Microstructured soft tissue grafts

Abstract

A soft tissue repair graft (500) is described that includes an anti-adhesion layer (502), a structural layer, and a positioning layer. These layers can be distinct or integrated into one substrate. The term "layer" is used to distinguish the function of the tissue repair graft, not to distinguish different layers of material. Different functional layers can include a single plane of material.

Description

Technical Field

[0001] This invention generally relates to apparatuses and methods in the field of soft tissue repair. More specifically, this invention relates to graft materials for soft tissue repair, comprising an anti-adhesion layer that inhibits postoperative adhesion formation and a fixation device that is independent of sutures and advantageously self-adhesive, distributing anchoring force over a large tissue area.

[0002] Adhesions are fibrous bands of connective tissue that form between body tissues and organs. They are usually not connected together, or they form in a way that differs from the normal connective tissue anatomy between body tissues and organs. Adhesions typically form after surgery in the abdominal or pelvic region. In some cases, adhesions can cause complications such as pain or obstruction of the organs they connect to.

[0003] Adhesions typically begin to form shortly after surgery and may continue to develop thereafter. There is no known effective treatment to reverse adhesion formation. If adhesions cause complications for the patient, the typical treatment is surgical removal. Therefore, the best approach to adhesion management is to prevent or limit adhesion formation. Background Technology

[0004] While no products are known to effectively reverse adhesion formation, various commercially available products exist that can prevent it. These products are not 100% effective, although their use is known to consistently reduce adhesion formation. These products come in many forms, such as gels and absorbable sheets, which are applied to the surgical site and gradually reabsorbed over several days.

[0005] In the repair of soft tissue defects, sheets, rather than gels, are often used in conjunction with reinforcing meshes. Typically, the sheet is attached to the mesh as a composite structure. The sheet can be formed on the mesh or attached by an adhesive. Typically, the mesh of the composite structure faces the soft tissue defect site, such as a hernia. It is advantageous to leave space between the mesh and the anti-adhesion layer to promote tissue ingrowth into the mesh and adhesion between the mesh and the soft tissue defect. Ideally, the mesh acts as a tissue scaffold, promoting healthy, rather than fibrotic, tissue growth between the mesh and the soft tissue defect.

[0006] However, a drawback of current products is the need for sutures or similar mechanisms to secure the device in place. In products like gels that cannot be mechanically fixed to tissue defects, a disadvantage has been found to be their poor ability to maintain the gel at the point of interest for a considerable period (e.g., hours, days, or weeks). Therefore, some products offer good mechanical fixation but have poor repositioning capabilities and can damage surrounding tissue, while others are repositionable but have poor long-term fixation capabilities.

[0007] Therefore, there is a need for a repositionable, self-adhesive repair graft to be placed at sites of interest, which can maintain its position without requiring mechanical fixation. Furthermore, there is a need for a device with repositionable properties that has sufficient adhesive strength to temporarily hold the device in place relative to the target tissue location during surgical procedures and in the absence of a positioning agent that requires coagulation or curing, whereas otherwise the tissue would be unsupported relative to the target tissue location. Summary of the Invention

[0008] According to this disclosure, various embodiments are described herein. In some embodiments, a positioning agent may be disposed on a soft tissue repair graft. The positioning agent may have adhesive properties sufficient to temporarily hold the surgical soft tissue repair prosthesis in place relative to a target tissue location during surgery, where it would otherwise be positioned unsupported relative to the target tissue location. In some embodiments, a mesh prosthesis may be held in a temporary position until it is permanently secured in place relative to the target tissue location using a device for permanent fixation. In some embodiments, the device for permanent fixation may include sutures, surgical staples, surgical U-staples, etc. The positioning agent, when applied to a surgical soft tissue repair prosthesis, may exhibit sufficient adhesive properties to resist gravity and hold it in place, for example, in the absence of coagulation or hardening of the positioning agent during implantation.

[0009] Embodiments of this disclosure may include a permanent fixative disposed on a soft tissue repair graft. In some embodiments, a positioning agent may act in combination with the permanent fixative, and together they have sufficient adhesive capability to hold the surgical soft tissue repair prosthesis in place relative to a target tissue location during surgery, which would otherwise be unsupported relative to the target tissue location. In some embodiments, the soft tissue repair graft can be permanently fixed by applying a normal force to the soft tissue repair prosthesis to accomplish the function of the fixative, wherein the positioning agent and fixative exhibit sufficient adhesive capability when applied to the surgical soft tissue repair prosthesis to resist gravity and hold it in place, for example, in the absence of coagulation or solidification of the positioning agent during the implantation procedure. In some embodiments, the fixative can provide sufficient fixation to hold the soft tissue repair prosthesis in place for a specified amount of time, such that adhesion formation between the target tissue surface and the mesh layer of the soft tissue repair prosthesis is limited.

[0010] Embodiments of this disclosure may include a method of implanting a surgical mesh prosthesis, wherein the method may include the step of positioning the surgical mesh prosthesis relative to the target tissue surface with a positioning agent disposed between a mesh layer of the prosthesis and a target tissue surface. The positioning agent may include adhesive properties sufficient to temporarily hold the mesh layer in place relative to the target tissue against gravity without coagulation or hardening of the positioning agent, or otherwise position it unsupported relative to the target tissue. In some embodiments, the positioning agent may be applied to the surface of the target tissue prior to positioning the surgical mesh prosthesis relative to the surface of the positioning agent. In some embodiments, the positioning agent may be applied to a first side of the surgical mesh prosthesis prior to positioning the surgical mesh prosthesis relative to the surface of the target tissue. The method may also include repositioning a surgical soft tissue repair prosthesis from a first location on the tissue to a second location on the tissue. In some embodiments, the method may further include detaching the surgical soft tissue repair prosthesis from the first location on the tissue and placing the surgical soft tissue repair prosthesis in the second location on the tissue without causing trauma or damage to the tissue.

[0011] Embodiments of this disclosure may include an implantable device having an anti-adhesion layer, a tissue scaffold layer, a positioning layer, and a permanent fixation layer. In some embodiments, one layer may be combined with another layer while both layers retain their capabilities and / or properties.

[0012] Embodiments of this disclosure may include a soft tissue repair graft comprising a first layer stacked on a second layer and a second layer stacked on a third layer. In some embodiments, the first layer may comprise a mesh formed of a non-absorbable polymeric material. The second layer may comprise a barrier layer formed of an absorbable or non-absorbable polymeric material. The third layer may comprise an absorbable or non-absorbable polymeric layer thereon having a first pattern disposed on the polymeric layer having a bioabsorbable material and a second pattern disposed thereon, the second pattern comprising the same polymer as the polymer comprising the third layer. In some embodiments, the second layer may have a first surface adjacent to the patient's intestine. The third layer may have a first surface adjacent to tissue including defects. In some embodiments, the first surface of the third layer may be in contact with tissue including defects. In some embodiments, the first layer may be flexibly attached to the second and third layers. In some embodiments, the first pattern of the third layer may generate an orthogonal attraction force that attracts the tissue-facing side of the third layer to the tissue with a force sufficient to drive the second pattern of the third layer into the tissue, thereby securing the soft tissue repair graft to the tissue.

[0013] Embodiments of this disclosure may include soft tissue repair grafts, wherein a first layer is non-absorbable, a second layer is absorbable, and a third layer is non-absorbable.

[0014] Embodiments of this disclosure may include soft tissue repair grafts, wherein a first layer is non-absorbable, a second layer is non-absorbable, and a third layer is absorbable.

[0015] Embodiments of this disclosure may include soft tissue repair grafts, wherein a first pattern may include microstructures capable of producing at least one of the following: a) capillary attraction; b) van der Waals attraction; c) Wenzel-Cassie interface; d) Schallamach capture interface; e) intrinsic fold capture interface; and f) inward growth surface.

[0016] Embodiments of this disclosure may include soft tissue repair grafts, wherein a first pattern may include hierarchically arranged microstructures comprising at least two surface sub-patterns with different surface energies. In some embodiments, when the first layer comes into contact with a water-wetting surface, the first sub-pattern may have a higher surface energy and become hydrophilic, while the second sub-pattern may have a lower surface energy and become hydrophobic.

