US 3276448 A
Description (OCR text may contain errors)
United States Patent 3,276,448 COLLAGEN COATED FABRIC PROSTHESIS Richard L. Kronenthal, Fair Lawn, N.J., assiguor to Ethicon, Inc., Somerville, N.J., a corporation of New Jersey No Drawing. Filed Dec. 14, 1962, Ser. No. 244,600 4 Claims. (Cl. 128-334) This invention relates to prostheses adapted to be placed in the human body, and to a process for manufacturing the same. More particularly, the invention is directed to prostheses formed of porous, non-absorbable fabric coated with collagen.
For purposes of clarity, the terms used herein are defined as follows:
Tendon collagen fibril means a thread-like collagen structure derived from beef tendon that is round in cross section. These fibrils in the completely dehydrated state measure about 500 to 2000 Angstroms in diameter.
Swollen tendon collagen fibril means a collagen fibril derived from beef tendon that has been swollen in acid solution. The diameters of swollen collagen fibrils range from less than 5000 Angstroms to about 90,000 Angstroms.
Monofilament means a single thread of oriented collagen fibrils as extruded through a single orifice in a spinnerette.
Multifilament means a group :of individual separate collagen monofilaments extruded through a spinnerette. Further details are provided in related copending application Serial No. 216,247, filed August 10, 1962, and in Example XII of U.S. Patent No. 3,114,372.
Strand means a group of collagen monofilaments that have been united to form a unitary structure.
Tape means a group of individual collagen monofilaments that have been united to form a unitary structure that is ribbon-like in shape.
Non-absorbable fibers means those fibers, synthetic or natural, which are not absorbed in an animal body, particularly a human body, when present therein over an extended period of time. A non-absorbable fabric is a fabric formed of non-absorbable fibers.
Associations of collagen and non-absorbable fibers means a combination of collagen filaments or strands and one or more non-absorbable fibers, formed by iweaving, knitting, braiding, crocheting, etc. the filaments or strands and fibers together into articles including tubes, which can be straight or Y-shaped.
In the surgical repair of hernias, tantalum gauze and inert fabrics have found considerable use, particularly in older patients who are recognized to have a reduced ability to rebuild tissue at the point of surgery. Tantalum gauze, however, has the undesirable property of work hardening and can curl up within the body, causing discomfort. Inert fabric prostheses have the disadvantage that they do not become a part of the body tissue. During surgery, some surgeons have tried to overcome this disadvantage by knotting catgut sutures randomly throughout the fabric prosthesis. However, this does not result in a uniformly integrated fabric prosthesis. Many intert fabric inserts frequently remain surrounded by a pool of sera after the healing process. A suitable prosthesis for strengthening the repair should be non-toxic, flexible and porous. The ideal prosthesis should retain its strength permanently in intimate contact with body fluids and should be readily accepted and incorporated into the tissues. Porosity is an important characteristic of such a prosthesis to avoid the formation of fluid pockets and to promote the growth through the fabric of repair tissue.
3,276,448 Patented Oct. 4, 1966 A primary object of the invention, therefore, is to provide a porous, non-absorbable fabric compatible with an animal body, and coated with collagen. A further object is to provide a porous, non-absorbable fabric which is coated with collagen and the pores of which are free of collagen. Another object is the provision of prostheses comprised of the fabric so coated with collagen and promoting the growth of body tissue into and through the prostheses during the healing process.
Still another object is the provision of a process for manufacturing the prostheses of this invention. And another object is the provision of a process for pretreating the fabric in the manufacture of the prostheses.
Additional objects will be apparent from the following discussion.
The foregoing objects are realized with an improved prostheses comprised of a porous, non-absorbable fabric coated with collagen, the pores of the fabric being free of collagen. It is an essential feature of the new prostheses that the pores thereof are open and not rendered blood tight by collagen fibrils. In this regard, they are distinct fromthose described by Artandi and Bechtol in related application Serial No. 92,620, filed March 1, 1961 (now abandoned), and application Serial No. 495,010 filed September 22, 1965.
