WO1996040302A1

WO1996040302A1 - Bioabsorbable space filling soft tissue prosthesis

Info

Publication number: WO1996040302A1
Application number: PCT/US1996/005525
Authority: WO
Inventors: Terry A. Hubbard
Original assignee: WL Gore and Associates Inc
Current assignee: WL Gore and Associates Inc
Priority date: 1995-06-07
Filing date: 1996-04-19
Publication date: 1996-12-19
Anticipated expiration: 1997-12-07
Also published as: AU5391996A

Abstract

A soft tissue prosthesis intended for implantation between the epicardium and adjacent tissue which will absorb fluid and expand to displace fluids that may cause epicardial thickening to occur. In the preferred form, the soft tissue prosthesis has a substrate of expanded, porous PTFE to which a gel is attached by coating or bonding. When dehydrated, the prosthesis is flexible. Preferred materials which may be attached to the substrate include gums, modified celluloses and hyaluronic acid derivates. Gelling agents and stiffeners may also be added. A method of preparing the prosthesis and a surgical procedure utilizing the prosthesis are also disclosed.

Description

TITLE OF THE INVENTION

BIOABSORBABLE SPACE FILLING SOFT TISSUE PROSTHESIS

Field of the Invention The present invention relates to a composite bioabsorbable and biocompatible soft tissue prosthesis which has an inert hydrophobic side and an absorbable hydrophilic side that will expand to absorb and displace fluids that have accumulated adjacent the prosthesis and more particularly the present invention relates to a soft tissue prosthesis intended primarily to be used as a pericardial prosthesis having a substrate of biocompatible material such as ePTFE with a coating or layer of bioabsorbable, swellable material bonded or adhered to it.

Background of the Invention A concern exists on the part of some cardiac surgeons that accumulations of fluid under pericardial prosthesis will cause epicardial thickening. The epicardium is one of three layers of tissue that form the wall of the heart and fibrous growth may occur as a result of accumulations of fluid beneath a membrane which is surgically implanted as part of the reconstruction procedure performed during cardiac surgery.

The present invention generally pertains to the use of a biocompatible soft tissue prosthesis having specialized characteristics for medical use and more particularly relates to a prosthesis having a substrate of ePTFE which will absorb secretions. It is known to laminate or otherwise modify ePTFE or other membranes to produce various products and product characteristics including the ability to absorb fluids.

The prior art suggests various types of patches and membranes for medical use. For example, U.S. Patent No. 5,135,755 discloses a wound secretion-absorbing hydrogel which is cross-linked on the basis of multi-valent alcohols, biopolymers and synthetic polymers and used as wound dressings. The hydrogels, according to the invention, promote accelerated healing and are transparent permitting observation of the wound healing process.

Patent No. 4,161 ,948 discloses an artificial membrane for wound dressings composed of two polypeptide layers, one of which contacts the wound. The membrane is biologically resorbable and the membrane serves as an artificial skin which is permeable to water and to drug solutions but practically impervious to outside pathogenic agents.

European Patent Application No. 0261470 discloses a bioabsorbable coating for surgical articles which comprises a polymer manufactured from at least the monomer caprolactone. The article can be a bioabsorbable suture or a ligature.

U.S. Patent No. 5,126,140 discloses a biocompatible thrombo-resistant substance for implantable and extracorporeal devices in contact with the vascular system. The biocompatible thrombo-resistant substance comprises a synthetic biocompatible material at least one bio-compatible base coat layer adhered to at least one surface of the material and the thrombogenesis inhibitor thrombomoduiin immobilized on the base coat layer via a component capable of binding the inhibitor without affecting its thrombogenesis inhibiting activity. U.S. Patent No. 5,087,243 shows an implantable delivery system for use in applying medicinal materials to a specific subcutaneous tissue sites in conjunction with an implanted defibulator.

Thus, while the prior art shows or suggests various types of materials in the surgical and medical field which are either bioabsorbable, swellable or both, these materials are predominantly used for dressings or as dermo-patch drug delivery systems. These various materials utilize substrates or membranes of different types such as membranes of Dacron, composite membranes of silicon rubber. More conventional materials such as polyethylene glycol, polyacrylates and, in some cases, polytetrafluoroethylene (PTFE), are also used. However, none of these substrates or membranes are suggested for specific use to expand to occupy space in a surgical area to minimize fibrosis.