[0017] Embodiments of this disclosure may include soft tissue repair grafts in which the attractive force generated by the first pattern is insufficient to fully drive the second pattern into the tissue layer. This configuration, and the engagement between the first and second patterns, can provide the soft tissue repair graft with the ability to be repositioned without tissue damage. In some embodiments, a slight normal force applied by the clinician can engage the second pattern with the tissue layer when the desired graft position is achieved. In some embodiments, the normal force applied by the clinician can further engage the second pattern that may already be at least partially engaged with the tissue layer.

[0018] Embodiments of this disclosure may include soft tissue repair grafts, wherein the second pattern consists of barbs or suitable tissue adhesion structures that resist removal from the tissue layer when the second pattern is invasively joined to the tissue layer by means of the first pattern or by external force.

[0019] Embodiments of this disclosure may include soft tissue repair grafts, wherein a second pattern is designed to maximally distribute the fixation force of the soft tissue repair graft over the contact area after implantation. In some embodiments, the soft tissue repair graft may detach from contact with a target surface. In some embodiments, the target surface may contact the uppermost microfeature of the hierarchical microstructure, but not directly with other microfeatures of the hierarchical microstructure. During detachment, the individual uppermost microfeature of the hierarchical microstructure may not apply a force greater than 0.025 kg / cm² to the target surface. 3 The force, and the volume (cm³) therein 3This can be the volume of a single, uppermost microstructural element. In some embodiments, the force required to completely detach the soft tissue repair graft from the target surface can be greater than 25 kg / cm². 2 , of which surface area (cm 2 () can be the contact area between the soft tissue repair graft and the tissue layer.

[0020] In some embodiments, during detachment, individual hierarchical microstructures may not be subjected to an application greater than 0.025 kg / cm² on the target surface. 3 The force, and the volume (cm³) therein 3 () can be the volume of each micro-feature arranged hierarchically.

[0021] In some embodiments, during detachment, individual micro-features that are not hierarchical may not be subjected to a force greater than 0.025 kg / cm² on the target surface. 3 The force, and the volume (cm³) therein 3 The micro-feature can be the volume of a micro-feature. In some embodiments, a single micro-feature can be a barbed micro-feature. In some embodiments, a barbed micro-feature can also be the uppermost micro-feature of a hierarchical microstructure.

[0022] Embodiments of this disclosure may include soft tissue repair grafts, which may include microstructural elements of a second pattern that are at least 50% longer than the longest microstructural element of the first pattern.

[0023] Embodiments of this disclosure may include soft tissue repair grafts having a fenestrated third layer to allow tissue to grow from the third layer and into the second layer.

[0024] Embodiments of this disclosure may include a soft tissue repair graft having a first layer, the first layer being a mesh having openings with a diameter between 0.5 mm and 6 mm.

[0025] Embodiments of this disclosure may include soft tissue repair grafts having a mesh formed of warp-knitted filaments, wherein the diameter of the filaments is between 5 micrometers and 100 micrometers.

[0026] Embodiments of this disclosure may include a mass per unit area of ​​less than 300 g / m². 2 Soft tissue repair grafts.

[0027] Embodiments of this disclosure may include soft tissue repair grafts comprising a self-adhesive layer, a prosthesis reinforcement layer, and an anti-adhesion layer, the graft configured to repair animal tissue. In some embodiments, each layer may be combined with another layer, but each layer may retain its properties. In some embodiments, the soft tissue repair graft may include an absorbable surgical barrier sheet, a mesh material sheet, and an adhesive material sheet, wherein the adhesive sheet may include at least first and second microstructures. In some embodiments, the adhesive sheet may include a plurality of windows that allow adhesion between defective tissue surfaces and the mesh sheet, wherein all three sheets are flexibly bonded, allowing lateral displacement of up to millimeters between the sheets.

[0028] Embodiments of this disclosure may include soft tissue repair grafts, wherein the three bonded sheets may include pre-formed and nested shapes that are substantially off-planar.

[0029] Embodiments of this disclosure may include soft tissue repair grafts comprising two membranes, one configured to facilitate fixation and inward tissue growth, and the second configured to prevent fixation and inward tissue growth. In some embodiments, no liquid adhesive or tissue binder is present on the membranes. In some embodiments, a mesh having an average pore size between 100 and 2000 micrometers may be disposed between the membranes. In some embodiments, the soft tissue repair graft may adhere to the defective tissue layer upon contact.

[0030] Embodiments of this disclosure may include soft tissue repair grafts, wherein an adhesion-blocking gel layer may replace a membrane layer to prevent fixation and inward tissue growth.

[0031] Embodiments of this disclosure may include soft tissue repair grafts, wherein the membrane for promoting fixation and inward tissue growth may include hierarchical microstructure portions and tissue-jointing portions.

[0032] Embodiments of this disclosure may include soft tissue repair grafts, wherein the self-adhesive layer is a combination of an attractive force generated by a first portion of hierarchical microstructures and a second portion of tissue penetration and retention, wherein the first portion causes fixation of the second portion. Attached Figure Description

[0033] Figure 1 This is an example demonstrating a hierarchical microstructure with a high branching ratio.

[0034] Figure 2A This is an illustration of an embodiment of the Wenzel-Cassie interface between the target surface and the microstructured surface.

[0035] Figure 2B This is an illustration of another embodiment of the Wenzel-Cassie interface between the target surface and the microstructured surface.

[0036] Figure 3A and Figure 3B This is an illustration of an embodiment of the present disclosure having an interface volume between the target surface and the microstructure.

[0037] Figure 4 Various embodiments of the microstructure geometry are depicted.

[0038] Figure 5 This is an illustration of an embodiment of the Wenzel-Cassie soft tissue repair device.

[0039] Figure 6 This is an illustration of an embodiment of the Wenzel-Cassie soft tissue repair device with a flexible layer.

[0040] Figure 7 This is an illustration of an embodiment of a two-stage soft tissue repair device.

[0041] Figure 8A and Figure 8B This is an illustration of an embodiment of the Wenzel-Cassie two-stage soft tissue repair device. Detailed Implementation

[0042] Reference will now be made in detail to embodiments of the present disclosure, one or more of which are set forth below. Each embodiment and example is provided by way of explaining the apparatus, composition, and materials of the present disclosure and is not intended to be limiting. Rather, the following description provides a convenient illustration of exemplary embodiments for carrying out the present disclosure. In fact, it will be apparent to those skilled in the art that various modifications and variations can be made to the teachings of the present disclosure without departing from the scope or spirit of the present disclosure. For example, features shown or described as part of an embodiment may be used with another embodiment to produce yet another embodiment. Therefore, the present disclosure is intended to cover such modifications and variations that fall within the scope of the appended claims and their equivalents. Other objects, features, and aspects of the present disclosure are disclosed in or will become apparent from the following detailed description. It will be understood by those skilled in the art that this discussion is merely a description of exemplary embodiments and is not intended to limit the broader aspects of the invention.

[0043] Exemplary applications of the apparatus and methods according to this disclosure are described in this section. These embodiments are provided merely to provide context and aid in understanding this disclosure. It will therefore be apparent to those skilled in the art that this disclosure can be practiced without some or all of these specific details. In other instances, well-known process steps have not been described in detail to avoid unnecessarily obscuring this disclosure. Other applications are possible, such that the following examples should not be considered limiting.

[0044] In the following detailed description, reference is made to the accompanying drawings, which form a part of the description and illustrate specific embodiments of the present disclosure by way of illustration. Although these embodiments have been described in sufficient detail to enable those skilled in the art to practice the invention, it should be understood that these examples are not limiting; other embodiments can be used, and changes can be made without departing from the spirit and scope of the present disclosure.

[0045] As used herein, the term "intersurface adhesion" can be understood as describing the adhesive forces formed between a microstructured surface and a contact surface. It should be understood that the term can be applied to both lateral translational resistance (shear) and normal translational resistance (peeling). The term can also be applied to the attractive forces generated when the surface tension of the liquid and the surface energy of the microstructured surface form an interface where the energy of both is minimized.

[0046] As used in this paper, the term "fractal dimension" applied to microstructured surfaces can be understood as describing a microstructured surface with a characteristic branching ratio.

