Hybridized surgical repair grafts

Abstract

A graft formed of a biologic material may include a crosslinked pattern extending across the surface of the biologic material. The pattern of crosslinked biologic material is configured to modify the mechanical properties of the graft to within a target range of compliance, strain and / or modulus. The total extent of crosslinked biologic material may be maintained below a maximum percentage while still achieving the target mechanical properties to prevent or reduce toxicity and inflammation. Further, the crosslinking may be limited to a relatively shallow depth into the biologic material.

Description

HYBRIDIZED SURGICAL REPAIR GRAFTSCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This patent application claims priority to U.S. provisional patent application no. 63 / 589,197, titled “HYBRIDIZED SURGICAL REPAIR GRAFTS,” filed on October 10, 2023, and herein incorporated by reference in its entirety.INCORPORATION BY REFERENCE

[0002] All publications and patent applications mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.BACKGROUND

[0003] Soft tissues within a body may benefit from repair or reinforcement due to a variety of reasons such as disease, enhancement, or trauma. It may be beneficial to use biologic materials, including in particular, collagen-based materials such as naturally occurring or synthetic extracellular matrix (e.g., collagen, elastin, fibronectin, laminin, etc.) which may be biocompatible; unfortunately such materials often lack the mechanical properties that are needed for repair and reinforcement. Although these biologic materials may be reinforced with one or more additional materials, including polymeric materials, this may involve increased processing time and expense, and may result in additional risks for biocompatibility and subsequent inflammation.

[0004] A graft (e.g., graft implant) that may be formed from a medical textile that may be used to repair or reinforce a soft tissue such as an unhealthy or modified tissue in the body. The tissue may be, for example, tissue that is no longer able to maintain its shape or physiological function such as a hernia or a tissue for which a shape or size change is desired such as breast size or shape change due to breast enhancement or breast reconstruction. A hernia is a condition in which part of an organ or fatty tissue protrudes through the wall of a surrounding tissue. Abdominal wall hernia surgery is one of the most common surgical procedures, and according to the U.S. Food and Drug Administration, more than 1 million hernia repairs are performed in the United States alone. Common adverse events associated with hernia repair surgery include pain, infection, hernia recurrence, adhesion formation, obstruction, bleeding, and fluid build-up. Breast reconstruction may be performed to reconstruct a breast after a mastectomy has been performed to remove a diseased due tocancer or as a prophylactic measure to prevent cancer. Common adverse events associated with breast reconstruction include infection, pain, delayed healing, and swelling.

[0005] Thus there is a need for improved surgical repair materials and medical textiles.SUMMARY OF THE DISCLOSURE

[0006] Described herein are biologic materials that may be used for surgery and / or implantation within a patient. In particular, described here are grafts (e.g., graft implants) that are modified by crosslinking over all or portion of one or more surfaces of the biologic material in order to control the mechanical properties of the graft. Although, as described herein, the mechanical properties of biologic materials may be modified by cross-linking, it is known that crosslinking of such biologic materials (e.g., collagen) is problematic, as the resulting cross-linked material is associated with toxicity and inflammation. Thus, the methods and apparatuses described herein may minimize the amount of exposed crosslinked material and may optimize or select the pattern of crosslinking in order to enhance the mechanical properties in a desired manner.

[0007] The apparatuses (grafts, implants, devices, etc.) and methods described herein may provide patterned crosslinked biologic materials that are modified by controlled crosslinking such that the resulting materials have desired mechanical properties, such as compliance (e.g., between 2-200% at 16 N / cm load, between 5-100% at 16 N / cm load, between 5-80% at 16 N / cm load, between 10-30% at 16 N / cm load, etc.), strain (e.g., between 2.25-200% at 0.7 N / cm load, between 0.5-100% at 0.3 N / cm load, between 5-100% at 0.7 N / cm load, between 1-50% at 0.3 N / cm load, between 10-30% at 0.7 N / cm load, between 2-30% at 0.3 N / cm load, etc.), modulus (e.g., between 10-400 MPa, between 100- 350 MPa, between 200-300 MPa, between 200-2000 MPa, between 200-1200 MPa, etc.), etc. The mechanical properties may be selected by determining the shape and extent of the crosslinking. For example, the graft materials described herein may have a pattern of crosslinking.

[0008] As mentioned, the apparatuses and methods described herein may minimize the amount of exposed crosslinking of the biologic material in order to minimize the risk of toxicity and inflammation. In particular, these methods and apparatuses may crosslink only partially through the thickness of the biologic material (e.g., to a depth that is a percentage of the total thickness, e.g., 80% or less, 75% or less, 70% or less, 65% or less, 60% or less, 55% or less, 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, etc.). In addition, the methods an apparatuses described herein may crosslinking on oneor both sides of the biologic material in a pattern that may enhance the mechanical properties such as one or more of stain, compliance and / or modulus.

[0009] In general, the biologic material may be formed of at least one layer of material that is crosslinked in a desired pattern and / or to partial thickness of the biologic material. The biologic material may be any appropriate biologic material, particularly naturally occurring or synthetic extracellular matrix materials such as collagen, elastin, fibronectin, laminin, etc. In some examples, the biologic material is made from a naturally occurring collagen such as avian collagen, bovine collagen, fish collagen, marine animal collagen, ovine collagen, or porcine collagen, or some combination of these. A collagen or other naturally occurring material may be harvested from any source, such as an organ or part of an organ, such as dermis, forestomach, intestine, pericardium, peritoneum, rumen (stomach), skin, stomach, tail, etc. of any organism. In other examples, collagen or another graft component may be manufactured by recombinant or other synthetic processes.

[0010] Any of the materials (e.g., biologic materials) described herein may include a crosslinked pattern that extend in a network over the surface of the material, e.g., spanning from a first edge region of the layer to an opposite edge region of the layer and / or across the entire surface, from edge to edge (e.g., from a few mm of the edges). The network may form a grid or other interlocking pattern.

[0011] In some examples the biologic materials may include one or more layers of different biologic materials and / or coatings. In some examples the biologic materials one or more layers may be crosslinked as described herein in order to modify a biomechanical property. The modified biomechanical property may include increased strength, durability, conformability or the like, which may be quantified, e.g., as strain, compliance and / or modulus. In some examples, the biologic materials may include multiple layers of material. A first layer may act as a shield for the second layer. For example, a first layer may be human skin and a second layer may be porcine skin. The first layer may act as a shield to provoke less of an inflammation response while the second layer may provide more strength. In some variations, crosslinking some or all of the biologic material may increase strength without relying on foreign (non-human) material.

[0012] The crosslinked biologic material that may include a biologic substrate having a thickness. The thickness of the biologic substrate may be crosslinked in a pattern and to a predetermined thickness. The portion of the biologic substrate that is crosslinked to a defined thickness, that may be less than the thickness of the biologic substrate) may be referred to as a first region; the portion of the biologic material that is not cross-linked may be referred to as a second region. Within the first region, the biologic substrate is crosslinked. Anyappropriate crosslinking technique may be used to crosslink the biologic material, including chemical, thermal, pressure, etc.

[0013] In some examples the crosslinked biologic substrate may include multiple layers that are or portions of the biologic substrate that have been bonded or linked together with one or more other biologic substrates. The biologic substrate may also include one or more regions where the biologic substrate is not crosslinked.

