Microstructured soft tissue grafts

Abstract

A soft tissue repair implant (500) is described that includes an anti-adhesion layer (502), a structural layer, and a placement layer. These layers may be separate or integrated into a single substrate. The term layer is used to distinguish functions of the tissue repair implant, rather than separate layers of material. Separate functional layers may comprise a single plane of material.

Description

[Technical Field]

[0001] The present invention relates to devices and methods in general in the field of soft tissue repair. More specifically, the present invention relates to implant materials for soft tissue repair, comprising an anti-adhesion layer that inhibits the formation of postoperative adhesions, and fixation means that advantageously self-adhere without relying on sutures and distribute fixation force over a wide tissue area. [Background technology]

[0002] Adhesions are fibrous connective tissue bands that form between tissues and organs in the body that are not normally joined together, or that form between tissues and organs in a manner contrary to normal connective tissue anatomy. Adhesions commonly form after surgery in the abdomen or pelvis. In certain cases, adhesions can cause complications such as pain or obstruction of the organs to which they are joined.

[0003] Adhesions generally begin to form immediately after surgery and may continue to develop thereafter. No effective treatment is known to reverse the formation of adhesions. If adhesions lead to complications in the patient, the typical treatment is surgical removal of the adhesions. Therefore, the best approach to managing adhesions is, overall, to prevent their formation or limit their formation.

[0004] While no product is known to effectively reverse adhesion formation, various products exist and are commercially available to prevent it. These products are not 100% effective, but their consistent reduction in adhesion formation is known. These products take many forms, such as gels and absorbable sheets, which are applied to the surgical site and gradually absorbed over several days.

[0005] In the repair of soft tissue defects, sheets, rather than gels, are typically used in combination with reinforcing meshes. Generally, the sheets are attached to the mesh as a composite structure. The sheets may be formed on the mesh or attached via adhesive. Typically, the mesh side of the composite structure faces the soft tissue defect, such as a hernia. It is advantageous to leave a space between the mesh and the anti-adhesion layer to promote tissue infiltration into the mesh and adhesion formation between the mesh and the soft tissue defect. Ideally, the mesh acts as a tissue scaffold, promoting healthy, rather than fibrous, tissue growth between the mesh and the soft tissue defect.

[0006] However, one drawback of current products is that the device needs to be fixed in the correct position using sutures or some similar mechanism. Products such as gels that cannot be mechanically fixed to the tissue defect have the disadvantage of being unable to maintain the gel in the desired position for a reasonably long period of time, such as several hours, several days, or several weeks. Therefore, some products can be fixed well through mechanical means but have poor repositionability and damage surrounding tissue, while others are repositionable but have poor long-term positioning. [Overview of the project] [Problems that the invention aims to solve]

[0007] Therefore, there is a need for a repositionable, self-adhesive reparative graft that can maintain positioning for placement in the desired location but does not require mechanical fixation. Furthermore, there is a need for a device with repositioning properties and adhesive strength suitable for temporarily holding the device in the correct position relative to the tissue at the target tissue site during a surgical procedure, without other support and without requiring solidification or curing of a positioning agent. [Means for solving the problem]

[0008] Various embodiments are described herein in accordance with this disclosure. In some embodiments, a positioning agent may be provided on a soft tissue repair graft. The positioning agent may have sufficient adhesive properties to temporarily hold a surgical soft tissue repair graft in the correct position relative to a target tissue site without other support during a surgical procedure. In some embodiments, a mesh graft may be held in a temporary position until it is permanently fixed to the target tissue site using a device for permanent fixation. In some embodiments, the device for permanent fixation may be sutures, surgical tacks, surgical staples, etc. When applied to a surgical soft tissue repair graft, the positioning agent may exhibit sufficient adhesive properties to hold it in the correct position against gravity without solidifying or hardening, for example, during an implantation procedure.

[0009] Embodiments of the present disclosure may include a permanent fixative provided on a soft tissue repair graft. In some embodiments, a positioning agent may work in conjunction with the permanent fixative to provide an adhesive capacity suitable for maintaining the surgical soft tissue repair device in the correct position relative to a target tissue site during a surgical procedure, without other support. In some embodiments, the soft tissue repair graft may be permanently fixed by completing the action of the fixative by applying a perpendicular force to the soft tissue repair device, in which case the positioning agent and fixative, when applied to the surgical soft tissue repair device, exhibit sufficient adhesive capacity to hold it in the correct position against gravity without the positioning agent solidifying or hardening, for example, during an implantation procedure. In some embodiments, the fixative may provide sufficient fixation to maintain the soft tissue repair device in the correct position over a specified period of time, such that adhesion formation between the target tissue surface and the mesh layer of the soft tissue repair device is limited.

[0010] Embodiments of the present disclosure may include a method for implanting a surgical mesh orthosis, the method of positioning the surgical mesh orthosis relative to the surface of the target tissue by placing a positioning agent between the mesh layer of the orthosis and the surface of the target tissue. The positioning agent may have an adhesive ability to the target tissue that is suitable for temporarily holding the mesh layer in the correct position against gravity without other support and without the positioning agent solidifying or hardening. In some embodiments, the positioning agent may be applied to the surface of the target tissue before positioning the surgical mesh orthosis relative to the surface of the positioning agent. In some embodiments, the positioning agent may be applied to a first surface of the surgical mesh orthosis before positioning the surgical mesh orthosis relative to the surface of the target tissue. The method may further include repositioning the surgical soft tissue orthosis from a first location on the tissue to a second location on the tissue. In some embodiments, the method may further include peeling the surgical soft tissue orthosis from the first location on the tissue and positioning the surgical soft tissue orthosis at the second location on the tissue without damaging or injuring the tissue.

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

[0012] Embodiments of the present disclosure may include a soft tissue repair graft comprising a first layer laminated on a second layer, the second layer being laminated on a third layer. In some embodiments, the first layer may include a mesh formed of a non-absorbable polymer material. The second layer may include a barrier layer formed of an absorbable or non-absorbable polymer material. The third layer may include an absorbable or non-absorbable polymer layer, on which a first pattern of a bioabsorbable material is arranged on the polymer layer, and a second pattern containing the same polymer as the third layer is arranged. In some embodiments, the second layer is a first surface adjacent to the patient's intestine. The third layer may have a first surface adjacent to the tissue containing the defect. In some embodiments, the first surface of the third layer may be in contact with the tissue containing the defect. 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 a vertical attractive force that pulls the tissue-facing side of the third layer toward the tissue with sufficient force to move the second pattern of the third layer into the tissue to fix the soft tissue repair graft in the tissue.

[0013] Embodiments of the present disclosure may include a soft tissue repair graft in which the first layer is non-absorbable, the second layer is absorbable, and the third layer is non-absorbable.

[0014] Embodiments of the present disclosure may include a soft tissue repair graft in which the first layer is non-absorbable, the second layer is non-absorbable, and the third layer is absorbable.

[0015] Embodiments of this disclosure describe a first pattern that generates at least one of the following: a) capillary attraction, b) van der Waals attraction, c) Wenzel-Cassie interface, d) Schallamach capturing interface, e) Eigenwrinkle capturing interface, and f) endophyte surface. It may include a soft tissue repair graft that contains microstructures that can be formed.

[0016] Embodiments of the present disclosure may include a soft tissue repair graft in which the first pattern comprises a hierarchically arranged microstructure having at least two surface subpatterns with different surface energies. In some embodiments, when the first layer is brought into contact with an aqueous wetted surface, the first subpattern may be hydrophilic with a higher surface energy pattern, and the second subpattern may be hydrophobic with a lower surface energy pattern.