[0047] As used herein, the term "Wenzel-Cassie interface" can be understood as referring to the interfacial volume formed between two solid surfaces. This interfacial volume may contain at least two fluids with different surface energies. It should be understood that "fluid" can refer to a liquid or a gas, or both.

[0048] As used in this paper, the term "surface energy" can be understood as the potential energy of surface molecules per unit area of ​​surface. The term "surface energy gradient," as used in this paper, can be understood as the change in the spatial derivative of the surface energy along a path connecting two surfaces.

[0049] The organization of interfacial volume in a Wenzel-Cassie interface can be understood as minimizing the surface energy gradient between the hierarchical microstructured surface and the liquid component at the Wenzel-Cassie interface. Therefore, the interfacial liquid and surface microstructures can typically associate in pairs, where the sum of the surface energy differences between each liquid-microstructure pair can be minimized.

[0050] As used in this article, the term "surface tension" can be understood as a description of the surface energy of a liquid. Surface tension can be understood as the amount of work done by the force that overcomes surface tension at a constant temperature to increase the surface area of ​​a liquid by one unit.

[0051] As will be understood by those skilled in the art, many of these phenomena may occur over time, in some cases within a timeframe of minutes. Therefore, the first microstructured surface that generates the Wenzel-Cassie interface can reduce the distance between the microstructured surface and the contact surface over time. If a second microstructure is used in combination with the first microstructure, and the second microstructure has a greater length than the first microstructure and is designed to mechanically engage soft tissue, the first microstructure can be used to drive the second tissue-engaging element into the soft tissue contact surface.

[0052] As used herein, the term "position strength" can be understood as a general term encompassing the self-adhesive properties of microstructured surfaces resulting from van der Waals interactions. Typically, position strength is associated with the Wenzel-Cassie interface. Position strength can be understood as non-invasive adhesion of contact surfaces characterized by forces per unit area. Position strength can be quantified in this disclosure in two ways: translational (shear) adhesion and peel (lift) adhesion.

[0053] As used herein, the term "area ratio" can be understood as referring to the porosity of a material, including but not limited to meshes or sheets. The area ratio can be the ratio of the porous area of ​​the material to the total area of ​​the sheet. Sheets with reduced areal density can be understood as having increased porosity.

[0054] As used herein, the term "barb" can be understood to refer to any micro-feature on a surface that is intended for invasive engagement of a contact surface. In some embodiments, a barb may be a smooth, tapered post or a post with an arrowhead-like structure.

[0055] As used in this article, the term "invasive" can be understood as referring to at least a portion of an object penetrating into a surface.

[0056] This disclosure relates to novel materials for soft tissue repair, particularly materials for hernia repair. These novel materials can be configured for a variety of applications, including but not limited to, as implants, such as grafts or soft tissue support devices. These materials can be implanted in patients, such as those suffering from a hernia or undergoing hernia repair surgery.

[0057] Advantageously, these materials (and any devices, such as apparatus and systems, including grafts, utilizing these materials) are particularly well-suited for surgical implantation over time in the repair of body wall cavities and can possess superior biomechanical or biochemical properties compared to those of prior art devices and materials. Specifically, the compliance of any device permanently fixed to the target tissue should match the compliance of the target tissue in order to produce optimal results and minimize complications from surgery. Conversely, compliance should be sufficient to correct tissue defects, at least after time has passed. Therefore, many biomechanical characteristics of prior art implantation devices represent a compromise between biocompatibility and therapeutic efficacy, and are thus inadequate.

[0058] Similarly, it is often true that adding a surgical barrier to a surgical stent can lead to a stiffer composite device. On the other hand, adhesions typically do not form after 7 days post-surgery. Therefore, the surgical barrier can be absorbable after a given period of time.

[0059] In some embodiments, the apparatus of this disclosure may include a tissue scaffold material. In some embodiments, the tissue scaffold material may be a mesh. The scaffold material may be a biowoven fabric, a medical fabric, or both. In some embodiments, the apparatus may further include an anti-adhesion layer that can be attached to the tissue scaffold material. In some embodiments, the anti-adhesion layer may be located at discrete locations on the scaffold material. It should be understood that “discrete” as used herein can be understood as including an anti-adhesion layer at separate and distinct locations on the scaffold material, and therefore not surrounding the entire surface area of ​​the scaffold material. In some embodiments, this location may include an anti-adhesion layer incorporated into the scaffold material and / or may be secured to the scaffold material. In some embodiments, the anti-adhesion layer may be secured to the scaffold material while still allowing sliding between the scaffold material and the anti-adhesion layer in areas near and / or between discrete anti-adhesion locations.

[0060] Tissue scaffolds can be composed of a variety of materials and / or compositions. In some embodiments, the tissue scaffold material can be biocompatible. In some embodiments, the scaffold material can include extracellular matrix, hernia repair scaffold, patch, and / or mesh, etc. Tissue scaffolds can be arranged in an open-cell geometry and may be referred to herein as a “mesh” in some embodiments. In some embodiments, the mesh can be biocompatible and / or bioabsorbable, and / or non-bioabsorbable. In some embodiments, the tissue scaffold can include a biocompatible membrane. Throughout the application, the tissue scaffold material may be collectively referred to as the first layer, regardless of whether the tissue scaffold consists of a plurality of sublayers (such as mesh and membrane together) or only a single layer.

[0061] Examples of tissue scaffolds can be formed from non-bioabsorbable materials. In some embodiments, these non-bioabsorbable materials may include filaments incorporated into the material. In some embodiments, the filaments may be threads, metal wires, braids, monofilaments, multifilaments, combinations thereof, etc. In some embodiments, the filaments may be incorporated by methods similar to weaving, sewing, or embroidering filaments into the tissue scaffold material. In some embodiments, the combination of filaments may include creating a pattern within the scaffold material. A first pattern may be combined using a non-bioabsorbable filament material, wherein the first pattern may be a grid or array of substantially parallel lines. In some embodiments, the first pattern may include multiple sub-patterns arranged offset from and / or overlapping each other, which together may create a larger pattern. The filament material forming the first pattern and / or the entire first pattern may have a lower compliance than a mesh. Therefore, the final compliance of the tissue scaffold may be the compliance of the mesh and the first pattern incorporated into the mesh.

[0062] In some embodiments, the second filament may be used in conjunction with or in combination with the first filament. The second filament may comprise a filament material different from the first filament. The second filament may be used in conjunction with the first filament to create a first pattern. In other embodiments, the first filament may create a first pattern, and the second filament may create a second pattern. It will be understood by those skilled in the art that any number of filaments and patterns can be used. It will also be understood that a single filament material can be used to create a single pattern and / or multiple patterns. And multiple filament materials can be used to create a single pattern and / or multiple patterns.

[0063] In some embodiments where the mesh is bioabsorbable, bioabsorbable filamentary materials may also be used. In some embodiments, the bioabsorbable material of the mesh and the bioabsorbable material of the filaments may have similar absorbability distributions, such that each material is absorbed at approximately the same rate in the same environment. In some embodiments, the filamentary material may include a different bioabsorbability distribution, such that the filaments are absorbed faster than the mesh material, or it may be absorbed more slowly. In a preferred embodiment, the filamentary material is absorbed faster than the bioabsorbable material of the mesh.

[0064] Material compliance (e.g., flexural modulus) refers to the mechanical property of a material that undergoes elastic deformation when subjected to applied force. It can be understood as the reciprocal of stiffness. Compliance can be described as percentage compliant strain. Materials that deform easily are considered compliant, while materials that resist deformation are considered rigid.

[0065] Some embodiments of this disclosure may include an anti-adhesion layer. In some embodiments, the anti-adhesion layer may include one or more layers of anti-adhesion material. It should be noted that the reference to "anti-adhesion layer" does not necessarily mean that the layer or material is "non-adhesive," but rather refers to a layer or material that prevents or substantially restricts the formation of "adhesion."

[0066] In some embodiments, the anti-adhesion material may comprise one or more layers of biofabricated and / or medical fabrics. In some embodiments, the material may preferably be an extracellular material, such as an extracellular matrix derived from one or more of the dermis, pericardium, peritoneum, intestine, stomach, or forestomach. It will be understood in this disclosure that the anti-adhesion layer may also be referred to as a “second layer.” However, the reference to “second layer” is not limited to the anti-adhesion layer.