[0014] In any of the patterned crosslinked biologic materials disclosed herein, a first region crosslinked region and a second un-crosslinked region may be shaped as stripes, islands or interlocking shapes. In some examples the pattern of the first, crosslinked material (which may penetrate only partially into the thickness of the biologic material) may be continuous over the surface of the biologic material in at least one direction (e.g., or one or more directions, including perpendicular directions, having an angle of approximately 90 degrees between the continuous directions). For example, the first (crosslinked) region surrounded by the second (un-crosslinked) region may be shaped as strips or stripes that are disposed across a surface of the biologic substrate (e.g., from side to side). In some examples, any of the patterns of crosslinked biologic materials forming the first region may be shaped in a grid pattern disposed across a surface of the biologic substrate; the first region may only partially penetrate the thickness of the biologic material. In some other examples, the first region is shaped in a diamond pattern disposed across a surface of the biologic substrate. In some examples the pattern of the crosslinked portion may be formed of straight lines, curved lines, interconnecting links, etc. the pattern of crosslinked material may be formed in a continuous or semi -continuous pattern, such that a pattern of lines or other shapes may extend to the edges of the biologic substrate (e.g., on one or both sides of the biologic substate).

[0015] The crosslinked regions may have any width (e.g., in the plane of the surface of the biologic material). For example, the first (crosslinked) region may include a plurality of stripes tapering from a wide to a narrow width disposed across a surface of the biologic substrate, or from a narrow to a wide width.

[0016] As mentioned, any appropriate crosslinking technique may be used to crosslink the biologic material. For example, the first (crosslinked) region may be crosslinked by an application of heat. In some other variations, the first region is crosslinked by an application of a chemical (e.g., cyanide, glutaraldehyde, etc.). In still other variations, the first region is crosslinked by an application of radiation. In other examples, the first region is crosslinked by an application of light. In some examples the biologic material may be crosslinked by the application of mechanical force (e.g. compression).

[0017] In any of the patterned crosslinked biologic materials disclosed herein, the crosslinked biologic substrate may extend partially or completely through a thickness of the biologic substrate. In particular, the patterned crosslinked region may extend partially through the thickness of the biologic substrate (e.g., 80% or less, 75% or less, 70% or less, 65% or less, 60% or less, 55% or less, 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, etc. though the thickness of the biologic material). In some examples the crosslinked region may extend less than a predetermined thickness (e.g., 0.001 mm or less, 0.005 mm or less, 0.01 mm or less, 0.05 mm or less, 0.08 mm or less, 0.1 mm or less, 0.2 mm or less, 0.3 mm or less, 0.4 mm or less, 0.5 mm or less, etc.).

[0018] Any of the patterned crosslinked biologic materials described herein may include a biologic substrate including a first biologic material, and a first coating disposed on a first surface of the biologic substrate. In some examples the first coating may comprise a second biologic material.

[0019] Any of the patterned crosslinked biologic materials described herein may include a second biologic material. The second biologic material may be different from the first biologic material. In some cases the second biologic material is the same as the first biologic material. For example the second biologic material may be a second layer adjacent to (and / or in some examples, laminated or otherwise attached to) the first layer. In any of the patterned crosslinked biologic materials described herein, the material may include a first coating that comprises a third biologic material, that may be different from the first and second biologic material.

[0020] In any of the patterned crosslinked biologic materials described herein, the first coating includes a particulate biologic material. In some of the patterned crosslinked biologic materials described herein, the first coating includes a solubilized biologic material. In some other examples of the patterned crosslinked biologic materials described herein may further include a second coating disposed on a second surface of the biologic substrate.Any of the patterned crosslinked biologic material described herein may include a crosslinked biologic substrate including a plurality of openings disposed across a surface of the crosslinked biologic substrate and a biologic material inserted into the plurality of openings. In any of the patterned crosslinked biologic materials described herein, the plurality of openings include slits cut into the crosslinked biologic substrate.

[0021] In any of the patterned crosslinked biologic materials described herein, the biologic material inserted in the plurality of openings is different than the crosslinked biologic substrate. In some variations, any of the patterned crosslinked biologic materials may include a first coating on the first side of the crosslinked biologic substrate. The firstcoating may include a third biologic material that is different from the first and second biologic material. In some other variations, the first coating may include a solubilized biologic material.

[0022] Any of the patterned crosslinked biologic materials described herein may include a second coating disposed on an opposite side of the biologic substrate.

[0023] Also described herein are materials formed of a biologic material having a patterned crosslinked biologic material and including one or more regions having a reservoir of a drug material or alternative biologic material. The drug material or alternative biologic material may be configured to be active (e.g., to promote tissue ingrowth, etc.). Any of the methods disclosed herein may include a method for forming a patterned crosslinked biologic material that include creating a plurality of regions (e.g., slits, pits, channels, reservoirs, etc.) into a substate that includes a first biologic material, expanding the substrate to create openings based on the plurality of regions, and filling the regions with a second biologic material and / or a drug material.

[0024] Any of the methods described herein can further include applying a coating of a biologic material to at least one of the top and bottom surface of the substrate. In some variations, the coating of the biologic material includes the second biologic material. In some other variations, the of the biologic material includes at least one of a particulate and a soluble biologic material.

[0025] In general, described herein are grafts for repair of tissue. These grafts may be sheets of biologic material (e.g., material present in or derived from extracellular matrix); these grafts may be modified to include a limited pattern of crosslinking of the biologic material, wherein the crosslinking pattern is configured to modify the mechanical properties of the biologic material to within a target range, e.g., of compliance, strain, bending stiffness, elasticity, uniaxial tension, burst strength, roughness, etc. The extent of the crosslinking may be limited, e.g., to 35% or less, 30% or less, 25% or less, etc. of the exposed surface area of the graft and / or to 25% or less (e.g., 22% or less, 20% or less, 18% or less, 16% or less, 15% or less, 14% or less, 13% or less, 12% or less, 11% or less, 10% or less, 9% or less, 8% or less, 7% or less, 6% or less, 5% or less, etc.) of the total volume of the biologic material in the graft. Limiting the amount of biologic material that is crosslinked in this manner may significantly reduce the risk of toxicity and / or inflammation when using the graft.

[0026] As used herein a “graft” may refer to a surgically implantable material, such as a sheet or structure formed as a sheet, that may be used to support, patch, restructure and / or repair a region of a patient’s body. The graft may be configured for use with a plastic surgical procedure and / or reconstruction surgical procedure, for use as a hernia repair and / orreinforcement procedure, for use a ligament repair and / or reinforcement procedure, and / or for use as a tendon repair / reinforcement procedure.

[0027] In general, the grafts described herein may be grafts of biologic material that are crosslinked in a limited pattern extending across the surface of the graft, such as an upper and / or lower surface of the graft. For example, a graft of biologic material may include: a layer of a biologic substrate having a thickness and including a pattern extending across a surface of the biologic substrate, wherein the pattern comprises a pattern of crosslinking of the biologic substrate, and wherein the percentage of the surface of the biologic substrate that is crosslinked is less than 35% of the surface. In some examples, the total amount of biologic material within the substrate that is crosslinked may be 30% or less (25% or less, 24% or less, 23% or less, 22% or less, 21% or less, 20% or less, 18% or less, 17% or less, 16% or less, 15% or less, 14% or less, 13% or less, 12% or less, 11% or less, 10% or less, etc.).