The prostheses of this invention are formed by knitting, weaving, braiding, crocheting, etc. non-absorbable fibers into the shape or form desired. The fibers are not absorbed by an animal body, as the human body, when present therein over extended time intervals, such as a decade. Examples of suitable materials are Vinyon-N, a resin manufactured by the Carbide and Carbon Corporation by copolymerizing vinyl chloride and acrylonitrile; Saran, a vinyl chloride polymer manufactured by the Dow Chemical Company; nylon, a polyamide resin made by polymerization of the hexamethylene diamine salt of adipic acid; Orlon, a synthetic fiber made from polyacrylonitrile; Dacron, a synthetic fiber made from terephthalic acid and ethylene glycol; Teflon, a tetrafluoroethylene polymer; polyolefins such as polyethylene and polypropylene; cotton and silk. Nylon, Orlon, Dacron and Teflon are products of the E. I. du Pont de Nemours 8: Co. Preferred herein are Dacron, Teflon and polyolefins.
It is to be understood that the non-absorbable fibers used herein can be knitted, woven, braided, crocheted, etc. into forms suitable for porous implants, in any manner known in the art, since such does not form a part of this invention.
Collagen used herein to coat the non-absorbable fabric corresponds to the type of connective tissue normally laid down by the body during the healing process. Thus, the collagen coating serves as a stimulus for body response during the post-operative period. The porous character of the fabric allows for rapid in-growth of fibroblasts and endothelial cells. All such features combine in concert to make possible rapid and satisfactory attachment of the prosthesis to the host tissues.
Collagen can be prepared as described in United States Patent No. 2,920,000 of H. R. Hoohstadt and E. R. Lieberman. Since it is diflicult to prepare a collagen dispersion containing more than 2 percent collagen because of ex tremely high viscosities of more concentrated dispersions, the collagen dispersions used in this invention generally contain from 0.1 to 2 percent by weight of collagen. The vehicle or liquid containing collagen can be one of a wide variety of materials, including: alcohols such as methanol; aqueous solutions of perfluoroacids, as shown in US. Patent Nos. 2,919,998 and 2,919,999; and aqueous cyanoacetic acid. Particularly preferred herein are collagen dispersions in a mixture of methanol and aqueous cyanoacetic acid.
The non-absorbable fabric, as in film or mesh form, can be coated with collagen by a number of techniques. The fabric can be immersed in a collagen dispersion for a suitable period of time, and the fabric can then be removed and allowed to drain and dry. Collagen is neutralized after the coated fabric is dry. Alternatively, a dispersion of collagen can be sprayed onto the fabric, followed by draining of the sprayed fabric.
When the fabric is immersed in a collagen dispersion, the fabric is coated with collagen and is thereafter treated to remove collagen present in the pores thereof. This is accomplished advantageously by directing a stream of inert gas against the coated fabric, particularly through the coated fabric. The stream is so adjusted that collagen held in the pores of the coated fabric is removed, while collagen coating the fabric structure is retained. There is little danger that the collagen coat will be removed from the fabric, since a relatively strong bonding of collagen and the fabric obtains. Representative of inert gases useful herein are air, nitrogen, and carbon dioxide. Since air is inexpensive and advantageous, it is preferred.
Still other techniques can be used herein. A fabric treated with collagen can be dried and then perforated to remove collagen from the pores thereof.
Temperatures of the impregnation step, draining (if such is used), neutralization and removal of collagen from the pores, are generally below about C. in each operation to avoid extensive degradation of collagen. Preferred for each operation are temperatures below about 25 C.
It is to be understood that any of the known tanning agents for use with collagen can be used herein. Chromium, formaldehyde, polyhydroxyphenols, etc. can be used alone or in combination. Particularly preferred, however, are the tanning procedures described in related applications Serial Numbers 85,289 and 85,302, both filed January 27, 1961.
In conjunction with the process for coating a nonabsorbable fabric with collagen, it has been discovered that a firmer bonding of collagen and the fabric results when the fabric is pretreated. The pretreatment involves successive contact with a solvent (A) for hydrophilic materials and a solvent (B) for hydrophobic materials. Solvents (A) and (B) are those which do not dissolve or attack the fiber. Solvents falling within category (A) include water and dilute aqueous solutions containing a detergent, among which are sulfates such as sodium lauryl sulfate, sulfonates such as sodium dodecyl benzene sulfonate, phosphates such as sodium tripolyphosphate, polyoxyalkylene derivatives of a hydroxy compound such as a condensate of 1 mol of nonyl phenol with 9 mols of ethylene oxide, quarternary ammonium compounds such as cetyltrimethylammonium chloride, etc. Representative of solvents (B) are: alcohols, typified by methyl, ethyl, n-propyl, isopropyl, n-butyl, secondaryand tertiary-butyl, etc.; ketones, typified by acetone, methyl ethyl, methyl n-propyl, diethyl, etc.; ethers, typified by dimethyl, diethyl, ethyl methyl, etc. Generally, a large excess of one or more solvents (A) and of one or more solvents (B), is used in the pretreatment of a non-adsorbable fiber. Pretreatment is conducted at temperatures from about C. to about 100 C., for time intervals ranging from about 60 minutes to about 1 minute with each solvent, (A) and (B); preferred conditions are the approximate ranges of 6070 C., for 10-5 minutes.
