WO2020144712A1

WO2020144712A1 - Coated mesh for hernia repair

Info

Publication number: WO2020144712A1
Application number: PCT/IN2020/050025
Authority: WO
Inventors: Dr. Atul SARDANA
Original assignee: Sardana Dr Atul
Priority date: 2019-01-13
Filing date: 2020-01-10
Publication date: 2020-07-16

Abstract

The present invention relates to a novel Hernia Mesh. More particularly, present invention discloses a dual layer hernia mesh. The present invention relates to hernia mesh made of a plastic hernia mesh with surface modification on one side using low temperature plasma and then coated with an optimal barrier layer made of bioabsorbable polymer(s) using nano-electrospray coating with adequate elasticity and strength, that prevents adhesion formation to bowel or other abdominal organs, but allows adequate tissues ingrowth and prevents delamination of the layers.

Description

TITLE OF THE INVENTION

Coated Mesh For Hernia Repair

FIELD OF THE INVENTION

The present invention relates to a novel Hernia Mesh. More particularly, present invention discloses a dual layer hernia mesh. The present invention relates to hernia mesh coated with a bioabsorbable barrier layer, that prevents adhesion formation on the coated side, allows adequate tissues ingrowth on the uncoated side, is coated such that layers do not delaminate and there is preservation of substrate mesh pores to allow free tissue fluid transmigration between both sides. BACKGROUND OF THE INVENTION

A hernia is an abnormal protrusion of a part or whole of an organ from the wall of the cavity in which it is contained. It occurs due to either a weakness in the wall, which may be congenital or acquired, or raised pressure in the cavity or a combination of both.

Although the term hernia can be used for bulges in other areas, it most often is used to describe hernias of the lower torso (abdominal-wall hernias). Hernia is categorized based on their cause or location and abdominal wall hernia may be classified into ventral or groin besides other locations which are rare.

The only effective treatment of a hernia is a surgery. The methods, by which hernia repairs are performed can be divided into two general categories: 1. Repair Under Tension methods, which involve an approximation of tissue edges and stitching them together to close the hernia defect. In this type of repair, stitches or sutures exert tension on tissue on each side of the hernia in order to keep it closed.

2. Tension-free Repair methods, which involve an implantation of a prosthetic plastic mesh, which is to complement the defect in the fascia and close the hernia defect without causing a tension in the surrounding tissue. The use of plastic meshes, most often made of polyester, polypropylene or expanded PTFE, enables a significant decrease in the recurrence rates.

The disadvantage of tension-free methods, especially for large abdominal hernias, is the patient's discomfort occurring a long time after implantation, which is associated with stiffening of the implant due to the ingrowth of a fibrous tissue.

Another shortcoming is introduction of a certain amount of alloplastic material into the patient's body, which is necessary to obtain sufficient strength of the implant, but which also prolongs the healing process and may trigger a foreign body reaction.

Among the most serious complications resulting from the use of surgical meshes are infections, reoccurrence, and adhesions, bowel obstruction, erosion, and fistula formation when the plastic hernia mesh is in direct contact with the bowel and other abdominal organs. This contributes to complications related to enterotomy or unplanned bowel resection and is associated with difficult adhesiolysis during subsequent abdominal surgeries. Surgical treatment of ventral hernias has changed by introducing the laparoscopy and specialized prosthetic materials for the reconstruction of the abdominal wall. There is widespread acceptance of laparoscopic ventral hernia repair, that is superior to open repair in terms of postoperative infectious complications, length of hospital stay, recurrence, blood loss and cosmetic outcome. The insertion of a mesh for tension free closure of the hernia defect is standard for laparoscopic repair, where in most cases it is required to place the mesh in direct contact with the bowel and other abdominal organs. Such a placement is called intraperitoneal onlay.

From a surgical point of view the mesh used for laparoscopic ventral hernia repair should have minimal adhesion formation with bowel and other abdominal organs, excellent tissue ingrowths for a strong repair and causes minimal change in abdominal wall compliance.

The requirements for an ideal Mesh for intraperitoneal onlay are:

• To physically separate anatomical structures during the early healing phase

• To induce a minimized inflammatory response in order to reduce both encapsulation and adhesions to the barrier itself

• To restore normal cleavage plans

There are number of patents and non-patent disclosures that describe the use of hernia mesh for hernia repair. One such disclosure is the US09054672 patent application which discloses hernia mesh with multiple layers. This invention relates to hernia mesh with anti-adhesive material, and bioabsorbable material, where both the layers act as bioabsorbable, unlike the present invention which discloses use of one non-bio absorbable and one bioabsorbable layer.