[0067] Embodiments of this disclosure may include a first layer (tissue scaffold material) and a second layer (anti-adhesion layer) attached to the first layer. In some embodiments, the combination of layers is configured in a manner that substantially does not alter the compliance of the first layer. In practice, this means that when attached together as described herein, the compliance of the first and second layers, individually or in combination, changes by no more than a few percent.

[0068] Some embodiments of this disclosure may include a first layer and a second layer attached together, wherein when the first layer and the second layer are attached together at discrete attachment sites, the compliance of the material may be within 20% or less of the compliance of the first layer alone, the second layer alone, or a combination of the first layer and the second layer when they are “stacked” on top of each other without attachment. It will be understood that, as used herein, “discrete” for “discrete attachment sites” may mean that each location where the first and second layers are attached to each other is individually separate and distinct from the other location. Discrete attachment sites can be any number of methods used to attach the first and second layers. In some embodiments, discrete attachment sites may include sutures connecting the first layer to the second layer. In some embodiments, the sites may be chemical or polymeric adhesives, such as biocompatible adhesives, at small discrete locations between the two layers, and adhering the first layer to the second layer. The adhesive may be any suitable biocompatible adhesive.

[0069] In some embodiments, discrete attachment sites may include regions with relatively small diameters, which may be regular or irregular in shape. Embodiments including sutures as discrete attachment sites may include a material woven or sewn between two layers, and the discrete attachment sites may have a diameter equal to that of the suture material. The suture material may be selected from filaments, threads, yarns, etc. The suture material may be biocompatible and / or bioabsorbable. In some embodiments, discrete attachment sites may have a diameter between about 1 micrometer and 10 millimeters.

[0070] Embodiments of this disclosure may include an anti-adhesion layer attached to a tissue scaffold material, wherein the anti-adhesion layer may be attached to the scaffold via a weave of material that bonds the layers together. In some embodiments, the weave of the material may include a suture pattern, which may include at least one filament, thread, or yarn comprising an anti-adhesion material. It should be understood that the suture pattern described herein may be a pattern of discrete attachment sites that can be arranged in a general pattern. A suture pattern may refer to a pattern of discrete attachment sites between two layers.

[0071] Embodiments of this disclosure may include stitch patterns, wherein the pattern may consist of multiple straight lines oriented along one or more axes of the material. In some embodiments, a subset of straight lines oriented along different axes of the material may intersect at least a portion of the multiple straight lines, which may form a grid pattern. Stitch patterns may include various designs and patterns. Some embodiments may include only multiple parallel lines. Some embodiments may include stitch patterns comprising multiple lines arranged in a zigzag pattern. Other embodiments may include stitch patterns comprising stitch patterns of discrete regions with different patterns.

[0072] Embodiments of this disclosure that include a subset of zigzag lines in a stitch pattern may include different amplitudes, frequencies, or amplitudes and frequencies relative to another subset of the zigzag lines in the stitch pattern.

[0073] Some embodiments may include a stitch pattern having multiple lines arranged in a pattern including multiple curves. Some embodiments may include a waveform pattern such as a sine wave, or an oscillating line pattern. A subset of lines in the curve pattern may have different amplitudes and frequencies, or amplitudes and frequencies, relative to another subset of lines in the curves of the stitch pattern. Some embodiments may include a continuous stitch pattern, while others may include breaks or interruptions along one or more locations along the pattern. The stitch pattern may include a corner lockstitch pattern.

[0074] Some embodiments of this disclosure may include a stitch pattern composed of filaments such as threads, yarns, etc. In one embodiment, the stitch pattern may include a single filament. In one embodiment, the stitch pattern may include an upper filament and a lower filament. The upper filament may have a larger diameter than the lower filament, may have a substantially the same diameter as the lower filament, or may have a smaller diameter than the lower filament.

[0075] The upper and lower filaments may include any one or more of chitosan, hyaluronic acid, icodextrin, fibroin, poly(L-lactide-co-D,L-lactide) / polylactic acid, polytetrafluoroethylene, or oxidized regenerated cellulose, including any blends thereof or polymers thereof.

[0076] Typically, the attachment between the first and second layers can be configured to flexibly attach the two layers such that the combination of the two layers does not change the compliance by more than a nominal amount (e.g., 10% or less). This flexible attachment configuration can be achieved at least in part by including unattached regions between discrete attachment sites, such that the first and second layers can move or slide relative to each other when the material is bent, pulled, or manipulated.

[0077] The density of discontinuous attachment sites can be uniform or non-uniform. As mentioned above, in some embodiments, discontinuous attachment sites can be distributed in a pattern such as a grid or overlapping grids. In some embodiments, the density of attachment sites can be relatively low. For example, the density of attachment sites can be less than about 10 attachments / mm. 2 .

[0078] In embodiments of this disclosure, wherein a second layer is attached to a first layer, the second layer may comprise one or more sheets of anti-adhesion layer material, such as ECM, silicone, polyurethane, or polylactic acid (PLA). In some embodiments, attachment of the second layer to the suture pattern described herein may provide one or more sheets of anti-adhesion layer material movable relative to the substrate. For example, the one or more sheets may be bonded to the first layer by a suture pattern comprising at least one filament. The filament material may be formed of any suitable material, including polymeric materials. In some embodiments, the filament material may be formed of the same material as the anti-adhesion layer sheet.

[0079] In some embodiments, the attachment suture pattern securing the first layer to the second layer may include a plurality of suture islands, whereby at least one filament may be positioned at discrete locations around the material. In some embodiments, the tissue scaffold material may include areas not attached between the suture islands (e.g., without a suture pattern or filament). Some embodiments may include a suture attachment pattern having a plurality of straight lines oriented along one or more axes of the substrate.

[0080] In some embodiments, a subset of straight lines oriented along different axes of the substrate may intersect at least a portion of multiple straight lines, thereby forming a grid pattern on at least a portion of the material. The stitch pattern may include various designs and patterns. Some embodiments may include only multiple parallel lines. Some embodiments may include a stitch pattern comprising multiple lines arranged in a zigzag pattern. Other embodiments may include stitch patterns comprising discrete regions with different patterns.

[0081] Embodiments of this disclosure that include a subset of zigzag lines in a stitch pattern may include different amplitudes, frequencies, or amplitudes and frequencies relative to another subset of the zigzag lines in the stitch pattern.

[0082] Some embodiments may include a stitch pattern having multiple lines arranged in a pattern including multiple curves. Some embodiments may include a waveform pattern such as a sine wave, or an oscillating line pattern. A subset of lines in the curve pattern may have different amplitudes and frequencies, or amplitudes and frequencies, relative to another subset of lines in the curves of the stitch pattern. Some embodiments may include a continuous stitch pattern, while others may include breaks or interruptions along one or more locations along the pattern. The stitch pattern may include a corner lockstitch pattern.

[0083] Some embodiments of this disclosure may include a stitch pattern composed of filaments such as threads, yarns, etc. In one embodiment, the stitch pattern may include a single filament. In one embodiment, the stitch pattern may include an upper filament and a lower filament. The upper filament may have a larger diameter than the lower filament, may have a substantially the same diameter as the lower filament, or may have a smaller diameter than the lower filament.

[0084] The upper and lower filaments may include any one or more of chitosan, hyaluronic acid, icodextrin, fibroin, poly(L-lactide-co-D,L-lactide) / polylactic acid, polytetrafluoroethylene, or oxidized regenerated cellulose, including any blends thereof or polymers thereof.

[0085] In some embodiments, the one or more anti-adhesion sheet materials may include any one or more of chitosan, hyaluronic acid, icodextrin, fibrin, poly(L-lactide-co-D,L-lactide) / polylactic acid, polytetrafluoroethylene, or oxidized regenerated cellulose, including any combination or polymer thereof.

