Two-component sealant system comprising a synthetic matrix and a biosynthetic adhesive for sealing resected surfaces of organs to control bleeding, fluid leakage, and air leakage

Abstract

A method for sealing a resected surface of an organ includes applying a synthetic matrix to the resected surface of the organ and applying an adhesive onto the synthetic matrix such that the adhesive penetrates through interstices in the synthetic matrix and contacts the interface between the synthetic matrix and the resected surface of the organ. The method also includes curing the adhesive to bond the synthetic matrix to the resected surface of the organ. The synthetic matrix is ​​a nonwoven mesh made of polyglactin 910 or any other synthetic or non-synthetic fabric with similar porosity or density. The adhesive is a biosynthetic or synthetic adhesive. After infiltrating the pores of the synthetic matrix and curing, the cured biosynthetic or synthetic adhesive mechanically interlocks with the synthetic matrix to adhere the synthetic matrix to tissue to create a sealing barrier.

Description

[Technical Field]

[0001] This patent application relates generally to surgical procedures and, more particularly, to systems, devices and methods for sealing resection surfaces of tissues and organs to manage bleeding, fluid leakage and air leakage. [Background technology]

[0002] Resection is a surgical procedure that involves cutting a portion of tissue or an organ. Resections performed on a wide variety of organs, including the liver, lungs, and gastrointestinal system, present surgeons with many unique challenges regarding the effective management of postoperative bleeding, fluid leaks, and air leaks.

[0003] During organ resection surgical procedures, surgeons manage major bleeding at the resection surface by using tourniquets, extensive sutures, etc. A significant number of surgeons use adhesive fluids (e.g., synthetic adhesives, fibrin glue gels), which are limited because they may run off the resection surface before fully hardening, or they may easily peel off after hardening because they lack adequate adhesion to the underlying tissue or lack adequate elastic properties.

[0004] Liver resection. A surgical procedure involving the removal of all or part of the liver is commonly referred to as hepatectomy. Partial hepatectomy is a preferred approach for removing solid tumors from the liver. During liver resection, the tissue periphery within the resected area is destroyed, exposing the internal parenchymal tissue and fluid system. Reestablishment of the proper periphery does not occur immediately but requires a continuous tissue healing process that can last from several days to several weeks. During the tissue healing process, the resected tissue may exude blood and / or leak organ-specific fluids (e.g., bile), which can cause postoperative complications. One study found that the bile leakage rate was approximately 5% after hepatectomy, dramatically increasing the patient's chances of postoperative complications.

[0005] Lung resection. Lung resection surgical procedures typically require a significant amount of tissue manipulation and handling, resulting in a high incidence of postoperative air leaks. Standardized techniques used to address air leaks involve suturing or stapling the lung tissue. However, these techniques are ineffective at creating an airtight seal due to the inherent friability of lung parenchymal tissue, especially in emphysema patients. In some cases, topical adhesives are applied directly over either the pleural strip or the staple line, but these techniques are often insufficient to prevent air leaks.

[0006] GI Resection. Gastrointestinal (GI) surgical procedures often involve resecting large segments of a patient's intestinal anatomy to effectively treat disease. After removing the GI tissue, surgeons are required to reconstruct the patient's digestive system. GI reconstruction is complex due to the delicate structure of the intestine, the limited blood supply to the lower colon, limited surgeon access to the complex anatomical structures, and pathologies that typically affect surrounding tissues. However, even when surgeons exercise great care during GI reconstructive surgical procedures, a certain percentage of patients experience complications resulting from leaks at the surgically created anastomosis sites. GI leaks can have devastating consequences, requiring additional surgeries and treatments that are often unsuccessful in managing the leak.

[0007] In view of the above complications, much effort has been made to effectively manage intraoperative and postoperative bleeding, as well as fluid and air leaks. For example, when resecting solid organs, surgeons typically manage major bleeding at the resection surface by using tourniquets and extensive sutures. Minor bleeding and fluid leaks are often managed by using adhesive fluids (e.g., synthetic adhesives, fibrin glue) to cover the resection surface, but these methodologies have had limited success because the adhesive fluids tend to run off the resection surface before hardening, or the hardened adhesives tend to lack adequate adhesion to the underlying tissue or to peel off after hardening due to lack of adequate elastic properties.

[0008] Covidien sells the VERISET® hemostatic patch for sealing excised tissue surfaces. The VERISET® hemostatic patch consists of an oxidized regenerated cellulose (ORC) layer and a reactive polyethylene glycol (PEG) layer. The patch is applied to the tissue surface by applying pressure to the surface. Due to the fact that the ORC matrix is ​​opaque, surgeons cannot evaluate the condition of the excised surface through the VERISET® hemostatic patch when applying pressure to the excised surface. The patch also has low flexibility and therefore may not achieve good tissue conformity or remain compliant with tissue movement.

[0009] In view of the above deficiencies, there is a continuing need for improved systems, devices and methods that enable surgeons to effectively seal resection surfaces of organs and tissues and prevent and / or successfully manage intra- and post-operative bleeding, fluid leakage and / or air leakage from the resection surfaces of tissues and organs.

[0010]

[0003] Today, many efforts are being made to seal resection surfaces of organs to control intraoperative bleeding, postoperative bleeding, fluid leakage, and air leakage. Some of these efforts involve applying a mesh to the resection surface, followed by the application of fibrin glue to seal the resection surface. However, animal model studies have shown that fibrin glue does not have the tissue bonding strength to adhere the mesh to the resection surface of the organ. Summary of the Invention [Means for solving the problem]

[0011] The present patent application overcomes the above-identified deficiencies and discloses preferred systems, devices and methods for effectively sealing the ablation surface to control bleeding, fluid leakage and air leakage.

[0012] In one embodiment, the systems, devices and methods involve the use of a two-component sealant that can be applied to resection surfaces of soft organs (e.g., liver, lung, GI system, pancreas) to control intraoperative and postoperative bleeding, fluid leaks (e.g., bile leaks), and / or air leaks.

[0013] In one embodiment, the first component of the two-component sealant may be a synthetic matrix (e.g., a mesh or nonwoven fabric) placed on the resected surface of the organ. In one embodiment, the synthetic matrix is ​​a nonwoven fabric matrix. In one embodiment, the synthetic matrix is ​​a biodegradable synthetic matrix.

[0014] In one embodiment, the synthetic matrix may be a synthetic substrate or patch, such as an absorbable synthetic substrate made of polyglactin 910 (PG910) material, manufactured and sold under the trademark VICRYL® polyglactin 910 material by Ethicon, Inc. of Somerville, New Jersey. In one embodiment, the polyglactin 910 material may include 90% glycolide and 10% L-lactide.

[0015] In one embodiment, the synthetic matrix that can be placed on the resected surface of the organ along with the second component of the two-component sealant can be a biosynthetic adhesive (e.g., albumin and PEG-SG mixture) in liquid or powder form.