[0028] For example, a graft of biologic material as described herein may be crosslinked in a pattern, the graft comprising: a layer of a biologic substrate having a thickness and including a pattern extending across a surface of the biologic substrate, wherein the pattern comprises a pattern of crosslinking of the biologic substrate, further wherein the pattern extends only partially into the thickness of the layer of the biologic substrate, and wherein the percentage of the surface of the biologic substrate that is crosslinked is less than 35% of the surface.

[0029] In some examples a graft of biologic material crosslinked in a pattern may include: a layer of a biologic substrate having a thickness and including a pattern extending across a surface of the biologic substrate, wherein the pattern comprises a pattern of crosslinking of the biologic substrate, further wherein the pattern extends only partially into the thickness of the layer of biologic substrate, wherein the pattern extends across the surface and is configured to provide a compliance of between 2-200% at 16N / cm load; and wherein the percentage of the surface of the biologic substrate that is crosslinked is less than 35% of the surface.

[0030] In any of these grafts, the pattern may extend only partially into the thickness of the layer of the biologic substrate. The pattern may extend between 5% and 80% of the thickness of the biologic substrate. The pattern may extend across the surface and may be configured to provide a compliance of between 2-200% at 16N / cm load.

[0031] For example, any of these grafts may be configured for use as a graft for plastic and / or surgical reconstruction and the pattern of crosslinking may be a grid pattern that provides a strain of between about 2.5 to 200% under a load of 0.7 N / cm, about 0.5-100% under a load of 0.3 N / cm, a strain of between about 5-100% under a load of 0.7 N / cm, astrain of about 1-50% under a load of 0.3 N / cm, a strain of between about 10 to 30% under a load of 0.7 N / cm, a strain of about 2-30% under a load of 0.3 N / cm, etc. The strain may refer to uniaxial strain (e.g., in a single axial direction), bi-axial, or multi-axial. The value of the strain may be adjusted by, e.g., adjusting the number of crosslinked Tines’ forming the pattern, and in particular, a grid pattern and / or the width of the lines forming the pattern. For example, the strain value (e.g., the percentage of deformation) may be increased by increased or decreased by adjusting the thickness (and / or depth) or the crosslinked lines forming the pattern. The overall pattern may comprise a grid or mesh-like pattern of intersecting lengths of crosslinked substrate extending across the surface (or more than one surface) of the biologic substrate. The length (e.g., “lines”) forming the pattern may be straight, curved, zigzagged, looping, etc. The pattern may be a regular, repeating pattern. In some examples the pattern is irregular.

[0032] The graft may be configured as a graft for hernia repair and / or reinforcement. Thus, the pattern of crosslinking of the biologic substrate may be configured to have a compliance of between about 2-200% at a 16 N / cm load, between about 5-80% at a 16 N / cm load, between about 10-30% at a 16 N / cm load, etc.

[0033] In some examples, the graft may be configured as a graft for ligament repair and / or reinforcement, and may be configured to have a modulus of between about 10-400 MPa, between about 100-350 MPa, between about 200-300 MPa, etc. In some examples, the graft may be configured as a graft for tendon repair and / or reinforcement, and may be configured to have a modulus of between about 200-2000 MPa, between about 200-1200 MPa, etc.

[0034] In any of these examples the biologic material may comprise an extracellular matrix material, e.g., the biologic material comprises one or more of: collagen, elastin, fibronectin, and / or laminin.

[0035] As mentioned, the pattern may comprise a grid pattern disposed across a surface of the biologic substrate. In some examples the pattern may comprise a repeating shape pattern (e.g., repeating diamond pattern, repeating circle pattern, repeating square pattern, repeating tringle pattern, repeating pentagonal pattern, repeating hexagonal pattern, repeating heptagonal pattern, repeating octagonal pattern, repeating trapezoidal pattern, etc.) disposed across a surface of the biologic substrate. The repeating shapes forming the pattern may be overlapping or non-overlapping. In some examples the repeating shapes overlap at one or more of the vertices of the shape. In some examples the pattern comprises a plurality of stripes tapering from a wide to a narrow width disposed across a surface of the biologicsubstrate and / or tapering from a narrow to a wide width disposed across a surface of the biologic substrate.

[0036] In general, the pattern of crosslinking of the biologic substrate may comprise a continuous pattern, e.g., extending across all or a majority of the surface of the graft. For example, a continuous pattern may extend across the surface of the biological substrate between two or more edges of the biological substrate that are oriented at an angle of between about 45 degrees and 135 degrees (e.g., between about 50-130 degrees, between about 55- 125 degrees, between about 60-120 degrees, between about 65-115 degrees, between about 70-110 degrees, between about 75-105 degrees, between about 80-100 degrees, between about 85-95 degrees, etc. or any subrange within these).

[0037] In some examples, the pattern may comprise a plurality of openings disposed across a surface of the crosslinked biologic substrate; and a biologic material inserted into the plurality of openings.

[0038] The biologic material may be crosslinked into the pattern in any appropriate way. For example, the pattern of crosslinking of the biologic substrate may be crosslinked by one or more of: thermal crosslinking, chemical crosslinking, radiation crosslinking, and optical crosslinking.

[0039] Also described herein are method of forming a graft of biologic material that is crosslinked in a pattern. For example, any of these methods may include: crosslinking a surface of a biologic material into a continuous pattern across a surface of the biologic substrate; wherein the percentage of the surface of the biologic substrate that is crosslinked is less than 35% of the surface. Crosslinking the surface of the biologic material may comprise crosslinking only partially into the thickness of the layer of the biologic substrate. In some examples crosslinking the surface of the biologic material comprises crosslinking the pattern into between 5% and 80% of the thickness of the biologic substrate.

[0040] As mentioned, the continuous pattern may extend across the surface of the biological substrate between two or more edges of the biological substrate that are oriented at an angle of between about 45 degrees and about 135 degrees (e.g., between about 50-130 degrees, between about 55-125 degrees, between about 60-120 degrees, between about 65- 115 degrees, between about 70-110 degrees, between about 75-105 degrees, between about 80-100 degrees, between about 85-95 degrees, etc. or any subrange within these).

[0041] The biologic material may comprise an extracellular matrix material. In some examples the biologic material comprises one or more of: collagen, elastin, fibronectin, and / or laminin. The pattern may comprise a grid pattern and / or a repeated shape pattern that is disposed across a surface of the biologic substrate. In some examples the pattern comprisesa repeating diamond pattern disposed across a surface of the biologic substrate. In some examples the pattern comprises a plurality of stripes tapering from a wide to a narrow width disposed across a surface of the biologic substrate.

[0042] As mentioned, the pattern of crosslinking of the biologic substrate may be crosslinked by one or more of: thermal crosslinking (e.g., the application of heat to the biologic material), chemical crosslinking (e.g., the application of an agent that reacts with amino acids in the biologic substrate to generate difunctional, trifunctional, and tetrafunctional cross-links), radiation crosslinking (e.g., the application of radiation to the biologic material), optical crosslinking (e.g., the application of light to the biologic material) and / or mechanical force (e.g., the application of pressure to crosslink the biologic material).