[0086] The above disclosure provides a material primarily comprising attaching an anti-adhesion layer to a tissue scaffold; however, the above disclosure can also be applied to attaching a tissue scaffold to a microstructured surface. In some embodiments, all three components (the first layer, the second layer, and the microstructured surface) can be provided simultaneously in a single attachment process. In some embodiments, the microstructured surface can also be incorporated into any layer disclosed herein. Although this disclosure can provide a microstructured layer, this layer can be integral with or incorporated into another layer.

[0087] Embodiments of this disclosure may include microstructured surfaces attached to or integrated into a tissue scaffold material. In some embodiments, the tissue scaffold material may consist of three layers, including a first layer, a second layer, and a microstructured layer. The microstructured layer may be configured to provide a material capable of maintaining positioning and / or anchoring to a surface.

[0088] When the interfacial volume between two surfaces comprises both a high-surface-tension material and a low-surface-tension material, interfacial adhesion can form between the two surfaces. This interfacial adhesion can be induced by the Wenzel-Cassie interface, which is attractive upon formation. The attractive aspect arises when the composition of the interfacial volume is organized to maximize the contact between the liquid interface and the microstructured surface. In a sense, the interfacial volume can diffuse into the microstructure, then be pinned within it, generating an adhesive effect or force.

[0089] While pinning forces may be small in any microscopic region of the interface, they can be surprisingly large in macroscopic regions.

[0090] Intersurface adhesion can take many forms, but it typically originates from the interaction of the spatially varying surface energy of a microstructured surface with the surface energy of various liquids and solids present on the contact surfaces. Often, combinations of multiple types of intersurface adhesion occur in real-world situations. A condition known as "stick-slip" may be associated with the formation of Schallamach waves. Stick-slip minimizes the destructive interactions between surfaces undergoing relative displacement. Stick-slip is characterized by the temporal distribution intervals of the interfacial states, including alternating conditions of near-zero adhesion and near-infinite adhesion.

[0091] Stick-slip can depend on the difference between shear force and peel force. When the target substrate is placed under sufficient compressive force, it can bend, producing orthogonal displacement, which can then lead to a peeling mode of detachment. De-adhesion can cause lateral translation (slippage), which can eliminate the orthogonal displacement, and the shear force is re-established. This phenomenon may be the cause of some of the repositioning aspects of the embodiments disclosed herein.

[0092] For example, in some embodiments, the microstructured surface can be designed with Schallamach waves, which may include design features such that orthogonal displacement of the target surface does not change the interfacial distance or volume, thus not generating peeling forces and preventing slippage. In embodiments where the target surface may experience compression waves from an external source, the periodic distribution of the gripping surface can be used to transmit the compression waves without altering the relationship between the microstructured surface and the target surface.

[0093] In some embodiments, the micro-features on the microstructured surface can be ordered, typically periodic, and exist at many “stacked” levels. When microstructures are formed periodically at several size scales, they can be said to be hierarchical and can have a fractal dimension greater than 2.

[0094] refer to Figure 1The microstructured surface 100 may include a branching ratio defined by three hierarchical micro-features 102, 104, and 106. In some embodiments, the center-to-center spacing (pitch) of the first micro-feature 102 may be 1000 micrometers, the second micro-feature 104 may be 100 micrometers, and the third micro-feature 106 may be 10 micrometers. The third micro-feature 106 may be disposed on the top surface 108 of the second micro-feature 104. The second micro-feature 104 may be disposed on the top surface 110 of the first micro-feature 102. Thus, line 112 may define a branching ratio, wherein the length 114 may be 10 times the length 116, and wherein the length 116 may be 10 times the length 118. Line 112 may define a fractal dimension of 2.1 = 2 + continuous length ratio, where 2 is the dimension of the surface without microstructure.

[0095] In some embodiments, the fluid with the lowest surface energy can be a gas with zero surface energy. (Reference) Figure 2A and Figure 2B A Wenzel-Cassie interface 200 can be formed between the contact surface 202 and the microstructured surface 204. The interface 200 can consist of a first liquid 206 and a second liquid 208. In some embodiments, the microstructured surface 204 can organize the interface 200, which is typically uniform in the first and second liquids 206, 208, around hierarchical microstructures 210, 212. This organization can cause the fluids 206, 208 to hierarchically segment into spatial local domains 214, 216. The total energy of the system may be reduced due to this organization, which may generate adhesive forces. The energy required to disrupt the Wenzel-Cassie interface may be approximately equal to the energy required to return the interface 200 to a uniform state.

[0096] Embodiments of this disclosure may include a first layer, a second layer, and a third layer, wherein the second and third layers are attached to the first layer. In some embodiments, the first layer is attached to the second layer on a first side of the first layer, and the first layer is attached to the third layer on a second side of the first layer. In some embodiments, the first layer may comprise a tissue scaffold material. The second layer may comprise an anti-adhesion composition. The third layer may include a microstructured surface. In some embodiments, the third layer may be combined with the first or second layer such that the microstructured surface is integral with the first or second layer.

[0097] In some embodiments, the third layer may include hierarchical microstructures, with the first micro-feature having the second micro-feature thereon. In some embodiments, the third micro-feature may be disposed around the second micro-feature. This successive "stacking" of micro-features may include additional micro-features disposed around previous micro-features. In some embodiments, the third layer, including a microstructured surface, may be configured to provide an adhesive effect, such that the combined layers can temporarily adhere to a target surface. In some embodiments, the third layer may include a microstructured surface that provides a fixation effect, such that the combined layers can be fixed relative to the target tissue for a more permanent time period and in the absence of a curing agent or hardener, or otherwise positioned unsupported relative to the target tissue.

[0098] This document also describes methods for preparing embodiments of the disclosed materials. Methods may include, for example, attaching an anti-adhesion layer material via one or more stitch attachment patterns to secure the anti-adhesion material to the scaffold material described or illustrated herein. In some embodiments, such methods may include weaving or stitching filament material such that one or more sheets comprising the anti-adhesion layer material can be attached to the scaffold material described or illustrated herein. In some embodiments, the scaffold may include a first pattern woven, stitched, or embroidered thereon using filament material having greater bioabsorbability than the scaffold material. For example, in some embodiments, the mesh may have high compliance properties in its natural state but may have a compliance-limiting stitch pattern woven, stitched, or embroidered thereon using filament material with lower compliance. The mesh may then be attached to the anti-adhesion layer via an attachment pattern of discrete attachment sites (e.g., sutures).

[0099] It will be understood by those skilled in the art that embodiments of this disclosure can be advantageously used for tissue repair. For example, methods for inhibiting adhesions and positioning and securing materials as implants are disclosed herein, all aspects of which are understood to be central in tissue repair or reconstruction in a subject in need. Such methods typically include implanting an implant or scaffold material comprising an anti-adhesion layer and a positioning / fixation layer, wherein the positioning / fixation layer may be sutured or embroidered into the implant or scaffold material. In some embodiments, the implant or scaffold material may include one or more anti-adhesion layers sutured to the implant or scaffold at a location within the body of a subject requiring tissue repair or reconstruction.

[0100] As used herein, “tissue” can be any tissue in the body, including soft tissue. In some methods, the tissue may include a hernia, such that the implant or soft tissue repair graft is used to repair the hernia. Once implanted, the anti-adhesion layer can inhibit adhesion between the in vivo tissue and the implant or scaffold, and can further inhibit adhesion between adjacent tissues adjacent to the implant in the body. It should be understood that fixation of the implant includes maintaining the positional association between the soft tissue defect and the scaffold. In some embodiments, the fixation portion can transfer restraint to the scaffold before the tissue grows inward into the scaffold. In some embodiments, the fixation portion can continue to provide support even after the scaffold has fully integrated into the body. It should be understood that the term “subject” can include humans or other animals (e.g., veterinary animals, non-human animals, etc.).

[0101] Some embodiments of this disclosure may include hernia repair grafts. In some embodiments, a hernia repair graft may consist of a first layer comprising a tissue scaffold layer, a second layer comprising an anti-adhesion layer, and a third layer for positioning or securing the graft to tissue, wherein the second and third layers are flexibly attached to the first layer in a pattern of discrete attachment sites. In some embodiments, the pattern of discrete attachment sites may alter the compliance of the stacked first, second, and third layers by less than 10%, and adjacent regions of the first, second, and third layers between discrete attachment sites may slide relative to each other.