[0016] In one embodiment, the synthetic matrix may be a flexible or conformable nonwoven matrix that is placed over the resected surface of the organ and adapted to conform to the shape of the resected surface and / or organ, hi one embodiment, the synthetic matrix is ​​bioabsorbable.

[0017] In one embodiment, the density of the synthetic matrix may be adjusted to maximize the adhesive and cohesive properties of the sealant to form an impermeable mechanical barrier. Adhesion and cohesive properties are preferably evaluated together by analyzing the system's ability to withstand a standard pressure applied to the surface of the synthetic matrix.

[0018] In one embodiment, the second component of the two-part sealant may be an adhesive, such as a pre-synthetic or synthetic adhesive. The adhesive may be in liquid or powder form.

[0019] In one embodiment, the adhesive may comprise a biocompatible reactive electrophile and a nucleophile. In one embodiment, the electrophile may comprise PEG-SG. In one embodiment, the nucleophile may be selected from any source of amine (NH) groups (e.g., primary amine moieties), any suitable protein or mixture of proteins, albumin, polyethylene glycol amine (PEG-NH), and a combination of albumin and PEG-NH.

[0020] In one embodiment, the biosynthetic adhesive may be a solution of protein (eg, albumin) or partially hydrolyzed protein (eg, peptone) and polyethylene glycol succinimidyl glutarate (ie, PEG-SG).

[0021] In this patent application, the term adhesive refers to a biosynthetic or synthetic adhesive in liquid or powder form that is used to adhere a synthetic matrix (i.e., an absorbable synthetic substrate made from polyglactin 910) to tissue (e.g., the resected surface of an organ).

[0022] In this patent application, the term sealant or sealing device refers to a combination of a synthetic matrix and a biosynthetic or synthetic adhesive in liquid or powder form that is used to adhere the synthetic matrix to tissue.

[0023] As described in more detail herein, the unique fiber structure of the nonwoven PG910 matrix has been determined to provide adequate support for biosynthetic or synthetic adhesives to cure in a manner that forms an excellent level of adhesion to form a fluid and / or airtight seal.

[0024] As disclosed in more detail herein, the order in which the first and second components are applied to the resection surface, as well as the particular composition of the biosynthetic adhesive, may affect the effectiveness of the sealant and therefore may be varied and / or tailored for effective use for a particular organ or application.

[0025] In one embodiment, the synthetic or nonwoven matrix and biosynthetic or synthetic adhesive may be applied in different forms and using different methods to control leakage, including but not limited to bleeding and fluid leakage from resected organs (e.g., liver, GI system) and / or air leakage from resected lungs.

[0026] In one embodiment, the biosynthetic or synthetic adhesive is applied to a biodegradable synthetic matrix (e.g., VICRYL® nonwoven PG910) placed on the resected surface of the organ. The biosynthetic adhesive may be a solution of protein or partially hydrolyzed protein (e.g., albumin) and polyethylene glycol succinimidyl glutarate (PEG-SG) that is premixed immediately before use.

[0027] In one embodiment, the density of the synthetic matrix is ​​controlled (ie, optimized) to ensure that the biosynthetic adhesive is retained by the synthetic matrix.

[0028] In one embodiment, the density of the synthetic matrix is ​​controlled (i.e., optimized) to ensure that the biosynthetic adhesive penetrates completely through the thickness of the synthetic matrix and contacts the resection surface to form a liquid and / or airtight seal on the resection surface.

[0029] In one embodiment, the two-component sealant is allowed a period of time (e.g., 30 seconds to 5 minutes) to adhere to the excised tissue, after which the combination of synthetic matrix and biosynthetic or synthetic adhesive preferably forms a seal at the excision surface to prevent bleeding, fluid leakage (e.g., bile), and / or air leakage.

[0030] In one embodiment, the biosynthetic adhesive may be applied to the surface of the synthetic matrix facing away from the resected surface of the tissue.

[0031] In one embodiment, the density of the matrix may be modified and / or optimized to maximize the cohesion resulting from the combination of the synthetic matrix and the biosynthetic adhesive. In one embodiment, the density of the matrix is ​​optimized (e.g., ensured to be sufficiently low) to allow the biosynthetic adhesive to penetrate through the synthetic matrix and achieve adhesion to the underlying tissue, allowing the biosynthetic or synthetic adhesive to penetrate the matrix and reach the tissue surface, where it can then crosslink with the tissue's surface molecules. In one embodiment, complete penetration of the biosynthetic adhesive into the interstices of the matrix desirably forms a cohesive, crosslinked hydrogel incorporating matrix fibers that function as a reinforcing scaffold.

[0032] In one embodiment, the density of the synthetic matrix is ​​preferably optimized to enhance its ability to retain the biosynthetic adhesive until the adhesive is crosslinked to optimize its cohesive properties. As described herein, the ability of the synthetic matrix to retain the biosynthetic adhesive increases with increasing matrix density up to a critical point. Beyond this critical point, the synthetic matrix density becomes too high, preventing sufficient penetration of the synthetic matrix by the biosynthetic adhesive and its retention by the synthetic matrix.

[0033] In one embodiment, the systems, devices, and methods disclosed herein provide an optimal matrix density range for the synthetic matrix, whereby the optical matrix density range is utilized to: 1) maximize biosynthetic adhesive penetration through the matrix; 2) maximize retention of the biosynthetic adhesive by the matrix; 3) maximize the ability of the system to withstand pressure applied to the matrix; 4) maximize the ability of the two-component sealant to stop bleeding and seal fluid and air leaks; and 5) maximize device compatibility with tissue.

[0034] In one embodiment, a method of sealing or providing hemostasis to an organ or wound preferably comprises applying a porous, flexible synthetic matrix to the organ or wound and applying an adhesive (e.g., a biosynthetic or synthetic adhesive, such as by spraying) on ​​top of the synthetic matrix, thereby allowing the adhesive to permeate through the synthetic matrix and reach the interface between the substrate and the organ, wound or excision surface.

[0035] In one embodiment, the method includes curing the adhesive to bond the synthetic matrix to the organ or wound.

[0036] In one embodiment, for soft tissue ablation, the porosity of the synthetic matrix is ​​preferably about 102 to 191 mg / cm 3 , more preferably about 102.7 to 190.7 mg / cm 3 , which is suitable for sealing soft tissue excisions.

[0037] In one embodiment, for high pressure bleeding, the porosity of the synthetic matrix is ​​preferably about 128-191 mg / cm 3 , more preferably about 128.7 to 190.7 mg / cm 3 , which is suitable for sealing high pressure bleeding.

[0038] In one embodiment, a method for sealing a resected surface of an organ to prevent bleeding, fluid leakage, and / or air leakage preferably includes applying a synthetic matrix to the resected surface of the organ, applying an adhesive, such as a biosynthetic or synthetic adhesive, onto the synthetic matrix such that the adhesive permeates through interstices in the synthetic matrix and contacts the interface between the synthetic matrix and the resected surface of the organ, and curing the adhesive to bond the synthetic matrix to the resected surface of the organ.

[0039] In one embodiment, the synthetic matrix is ​​a biodegradable, porous, flexible substrate.

