Surgical materials

Abstract

The present disclosure relates to novel surgical materials, including mesh and polymer compositions, and their use in the treatment of hernias and related diseases and conditions. The present disclosure also relates to methods of making the surgical materials.

Description

Technical Field

[0001] The present invention relates to surgical materials comprising polymer compositions and their use in the treatment of hernias and all diseases and conditions that require providing support to weakened, abnormal, or damaged tissue. The present disclosure also relates to methods of manufacturing surgical materials.

Background Art

[0002] A hernia is the protrusion of an organ from the cavity in which it is normally contained. For the treatment of a hernia, a mesh can be placed at the weakened site of the tissue. The mesh can be fixed to the site using staples, suturing threads, self-fixing meshes, or adhesives. Currently available fixing methods have drawbacks such as weak fixing strength, pain, poor usability, and / or tissue damage. Furthermore, suturing threads are difficult to place in minimally invasive procedures and take a long time. The mesh can be placed at various positions between the layers of the abdominal wall, and the position of the mesh may depend on the surgeon's preference and the patient's medical history. Since the mesh is placed between two layers of tissue, a lower fixing force is often required. However, in some specific procedures such as intraperitoneal mesh placement (IPOM), the mesh is placed intraperitoneally and contacts only one layer of tissue, so a higher fixing strength is required. The tacker may be resorbable (e.g., PGLA) or not (e.g., titanium). Although performing IPOM is very simple, there is a high risk of undesirable adhesions to the internal organs (Gungor et al., 2010), and the pain caused by the fixing method (usually 1 to 2 rows of staples, supplemented by transfascial sutures in some cases) is strong.

[0003] The choice of fixation method varies depending on the surgeon's preference, the location of the hernia, the chosen approach, and the patient. In inguinal scenarios, minimal fixation is usually required, so self-fixing mesh (ProGrip®-Medtronic), a few rivets, or even fibrin adhesive are frequently used. When the hernia is approached via open surgery, sutures are used in most cases. Currently, there are several methods for fixing mesh to tissue, including rivets, sutures, and surgical adhesives made of fibrin or cyanoacrylate. However, all of these methods have at least one of the following drawbacks: pain 1 ,adhesion 2、3 , or performance (i.e., fixing strength) and / or poor usability. The rivets have several limitations, but are not limited to the following: (1) This fixation method is permeable and can cause acute and / or chronic postoperative pain. (2) The rivets can cause visceral attachment. (3) Depending on the location of the hernia, there is a risk of accidental tissue puncture due to insufficient placement angle (some require a 90° angle and the application of back pressure to maximize rivet penetration). (4) The mesh cannot be repositioned once it has been placed. (5) The mesh may become off-center when the rivets are applied, making it difficult to position the mesh flat. Despite all these limitations, rivets remain the standard treatment for IPOM fixation unless a more suitable alternative is available.

[0004] The following various adhesives have been tested in the context of intraperitoneal placement, but none are yet optimal and are not widely adopted: (1) Fibrin mesh has not shown satisfactory clinical outcomes in IPOM repair, despite its use in inguinal hernia and some ventral hernia surgeries, possibly due to insufficient fixation strength. (2) Cyanoacrylate adhesives are sometimes used for inguinal repair, but their use is currently limited due to poor usability (i.e., reaction with bodily fluids), known tissue toxicity, and impaired cell function. 4,5All compounds must be applied in situ to the mesh, and due to their self-polymerizing properties, pre-coating of the mesh is impossible, making standardization impossible. Furthermore, all compounds have low viscosity and may drip onto the surrounding tissue. Because self-polymerization and dripping onto the surrounding tissue cannot be controlled, the mesh cannot be repositioned as needed. Therefore, there remains an unmet medical need for new surgical meshes and fixation methods for securing the mesh to tissue, particularly for hernia patients undergoing IPOM procedures. [Overview of the Initiative]

[0005] In some embodiments, the surgical material includes any substrate having a surface, more specifically a tissue repair support such as a surgical patch, for example a polymer composition applied to a mesh substrate, the polymer composition having a post-it effect that allows the surgical material to be placed and repositioned on body tissue during surgery, and the polymer composition is activated after being placed on body tissue to allow the surgical material to adhere to the tissue. In some embodiments, the polymer composition is the composition described in PCT / EP2020 / 079941. In some embodiments, the polymer composition is activated by light. In some embodiments, the mesh is circular, and the ratio of the mass of the polymer composition to the total length of the polymer pattern (e.g., perimeter of the inner crown + perimeter of the outer crown) is about 0.03 g / cm to about 0.08 g / cm, more specifically about 0.04 g / cm to about 0.06 g / cm.