[0017] Embodiments of the present disclosure may include a soft tissue repair graft in which the attractive force generated by the first pattern is insufficient to fully move the second pattern into the tissue layer. Such configuration and cooperation between the first and second patterns may allow the soft tissue repair graft to be repositioned without damaging the tissue. In some embodiments, once the ideal graft position is achieved, a small vertical force applied by the physician may engage the second pattern with the tissue layer. In some embodiments, the vertical force applied by the physician may further engage the second pattern, which may already be at least partially engaged with the tissue layer.

[0018] Embodiments of the present disclosure may include a soft tissue repair graft in which the second pattern includes barbs or appropriate tissue adhesion structures that resist removal from the tissue layer when the second pattern is invasively engaged in the tissue layer by the first pattern or an external force.

[0019] Embodiments of the present disclosure may include a soft tissue repair graft in which the second pattern is designed to maximize the distribution of the fixation force of the soft tissue repair graft across the entire contact area after implantation. In some embodiments, the soft tissue repair graft may be separated from contact with the target surface. In some embodiments, the target surface may be in contact with the topmost microfeature of the hierarchical microstructure, but not in direct contact with other microfeatures of the hierarchical microstructure. During the separation process, a single topmost microfeature of the hierarchical microstructure may have a fixation force of 0.025 kg / cm³. 3 It is not necessary to apply a force exceeding this to the target surface, and the volume here (cm 3 ) may be the volume of a single topmost microstructural element. In some embodiments, the force required to completely separate the soft tissue repair graft from the target surface is 25 kg / cm². 2 It is fine if it is greater than the surface area (cm²) 2 ) is the contact between the soft tissue repair graft and the tissue layer. It can be the contact area.

[0020] In some embodiments, during the separation process, a single hierarchical microstructure need not apply a force exceeding 0.025 kg / cm 3 to the target surface, where the volume (cm 3 ) may be the volume of the individually hierarchically arranged microforms.

[0021] In some embodiments, during the separation process, a single non-hierarchical microform need not apply a force exceeding 0.025 kg / cm 3 to the target surface, where the volume (cm 3 ) may be the volume of the microform. In some embodiments, the single microform may be a barb-containing microform. In some embodiments, the barb-containing microform may be the topmost microform of the hierarchical microstructure.

[0022] Embodiments of the present disclosure may include a soft tissue repair graft that includes microstructural elements of a second pattern that are at least 50% longer than the longest microstructural elements of the first pattern.

[0023] Embodiments of the present disclosure may include a soft tissue repair graft in which a third layer is perforated to allow tissue growth from the tissue into the second layer through the third layer.

[0024] Embodiments of the present disclosure may include a soft tissue repair graft in which a first layer is a mesh having continuous air pores with a diameter of 0.5 mm to 6 mm.

[0025] Embodiments of the present disclosure may include a soft tissue repair graft having a mesh formed of warp filaments, the diameter of the filaments being 5 microns to 100 microns.

[0026] Embodiments of the present disclosure may include a soft tissue repair graft having a unit area mass of less than 300 g / m 2 .

[0027] Embodiments of the present disclosure may include a soft tissue repair graft comprising a self-adhesive layer, a device-reinforcement layer, and an anti-adhesion layer, the graft being configured to repair animal tissue. In some embodiments, each layer may be combined with another layer, while each layer maintains its properties. In some embodiments, the soft tissue repair graft may comprise a sheet of absorbable surgical barrier, a sheet of mesh material, and a sheet of adhesive material, the adhesive sheet may comprise at least first and second microstructures. In some embodiments, the adhesive sheet may comprise a plurality of perforations to allow adhesion between the defect tissue surface and the mesh sheet, all three sheets being joined flexibly and allowing lateral displacement of up to millimeters between the sheets.

[0028] Embodiments of the present disclosure may include a soft tissue repair graft in which three joined sheets may include a pre-formed nesting shape that is significantly deviated from the plane.

[0029] Embodiments of the present disclosure may include a soft tissue repair graft comprising two membranes: one membrane configured to promote fixation and tissue endografting, and a second membrane for preventing fixation and tissue endografting. In some embodiments, no liquid adhesive or tissue binder is present on the membranes. In some embodiments, a mesh may be placed between the membranes having an average pore size of 100 to 2000 microns. In some embodiments, the soft tissue repair graft may adhere to the defect tissue layer by contact.

[0030] Embodiments of the present disclosure may include a soft tissue repair graft in which an adhesive blocking gel layer may be placed in place of a membrane layer for fixation and preventing tissue endografting.

[0031] Embodiments of the present disclosure may include a soft tissue repair graft in which a membrane for fixation and tissue endografting may include a hierarchical microstructure portion and a tissue engagement portion.

[0032] Embodiments of the present disclosure may include a soft tissue repair graft in which the self-adhesive layer is a combination of an attractive force generated by a first portion which is a hierarchical microstructure and a second portion which penetrates and maintains itself in the tissue, with the first portion fixing the second portion. [Brief explanation of the drawing]

[0033] [Figure 1] Figure 1 shows an embodiment of a hierarchical microstructure that illustrates the branching ratio. [Figure 2A] Figure 2A shows one embodiment of the Wenzel-Cassie interface between the target surface and the microstructured surface. [Figure 2B] Figure 2B illustrates another embodiment of the Wenzel-Cassie interface between the target surface and the microstructured surface. [Figure 3A] Figure 3A shows an embodiment of the present disclosure having an interface volume between the target surface and the microstructure. [Figure 3B] Figure 3B is a diagram of an embodiment of the present disclosure having an interface volume between the target surface and the microstructure. [Figure 4] Figure 4 shows various embodiments of the microstructure shape. [Figure 5] Figure 5 shows an embodiment of the Wenzel-Cassie soft tissue repair device. [Figure 6] Figure 6 shows an embodiment of a Wenzel-Cassie soft tissue repair device with a flexible layer. [Figure 7] Figure 7 shows an embodiment of a two-level soft tissue repair device. [Figure 8A] Figure 8A shows an embodiment of the Wenzel-Cassie 2-level soft tissue repair device. [Figure 8B] Figure 8B shows an embodiment of the Wenzel-Cassie 2-level soft tissue repair device. [Modes for carrying out the invention]

[0034] One or more examples of embodiments of the Disclosure shown below in this Specification will be described in detail below. Each embodiment and example is provided as a description of the devices, compositions, and materials of the Disclosure, and is not limited thereto. Rather, the following description provides a convenient example for carrying out exemplary embodiments of the Disclosure. In fact, it will be apparent to those skilled in the art that various modifications and changes can be made to the teachings of the Disclosure without departing from the scope or spirit of the Disclosure. For example, features shown or described as part of one embodiment can be used in conjunction with another embodiment to obtain further embodiments. Accordingly, the Disclosure is intended to encompass such modifications and changes as being within the scope of the appended claims and their equivalents. Other objects, features, and aspects of the Disclosure are disclosed in or apparent from the following detailed description. Those skilled in the art should understand that the considerations of the Invention are merely descriptions of exemplary embodiments and are not intended to limit the broader aspects of the Disclosure.

[0035] This section describes exemplary applications of apparatus and methods relating to this disclosure. These examples are provided solely to add context to this disclosure and to aid in its understanding. Therefore, it will be apparent to those skilled in the art that this disclosure can be practiced without some or all of these specific details. In other cases, known process steps are not described in detail to avoid unnecessarily complicating this disclosure. Other applications are possible, and therefore the following examples should not be construed as limiting.

[0036] In the following detailed description, specific embodiments of this disclosure form part of the description and are examples of the description. The accompanying drawings shown are referenced. While these embodiments are described in sufficient detail so that those skilled in the art can practice the invention, these examples are not limiting, and it is understood that other embodiments may be used and modifications may be made without departing from the spirit and scope of this disclosure.