[0040] In one embodiment, the synthetic matrix is ​​a nonwoven mesh made of polyglactin 910.

[0041] In one embodiment, the synthetic matrix and adhesive are preferably at least partially transparent to allow the surgeon to see through the synthetic matrix during placement and / or repositioning of the synthetic matrix on the resected surface of the organ.

[0042] In one embodiment, when used to seal soft tissue excisions, the synthetic matrix preferably has a density of 102 to 191 mg / cm 3 , more preferably 102.7 to 190.7 mg / cm 3 It has a density range of

[0043] In one embodiment, the biosynthetic adhesive desirably comprises a partially hydrolyzed protein (eg, albumin) and polyethylene glycol succinimidyl glutarate (PEG-SG).

[0044] In one embodiment, the biosynthetic adhesive may be a mixture of a 10% albumin solution and a 75 mg / ml PEG-SG solution.

[0045] In one embodiment, the biosynthetic adhesive may be in liquid or powder form.

[0046] In one embodiment, after the biosynthetic or synthetic adhesive is applied to the synthetic matrix and cured, the adhesive mechanically interlocks with the fibers of the synthetic matrix and preferably chemically crosslinks with the fibers of the synthetic matrix.

[0047] In one embodiment, a method for sealing a resected surface of an organ includes applying a porous, bioabsorbable synthetic matrix, preferably made of polyglactin 910, to the resected surface of the organ; applying an adhesive (e.g., a biosynthetic adhesive comprising albumin and polyethylene glycol succinimidyl glutarate (PEG-SG)) onto the synthetic matrix such that the adhesive permeates through the pores of the synthetic matrix and contacts the interface between the synthetic matrix and the resected surface of the organ; and allowing the adhesive to cure to bond the synthetic matrix to the resected surface of the organ.

[0048] In one embodiment, prior to applying the porous bioabsorbable synthetic matrix to the resected surface of the organ, the method may include a preliminary step of pre-applying an adhesive onto the resected surface of the organ, and then applying the synthetic matrix over the pre-applied adhesive.

[0049] In one embodiment, a kit for sealing resected surfaces of an organ includes a synthetic matrix preferably comprising a nonwoven mesh made of polyglactin 910 and an adhesive comprising biocompatible reactive electrophiles and nucleophiles.

[0050] In one embodiment, the adhesive may be a biosynthetic adhesive comprising a partially hydrolyzed protein such as albumin and polyethylene glycol succinimidyl glutarate (PEG-SG).

[0051] In one embodiment, the kit may include a dual syringe for dispensing the biosynthetic adhesive. The dual syringe may include a first syringe barrel containing a 20% albumin solution and a second syringe barrel containing a 150 mg / ml PEG-SG solution. The two components are preferably mixed together upon dispensing from the dual syringe to form the curable biosynthetic adhesive, or mixed in situ on a matrix that is applied to tissue.

[0052] In one embodiment, a kit for sealing an organ or wound or for providing hemostasis preferably includes an absorbent synthetic porous matrix (e.g., a nonwoven matrix or patch), such as a VICRYL® nonwoven PG910 substrate and a binary adhesive comprising albumin and PEG-SG. [Brief explanation of the drawings]

[0053] [Figure 1] 1 shows the chemical formula of polyethylene glycol succinimidyl glutarate (PEG-SG), part of a biosynthetic adhesive, according to one embodiment of the present patent application. [Figure 2] 1 shows a schematic example of a protein (albumin) that is part of a biosynthetic adhesive according to one embodiment of the present patent application. [Figure 3] FIG. 1 is a plan view of a composite matrix according to one embodiment of the present patent application. [Figure 4] 1 shows a schematic example of a combination of a biosynthetic adhesive and a synthetic matrix according to one embodiment of the present patent application. [Figure 5] 1 shows a schematic example of a biosynthetic adhesive cross-linked with a synthetic matrix for sealing the resected surface of tissue, represented by the letter T, according to one embodiment of the present patent application. [Figure 6] 1 is a composite matrix of a two-component sealant used to seal resection surfaces of tissue, according to one embodiment of the present patent application. [Figure 7] 7 shows the synthetic matrix of FIG. 6 immobilized on a 45-degree inclined plane after application of 10% albumin, 75 mg / ml 4-arm PEG-SG-10K, 50 mM carbonate (pH=8.0) biological adhesive, according to one embodiment of the present patent application. [Figure 8] 1 is a graph plotting the retention and penetration of a biosynthetic adhesive into synthetic matrices having different density levels, according to an embodiment of the present patent application. [Figure 9] 1 is a graph plotting biosynthetic adhesive penetration through synthetic matrices with different density levels, according to an embodiment of the present patent application. [Figure 10] 1 has two arrows indicating the depth of biosynthetic adhesive penetration through a first synthetic matrix (Matrix 1) having a density of 93.0 mg / cm3 according to one embodiment of the present patent application. [Figure 11] It has two arrows indicating the depth of biosynthetic adhesive penetration through a second synthetic matrix (Matrix 2) having a density of 120.5 mg / cm3 according to one embodiment of the present patent application. [Figure 12] 1 has two arrows indicating the depth of biosynthetic adhesive penetration through a third synthetic matrix (Matrix 3) having a density of 131.2 mg / cm3 according to one embodiment of the present patent application. [Figure 13] 1 has two arrows indicating the depth of biosynthetic adhesive penetration through a fourth synthetic matrix (Matrix 4) having a density of 178.2 mg / cm3 according to one embodiment of the present patent application. [Figure 14] 1 has two arrows indicating the depth of biosynthetic adhesive penetration through a fifth synthetic matrix (Matrix 5) having a density of 247.0 mg / cm3 according to one embodiment of the present patent application. [Figure 15] 1 is a graph plotting burst pressure levels of synthetic matrices having different density levels, according to an embodiment of the present patent application. [Figure 16] 1 is a graph plotting burst pressure levels of synthetic matrices with different density levels for soft tissue ablation and high pressure bleeding, according to an embodiment of the present patent application. [Figure 17] 1 is a graph plotting burst pressure levels of synthetic matrices having different density levels, according to an embodiment of the present patent application. [Figure 18A] 1 illustrates a method for resecting a liver according to one embodiment of the present patent application. [Figure 18B] 18B illustrates a method of placing a synthetic matrix on the resected surface of the liver shown in FIG. 18A, according to one embodiment of the present patent application. [Figure 18C]18B shows the synthetic matrix of FIG. 18B after a biosynthetic adhesive has been applied to the synthetic matrix to seal the resected surface of the liver shown in FIG. 18A, according to one embodiment of the present patent application. [Figure 19A] 1 illustrates a first stage of a surgical method, including resecting a liver lobe, according to one embodiment of the present patent application. [Figure 19B] 10 illustrates a second step of the surgical method, which involves spraying a biosynthetic adhesive onto the resected surface of the liver lobe, according to one embodiment of the present patent application. [Figure 19C] 10 illustrates a third step of the surgical method, including placing a synthetic matrix on the sprayed resection surface of the liver lobe, according to one embodiment of the present patent application. [Figure 19D] 19C shows the synthetic matrix of FIG. 19C after being sprayed with a biosynthetic adhesive sealant. [Figure 19E] 1 shows the curing stages of a biosynthetic adhesive. [Figure 19F] 10 illustrates another stage of the surgical method, including removing the clamp and re-establishing blood flow to the resected liver lobe, according to an embodiment of the present patent application. [Figure 19G] The resected surface of a liver lobe is shown after the synthetic matrix has been peeled away to demonstrate that bleeding reoccurs when the synthetic matrix is ​​removed from the resected surface of the liver lobe. DETAILED DESCRIPTION OF THE INVENTION

[0054] In one embodiment, the two-component sealant is preferably applied to the resection surface of a soft organ to prevent intra- and post-operative bleeding, fluid leakage (e.g., bile), and / or air leakage (e.g., lung) from the resection surface.

