WO2002032346A1 - Coated surgical mesh - Google Patents

Coated surgical mesh Download PDF

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Publication number
WO2002032346A1
WO2002032346A1 PCT/US2000/028497 US0028497W WO0232346A1 WO 2002032346 A1 WO2002032346 A1 WO 2002032346A1 US 0028497 W US0028497 W US 0028497W WO 0232346 A1 WO0232346 A1 WO 0232346A1
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WIPO (PCT)
Prior art keywords
β
glucan
surgical mesh
surgical
mesh
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Application number
PCT/US2000/028497
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French (fr)
Inventor
Barbara Klein
Original Assignee
Brennen Medical, Inc.
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Publication date
Application filed by Brennen Medical, Inc. filed Critical Brennen Medical, Inc.
Priority to PCT/US2000/028497 priority Critical patent/WO2002032346A1/en
Publication of WO2002032346A1 publication Critical patent/WO2002032346A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION, OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/005Ingredients of undetermined constitution or reaction products thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION, OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08Materials for coatings
    • A61L31/10Macromolecular materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/0063Implantable repair or support meshes, e.g. hernia meshes

Abstract

The present invention discloses surgical meshes to which an immunostimulating agent is applied to promote the rapid integration of the surgical mesh into body tissues at the surgical site.

Description

COATED SURGICAL MESH

FIELD OF THE INVENTION

The present invention is drawn to a surgical mesh coating which facilitates the incorporation of a surgical mesh into a surgical site.

BACKGROUND OF THE INVENTION

It has become well known in the surgical arts to utilize various organic

(autologous and homologous) and synthetic surgical meshes at a surgical site to reinforce the tissues being repaired. Surgical meshes typically take the form of porous, gauze-like sheets of material. Common uses of surgical meshes include the repair of herniations and use as a structural member in gynecological surgeries.

Surgical meshes are porous, gauze-like sheet materials which may be woven or spun from a variety of organic and synthetic materials. The materials from which surgical meshes are made must be biocompatible, chemically and physically inert, non-carcinogenic, mechanically strong, and easily fabricated and sterilized. Most synthetic surgical meshes are woven from monofilament or multifilament fibers to form a mesh having pores of varying sizes and geometries. Other synthetic surgical meshes are formed in a node and fibril arrangement in which the mesh is comprised of larger sections or nodes which are interconnected by fibrils of the mesh material. A non-exhaustive list of common surgical meshes is given in Table 1 below.

Figure imgf000003_0001

Table 1

Organic surgical meshes are typically derived from human or animal sources. Homologous surgical meshes may be derived from the tissues of a donor, from animal tissues, or from cadaveric tissues. Autologous surgical meshes are meshes that are derived from a patient's own body, and may comprise dermographs, fascia tissues, and dura mater.

The most common use of surgical meshes involves the reinforcement of hemiations. Surgical meshes are also used in gynecological procedures including abdominal sacrocolopopexy and as suburethral slings. Other procedures which require surgical meshes include laparosopic retropubic urethropexy, intraperitoneal placement for adhesion prevention, the repair of pelvic floor hernias, rectoceles, and cystoceles. It is to be understood that the aforementioned surgical procedures do not comprise a complete list of all uses of organic and synthetic surgical meshes. New and varied uses for surgical meshes are being discovered on an ongoing basis and the present invention is to be construed to be applicable to all present and future uses of surgical meshes.

In many surgical procedures, it is desirable that a surgical mesh become incorporated into the tissues surrounding a surgical site. One example of such a surgical procedure is the reinforcement of a herniation. In the repair of a hernia, and after the hernia has itself been closed using standard surgical techniques, a surgical mesh of appropriate size and shape is placed over the newly repaired hernia and secured in place using sutures, staples, surgical adhesives, or any other suitable connecting means. As the tissues surrounding the surgical site heal, granulation tissues growing at and around the surgical site begin to produce an extracellular matrix which, in a process called fibrosis, infiltrates and attaches to the material of the surgical mesh secured over the surgical site. Incorporation of the surgical mesh into the surgical site by the extracellular matrix strengthens the tissues at the surgical site and helps prevent re-injury.

