Bioadhesive patch

Abstract

A patch to be placed over an injury or defect in tissue in a biological structure having a lumen and preventing migration of contents of the biological structure through the injury or the defect. The patch includes an adhesive layer configured to adhere to the biological tissue via formation of hydrogen or covalent bonds with chemical groups present in the biological tissue and a backing layer coupled to and coextensive with the adhesive layer, the backing layer configured to be impervious to the contents.

Description

BIOADHESIVE PATCHBACKGROUND

[0001] The gastrointestinal (GI) tract is a complex system of organs responsible for the digestion of food, absorption of nutrients, and expulsion of waste. It includes the mouth, esophagus, stomach, small intestine, large intestine, and anus. Further, the pancreas, gallbladder, and liver are important organs associated with the digestive system. The GI tract is lined with several layers of specialized tissue that prevent digestive contents from leaking into the surrounding body cavities. Leakage of such contents can lead to severe inflammatory and infectious responses, potentially resulting in life-threatening conditions such as sepsis and multiorgan failure.

[0002] Injuries to the GI tract and associated organs can occur due to various reasons, including blunt and penetrating trauma, disease processes such as ulcers, colitis, and cancers, and surgical procedures. In particular, surgical removal and reconstruction of a portion of the GI tract, such as in the treatment of colon cancer or colitis, can result in leakage. Further, injury to the liver and / or pancreas can leads to disruption and leakage of bile and enzymes. This is a common issue, with hundreds of thousands of such procedures performed annually in the United States alone.

[0003] Currently, the primary method for repairing an injury to the GI tract or forming an anastomosis following GI tract removal is through the placement of sutures or the utilization of surgical staplers. However, despite these methods, a substantial portion of repairs and anastomosis formations result in inadequate wound healing, leading to leakage and potentially life-threatening complications.

[0004] Adhesive compounds have been explored in various medical applications for their potential to adhere to tissue surfaces and provide a barrier to prevent leakage. These compounds typically consist of polymers that form bonds with the tissue surface, resulting in adhesive properties. The polymers may include amino acids and other related compounds. However, the development of an adhesive compound specifically designed for adherence to the GI tract presents its own set of challenges, including the dynamic nature of the GI tract and the harsh environment within it.SUMMARY

[0005] The present disclosure generally relates to the field of medical technology, specifically to bioadhesive composites designed for adherence to any biological structure having a lumen to prevent leakage and promote healing. In some embodiments, the bioadhesive composites could be used in connection with the GI tract.

[0006] In one embodiment, the present disclosure is directed to a patch to be placed over an injury or defect in a biological structure comprising a lumen and preventing migration of contents from the biological structure through the injury or the defect, the patch comprising: an adhesive layer configured to adhere to the GI tissue via formation of hydrogen and / or covalent bonds with chemical groups present in the GI tissue; and a backing layer coupled to and coextensive with the adhesive layer, the backing layer configured to be impervious to the GI content.

[0007] In some embodiments of the patch, the patch further comprises a dehydrated human amnion / chorion membrane (dHACM) allograft.

[0008] In some embodiments of the patch, the dHACM allograft is incorporated into the adhesive layer.

[0009] In some embodiments of the patch, the dHACM allograft is incorporated into the backing layer.

[0010] In some embodiments of the patch, the dHACM allograft is incorporated into both the adhesive layer and the backing layer.

[0011] In some embodiments of the patch, the adhesive layer comprises an amino acid, a lipoic acid, a derivative thereof, or a combination thereof.

[0012] In some embodiments of the patch, the chemical groups comprise hydroxyl groups, carboxyl groups, amine groups, disulfide groups, or any combination thereof.

[0013] In some embodiments of the patch, the adhesive layer further comprises a mucoadhesive.

[0014] In some embodiments of the patch, the mucoadhesive comprises polyvinyl alcohol.

[0015] In some embodiments of the patch, the biological structure comprises a gastrointestinal (GI) tract and the contents comprise GI contents.