[0037] As used herein, “inter-surface adhesion” may be understood to mean the adhesion formed between a microstructured surface and a contact surface. It is understood that this term may apply to resistance to lateral movement (shear) and resistance to vertical movement (delamination). This term may also apply to attractive forces generated when the surface tension of a liquid and the surface energy of a microstructured surface form an interface in which both energies are minimized.

[0038] As used herein, the term “fractal dimension” applied to microstructured surfaces can be understood to refer to a microstructured surface having a characteristic branching ratio.

[0039] As used herein, the term “Wenzel-Cassie interface” may be understood to mean the interfacial volume formed between two solid surfaces. The interfacial volume may contain at least two fluids with different surface energies. “Fluid” may be understood to mean either a liquid or a gas or both.

[0040] As used herein, the term "surface energy" may be understood to mean the potential energy of surface molecules per unit area of ​​a surface. As used herein, the term "surface energy gradient" may be understood to mean the variation in the spatial derivative of the surface energy along the path through which two surfaces join.

[0041] The organization of interfacial volume at the Wenzel-Cassie interface can be understood as minimizing the surface energy gradients of the hierarchical microstructured surface and liquid component at the Wenzel-Cassie interface. Therefore, the interfacial liquid and surface microstructure can generally be related as pairs, in which case the sum of the surface energy differences of each liquid-microstructure pair can be minimized.

[0042] As used herein, the term “surface tension” may be understood to represent the surface energy of a liquid. Surface tension may be understood as the amount of work that, at a given temperature, acts to increase the area of ​​the liquid surface by unity against the force of surface tension.

[0043] Those skilled in the art will understand that many of these phenomena can occur over time, in some cases within a few minutes. Therefore, a first microstructured surface that generates a 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 is longer than the first microstructure and designed to mechanically engage with the soft tissue, the first microstructure can act to move the second tissue-engaging element to the soft tissue contact surface.

[0044] As used herein, the term "positional strength" means Positioning strength can be understood to include a general meaning representing the self-adhesion properties of microstructured surfaces resulting from Van der Waals interactions. Generally, positioning strength may be associated with the Wenzel-Cassie interface. Positioning strength can be understood as the non-invasive adhesion of contact surfaces characterized by force per unit area. Positioning strength can be quantified in this disclosure in two ways: lateral (shear) adhesion and peel (lift) adhesion.

[0045] As used herein, the term “area ratio” may be understood to mean the porosity of a material, including but not limited to meshes or sheets. The area ratio may be the ratio of the pore area of ​​the material to the total area of ​​the sheet. A sheet with a lower area density may be understood to have increased porosity.

[0046] As used herein, the term “barb” can be understood to mean any micro-form on a surface that is intended to invasively engage with a contact surface. In some embodiments, a barb may be a smooth tapered pillar or a pillar with a scaly structure.

[0047] As used herein, the term “invasive” may be understood to mean that at least a portion of an object penetrates from its surface into the interior.

[0048] This disclosure relates to novel materials for soft tissue repair, particularly for hernia repair. These novel materials may be configured to be suitable for a variety of applications, including, but not limited to, implants such as grafts or soft tissue support devices. These materials may be implanted in patients, such as patients with hernias or patients undergoing hernia repair surgery.

[0049] Advantageously, these materials (and any devices and systems including grafts made from these materials) are particularly well suited for surgical implantation over time in the repair of body wall cavities and may possess advantageous biomechanical or biochemical properties compared to prior art devices and materials. In particular, the compliance of any device permanently fixed to the target tissue should match the compliance of the target tissue to ensure the best possible outcome from surgery and minimize complications. Conversely, the compliance should be sufficient to correct the tissue defect, at least after a period of time. Therefore, many biomechanical features of prior art implant devices are a compromise between biocompatibility and therapeutic effect, and are therefore insufficient.

[0050] Similarly, it is generally true that adding a surgical barrier to the surgical scaffold makes this combined device more rigid. On the other hand, adhesion formation does not typically occur 7 days after surgery. Therefore, the surgical barrier may be absorbable after a certain period of time.

[0051] In some embodiments, the apparatus of the present disclosure may include tissue scaffolding material. In some embodiments, the tissue scaffolding material may be a mesh. The scaffolding material may be a biotextile, a medical textile, or both a biotextile and a medical textile. In some embodiments, the apparatus may also include an anti-adhesion layer which may be attached to the tissue scaffolding material. In some embodiments, the anti-adhesion layer may be located in separate locations on the scaffolding material. "Separate" as used herein may be understood to include the anti-adhesion layer being in separate and distinct locations on the scaffolding material and not covering the approximately entire area of ​​the scaffolding material. In some embodiments, the locations may include an anti-adhesion layer incorporated into the scaffolding material and / or it may be fixed on the scaffolding material. In some embodiments, the anti-adhesion layer may be fixed on the scaffolding material, but at the same time, sliding movement between the scaffolding material and the anti-adhesion layer is still possible in areas adjacent to and / or between the locations of the separate anti-adhesion locations.

[0052] The tissue scaffold may comprise a variety of materials and / or compositions. In some embodiments, the tissue scaffold material may be biocompatible. In some embodiments, the scaffold material may comprise an extracellular matrix, a hernia repair scaffold, a patch, and / or a mesh, etc. The tissue scaffold is, They may be arranged in an open-cell shape and, in some embodiments, may be referred to herein as “mesh.” In some embodiments, the mesh may be biocompatible and / or bioabsorbable and / or non-bioabsorbable. In some embodiments, the tissue scaffold may include a biocompatible film. Throughout this application, tissue scaffold materials may be collectively referred to as the first layer, whether the tissue scaffold consists of many sublayers, such as mesh and film together, or a single layer.

[0053] Embodiments of the tissue scaffold may 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 sewing threads, wires, braids, monofilaments, multifilaments, or combinations thereof. In some embodiments, the filaments may be incorporated into the tissue scaffold material by a method similar to weaving, sewing, or embroidery of filaments. In some embodiments, the incorporation of filaments may include generating a pattern within the scaffold material. The first pattern may be incorporated using the non-bioabsorbable filament material, and the first pattern may be a grid or array of substantially parallel lines. In some embodiments, the first pattern may include a plurality of subpatterns that are offset from each other and / or overlap, which together may create a larger pattern. The filament material forming the first pattern and / or the first pattern as a whole may have lower compliance than the mesh. Thus, the final compliance of the tissue scaffold may be the compliance of the mesh and the first pattern incorporated into the mesh.

[0054] In some embodiments, a second filament may be used together with or in combination with the first filament. The second filament may contain a different filament material than the first filament. In some embodiments, the second filament may be used together 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. Those skilled in the art will understand that any number of filaments and patterns may be used. It will also be understood that a single filament material may be used to produce a single pattern and / or multiple patterns. Furthermore, multiple filament materials may be used to produce a single pattern and / or multiple patterns.

[0055] In some embodiments where the mesh is bioabsorbable, a bioabsorbable filament material may be used. In some embodiments, the bioabsorbable material of the mesh and the bioabsorbable material of the filament may have similar absorbency profiles so that each material is absorbed at approximately the same rate in the same environment. In some embodiments, the filament material may have a different bioabsorbency profile so that the filament is absorbed more quickly or more slowly than the mesh material. In a preferred embodiment, the filament material is absorbed more quickly than the mesh bioabsorbable material.

[0056] Material compliance (e.g., flexural modulus) can refer to the mechanical properties of a material that undergoes elastic deformation under an applied force. It can be understood as the reciprocal of stiffness. Compliance is expressed as a percentage of compliance strain. This can be expressed as follows: Materials that deform easily are considered to have compliance, while materials that resist deformation are considered to have rigidity.