[0055] 1 and 2, in one embodiment, a two-component sealant for resected surfaces of soft organs preferably includes an adhesive 100, such as a biosynthetic adhesive, which may be applied in liquid or powder form onto a synthetic matrix. In one embodiment, the biosynthetic adhesive may be a solution including a mixture of polyethylene glycol succinimidyl glutarate, also known as PEG-SG, and a protein (e.g., albumin).

[0056] Polyethylene glycol succinimidyl glutarate (PEG-SG) has a well-established safety profile in medical devices and is used in sealant products such as Duraseal and Coseal. Succinimidyl glutarate reacts with amine groups on proteins, such as collagen, under mildly alkaline conditions to form amide bonds. Delaminable ester crosslinkers engineered into PEG allow the polymer to degrade in vivo. This form of PEG also offers the ability to crosslink across multiple collagen fibers due to its long spacer region, which allows intermolecular crosslinking.

[0057] FIG. 1 shows the chemical structure of polyethylene glycol succinimidyl glutarate (ie, PEG-SG).

[0058] FIG. 2 shows a simplified schematic diagram of a protein (i.e., albumin).

[0059] 3, in one embodiment, the two-component sealant preferably includes a synthetic matrix 102 adapted to be placed on the resected surface of a soft organ. In one embodiment, the synthetic matrix 102 may be a mesh matrix or a nonwoven matrix that is placed on the resected surface along with a biosynthetic adhesive 100 (FIGS. 1 and 2). In one embodiment, the nonwoven matrix is ​​flexible and / or conformable and is adapted to be placed on the resected tissue surface, with the biosynthetic adhesive 100 applied to the synthetic matrix 102.

[0060] In one embodiment, the synthetic matrix 102 preferably includes fibers 104 and interstices 106 disposed between the fibers 104 .

[0061] In one embodiment, the biosynthetic adhesive is a cross-linkable liquid adhesive that is applied to the nonwoven matrix 102. The biosynthetic adhesive is adapted to penetrate through the interstices 106 of the synthetic matrix 102 such that the synthetic matrix 102 retains the biosynthetic adhesive, so that the adhesive hardens and mechanically interlocks and / or chemically cross-links with the fibers 104 of the synthetic matrix 102.

[0062] In one embodiment, the density of the synthetic matrix 102 may be adjusted (i.e., optimized) to maximize the ability of the adhesive to adhere to tissue and the cohesiveness of the sealant to form an impermeable mechanical barrier over the resected surface of the organ. In one embodiment, adhesion and cohesiveness may be evaluated together by assessing the system's ability to withstand a standard pressure applied to a major surface of the synthetic matrix 102.

[0063] 4 and 5, in one embodiment, after synthetic matrix 102 is applied across the tissue resection surface T, biosynthetic adhesive 100 may be applied to the surface of synthetic matrix 102 facing away from the tissue resection surface T. In one embodiment, the density of synthetic matrix 102 is selected to ensure that the density is low enough to allow biosynthetic adhesive 100 to penetrate completely through the thickness of synthetic matrix 102 and reach the tissue resection surface, where it may harden, crosslink with surface molecules, and achieve adhesion to the underlying tissue. In one embodiment, biosynthetic adhesive 100 is preferably formulated to penetrate completely through the interstices of synthetic matrix 102, incorporating the fibers of the synthetic matrix to create a cohesive crosslinked hydrogel that acts as a reinforcing scaffold that seals the tissue resection surface T.

[0064] In one embodiment, the cohesion resulting from the cross-linked hydrogel reinforcement may be increased by controlling the density of the synthetic matrix 102.

[0065] In one embodiment, the design parameters of the synthetic matrix 102 are selected to optimize the synthetic matrix's ability to retain the biosynthetic adhesive 100 for a sufficient period of time, allowing the adhesive to cure and mechanically interlock and / or chemically crosslink with the fibers 104 of the synthetic matrix 102, which in turn optimizes the cohesive properties of the two-part sealant. The ability of the synthetic matrix to retain the biosynthetic adhesive is preferably increased by increasing the matrix density up to a predetermined density level (i.e., a critical point, optimized density level). Above the predetermined density level, the density of the synthetic matrix increases to allow sufficient penetration of the biosynthetic adhesive through the thickness of the synthetic matrix and retention of the biosynthetic adhesive by the synthetic matrix.

[0066] In one embodiment, the specifications and design parameters of the biosynthetic adhesive 100 and synthetic matrix 102 are established by identifying an optimal matrix density range that maximizes penetration of the biosynthetic adhesive (e.g., liquid) through the thickness of the synthetic matrix, retention of the biosynthetic adhesive by the synthetic matrix, and the ability of the system to withstand pressures resulting from bleeding, fluid leaks, and air leaks, thereby maximizing the functionality of the two-component sealant to stop bleeding and seal fluid and air leaks.

[0067] In one embodiment, a synthetic matrix (e.g., VICRYL® PG910 mesh) may be functionalized with amine groups to allow for the formation of covalent bonds between the synthetic matrix and PEG molecules (i.e., PEG-SG), which ultimately covalently bond the synthetic matrix molecules to tissue. A protein solution or partial protein digest may be applied to the synthetic matrix and excised area as a PEG-SG substrate, as disclosed herein, to form a sealant.

[0068] Figures 4 and 5 show the reaction of PEG-SG4 (4-arm version) with albumin. The amine (NH2) groups (e.g., primary amine moieties) of the protein shown in Figures 4 and 5 react with the succinimidyl glutarate of PEG to form a covalent (amide) bond. PEG-SG4 can also react with proteins on tissue surfaces (e.g., collagen), providing adhesion of the crosslinked polymer to the tissue surface.

[0069] In one embodiment, experiments were conducted to determine the optimal density level for a synthetic matrix. In one embodiment, five matrices were evaluated, each having a comparable volume but different density. In one embodiment, the first synthetic matrix specimen (i.e., Matrix 1) had a density of about 93.0 mg / cm 3 and the second composite matrix specimen (i.e., Matrix 2) had a density of about 120.5 mg / cm 3 and the third composite matrix specimen (i.e., Matrix 3) had a density of about 131.2 mg / cm 3 and the fourth composite matrix specimen (i.e., Matrix 4) had a density of about 178.2 mg / cm 3 and the fifth composite matrix specimen (i.e., Matrix 5) had a density of about 247.0 mg / cm 3 A chart showing the different densities of the five different specimens is shown below.