Also, the Application No. US62327494 discloses the hernia mesh that prevents the issue of delamination of two layers. The prior art discloses stitching the two layers together. Such stitching is not possible when a very thin biopolymer layer anti-adhesive layer is used.

The present invention overcomes the drawback in the prior art by using a novel combination of surface modification of a plastic substrate mesh and then nano-electrospray coating it on one side with an optimal layer of a bioabsorbable barrier layer. The surface modification is aimed at increasing the bonding of the bio absorbable barrier layer to the plastic substrate mesh which is achieved by low temperature plasma treatment. Subsequently nano-electiospray coating will coat a very thin layer of anti adhesive coating on one side.

In a non-patent literature, one such disclosure is by C. Labay, et al titled as "Low-temperature plasma treatments in the design of polypropylene" which discloses use of plasma technology to modify the surface properties of PP mesh. The prior art relates to use of plasma technology to do graft polymerization of antibiotic and further coating with PEG to prevent incidence of infection.

On the other hand, present invention is using low temperature plasma to modify the surface of the polypropylene (PP) mesh in order to deposit a thin layer of (poly(L-lactide-e-caprolactone) PLCL or other polymer(s) to avoid scarring and adhesion on that side. Present invention is directed to overcome the limitations of the product besides others now available in the market namely;

a. Coating on both sides prevents the mesh to be incorporated on the peritoneal/ abdominal wall side and causes mesh migration and surgical failure.

b. the use of biological active agent in this case may lead to mesh rejections.

c. the way these layers were attached causes delamination.

Whereas the present invention intends to coat only one side by using a bioabsorbable polymer and prevent delamination by first modifying the surface of the substrate mesh with low temperature plasma and then depositing charged nano droplets of the bioabsorbable polymer on the modified surface.

Existing state of the art indicates that the meshes available in the market have an issue of the layers getting delaminated. Delamination occurs due to the forces applied to the mesh by the body and the difference in the elasticity profile of the two materials. This delamination exposes the non- bioabsorbable/ slowly absorbable polymer to the intestine and other abdominal organs, leading to adhesions and dense scar formation which may lead to complications which can be life threatening.

To overcome this issue, present invention discloses a novel combination of Surface Modification using Plasma Etching and Nano-Electrospray Coating to provide a dual layer hernia mesh that prevents adhesion formation on the coated side, allows adequate tissues ingrowth on the uncoated side, is coated such that layers do not delaminate and there is preservation of substrate mesh pores to allow free tissue fluid transmigration between both sides.

OBJECTS OF THE INVENTION

The main object of the present invention is to provide a hernia mesh.

Another object of the present invention is to provide a dual layer hernia mesh. Yet another object of the present invention is to provide a dual layer hernia mesh with a bioabsorbable barrier layer, that can prevent adhesion formation.

Yet another object of the present invention is to provide a dual layer hernia mesh with a bioabsorbable barrier layer with adequate elasticity and strength and also allows adequate tissue ingrowth.

Yet another object of the present invention is to prevent the delamination of layers of a hernia mesh.

Yet another object of the present invention is to provide a hernia mesh where the surface modification is achieved by using low temperature plasma. Yet another object of the present invention is to provide a hernia mesh coated with an optimal barrier layer using nano-electrospray coating.

Yet another object of the present invention is to provide a dual layer hernia mesh with preservation of substrate mesh pores to allow free tissue fluid transmigration between both sides.

SUMMARY OF THE INVENTION

Accordingly, the present invention discloses hernia mesh. The present invention is a dual layer hernia mesh with a bioabsorbable barrier layer, that can prevent adhesion formation on the coated side, allows adequate tissues ingrowth on the uncoated side, is coated such that layers do not delaminate and there is preservation of substrate mesh pores to allow free tissue fluid transmigration between both sides.

Present invention discloses dual layer hernia mesh. The mesh consists of a bioabsorbable layer and a non-bioabsorbable layer.

On one side of the non-bioabsorbable polymer layer, surface modification is achieved by coating a bioabsorbable polymer that will prevent tissue adhesion (barrier layer).

The present invention is disclosed by non-limiting examples:

In one of the embodiment of the present invention, the surface modification of said mesh is achieved by first etching one side of mesh using low temperature plasma in order to increase the free surface energy and then electrospraying nanodroplets of the bioabsorbable polymer to achieve a strong bonding between the two materials of the Dual Layer Mesh in order to prevent delamination.