[0043] In some examples the grafts of biologic material describe herein may have a crosslinked in a pattern on the surface that is greater than 35% of the surface area (e.g., between 5% to 100%), but may extend only partially into the thickness of the biologic substrate (e.g., less than 50%, less than 45%, less than 40%, less than 30%, less than 25%, less than 20%, less than 15%, less than 10%, etc.). In some cases the crosslinked pattern may be formed as a thin-film thickness (such as a film or coating). For example, the graft may include a layer of a biologic substrate having a thickness and including a pattern extending across a surface of the biologic substrate wherein the pattern comprises a pattern of crosslinking of the biologic substrate, and wherein the portion of the surface of the biologic substrate that is crosslinked penetrates less than 30% of the thickness of the biologic substrate.

[0044] In general, these grafts may be formed with the crosslinked pattern on just one side. In some examples the crosslinked pattern may be formed on both sides (e.g., of the sheet of biologic material).

[0045] In any of these examples, crosslinking the surface of the biologic substrate in the pattern may result in pattern having a plurality of openings formed by the pattern; in any of these examples a material (e.g., a drug agent, including but not limited to a drug agent to promote tissue ingrowth) may be included or added to the openings.

[0046] In any of these grafts, the method may include adding a second biologic material to the first biologic material. For example, a second biologic material may be applied over or against the first biologic material, including covering the crosslinked pattern. In some examples, the method may include applying a coating of a second biologic material to at least one of the top and bottom surface of the substrate.

[0047] All of the methods and apparatuses described herein, in any combination, are herein contemplated and can be used to achieve the benefits as described herein.BRIEF DESCRIPTION OF THE DRAWINGS

[0048] The novel features of the invention are set forth with particularity in the claims that follow. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:

[0049] FIG. 1 shows an example of a biologic composite.

[0050] FIG. 2 shows another example of a biologic composite.

[0051] FIG. 3 shows yet another example of a biologic composite.

[0052] FIG. 4 shows multiple examples of patterned crosslinked biologic material.

[0053] FIG. 5 shows examples of coated biologic materials.

[0054] FIG. 6 shows other examples of patterned crosslinked biologic materials.

[0055] FIG. 7A schematically illustrates one example of a method of forming a patterned crosslinked biologic material (e.g., graft).

[0056] FIG. 7B is a flowchart showing an example method for forming a patterned crosslinked biologic material such as the patterned crosslinked biologic material described with respect to FIG. 6.DETAILED DESCRIPTION

[0057] Described herein are surgical repair grafts and medical textiles for soft tissue repair that are selectively crosslinked to advantageously select and / or match the biomechanical properties of tissue during healing and recovery. These apparatuses (e.g., grafts, including medical textiles) may be configured so that the pattern of crosslinking includes crosslinked regions that only partially penetrate the thickness of the biologic material forming the apparatus. This partial penetration of crosslinking may prevent or reduce a foreign body response in the patient into whom the apparatus is implanted.

[0058] For example, described herein are biologic materials, composites, hybrids, and the like (collectively referred to as biologies) that may be used for surgical repairs or any other medical uses. The biologies may include one or more separate biologic materials arranged as substrates, coatings, a mixture of substrates and coatings, and in some examples, hybridized substrates that include a first type of biologic material interspersed with a second type of biologic material. The biologic material is crosslinked to modify the biomechanical properties of the apparatus (generically referred to as a graft herein). As used herein, a crosslinked biologic material may refer to any biologic material where a portion of the biologic material (in some examples, a limited thickness and surface region of the biologic material) has beenreacted to form molecular connections, e.g., between amino acids forming the biologic material. In some examples, crosslinked biologic material may have a greater strength compared to non-crosslinked biologic material. Example uses for any of the biologic material described herein may include guided bone regeneration, breast reconstruction, hernia repair, wound dressings, and addressing pelvic floor dysfunction. Further uses may include supporting or repairing a body tissue such as for breast reconstruction, hernia repair, pelvic organ prolapse treatment, and so forth. In some examples it may be implanted or used to serve as a source of a desired agent.

[0059] FIG. 1 shows an example of a biologic composite 100. The biologic composite 100 may be formed from two or more separate layers of biologic material. In some examples, the biologic composite 100 (or any other biologic composite described herein) may be implanted within a patient and used for soft tissue repair such as, but not limited to, hernia and breast reconstruction surgeries. In some other examples, biologic composites may be used as a surgical repair graft that may be implanted into a body (e.g., an animal or mammalian body).

[0060] As used herein the term “biologic” or “biologic material” may refer to biotextile material made from an extracellular matrix (ECM) and / or may be synthesized to mimic the properties of an extracellular matrix. In some examples, a biologic material may be made from or may include naturally occurring or synthetic extracellular matrix materials such as collagen, elastin, fibronectin, INTERGARD™, laminin, TIGR®, ULTRAPRO™ and so on. In some examples, the biologic material is made from a naturally occurring collagen such as avian collagen, bovine collagen, fish collagen, marine animal collagen, ovine collagen, or porcine collagen. A collagen or other naturally occurring material may be harvested from any source, such as an organ or part of an organ, such as dermis, forestomach, intestine, pericardium, peritoneum, rumen (stomach), skin, stomach, tail, etc. of any organism. In other examples, collagen or another graft component may be manufactured by recombinant or other synthetic processes.

[0061] A carrier matrix as used herein includes a plurality of particles configured to carry and hold an agent for use in (or on) the body. In general, an agent in a carrier matrix is an active agent configured for release into the body to have an effect in the body and a carrier matrix is at least partially biodegradable to release the active agent into the body, but this is not necessarily the case. For example, a carrier matrix may hold a fluoroscopic agent for use for imaging purposes and the carrier matrix or part of a carrier matrix may not degrade and the fluoroscopic agent may remain in the carrier matrix. In some embodiments, a carrier matrix attached to a biologic material is discontinuous.

[0062] Characteristics of the biologic composite 100 may be determined by characteristics associated with each of the included individual layers. In some examples, overall characteristics of the biologic composite 100 may be determined, at least in part, by the thicknesses of the individual layers, as well as how the layers were joined together.

[0063] The biologic composite 100 may be formed from any number of layers 110. For example, the biologic composite 100 may include a first layer 120 and a second layer 130. Although only two layers are shown here, in other examples, the biologic composite 100 may include any number of feasible layers. Each layer may contain, wholly or partially, a substrate. Thus, the first layer 120 may include a first substrate 121 and the second layer 130 may include a second substrate 131.

[0064] In general, the substrates 121 and 131 included in the layers 110 may be the same or different depending on the desired characteristics of the biologic composite 100. In a first example, the layers 110 may include only polymer or polymer-based substrates. Example polymers may include polypropylene. In a second example, the layers 110 may include only biologic or biologically-based substrates. Example biologic materials may be derived from pig, human, cow, fish, etc. sources. In some other examples, the layers 110 may include a mixture of polymer and biologic substrates. In some cases, a layer can be a hybrid layer that includes polymer and biologic material. For example either the first layer 120 and / or the second layer 130 may include a polymer mesh coated with a biologic or a biologic material reinforced with a sewn in polymer, or a biologic with knitted polymer mesh attached.