[0016] In one embodiment, the present disclosure is directed to a bioadhesive composite for adherence to the GI tract, comprising: a bioadhesive layer designed to adhere to the surfaces ofthe GI tract, said bioadhesive layer comprising compounds with adhesive properties derived from interactions and formation of hydrogen and various covalent bonds among hydroxyl groups, carboxyl groups, amine groups and disulfide groups; and a non-adhesive backing layer designed to prevent contact of the extra-GI tissues to the adhesive layer and to provide an impervious layer to gas, liquids, and / or solids.

[0017] In some embodiments of the bioadhesive composite, the bioadhesive layer comprises polymers consisting of amino acids selected from the group consisting of lysine, arginine, and cysteine.

[0018] In some embodiments of the bioadhesive composite, the amino acids form covalent bonds with the GI tissue surface through their amine groups.

[0019] In some embodiments of the bioadhesive composite, the bioadhesive layer further comprises lipoic acid or its derivatives.

[0020] In some embodiments of the bioadhesive composite, the bioadhesive layer further comprises mucoadhesives to enhance the bonding properties to the surfaces of the GI tract.

[0021] In some embodiments of the bioadhesive composite, the non-adhesive backing layer comprises biocompatible, inert substances selected from the group consisting of hydrogels and polyurethane.

[0022] In some embodiments of the bioadhesive composite, the non-adhesive backing layer further comprises amnion and / or chorion membrane structures.

[0023] In some embodiments of the bioadhesive composite, the bioadhesive composite is configured to maintain its adhesive properties for a period of several days to weeks.

[0024] In some embodiments of the bioadhesive composite, the bioadhesive composite is biodegradable, and its degradation products are naturally found and absorbed in the human body.

[0025] In some embodiments of the bioadhesive composite, the bioadhesive composite further comprises a dehydrated human amnion / chorion membrane (dHACM) allograft incorporated into the adhesive layer or the backing layer.

[0026] In one embodiment, the present disclosure is directed to a method for preventing leakage and promoting healing in the GI tract, comprising: applying a bioadhesive composite to a defect, injury, or anastomosis in the GI tract, said bioadhesive composite comprising a bioadhesive layer designed to adhere to the surfaces of the GI tract and a non-adhesive backinglayer; and maintaining the bioadhesive composite in place until the GI tissues have healed and no longer pose a risk of leakage.

[0027] In some embodiments of the method, the bioadhesive layer comprises polymers consisting of amino acids selected from the group consisting of lysine, arginine, and cysteine.

[0028] In some embodiments of the method, the amino acids form covalent bonds with the GI tissue surface through their amine groups.

[0029] In some embodiments of the method, the bioadhesive layer further comprises lipoic acid or its derivatives.

[0030] In some embodiments of the method, the bioadhesive composite further comprises a dHACM allograft incorporated into the adhesive layer or the backing layer.

[0031] In one embodiment, the present disclosure is directed to a bioadhesive composite for adherence to the GI tract, comprising: a bioadhesive layer designed to adhere to the surfaces of the GI tract, said bioadhesive layer comprising compounds with adhesive properties derived from interactions and formation of hydrogen and various covalent bonds among hydroxyl groups, carboxyl groups, amine groups and disulfide groups; a non-adhesive backing layer designed to prevent contact of the extra-GI tissues to the adhesive layer and to provide an impervious layer to gas, liquids, and / or solids; and a dHACM incorporated into the bioadhesive composite.

[0032] In some embodiments of the bioadhesive composite, the bioadhesive layer comprises polymers consisting of amino acids selected from the group consisting of lysine, arginine, and cysteine.

[0033] In some embodiments of the bioadhesive composite, the amino acids form covalent bonds with the GI tissue surface through their amine groups.

[0034] In some embodiments of the bioadhesive composite, the bioadhesive layer further comprises lipoic acid or its derivatives.

[0035] In some embodiments of the bioadhesive composite, the non-adhesive backing layer comprises biocompatible, inert substances selected from the group consisting of hydrogels and polyurethane.FIGURES

[0036] FIG. 1 depicts a diagram of a GI patch, in accordance with an embodiment of the present disclosure.