Summary of the Invention

Expanded, porous PTFE films have acquired wide acceptance since their introduction because of their unique qualities. Expanded PTFE films have been used alone or laminated to other substrates or impregnated with various compositions to produce a range of products. It has been found that a substrate of expanded PTFE having a layer, film or coating of bioabsorbable, swellable material bonded to it performs well as a space-filling soft tissue prosthesis, particularly in the pericardial environment. Accordingly, the present invention relates to an absorbable layer which will swell and displace any fluids that have accumulated between a surface of the membrane and an internal organ or tissue to minimize fluid accumulation. One particular application is the prevention of epicardial thickening by use of a soft tissue prosthesis fabricated using a substrate of a biocompatible material such as expanded PTFE. The preferred material is that material sold under the designation GORE-TEX® Surgical Membrane available from W.L. Gore & Associates of Flagstaff, Arizona. The preferred material is fabricated by expanding porous PTFE to create a membrane of porous, expanded PTFE having a microstructure of nodes interconnected by fibrils. The manufacture of a porous, expanded PTFE membrane is described in detail in U.S. Patent Nos. 3,953,566 and 4,187,390 incorporated by reference herein.

A layer or coating of a bioabsorbable, swellable material is bonded or otherwise applied or adhesed to the biomaterial substrate. The coating material preferably is a weak gel or a highly viscous fluid when hydrated. When dehydrated, the composite prosthesis is flexible and in use is initially placed with the absorbable side adjacent the surgical site. The absorbable material will swell to displace fluids that have accumulated adjacent the tissue such as the epicardium. The preferred material applied to the membrane has no or a very low yield strength when hydrated. Gums such as Xanthan gum, modified celluloses such as carboxymethyl cellulose (CMC), hydroxylpropylmethyl cellulose, and hyaluronic acid derivatives are good examples. Gelling agents may also be used to stiffen the hydrated membrane. The dried membrane may also be plasticized with a plasticizer such as glycerol or glycerine to improve workability and flexibility.

Detailed Description of the Preferred Embodiment

As is well known, GORE-TEX® Surgical Membrane of the type described above is widely used for the reconstruction and repair of the pericardium or peritoneum. GORE-TEX® Surgical Membrane is a unique configuration of expanded PTFE that maintains long-term flexibility and limits tissue attachment between adjacent tissue structures. Many years of clinical experience have established that GORE-TEX® Surgical Membrane provides an effective plane of dissection without adding to patient morbidity and mortality. Adhesion formation is limited due to the structure of the material. Re-entry into the pericardial space is facilitated and complications associated with re-entry are minimized. The surgical membrane is packaged sterile and various implant techniques have been used in reconstructing the integrity of the pericardium following cardiac surgery. Current technology supports placement of the ePTFE surgical membrane between the epicardial surface of the heart and the pericardium or on the outer surface of the residual pericardium. Nonabsorbable sutures are commonly used to anchor the surgical membrane to the pericardium. Clips may also be used to anchor the surgical membrane and have the advantage of acting as locators when standard imaging techniques are subsequently used.

At initial implant, the ePTFE membrane is a white, generally opaque material and after implantation the material becomes wetted with proteinaceous aqueous fluids and turns translucent due to the porous nature of the material. This is an advantage as if re-operation is necessary, it may be possible for the surgeons to view the epicardial anatomy of the heart surface through the membrane.

While the advantages of placement of a surgical membrane between the epicardial surface of the heart and the pericardium or the surface of the residual pericardium are well known, some surgeons are concerned about accumulation of fluid that occurs between the membrane and body tissue.

Whenever a closure of the pericardial sack is performed, it is common surgical practice to place a drain at the surgical site to remove accumulating fluid. Depending upon the procedure, additional drains such as plural cavities may be placed and use of a closed suction draining system may be utilized to avoid contamination. Post-operatively, these drains are removed and trapped blood, proteinaceous material and fluid may then accumulate next to the epicardial surface may cause a slight thickening of the epicardium.

Accordingly, the purpose of the present invention is to address the perception or concern of some cardiac surgeons that accumulations of fluid under the pericardial prosthesis will cause such a thickening.

In accordance with the present invention, a soft tissue prosthesis is provided which is generally termed a "space-filling soft tissue prosthesis" that is applied to a surgical site and expands to occupy space between the prosthesis and adjacent tissue or organs such as the pericardial surface. By providing such an absorbable, swellable soft tissue prosthesis, accumulation of fluids in any significant amount is minimized.