The rate of recovery of a patient who has undergone a surgery utilizing a surgical mesh is strongly related to the rate at which the surgical mesh is incorporated into the tissues surrounding the surgical site. The rate of incorporation of the surgical mesh as well as the potential for infection and the potential for clinical complications is in turn related to the physical properties of the surgical mesh used. For example, synthetic meshes having pores or interstices of less than 10 μm in size may theoretically promote infection in that small bacteria (less than 1 μm in size) may enter the surgical site through the mesh, while important and larger macrophages and polymorphonuclear leukocytes are prevented from passing through the mesh to the surgical site. In addition, the number, size, and shape of the pores play an important role in tissue bonding to the surgical mesh. Generally, surgical meshes having larger pore sizes are difficult for fibroblasts to adhere to. Furthermore, if a surgical mesh is too stiff, it may cause continuing mechanical injury to the tissues surrounding the surgical site with which it comes into contact. In these cases, a prolonged inflammatory reaction may significantly increase patient recovery time and may also cause clinical complications such as mesh extrusion and enteric fistulas.

OBJECTS OF THE INVENTION

Because the ailments which require the use of surgical meshes are typically quite serious, recovery from surgeries undertaken to alleviate or cure these ailments can be protracted. Therefore, it is desirable to facilitate or speed up the healing and recovery process where surgical meshes are used.

Accordingly, it is an object of the present invention to provide a coating for a surgical mesh that promotes the rapid incorporation of the surgical mesh into the tissues surrounding the surgical site to which the mesh has been grafted. Another object of the present invention is to stimulate the immune system to prevent surgical site infections. Yet another object of the present invention is permit the use of synthetic surgical meshes that are more difficult to incorporate into the tissue surrounding a surgical site.

SUMMARY OF THE INVENTION

The present invention essentially comprises a biocompatible surgical mesh having applied thereto a β-D-glucan composition. Preferably, the β-D-glucan composition is a cereal derived β-D-glucan made from one of oats, barley, or wheat, however other sources of β-D-glucan are also contemplated. Examples of other suitable sources of β-D-glucan include microbial sources such as yeast, bacteria, and fungus. The biocompatible surgical mesh is typically used for reinforcing a surgical site and may be synthetic or organic in origin. Synthetic surgical meshes are commonly made from polypropylene, polytetrafluoroethylene, expanded polytetrafluoroethylene, polyethylene terephthalate, polyglycolic acid, polyglactin, dacron-polythene reinforced silicone and polyethylene among others. Organic surgical meshes may be derived from human sources, animal sources, and cadaveric sources.

One method of applying an imunostimulating agent such as β-D-glucan to a biocompatible surgical mesh comprises the steps of preparing an aqueous solution of a cereal derived β-D-glucan , immersing a pre-selected surgical mesh in the aqueous solution of β-D-glucan , and evaporating the water component of the aqueous solution. Alternatively, one may prepare sheets of β-D-glucan and apply these preformed sheets of β-D-glucan to a pre-selected surgical mesh. The sheets are formed by preparing an aqueous solution comprising a cereal derived β-D-glucan and placing the aqueous solution in a drying tray to evaporate the water component of the solution, the residue is in the form of a β-D-glucan sheet. Sheets of β-D- glucan so formed are then applied to the surgical mesh by means of a suitable adhesive or by wetting the surgical mesh to partially dissolve the sheet of β-D-glucan

DESCRIPTION OF THE DRAWINGS

Figure 1 is an electron micrograph of a portion of an uncoated polypropylene surgical mesh that was implanted in a test animal for a duration of five days;