[0070] [Table 1]

[0071] 6 and 7, in one embodiment, to evaluate the ability of different matrices 102 to absorb and retain a biosynthetic adhesive, each matrix was sized to be a 6 x 6 cm square matrix. In one embodiment, each matrix was held at an approximately 45-degree angle on a test substrate 108. In one embodiment, a biosynthetic adhesive (i.e., 10% albumin, 75 mg / mL 4-arm PEG-SG-10k, 50 mM carbonate at pH = 8.0) was sprayed onto each 6 x 6 cm square matrix using a spray device such as the Evicel® airless spray accessory. After being applied to the synthetic matrix 102, the biosynthetic adhesive was allowed to cure for 2 minutes. Each matrix was evaluated to measure the retention of the biosynthetic adhesive by the synthetic matrix and the penetration of the biosynthetic adhesive through the thickness of the synthetic matrix.

[0072] In one embodiment, the retention of biosynthetic adhesive by each of five synthetic matrix samples (i.e., Matrix 1, Matrix 2, Matrix 3, Matrix 4, and Matrix 5) was measured gravimetrically. In other words, synthetic matrix samples with different densities were studied to evaluate the retention of biosynthetic adhesive. Using a one-way ANOVA test, it was demonstrated that there was a significant difference (P<0.05) in penetration and retention at different densities. 3 and a synthetic matrix specimen (i.e., Matrix 1) having a density of 247 mg / cm 3 The lowest biosynthetic adhesive retention was observed when testing synthetic matrix specimens (i.e., Matrix 5) having a density of 178.2 mg / cm 3 It was observed that the synthetic matrix specimen having a density of 178.2 mg / cm (i.e., Matrix 4) provided the greatest biosynthetic adhesive retention. 3 and 93.0 mg / cm. 3 , 120.5 mg / cm 3 , 131.2 mg / cm 3 and 247 mg / cm 3These represent 75%, 25%, 23%, and 80% increases in biosynthetic adhesive retention compared to the other specimens in the .

[0073] In one embodiment, the ability of the biosynthetic adhesive to penetrate or pass through synthetic matrix specimens with different densities was evaluated by confocal microscopy. In one embodiment, a cross section of each synthetic matrix was imaged and measured via image processing methods.

[0074] Biosynthetic adhesive retention data and biosynthetic adhesive penetration data are shown together in Figure 8. At low matrix densities, the biosynthetic adhesive can penetrate completely through the synthetic matrix. As the matrix density increases, the ability of the matrix to absorb the biosynthetic adhesive increases. If the matrix density becomes too great and it is no longer possible for the biosynthetic adhesive to penetrate completely through the depth of the matrix, the biosynthetic adhesive will no longer be able to penetrate completely as it does at low matrix densities. The inability of the sealant to penetrate through the matrix reduces the matrix's ability to retain the sealant, which allows the sealant to easily flow from the exposed surface of the matrix. Without complete sealant penetration of the matrix, the sealant will not be able to bond with the underlying tissue in vivo.

[0075] As shown in the graph in Figure 8, the Kruskal-Wallis test showed a value of 178.2 mg / cm 3 The results demonstrated that there was complete penetration of the biosynthetic adhesive through the fourth synthetic matrix specimen (i.e., Matrix 4) having a matrix density of 1.0, followed by a significant 73% decrease during penetration through the denser synthetic matrices. In the graph shown in Figure 8, error bars represent one (1) standard deviation.

[0076] Figure 9 is a graph showing biosynthetic adhesive penetration through the thickness of matrix specimens at different matrix densities. Due to the nature of the PG910 matrix, as the density of the matrix increases, there is a corresponding increase in the thickness of the matrix itself.3 Up to a matrix density of 178.2 mg / cm, the sealant penetrates completely through the matrix and the thickness of the biosynthetic adhesive also increases. 3 Above a matrix density of 247 mg / cm, the thickness of the biosynthetic adhesive will decrease dramatically, while the matrix thickness continues to increase. This is due to insufficient penetration of the biosynthetic adhesive through the matrix. For example, above a matrix density of 247 mg / cm, the thickness of the biosynthetic adhesive will decrease dramatically. 3 At a matrix density of , the distance of biosynthetic adhesive penetration through the matrix is ​​178.2 mg / cm 3 9. In the graph shown in FIG. 9, the error bars represent one (1) standard deviation.

[0077] Figures 10-14 show representative confocal microscopy images of biosynthetic adhesive penetration through the thickness of five synthetic matrix specimens with different densities. In Figures 10-14, the distance between the two red arrows indicates the sealant penetration through the respective matrix.

[0078] Figure 10 shows the 93.0 mg / cm 3 FIG. 11 shows the first matrix specimen (Matrix 1) having a density of 120.5 mg / cm 3 Figure 12 shows a second matrix specimen (Matrix 2) with a density of 131.2 mg / cm 3 Figure 13 shows a third matrix specimen (Matrix 3) with a density of 178.2 mg / cm 3 FIG. 14 shows a fourth matrix specimen (Matrix 4) having a density of 247.0 mg / cm 3 1 shows a fifth matrix specimen (Matrix 5) having a density of

[0079] 93.0-178.2 mg / cm 3 The synthetic matrix specimens (i.e., matrix specimens 1-4) with a density of 247.0 mg / cm were completely infiltrated by the biosynthetic adhesive. 3The biosynthetic adhesive penetration through a synthetic matrix specimen (shown in Figure 14, Matrix Specimen 5) with a density of 178.2 mg / cm 3 The density of the composite matrix specimen (shown in FIG. 13, matrix specimen 4) was less than 52% of that of the composite matrix specimen (shown in FIG. 13, matrix specimen 4).

[0080] In one embodiment, the functional significance of the observed differences in retention and penetration of the biosynthetic adhesive was evaluated via a benchtop hydraulic burst pressure test. In one embodiment, a synthetic matrix specimen with a previously cured biosynthetic adhesive was mounted in a test fixture. Saline was pumped under the matrix specimen at a rate of 2 mL / min until failure. The maximum pressure at failure was recorded. Synthetic matrix specimens with five different density levels, as disclosed herein, were evaluated. Referring to FIG. 15, the 178 mg / cm 3 A composite matrix specimen having a density of 93.0 cm / mg (i.e., Matrix 4 in Figure 13) achieved a burst pressure of 317 mmHg, which is 3 This is 73 times better than the synthetic matrix specimen (i.e., Matrix 1 in Figure 10) which has a density of 120.5 cm / mg 3 This is six times better than the synthetic matrix specimen (i.e., Matrix 2 in Figure 11) which has a density of 131.2 cm / mg 3 This is 1.78 times better than the synthetic matrix specimen (i.e., Matrix 3 in Figure 12) which has a density of 247 mg / cm 3 15 is five times better than the synthetic matrix specimen (i.e., Matrix 5 in Figure 14) having a density of 178 mg / cm. In the graph shown in Figure 15, the error bars represent one (1) standard deviation. Testing using a Welch ANOVA test resulted in a 3 It was determined that a synthetic matrix specimen having a density of 0.01 (i.e., Matrix 4 in FIG. 13) was significantly better at sealing the resected surface of the organ than other synthetic matrix specimens having different densities.