[0057] Some embodiments of this disclosure may include an anti-adhesion layer. In some embodiments, the anti-adhesion layer may comprise one or more layers of anti-adhesion material. The reference to “anti-adhesion layer” does not necessarily indicate that the layer or material is “non-adhesive,” but rather that it refers to a form of “adhesion.” It should be noted that this refers to a layer or material that prevents or substantially limits formation.

[0058] In some embodiments, the anti-adhesion layer may comprise one or more layers of biotextile and / or medical textile. In some embodiments, the material may preferably be an extracellular matrix, such as an extracellular matrix derived from one or more of the dermis, pericardium, peritoneum, intestine, stomach, or foregum. It is understood that in this disclosure, the anti-adhesion layer may also be referred to as the “second layer.” However, the reference to the “second layer” is not limited to the anti-adhesion layer.

[0059] Embodiments of this disclosure may include a first layer (tissue scaffolding material) together with a second layer (anti-adhesion layer) attached to the first layer. In some embodiments, the combination of layers is configured so as not to substantially alter the compliance of the first layer. In practice, this may mean that the compliance of the first and second layers does not change by more than a few percent when attached together, separately or together, as described herein.

[0060] Some embodiments of this disclosure may include a first and second layer attached together, in which case the compliance of the material may be no more than 20% of the compliance of the first layer alone, the second layer alone, or the combination of the first and second layers when they are “laminated” but not attached, if the first and second layers are attached together at separate attachment sites. When “separate” is used herein for “separate attachment sites,” it may be understood to mean that each location where the first and second layers are attached to each other is individually separate and distinct from other locations. Separate attachment sites may be any number of methods for attaching the first and second layers. In some embodiments, separate attachment sites may include stitches connecting the first layer to the second layer. In some embodiments, the sites may be a chemical or polymer adhesive between two layers at small, separate locations, such as an adhesive or glue material that is biocompatible and bonds the first layer to the second layer. The adhesive may be any suitable biocompatible adhesive.

[0061] In some embodiments, the separate attachment area may include a relatively small diameter region, which may have a regular or irregular shape. Embodiments including a stitch as the separate attachment area may include a woven or stitched material between the two layers, and the separate attachment area may have a diameter of the stitch material. The stitch material may be selected from filaments, sewing threads, weaving threads, etc. The stitch material may be biocompatible and / or bioabsorbable. In some embodiments, the separate attachment area may have a diameter of about 1 micron to 10 mm.

[0062] Embodiments of the present disclosure may include an anti-adhesion layer connected to a tissue scaffolding material, the anti-adhesion layer being connected to the scaffolding via a weaving of the material that connects these layers together. It may be. In some embodiments, the weave of the material may include a stitch pattern which may include at least one filament, sewing thread, or weaving thread containing an anti-adhesion material. It is understood that the stitch pattern described herein may be a pattern of separate attachment points which may be arranged in the overall pattern. Thus, the stitch pattern may mean a pattern of separate attachment points between two layers.

[0063] Embodiments of the present disclosure may include a stitch pattern, which may include a plurality of 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 plurality of straight lines to form a grid pattern. The stitch pattern may include a variety of designs and patterns. Some embodiments may include only a plurality of parallel lines. One embodiment may include a stitch pattern comprising a plurality of lines arranged in a zigzag pattern. Another embodiment may include a stitch pattern comprising separate regions having different patterns.

[0064] Embodiments of the present disclosure, which include a stitch pattern having a subset of lines in a zigzag design, may include different amplitudes, frequencies, or amplitudes and frequencies for another subset of lines in the stitch pattern that are zigzag.

[0065] Some embodiments may include a stitch pattern having multiple lines arranged in a pattern containing multiple curves. Some embodiments may include a wave pattern, such as a sine wave, or a vibrating line pattern. A subset of lines in a curve pattern may have different amplitudes, frequencies, or amplitude and frequency with respect to another subset of lines that are curves in the stitch pattern. Some embodiments may include a continuous stitch pattern, while others may include breaks or interruptions at one or more locations along the pattern. The stitch pattern may include a corner-lock stitch pattern. good.

[0066] Some embodiments of the present disclosure may include a stitch pattern which may include filaments such as sewing thread or weaving thread. 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, substantially the same diameter as the lower filament, or a smaller diameter than the lower filament.

[0067] The upper and lower filaments may contain one or more of the following, including chitosan, hyaluronic acid, icodextrin, fibrin, poly(L-lactide-co-D,L-lactide) / polylactic acid, polytetrafluoroethylene, or oxidized regenerated cellulose, any blended combination thereof, or polymers thereof.

[0068] Generally, the mounting of the first and second layers may be configured to mount the two layers flexibly so that the combination of the two layers does not change compliance beyond a nominal value (e.g., 10% or less). This flexible mounting configuration can be achieved, at least in part, by including unmounted areas between the separate mounting points so that the first and second layers can move or slide relative to each other when the material is bent, stretched, or manipulated.

[0069] The density of the individual mounting points may be uniform or non-uniform. As mentioned above, in some embodiments, the individual mounting points may be distributed in a pattern such as a grid or overlapping grids. In some embodiments, the density of the mounting points may be relatively low. For example, the density of mounting points may be about 10 mounting points / mm 2 It can be less than [amount].

[0070] In embodiments of the present disclosure in which 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, attaching the second layer with a stitch pattern as described herein may make one or more sheets of anti-adhesion layer material movable relative to the substrate. For example, one or more sheets may be bonded to the first layer with a stitch pattern comprising at least one filament. The filament material may be formed of any suitable material, including a polymer material. In some embodiments, the filament material may be formed of the same material as the anti-adhesion layer sheets.

[0071] In some embodiments, the attachment stitch pattern that secures the first layer to the second layer may include a plurality of stitch islands, thereby allowing at least one filament to be positioned at a separate location near the material. In some embodiments, the tissue scaffold material may include areas between the stitch islands that are not attached (e.g., without stitch patterns or filaments). Some embodiments may include a stitch attachment pattern having a plurality of straight lines oriented along one or more axes of the substrate.

[0072] In some embodiments, a subset of straight lines oriented along different axes of the substrate may intersect at least a portion of the multiple straight lines, thereby forming a grid pattern on at least a portion of the material. The stitch pattern may include a variety of designs and patterns. Some embodiments may include only a plurality of parallel lines. Some embodiments may include a stitch pattern including a plurality of lines arranged in a zigzag pattern. Other embodiments may include a stitch pattern with separate regions having different patterns.

[0073] Embodiments of the present disclosure, which include a stitch pattern having a subset of lines in a zigzag design, may include different amplitudes, frequencies, or amplitudes and frequencies for another subset of lines in the stitch pattern that are zigzag.

[0074] Some embodiments may include a stitch pattern having multiple lines arranged in a pattern containing multiple curves. Some embodiments may include a wave pattern, such as a sine wave, or a vibrating line pattern. A subset of lines in a curve pattern may have different amplitudes, frequencies, or amplitude and frequency with respect to another subset of lines that are curves in the stitch pattern. Some embodiments may include a continuous stitch pattern, while others may include breaks or interruptions at one or more locations along the pattern. The stitch pattern may include a corner lock stitch pattern.

[0075] Some embodiments of the present disclosure may include a stitch pattern which may include filaments such as sewing thread or weaving thread. 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, substantially the same diameter as the lower filament, or a smaller diameter than the lower filament.

[0076] The upper and lower filaments may contain one or more of the following, including chitosan, hyaluronic acid, icodextrin, fibrin, poly(L-lactide-co-D,L-lactide) / polylactic acid, polytetrafluoroethylene, or oxidized regenerated cellulose, any blended combination thereof, or polymers thereof.

[0077] In some embodiments, one or more anti-adhesion layer sheets may include, but are not limited to, chitosan, hyaluronic acid, icodextrin, fibrin, poly(L-lactide-co-D,L-lactide) / polylactic acid, polytetrafluoroethylene, or oxidized regenerated cellulose, or any combination thereof or polymers thereof, and may comprise one or more of these.