[0037] FIG. 2A depicts a diagram of a GI patch having dHACM incorporated into the adhesive layer in a first configuration, in accordance with an embodiment of the present disclosure.

[0038] FIG. 2B depicts a diagram of a GI patch having dHACM incorporated into the adhesive layer in a second configuration, in accordance with an embodiment of the present disclosure.

[0039] FIG. 2C depicts a diagram of a GI patch having dHACM incorporated into the adhesive layer in a third configuration, in accordance with an embodiment of the present disclosure.

[0040] FIG. 2D depicts a diagram of a GI patch having dHACM incorporated into the adhesive layer in a fourth configuration, in accordance with an embodiment of the present disclosure.

[0041] FIG. 2E depicts a diagram of a GI patch having dHACM incorporated into the adhesive layer in a fifth configuration, in accordance with an embodiment of the present disclosure.

[0042] FIG. 3A depicts a diagram of a GI patch having dHACM incorporated into the backing layer in a first configuration, in accordance with an embodiment of the present disclosure.

[0043] FIG. 3B depicts a diagram of a GI patch having dHACM incorporated into the backing layer in a second configuration, in accordance with an embodiment of the present disclosure.

[0044] FIG. 3C depicts a diagram of a GI patch having dHACM incorporated into the backing layer in a third configuration, in accordance with an embodiment of the present disclosure.

[0045] FIG. 3D depicts a diagram of a GI patch having dHACM incorporated into the backing layer in a fourth configuration, in accordance with an embodiment of the present disclosure.

[0046] FIG. 3E depicts a diagram of a GI patch having dHACM incorporated into the backing layer in a fifth configuration, in accordance with an embodiment of the present disclosure.

[0047] FIG. 4A depicts a diagram of a GI patch having dHACM incorporated into both the adhesive and backing layers in a first configuration, in accordance with an embodiment of the present disclosure.

[0048] FIG. 4B depicts a diagram of a GI patch having dHACM incorporated into both the adhesive and backing layers in a second configuration, in accordance with an embodiment of the present disclosure.

[0049] FIG. 4C depicts a diagram of a GI patch having dHACM incorporated into both the adhesive and backing layers in a third configuration, in accordance with an embodiment of the present disclosure.

[0050] FIG. 4D depicts a diagram of a GI patch having dHACM incorporated into both the adhesive and backing layers in a fourth configuration, in accordance with an embodiment of the present disclosure.

[0051] FIG. 4E depicts a diagram of a GI patch having dHACM incorporated into both the adhesive and backing layers in a fifth configuration, in accordance with an embodiment of the present disclosure.

[0052] FIG. 4F depicts a diagram of a GI patch having dHACM incorporated into both the adhesive and backing layers in a sixth configuration, in accordance with an embodiment of the present disclosure.DETAILED DESCRIPTION

[0053] As used herein, the singular forms “a,” “an,” and “the” include plural references, unless the context clearly dictates otherwise. Thus, for example, reference to a “protein” is a reference to one or more proteins and equivalents thereof known to those skilled in the art, and so forth.

[0054] As used herein, the term “about” means plus or minus 10% of the numerical value of the number with which it is being used. Therefore, about 50 mm means in the range of 45 mm to 55 mm.

[0055] As used herein, the term “consists of’ or “consisting of’ means that the device or method includes only the elements, steps, or ingredients specifically recited in the particular claimed embodiment or claim.

[0056] In embodiments or claims where the term “comprising” is used as the transition phrase, such embodiments can also be envisioned with replacement of the term “comprising” with the terms “consisting of’ or “consisting essentially of.”

[0057] As used herein, the term “subject” includes, but is not limited to, humans and nonhuman vertebrates such as wild, domestic, and farm animals.

[0058] As used herein, the term “biocompatible” refers to materials exhibiting non-harmful compatibility with living tissue. Biocompatibility is a broad term that describes a number of materials, including bioinert materials, bioactive materials, bioabsorbable materials, biostable materials, biotolerant materials, or any combination thereof.