[0006] In some embodiments, a method for treating a hernia includes the steps of i) placing a surgical material on the herniated defect, the surgical material preferably comprising a polymer composition such as that described in PCT / EP2020 / 079941 (incorporated herein by reference), and ii) activating the polymer composition to cause the surgical material to adhere to the body tissue adjacent to the herniated defect. In some embodiments, the method may further include repositioning the surgical material as necessary after step i) and before step ii). In some embodiments, the polymer composition may be activated by light during step ii). In some embodiments, a method for producing a surgical material may include applying a polymer composition, such as that described in PCT / EP2020 / 079941, onto a mesh substrate, the polymer composition being activated during surgery to allow the surgical material to adhere to tissues in the body. The accompanying drawings incorporated herein and constituting part of this specification illustrate the disclosed embodiments and, together with this specification, explain the principles of the disclosed embodiments. [Brief explanation of the drawing]

[0007] [Figure 1] Figure 1 shows the various layers of the abdominal wall where the mesh can be implanted. 6 [Figure 2] Figure 2 shows the mesh strength of two commercially available composite meshes, Ventralight® ST and Symbotex®. [Figure 3] [on hold] [Figure 4] Figure 4 shows the implantation of the surgical material of this disclosure compared to Absorbatacks® in a porcine model. [Figure 5] Figure 5 shows an exemplary surgical material of this disclosure. [Figure 6] Figure 6 shows a comparison of acute rupture results between surgical materials with a double crown pattern and surgical materials with a full coating pattern. [Figure 7]Figure 7 shows the acute rupture performance of the surgical material of this disclosure at different ratios of the two polymers. [Figure 8] Figure 8 shows the configuration of the lap shear test. [Figure 9] Figure 9 shows the configuration of the burst ball test. [Figure 10] Figure 10 shows the acute wrap shear performance of the surgical materials of this disclosure compared to fibrin. [Figure 11] Figure 11 shows an overview of the acute performance of burst balls using various meshes. [Figure 12] Figure 12 shows the study design for the chronic animal study. [Figure 13] Figure 13 shows the appearance of the mesh within 90 days after transplantation. The first row shows the surgical material of this disclosure, and the second row shows Absorbatacks®. [Figure 14] [on hold] [Figure 15] [on hold] [Figure 16] Figure 16 shows the tissue tolerance and cell infiltration of meshes coated with polymer compositions (surgical materials) or meshes fixed with Absorbatacks®. [Figure 17] Figure 17(a) shows the composition of the burst ball. Figure 17(b) shows the results of a 3-month burst ball test of the surgical disclosure of this disclosure compared to Absorbatacks®. [Figure 18] Figure 18(a) shows the configuration of the T-peel test. Figure 18(b) shows the engraftment strength of the surgical material of the present invention compared to Absorbatacks®. [Figure 19] Figure 19 shows an overview of a chronic test demonstrating that the polymer compositions POL004 and Absorbatacks® have equivalent performance. [Figure 20] Figure 20 shows the acrylate conversion rate of polymer compositions when various meshes are used. [Figure 21]Figures 21(a) to 21(c) show exemplary ratio and / or mass calculations based on a specific mesh and / or polymer pattern. [Figure 22] Figure 22 shows the results of the burst ball test of POL004 after 3 months, compared with SorbaFix (trademark) fixed to Ventralight (trademark).

Mode for Carrying Out the Invention

[0008] Polymer Composition In some embodiments, "polymer composition" refers to any polymer composition, such as those described in PCT / EP2020 / 079941, the content of which is incorporated herein by reference. In some embodiments, "polymer composition" refers to any polymer composition described in US Application No. 15 / 737,103 based on PCT / EP2016 / 064015, US Application No. 15 / 737,143 based on PCT / EP2016 / 064016, or WO2019 / 180208, the content of which is incorporated herein by reference. In some other embodiments, "polymer composition" refers to any polymer composition described in US Patent No. 7,722,894 and US Patent No. 8,143,042, US Patent No. 10,179,195, US Patent No. 9,724,447, US Application No. 16 / 206,937, or EP3005221, the content of which is incorporated herein by reference. According to some preferred embodiments, suitable polymers are selected from the group consisting of poly(glycerol sebacate acrylate) or derivatives thereof, such as aminated PGSA (WO2021 / 078962). According to a preferred embodiment, the polymer is a poly(glycerol sebacate acrylate) derivative having the following structure:

[0009]

Chemical Formula

[0010] In some embodiments, “polymer composition” refers to an adhesive composition which is a photocurable compound. “Photocurable compound” refers to a compound configured to polymerize or otherwise cure when it receives appropriate radiant energy, more specifically radiant energy in the form of light from a light source. According to a preferred embodiment, the light is visible light, more preferably visible blue light. The photocurable compound may contain a prepolymer and a photoinitiator, the photoinitiator being able to induce polymerization of the prepolymer when exposed to light of a specific wavelength. According to at least one embodiment, the photoinitiator is sensitive to ultraviolet (UV) light. According to at least one embodiment, the photoinitiator is sensitive to radiation with a wavelength of 405 nm.