Figure 2 is an electron micrograph of a portion of a β-D-glucan coated polypropylene surgical mesh that was implanted in a test animal for a duration of five days;

Figure 3 is a drawing of a generalized chemical structure of a microbe-derived (1-3) β-D-glucan that may be used in the surgical mesh coating of the present invention;

Figure 4 is a drawing of a generalized chemical structure of a microbe-derived (1-3)(1 -6) β-D-glucan that may be used in the surgical mesh coating of the present invention; and

Figure 5 is a drawing of the generalized chemical structure of mixed-linkage cereal-derived (1 -3)(1 -4) β-D-glucan that may be used in the surgical mesh coating of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The objectives and advantages of the invention will be more fully developed in the following description, made in conjunction with the accompanying drawings and wherein like reference characters refer to the same or similar parts throughout the several views. And, although the disclosure hereof is detailed and exact to enable those skilled in the art to practice the invention, the physical embodiments herein disclosed merely exemplify the invention which may be embodied in other specific structure. While the preferred embodiment has been described, the details may be changed without departing from the invention, which is defined by the claims.

A surgical mesh constructed and arranged according to the present invention comprises a pre-selected surgical mesh material, either organic or synthetic, which has applied thereto a β-D-glucan composition. As used herein, the term "applied" is intended to embrace both coating and/or impregnating. Based on animal studies, it is anticipated that the addition of the β-D-glucan coating of the present invention will significantly reduce the recovery time of a patient. B-D-glucan s may be derived from a number of different materials but in general, β-D-glucan s are derived from cereal sources such as oats, barley and wheat or microbial sources such as bacteria, yeast, and fungi.

B-D-glucan s, and especially cereal derived β-D-glucan s, induce rapid differentiation of human monocytes into macrophages, the primary cell type associated with both wound healing and immunostimulation. While any β-D-glucan may be used to coat a surgical mesh in accordance with the present invention, it is preferred to utilize cereal derived β-D-glucan s to coat a chosen surgical mesh.

The stimulating effect of the β-D-glucan compound helps to prevent or to fight infection at the surgical site and will promote the rapid incorporation of the surgical mesh into the tissues at the surgical site. Furthermore, surgical meshes to which tissues do not easily adhere, such as polytetrafluoroethylene (PTFE) and expanded polytetrafluoroethylene (ePTFE), may, through the increased stimulation of fibrosis made possible by the use of a β-D-glucan coating, be more successfully used in situations requiring the surgical mesh to become incorporated into the tissues surrounding the surgical site. The addition of a β-D-glucan composition to a surgical mesh will also allow the use of more flexible surgical meshes which might not otherwise be conducive to tissue incorporation or adhesion in place of more rigid surgical meshes which are more prone to causing clinical complications.

B-D-glucan coatings may also be applied to organic surgical meshes derived from autologous and homologous sources. A β-D-glucan coating will provide a smooth lubricated surface on a surgical mesh which will facilitate the surgical placement of the mesh.

Compounds classified as beta-glucans comprise a large group of high molecular weight polymers containing glucopyranosyl units in beta-linked chains. Beta-glucans are found in essentially all living cells which are enclosed by cell walls, with considerable structural variation dependent on source. They are highly unbranched homopolysaccharides and isomehcally diaposed to α-D-glucan (e.g. starch) which is typically non-functional as a structural support component of the cell.

As depicted in Figure 3, glucans derived from microbes have been generally characterized as essentially comprising (1-3) - linked chains of glucopyranosyl units. With the recent advances in test identification methods, yeast-derived glucans having primarily (1 -3)-linkages with a relatively small number of (1-6)-linkages (Figure 4) have been identified. Yeast-derived glucan polymers are often associated with mannose, and typically have a helically coiled chain shape.