[0059] As used herein, the term “biodegradable” refers to materials that naturally dissolve or are absorbed by living tissue over time, particularly into innocuous byproducts that are non- harmful (i.e., non-toxic) to living tissue.

[0060] As used herein, the term “patch” refers to constructs of one or more layers that have a variety of different sizes and / or configurations. A “patch” could alternatively be referred to as a “sheet,” “strip,” or “scaffold.”

[0061] The present disclosure is generally directed to bioadhesive patches that are designed to be used for patching, covering, or overlaying a wound (e.g., an anastomosis, a tear, or a fistula) or defect in a biological structure having a lumen to perform contents from the biological structure from leaking through the wound or defect. In some embodiments, the biological structures could include a GI tract and the patches could be designed to prevent leakage of GI material (e.g., bowel content or stool) therethrough. The wounds or defects that the bioadhesive patches are designed to address could be caused through natural means, from trauma, or due to surgical procedures. In some embodiments, the patches could include multiple layers that are configured to serve different functions (e.g., adhesion and blocking fluid). In some embodiments, the patches could be placed in connection with a surgical procedure that is either attempting to address the wound or that resulted in the wound. Various embodiments of such patches are discussed below.Bioadhesive Patch

[0062] Referring now to FIG. 1, there is a diagram of an illustrative embodiment of a bioadhesive patch 100. The bioadhesive patch 100 can include a first or adhesive layer 102 and a second or backing layer 104 opposing the adhesive layer 102. The adhesive layer 102 can beconfigured to contact and adhere to the surface of a biological structure and / or tissue in order to hold the patch 100 in place over, for example, a wound. In one embodiment, the adhesive layer 102 can include or be constructed from one or more materials that are configured to adhere to GI tissue. The backing layer 104 can be configured to provide a fluid impermeable or substantially impermeable barrier that prevents leakage of contents (e.g., GI contents) through the wound. In one embodiment, the backing layer 104 can be configured to provide additional mechanical strength to the patch 100 in order to accommodate distension and contraction of the biological structure during normal physiological activities. In some embodiments, the patch 100 can further provide a scaffold or structure for supporting the growth of biological tissue in order to facilitate healing of the wound or defect.

[0063] The bioadhesive patch 100 can be configured for use in any biological structure having a lumen. In one illustrative embodiment, the bioadhesive patch 100 can be configured for use in the GI tract or associated organs (e.g., the liver, pancreas, or gallbladder). In particular, the bioadhesive patch 100 be configured to adhere to GI tissue or tissue of organs associated with the GI tract. In other embodiments, the bioadhesive patch 100 can be configured for use in vessels (e g., arteries or veins), the esophagus, the trachea, or any other biological structures having lumens. Accordingly, the bioadhesive patch 100 can be configured to seal an injury and prevent leakage of bile, enzymes, blood products, and other biological materials therethrough.

[0064] The adhesive layer 102 can include or be constructed from materials that are configured to adhere to biological tissue via a variety of different chemical or other adhesive mechanisms. In various embodiments described in greater detail below, the adhesive layer 102 could include compounds configured to form chemical bonds (e.g., hydrogen or covalent bonds) with chemical groups commonly present in particular types of biological tissues (e.g., GI tract tissue), mucoadhesives, and combinations thereof.

[0065] In some embodiments, the adhesive layer 102 can include materials or compounds (e.g., polymers) that are configured to interact with and form hydrogen or other covalent bonds with hydroxyl groups, carboxyl groups, amine groups, and / or disulfide groups. Hydrogen bonds can form between an acid (e.g., carboxylic acid) and a base (e.g., an amine). Covalent bonds can form with, for example, amine groups of lysine and arginine or disulfide amino acids and lipoic acid-derived compounds. In one illustrative embodiment, the adhesive layer 102 can include various amino acids (e.g., lysine, arginine, and cysteine), lipoic acids, and any derivatives orcombinations thereof. Lysine and arginine function as an adhesive with GI tissue because they have a free amine group which serves to form covalent bonds with GI tissue. In addition to covalent bonds, hydrogen bonding interactions readily occurs when an amine group (i.e., a basic group) combines with an acidic group (e.g., carboxylic acid) and forms hydrogen bonds, which also creates adhesive properties. Cysteine functions as an adhesive with GI tissue because GI tissue interacts with its carboxyl group and amine group to form hydrogen bonds and disulfide bonds. Lipoic acids and derivatives thereof (e.g., lipoic acid polydisulfides) function as adhesives with GI tissue because these compounds have a variety of different bond interactions with the biological structure surface, including interactions with hydrophilic groups, amine groups, and carboxyl groups present in GI tissue.