[0011] In some embodiments, the polymer backbone of the prepolymer comprises polymer units of the general formula (-AB-)n, where A is derived from a substituted or unsubstituted polyol or a mixture thereof, B is derived from a substituted or unsubstituted polyacid or a mixture thereof, and n is an integer greater than 1. The polymer backbone consists of repeating monomer units of the general formula -AB-. The term "substituted" has its usual meaning in chemical nomenclature and is used to describe compounds in which hydrogen atoms on the primary carbon chain are substituted with substituents such as alkyl, aryl, carboxylic acid, ester, amide, amine, urethane, ether, or carbonyl. Component A of the prepolymer may be derived from polyols or mixtures thereof, such as diols, triols, tetraols or higher. Suitable polyols include diols, e.g., alkanediols, preferably octanediol; triols, e.g., glycerol, trimethylolpropane, trimethylolpropane ethoxylate, triethanolamine; tetraols, e.g., erythritol, pentaerythritol; and higher polyols, e.g., sorbitol. Furthermore, component A may be derived from unsaturated polyols such as tetradeca-2,12-diene-1,14-diol and polybutadienediol, or other polyols including macromonomer polyols such as polyethylene oxide, polycaprolactone triol, and N-methyldiethanolamine (MDEA) may also be used. Preferably, the polyol is substituted or unsubstituted glycerol. Component B of the prepolymer is derived from a polyacid or a mixture thereof, preferably a diacid or triacid. Exemplary acids include, but are not limited to, glutaric acid (5 carbon atoms), adipic acid (6 carbon atoms), pimelic acid (7 carbon atoms), sebacic acid (8 carbon atoms), azelaic acid (9 carbon atoms), and citric acid. Exemplary long-chain diacids include diacids having more than 10, more than 15, more than 20, and more than 25 carbon atoms. Nonaliphatic diacids may also be used. For example, polyol-diacid copolymers can be produced using the above diacid versions having one or more double bonds. Preferably, the polyacid is substituted or unsubstituted sebacic acid.

[0012] Examples of suitable UV-sensitive photoinitiators include 2-dimethoxy-2-phenylacetophenone, 2-hydroxy-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone (Irgacure 2959), 1-hydroxycyclohexyl-1-phenyl ketone (Irgacure 184), 2-hydroxy-2-methyl-1-phenyl-1-propanone (Darocur 1173), 2-benzyl-2-(dimethylamino)-1-[4-morpholinyl)phenyl]-1-butanone (Irgacure 369), methylbenzoyl formate (Darocur MBF), and oxyphenyl-acetic acid-2-[2-oxo-2-phenylacetoxy-ethoxy]ethyl ester (Irgacure Examples include, but are not limited to, 754), 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone (Irgacure 907), diphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide (Darocur TPO), phosphine oxide, phenylbis(2,4,6-trimethylbenzoyl) (Irgacure 819), and combinations thereof. According to another embodiment, the photoinitiator is sensitive to visible light (usually blue or green light).

[0013] Examples of visible light-sensitive photoinitiators include, but are not limited to, diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide, eosin Y disodium salt, N-vinyl-2-pyrrolidone (NVP), triethanolamine, and camphorquinone. According to some embodiments, the polymer composition further comprises bioactive agents (e.g., antibiotics, tissue growth factors, ...). According to several embodiments, the viscosity of the polymer composition is 500 to 100,000 cP, more preferably 1,000 to 50,000 cP, even more preferably 2,000 to 40,000 cP, and most preferably 2,500 to 25,000 cP. Viscosity analysis is performed using a Brookfield DV-II+Pro viscometer equipped with a 2.2 mL chamber and an SC4-14 spindle, with the analysis speed varied in the range of 5 to 80 rpm. The above viscosities are present in the temperature range relevant to medical applications, i.e., from room temperature to 40°C, preferably down to 37°C.

[0014] surgical materials In some embodiments of this disclosure, the surgical material includes a mesh coated with a polymer composition, such as the polymer described in PCT / EP2020 / 079941, for example. In some other embodiments, the polymer composition may be one described in other patent applications incorporated herein by reference. In some other embodiments, the polymer composition may be any polymer composition having adhesive and / or sealant properties. In some embodiments, depending on the mesh standard, the ratio of the mass of the polymer composition to be applied to the total length of the polymer pattern (e.g., perimeter of the inner crown + perimeter of the outer crown) may be about 0.03 g / cm to about 0.08 g / cm, and more specifically about 0.04 g / cm to about 0.06 g / cm. In other embodiments, the ratio may be 0.03 g / cm, 0.035 g / cm, 0.04 g / cm, 0.045 g / cm, 0.05 g / cm, 0.055 g / cm, 0.06 g / cm, 0.065 g / cm, 0.07 g / cm, or higher. Figure 21 shows the determination of a specific ratio and / or the mass of the polymer composition based on a specific mesh and / or polymer pattern. The amount of polymer composition may depend on the mesh composition. For example, if the mesh is tightly woven, more polymer composition can be applied to the mesh compared to when the mesh is loosely woven. As shown in Figure 5, the coating may be applied according to a certain pattern. Alternatively, the coating may be applied to the entire surface of the mesh. In at least one embodiment, the coating may be applied in any variety of patterns. For example, the polymer composition may be coated in dots rather than lines. According to some embodiments, the coating may be applied to a circular, elliptical, or rectangular mesh, and the pattern may be coated according to a circular, elliptical, or rectangular pattern.