[0065] The first layer 120 may be bonded (joined, attached) to the second layer 130 using any feasible means including, for example, pressure, heat, adhesive, stitching, hydrogen bonds, and the like. The joining or attaching together of the first layer 120 to the second layer 130 may include procedures, chemicals, pressures, and the like that are compatible with constituent parts of the first layer 120 and the second layer 130. For example, an adhesive may be selected to join the first layer 120 to the second layer 130 that can attach but not damage the first layer 120 and the second layer 130.

[0066] In some examples, each layer of the composite biologic 100 may have different thicknesses in order to impart a particular characteristic to the composite biologic 100. For example, the first layer 120 can be thinner than the second layer 130. In other examples, any one layer can be thicker or thinner with respect to any other layer. The differing thicknesses may provide a desired characteristic (e.g., biomechanical property) for the biologic composite 100. In some cases, a desired biomechanical property of the biologic composite 100 may advantageously be similar to biomechanical properties of the tissues they are replacing orrepairing. Example biomechanical properties may include, for example, bending stiffness, compliance, elasticity, uniaxial tension, burst strength, roughness, and so on.

[0067] FIG. 2 shows another example of a biologic composite 200. The biologic composite 200 may be formed from two or more separate layers of material. In some examples, the biologic composite 200 may include only biologic material. Thus, a first layer 220 and a second layer 230 may each be formed from or include biologic material. The biologic material for the layers 220 and 230 may be the same or different. For example, the first layer 220 and the second layer 230 may each be formed from or include porcine skin. In another example, the biologic material for the first layer 220 and the second layer 230 can be different. For example, the first layer 220 may include porcine skin and the second layer 230 may include human skin.

[0068] Similar to as described for the biologic composite 100 of FIG. 1, the first layer 220 may be bonded to the second layer 230 using any feasible means such as pressure, heat, adhesive, stitching, hydrogen bonds, and the like.

[0069] In some examples, each biologic layer may be selected in order to provide a particular biomechanical property to the biologic composite 200. For example, the first layer 220 can be porcine skin and the second layer 230 can be human skin. When implanted the second layer 230 may provoke less of an inflammation reaction while the first layer 220 provides more strength. In some examples, the second layer 230 can shield the first layer 220 from inflammation or other adverse response from the implant patient.

[0070] FIG. 3 shows another example of a biologic composite 300. The biologic composite 300 may be formed from two or more separate layers. In some examples, the biologic composite 300 may include a layer of non-crosslinked biologic material and at least one layer of a crosslinked biologic material. For example, a first layer 320 may include a noncrosslinked biologic material and a second layer 330 may include crosslinked biologic material. In other examples, the first layer 320 may include crosslinked biologic material and the second layer 330 may include non-crosslinked biologic material. A crosslinked biologic material may refer to any biologic material where some or all of the biologic material (in some examples, a layer of molecules of the biologic material) has been linked or bonded together. Crosslinked biologic materials may possess different biomechanical properties with respect to non-crosslinked biologic materials. In some variations, if the biologic composite 300 includes a crosslinked layer and a non-crosslinked layer, then the biologic material used for each layer may be the same. In some other variations, the biologic composite 300 may include different biologic materials for the crosslinked and non-crosslinked layers.

[0071] In some examples, crosslinked biologic material may have a greater strength compared to non-crosslinked biologic material. Similar to as described for the biologic composite 100 of FIG. 1, the first layer 320 may be bonded to the second layer 330 using any feasible means such as pressure, heat, adhesive, stitching, hydrogen bonds, or the like.

[0072] The biologic composite 300 may have biomechanical properties provided by the combination of the first layer 320 and the second layer 330. Similar to as described in FIG. 1, in some examples the first layer 320 of non-crosslinked material may shield the second layer 330 of crosslinked material. In addition, the second layer 330 may provide increased strength compared to the first layer 320.

[0073] Any of the grafts described herein may be formed of at least one layer of biologic material (e.g. collagen or other ECM material) that is crosslinked in a pattern in a limited manner across the surface of the biologic material. FIG. 4 shows multiple examples of patterned crosslinked biologic material 400. The patterned crosslinked biologic material 400 may begin or originate with a single layer (substrate) of non-crosslinked biologic material 410. Any feasible biologic material may be used. Patterned crosslinking the biologic material 410 may create a hybrid, mesh, or mesh-like structure within the biologic material 410. In some cases, this structure can advantageously create a stronger, yet still conformal, support system.

[0074] In a first variation, a first example patterned crosslinked biologic material 420 may include a first zone 421 and a second zone 422. Each of the zones may either be crosslinked or non-crosslinked. For example the first zone 421 (shown with a first shading) may indicate a crosslinked region and the second zone 422 (shown with a second shading) may indicate a non-crosslinked region. In other embodiments, the first zone 421 may be a non-crosslinked region while the second zone 422 may be a crosslinked region. Although shown as substantially rectangular shape here, the first zone 421 and the second zone may have any feasible shape.

[0075] In some variations, the crosslink and non-crosslinked regions may be used to preferentially change the biomechanical properties of some of the regions of the biologic material 410. For example, a crosslinked region may be stiffer than a non-crosslinked region. Thus, any region or zone may be preferentially crosslinked to not only add stiffness, but in some examples affect how the biologic material 420 may deform or bend when subjected to external forces.

[0076] In a second variation, a second example patterned crosslinked biologic material 430 may include a first zone 431 (shown with a first shading) and a second zone 432. Each of the zones may either be crosslinked or non-crosslinked. For example, the first zone 431 maybe a non-crosslinked region and the second zone 432 may be a crosslinked region. In other examples, the first zone 431 may be a crosslinked region and the second zone 432 may be a non-crosslinked region.

[0077] In some examples, a crosslinked region can generally be implemented as crosslinked strips that alternate with non-crosslinked strips. The widths of the first zone 431 and the second zone 432 may be relatively constant. For example, as shown, the strips of the first zone 431 can be wider than the strips of the second zone 432. In some other variations, the strips of the first zone 431 can be narrower than the strips of the second zone 432. In still other variations, the stripes of the first zone 431 can have a width similar to the second zone 432. The alternating zones of crosslinked and non-crosslinked biologic material may provide a uniform or substantially-uniform distribution of crosslinked regions within the biologic material 410. The uniform distribution of crosslinked regions may provide a uniform distribution of biomechanical properties with respect to the biologic material 430.

[0078] In some variations, shapes of the first zone 431 and / or the second zone 432 may be tapered as they traverse the biologic material 430. For example the first zone 431 may begin wide on a first edge of the biologic material 430 and taper to a narrower width on the opposite (second) edge of the biologic material 430. In this manner, the properties of the crosslinked biologic material can taper from the first edge to the second edge of the biologic material 430.

[0079] In a third variation, a third example patterned crosslinked biologic material 440 can include a first zone 441 and a second zone 442. In some examples, the first zone 441 (shown with a first shading) may be a non-crosslinked region while the second zone 442 (shown with a second shading) may be a crosslinked region. As shown, the second zone 442 may form a grid of crosslinked biologic material that surrounds non-crosslinked biologic material. In some examples, the grid provided by the first zone 441 may provide a uniform distribution (a mesh-like structure) of crosslinked biologic material within the biologic material 430. The mesh-like structure can add strength to the biologic material 410 while still maintaining conformability.