[0081] For soft tissue resection, pressures of 9 mmHg can be expected, but in one embodiment, a safety factor of 3 is preferably applied to ensure desired performance. For high-pressure bleeding, the upper clinical pressure limit can reach 160 mmHg.

[0082] Referring to FIG. 16, to determine the minimum required matrix density for adequate sealing, a quadratic regression model of the burst pressure data versus matrix density was generated in Microsoft Excel (R 2 = 83.65%). Using a response optimization algorithm in Minitab 18 (statistical analysis software provided by MINITAB), the minimum matrix densities resulting in burst pressures of 27 mmHg and 160 mmHg were determined. The minimum matrix densities were 102.7 mg / cm, respectively. 3 and 128.7 mg / cm 3 In the graph shown in Figure 16, the error bars represent one (1) standard deviation.

[0083] Referring to Figure 17, the maximum matrix density for adequate sealing is limited to that which allows complete penetration of the biosynthetic adhesive through the thickness of the synthetic matrix. For the sealant thickness data, a quadratic regression model was calculated in Microsoft Excel (R 2 = 97.35%). The maximum matrix density was defined as the matrix density that resulted in sealant penetration greater than the average thickness of the matrices tested (i.e., 430 μm). Using a response optimization algorithm in Minitab 18, the maximum matrix density resulting in a biosynthetic adhesive penetration of 430 μm was determined to be 190.7 mg / cm. 3 In the graph shown in Figure 17, error bars represent one (1) standard deviation.

[0084] Thus, in one embodiment, the optimal matrix density used to seal soft tissue excisions is about 102 to 191 mg / cm 3 , more preferably 102.7 to 190.7 mg / cm 3and the optimal matrix density used to seal high-pressure bleeding is approximately 128-191 mg / cm 3 , more preferably 128.7 to 190.7 mg / cm 3 is.

[0085] To demonstrate that the synthetic matrix at the selected density functions adequately to seal the resection surface, 107.9 mg / cm 3 Synthetic matrix specimens with a density of 0.01 were used in liver lobe resections and shown to be effective in achieving hemostasis.

[0086] Referring to Figure 18A, in one embodiment, the liver undergoes a partial lobectomy. Referring to Figures 18B and 18C, 107.9 mg / cm 3 A synthetic matrix 102 having a density of 0.01 μm and a biosynthetic adhesive were applied to a partial liver lobectomy using the systems, devices, and methods disclosed herein. The combination of the synthetic matrix and biosynthetic adhesive sealed the resection surface, preventing bleeding and fluid leakage and achieving hemostasis.

[0087] In one embodiment, a sealant comprising a synthetic mesh and a biosynthetic adhesive is applied together onto the resected surface of the soft organ, which may be applied in different forms and ways as described below to control bleeding, fluid leakage, and air leakage.

[0088] In one embodiment, a biodegradable synthetic matrix (e.g., VICRYL® nonwoven PG910) is placed on the resection surface, followed by application of a biosynthetic adhesive (e.g., albumin solution and PEG-SG adhesive solution) on top of the synthetic PG910 mesh. After 1-5 minutes, the combination of the synthetic matrix and biosynthetic adhesive preferably forms a sealant at the resection surface.

[0089] In one embodiment, a biosynthetic adhesive (eg, in liquid form) may be applied to a synthetic matrix, which may then be applied to the excised tissue.

[0090] In one embodiment, a biosynthetic adhesive (e.g., in liquid form) may be applied to the excised tissue, and then a synthetic matrix may be applied to the excised tissue so that it contacts the previously applied biosynthetic adhesive.

[0091] In one embodiment, after the synthetic matrix is ​​placed on the resection surface, additional biosynthetic adhesive may be applied onto the placed synthetic matrix.

[0092] In one embodiment, PEG-SG (and optionally albumin) is pre-coated onto a synthetic matrix (e.g., VICRYL® PG910 mesh), which is dried onto the wet excised tissue to achieve a seal.

[0093] In one embodiment, the PEG-SG and albumin components of the biosynthetic adhesive are applied to the excised tissue as a powder mixture, followed by placement of a dry synthetic matrix (e.g., VICRYL® PG910 mesh) over the wet excised tissue to achieve sealing. Dry storage preferably allows for long-term storage of the product at room temperature. In certain preferred embodiments, the powder mixture may have a ratio of PEG-SG to albumin of the following ratios: 0 / 100%, 20 / 80%, 40 / 60%, 50 / 50%, 60 / 40%, 80 / 20%, and 100 / 0%, respectively.

[0094] In one embodiment, PEG-SG may be pre-coated onto a synthetic substrate (e.g., VICRYL® PG910 mesh), an albumin solution may be applied to the synthetic matrix and / or the excised tissue, and the synthetic matrix may be immediately applied to the excised tissue to achieve a seal.

[0095] In another embodiment, the mesh may be used as a buttress material for a linear staple having a wide edge (wider than a linear anvil, a stapler anvil design for delivering buttress material wider than the width of the anvil as disclosed in #153034), followed by application of a fluid adhesive onto the mesh to provide sealing of exposed tissue (e.g., during soft organ resection using a linear stapler).

[0096] Example 1. Use of a Synthetic Matrix and Biosynthetic Adhesive as a Sealant in a Pig Model of Liver Resection. The systems, devices, and methods disclosed herein were used as sealants in a pig model of liver resection as follows: A liver lobe was resected using a scalpel, and the liver was clamped to minimize blood flow to the resected lobe. A biosynthetic adhesive solution was prepared using a dual-syringe system (e.g., an Evicel device) holding 5 ml in each syringe: 1) a 20% albumin solution and 2150 mg / ml PEG-SG solution. The contents of the two syringes were mixed within the spray tip of the device as they were sprayed onto the resected liver surface (e.g., approximately 5 ml). A synthetic mesh (e.g., nonwoven VICRYL® PG910 mesh) was then placed on the resected surface. The synthetic matrix preferably conforms to the geometry of the resected tissue. Additional biosynthetic adhesive (e.g., approximately 5 mL) was sprayed onto the synthetic matrix without pressure being applied to the synthetic matrix. After two minutes, the clamps were removed to restore normal blood flow to the resected lobe. No bleeding or fluid leakage from the resection surface was visually observed. After the adhesive hardened, sutures may be passed through the cured sealant device (i.e., the combination of synthetic mesh and cured adhesive) to help secure the sealant device to the resected organ. The cured sealant device may function as a buttress to reduce stress around the suture holes. After several minutes, the sealant was removed, but this required significant force due to the strong adhesion of the synthetic matrix and biosynthetic adhesive to the resected tissue, and rebleeding was observed. The study in Example 1 demonstrates the efficacy of the sealant system, device, and method disclosed herein and its superiority over other tested matrices with the same adhesive.