[0015] In some embodiments, the polymer composition is applied according to a double crown pattern. The outer crown of the coating pattern allows for smooth continuity between the mesh and tissue, minimizing the risk of mesh detachment and visceral adhesion. In some embodiments, an inner ring can be used for reasons such as (1) providing homogeneous fixation on the mesh and maximizing contact between the mesh and target tissue, and (2) theoretically reinforcing areas closer to the defect. In some embodiments, when the polymer composition is applied according to a double crown pattern, the distance between the two crowns can be randomly selected. In some embodiments, the ratio of the length of the inner crown to the length of the outer crown may be about 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, or 0.8. In some embodiments, the ratio of the length between the outer crown and the inner crown may be about 0.55 to about 0.65. In some embodiments, the ratio of the length between the outer crown and the inner crown may start from about 0.6. In some embodiments, the coating pattern includes only the outer ring. In some other embodiments, the coating pattern may include the outer ring and any additional patterns within the outer ring.

[0016] Surgical materials can be used to treat hernias and any disease and condition requiring support for weakened, abnormal, or damaged tissue (e.g., perforated tissue such as a fistula). In some embodiments, the surgical material is a mesh pre-coated with a polymer composition. After the surgical material is placed over the defect by a physician, the polymer composition may be activated, for example, using light. According to some embodiments, this light is visible light, more preferably visible blue light. In some embodiments, the light may be provided via an endoscope and an LED module. In some embodiments, the diameter of the endoscope may be about 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, or 13 mm. In some embodiments, the endoscope may have a diameter of about 10 mm. In some embodiments, the LED module may have a light intensity of about 5 W, 6 W, 7 W, 8 W, 9 W, 10 W, 11 W, 12 W, 13 W, 14 W, or 15 W. For example, the LED module may have a light intensity of about 10 W.

[0017] Advantages of surgical materials In some embodiments of this disclosure, the surgical material includes a mesh coated with a polymer composition. This surgical material has several advantages. Non-penetrating fixation: Unlike rivets, the polymer composition is non-penetrating, suggesting it may reduce postoperative pain associated with mesh fixation, making it acceptable to surgeons and specialists and beneficial to patients. Furthermore, non-penetrating fixation prevents damage to the mesh or surgical substrate, potentially reducing the occurrence of adhesions when used intraperitoneally. Easy to use and easy to arrange - Post-it effect: The viscosity of the polymer composition allows it to be applied to the mesh before being rolled into and inserted into the abdominal cavity. This is considerably simpler, more standardized (similar patterns and polymer amounts), and faster than in-situ application as proposed in earlier methods (intra-abdominal wall), such as the use of human fibrin adhesives (e.g., Tissucol / Tisseel), fibrin adhesives (Baxter Healthcare, Deerfield, USA, Illinois), or cyanoacrylate adhesives. These tissue adhesives are typically applied dottedly across the mesh by the surgeon using a laparoscopic applicator.

[0018] Once the mesh and polymer composition enter the abdominal cavity, the Post-it effect allows for easy placement and repositioning of the mesh over the defect. The Post-it effect is the ability of the polymer composition to provide adhesion to the tissue wall of the mesh before it is firmly fixed to the tissue by activation, giving the surgeon the ability to reposition the mesh as desired during surgery, for example. This Post-it effect depends on the degree of adhesion of the polymer composition before photoactivation. The Post-it effect allows for proper centering / placement of the mesh over the defect, which can avoid or reduce hernia recurrence, one of the risks for surgeons. The terms "reposition" or "re-position" also include the meaning of "adjusting the placement of the mesh" and / or "readjusting". On-demand activation: Surgical materials can be activated once placed on the defect. On-demand activation provides greater control over mesh placement, as the physician can decide when to activate the polymer composition. In some embodiments, the polymer composition can be activated by light, for example, 405 nm LED light. In other embodiments, the polymer composition can be activated by a laparoscopic solution.

[0019] Complete sealing solution Figure 4 shows the implantation of the surgical material of this disclosure into a porcine model compared to a mesh fixed with Absorbatacks®. As shown in Figure 4, the placement of the polymer composition at the mesh boundary resulted in a very smooth transition between the mesh and the tissue. This was the case when implanted using a double crown pattern, as shown in Figure 4, and not with rivets. The surgical material composition also exhibits less wrinkling and better fixation to the target tissue than mesh fixed with Absorbatacks®. Treatment methods for hernias or similar conditions In some embodiments, the surgical materials of this disclosure can be used to treat hernias or similar conditions, such as any disease or condition requiring support to weakened, abnormal, or damaged tissue (e.g., tissue having a hole, such as a fistula). The surgical materials may function as a scaffold for cells to proliferate for the purpose of reinforcing the site of injury. The surgical materials of this disclosure comprise a mesh and a polymer composition. In some embodiments, the polymer composition may be pre-coated onto the composite mesh before being shipped to a medical facility such as a hospital. However, in at least one embodiment, a physician may apply the polymer composition to the mesh in situ before implantation.