The hernia mesh is comprised of a non-bioabsorbable polymer layer which can be knitted, woven, spun or made of nonwoven fabric. This layer allows adequate strength and elasticity and permits tissue ingrowth on the parietal side of the hernia defect upon implantation. The layer is coated with the nanodroplets of a bioabsorbable polymer in optimal density and thickness such that the elastic properties of the non-bioabsorbable polymer are not affected and there is a tight surface cover to prevent adhesion formation with viscera once implanted.

Studies indicate that the meshes available in the market have an issue of the layers getting delaminated. Delamination occurs due to the forces applied to the mesh by the body and the difference in the elasticity profile of the two materials. This delamination exposes the non-bioabsorbable/ slowly absorbable polymer to the intestine and other abdominal viscera, leading to adhesions and dense scar formation which may lead to complications which can be life threatening.

To overcome this issue, present invention discloses a novel combination of plasma etching and nano-electrospray coating to prevent delamination.

The plasma etching makes the substrate mesh more adhesive by modifying its surface and nano-electrospray coating delivers charged polymer nano droplets to deposit a thin layer of anti-adhesive (bioabsorbable polymer) coating on one side of the substrate mesh thereby converting it to dual layer mesh.

BRIEF DESCRIPTION OF DRAWINGS:

Figure 1 depicts Contact Angle Goniometry image showing the static Contact Angle with water droplet on Polypropylene Surface Before Low

Temperature Plasma Etching.

Figure 2 depicts Goniometry image showing the Reduction of static Contact Angle with water droplet on Polypropylene Surface After Low Temperature Plasma Etching. Figure 3 depicts Scanning Electron Microscopy image of the surface of the substrate mesh before any treatment or coating at 2,000 X Magnification Figure 4 depicts Scanning Electron Microscopy image of the substrate mesh coated with nanodroplets of barrier layer on one side at 5,000 X Magnification

Figure 5 depicts Scanning Electron Microscopy image of the substrate mesh devoid of any nanodroplets coating with the barrier layer on the other side at 2,000 X Magnification

Figure 6 depicts Scanning Electron Microscopy image of the substrate mesh coated with nanodroplets of barrier layer on one side with preservation of the pores of the Substrate Mesh at 400 X Magnification

DETAILED DESCRIPTION OF THE INVENTION WITH ILLUSTRATIONS AND NON-LIMITING EXAMPLES:

Accordingly, the present invention discloses a hernia mesh. The present invention is a dual layer hernia mesh comprising of substrate mesh (11) made up of non-bioabsorbable layer, said substrate mesh is coated with a bioabsorbable barrier layer (10), that can prevent adhesion formation on the coated side, allows adequate tissue ingrowth on the uncoated side, is coated such that layers do not delaminate and there is preservation of substrate mesh pores to allow free tissue fluid transmigration between both sides. Surgical treatment of ventral hernias has changed by introduction of laparoscopy and specialized prosthetic materials for the reconstruction of the abdominal wall. There is widespread acceptance of laparoscopic ventral hernia repair, that is superior to open repair in terms of postoperative infectious complications, length of hospital stay, recurrence, blood loss and cosmetic outcome. The insertion of a mesh for tension free closure of the hernia defect is standard for laparoscopic repair, where in most cases it is required to place the mesh in direct contact with the bowel and other abdominal organs. Such a placement is called intraperitoneal onlay.

The requirements for an ideal mesh for intraperitoneal onlay are:

• To physically separate anatomical structures during the early healing phase

• To restore normal cleavage plans

The present invention intends to achieve all the above-mentioned requirements. The present invention provides for plasma etching of substrate mesh (11) to obtained modified surface (14). Said etching makes the substrate mesh (non-bioabsorbable scar forming mesh) more adhesive on one side. The modified surface (14) is then coated with a bioabsorbable polymer by nano-electrospray coating to deliver a charged very thin layer of anti-adhesive (bioabsorbable polymer) coating on that side, forming said dual layer hernia mesh comprising of substrate mesh (11) coated with the barrier layer (10). The nano-electrospray coating is carried out by first modifying the surface of the substrate mesh (11) with low temperature plasma and then depositing charged nano droplets of the biopolymer on the modified surface (14) that prevents delamination.

Hence, the present invention discloses a dual layer hernia mesh having a bioabsorbable Barrier Layer (10) coated on a substrate mesh (11).