The prosthesis consists of a substrate of expanded PTFE having a layer or coating of bioabsorbable, swellable material bonded to it to form a composite membrane. This material may be a weak gel or a highly viscous fluid when hydrated. When dehydrated, the material is a flexible film. In use, the composite structure of the substrate and coating is positioned with the absorbable side adjacent the surgical site which would normally be disposed downwardly. As fluids tend to collect at the site, the absorbable layer will hydrate and swell displacing any fluids that have accumulated beneath the prosthesis.

The preferred swellable material bonded to the substrate has no or low- yield strength when hydrated. Gums such as plant gums and mucilages, Xanthan gum, modified celluloses such as carbomethylcellulose (CMC), hydroxypropylmethylcellulose (HPMC) and Hyaluronic acid derivatives are preferred.

However, due to the dynamic environment surrounding the heart, these materials, in some instances, can migrate from the preferred site quickly and, accordingly, gelling agents may be used to stiffen the hydrated membrane. Good gelling agents for this purpose are hydrophilic colloids and may be selected from the following groups: algins, alginates, elastic gelatins, hyaluronic acid, and polyetherglycols such as polyethylene glycol.

The membrane may also be stiffened by cross-linking with a cross-linking agent such as a polyvalent aldehyde compound of glutaraldehyde, dialdehyde starch, calcium ions or boric acid, etc. In a cross-linking step, the expanded ePTFE substrate having first been treated with the swellable material is then treated with a cross-linking agent. The hydrating swellable material may be applied in various ways and may be adhered to a surface of the ePTFE substrate or may be bonded to a surface of the ePTFE or may be applied as a coating and allowed to dry. The dried composite product may then be plasticized with a suitable plasticizer glycerin to improve handling.

The foregoing description is provided to aid in a complete, nonlimiting understanding of the invention. Since many variations of the invention may be made without departing from the spirit and scope of the invention, the breadth of the invention resides in the claims hereinafter appended. The invention and its objects and advantages are further illustrated by the following examples which describe several ways of making a prosthesis according to the invention.

Example 1 : A preferred material may be fabricated by preparing a solution for one part carbomethylcellulose (CMC) to two parts glycerin with up to one part calcium alginate in a 0.7% saline solution. The concentration of the solution may be variable but should be greater than about 4% CMC and is used to make a film which is then dried. The dried film is then placed on a substrate of wetted, expanded PTFE. The expanded PTFE being wetted with the above solution.

The composite structure is then allowed to dry and the resulting composite structure is suitable as a pericardial prosthesis as described above.

The completed soft tissue prosthesis is sterilized by conventional autoclaving techniques and provided to the surgeon in suitable sterile packaging. The prosthesis is surgicaliy implantable as described above being particularly useful in reconstructing the integrity of the pericardium following cardiac surgery to fill voids which may exist under the conventional graft. After a period of time the swellable material will absorb leaving the expanded PTFE substrate as a permanent membrane in the patient.

Example 2:

A solution is initially prepared from one part CMC to two parts glycerin with up to one part calcium alginate in a 0.7% saline solution. A concentration in the range of 0.5% to 1.5% CMC is maintained and some of the solution is applied to a glass plate by conventional coating techniques and allowed to dry to form a film. The remainder of the solution is applied to the ePTFE substrate material by conventional coating techniques as by immersion to cause the solution to impregnate the GSM. Impregnation is enhanced by application of hydrostatic pressure in the range of 150 to 1000 PSIG. Once impregnation has occurred, normally after about 5 minutes, the substrate is removed from the hydrostatic chamber and the film is applied to the impregnated substrate. The composite is allowed to dry and is then sterilized and packaged as described above.

While the invention has been described in detail and with reference to specific embodiments, it will be apparent to one skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the appended claims

Claims

CLAIMS:

1. A soft tissue prosthesis for reducing accumulation of fluid at surgical sites comprising a biocompatible substrate treated with an absorbable material whereby the absorbable material will swell to displace fluids adjacent a surface of the prosthesis.

2. The soft tissue prosthesis of Claim 1 wherein said biocompatible substrate is expanded porous PTFE having a microstructure characterized by nodes interconnected by fibrils and having been expanded.

3. The soft tissue prosthesis of Claim 1 wherein said absorbable material is selected from the group consisting of gums, cellulose derivatives and Hyaluronic acid derivatives.