[0078] The above disclosure provides a material that primarily involves attaching an anti-adhesion layer to a tissue scaffold, but the above disclosure may also be applied to attaching a tissue scaffold to a microstructured surface. In some embodiments, all three parts (a first layer, a second layer, and a microstructured surface) may be provided simultaneously in a single attachment procedure. In some embodiments, The microstructured surface may be incorporated into any of the layers disclosed herein. This disclosure may provide a microstructured layer, which may be integrated with or incorporated into another layer.

[0079] Embodiments of the present disclosure may include a microstructured surface attached to or integrated with a tissue scaffolding material. In some embodiments, the tissue scaffolding material may include three layers, including a first layer, a second layer, and a microstructured layer. The microstructured layer may be configured to provide the material with the ability to maintain positioning and / or fixation to the surface.

[0080] Intersurface adhesion can be formed between two surfaces when the interfacial volume between the two surfaces contains both high-surface-tension and low-surface-tension materials. This intersurface adhesion may be caused by a Wenzel-Cassie interface, which is attractive when formed. The attractive aspect occurs when the components of the interfacial volume are organized so that the liquid interface is in maximum contact with the microstructured surface. In a sense, the interfacial volume can diffuse into the microstructure, where it becomes pinned, generating an adhesive effect or adhesive force.

[0081] While the pinning force in any micro-region of the interface may be small, the pinning force across the entire macro-region can be unexpectedly large.

[0082] Surface adhesion can take many forms, but generally arises from the interaction between the spatially fluctuating surface energy of a microstructured surface and the surface energies of various liquids and solids present on the contact surface. In real-world situations, combinations of multiple types of surface adhesion often occur. For example, the state known as "stick-slip" can be associated with the formation of Scharamach waves. The stick-slip phenomenon minimizes destructive interactions between surfaces undergoing relative displacement. Stick-slip can be characterized by a temporally distributed interval between interface states that alternate between near-zero adhesion and near-infinite adhesion.

[0083] Stick-slip can depend on the difference between shear force and delamination force. When a target substrate is subjected to sufficient compressive force, it may bend and create vertical displacement, which may then lead to a dehesion mode. Dehesion can cause lateral movement (slip) that eliminates the vertical displacement and restores the shear force. This phenomenon may be part of the repositionable aspects of the embodiments of the present invention disclosed herein.

[0084] For example, in some embodiments, the microstructured surface may be designed to have Scharramach waves, which may include design features that prevent slip phenomena without generating peeling forces, such that the displacement of the target surface perpendicular to the surface does not change the interfacial distance or volume. In embodiments where the target surface may be subjected to compressive waves from external forces, gripping surfaces may be included. The periodic distribution of ) may allow the compression wave to be moved without changing the relationship between the microstructured surface and the target surface.

[0085] In some embodiments, microstructures on a microstructured surface may be aligned typically periodically and at multiple "overlapping" levels. When microstructures are formed periodically across multiple size scales, they can be hierarchical and may have more than two fractal dimensions.

[0086] Referring to Figure 1, the microstructured surface 100 has three hierarchical micro-shapes 102. The branching ratio may be determined by 104 and 106. In some embodiments, the first microfeature 102 may have a center-to-center (pitch) of 1000 microns, the second microfeature 104 may be 100 microns apart, and the third microfeature 106 may be 10 microns apart. The third microfeature 106 may be positioned on the upper surface 108 of the second microfeature 104. The second microfeature 104 may be positioned on the upper surface 110 of the first microfeature 102. Thus, the line 112 can define a branching ratio where length 114 may be 10 times the length 116, and length 116 may be 10 times the length 118. The line 112 can define a fractal dimension of 2.1 = 2 + ratio of consecutive lengths, where 2 is the dimension of a surface without microstructure.

[0087] In some embodiments, the fluid with the minimum surface energy may be a gas with zero surface energy. Referring to Figures 2A and 2B, a Wenzel-Cassie interface 200 may be formed between a contact surface 202 and a microstructured surface 204. The interface 200 may contain a first liquid 206 and a second liquid 208. In some embodiments, the microstructured surface 204 may organize the interface 200, which is normally homogeneous within the first and second liquids 206, 208, around a hierarchical microstructure 210, 212. This organization may separate the fluids 206, 208 into spatially localized domains 214, 216. The total energy of the system may decrease by this organization, thereby creating an adhesive force. The energy required to disturb the Wenzel-Cassie interface may be approximately equal to the energy required to return the interface 200 to a homogeneous state.

[0088] Embodiments of the present disclosure may include a first layer, a second layer, and a third layer, the second and third layers being attached to the first layer. In some embodiments, the first layer is attached to the second layer on the first side of the first layer, and the first layer is attached to the third layer on the second side of the first layer. In some embodiments, the first layer may include a tissue scaffolding material. The second layer may include 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 integrated with the first or second layer.

[0089] In some embodiments, the third layer may include a hierarchical microstructure in which a first microstructure has a second microstructure on top of it. In some embodiments, the third microstructure may be positioned near the second microstructure. This continuous “overlap” of microstructures may include further microstructures positioned near the preceding microstructure. In some embodiments, the third layer, including the microstructure surface, may be configured to provide an adhesive effect so that the combined layers can temporarily adhere to a target surface. In some embodiments, the third layer may include a microstructure surface that provides a fixing effect so that the combined layers can be fixed to the target surface for a more permanent period of time without other support to the target tissue and without any solidifying or curing agents.

[0090] Methods for manufacturing embodiments of the disclosed materials are also described herein. The methods may include, for example, attaching the anti-adhesion layer material to a scaffolding material described or illustrated herein by means of one or more stitch attachment patterns. In some embodiments, such methods may include weaving or sewing a filament material so that one or more sheets containing the anti-adhesion layer material can be attached to a scaffolding material described or illustrated herein. In some embodiments, the scaffolding may include a first pattern on which a filament material having higher bioabsorbability than the scaffolding material is woven, sewn, or embroidered. For example, in some embodiments, a mesh may have high compliance characteristics in its original state, but which is woven, sewn, or embroidered on which a filament material with lower compliance is woven, sewn, or embroidered. It may have a stitch pattern that restricts movement. Subsequently, the mesh may be attached to the anti-adhesion layer via attachment patterns (e.g., stitches) at separate attachment points.

[0091] Those skilled in the art will understand that embodiments of the present disclosure may be beneficial and useful for tissue repair. For example, disclosed herein are methods for preventing adhesion, positioning a material as an implant, and fixing the material, and all embodiments thereof will be understood to be important for tissue repair or reconstruction in the subject where required. Such methods may generally involve implanting an implant or scaffold material including an anti-adhesion layer and a positioning / fixation layer, the positioning / fixation layer may be sutured or embroidered to 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 in the body of the subject where tissue repair or reconstruction is required.

[0092] As used herein, “tissue” may refer to any tissue within the body, including soft tissue. In some cases, the tissue may include a hernia, thereby the implant or soft tissue repair graft being used to repair a hernia formation. Once implanted, the anti-adhesion layer can prevent adhesion between the body tissue and the implant or scaffold, and further, it can also prevent adhesion between adjacent body tissues near the implant. It is understood that the fixation of the implant includes maintaining the positional relationship between the soft tissue defect and the scaffold. In some embodiments, the fixation portion may transmit restraining force to the scaffold before tissue infiltration into the scaffold. In some embodiments, the fixation portion may continue to provide support even after the scaffold has fully integrated with the body. It is understood that the use of the term “subject” may include humans or other animals (e.g., domesticated animals, non-human animals, etc.).