[0102] In some embodiments, a hernia repair graft may include a first layer comprising a knitted, non-bioabsorbable mesh and a first pattern embroidered into the mesh with a bioabsorbable material. The hernia repair graft may also include a second layer comprising at least one anti-adhesion sheet attached along the first layer to discrete attachment sites such that adjacent discrete attachment sites are separated by a distance between 1 mm and 20 mm. The hernia repair graft may also include a third layer comprising at least one microstructured material sheet attached along the first layer to discrete attachment sites such that adjacent discrete attachment sites are separated by a distance between 0.1 mm and 10 mm, and adjacent regions of the first, second, and third layers between the discrete attachment sites are slidable relative to each other.

[0103] In some embodiments of this disclosure, a hernia repair graft may include a first layer attached to a second layer and a third layer attached to the first layer. The second layer may include an anti-adhesion layer formed of absorbable material and a first pattern sutured into the second layer with bioabsorbable material. The first layer may include a scaffold material comprising a plurality of extracellular matrix (ECM) sheets. The third layer may include a positioning / fixation material comprising hierarchical microstructures for positioning the material and tissue-penetrating barbs for fixing the material. The third layer may have at least a portion composed of polypropylene. The second and third layers may be flexibly attached to the first layer with a second pattern of discrete suture attachment sites, wherein the second pattern of the discrete suture attachment sites has a lower density than the first pattern sutured into the anti-adhesion sheet. In some embodiments, adjacent discrete attachment sites may be separated by a distance of 1 mm to 20 mm. The hernia repair graft may also include a third layer comprising at least one microstructured material sheet attached along the first layer to discrete attachment sites such that adjacent discrete attachment sites are separated by a distance between 0.1 mm and 10 mm, and adjacent regions of the first, second, and third layers between the discrete attachment sites can slide relative to each other.

[0104] In any of the graft embodiments disclosed herein, a first pattern (e.g., a reinforcement pattern) may be applied to a third layer, wherein the third pattern (e.g., an attachment pattern) may be a third suture pattern for discrete attachment sites. In the plane of the third layer, the third pattern may have a lower density than the first pattern.

[0105] Typically, tissue scaffolds can be composed of meshes. These meshes can be knitted, woven, or shaped. The mesh can be formed from polypropylene, polytetrafluoroethylene (PTFE), nylon, polyester, or combinations thereof. The mesh can have an opening diameter between 1 mm and 10 mm. The mesh can be formed from warp-knitted filaments with diameters between 1 micrometer and 250 micrometers. For example, the mesh can be formed from warp-knitted filaments with diameters between 3 micrometers and 100 micrometers. The mesh can be formed from multiple fibers (multifilaments) or monofilaments woven together. In some variations, multifilament fibers (used in either or both of the mesh and suture material) may be preferred because they are stronger.

[0106] Typically, the positioning / fixation layer may comprise a polymer sheet with windows to allow tissue to grow from the tissue surface to the scaffold layer. The positioning portion of the layer may include a microstructured surface. The microstructures may be hierarchically arranged with a fractal dimension greater than 2. Generally, the higher the fractal dimension, the greater the positioning strength. The positioning portion of the layer can provide placement of the implant into the tissue, which is beneficial for surgical placement, especially laparoscopic placement.

[0107] In some embodiments, the third layer may include a fixing aspect that can intrusively engage the contact surface. Now refer to Figure 3A A soft tissue graft 300 is shown. The soft tissue graft may include a positioning / fixation layer 301. In some embodiments, the tissue bonding structure 302 may be a tapered column 303. In some embodiments, the tissue bonding structure 302 may be a barbed micro-feature 304. The barbs 305 can be used for invasively bonding to a target surface 312; however, the bonding of the barbs can reduce the repositionability of the soft tissue graft 300. Thus, the positioning / fixation layer 301 may be configured such that the barbed micro-feature 304 is positioned at a greater distance 306 from the target surface 312 relative to another barbed micro-feature 304. A plurality of barbed micro-features 304 may be configured such that a subset of the plurality of barbed micro-features has an increasing distance from the target surface 312. This configuration with various distances from the target surface 312 allows for an increasing number of barbs 305 to bond to the target surface over time. In some embodiments, the tissue bonding structure 302 may include a microstructure ring 308. The microstructure ring 308 can limit the depth of invasive engagement between the tissue-attaching structure 302 and the target tissue 312. In some embodiments, the microstructure ring 308 can be configured such that the ring provides a weak stop, which can be overcome by additional pressure applied by the clinician, thereby providing greater fixation of the soft tissue graft 300 to the target surface 312 at the desired time.

[0108] In some embodiments, the positioning force may be provided by microstructures 314 and 316 and an interface volume 318 comprising at least two fluids 320 and 322.

[0109] In some embodiments, the positioning-fixation layer may be fenestrated. The fenestration can be of any actual size relative to the dimensions of the soft tissue repair graft 300. An important consideration is that the positioning and fixation strength of the soft tissue graft 300 is proportional to the surface area of ​​the microstructured surface 301. Therefore, for a given fractal dimension and barb density, a larger area ratio results in greater positioning and fixation strength.

[0110] For surgical procedures and related implants, the center of the implant is first located, and the rest of the implant is arranged to fit this initial position, with the area ratio decreasing radially from the center of the implant.

[0111] For surgical procedures and related implants that primarily locate the periphery of the implant, the area ratio can be maximized near the periphery. The area ratio can be discretized into localized areas with high area ratios, which can mimic conventional pinning and / or suturing procedures. In some embodiments, some areas may be filled only with barbs, and other areas may be filled only with barbless microstructures.

[0112] In some embodiments of this disclosure, the distribution of positioning structures (microstructures) and fixation structures (barbs) can typically be different within soft tissue grafts or medical implants. Similarly, in some embodiments, the location and density of barbs along tissue engagement features can vary across the entire surface of the positioning / fixation layer.

[0113] In some embodiments, the positioning / fixation layer may further include a substrate surface on which microstructures and / or tissue bonding structures are disposed. In some embodiments, the microstructures and / or tissue bonding structures are integral with the substrate surface, and therefore may be composed of the same material / composition. In some embodiments, the microstructures and / or tissue bonding structures may be disposed around the substrate surface and composed of a different material than the substrate surface. In one embodiment, the microstructures and / or tissue bonding structures may be imprinted onto a substrate material. In some embodiments, the tissue bonding structures may include metal or hard plastic barbs applied at selected locations on the imprinted substrate.

[0114] Now for reference Figure 3B The positioning / fixation layer 301 may include a hierarchical microstructure 310. This hierarchical microstructure may include a first microfeature 314 and a second microfeature 316, wherein the second microfeature is disposed around the first microfeature. In some embodiments, the first microfeature may have a larger size than the second microfeature. In some embodiments, the positioning / fixation layer may include a tissue-bonding structure 302. The tissue-bonding structure 302 may include a barbed end 305 having a microstructure ring 308 disposed around a tapered column. As previously disclosed, the microstructure ring 308 may serve as a weak stop to initially prevent further insertion of the tissue-bonding structure 302 into the target surface 312. The microstructure ring 308 may be inserted into the target surface 312 using additional pressure or force. In some embodiments, the positioning force may be provided by the hierarchical microstructures 314, 316 and an interface volume 318 comprising at least two fluids 320, 322. In some embodiments, the fixation force may be provided by the tissue-bonding structure 302. The soft tissue graft 300 may be initially placed around the target surface 312, and the initial positioning capability of the soft tissue graft may be maintained by the hierarchical microstructure 310. Once the position of the soft tissue graft 300 is acceptable to the clinician, or within certain requirements / parameters, the soft tissue graft can be fixed in place by applying pressure to the graft, thereby attaching the tissue bonding structure 302 to the target surface 312.