The mixed linkage glucan polymers found in cereals are quite different from yeast-derived and bacteria-derived polymers. Glucans derived from cereal grains such as oats, barley, and wheat, as shown in Figure 5, have (1 -3) and (1 -4) linkages and generally have a linear or kinked linear chain. Cereal-derived glucan (CDG) may be characterized as follows;

a. CDG is a long chain, unbranched polysaccharide which typically comprises about 3-4 percent of oat and barley grains. The CDG concentration is greater, e.g. 7-10 percent, in the milled bran fraction of oats.

b. CDG is found in the endosperm and aleurone cell walls of most cereal grains. The microbe-derived glucans occur in the cell wall of the yeast or bacteria.

c. CDG is a mixed-linkage molecule containing about 70 percent (1 -4)- linkages and about 30 percent (1 -3)-linkages. The (1 -3)-linked units mostly occur singly whereas the (1 -4)-linked units typically occur in groups of three or four glucopyranosyl units. Thus, the resultant structure is a series of short runs of 3 or 4 (1 -4)-linked glucopyranosyl units, adjacent runs connected by (1 -3) linkages. The frequencies of the groups of three (cellotriosyl) and four (cellotetraosyl) glucopyranosyl units also tend to be characteristic of the source, being affected by cereal variety, tissue age, and stage of maturity. Oat-derived CDG typically has more of the groups of three consecutive (1 -4)-linked glucopyranosyl units than does barley- derived CDG. The ratio of trisaccharide to tetrasaccharide groups is about 2:1 for oats and closer to 3:1 for barley. CDG differs from microbe-derived glucans, which have all (1 -3)-linkages or mostly (1 -3)-linkages with some

(1 -6)-linkages.

d. CDG is a linear molecule, while yeast-derived glucan forms a helical shape.

e. The degree of polymerization of CDG is in the range of about 1200-1800. On the other hand, yeast-derived β-D-glucan has a much lower degree of polymerization, i e about 60-80 Cellulose, the primary constituent of plant cell walls, has all β (1 -4) linkages and a degree of polymerization of about 10,000 to 15,000

f CDG forms viscous solutions in warm water On the other hand, yeast- derived glucan is insoluble in water but dispersible in aqueous systems

g CDG occurs within the grain with a fairly broad range of MW, i e about 200,000 to 700,000 The molecular weight is believed to be dependent upon the grain species, grain source, glucan extraction conditions and particular laboratory Microbe-derived glucan has a much lower molecular weight, in the range of about 10,000 to 14,000 Cellulose has a molecular weight of about 700,000

h The use of CDG as a food component has been studied extensively by various researchers, studies have included the use of CDG in regulation of glucose metabolism, hypoglycemic response, reduction in serum cholesterol, and the like

Thus, in terms of chemical structure and molecular weight, CDG is much more like cellulose than are the microbial-deπved glucans CDG, especially that derived from oats and barley, induces rapid differentiation of human monocytes into macrophages, the primary cell type associated with both wound healing and immunostimulation

Preferably a β-D-glucan coating is applied to a surgical mesh by being sprayed onto the surgical mesh Alternatively, a surgical mesh may be immersed in the beta glucan composition which is later dried Other methods for applying a β-D- glucan coating to a surgical mesh include painting the beta glucan onto a surgical mesh using a brush or rollers or bonding a preformed sheet or film of β-D-glucan to a surgical mesh. To form a sheet or film of β-D-glucan , an aqueous solution of β-D- glucan is prepared and placed in a drying tray. B-D-glucan will, upon evaporation of the water of the aqueous solution, form a pliable sheet or film which may be glued to a pre-selected surgical mesh using a suitable adhesive. Alternatively, the β-D-glucan sheet or film may be adhered to a pre-selected surgical mesh by first wetting the mesh and then applying the β-D-glucan film to the prepared mesh.

It has also been found helpful in the application of a β-D-glucan coating to a surgical mesh to apply pressure to the surgical mesh being coated. It is preferred to completely impregnate the surgical mesh with the beta glucan composition. However, it may be desirable in certain situations to apply beta glucan compositions to only a single side of a surgical mesh. It is to be understood that a β-D-glucan coating may be applied to a surgical mesh in any manner and is not limited to the examples set forth herein.