[0020] In some embodiments, the surgical materials of this disclosure can be used to treat hernias or similar conditions. In some embodiments, the surgical materials of this disclosure can be used in IPOM. In some other embodiments, the surgical materials can be used to treat other similar indications and can be placed in various locations, for example, in ventral-dorsal or inguinal surgery. In some embodiments, the surgical materials can be used to treat humans or animals. In some embodiments, the surgical material can be placed on the defect by a physician. The surgical material has a Post-it effect depending on its degree of adhesion before activation. Therefore, in some embodiments, the physician can reposition the surgical material as needed. Once the surgical material is properly placed on the defect, the polymer composition can be activated, for example, by light or a laparoscopic solution. In at least one embodiment, light can be provided via an endoscope and an LED module. In some embodiments, the diameter of the endoscope may be about 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, or 13 mm. In some embodiments, the endoscope may have a diameter of about 10 mm. In some embodiments, the LED module may have a light intensity of about 5 W, 6 W, 7 W, 8 W, 9 W, 10 W, 11 W, 12 W, 13 W, 14 W, 15 W, or more. For example, the LED module may have a light intensity of about 10 W.

[0021] Method for manufacturing surgical materials In some embodiments, the surgical materials of this disclosure include a polymer composition, such as the polymer described in PCT / EP2020 / 079941, coated on a composite mesh. In some other embodiments, the polymer composition may be one described in other patent applications incorporated herein by reference. In some other embodiments, the polymer composition may be any polymer composition having adhesive and / or sealant properties. In some embodiments, the polymer composition can be coated using a coating apparatus, which allows for the standardization of surgical material products. In some embodiments, the polymer composition may be pre-coated onto a mesh, such as a composite mesh, before being shipped to a medical facility such as a hospital. However, in at least one embodiment, a physician can apply the polymer composition onto the mesh in-situ before implantation.

[0022] In some embodiments, depending on the mesh standard, the ratio of the mass of the polymer composition applied to the total polymer pattern length (e.g., perimeter of the inner crown + perimeter of the outer crown) may be about 0.03 g / cm to about 0.08 g / cm, and more specifically about 0.04 g / cm to about 0.06 g / cm. In other embodiments, the ratio may be 0.03 g / cm, 0.035 g / cm, 0.04 g / cm, 0.045 g / cm, 0.05 g / cm, 0.055 g / cm, 0.06 g / cm, 0.065 g / cm, 0.07 g / cm, or higher. The amount of polymer composition may depend on the mesh composition. If the mesh is tightly woven, more polymer composition can be applied to the mesh compared to when the mesh is loosely woven. As shown in Figure 5, the coating can be applied according to a specific pattern. Alternatively, the coating may be applied to the entire surface of the mesh. In at least one embodiment, the coating may be applied in any variety of patterns. For example, the polymer composition may be coated in dots rather than lines. In some embodiments, the polymer composition is applied according to a double crown pattern. When the polymer composition is coated according to a double crown pattern, the distance between the two crowns may be randomly selected. In some embodiments, the ratio of the length of the inner crown to the length of the outer crown may be about 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, or 0.8. In some embodiments, the ratio of the lengths between the outer and inner crowns may be about 0.55 to about 0.65. In some embodiments, the ratio of the lengths between the outer and inner crowns may start from about 0.6.

[0023] In some embodiments, the coating pattern includes only the outer ring. In some other embodiments, the coating pattern may include the outer ring and any additional patterns within the outer ring. Surgical materials can be used to treat hernias or other similar conditions. In some embodiments, the surgical material is placed on the defect by a physician. Due to its adhesiveness before activation, the surgical material has a Post-it effect. Therefore, in some embodiments, the physician can reposition the surgical material as needed. Once the surgical material is properly placed on the defect, the polymer composition can be activated, for example, by light or a laparoscopic solution. [Examples]

[0024] Examples are provided below to further illustrate and illustrate various tests using the surgical materials of this disclosure. It should be understood that the scope of this disclosure is not limited in any way by the scope of the following examples. The following abbreviations are defined as follows: [Table 1]

[0025] (Example 1) Testing with three types of commercially available composite meshes The surgical material of the present invention comprises a polymer composition applied to a mesh. The mesh is characterized by various aspects, including the material used, pore size, mass, and elasticity. The mesh can be synthetic, biosynthetic, or biological. Synthetic meshes are mainly made from polyester, polypropylene, and ePTFE. Biological meshes are preferred in contaminated areas. When the mesh is not in contact with internal organs (inguinal and ventral surgery other than IPOM), the use of an uncoated synthetic mesh is recommended. In IPOM, a composite mesh is used because it is placed in contact with the internal organs. The mesh has a two-sided structure, with a non-absorbable side that promotes tissue regeneration and an absorbable side (or a non-absorbable side, depending on the manufacturer) that prevents adhesion between the mesh and the internal organs. Preclinical studies focused on three commercially available composite meshes, examining three key products: Symbotex® from Medtronic, Ventralight® ST from Bard, and Proceed® from Ethicon. Details of the reabsorbable fixation devices for these three products are shown in Appendix 1.