[0093] Some embodiments of the present disclosure may include a hernia repair graft. In some embodiments, the hernia repair graft may include a first layer including a tissue scaffold layer, a second layer including an anti-adhesion layer, and a third layer for positioning or fixing the graft to the tissue, the second and third layers being flexibly attached to the first layer using separate attachment site patterns. In some embodiments, the separate attachment site patterns may vary the compliance of the laminated first, second, and third layers by less than 10%, and adjacent areas of the first, second, and third layers between the separate attachment sites may slide relative to each other.

[0094] In some embodiments, the hernia repair graft may include a first layer comprising a woven non-bioabsorbable mesh and a first pattern embroidered on the mesh using a bioabsorbable material. The hernia repair graft may further include a second layer comprising at least one sheet of anti-adhesion material attached at separate attachment sites along the first layer such that adjacent separate attachment sites can be separated by a distance of 1 mm to 20 mm. The hernia repair graft may further include a third layer comprising at least one sheet of microstructured material attached at separate attachment sites along the first layer such that adjacent separate attachment sites can be separated by a distance of 0.1 mm to 10 mm, and adjacent regions of the first, second, and third layers between separate attachment sites can slide relative to each other.

[0095] In some embodiments of this disclosure, the hernia repair graft may include a first layer attached to a second layer, and a third layer attached on the first layer. The second layer may include an anti-adhesion layer formed of an absorbable material, and a first pattern stitched to the second layer using a bioabsorbable material. The first layer may include a scaffold material comprising multiple sheets of extracellular matrix material (ECM). The third layer may include a positioning / fixation material comprising a hierarchical microstructure for positioning the material and barbs penetrating the tissue for fixing the material. The third layer may have at least a portion comprising polypropylene. The layers may be flexibly attached to the first layer using a second pattern of separate stitched attachment sites, the second pattern of separate stitched attachment sites being less dense than the first pattern stitched to the anti-adhesion sheet. In some embodiments, adjacent separate attachment sites may be separated by a distance of 1 mm to 20 mm. The hernia repair graft may further include a third layer comprising at least one sheet of microstructured material attached along the first layer at separate attachment sites such that adjacent separate attachment sites can be separated by a distance of 0.1 mm to 10 mm, and adjacent regions of the first, second, and third layers between the separate attachment sites can slide relative to each other.

[0096] In any embodiment of the graft disclosed herein, the first pattern (e.g., a reinforcement pattern) may be applied to a third layer, and the third pattern (e.g., an attachment pattern) may be a third stitch pattern of a separate attachment site. The third pattern may have a lower density than the first pattern in the plane of the third layer.

[0097] Generally, the tissue scaffold may include a mesh. The mesh may be a knitted mesh, a woven mesh, or a molded mesh. The mesh may be made of polypropylene, polytetrafluoroethylene (PTFE), nylon, polyester, or a combination thereof. The mesh may have an open-cell pore diameter of 1 mm to 10 mm. The mesh may be made of warp-knitted filaments having a diameter of 1 micron to 250 microns. For example, the mesh may be made of warp-knitted filaments having a diameter of 3 microns to 100 microns. The mesh may be made of multiple fibers knitted together (multifilament) or monofilament. In some variations, multifilament fibers (in either the mesh or the sewing material, or both) may be preferred because they may be stronger.

[0098] Generally, the positioning / fixation layer may include a perforated polymer sheet to allow tissue growth from the tissue surface to the scaffold layer. The positioning portion of the layer may include a microstructured surface. The microstructure may be arranged hierarchically with a fractal dimension greater than 2. Generally, the higher the fractal dimension, the stronger the positioning strength. The positioning portion of the layer can result in the placement of the implant in the tissue, thereby facilitating surgical placement, especially laparoscopically.

[0099] In some embodiments, the third layer may include a fixation mechanism that can invasively engage the contact surface. Referring here to Figure 3A, a soft tissue graft 300 is illustrated. The soft tissue graft may include a positioning / fixation layer 301. In some embodiments, the tissue engagement structure 302 may be a tapered pillar 303. In some embodiments, the tissue engagement structure 302 may be a barbed microstructure 304. Barbs 305 may be used to invasively engage the target surface 312, but the engagement of the barbs may reduce the repositionability of the soft tissue graft 300. Therefore, the positioning / fixation layer 301 may be configured such that a barbed microstructure 304 is located at a longer distance 306 from the target surface 312 than another barbed microstructure 304. Multiple barbed microstructures 304 may be configured such that different subsets of the multiple barbed microstructures have increasing distances from the target surface 312. Such configurations, having varying distances from the target surface 312, may allow the number of barbs 305 engaging with the target surface to be increased as a function of time. In some embodiments, the tissue engagement structure 302 may include a microstructure ring 308. The microstructure ring 308 may limit the depth of invasive engagement between the tissue engagement structure 302 and the target tissue 312. In some embodiments, the microstructure ring 308 may be configured to provide a weak stop that can be overcome by the application of additional pressure by a physician, and thus, at the desired time, the soft tissue graft 300 It is more firmly fixed to the target surface 312.

[0100] In some embodiments, positioning forces may be provided by microstructures 314 and 316, as well as an interface volume 318 containing at least two fluids 320 and 322.

[0101] In some embodiments, the positioning-fixation layer may be perforated. The perforations may be of any practical size relative to the size of the soft tissue repair graft 300. An important consideration is that the strength of positioning and fixation of the soft tissue graft 300 is proportional to the surface area of ​​the microstructured surface 301. Therefore, the larger the area ratio, the greater the strength of positioning and fixation for a given fractal dimension and barb density.

[0102] In surgical procedures and related implants, if the center of the implant is positioned first, and the rest of the implant is positioned to fit this initial position, the area ratio may decrease radially from the center of the implant.

[0103] In surgical procedures and related implants, when the peripheral portion of the implant is first positioned, the area ratio may be greatest near the periphery. The area ratio may be discretized into local areas with a high area ratio, and these areas may mimic conventional fastening and / or suturing procedures. This is possible. In some embodiments, some regions may have only barbs, while other regions may have only barbless microstructures.

[0104] In some embodiments of this disclosure, the distribution of positioning structures (microstructures) and fixation structures (barbs) may vary within the soft tissue graft or medical implant in general. Similarly, in some embodiments, the position and density of barbs along tissue engagement features may vary across the entire surface of the positioning / fixation layer.

[0105] In some embodiments, the positioning / fixing layer may further include a substrate surface on which microstructures and / or structural engagement structures are placed. In some embodiments, the microstructures and / or structural engagement structures are integral with the substrate surface and may therefore be composed of the same material / composition. In some embodiments, the microstructures and / or structural engagement structures may be located near the substrate surface and may be composed of a different material than the substrate surface. In one embodiment, the microstructures and / or structural engagement structures may be embossed on the material of the substrate. In some embodiments, the structural engagement structures may include metal or rigid plastic barbs applied to selected locations on the embossed substrate.

[0106] Referring to Figure 3B, the positioning / fixing layer 301 may include a hierarchical microstructure 310. The hierarchical microstructure may include a first microstructure 314 and a second microstructure 316, the second microstructure being positioned near the first microstructure. In some embodiments, the first microstructure may have larger dimensions than the second microstructure. In some embodiments, the positioning / fixing layer may include a tissue engagement structure 302. The tissue engagement structure 302 may include a barbed end 305 with a microstructure ring 308 positioned near a tapered pillar. As previously disclosed, the microstructure ring 308 may act as a weak stop to initially prevent further insertion of the tissue engagement structure 302 into the target surface 3012. With additional pressure or force, the microstructure ring 308 can be inserted into the target surface 312. In some embodiments, positioning force may be provided by hierarchical microstructures 314, 316 and an interface volume 318 containing at least two fluids 320, 322. In some embodiments, fixation force may be provided by a tissue engagement structure 302. The soft tissue graft 300 may initially be positioned near the target surface 312, and the initial positioning of the soft tissue graft may be maintained by the hierarchical microstructures 310. If the position of the soft tissue graft 300 is acceptable to the physician, or if there is a particular Within the requirements / parameters, the soft tissue graft can be fixed in the correct position by applying pressure to the graft, thereby engaging the tissue engagement structure 302 with the target surface 312.