Example 1

A suitable polypropylene surgical mesh was obtained from Cousins Biotech, SAS, France (BIOMESH® W1 ). The selected surgical mesh had characteristics including a weight of 50g/m2 and a thickness of 0.30 mm.

A 0.5 weight percent β-D-glucan (oat derived) aqueous solution was prepared. Two 10 cm x 30 cm BIOMESH® W1 surgical meshes were placed in a 10 inch x 15 inch drying tray in a laminar flow hood. 250g of a β-D-glucan aqueous solution was poured into the trays with the prepared surgical meshes. Each of the surgical meshes were completely immersed in the β-D-glucan solution. The surgical meshes were then allowed to dry at 20-25°C over a period of 48 hours. The now- coated surgical meshes were then packaged, sealed, and sterilized using commonly known procedures.

A double blind intramuscular implantation animal study was then completed according to USP XXIII and ISO 10993 procedures comparing the β-D-glucan coated surgical mesh and an identical uncoated polypropylene mesh.

After five days, the coated and uncoated surgical meshes were removed from their intramuscular implantation sites. Macroscopic observations of the respective surgical meshes showed dramatic differences between the two biopsies. The uncoated surgical mesh was relatively clear of ingrown fibrous tissues and was very easily removed from the surrounding tissue by simply pulling on the surgical mesh. Conversely, the β-D-glucan coated surgical mesh was difficult to distinguish from the surrounding tissue at the biopsy site and was difficult to remove. The β-D-glucan coated surgical mesh showed substantial integration of the surrounding tissue whereas the uncoated mesh was still relatively unincorporated.

Figure 1 is an electron micrograph of a portion of the uncoated surgical mesh after being implanted for a duration of five days. The magnification of Figure 1 is approximately 250X. As can be seen in Figure 1 , incorporation of the uncoated surgical mesh by an extracellular matrix has only begun. The fibers of the uncoated polypropylene surgical mesh are clearly visible. Referring next to Figure 2 which is an electron micrograph of a portion of the β-D-glucan coated polypropylene surgical mesh after a duration of five days, it can be seen that considerable colonization by fibrous tissue has taken place within the coated surgical mesh. In Figure 2, the coated surgical mesh itself is not clearly visible and is extensively covered by a new extracellular matrix. The foregoing is considered as illustrative only of the principles of the invention. Furthermore, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation shown and described. While the preferred embodiment has been described, the details may be changed without exceeding the broad scope of the invention, which is defined by the claims.