[0026] MEDTRONIC - Symbotex (trademark): MEDTRONIC's mesh is a polyester-based mesh coated with collagen and glycerol. This mesh is highly translucent (allowing light to pass through for the activation step when used in combination with polymer composition POL004, see below), easy to handle after hydration (neither too soft nor too hard), and exhibits a bioabsorbable coating that remains in place after handling. ETHICON Inc. - Proceed (registered trademark): Ethicon's mesh is made of polypropylene and coated with oxidized cellulose. This mesh has lower light transmittance than other composite meshes and requires suitable photoactivation conditions (e.g., time, intensity) when combined with polymer compositions. This mesh does not require hydration.

[0027] BARD-Ventralight(TM) ST: Bard's mesh is manufactured from polypropylene and PGA coated with sodium hyaluronate (HA), carboxymethylcellulose (CMC), and polyethylene glycol (PEG) hydrogels. Because the mesh is very soft after hydration, it is difficult to maintain its position when fastening it with rivets. The polymer composition (disclosed in PCT / EP2020 / 079941, hereafter referred to as "POL004") was applied to three types of commercially available composite meshes, and their performance was tested. POL004 is the following poly(glycerol sebacate acrylate) derivative:

[0028] [ka] In the above structure, n and p can be independent integers of 1 or greater. As shown in Figure 2, the stiffness of the mesh weave varies, which can affect the performance of surgical material products, and it may be necessary to adjust the amount of polymer required.

[0029] (Example 2) Testing of coating patterns As shown in Figure 5, various coating patterns were tested using ExVivo (using Symbotex®) to compare full coating, where the product coats the entire mesh, with double crown coating. Figure 6 shows the results of acute rupture tests on surgical materials when polymer composition POL004 was applied in a double crown pattern, compared to when it was applied to the entire mesh. As shown in Figure 6, the performance of the two coating patterns was similar. Therefore, the boundary below the double crown coating pattern can be used to minimize the product volume and reduce the polymer ratio.

[0030] (Example 3) Tests on the amount of polymer composition To define the required product quantity, the following criteria were used: (1) sufficient product to obtain the boundary below the double crown coating pattern, (2) satisfactory acute fixation strength performance (quantified using the composition of burst balls), and (3) good Post-it effect (quantified using a fresh pig carcass model). Symbotex(trademark) The first mesh tested in combination with the polymer composition POL004 was Symbotex® (manufactured by Medtronic). The amount of product used in this mesh was based on empirical evidence according to the criteria mentioned above. A ratio of 0.04 g / cm (equivalent to 3 g for a 15 cm diameter circular mesh using a boundary under a double crown coating pattern) was achieved. Good performance was observed using this product quantity.

[0031] Proceed (registered trademark) In the case of the Proceed® mesh, the inventors used the same amount of POL004 as they did for the Symbotex® mesh. Ventralight(TM) ST As shown in Figure 2, in the case of Ventralight® ST mesh, the polymer may bond together at the mesh weave. In this mesh, the amount of POL004 was increased to achieve performance similar to that of surgical materials using Symbotex® mesh. It was concluded that a ratio of 0.055 g / cm² was sufficient to obtain satisfactory Post-it effect and sufficient fixation strength with this mesh. Figure 7 shows the acute rupture performance of the surgical material of this disclosure at two polymer ratios. The configuration shown in Figure 9 was used for the tests.

[0032] (Example 4) Usability performance test Symbotex(trademark) The polymer composition POL004 was tested in parallel with Absorbatacks®, the current standard treatment, by fixing Symbotex® mesh with POL004. These tests were performed on recently euthanized pig carcasses to evaluate both the acute performance and usability of the polymer. The pig model was considered suitable for evaluating product usability because it resembles a human model. A midline hernia was formed and repaired using either (1) POL004 + Symbotex™ or (2) Absorbatacks™ + Symbotex™ (classically, this procedure was performed using a laparoscopic IPOM approach). Next, the experimenter (a surgeon) presented his opinion on how to evaluate the solutions on a scale from 5 points ("completely agree") to 1 point ("completely disagree"). As expected, the most highly valued advantage of the polymer was its ease of use, and the following improvements were made by using the polymer: (1) the ability to center the mesh in the defect due to the "Post-it" effect and marker coating pattern of POL004; (2) the ability to flatten the mesh on the defect without forming penetrating fixation points that disrupt the continuity of the mesh and tissue; and (3) the ability to reposition the mesh before photoactivation.