[0066] In addition to providing adhesive properties, the aforementioned materials or compounds configured to interact with and form hydrogen or other covalent bonds with chemical groups found in GI tissue could also provide additional beneficial properties, including structural stability. For example, disulfide amino acids polymerize with the formation of hydrogen bonds, chemically forming amides that stabilize the tertiary structure of the adhesive layer 102. Accordingly, the use of disulfide amino acids provide additional mechanical integrity to the adhesive layer 102 that can allow the adhesive layer 102 to remain adhered in place without shearing or breaking away from the GI tissue within the dynamic GI environment.

[0067] The adhesive layer 102 can also include additional materials or compounds in order to augment the properties of the adhesive layer 102 (or the biological structure surface) and / or provide additional properties. In one embodiment, the adhesive layer 102 can include a mucoadhesive, such as polyvinyl alcohol. Certain types of mucoadhesives can form hydrogen bonds with compounds present within the biological structure surface tissue. Incorporating one or more mucoadhesives into the adhesive layer 102 can be beneficial in order to, for example, assist with the initial placement of the patch 100 at the defect or injury.

[0068] In some cases, the mucoadhesives may be incorporated into the bioadhesive layer in a specific ratio or proportion. The specific ratio or proportion of mucoadhesives in the adhesive layer 102 may be determined based on various factors, such as the desired adhesive properties of the adhesive layer 102, the specific application of the patch 100, and the characteristics of the biological structure surface to which the patch 100 is to be adhered. The mucoadhesives may be mixed with the other components of the adhesive layer 102, such as the amino acids and lipoicacid or its derivatives, to form a homogeneous mixture. The mixture may then be applied to the biological structure surface to form the adhesive layer 102 of the patch 100.

[0069] In other embodiments, the mucoadhesives may be incorporated into the adhesive layer 102 through a specific process or method. The process or method may involve various steps, such as mixing the mucoadhesives with the other components of the adhesive layer 102, applying the mixture to the biological structure surface, and allowing the mixture to adhere to the surface. The specific process or method used to incorporate the mucoadhesives into the adhesive layer 102 may be determined based on various factors, such as the desired adhesive properties of the adhesive layer 102, the specific application of the patch 100, and the characteristics of the biological structure surface to which the patch 100 is to be adhered.

[0070] In some embodiments, the adhesive layer 102 can be configured to maintain its adhesive properties within the biological environment for at least a defined time period. In other words, the adhesive layer 102 can be configured to remain adhered to the biological tissue for a defined time period. The defined time period can be an amount of time sufficient to allow the wound healing process at the target tissue to be completed, for example. In one embodiment, the defined time period could include several days to weeks. In one illustrative embodiment, the defined time period could include two to three weeks.

[0071] The adhesive layer 102 can include or be constructed from biocompatible and / or biodegradable materials. In particular, the adhesive layer 102 can include materials that do not result in significant inflammation, physiologic, or immunological reactivity by a human body. In some embodiments, the degradation byproducts of the adhesive layer 102 can include compounds or molecules that are naturally found within and absorbed by a human body. In particular, as the patch 100 and / or the adhesive layer 102 breaks down, the resulting components may be substances that are naturally present in the body and can be safely absorbed and metabolized. For instance, the amino acids and lipoic acid or its derivatives in the adhesive layer 102 may break down into individual amino acids and lipoic acid molecules, which are naturally found in the body and can be absorbed and used in various biological processes. Similarly, the hydrogels and polyurethane in the backing layer 104 may break down into smaller molecules that can be safely absorbed in the body without causing toxicity.