[0097] Figures 19A-19G show implementation of Example 1, which involves a combination of PG910 mesh and liquid albumin / PEG-SG adhesive used as a sealant in a porcine model of liver resection. Figure 19A shows the resection surface and clamped liver lobe. Figure 19B shows the adhesive sealant sprayed onto the resection surface. Figure 19C shows a synthetic matrix 102 (e.g., VICRYL® PG910 mesh) positioned on the sprayed resection surface. Figure 19D shows the synthetic matrix 102 after being sprayed with the biosynthetic adhesive sealant. Figure 19E shows a two-minute waiting period to allow the biosynthetic adhesive to harden. Figure 19F shows clamp removal and re-establishment of blood flow to the resected lobe, such that no bleeding is observed in the treatment area. Following sealant polymerization, the VICRYL® mesh combined with albumin / PEG-SG demonstrated sufficient efficacy as a sealant. FIG. 19G shows the ablation surface after the sealant has been peeled away, which results in additional bleeding from the ablation surface.

[0098] Example 2. Use of a sealant system during a solid tumor resection surgical procedure. In a lung tumor resection surgical procedure, a sealant system is used in patients undergoing lung resection. Immediately after tumor resection in the operating room, a sealant system comprising a synthetic matrix and a biosynthetic adhesive is placed in areas at risk of leak (e.g., staple lines, raw, exposed pleural surfaces) to achieve a seal in the resected area(s). The sealant system was applied to the resected organ using laparoscopic and non-laparoscopic methods. The study demonstrated the effectiveness of the combination of a synthetic matrix and a biosynthetic adhesive in sealing pulmonary air leaks compared to other matrices used with fibrin glue.

[0099] In one embodiment, the sealant systems, devices, and methods disclosed herein utilize a two-component sealant comprising a synthetic matrix and a biosynthetic adhesive. The two-component sealant provides the surgeon with more flexibility in sealing the excised tissue by allowing the surgeon to apply the biosynthetic adhesive to both the synthetic matrix and / or the excised tissue before placing the synthetic matrix over the excised tissue. In one embodiment, after the synthetic matrix is ​​positioned over the excised tissue, a supplemental biosynthetic adhesive may be applied to specific locations, if desired.

[0100] In one embodiment, the synthetic matrix of the two-part sealant system is flexible to conform to uneven surfaces, such as uneven resection surfaces of organs.

[0101] In one embodiment, the synthetic matrix provides reinforced structural support (ie, scaffolding) that is substantially greater than can be achieved by using a liquid sealant alone.

[0102] In one embodiment, the two-component sealant system is designed to seal the ablation surface to prevent and / or control bleeding, fluid leakage, and air leakage.

[0103] The sealant system disclosed herein is not dependent on the patient's coagulation system. Thus, surgeons can achieve hemostasis and sealing regardless of the patient's coagulation status, which can be compromised in patients undergoing resection because most coagulation proteins are produced in the liver. The sealant system may also be used for patients on antiplatelet and anticoagulant therapy, e.g., aspirin, heparin, or warfarin.

[0104] In one embodiment, the two-component sealant system is transparent, allowing the surgeon to visually inspect the resection surface after sealing. The surgeon's visibility and confirmation that treatment is effective is important and cannot be achieved with opaque liquid sealants and / or opaque patches. In one embodiment, the transparency of the sealant may reduce the possibility of induced damage due to poor visualization at the resection site.

[0105] In one embodiment, the two-component treatment system disclosed herein preferably provides strong adhesion to the excised tissue, although the synthetic matrix may be manually removed and replaced as needed to form a suitable seal. In one embodiment, the combination of the synthetic matrix and biosynthetic adhesive provides strong adhesion to the excised tissue via direct covalent bonding with proteins on the tissue surface.

[0106] In one embodiment, a two-part sealant system allows for varying the properties of each component of the system to optimize retention of the biosynthetic adhesive by the synthetic matrix and penetration of the biosynthetic adhesive through the thickness of the synthetic matrix. As a result, the specific formulation of the biosynthetic adhesive and synthetic matrix may be altered to enable specific properties (e.g., degradation rate, strength).

[0107] In one embodiment, the adhesive may comprise a synthetic adhesive. In one embodiment, the adhesive may comprise a biocompatible reactive electrophile and a nucleophile. In one embodiment, the electrophile may comprise PEG-SG. In one embodiment, the nucleophile may be selected from any source of NH groups, any suitable protein or protein mixture, albumin, polyethylene glycol amine (PEG-NH), and a combination of albumin and PEG-NH.

[0108] While the above description is of embodiments of the present invention, other and further embodiments of the invention may be made without departing from the basic scope of the invention, which is limited only by the appended claims. For example, it is intended that the present invention be such that any feature shown in any embodiment described herein or incorporated by reference herein can be incorporated with any feature shown in any embodiment described herein or incorporated by reference herein and still fall within the scope of the present invention.

[0109] [Embodiment] (1) A method for sealing a resected surface of an organ, comprising: applying a synthetic matrix to the resected surface of the organ; applying an adhesive onto the synthetic matrix such that the adhesive penetrates through interstices of the synthetic matrix and contacts the interface between the synthetic matrix and the resected surface of the organ; and curing the adhesive to bond the synthetic matrix to the resected surface of the organ. (2) The method of embodiment 1, wherein the synthetic matrix is ​​a biodegradable, porous, flexible substrate. (3) The method of embodiment 1, wherein the synthetic matrix comprises a nonwoven mesh made of polyglactin 910. (4) The method of claim 1, wherein the synthetic matrix and the adhesive are at least partially transparent. (5) The synthetic matrix contains fibers and has a density of 102.7 to 190.7 mg / cm 3 2. The method of claim 1, wherein the density range is

[0110] (6) The synthetic matrix contains fibers and has a density of 128.7 to 190.7 mg / cm 3 2. The method of claim 1, wherein the density range is 7. The method of claim 1, wherein the adhesive comprises a biosynthetic adhesive or a synthetic adhesive. 8. The method of claim 1, wherein the adhesive comprises a biocompatible reactive electrophile and a nucleophile. 9. The method of claim 8, wherein the electrophile comprises polyethylene glycol succinimidyl glutarate ester (PEG-SG). 10. The method of claim 9, wherein the nucleophile is selected from the group consisting of any source of amine (NH2) groups, any suitable protein or mixture of proteins, albumin, polyethylene glycol amine (PEG-NH2), and a combination of albumin and PEG-NH2.

