieved by a tenter arrangement wherein opposite sides of the tape are seized manually or by hooks and the tape is expanded 100-150 fold perpendicular to direction of extrusion.

The transverse drafting imparts to the fibers several changes in that (1) they lose their parallel orientation, (2) the area of the fiber sheet increases, (3) its thickness decreases, and (4) the void content of the network increases.

The Web, after transverse drafting and drying, may be as thin as 2 microns and ranging up to about 50 microns. The transverse drafting is preferably achieved in cold water leaving an alkaline pH. This step is described in Belgium Pat. No. 751,610.

Step 3. Dilute Acid Treatment and Freeze Drying. The web which had previously been subjected to dilute basic treatment in the extraction step is now acidified to insolubilize the remainder of any ethylene-acrylic acid copolymer which deposits on the polyolefin web, giving it added strength. Additionally, the web is subjected to freezing, e.g., by immersing in hexane cooled with dry ice and freeze drying under vacuum (1 mm Hg pressure) to produce a highly porous dry web. An optional added step includes a machine direction drafting of the gossamer-type fiber web 2-3 times its original width to improve uniformity.

A substantial portion of the work above is reported in the literature by a group of scientists headed by Dr. J. S. Byck from the Union Carbide Corporation partly under a contract for NIH (Contract PH-43-68-1388, published by the National Technical Information Service under PB 187-485 and PB 201-935, covering work from June 1968 - September 1970, with a last library received date of Aug. 23, 1971).

SPECIFICITY OF MATERIALS

The starting material for extrusion preferably contains 50-60 percent polypropylene (and optimally 55-60 percent) with the balance being an ethylene-acrylic acid copolymer immiscible in polypropylene and capable of being water extracted from the mixture when converted into alkali and/or ammonia and/or amine salt form. Lowering the polypropylene content below 50 percent leads to an incoherent product. Polyethylene and polystyrene are less preferred alternatives to polypropylene.

The ethylene-acrylic acid copolymer fraction, whose parameters are controlled by solubility in dilute aqueous alkaline solutions, has been adequately described in the prior art as for example, in Belgian Pat. No. 751,610 (Union Carbide, 1970). In this patent it is noted that in the immiscible polymer mixture polypropylene and ethylene/acrylic and/or methacrylic acid copolymers, a polyol extraction aid is utilized and that the product is an immiscible polymer blend suitable for later rapid extraction of the acrylate fraction. The extractable copolymers noted in the above patent contain at least 14 percent acrylic and generally in the range 14-55 percent acrylic or methacrylic and the remainder is ethylene. A preferred extraction assistant is glycerine.

Most preferred copolymers are those containing a percentage of salt form of the acrylic or methacrylic acid ranging from 20-75 percent conversion of the carboxyl groups. The salt form enhances water solubility and capability of disolution of the copolymer after extrusion. The salt forms, such as alkali metal, ammonia, and amine type salt varieties, are more amply described in U.S. Pat. No. 3,264,272 Rees (DuPont) and U.S. Pat. No. 3,321,819 Walter et al (Union Carbide). A substantial improvement in the speed and efficacy of the leaching step is achieved by using these acrylate copolymers partially in the salt form. They may also be described as ionomers with cross linking potential through salt forming monovalent cations. A preferred variety may also be described as ethylene-acrylic acid interpolymer alkali metal salts.

FIBER BONDING AGENT AND ADHESIVE

In order to utilize the work product of the prior art above, it was necessary to bond the network to nonporous substrates and this, due to a variety of factors, required the selection of a specific material. The solution to the problem involved the utilization of the properties of parylene polymers (poly Para-xylylenes) which provided the necessary thin films by vapor vacuum sublimation and deposition. These films formed a coherent conformal coating which can be made pin-hole free in films as thin as 250 A units. Thus, vapor deposition of a parylene film on the microfiber web results in an encapsulation of each fiber in a parylene sheath as well as a formation of a continuous parylene film in the interface of an impermeable substrate, such as silicone rubber or polyurethane. The composition and technology of para-xylylene polymers (parylene) are taught in one or more of the following Union Carbide U.S. Pat. Nos. 3,288,728 Gorham 3,342,754 Gorham 3,429,739 Tittmann et al.

A preferred fiber bonding agent utilized is Parylene C or poly(chloro-para-xylylene) of Union Carbide. It has been found that a coating of Parylene C on the microfiber web, in the nature of a coating thickness of about 5,000 A units, results in a loss of porosity only of about 6 percent. In general, a polyxylylene coating of about 1,000 A units in thickness appears to be sufficient to provide the necessary adhesion and reinforcement. The modus of utilization of the polyxylylenes on the web may also be described as a sheath encapsulation achieved by vapor deposition.