[0072] Biological environments (e.g., the GI environment) can be dynamic and readily moving. Therefore, the adhesive layer 102 can have sufficient mechanical properties toaccommodate the movement of the biological environment, while still remaining adhered to the surface of the biological structure surface and without being sheered by the movement of the biological environment. In other words, the adhesive layer 102 can have sufficient mechanical properties to prevent leaks when implanted in a subject. In some embodiments, the adhesive layer 102 can exhibit sufficient elasticity to conform to the movement of the GI environment. In particular, the adhesive layer 102 can exhibit sufficient elasticity to accommodate distension and contraction of the GI tract during normal physiological function. In some embodiments, the adhesive layer 102 can exhibit sufficient sheer, tensile, and burst strength to avoid being sheered by the movement of the GI environment.

[0073] Accordingly, the adhesive layer 102 is configured to adhere to the surface of the target tissue (e.g., GI tissue), have sufficient mechanical properties (e g., strength and elasticity) to remain adhered to the biological structure surface (e.g., GI tract surface), and mitigate the migration of contents (e.g., GI contents) through the defect or injury to which the patch 100 is applied.

[0074] The backing layer 104 serves a number of purposes, including preventing contact of the adjacent tissues (e.g., extra-GI tissues) to the adhesive layer 102 and providing an impervious or substantially impervious layer to gas, liquids, and / or solids so that the patch 100 can block the migration of the biological structure contents through the defect or injury. In some embodiments, the backing layer 104 can extend about the adhesive layer 102 such that it is coextensive with a surface of the adhesive layer 102 or otherwise covers the adhesive layer 102, while still leaving at least one surface of the adhesive layer 102 uncovered so that it can be adhered to biological tissue. Because the adhesive layer 102 is typically porous in nature, it can be beneficial for the backing layer 104 to be configured to prevent leakage of the biological structure contents through the patch 100. In one embodiment, the backing layer 104 can define a hydrophilic surface extending over the adhesive layer 102. In some embodiments, the backing layer 104 can be configured to be inert such that it does not exhibit adhesive properties with living tissue, GI contents, and so on. Accordingly, the backing layer 104 allows the adhesive layer 102 to bond to the biological structure surface area around the injury or defect, while preventing extra-intestinal tissues to the opposing side of the adhesive layer 102.

[0075] In some embodiments, the backing layer 104 can be configured to provide additional mechanical support to the adhesive layer 102. In other embodiments, the backing layer 104 doesnot provide additional mechanical support to the adhesive layer 102. As with the adhesive layer 102, the backing layer 104 can be constructed from suitable materials and / or using suitable techniques to exhibit elastic properties such that the backing layer 104 can conform to the dynamic shape, size, and movement of the biological environment. In embodiments, where the patch 100 is configured to be deployed within the GI tract, the backing layer 104 can be constructed from suitable materials and / or using suitable techniques to exhibit elastic properties such that the backing layer 104 can conform to the dynamic shape, size, and movement of the GI environment. In particular, the backing layer 104 can exhibit sufficient elasticity to accommodate distension and contraction of the GI tract during normal physiological function. Further, the backing layer 104 can be configured to maintain its function (i.e., not biodegrade) for a time period equal to or longer than the length of time that the adhesive layer 102 maintains its adhesive properties. Accordingly, the backing layer 104 can therefore providing a fluid and / or vapor-impervious barrier for at least as long as the adhesive layer 102 maintain its functionality.

[0076] In some embodiments, the backing layer 104 can include or be constructed from a variety of inert and / or non-adhesive compounds or substances that exhibit the aforementioned mechanical and barrier properties. In some embodiments, the backing layer 104 can include hydrogels or polyurethane.