[0111] 11. The method of claim 7, wherein the biosynthetic adhesive comprises a partially hydrolyzed protein and PEG-SG. 12. The method of claim 11, wherein the partially hydrolyzed protein comprises albumin. (13) The method of embodiment 12, wherein the biosynthetic adhesive comprises a mixture of a 10% albumin solution and a 75 mg / ml PEG-SG solution. 14. The method of claim 1, wherein the adhesive is in liquid or powder form and is crosslinked with the fibers of the synthetic matrix. (15) A method for sealing a resected surface of an organ, comprising: applying a porous bioabsorbable synthetic matrix made of polyglactin 910 to the resected surface of the organ; applying an adhesive onto the synthetic matrix such that the adhesive penetrates through the pores of the synthetic matrix and contacts the interface between the synthetic matrix and the resected surface of the organ; and curing the adhesive to bond the synthetic matrix to the resected surface of the organ.

[0112] 16. The method of claim 15, wherein the adhesive is a biosynthetic adhesive or a synthetic adhesive. (17) The synthetic matrix contains fibers and has a density of 102.7 to 190.7 mg / cm 3 and the cured adhesive is crosslinked with the fibers of the synthetic matrix. (18) The synthetic matrix contains fibers and has a density of 128.7 to 190.7 mg / cm 3 and the cured adhesive is crosslinked with the fibers of the synthetic matrix. (19) The method of embodiment 15, further comprising pre-applying the adhesive onto the resected surface of the organ prior to the step of applying a porous bioabsorbable synthetic matrix. (20) A kit for sealing a resected surface of an organ, comprising: a synthetic matrix comprising a nonwoven mesh made of polyglactin 910; and an adhesive comprising a biocompatible reactive electrophile and a nucleophile.

[0113] (21) The kit according to embodiment 20, wherein the adhesive is a biosynthetic adhesive comprising a partially hydrolyzed protein and PEG-SG. (22) further comprising a dual syringe for dispensing the biosynthetic adhesive, the dual syringe comprising a first syringe barrel and a second syringe barrel; the first syringe barrel containing a 20% albumin solution; 22. The kit of embodiment 21, wherein the second syringe barrel contains a 150 mg / ml PEG-SG solution. (23) The synthetic matrix is ​​porous and has a density of 102.7 to 190.7 mg / cm 3 21. The kit of embodiment 20, having a density range of: (24) The synthetic matrix is ​​porous and has a density of 128.7 to 190.7 mg / cm 3 21. The method of embodiment 20, wherein the density range is (25) The kit of embodiment 20, wherein the adhesive is in liquid or powder form.

Claims

1. 1. A kit for sealing a resected surface of an organ, comprising: a synthetic matrix comprising a nonwoven mesh made of polyglactin 910; an adhesive comprising a biocompatible reactive electrophile and a nucleophile; The adhesive is a biosynthetic adhesive comprising a partially hydrolyzed protein and PEG-SG.

2. a dual syringe for dispensing the biosynthetic adhesive, the dual syringe including a first syringe barrel and a second syringe barrel; the first syringe barrel containing a 20% albumin solution; 2. The kit of claim 1, wherein the second syringe barrel contains a 150 mg / ml PEG-SG solution.

3. The synthetic matrix is ​​porous and has a density of 102.7 to 190.7 mg / cm ３ 2. The kit of claim 1, wherein the density range is

4. The synthetic matrix is ​​porous and has a density of 128.7 to 190.7 mg / cm ３ 2. The kit of claim 1, wherein the density range is

5. The kit of claim 1 , wherein the adhesive is in liquid or powder form.

6. 1. A kit for use in a method of sealing a resected surface of an organ, said kit comprising a synthetic matrix and an adhesive, said method comprising: applying the synthetic matrix to the resected surface of the organ; applying the adhesive onto the synthetic matrix such that the adhesive penetrates through interstices of the synthetic matrix and contacts the interface between the synthetic matrix and the resected surface of the organ; and curing the adhesive to bond the synthetic matrix to the resected surface of the organ. the adhesive comprises a biocompatible reactive electrophile and a nucleophile; The kit, wherein the electrophile comprises polyethylene glycol succinimidyl glutarate ester (PEG-SG).

7. A kit for use in a method of sealing a resected surface of an organ, said kit comprising a synthetic matrix and an adhesive, said method comprising: applying the synthetic matrix to the resected surface of the organ; applying the adhesive onto the synthetic matrix such that the adhesive penetrates through interstices of the synthetic matrix and contacts the interface between the synthetic matrix and the resected surface of the organ; and curing the adhesive to bond the synthetic matrix to the resected surface of the organ. the adhesive comprises a biosynthetic adhesive; The biosynthetic adhesive comprises a partially hydrolyzed protein and PEG-SG.

8. 8. The kit of claim 7, wherein the partially hydrolyzed protein comprises albumin.

9. 9. The kit of claim 8, wherein the biosynthetic adhesive comprises a mixture of a 10% albumin solution and a 75 mg / ml PEG-SG solution.

10. 8. The kit of claim 6 or 7, wherein the synthetic matrix is ​​a biodegradable, porous, flexible substrate.

11. 8. The kit of claim 6 or 7, wherein the synthetic matrix comprises a nonwoven mesh made of polyglactin 910.

12. 8. The kit of claim 6 or 7, wherein the synthetic matrix and the adhesive are at least partially transparent.

13. The synthetic matrix comprises fibers and has a density of 102.7 to 190.7 mg / cm ３ 8. The kit of claim 6 or 7, having a density range of:

14. The synthetic matrix comprises fibers and has a density of 128.7 to 190.7 mg / cm ３ 8. The kit of claim 6 or 7, having a density range of:

15. The nucleophile is an amine (NH ２ ) groups, any suitable protein or protein mixture, albumin, polyethylene glycol amine (PEG-NH ２ ), and albumin and PEG-NH ２ 7. The kit of claim 6, wherein the combination is selected from the group consisting of:

16. 8. The kit of claim 6 or 7, wherein the adhesive is in liquid or powder form and is cross-linked with the fibers of the synthetic matrix.

17. The kit of claim 1, wherein the kit is for use in a method of sealing the resected surface of the organ, the method comprising: applying the porous, bioabsorbable synthetic matrix made of polyglactin 910 to the resected surface of the organ; applying the adhesive onto the synthetic matrix such that the adhesive penetrates through the pores of the synthetic matrix and contacts the interface between the synthetic matrix and the resected surface of the organ; and curing the adhesive to bond the synthetic matrix to the resected surface of the organ.

18. The synthetic matrix comprises fibers and has a density of 102.7 to 190.7 mg / cm ３ 18. The kit of claim 17, wherein the adhesive has a density range of 0.1 to 1.5 mm, and the cured adhesive is crosslinked with the fibers of the synthetic matrix.

19. The synthetic matrix comprises fibers and has a density of 128.7 to 190.7 mg / cm ３ 18. The kit of claim 17, wherein the adhesive has a density range of 0.1 to 1.5 mm, and the cured adhesive is crosslinked with the fibers of the synthetic matrix.

20. The kit described in claim 17, wherein the method further comprises pre-applying the adhesive onto the resected surface of the organ prior to the step of applying the synthetic matrix.

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