[0107] Next, referring to Figure 4, various examples of barb-designed structural engagement structures 400 are shown. Example 4A includes a conical structure 402 having a circular cross-section. The surface 403 is annularly shaped It may be provided with barbs 404 that surround and protrude inward. Example 4B is, The structure 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, which may allow fluid trapped inside 412 to be discharged so that tissue can enter the interior. The cut surface 414 may allow tissue to easily enter the interior 412. Example 4C is a conical structure 416 having a circular cross-section. Includes. Separate barb projections 418 are distributed in the axial direction. Adjacent barbs may be offset from each other along the height direction of the structure. Example 4D has a circular cross-section. Includes a conical structure 420. Continuous barb projections 422 may be arranged helically around the surface of the structure. Example 4E includes a blade-shaped section 424. Section 424 is The structure may be curved inward, with a separate barbed projection 426 on one side and a cross-section 428 on the opposite side. Example 4F is a conical structure with a longitudinally grooved surface 434. The structure 430 includes a conical structure with a cutting point 432. The valleys 436 of the longitudinal groove may include barb projections 438. Example 4G includes a conical structure 440 having a circular cross-section. The surface of the conical structure 440 may include flexible barb projections 442 positioned thereon. In some embodiments, the flexible barb projections 442 may include a curved contour. Example 4H includes a circular arrangement of flexible fibers 444 which are pressed onto the surface. When trained, it can expand radially. Example 4I is a solid circle with a circular cross-section. It includes a hollow cylindrical structure 448 having a conical structure 450 in the center. The structure 448 may include an outer wall 452, which may include a barbed projection 454 located on the inner portion of the outer wall. Example 4J includes a blade-like structure 456 having a recessed axial longitudinal groove 458. The structure 456 may include a cutting edge 460 on which a barbed projection 462 is positioned. Example 4K includes a structure 464 having two pointed parts. The first pointed part The portion 466 may have a blade-like, inwardly curved structure. It may further include a barbed projection 468 positioned thereon. The second pointed portion 470 may include a tapered cylindrical pinning structure. Example 4L has a rigid fibrous barbed projection 474 The structure includes a needle-like structure 472 positioned on top. The barb projections 474 may branch out toward the base 478 of the structure 472 at bifurcation nodes, which increase with each barb.

[0108] The subject matter disclosed in this invention will be further illustrated by the following specific but non-limiting examples. These examples may include compilations of data representative of data collected at various points in the development and experimentation process for the subject matter disclosed in this invention. These examples are intended to be illustrative and are neither exhaustive nor limiting. [Examples]

[0109] Example 1 Soft tissue repair grafts using Wenzel-Cassie fixation.

[0110] Referring to Figure 5, a soft tissue repair graft 500 is illustrated. In some embodiments, the soft tissue repair graft 500 may include an anti-adhesion layer 502 which may include an absorbable layer having a thickness of 5 to 1000 microns. The absorbable layer may be composed of a biocompatible material such as polylactic acid, polycaprolactone, or polyester urethane. The soft tissue repair graft may further include a tissue scaffold layer 504 which may be attached to the anti-adhesion layer 502 via connecting portions 506. The connecting portions 506 may be continuous or separate. In some embodiments, the connecting portions 506 may contain an adhesive. In some embodiments, the connecting portions contain a solution of the polymer constituting the anti-adhesion layer 502 and the tissue scaffold layer 504. The tissue scaffold layer 504 may be cured around the strands 508. The tissue scaffold layer 504 may be continuous or a woven fabric such as a mesh as shown in Figure 5. In some embodiments, the strands 508 of the tissue scaffold layer 504 may include at least portions where the strand surface is coated and away from the connecting portion 506. In some embodiments, the tissue scaffold layer 504 may contain a non-absorbent material such as polypropylene, polyester, or polyurethane. In some embodiments, the tissue scaffold layer 504 may contain an absorbent material. In some embodiments, the soft tissue graft 500 may include a microstructure layer 510 that can be repositioned on the target surface 512 without damaging the target surface. In some embodiments, the target surface 512 may be biological tissue. The microstructure layer 510 may include separate island portions or it may be a continuous layer. The microstructure layer 510 may include a base layer 514 on which microstructures 516 may be placed. In some embodiments, the microstructures 516 may be formed directly on the tissue scaffold layer 504. The microstructure layer 510 may be attached to the tissue scaffold layer 504 through different connecting parts 518, or using the same connecting parts 506 disclosed when attaching the adhesion prevention layer 502 to the tissue scaffold layer 504.

[0111] In some embodiments, the microstructure 516 may include a hierarchical microstructure 519. For example, in some embodiments, the hierarchical microstructure may include a first microstructure 520 which is a sinusoidal pattern. The sinusoidal pattern 520 may have an amplitude in the range of 100 to 1000 microns. In addition, the sinusoidal pattern 520 may also have a pitch in the range of 100 to 1000 microns. In some embodiments, a second microstructure 522 in the form of a pillar may have a diameter in the range of 10 to 100 microns, a pitch in the range of 10 to 100 microns, and a height in the range of 10 to 300 microns. The second microstructure may be located near the first microstructure. In some embodiments, the second microstructure pillar 522 may have a cross-section of a circular, square, triangular, rectangular, or any other polygonal shape. In some embodiments, a third microstructure may be located near the second microstructure 526. The third microstructure 526 may be smooth or have a design, as shown in Figure 4, in order to invasively engage with the target surface 512. Various degrees of target surface configuration, including no penetration, can be achieved by changing the degree of target surface penetration without impairing Wenzel-Cassie type positioning.

[0112] In some embodiments, the microstructure layer 510 may comprise one of the materials already enumerated in this disclosure. In some embodiments, the microstructure layer 510 may comprise any suitable implantable material and / or biocompatible material, including metals and high durometer hardness materials such as PET. Embodiments that may include a substrate portion 514 may include a substrate portion that is made of an elastic (low durometer hardness) material. In some embodiments, the microstructure layer 516 disposed on the substrate portion 514 may be made of a high durometer hardness material. This combination of the substrate portion 514 and the microstructure 516 may allow the microstructure layer 510 to conform to the target surface 512 to the greatest extent possible.

[0113] While the examples presented herein relate to specific embodiments of repairing biological soft tissue, it should be understood that embodiments of this disclosure may be applicable to any application where a defect on a target surface should be reinforced and / or supported.

[0114] As an example, the following microstructures were placed in the soft tissue grafts of this disclosure. [Table 1]

[0115] When placed on animal tissue, this soft tissue graft resisted displacement under a shear force of 258 ± 17 grams per square centimeter of the contact surface.

[0116] Example 2 A hernia repair device that can be repositioned and has flexible placement options.

[0117] Referring now to Figure 6, a soft tissue repair device is illustrated. The soft tissue repair device 600 may include an anti-adhesion layer 602 containing polylactic acid, a tissue scaffold layer 604 containing a polyurethane-coated polypropylene mesh, and a third microstructure layer 606 containing microstructured polylactic acid. The microstructure layer 606 may include hierarchical microforms including a first circular pillar 608 having a diameter in the range of 10 to 100 microns, a pitch in the range of 10 to 100 microns, and a height in the range of 30 to 120 microns, and a second circular pillar 610 positioned on the first pillar 608. The second pillar 610 may have a diameter in the range of 10 to 50 microns, a pitch in the range of 10 to 50 microns, and a height in the range of 30 to 80 microns.