VERTICAL DRAFTING (THE PRESENT INVENTION)

Vertical drafting is a procedure by which the expanded webs of the prior processing can be further opened into nonwoven networks wherein the strata near the surface to be exposed to blood contain extremely large pores.

In this process adhesive-coated polymer film is pressed against the surface of a microfiber web bonded to a nonporous substrate, e.g., a polyurethane film or silicone rubber such as might be utilized for the interior of a hemispherical pump diaphragm (Baylor/Statham Ventricular Bypass Pump) or a silicone rubber pumping chamber (Helical Materials Test Pump).

In general, vertical drafting may be achieved according to the present invention by coating a base of polyurethane film (nonporous) with a pressure-sensitive adhesive, then bringing the coated base in contact with a square of nonwoven polypropylene fabric already bonded to a nonporous substrate, applying a measured weight, and then vertically separating the polyurethane film away from the polypropylene fabric. This vertical drafting technique consists of applying vertical stress to the web which forcibly dislocates a significant number of fibers from the original points of attachment. As a standard, prior to separation, a weight was placed on the polyurethane film for one minute of about 35 g/in.sup.2. If repeated 1 to 2 times, a distinct change in texture of the mid layer of the sandwich occurs, leaving a gossamer web of extremely low density on each section. A substantial percent of pores present are 20 to 40 or more microns across as determined by examination using a scanning electron microscope. It has further been found that where the webs were vertically drafted, cells, such as Wish amnion cells, are able to penetrate through the pores of the upper layer of the fiber web and grow beneath the upper-most layer of fabric by spreading to the surface of the denser layers beneath. Under optimum conditions, three vertical drafting cycles on the same web produce a microfiber web, which is highly porous throughout its thickness, and a sequence of four drafting cycles appears in some cases to yield fiber webs which contain large bare areas of pore diameter .gtoreq.100 microns, which are significantly larger than single cells.

Electron microscope studies of webs and layers produced after vertical drafting show that gossamer-type webs are produced containing fibers averaging <1 micron in diameter and in the range 0.05 - 1.0 micron diameter overall. Further, the vertical drafting technique increases substantially the porosity of the uppermost layer of fibers of the web most remote from the surface of the solid substrate so that in the vertically drafted web, 10-50 microns in depth or thickness, a substantial percentage of web porosity in the 20-40 micron range resulted at that uppermost layer, thus permitting access of cells (e.g., 10 microns in diameter) to the interior of that layer. Repeated drafting procedures, optimally totaling three, produced increased uniformity of pore structure of the web. The pore size or surface openings of the vertically drafted web were measured using the largest transverse direction.

Thus, vertical drafting is a procedure by which freeze dried microfiber webs can be opened and the result is that the strata near the surface contain comparatively large pores. Additional vertical drafting increases the three-dimensional character of the network with a number of fibers oriented almost perpendicular to the substrate surface. This procedure differs from the previously known transverse drafting where few, if any, such fibers can be seen in this position. Further it was noted that the vertical drafting technique forcibly dislocates a significant number of fibers from their original point of attachment.

EXAMPLE 1

Preparation of Polymer Film Coated with Vertically Drafted Microfiber Web

Vertically drafted microfiber webs were prepared from nonwoven polypropylene fabric consisting of fibers which are one micron or less in diameter. The average thickness of the fabric can be made as little as 10 or as much as 50 microns. A 4 inch long strip of fabric was cut from a 2 inch wide roll of the nonwoven material. Strips of paper were adhered to the sides of the long edges of the piece of fabric. By gradually pulling the paper strips in opposite directions, the piece of fabric was tentered to form a square which is about 4 inch on a side. A square of half mil (0.0005 inch) thick solution cast polyurethane film was mounted on a flat 3 3/4 inch .times. 3 3/4 inch glass or plastic plate and was coated with a layer of pressure sensitive adhesive. The coating was applied by spraying or brushing on and was applied to a thickness of about 10 microns. The square of nonwoven polypropylene fabric was then brought into contact with the adhesive coated side of the polyurethane film and was thus adhered to the surface of the film. A sheet of two-and-one-half mil polypropylene film was then coated with a layer of pressure sensitive adhesive about 10 microns in thickness. The fabric covered polyurethane film was then placed on polypropylene sheet with the fiber coated side in contact with the adhesive layer on the polypropylene. A weight was placed on top of the polyurethane film, such that a pressure of about 35 g./in..sup.2 was applied and was kept in place for one minute. The weight was removed and the polyurethane film was carefully pulled away from the adhesive coated polypropylene sheet. Polypropylene fibers remained adherent to both surfaces. After the polyurethane and polypropylene films were pulled completely apart, so that no fibers remained simultaneously attached to both surfaces, any loosely attached fibers were removed from the fabric coating on the polyurethane film by picking them off with tweezers. The resulting fabric coating exhibited two layers. The uppermost layer was a random network of nonwoven fibers containing a substantial number of openings of 20-40 microns and up to about 100 microns wide (measured in the largest transverse direction). An underlying layer, closest to the surface of the polyurethane film, was a denser network of nonwoven fibers containing openings up to about 20 microns wide.