[0080] In other examples, the first zone 441 may be a crosslinked region and the second zone 442 may be a non-crosslinked biologic region. The non-crosslinked second zone 442 may create a mesh-like non-crosslinked structure (or islands of crosslinked biologic material) within the biologic material 410. The interruption of elasticity in isolated regions may increase overall strength while maintaining overall elasticity.

[0081] Although only three variations of the biologic material 420, 430, and 440 are shown, other variations are possible. Persons skilled in the art will recognize that the first andsecond zones may have regular or irregular geometric shapes. In some variations, a plurality of zones may include different crosslinked biologic material.

[0082] The regions of crosslinked biologic material may vary in depth (penetration of the crosslinked material into the biologic material 410). For example, the crosslinked biologic material may range from a thin-film thickness, to a partial thickness, or to a full thickness of the biologic material 410. In some examples the depth of the crosslinking may be relative to the total depth of the substrate biologic material (e.g., 85% or less, 80% or less, 75% or less, 70% or less, 65% or less, 60% or less, 55% or less, 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, 10% or less, etc.). In some examples the depth of crosslinking may be fixed depth (e.g., 0.1 mm or less, 0.09 mm or less, 0.08 mm or less, 0.07 mm or less, 0.06 mm or less, 0.05 mm or less, 0.04 mm or less, 0.03 mm or less, 0.02 mm or less, 0.01 mm or less, etc.). Differing thicknesses of crosslinked biologic material can affect the biomechanical properties of the biologic material 420, 430, and 440.

[0083] The crosslinked regions described herein can be formed with any feasible method or procedure. In some examples, the crosslinked biologic regions may be formed by the application of chemicals to regions (strips, islands, gridlines, etc.) of the biologic material 410 where the crosslinked biologic material is desired. The pattern and / or amount of chemicals applied and / or the duration of the application may affect the depth (penetration) and degree of crosslinked biologic material. Example of agents that may be used for chemical crosslinking may include, but are not limited to glutaraldehyde, riboflavin, and acetic acid.

[0084] In some variations, the crosslinked biologic regions may be formed by an application of heat to regions (strips, islands, gridlines, etc.) of the biologic material 410 where the crosslinked biologic material is desired. The temperatures and / or duration of the heat exposure may affect the depth of crosslinked biologic material. Any appropriate temperature may be used, including, e.g., temperature ranges of between about 42 to 102 degrees Celsius; the temperature may be maintained for any appropriate time (e.g., seconds to hours). In some examples, thermal crosslinking may be combined with dehydration, e.g., by applying suction / vacuum to remove water, providing dehydrotheramally (DHT) cross linking. Various combinations of heat and vacuum could be used, for any appropriate time period.

[0085] In some variations, the crosslinked biologic regions may be formed by an application of light. For example, a light source can be positioned close to (or in some cases touching) a surface of the biologic material 410 to form the crosslinked biologic regions. Thus, light can be exposed to regions (strips, islands, gridlines, etc.) of the biologic material 410 where crosslinked biologic material is desired. The light can deliver energy to regions ofthe biologic material 410 to cause crosslinking. Example light sources can be directional, polarized, colored, or include specific wavelengths and / or intensity combinations. For example, ultraviolet light may be applied (e.g., within the range of about 230 - 400 nm), for any appropriate duration of time (e.g., seconds to hours).

[0086] In addition to light, other types of radiation may be used to crosslink the biological material substrate. For example, gamma irradiation at 0.1-40 kGy, at a rate of about 0.1-10 kGy / hour may be used to form the crosslinked pattern. In any of these methods, the crosslinked biologic regions may be formed by an application of radiation from a radiation source positioned close to (or in some cases touching or compressing) a surface of the biologic material 410 to form the crosslinked biologic regions. In this manner, radiation can be exposed to regions (strips, islands, gridlines, etc.) of the biologic material 410 where crosslinked biologic material is desired. The radiation can deliver energy to regions of the biologic material 410 to cause crosslinking. Example radiation sources can be directional, polarized, or include specific wavelengths and / or intensity combinations.

[0087] In general, any of the crosslinking techniques used herein may be combined. For example, heat and chemical crosslinking (e.g., use of glutaraldehyde with heat, etc.). In any of these examples materials may be blended and / or introduced into the biologic material (e.g., collagen) to selectively cross-link regions. For example, one or more natural polymers such as, but not limited to, silk and cellulose can be used. Synthetic polymers like polylactic acid (PLA) and polyvinyl alcohol (PVA) can be used. Inorganic materials like hydroxyapatite can be used.

[0088] FIG. 5 shows examples of coated biologic materials 500. The coated biologic materials 500 may begin or originate with a single layer (substrate) of crosslinked or noncrosslinked biologic material 510. Any feasible biologic material may be used.

[0089] A first coated biologic material 520 may include a coating 521 on one side (surface) of the biologic material 510. In some examples, the coating 521 may include any ground up biologic material. The coating 521 can be the same biologic material as used in the biologic material 510 or a different biologic material. In some cases, the coating 521 may include a combination of two or more biologic materials. The coating 521 can affect the biomechanical properties of the biologic material 510. In some other examples, the coating 521 can be a particulate or a soluble biologic material. In some variations ,the coating 521 may be formed from two or more different biologic materials. In general, the coating 521 can affect the biomechanical properties of the biologic material 510 without substantially increasing thickness.

[0090] A second coated biologic material 530 may include a first coating 531 on a first side and a second coating 532 on a second (opposing) side or surface. The first coating 531 and the second coating 532 can be similar to any of the coatings described above with respect to the first coated biologic material 520. In some examples, the first coating 531 may be the same or different as the second coating 532. That is, the second coating 532 may include the same or different materials with respect to the first coating 531. In some examples, coatings on both sides of the second coated biologic material 530 may advantageously provide increased strength and / or rigidity to the biologic material 510 without substantially increasing thickness.

[0091] FIG. 6 shows other examples of patterned crosslinked biologic materials 600. The biologic materials 600 may begin or originate with a single layer (substrate) of biologic material 610. The biologic material 610 can be crosslinked or non-crosslinked. Any feasible biologic material may be used. Slits 611 may be cut or otherwise inserted into a first and / or a second side of the biologic material 610.

[0092] An example patterned crosslinked biologic material 620 is shown. In some examples, edges of the biologic material 610 may be pulled to expand the slits 611 into openings or pores. The openings can be filled with a biologic filler 621. The biologic filler 621 can be a biologic material that is the same as or different than the first biologic material 610. In some variations, the biologic filler 621 can be a crosslinked or a non-crosslinked material. In addition, a first coating 622 may be applied to a first side of the biologic material 620. The first coating 622 can be any feasible coating as described herein. For example, the first coating 622 can be a ground up biologic, a particulate biologic, or a soluble biologic.

[0093] Another example patterned crosslinked biologic material 630 is shown. Similar to the biologic material 620, edges of the biologic material 610 may be pulled to expand the slits 611 into openings. In this example, a first side of the second patterned crosslinked material 630 can receive a first biologic filler 631 and receive a first coating 632. In addition, a second side of the biologic material 630 can receive a second biologic filler (not shown) and a second coating 633. The first biologic filler 631 may be the same or different than the second biologic filler. The first coating 632 may be the same or different than the second coating 633. In some examples, any of the biologic fillers and coatings may provide increased strength and / or rigidity to the biologic material 610 without substantially increasing thickness.Method of forming

[0094] Any appropriate methods may be used to form the grafts described herein. FIGS. 7A and 7B schematically illustrate two examples of methods of forming grafts as described herein.