The present invention is more fully described and exemplified in the following examples. It is to be understood, however, that my invention is not to be limited to any specific form or materials or construction set forth in the examples, but is limited solely by the description in this Specification and the appended claims. Throughout the Specification and the examples which follow, all
quantities are expressed in parts by weight unless otherwise indicated.
Example I 4.33 grams of Dacron mesh (40 denier multifilament Dacron 12.5 inch square) was immersed in a gel prepared by diluting a collagen dispersion comprising 0.8 part of collagen, 0.4 part cyanoacetic acid, 49.4 parts water and 49.4 parts of methyl alcohol with an equal volume of methyl alcohol at room temperature (20 C.). The mesh was removed from the dispersion and allowed to drain vertically for about five minutes at room temperature. Compressed air was blown through the mesh to remove any collagenous film remaining across the interstices. If the orifice pressure is about 20 lbs. and the orifice is 4 mm. in diameter, a distance of approximately 3" between the orifice and the mesh is advantageous. Using the same orifice at 35 lbs. pressure, approximately 12" is advantageous between the orifice and the mesh. Shorter distances or higher pressures were found to blow too much collagen from the mesh while longer distances and lower pressures did not completely remove the collagen dispersion from the interstices. The mesh was allowed to dry for several hours at room temperature. The collagen on the mesh fabric was then neutralized with parts of 10% aqueous ammonia and was tanned with 100 parts formaldehyde (1% aqueous solution). Mesh, so obtained, contains approximately 10% by weight of collagen on the surface of the Dacron fibers. When implanted in the subcutaneous tissue of rats, the coated mesh elicited a greater amount of tissue response and fibroplasia than the uncoated mesh and was more readily incorporated by the host tissue.
Example II A piece of Dacron mesh (the same size and Weight as in Example I) was washed successively with 100 parts of hot water (60 C.), with 100 parts of isopropyl alcohol (25 C.) and 100 parts of acetone (25 C.). It was then dried in the air. The dried mesh was placed in a stainless-steel, Teflon coated tray measuring 15" x 9" x /2" containing a A;" layer of collagen dispersion containing 0.8 part of collagen fibrils and 49.4 parts of methyl alcohol, and 49.4 parts of water and 0.4 part of cyanoacetic acid, and another A2" layer of the same dispersion was placed on top of the fabric. The collagen dispersions and mesh were in contact for 24 hours at 25 C. The resulting laminate then was neutralized with 100 parts of 10 percent aqueous ammonia. It was tanned with 100 parts of formaldehyde (1 percent) and removed from the tray. Edges of the mesh were trimmed to remove excess collagen. The laminate was strong, uniform and very resistant to separation. These characteristics continued when the film was wet with water. Only very severe stretching or deformation freed an edge of the collagen from the Dacron mesh and, once freed, it resisted further delarnination.
It is found that Dacron and collagen are more firmly bound by virtue of the pretreatment of Dacron, than when the pretreatment is omitted. In fact, pretreated Dacron and collagen are more firmly bound than when brought together by any other technique.
While the invention has been described in detail according to the articles and manufacture thereof, it is to be understood that changes and modifications can be made (without departing from the spirit or scope of the invention) and it is intended in the appended claims to cover such changes and modifications.
1. A surgical prosthesis comprising:
a porous fabric of non-absorbable interlocking fibers;
said fibers being coated with collagen fibrils throughout their area of contact only, whereby the pores 5 of the fabric are open to the rapid ingrowth of body tissue through the prosthesis.
2. The surgical prosthesis of claim 1 wherein the porous fabric is tubular in form.
3. The surgical prosthesis of claim 1 wherein the porous fabric is a synthetic material made from terephthalic acid and ethylene glycol.
4. The surgical prosthesis of claim 1 wherein the porous fabric is a synthetic material made of a tetrafluoroethylene polymer.
References Cited by the Examiner UNITED STATES PATENTS RICHARD A. GAUDET, Primary Examiner.
DALTON L. TRULUCK, Examiner.