[0077] In some embodiments, the patch 100 can further include amnion and / or chorion membrane structures. In certain embodiments, an amniotic membrane can include a plurality of layers where each layer may be one of amnion or chorion. In some embodiments, a membrane may include one, two, or three or more layers of amnion and no layers of chorion. In other embodiments, all layers may be chorion. In certain other embodiments layers of amnion and chorion may be combined. In certain embodiments, the amniotic membrane incudes at least two distinct layers: the inner amnion and the outer chorion. The amnion, which interfaces with the fetus, includes an epithelial layer, a basement membrane, a compact layer, and a fibroblast layer. The fibroblast layer is particularly rich in type I and III collagen and is vital to the tissue’s mechanical strength. Types V and VI collagen also create critical connections between the fibrous network and the basement membrane, which contains type IV collagen. The amniotic membrane also encompasses extracellular matrix components (e.g., fibronectin and laminin) that are distributed throughout the tissue. The amnion is separated from the chorion by an intermediate spongy layer that is rich in collagen III, proteoglycans, and glycoproteins. Thechorion includes a reticular layer with collagens I, III, IV, V, and VI, proteoglycans, and a basement membrane layer containing collagen IV, fibronectin, and laminin. This composition of the amniotic membrane is critical for its barrier function, synthesis of growth factors and cytokines, and regulation of amniotic fluid pH.

[0078] Amniotic membranes are harvested from donors and undergo washing and cleaning in buffered solutions. A specific processing method, the PURION process, involves gentle cleansing, lamination, and dehydration of the amnion and chorion tissues under controlled conditions. This results in dehydrated human amnion / chorion membrane (dHACM) allografts, which can be used in membrane and micronized forms. The micronized tissue is cryo-milled and sieved for particulate sizing, then reconstituted in saline solution for administration as a flowable allograft. dHACM contains a high concentration of growth factors, cytokines, chemokines, and protease inhibitors, stimulating paracrine responses in fibroblasts, endothelial cells, and various stem cells to promote tissue healing and repair. The bioactive and structural proteins (e.g., collagens and proteoglycans) makes amniotic membrane allografts beneficial in various clinical applications, especially soft tissue healing. In animal studies it has been shown to possess considerably higher levels of neoangiogenesis, fibroblast activity, collagen deposition, and hydroxyproline concentrations compared to the control groups. Furthermore, dHACM is associated with anti -adhesion formation attributed to its inherent anti-inflammatory properties, which mitigate the scaring process. Accordingly, in some embodiments the present invention can be used to prevent adhesion formation.

[0079] In various embodiments, the specific ratio or proportion of amnion and / or chorion membrane structures in the patch 100 may be determined based on various factors, such as the desired properties of the patch 100 or the layers 102, 104 thereof, the specific application of the patch 100, and the characteristics of the biological structure surface to which the patch 100 is to be adhered.

[0080] In some embodiments shown in FIGS. 2A-2E, dHACM 106 can be incorporated into the adhesive layer 102 (i.e., the biological structure-facing side of the patch 100). In one embodiment shown in FIG. 2A, the dHACM 106 could cover or be coextensive with the adhesive layer 102. In other embodiments shown in FIGS 2B-2E, the dHACM 106 could be deposited or arranged on the adhesive layer 102 in various patterns or other arrangements. In some embodiments shown in FIGS. 3A-3E, dHACM 106 can be incorporated into the backinglayer 104 (i.e., the side of the patch 100 facing away from the biological structure when the patch 100 is secured thereto). In one embodiment shown in FIG. 3 A, the dHACM 106 could cover or be coextensive with the backing layer 104. In other embodiments shown in FIGS 3B-3E, the dHACM 106 could be deposited or arranged on the backing layer 104 in various patterns or other arrangements. In still other embodiments shown in FIGS. 4A-4F, the dHACM 106 could be incorporated into both the adhesive layer 102 and the backing layer 104. The dHACM could 106 be arranged in the same or different patterns or arrangements on the layers 102, 104 of the patch. The dHACM may be incorporated into the patch 100 using a variety of different techniques and in different manners, providing flexibility in the design and application of the patch 100. The specific method of incorporating the dHACM 106 into the adhesive layer 102 and / or the backing layer 105 may depend on various factors, such as the desired properties of the patch 100, the specific application of the patch 100, and the characteristics of the biological structure surface to which the patch 100 is to be adhered.