[0033] Proceed (registered trademark) Similar tests were conducted on Proceed® mesh, using Securestraps® as a control. The use of the polymer of the present invention resulted in improved usability compared to rivets. Ventralight(TM) ST Similar tests were performed on Ventralight® meshes using SorbaFix® or SorbaFix® and Echo 2 Positioning System® as control. The results of field testing by surgeons regarding both meshes are shown in the table below. This table shows that surgical materials with polymer compositions such as POL004 are easy to centralize, easily conform to the wall well, and are easy to reposition, thus resulting in an overall improvement in the overall surgical procedure. * The symbols are based on interpretations derived from surgeon feedback. [Table 2]

[0034] (Example 5) Photoactivation Test The experiment was conducted to confirm that the polymer composition could be efficiently photoactivated through the mesh in an optimal time, meaning that the polymer would reach a sufficiently cross-linked state to exhibit adhesive properties without extending the handling time. The polymer composition was applied in a double crown pattern between dots and activated by a prototype light source for use in minimally invasive surgery. The light source consists of 405 nm LEDs. The photoactivation of polymer compositions through a mesh was evaluated in two experimental systems. First, the transmittance of the mesh was measured under irradiation with a wavelength of 405 nm. The light intensity transmitted through the mesh when the light source is at a distance of 1 cm is shown in the table below:

[0035] [Table 3] Secondly, the degree of crosslinking of the polymer composition after light irradiation was quantified using Fourier transform infrared spectroscopy (FTIR), and the acrylate conversion rate was quantified. As shown in Figure 20, it has been demonstrated that high acrylate conversion rates (over 90%) can be achieved for polymer compositions when various meshes are used. The polymerization time or intensity also depends on the light transmittance characteristics of the mesh used, as well as the characteristics of the light source. As shown in Figures 21(a) to (c), the ratio and / or mass calculations may vary depending on the selected mesh and / or polymer pattern.

[0036] Results of preclinical trials Various types of tests can be conducted to evaluate the product performance of surgical materials and compare it to the use of rivets (standard treatment): [Table 4]

[0037] Preclinical trial 1. Acute wrap shear performance in ExVivo As shown in Figure 10, an acute ex vivo test was conducted to compare the performance of POL004 with that of a fibrin product fixed to Symbotex® mesh. The lap shear method was used. The test results are shown in Figure 10. Preclinical trial 2. Acute burst ball performance in Exvivo As shown in Figure 11, the graph below compares the burst ball performance of three commercially available mesh polymer compositions with that of a standard treatment fixation method (fasteners). Securestraps® demonstrated the highest performance among all commercially available products. Overall, the hernia mesh products of this disclosure, with the exception of Securestraps®, achieved 61-84% of the rivet performance. These results should be compared to the maximum abdominal pressure maintained by the human abdominal wall. This pressure is 170 mmHg (2 N / cm²) during coughing or jumping. 2 It reaches approximately 12 cm. 2 In the case of a defect (4 cm in diameter), the mesh should withstand a load equivalent to at least approximately 25 N. This suggests that POL004 exhibits sufficient fixing strength to maintain the mesh in the defect area until the wall is repaired.

[0038] Preclinical trial 3. Chronic performance of Symbotex® mesh. The chronic studies were conducted using a pig model with a 3-4 cm resected defect and a midline hernia with intact peritoneum. As shown in Figure 17(b), based on the burst ball performance results of a 3-month chronic test, the surgical material containing POL004 demonstrated performance equivalent to Absorbatacks™ fixing the Symbotex™ mesh with respect to the indicated properties. As shown in Figure 22, similar results were obtained with the Ventralight™ mesh, indicating that POL004 performed equivalently to or better than Sorbafix™. Details of the chronic trial are shown in Figures 12 to 18. Figure 12 shows the design of the chronic trial in three steps. Figure 13 shows the appearance of the mesh at various time points up to 3 months during the trial. Figure 16 shows the tissue tolerance and engraftment of the surgical material compared to the control after 3 months of transplantation. The method included: n=2 animals per group, midline model used, Mobat pentachrome staining. Figure 16 shows the following: (1) Mild tissue engraftment was observed at all transplantation sites regardless of the fixation method. (2) In both groups, fibrous tissue was diffused throughout the mesh. (3) Local tolerance of POL004 was considered good at all time points.

[0039] Figure 17(a) shows the configuration of the burst ball. Figure 17(b) shows the results of a 3-month burst ball test of the surgical disclosure of the present invention compared with Absorbatacks®. The mechanical testing equipment used was (1) Instron, (2) 5kN load cell, and (3) compression at a speed of 25.4 mm / min. The burst ball configuration was (1) maxillary with a central diameter of 15 cm, (2) plunger with a diameter of 2.54 cm, and (3) eight through screws for securing tissue to the configuration. Under all conditions shown in Figure 17(b), the mesh and tissue were penetrated before the interface between the mesh and tissue was destroyed. Figure 18(a) shows the configuration of the T-peel test. Figure 18(b) shows the engraftment strength of the surgical material of the present invention compared with Absorbatacks®. The mechanical testing equipment used was (1) Instron, (2) 500N load cell, and (3) compression at a speed of 25 mm / min. The tissues used were (1) fresh pig abdominal wall, (2) one remaining muscle layer, and (3) 6 × 2 cm tissue after 3 months of engraftment. As shown in Figure 18(b), similar engraftment strengths were obtained between the POL004 group and the Absorbatacks® group.