4. The soft tissue prosthesis of Claim 1 wherein the substrate is further treated with a stiffening agent.

5. The soft tissue prosthesis of Claim 4 wherein said stiffening agent is selected from the group consist of algins, alginates, gelatin, hyaluronic acid, polyethylene glycol and mixtures thereof.

6. The soft tissue prosthesis of Claim 1 wherein said absorbable material is a weak gel and wherein said soft tissue prosthesis is further treated with a cross-linking reagent linking the biocompatible substrate to the weak gel.

7. The soft tissue prosthesis of Claim 6 wherein said cross-linking reagent is selected from the group consisting of polyvalent aldehyde compound of glutaraldehyde, dialdehyde starch, calcium ions or boric acid.

8. The soft tissue prosthesis of Claim 3 wherein said cellulose derivatives are selected from the group consisting of carbomethyl cellulose and hydroxpropylmethyl cellulose.

9. A soft tissue prosthesis for reducing accumulation of fluid at surgical sites comprising a substrate of expanded porous PTFE having opposite surfaces with an absorbable material in the form of a weak gel when hydrated bonding it to least one surface.

10. A method of providing a swellable soft tissue prosthesis comprising the steps of:

(a) providing an expanded PTFE substrate having a microstructure characterized by nodes interconnected by fibrils; and

(b) applying a coating of a bioabsorbable, swellable material which when dehydrated is flexible and which in the presence of fluids will hydrate and expand forming a weak gel or highly viscous fluid.

11. The method of Claim 10 wherein said coating is applied as a dried film placed on the substrate with the substrate being in a wetted condition.

12. The method of Claim 10 wherein said coating is applied as a solution.

13. The method of Claim 12 wherein said applied solution is applied under a vacuum to impregnate the material.

14. The method of Claim 12 wherein said coating is selected from the group consisting of algins, alginates, elastic gelatins, Hyaluronic acid derivatives and polyetherglycols.

15. The method of Claim 12 further including the step of stiffening the coated substrate.

16. The method of Claim 15 wherein said stiffening is accomplished by cross-linking with a cross-linking agent.

17. The method of Claim 15 wherein stiffening is accomplished by applying a gelling agent.

18. The method of preparing a soft tissue prosthesis comprising the steps of: (a) preparing a solution from approximately one part CMC to two parts glycerin and with up to one part calcium alginate in a 7% saline solution;

(b) preparing a film from the solution; (c) allowing the film to dry; and

(d) applying the dried film to a wetted biocompatible substrate and allowing the structure to dry to form a prosthesis.

19. The method of Claim 18 further including the steps of sterilizing and packaging the soft tissue prosthesis.

20. A method of preparing a swellable soft tissue prosthesis comprising:

(a) preparing a solution from approximately one part CMC to two parts glycerin with up to one part calcium alginate in a saline solution;

(b) forming a film from part of the solution of step (a);

(c) applying the solution to a biocompatible substrate under hydrostatic pressure to impregnate the substrate; and (d) withdrawing the impregnated substrate and applying the film thereto to form a composite and allowing the composite to dry.

21. The method of Claim 20 further including the steps of sterilizing and packaging the dressing.

22. A method of preparing a swellable soft tissue prosthesis comprising:

(a) preparing a solution from a 0.5% to 5% hyaluronic acid derivatives; (b) forming a film from some of the solution by applying the film to a surface;

(c) applying the solution to a biocompatible substrate under hydrostatic pressure to impregnate the substrate with the solution;

(d) withdrawing the impregnated substrate and applying the film thereto to form a composite; and (e) allowing the composite to dry.

23. A surgical procedure for pericardial reconstruction comprising:

(a) placing a biocompatible membrane between the epicardial surface and adjacent tissue;

(b) providing a prosthesis having dehydrated swellable, biocompatible, bioabsorbable layer having a hydratable surface;

(c) positioning the prosthesis between the surgical membrane and the tissue with the hydratable surface adjacent the tissue; and " (d) closing the adjacent tissue, leaving the membrane and prosthesis in place to absorb accumulations of fluid beneath the membrane.

24. The surgical procedure of Claim 23 wherein said prosthesis is expanded PTFE with nodes interconnected by fibrils which has been treated with a hydrating gel.

25. A soft tissue prosthesis for minimizing accumulation of fluids under a pericardial prosthesis comprising a composite substrate having a hydrophilic surface and a bioabsorbable surface.