[0081] In some embodiments, a hemostatic agent can further be incorporated into or utilized in conjunction with the patch 100. A hemostatic agent can be useful when the injury or defect that is being repaired via the patch 100 is especially viscous or is adjacent to a blood vessel that could result in additional bleeding during the course of implanting the patch 100 or the healing of the wound or defect.

[0082] This disclosure is not limited to the particular systems, devices and methods described, as these may vary. The terminology used in the description is for the purpose of describing the particular versions or embodiments only and is not intended to limit the scope of the disclosure.

[0083] The following terms shall have, for the purposes of this application, the respective meanings set forth below. Unless otherwise defined, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art. Nothing in this disclosure is to be construed as an admission that the embodiments described in this disclosure are not entitled to antedate such disclosure by virtue of prior invention.

[0084] While the present disclosure has been illustrated by the description of exemplary embodiments thereof, and while the embodiments have been described in certain detail, it is not the intention of the Applicants to restrict or in any way limit the scope of the appended claims to such detail. Additional advantages and modifications will readily appear to those skilled in theart. Therefore, the disclosure in its broader aspects is not limited to any of the specific details, representative devices and methods, and / or illustrative examples shown and described. Accordingly, departures may be made from such details without departing from the spirit or scope of the Applicant’s general inventive concept.

[0085] With respect to the use of substantially any plural and / or singular terms herein, those having skill in the art can translate from the plural to the singular and / or from the singular to the plural as is appropriate to the context and / or application. The various singular / plural permutations may be expressly set forth herein for sake of clarity.

[0086] In addition, even if a specific number is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number (for example, the bare recitation of “two recitations,” without other modifiers, means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to “at least one of A, B, and C, et cetera” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (for example, “a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and / or A, B, and C together, et cetera). In those instances where a convention analogous to “at least one ofA, B, or C, et cetera” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (for example, “a system having at least one of A,B, or C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and / or A, B, and C together, et cetera). It will be further understood by those within the art that virtually any disjunctive word and / or phrase presenting two or more alternative terms, whether in the description, sample embodiments, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or “B” or “A and B.”

[0087] In addition, where features of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group.

[0088] Various of the above-disclosed and other features and functions, or alternatives thereof, may be combined into many other different systems or applications. Various presentlyunforeseen or unanticipated alternatives, modifications, variations or improvements therein may be subsequently made by those skilled in the art, each of which is also intended to be encompassed by the disclosed embodiments.

Claims

CLAIMS1. A patch to be placed over an injury or defect in a biological structure comprising a lumen and preventing migration of contents from the biological structure through the injury or the defect, the patch comprising: an adhesive layer configured to adhere to the biological tissue via formation of hydrogen and / or covalent bonds with chemical groups present in the biological tissue; and a backing layer coupled to and coextensive with the adhesive layer, the backing layer configured to be impervious to the contents.

2. The patch of claim 1, further comprising a dehydrated human amnion / chorion membrane (dHACM) allograft.

3. The patch of claim 2, wherein the dHACM allograft is incorporated into the adhesive layer.

4. The patch of claim 2, wherein the dHACM allograft is incorporated into the backing layer.

5. The patch of claim 2, wherein the dHACM allograft is incorporated into both the adhesive layer and the backing layer.

6. The patch of any one of claims 1-5, wherein the adhesive layer comprises an amino acid, a lipoic acid, a derivative thereof, or a combination thereof.

7. The patch of any one of claims 1-6, wherein the chemical groups comprise hydroxyl groups, carboxyl groups, amine groups, disulfide groups, or any combination thereof.

8. The patch of any one of claims 1-7, wherein the adhesive layer further comprises a mucoadhesive.

9. The patch of claim 8, wherein the mucoadhesive comprises polyvinyl alcohol.

10. The patch of any one of claims 1-9, wherein the biological structure comprises a gastrointestinal (GI) tract and the contents comprise GI contents.

11. Use of the patch of any one of claims 1-10 to prevent an adhesion.

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