EXAMPLE 2

Preparation of Polymer Film Coated with a 3-Fold Vertically Drafted Microfiber Web

A vertically drafted microfiber web was prepared, as in the example above, bonded to a half mil polyurethane film. The fiber covered surface of the film was then brought into contact, for a second time, with an adhesive coated sheet of polypropylene film. The two surfaces were pulled apart as above, and the procedure was repeated for a third time. The resulting fabric consisted of only a single zone of fibers having the same high porosity described above for the upper-most region of the microfiber web which had been vertically drafted once.

EXAMPLE 3

Preparation of Cylindrical Tubes Lined with Vertically Drafted Microfiber Web

Cylindrical plastic tubes, suitable for use as artificial blood vessels or other implantable conduits, were lined with an ultrathin coating of vertically drafted microfiber web. A smooth-walled cylindrical tube (20 mm o. d. .times. 50 mm), with a wall thickness of about 1 mm, was fabricated by injection molding a thermoplastic polyurethane. The tube was slit, by making a straight cut in one wall parallel to the axis of the tube, and was then coated on the interior surface with a layer of pressure sensitive adhesive about 10 microns thick. A square of tentered nonwoven polypropylene fabric, prepared as in the example above, was placed on a flat sheet of paper and stretched taut between two weights. The slit, adhesive coated tube was uncurled to form a flat sheet, after which the adhesive coated side was pressed against the nonwoven fabric. Excess fabric was trimmed from around the edges of the flattened slit tube and the fabric covered side was then pressed against an adhesive coated polypropylene sheet, prepared as in Example 1. A weight was placed on top of the flattened tube, such that a pressure of approximately 35 g./in..sup.2 was applied and was kept in place for 1 minute. The weight was then removed and the tube was carefully pulled away from the adhesive coated polypropylene sheet. Any loosely attached fibers were then removed. The slit edges of the tube were brought into contact with one another in precise alignment using an external cylindrical holder and were fused together using an electrically heated knife edge. The resulting cylindrical tube contained a vertically drafted microfiber lining similar in fiber network openings to that described in Example 1 above.

The terms "acrylate" and "acrylate fraction," etc., as used in this specification and claims, are consonant with those described in Davidson, R. L., and Sittig, M., Water-Soluble Resins, II, (1968), pages 154-174, "Polyacrylic Acid and Its Homologs." They are further limited to hydrophilic or water soluble acrylic and methacrylic acid copolymers and salts thereof, excluding such difficultly hydrolyzable varieties as poly(methyl-methacrylate). A preferred acrylate fraction in the present invention is the copolymer ethylene/acrylic acid.

Claims

The embodiments of this invention in which an exclusive property or privilege is claimed are defined as follows:

1. The intimal lining for a circulatory assist device comprising a tissue layer growing on and anchored to an elastomeric substrate with a highly porous non-woven vertically drafted web, said web having a vertical thickness dimension of about 10-50 microns and a substantial percentage of surface pores in the range 20-100 microns and in which the fibers have an average fiber diameter of about 0.05 - 1.0 micron, said web having been produced from an elongated high modulus polyolefin microfiber tape which has been vertically drafted.

2. The intimal lining for a circulatory assist device according to claim 1 in which a polyxylylene conformal coating has been applied to the web.

3. The intimal lining for a circulatory assist device comprising an elastomeric substrate selected from at least one member of the group consisting of polyurethane and silicone rubber and a vertically expanded highly porous non-woven polypropylene web lining, said lining having a vertical thickness dimension of about 10-50 microns and a substantial percentage of surface pores in the range 20-100 microns and in which the fibers have an average fiber diameter of about 0.05 - 1.0 micron.

4. A circulatory assist device comprising a pump means with associated inlet and outlet valves and means for connecting said pump to a human arterial blood supply containing at least in the pump chamber a non-porous elastomeric substrate with an intimal lining consisting of a vertically expanded highly porous non-woven microfiber web of polypropylene fibers 10-50 microns deep and containing a substantial percentage of surface pores in the range 20-100 microns and in which the fibers have an average fiber diameter of about 0.05 - 1.0 micron.

5. The device according to claim 4 wherein the elastomer substrate is a polyurethane.

6. The device according to claim 4 wherein the elastomeric substrate is a silicone rubber.