[0095] In FIG. 7A, the method 750 may include crosslinking a pattern into a surface of a biologic material. This step may include crosslinking the surface of the biologic material in a continuous pattern across the surface of the biologic material 752. As mentioned above, any appropriate technique (or combination of techniques) for crosslinking may be used, including thermal, chemical, mechanical / pressure, dehydration, radiation (including but not limited to optical), etc.

[0096] During the crosslinking the method may include controlling the depth of crosslinking (e.g., by controlling the applied energy over time) into the surface of the biologic material 754. Further, when forming the pattern of crosslinking, the method may include extending the pattern between two or more edges of the biological material substrate 756.

[0097] Optionally, as described above, any of these methods may include applying a second biologic material over (including in particular, over the crosslinked pattern) the first biologic material 758. In some cases it may be helpful to attach (e.g. bond, stitch, etc.) the second layer to the first layer.

[0098] FIG. 7B is a flowchart showing an example method 700 for forming a patterned crosslinked biologic material such as the patterned crosslinked biologic material described with respect to FIG. 6. Some examples may perform the operations described herein with additional operations, fewer operations, operations in a different order, operations in parallel, and some operations differently.

[0099] The method 700 begins in block 702 as a biologic substate is obtained. Any feasible biologic can be used. The biologic substrate can be a crosslinked or a noncrosslinked substrate. Next, in block 704 slits are created in the biologic substrate. In some examples, the slits may be made in a single direction or in multiple directions. The slits may be made with a knife, blade, or other suitable cutting or slicing tool. In some examples, a die with a plurality of blades may be pressed into the biologic substrate to form the slits. In some variations, slits may be created on opposing sides of the biologic substrate.

[0100] Next, in block 706 the biologic substrate is expanded to create openings. For example, two or more edges of the biologic substate can be grasped and pulled causing the slits created in block 704 to expand into openings. Next, in block 708 the openings are filled with a biologic material. The biologic material can be any feasible biologic material including crosslinked and non-crosslinked biologic material. In some examples, biologic material maybe inserted into openings on opposing sides of the biologic substrate. In some other examples, the biologic material used to fill the openings may be the same as, or different than the initial biologic substrate.

[0101] Next, in block 710, a coating may be applied to one or more surfaces of the biologic substrate. This operation is optional, as indicated with dashed lines in FIG. 7B. The coatings may be any feasible coating including ground up biologic material, particulate biologic material, and / or soluble biologic material.

[0102] As a result of the method 700, the biologic substrate may have a mesh or meshlike structure. In some instances (such as when the initial biologic substrate has been crosslinked), the resulting the mesh structure can advantageously have a stronger, yet still conformal, support system.

[0103] When a feature or element is herein referred to as being "on" another feature or element, it can be directly on the other feature or element or intervening features and / or elements may also be present. In contrast, when a feature or element is referred to as being "directly on" another feature or element, there are no intervening features or elements present. It will also be understood that, when a feature or element is referred to as being "connected", "attached" or "coupled" to another feature or element, it can be directly connected, attached or coupled to the other feature or element or intervening features or elements may be present. In contrast, when a feature or element is referred to as being "directly connected", "directly attached" or "directly coupled" to another feature or element, there are no intervening features or elements present. Although described or shown with respect to one embodiment, the features and elements so described or shown can apply to other embodiments. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed "adjacent" another feature may have portions that overlap or underlie the adjacent feature.

[0104] Terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. For example, as used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and / or "comprising," when used in this specification, specify the presence of stated features, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups thereof. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items and may be abbreviated as " / ".

[0105] Spatially relative terms, such as "under", "below", "lower", "over", "upper" and the like, may be used herein for ease of description to describe one element or feature'srelationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if a device in the figures is inverted, elements described as "under" or "beneath" other elements or features would then be oriented "over" the other elements or features. Thus, the exemplary term "under" can encompass both an orientation of over and under. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Similarly, the terms "upwardly", "downwardly", "vertical", "horizontal" and the like are used herein for the purpose of explanation only unless specifically indicated otherwise.

[0106] Although the terms “first” and “second” may be used herein to describe various features / elements (including steps), these features / elements should not be limited by these terms, unless the context indicates otherwise. These terms may be used to distinguish one feature / element from another feature / element. Thus, a first feature / element discussed below could be termed a second feature / element, and similarly, a second feature / element discussed below could be termed a first feature / element without departing from the teachings of the present invention.

[0107] Throughout this specification and the claims which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” and “comprising” means various components can be co-jointly employed in the methods and articles (e.g., compositions and apparatuses including device and methods). For example, the term “comprising” will be understood to imply the inclusion of any stated elements or steps but not the exclusion of any other elements or steps.

[0108] In general, any of the apparatuses and methods described herein should be understood to be inclusive, but all or a sub-set of the components and / or steps may alternatively be exclusive, and may be expressed as “consisting of’ or alternatively “consisting essentially of’ the various components, steps, sub-components or sub-steps.

[0109] As used herein in the specification and claims, including as used in the examples and unless otherwise expressly specified, all numbers may be read as if prefaced by the word "about" or “approximately,” even if the term does not expressly appear. The phrase “about” or “approximately” may be used when describing magnitude and / or position to indicate that the value and / or position described is within a reasonable expected range of values and / or positions. For example, a numeric value may have a value that is + / - 0.1% of the stated value (or range of values), + / - 1% of the stated value (or range of values), + / - 2% of the stated value (or range of values), + / - 5% of the stated value (or range of values), + / - 10% of the statedvalue (or range of values), etc. Any numerical values given herein should also be understood to include about or approximately that value, unless the context indicates otherwise. For example, if the value " 10" is disclosed, then "about 10" is also disclosed. Any numerical range recited herein is intended to include all sub-ranges subsumed therein. It is also understood that when a value is disclosed that "less than or equal to" the value, "greater than or equal to the value" and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value "X" is disclosed the "less than or equal to X" as well as "greater than or equal to X" (e.g., where X is a numerical value) is also disclosed. It is also understood that the throughout the application, data is provided in a number of different formats, and that this data, represents endpoints and starting points, and ranges for any combination of the data points. For example, if a particular data point “10” and a particular data point “15” are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0110] Although various illustrative embodiments are described above, any of a number of changes may be made to various embodiments without departing from the scope of the invention as described by the claims. For example, the order in which various described method steps are performed may often be changed in alternative embodiments, and in other alternative embodiments one or more method steps may be skipped altogether. Optional features of various device and system embodiments may be included in some embodiments and not in others. Therefore, the foregoing description is provided primarily for exemplary purposes and should not be interpreted to limit the scope of the invention as it is set forth in the claims.[OHl] The examples and illustrations included herein show, by way of illustration and not of limitation, specific embodiments in which the subject matter may be practiced. As mentioned, other embodiments may be utilized and derived there from, such that structural and logical substitutions and changes may be made without departing from the scope of this disclosure. Such embodiments of the inventive subject matter may be referred to herein individually or collectively by the term “invention” merely for convenience and without intending to voluntarily limit the scope of this application to any single invention or inventive concept, if more than one is, in fact, disclosed. Thus, although specific embodiments have been illustrated and described herein, any arrangement calculated to achieve the same purpose may be substituted for the specific embodiments shown. This disclosure is intendedto cover any and all adaptations or variations of various embodiments. Combinations of the above embodiments, and other embodiments not specifically described herein, will be apparent to those of skill in the art upon reviewing the above description.