[0040] Many of the features and advantages of this disclosure are evident from the detailed specification, and the accompanying claims are intended to cover all such features and advantages of this disclosure that fall within the true intent and scope of this disclosure. Furthermore, since numerous modifications and variations should be readily conceivable to those skilled in the art, it is not desirable to limit this disclosure to the configuration and operation as illustrated and described, and therefore, there is room for all suitable modifications and equivalents that fall within the scope of this disclosure. Furthermore, those skilled in the art will understand that the ideas on which this disclosure is based can be readily used as a basis for designing other structures, methods, and systems for carrying out some of the purposes of this disclosure. Accordingly, the claims are not to be considered limited by the foregoing description or examples. Another aspect of the present invention may be as follows: [1] A surgical material comprising a polymer composition applied to a mesh substrate, wherein the polymer composition has a Post-it effect that allows the surgical material to be repositioned on body tissue during surgery, and the polymer composition is activated after being placed on the body tissue to cause the surgical material to adhere to the tissue. [2] The surgical material according to [1], wherein the polymer composition comprises poly(glycerol sebacate acrylate) or a derivative thereof. [3] The surgical material according to [1], wherein the polymer composition is activated by light. [4] The surgical material according to [1], wherein the mesh is circular and the ratio of the weight of the polymer composition to the diameter of the mesh is about 0.04 g / cm to about 0.06 g / cm. [5] A method for treating a hernia, i) A step of placing the surgical material described in [1] above onto a herniated defect, wherein the surgical material preferably comprises a polymer composition containing poly(glycerol sebacate acrylate) or a derivative thereof; and ii) A method comprising the step of activating the polymer composition to cause the surgical material to adhere to internal tissue adjacent to the herniated defect. [6] The method for treating a hernia according to [5], further comprising rearranging the surgical material as necessary after step i) and before step ii). [7] The method for treating a hernia according to [5], wherein the polymer composition is activated by light during step ii). [8] A method for producing a surgical material, comprising applying a polymer composition containing poly(glycerol sebacate acrylate) or a derivative thereof onto a mesh substrate, wherein the polymer composition is activated during surgery to allow the surgical material to adhere to tissues in the body.

[0041] I. Literature TIFF0007870286000007.tif134166 TIFF0007870286000008.tif64167

Claims

1. A surgical material for use in surgery, comprising a mesh substrate and a polymer composition on the mesh substrate, wherein the polymer composition has a Post-it effect that allows the surgical material to be repositioned on body tissue during surgery, the surgery comprises activating the polymer composition after it has been placed on the body tissue to cause the surgical material to adhere to the tissue, the polymer composition is arranged on the mesh substrate in a double crown pattern having an inner crown and an outer crown, the ratio of the mass of the polymer composition to the total polymer pattern length is about 0.03 g / cm to about 0.08 g / cm, the total polymer pattern length is the perimeter of the inner crown + the perimeter of the outer crown, the polymer composition comprises a derivative of poly(glycerol sebacate acrylate), and the derivative of poly(glycerol sebacate acrylate) has the following structure (In the formula, n and p are independent integers greater than or equal to 1.) Surgical material having [a certain characteristic].

2. The surgical material according to claim 1, wherein the polymer composition is an adhesive composition comprising a photocurable compound containing a prepolymer and a photoinitiator.

3. The surgical material according to claim 2, wherein the photoinitiator is sensitive to visible light.

4. The surgical material according to claim 1, wherein the mesh substrate is circular, elliptical, or rectangular, and the double crown pattern is a circular, elliptical, or rectangular pattern.

5. The surgical material according to claim 1, wherein the ratio of the mass of the polymer composition to the total polymer pattern length is about 0.04 g / cm to about 0.06 g / cm.

6. The surgical material according to claim 1, wherein the ratio of the lengths between the outer crown and the inner crown is about 0.55 to about 0.

65.

7. The surgical material according to claim 6, wherein the ratio of the lengths between the outer crown and the inner crown is approximately 0.

6.

8. The surgical material according to claim 1, wherein the polymer composition is arranged at the boundary of the mesh substrate.

9. A surgical material according to claim 1, used for treating hernias.

10. A method for manufacturing surgical materials, comprising coating a mesh substrate with a polymer composition containing a derivative of poly(glycerol sebacate acrylate), The polymer composition is activated during surgery to allow surgical materials to adhere to body tissues. The polymer composition is coated according to a double crown pattern having an inner crown and an outer crown, and The ratio of the mass of the polymer composition to the total polymer pattern length is approximately 0.03 g / cm to approximately 0.08 g / cm, the total polymer pattern length is the sum of the circumference of the inner crown and the circumference of the outer crown, and the derivative of the poly(glycerol sebacate acrylate) has the following structure (wherein the formula n and p are independent integers of 1 or more) method.

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