[0115] Now for reference Figure 4Various examples of tissue engagement structures 400 with barbed designs are given. Example 4A includes a tapered structure 402 with a circular cross-section. Surface 403 may be provided with circularly wrapped, downward-curved protruding barbs 404. Example 4B includes a hollow cylinder 406 with an engaging internal structure 408. The outer surface 409 of the hollow cylinder 406 may include at least one hole 410 that allows fluid trapped in the interior 412 to be drained, allowing tissue to enter the interior. A cut surface 414 allows tissue to easily enter the interior 412. Example 4C includes a tapered structure 416 with a circular cross-section. Discrete barbed protrusions 418 are axially distributed. Adjacent barbs may be offset from each other along the height of the structure. Example 4D includes a tapered structure 420 with a circular cross-section. Continuous barbed protrusions 422 may be helically arranged around the surface of the structure. Example 4E includes a blade-shaped cross-section 424. Cross section 424 may be downwardly curved, with discrete barb protrusions 426 disposed thereon on one side, and a cut surface 428 on the opposite side. Example 4F includes a conical structure 430 with a grooved surface 434 and a conical structure with a cut point 432. The valley 436 of the groove may include barb protrusions 438. Example 4G includes a conical structure 440 with a circular cross section. The surface of the conical structure 440 may include flexible barb protrusions 442 disposed thereon. In some embodiments, the flexible barb protrusions 442 may include a curved profile. Example 4H includes a circular arrangement of flexible fibers 444 that can be radially spread when pressed against a surface. Example 4I includes a hollow cylindrical structure 448 having a central solid conical structure 450 with a circular cross section. Structure 448 may include an outer wall 452, which may include barb protrusions 454 disposed on an inner portion of the outer wall. Example 4J includes a blade-like structure 456 with a recessed axial groove 458. Structure 456 may include a cut edge 460 thereon having barbed protrusions 462. Example 4k includes a structure 464 having two forked teeth. The first forked tooth 466 may have a blade-like downward curved structure. It may also include barbed protrusions 468 thereon. The second forked tooth 470 may include a tapered cylindrical pin joint structure. Example 4L includes a needle-like structure 472 thereon having rigid fibrous barbed protrusions 474. The barbed protrusions 474 may be branched, with each barb's branching node increasing toward the base 478 of the structure 472.

[0116] The subject matter disclosed herein is further illustrated by the following specific, but non-limiting, examples. The following embodiments may include data compilations representing data collected at different times during the development and experimentation of the subject matter of this disclosure. The following examples are intended to be illustrative, not exhaustive or limiting.

[0117] Example 1

[0118] Soft tissue repair grafts fixed with Wenzel-Cassie

[0119] refer to Figure 5 The image illustrates a soft tissue repair graft 500. In some embodiments, the soft tissue repair graft 500 may include an anti-adhesion layer 502, which may consist of an absorbable layer with a thickness between 5 and 1000 micrometers. The absorbable layer may be made of a biocompatible material, such as polylactic acid, polycaprolactone, polyester polyurethane, etc. The soft tissue repair graft may also include a tissue scaffold layer 504, which may be attached to the anti-adhesion layer 502 via connection sites 506. The connection sites 506 may be continuous or discrete. In some embodiments, the connection sites 506 may be composed of an adhesive. In some embodiments, the connection sites may consist of a solution of a polymer comprising the anti-adhesion layer 502 and strands 508 of the tissue scaffold layer 504 cured together. The tissue scaffold layer 504 may be continuous or woven, for example, as shown in the image. Figure 5 The mesh shown. In some embodiments, the strands 508 of the tissue scaffold layer 504 may include at least a portion of the strand surface, which is coated and different from the connection sites 506. In some embodiments, the tissue scaffold layer 504 may include a non-absorbable material, such as polypropylene, polyester, polyurethane, etc. In some embodiments, the tissue scaffold layer 504 may include an absorbable material. In some embodiments, the soft tissue graft 500 may include a microstructure layer 510, which can be repositioned on a target surface 512 without damaging the target surface. In some embodiments, the target surface 512 may be living tissue. The microstructure layer 510 may include discrete islands or may be a continuous layer. The microstructure layer 510 may include a base layer 514, and microfeatures 516 may be disposed on the base layer 514. In some embodiments, the microfeatures 516 may be formed directly on the tissue scaffold layer 504. The microstructure layer 510 may be attached to the tissue scaffold layer 504 via different connections 518 or using the same connections 506 disclosed in attaching the anti-adhesion layer 502 to the tissue scaffold layer 504.

[0120] In some embodiments, microfeature 516 may be composed of hierarchical microstructures 519. For example, in some embodiments, the hierarchical microstructure may include a first microstructure as a sinusoidal pattern 520. The sinusoidal pattern 520 may have an amplitude in the range of 100 to 1000 micrometers. Additionally, the sinusoidal pattern 520 may have a pitch in the range of 100 to 1000 micrometers. In some embodiments, a second microstructure in the form of a column 522 may have a diameter in the range of 10 to 100 micrometers, a pitch in the range of 10 to 100 micrometers, and a height in the range of 10 to 300 micrometers. The second microstructure may be disposed around the first microstructure. In some embodiments, the second microstructure column 522 may include a cross-section of a circle, square, triangle, rectangle, or any other polygonal shape. In some embodiments, a third microstructure may be disposed around the second microstructure 526. The third microstructure 526 may be smooth or... Figure 4 The design shown is invasively coupled to the target surface 512. Various degrees of target surface localization can be achieved by varying the degree of penetration (including no penetration) without compromising the localization capability of the Wenzel-Cassie type.

[0121] In some embodiments, the microstructure layer 510 may be composed of one of the materials previously listed in this disclosure. In some embodiments, the microstructure layer 510 may be composed of any suitable implantable and / or biocompatible material, including metals and high-hardness materials such as PET. Embodiments that may include a substrate portion 514 may include a substrate portion composed of an elastomeric (low-hardness) material. In some embodiments, the microstructure 516 disposed on the substrate portion 514 may be a high-hardness material. This combination of the substrate portion 514 and the microstructure 516 allows the microstructure layer 510 to conform to the target surface 512 to the greatest extent possible.

[0122] It should be understood that although the examples given herein relate to specific aspects of repairing soft living tissue, embodiments of this disclosure are applicable to any application where defects in the target surface will be reinforced and / or supported.

[0123] By way of example, the following microstructures are used on the soft tissue grafts of the present invention.

[0124] Table 1

[0125] shape arrangement width spacing high Layer 1 sine triangle 750μm 750μm 220μm Layer 2 Groove Circular triangle 35μm 45μm 45μm Layer 3 round triangle 3μm 6μm 4μm

[0126] When placed on animal tissue, this soft tissue graft resists displacement under a shear force of 258 + / - 17 g / cm² surface contact.

[0127] Example 2

[0128] A hernia repair device with flexible positioning that can be repositioned.

[0129] Now for reference Figure 6 The diagram illustrates a soft tissue repair device. The soft tissue repair device 600 may include an anti-adhesion layer 602 comprising polylactic acid, a tissue scaffold layer 604 comprising a polypropylene mesh coated with polyurethane, and a third microstructure layer 606 comprising microstructured polylactic acid. The microstructure layer 606 may be composed of hierarchical micro-features, including a first cylinder 608 having a diameter in the range of 10 to 100 micrometers, a spacing in the range of 10 to 100 micrometers, and a height in the range of 30 to 120 micrometers, and a second circular cylinder 610 disposed on the first cylinder 608. The second cylinder 610 may have a diameter in the range of 10 to 50 micrometers, a spacing in the range of 10 to 50 micrometers, and a height in the range of 30 to 80 micrometers.

[0130] Performed with and without applying normal force. Figure 6 The test described in this embodiment was conducted with an applied normal force of 50 g / cm. 2 Tests were conducted under shear and normal forces (peeling).

[0131] Shear force setting:

[0132] Immerse two pieces of beef of uniform thickness (approximately 2cm) in water and place them side by side. With initial hand pressure, place the composite mesh side down on top of each piece of meat. Ensure no gaps are created.

[0133] One piece of meat is sewn at its corners and then sewn in the middle to a rigid plastic sheet. Another piece of meat is sewn at five equidistant points along its distal edge. The five sutures are pulled together and secured to a thick rope such that the force in each suture is approximately equal when the rope is pulled. The rope is traveled around a pulley to a 90-degree position and attached to the head of the Instron. The pulley and meat are aligned so that the tension generated on the rope is in the plane of the meat. The meat is kept moist by randomly spraying it with salt water. Experiments that generate torque in the meat are discarded. The head speed is 5 cm / min. The force per unit area of ​​meat-mesh contact is calculated.