Claims

CLAIMSWhat is claimed is:

1. A graft of biologic material crosslinked in a pattern, the graft comprising: a layer of a biologic substrate having a thickness and including a pattern extending across a surface of the biologic substrate; wherein the pattern comprises a pattern of crosslinking of the biologic substrate; and wherein the percentage of the surface of the biologic substrate that is crosslinked is less than 35% of the surface but spans from a first edge region of the layer to an opposite edge region of the layer.

2. The graft of claim 1, further wherein the pattern extends only partially into the thickness of the layer of the biologic substrate.

3. The graft of claim 2, wherein the pattern extends between 5% and 80% of the thickness of the biologic substrate.

4. The graft of claim 1, wherein the pattern extends across the surface and is configured to provide a compliance of between 2-200% at 16N / cm load.

5. The graft of claim 1, wherein the biologic material comprises an extracellular matrix material.

6. The graft of claim 1, wherein the biologic material comprises one or more of: collagen, elastin, fibronectin, and / or laminin.

7. The graft of claim 1, wherein the pattern comprises a grid pattern disposed across a surface of the biologic substrate.

8. The graft of claim 1, wherein the pattern comprises a repeating diamond pattern disposed across a surface of the biologic substrate.

9. The graft of claim 1, wherein the pattern comprises a plurality of stripes tapering from a wide to a narrow width disposed across a surface of the biologic substrate.

10. The graft of claim 1, wherein the pattern of crosslinking of the biologic substrate is crosslinked by one or more of: thermal crosslinking, chemical crosslinking, radiation crosslinking, and optical crosslinking.

11. The graft of claim 1, wherein the pattern of crosslinking of the biologic substrate comprises a continuous pattern.

12. The graft of claim 11, wherein the continuous pattern extends across the surface of the biological substrate between two or more edges of the biological substrate that are oriented at an angle of between 45 degrees and 135 degrees.

13. The graft of claim 1, wherein the pattern of crosslinking of the biologic substrate results in the graft having a strain of between 2.5 to 200% under a load of 0.7 N / cm.

14. The graft of claim 1, wherein the pattern of crosslinking of the biologic substrate results in the graft having a strain of between 10 to 30% under a load of 0.3 N / cm.

15. The graft of claim 1, wherein the pattern of crosslinking of the biologic substrate results in the graft having a compliance of between 2-200% at a 16 N / cm load.

16. The graft of claim 1, wherein the pattern of crosslinking of the biologic substrate results in the graft having a compliance of between 10-30% at a 16 N / cm load.

17. The graft of claim 1, wherein the pattern of crosslinking of the biologic substrate results in a graft having a modulus of between 10-400 MPa.

18. The graft of claim 1, wherein the pattern of crosslinking of the biologic substrate results in a graft having a modulus of between 200-2000 MPa.

19. The graft of claim 1, wherein the pattern comprises a plurality of openings disposed across a surface of the crosslinked biologic substrate; and a biologic material inserted into the plurality of openings.

20. A graft of biologic material crosslinked in a pattern, the graft comprising: a layer of a biologic substrate having a thickness and including a pattern extending across a surface of the biologic substrate; wherein the pattern comprises a pattern of crosslinking of the biologic substrate; further wherein the pattern extends only partially into the thickness of the layer of the biologic substrate; and wherein the percentage of the surface of the biologic substrate that is crosslinked is less than 35% of the surface.

21. A graft of biologic material crosslinked in a pattern, the graft comprising:a layer of a biologic substrate having a thickness and including a pattern extending across a surface of the biologic substrate; wherein the pattern comprises a pattern of crosslinking of the biologic substrate; further wherein the pattern extends only partially into the thickness of the layer of biologic substrate; wherein the pattern extends across the surface and is configured to provide a compliance of between 2-200% at 16N / cm load; and wherein the percentage of the surface of the biologic substrate that is crosslinked is less than 35% of the surface.

22. A method of forming a graft of biologic material crosslinked in a pattern, the method comprising: crosslinking a surface of a biologic material into a continuous pattern across a surface of the biologic substrate; wherein the percentage of the surface of the biologic substrate that is crosslinked is less than 35% of the surface.

23. The method of claim 22, wherein crosslinking the surface of the biologic material comprises crosslinking only partially into the thickness of the layer of the biologic substrate.

24. The method of claim 22, wherein crosslinking the surface of the biologic material comprises crosslinking the pattern into between 5% and 80% of the thickness of the biologic substrate.

25. The method of claim 22, wherein the crosslinked pattern is configured to provide a compliance of between 2-200% at 16N / cm load.

26. The method of claim 22, wherein the biologic material comprises an extracellular matrix material.

27. The method of claim 22, wherein the biologic material comprises one or more of: collagen, elastin, fibronectin, and / or laminin.

28. The method of claim 22, wherein the pattern comprises a grid pattern disposed across a surface of the biologic substrate.

29. The method of claim 22, wherein the pattern comprises a repeating diamond pattern disposed across a surface of the biologic substrate.

30. The method of claim 22, wherein the pattern comprises a plurality of stripes tapering from a wide to a narrow width disposed across a surface of the biologic substrate.

31. The method of claim 22, wherein the pattern of crosslinking of the biologic substrate is crosslinked by one or more of: thermal crosslinking, chemical crosslinking, radiation crosslinking, and optical crosslinking.

32. The method of claim 22, wherein the continuous pattern extends across the surface of the biological substrate between two or more edges of the biological substrate that are oriented at an angle of between 45 degrees and 135 degrees.

33. The method of claim 22, wherein crosslinking the surface of the biologic substrate in the pattern results in the graft having a strain of between 2.5 to 200% under a load of 0.7 N / cm.

34. The method of claim 22, wherein crosslinking the surface of the biologic substrate in the pattern results in the graft having a strain of between 10 to 30% under a load of 0.3 N / cm.

35. The method of claim 22, wherein crosslinking the surface of the biologic substrate in the pattern results in the graft having a compliance of between 2-200% at a 16 N / cm load.

36. The method of claim 22, wherein crosslinking the surface of the biologic substrate in the pattern results in the graft having a compliance of between 10-30% at a 16 N / cm load.

37. The method of claim 22, wherein crosslinking the surface of the biologic substrate in the pattern results in a graft having a modulus of between 10-400 MPa.

38. The method of claim 22, wherein crosslinking the surface of the biologic substrate in the pattern results in a graft having a modulus of between 200-2000 MPa.

39. The method of claim 22, further comprising adding a biologic material into a plurality of openings formed by the pattern.

40. The method of claim 22, further comprising bonding a second biologic material to the first biologic material.

41. The method of claim 22, further comprising applying a coating of a second biologic material to at least one of a top and bottom surface of the substrate.

Images