The substrate mesh (11) is a non-bioabsorbable or slowly absorbing/ partially absorbing polymer mesh that may be knitted, woven, spun, non- woven and other manufacturing techniques used to make alloplastic meshes for hernia repair. It can be made of polymers such as polypropylene, polyester, PVDF and other alloplastic material used to make hernia meshes. This layer allows adequate strength and elasticity and permits tissue ingrowth on the peritoneal/ abdominal wall of the hernia defect upon implantation.

The coated barrier layer (10) is made of (poly(L-lactide-E-caprolactone) PLCL in varying ratios or any other bioabsorbable polymer or a combination of bioabsorbable polymers, such that it can prevent adhesion formation on the coated side, is coated such that layers do not delaminate and substrate mesh pores are preserved to allow free tissue fluid transmigration between both sides. The advantage of selecting (poly (L-lactide-c-capro lactone) PLCL copolymer for the barrier layer (10) can be summarized into three reasons.

• Firstly, when PCL is copolymerized with PLA to form a PLCL copolymer, the rate of degradation becomes faster than for either homopolymers. We require a degradation profile beyond 21 days after which the sooner the polymer degrades the better it is for our application.

• Secondly PLCL scaffolds are very elastic and mechanically strong. The mechanical properties differ widely according to the ratio of e-CL and

LA in the copolymerization. PLCL scaffolds are very flexible but are rubber like elastic to maintain a complete recovery even under cyclic loading. We require the barrier Layer (10) to be at least as elastic or more than the substrate mesh (11) so that it does not restrict its abdominal wall compliance after implantation, which when reduced is known to cause mesh related pain, life style restrictions in patients with meshes and other complications.

• And lastly due to its Biocompatibility and safety when used for long term implantation.

On one side of the substrate mesh (11), surface modification is achieved by coating said Bioabsorbable polymer that prevents adhesion of the mesh (10) to bowel and other abdominal organs on the visceral side of the dual layer hernia mesh.

Figure 1 shows the contact angle of a droplet of water on a normal polypropylene surface (11). Figure 2 is the contact angle of a droplet of water on a low temperature plasma etched polypropylene surface (14). There is significant reduction in the contact angle which shows the increase in free surface energy and leads to a strong bonding of the bioabsorbable polymer(s) to the modified surface. The contact angle measurement using goniometiy is a surface characterization technique to determine the change in free surface energy and bonding on any surface before and after treatment.

Figure 3 Scanning Electron Microscopy image of the surface of the uncoated substrate mesh (11) before any treatment or coating at 2,000 X Magnification

Figure 4 Scanning Electron Microscopy image of the substrate mesh coated with nanodroplets of barrier layer on one side (10) on the etched surface at 5,000 X Magnification

Figure 5 Scanning Electron Microscopy image of the substrate mesh devoid of any nanodroplets coating with the barrier layer on the other side after nano-electrospray coating at 2,000 X Magnification

The present invention also discloses a process to obtain said coated mesh (10). One side of said substrate mesh (11) is etched using low temperature plasma treatment to achieve a surface modified substrate mesh. Said surface modified substrate mesh is coated by electro spraying nanodroplets of the bioabsorbable polymer to obtain a barrier layer, thereby forming dual layer hernia mesh (10).

The dual layer mesh (10) comprising of said barrier Layer made of bioabsorbable polymer(s) coated on said substrate mesh (11) prevents adhesion formation on the coated side and allows adequate tissues ingrowth on the uncoated side, with the barrier layer and the substrate mesh having a strong bonding such that layers do not delaminate and there is preservation of the substrate mesh pores to allow free tissue fluid transmigration between both sides (Fig. 6). The coating of said barrier layer by using low temperature gas plasma is created by DC or RF application either in vacuum or air in order to increase the free surface energy and bonding of the bioabsorbable polymer(s) to the non-bioabsorbable or slowly absorbing/ partially absorbing polymer surface.

The electrospraying nanodroplets of the bioabsorbable polymer(s) onto the surface modified substrate mesh provides a strong bonding between the substrate mesh and the barrier layer in order to prevent delamination. The nanodroplets are placed in optimal density and thickness such that the elastic properties of the non-bioabsorbable polymer are not affected and there is a tight surface cover to prevent adhesion with bowel or viscera on the visceral side of the dual layer hernia mesh (10). The present invention is explained by non-limiting examples:

In one of the embodiments of the present invention, the surface modification is achieved by:

(1) Etching one side of the Substrate Mesh (11) which eventually be coated with the Barrier Layer by using low temperature gas plasma created by DC or RF application either in vacuum or air in order to increase the free surface energy and the bonding of the bioabsorbable polymer to the non- bioabsorbable or slowly absorbing/ partially absorbing polymer surface. (2) Electro spraying nanodroplets of the bioabsorbable polymer onto the etched surface of the substrate mesh to achieve said barrier layer on one side with a strong bonding between the two materials of the dual layer mesh in order to prevent delamination. The nanodroplets are placed in optimal density and thickness such that the elastic properties of the non- bioabsorbable polymer are not affected and there is a tight surface cover to prevent adhesion formation with bowel or abdominal organs once implanted. Besides preventing delamination and providing said uniform barrier layer coating, this process also preserves the pores of the substrate mesh allowing free tissue fluid transmigration between both sides (Fig. 6). If the pore size is reduced or obscured due to any coating on the Substrate Mesh as is the case with predicates, it restricts tissue fluid to move from the peritoneal cavity to the hernia sac which leads to post operative seroma formation in the hernia sac and infections.

Claims

im:

1. A coated mesh (10) for hernia repair, characterized in that,

said mesh is a dual layer hernia mesh (10) comprising of:

a first non-bioabsorbable or slowly absorbing/ partially absorbing polymer layer or substrate mesh (11),

a second optimal bioabsorbable layer or barrier Layer (12) coated on the substrate mesh with specific surface modification to obtain said dual layer hernia mesh (10),

wherein said dual layer hernia mesh (10) is capable of preventing adhesion formation on the coated side, allows adequate tissues ingrowth on the uncoated side, is coated such that layers do not delaminate and there is preservation of substrate mesh pores to allow free tissue fluid transmigration between both sides.

2. The coated mesh (10) as claimed in claim 1, wherein said substrate mesh (11) is a non-bioabsorbable or slowly absorbing/ partially absorbing polymer mesh selected from a group of polypropylene, polyester, PVDF or other alloplastic material.

3. The coated mesh (10) as claimed in claim 1, wherein said substrate mesh (11) can be knitted, woven, spun, non-woven or made using other manufacturing techniques used to make alloplastic meshes for hernia repair.

4. The coated mesh (10) as claimed in claim 1 wherein said barrier layer (12) is made up of bioabsorbable polymers in varying ratios.

5. The coated mesh (10) as claimed in claim 4 wherein said barrier layer (12) is made of poly(L~lactide-e~caprolactone (PLCL) comprising of e-CL and LA in varying ratios in the copolymerization.

6. The coated mesh (10) as claimed in claim 1 wherein said surface modification is achieved by low temperature plasma treatment of said substrate mesh (11) for increasing bonding with the barrier layer (12) in said dual layer hernia mesh (10) in order to prevent delamination.

7. The coated mesh (10) as claimed in claim 1 and 6 wherein said substrate mesh (11) is coated with nano-electro spray coating on one side of the plasma treated substrate mesh (11) with an optimal layer of said bioabsorbable polymer(s) to get an optimal density and thickness layer to form a barrier layer (12) to prevent tissue adhesion on the visceral side of the dual layer hernia mesh.

8. A process to obtain said coated mesh (10) as claimed in claim 1, said process comprising the steps of:

a) etching one side of said substrate mesh (11) using low temperature plasma treatment to achieve a surface modified substrate mesh, and

b) electro spraying nanodroplets of the bioabsorbable polymer on the surface modified substrate mesh to obtain a barrier layer (12),

wherein said coated mesh (10) is a dual layer mesh comprising barrier layer (12) made of bioabsorbable polymer(s) coated on a Substrate Mesh (11) such that it prevents adhesion formation on the coated side and allows adequate tissues ingrowth on the uncoated side, with the barrier layer (12) and substrate mesh (11) having a strong bonding such that layers do not delaminate and there is preservation of substrate mesh pores to allow free tissue fluid transmigration between both sides.

9. The process as claimed in claim 8 wherein said coating of said barrier layer (10) by using low temperature gas plasma is created by DC or RF application either in vacuum or air in order to increase the free surface energy and bonding of the bioabsorbable polymer(s) to the non-bioabsorbable or slowly absorbing/ partially absorbing polymer surface.

10. The process as claimed in claim 8 wherein said electro spraying nanodroplets of the bioabsorbable polymer(s) onto the surface modified Substrate Mesh (11) provides a strong bonding between the substrate mesh (11) and the barrier layer (12) in order to prevent delamination.

11. The process as claimed in claim 8 wherein said nanodroplets are placed in optimal density and thickness such that the elastic properties of the non-bioabsorbable polymer are not affected and there is a tight surface cover to prevent adhesion with bowel or viscera on the visceral side of the dual layer hernia mesh.