Claims

CLAIMSWhat is claimed is:
1. A biocompatible surgical mesh for implantation at a surgical site having applied thereto a β-D-glucan composition.
2. The biocompatible surgical mesh for implantation at a surgical site of claim 1 wherein the β-D-glucan composition is derived from one of oats, barley, or wheat.
3. The biocompatible surgical mesh for implantation at a surgical site of claim 1 wherein the β-D-glucan composition is derived from one of yeast, bacteria, and fungus.
4. A biocompatible surgical mesh for implantation at a surgical site for reinforcing said surgical site comprising: a surgical mesh fabricated from a synthetic material chosen from a group comprising polypropylene, polytetrafluoroethylene, expanded polytetrafluoroethylene, polyethylene terephthalate, polyglycolic acid, polyglactin, and dacron-polythene reinforced silicone, said surgical mesh having applied thereto an imunostimulating agent.
5. The biocompatible surgical mesh for implantation at a surgical site of claim 4 wherein said imunostimulating agent comprises a cereal derived β-D-glucan composition.
6. The biocompatible surgical mesh for implantation at a surgical site of claim 4 wherein the β-D-glucan composition is derived from one of yeast, bacteria, and fungus.
7. A biocompatible surgical mesh for implantation at a surgical site for reinforcing said surgical site comprising an organic surgical mesh, said organic mesh having applied thereto an imunostimulating agent.
8. The biocompatible surgical mesh for implantation at a surgical site of claim 7 wherein said organic mesh is derived from one of a human source, an animal source, and a cadaveric source.
9. The biocompatible surgical mesh for implantation at a surgical site of claim 7 wherein said imunostimulating agent is a cereal derived β-D-glucan composition.
10. The biocompatible surgical mesh for implantation at a surgical site of claim 9 wherein said β-D-glucan composition is derived from one of a group comprising oats, barley, and wheat.
11. The biocompatible surgical mesh for implantation at a surgical site of claim 7 wherein said imunostimulating agent is derived from one of yeast, bacteria, and fungus.
12. A biocompatible surgical mesh for implantation at a surgical site comprising a mesh matrix having applied thereto a cereal derived β-D-glucan composition.
13. The biocompatible surgical mesh for implantation at a surgical site of claim 12 wherein said mesh matrix is fashioned of a material selected from a group comprising polypropylene, polytetrafluoroethylene, expanded polytetrafluoroethylene, polyethylene terephthalate, polyglycolic acid, polyglactin, dacron-polythene reinforced silicone and polyethylene.
14. The biocompatible surgical mesh for implantation at a surgical site of claim 13 wherein said β-D-glucan composition is derived from one of a group comprising oats, barley, and wheat.
15. The biocompatible surgical mesh for implantation at a surgical site of claim 12 wherein said surgical mesh is derived from one of a human source, an animal source, and a cadaveric source.
16. The biocompatible surgical mesh for implantation at a surgical site of claim 15 wherein said β-D-glucan composition is derived from one of a group comprising oats, barley, and wheat.
17. A method of applying an imunostimulating agent to a biocompatible surgical mesh comprising the steps of: a. preparing an aqueous solution comprising a β-D-glucan ; b. immersing a pre-selected surgical mesh in said aqueous solution; and c. evaporating the water component of the aqueous solution.
18. The method of applying an imunostimulating agent to a biocompatible surgical mesh of claim 17 wherein said β-D-glucan is a cereal derived β-D-glucan .
19. The method of applying an imunostimulating agent to a biocompatible surgical mesh of claim 17 wherein said β-D-glucan is derived from one of oats, barley and wheat.
20. The method of applying an imunostimulating agent to a biocompatible surgical mesh of claim 17 wherein said β-D-glucan is derived from one of yeast, bacteria, and fungus.
21. A method of applying an imunostimulating agent to a biocompatible surgical mesh comprising the steps of: a. preparing an aqueous solution comprising a β-D-glucan ; b. placing said aqueous solution in a drying tray; c. evaporating the water component of said aqueous solution to produce a sheet of β-D-glucan ; and d. applying said sheet of β-D-glucan to said surgical mesh.
22. The method of applying an imunostimulating agent to a biocompatible surgical mesh of claim 21 further comprising the steps of: a. applying an adhesive to said surgical mesh to secure said sheet of β- D-glucan to said surgical mesh.
23. The method of applying an imunostimulating agent to a biocompatible surgical mesh of claim 21 further comprising the steps of: a. applying water to said surgical mesh to secure said sheet of β-D- glucan to said surgical mesh.
24. The method of applying an immunostimulating agent to a biocompatible surgical mesh of claim 21 wherein said β-D-glucan is a cereal derived β-D- glucan .
25. The method of applying an immunostimulating agent to a biocompatible surgical mesh of claim 21 wherein said β-D-glucan is derived from one of oats, barley and wheat.
26. The method of applying an immunostimulating agent to a biocompatible surgical mesh of claim 21 wherein said β-D-glucan is derived from one of yeast, bacterial, and fungi.
PCT/US2000/028497 2000-10-13 2000-10-13 Coated surgical mesh WO2002032346A1 (en)

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