[0134] In the normal lever arm of the study, another plastic sheet was placed on top of the meat / mesh composition and weighed uniformly to 50 g / cm². 2 .

[0135] In the arm studied, which contained only a mesh, the mesh was sutured at four locations on each piece of meat, for a total of eight sutures. The bite length was approximately 1 cm.

[0136] Normal force setting:

[0137] In addition to pulling a third piece of meat through the gap between the two pieces, one of the pieces is sewn shut, similar to a shear force setting. The tension is provided by the sutures passing through the mesh. No normal force is applied at the gap.

[0138] Suture: Prolene 5-0.

[0139] Research Group 1: Shear force without normal force.

[0140] Research Group 2: Shear Force and Normal Force.

[0141] Research Group 3: Shear force of sutures only

[0142] Research Group 4: Normal force that applies normal force.

[0143] result:

[0144]

[0145]

[0146] Normal intra-abdominal pressure

[0147] N=10, mesh area: 8cm×16cm, force in grams.

[0148] Example 3

[0149] Two-stage soft tissue repair device

[0150] In many applications of this disclosure, it may be desirable to place the device on a target surface, allow the device to temporarily adhere, reposition the device to a more desired location, and then activate a more permanent fixation of the device to the target surface. It should be understood that "more permanent" does not mean irreversible fixation, but rather a fixation that lasts longer than temporary adhesion.

[0151] Now for reference Figure 7 The two-stage soft tissue repair device 700 may include a polypropylene mesh 702 bonded to a peripheral microstructure layer 704. The peripheral microstructure layer may include a first microstructure 706, which includes a tip portion 708, a barb portion 710, and a stop portion 712. When the device 700 is positioned on a target surface 714 using slight pressure, the device 700 can invasively engage the target surface, with only the tip portion 708 engaging the target surface. This engagement provides adhesion between the device 700 and the target surface, but adhesion allows for easy repositioning of the device. When additional force is applied to the device 700 in direction 716, the barb 710 can invasively engage the target surface 714 and provide more permanent fixation, causing the device to adhere in a non-repositionable location. The stop 712 can be used to limit the depth to which the barb 710 can be allowed to engage the target surface 714.

[0152] Example 4

[0153] Wenzel-Cassie Dual-Layer Soft Tissue Repair Device

[0154] Now for reference Figure 8A and Figure 8B A two-stage soft tissue repair device 800 is shown. This two-stage soft tissue repair device 800 may include a polypropylene mesh 802 bonded to a microstructure layer 804, the microstructure layer 804 including a Wenzel-Cassie microstructure 806 and a target penetration structure 808. The Wenzel-Cassie structure 806 may consist of graded composite material columns 810. The target penetration structure 808 may include columns 811 with barbs 812. Under light pressure, the target surface 814 ( Figure 8A It can remain in a non-deformable state, such as its natural state. When greater pressure is applied to the device 800, the target surface 814 can deform, allowing the target surface to deform around the Wenzel-Cassie structure 806 and contact the target penetration structure 808, as shown at position 816. Figure 8B When the pressure is released from the device 800, the device and the target surface are fixed, so that the device will remain in place for a considerable period of time, approximately several hours, days and / or weeks.

[0155] Example 5

[0156] Soft tissue devices for grasping

[0157] The soft tissue adhesion device includes the microstructure of Example 2, which is bonded to an elastomeric rubber sheet, via a 1 g / cm 2 The device's ability to lift soft tissues such as meat, fruit, and vegetables is tested by measuring shear force under normal force.

[0158] The soft tissue adhesion device was placed on a planar slice of the test specimen, with a weight of 1 g / cm³. 2 The sample is then stretched within the plane of the test specimen. All test specimens are moistened by immersion in water prior to testing.

[0159] result:

[0160]

[0161]

[0162] *If the slip is due to depolymerization of the test analyte, then it is yes; if it is due to microstructure slip, then it is no.

[0163] Therefore, although specific embodiments of the novel and useful microstructured soft tissue grafts of the present invention have been described, these references are not intended to be construed as limiting the scope of the invention as set forth in the following claims.

Claims

1. A soft tissue repair graft, comprising: The first layer comprises a biocompatible, non-bioabsorbable polymeric mesh. The second layer comprises an anti-adhesion polymer material; The third layer includes a microstructured surface, wherein the microstructured surface includes a first microstructured pattern and a second microstructured pattern, the first microstructured pattern being a hierarchical microstructure having at least a first microfeature and a second microfeature, wherein the second microfeature is disposed around the first microfeature, and the second microstructured pattern having a tissue-bonding structure configured to invasively bond to a target surface, wherein the hierarchical microstructure and the tissue-bonding structure are located at different positions on the microstructured surface. The second microstructured pattern is configured to distribute the force across the contact area of ​​the target surface when a force is applied to the soft tissue repair graft to invasively join the second microstructured pattern, and wherein when the soft tissue repair graft separates from the target surface, no individual micro-feature of the second microstructured pattern is subjected to a force greater than 0.025 kg / cm². 3 The force, in which the volume cm 3 It is the volume of the microstructure, and the separation force within it is greater than 25 kg / cm². 2 , of which the surface area is cm 2 It is the contact area between the soft tissue repair graft and the target surface; and The second layer is arranged around the first layer, and the third layer is arranged around the second layer.

2. The soft tissue repair graft according to claim 1, characterized in that, The anti-adhesion polymer material includes a bioabsorbable material, and the microstructured surface includes a non-bioabsorbable polymer material.

3. The soft tissue repair graft according to claim 1, characterized in that, The anti-adhesion polymer material includes a bioabsorbable polymer material, and the microstructured surface includes a bioabsorbable polymer material.

4. The soft tissue repair graft according to claim 1, characterized in that, The anti-adhesion polymer material includes non-bioabsorbable polymer materials, and the microstructured surface includes non-bioabsorbable polymer materials.

5. The soft tissue repair graft according to claim 1, characterized in that, The anti-adhesion polymer material includes non-bioabsorbable polymer materials, while the microstructured surface includes bioabsorbable polymer materials.

6. The soft tissue repair graft according to claim 1, characterized in that, The microstructured surface comprises a first bioabsorbable polymer material, and wherein the first microstructured pattern comprises a second bioabsorbable polymer material, and the second microstructured pattern comprises the first bioabsorbable polymer material.

7. The soft tissue repair graft according to claim 1, characterized in that, The microstructured surface comprises a non-bioabsorbable polymer material, wherein the first microstructured pattern comprises a bioabsorbable polymer material, and the second microstructured pattern comprises the non-bioabsorbable polymer material.

8. The soft tissue repair graft according to claim 1, characterized in that, The third layer includes a window that allows tissue growing from the target surface to penetrate the third layer window and enter the first layer.

9. The soft tissue repair graft according to claim 1, characterized in that, The polymeric mesh includes pores with diameters between 0.5 mm and 6 mm.

10. The soft tissue repair graft according to claim 1, characterized in that, The polymer mesh comprises warp-knitted filaments with diameters between 5 micrometers and 100 micrometers.

11. The soft tissue repair graft according to claim 1, characterized in that, The graft has a content of less than 300 g / m³. 2 Mass per unit area.

12. The soft tissue repair graft according to claim 1, characterized in that, The first layer further includes a first surface and a second surface, wherein the second layer is attached to at least a portion of the first surface of the first layer, and the third layer is attached to at least a portion of the second surface of the first layer.

13. The soft tissue repair graft according to claim 12, characterized in that, The second layer is attached to at least a portion of the first surface of the first layer at attachment sites, the attachment sites including first filaments for attaching the first layer and the second layer together, wherein adjacent attachment sites are spaced between 1 mm and 20 mm apart.

14. The soft tissue repair graft according to claim 13, characterized in that, The third layer is attached to at least a portion of the second surface of the first layer at attachment sites, the attachment sites including second filaments for attaching the first layer and the third layer together, wherein adjacent attachment sites are spaced apart by a distance between 0.1 mm and 10 mm.

15. The soft tissue repair graft according to claim 14, characterized in that, The filaments are bio-absorbable.

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