[0118] In Figure 6, the above-described embodiment was tested with and without a vertical force applied. The applied vertical force was 50 g / cm². 2 The tests were conducted using shear force and vertical force (peeling).

[0119] Setting the shear force:

[0120] Two uniformly thick (approximately 2 cm) slices of beef shoulder were submerged in water and placed side by side. A composite mesh was placed face down on each slice of meat, applying initial pressure by hand. No gaps were created.

[0121] One sheet of meat was sutured to a rigid plastic sheet at its corner and one point in the middle. The other sheet of meat was sutured at five equidistant points at its distal end. The five sutures were pulled together and secured to a thick cord so that the force on each suture was approximately equal when the cord was pulled. The cord was passed around a pulley at a 90-degree angle and attached to the head of an Instron machine. The pulley and meat were arranged so that the tension applied to the cord was within the plane of the meat. The meat was kept moist by sprinkling it with saline solution as needed. Experiments in which the meat twisted were discarded. The head speed was set to 5 cm / min. The force per unit area of ​​the meat-mesh contact area was calculated.

[0122] In the vertical force arm of the test, another plastic sheet was placed on top of the meat / mesh combination, with a load of 50 g / cm². 2 The load was applied uniformly up to that point.

[0123] In the test arm with only mesh, the mesh was sutured to each plate of meat in four places, for a total of eight sutures. The bite depth was approximately 1 cm.

[0124] Setting the vertical force:

[0125] This setting is similar to the shear force setting, except that a third piece of flesh is pulled through the gap between the two pieces of flesh, one of which is fixed by a suture. The pulling force is applied by the suture line that penetrates the mesh. No perpendicular force is applied to the gap. Suture: Prolene 5-0

[0126] Test arm 1: Shear force without vertical support

[0127] Test arm 2: Shear force with vertical force applied

[0128] Test arm 3: Shear force with sutures alone

[0129] Test arm 4: Vertical force due to applied vertical force

[0130] result: [Table 2]

[0131] Example 3 Two-level soft tissue repair device

[0132] In many applications of this disclosure, it may be desirable to place a device on a target surface, temporarily adhere the device, reposition the device to a more desirable location, and then activate a more permanent fixation of the device to the target surface. It is understood that "more permanent" refers to a fixation that lasts longer than temporary adhesion, rather than irreversible fixation.

[0133] Referring here to Figure 7, the two-level soft tissue repair device 700 may comprise a polypropylene mesh 702 bonded to a peripheral microstructure layer 704. The peripheral microstructure layer may include a first microstructure 706 comprising a tip portion 708, a barbed portion 710, and a stop portion 712. When the device 700 is placed on the target surface 714 using light pressure, the device 700 can invasively engage with the target surface, in which case only the tip portion 708 engages with the target surface. This engagement can provide adhesion of the device 700 to the target surface, but this adhesion may allow for easy repositioning of the device. If further force is applied to the device 700 in direction 716, the barb 710 can invasively engage with the target surface 714 so that the device adheres to a position where it cannot be repositioned, providing more permanent fixation. The stop portion 712 may be used to limit the depth to which the barb 710 can engage with the target surface 714.

[0134] Example 4 Wenzel-Cassie 2-level soft tissue repair device

[0135] Referring here to Figures 8A and 8B, a two-level soft tissue repair device 800 is illustrated. The two-level soft tissue repair device 800 may comprise a polypropylene mesh 802 bonded to a microstructure layer 804, which includes a Wenzel-Cassie microstructure 806 and a target penetration structure 808. The Wenzel-Cassie structure 806 may include a hierarchical composite pillar 810. The target penetration structure 808 may include a pillar 811 with barbs 812. Under light pressure, the target surface 814 (Figure 8A) may be maintained in an undeformed state, such as its original state shown in position 814. When greater pressure is applied to device 800, the target surface 814 may deform around the Wenzel-Cassie structure 806, as shown in position 816 (Figure 8B), allowing the target surface to deform and come into contact with the target entry structure 808. When the pressure is released from device 800, the device and the target surface are fixed in place so that the device remains in the correct position for substantial periods of time on the order of hours, days, and / or weeks.

[0136] Example 5 Soft tissue devices for grasping

[0137] The soft tissue bonding device comprises the microstructure of Example 2 bonded to an elastic rubber sheet. This device has the ability to lift soft tissues such as meat, fruits, and vegetables at a rate of 1 g / cm³. 2 The test was conducted by measuring the shear force under a vertical force.

[0138] Place the soft tissue bonding device on a flat slice of the test specimen, and apply 1 g / cm². 2 The load was applied and the test specimen was pulled within its plane. All test specimens were moistened by immersion in water before the test.

[0139] result: [Table 3]

[0140] Therefore, while specific embodiments of the present invention relating to novel and useful microstructured soft tissue grafts have been described, such references are not intended to be construed as limitations on the scope of the invention, except as set forth in the following claims.

Claims

1. A soft tissue repair graft, A first layer containing a biocompatible, non-bioabsorbable polymer mesh, A second layer containing an adhesion-preventing polymer material, A third layer comprising a microstructured surface, wherein the microstructured surface comprises a first microstructured pattern and a second microstructured pattern, the first microstructured pattern having at least a first microform and a second microform, the first and second microforms being arranged hierarchically, and the second microstructured pattern having barbed microforms configured to invasively engage with a target surface, A soft tissue repair graft comprising, wherein the first layer further comprises a first surface and a second surface, the second layer being attached to at least a portion of the first surface of the first layer, and the third layer being attached to at least a portion of the second surface of the first layer.

2. The soft tissue repair graft according to claim 1, wherein the adhesion-preventing 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, wherein the adhesion-preventing polymer material comprises a bioabsorbable polymer material, and the microstructured surface comprises a bioabsorbable polymer material.

4. The soft tissue repair graft according to claim 1, wherein the adhesion-preventing polymer material comprises a non-bioabsorbable polymer material, and the microstructured surface comprises a non-bioabsorbable polymer material.

5. The soft tissue repair graft according to claim 1, wherein the adhesion-preventing polymer material comprises a non-bioabsorbable polymer material, and the microstructured surface comprises a bioabsorbable polymer material.

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

8. The second microstructure is configured to distribute force across the entire contact area of ​​the target surface when the force is applied to the soft tissue repair graft to invasively engage the second microstructure, and when the soft tissue repair graft is separated from the target surface, any single microstructure of the second microstructure distributes 0.025 kg / cm³ per volume of the single microstructure. ３ The separation force should not exceed 25 kg / cm² per unit of contact area between the soft tissue repair graft and the target surface. ２ A soft tissue repair graft exceeding the limits of claim 1.

9. The soft tissue repair graft according to claim 1, wherein the third layer includes perforations, thereby allowing tissue growth from the target surface to penetrate through the perforations in the third layer to the first layer.

10. The soft tissue repair graft according to claim 1, wherein the biocompatible, non-bioresorbable polymer mesh includes pores with a diameter of 0.5 mm to 6 mm.

11. The soft tissue repair graft according to claim 1, wherein the biocompatible, non-bioresorbable polymer mesh comprises longitudinally knitted filaments having a diameter of 5 microns to 100 microns.

12. 300g / m ２ A soft tissue repair graft according to claim 1, having a unit area mass of less than 1.

13. The soft tissue repair graft according to claim 1, wherein the second layer is attached to at least a portion of the first surface of the first layer at attachment sites, the attachment sites include a first filament for attaching the first and second layers together, and adjacent attachment sites are separated by a distance of 1 mm to 20 mm.

14. The soft tissue repair graft according to claim 13, wherein the third layer is attached to at least a portion of the second surface of the first layer at attachment sites, the attachment sites include a second filament for attaching the first and third layers together, and adjacent attachment sites are separated by a distance of 0.1 mm to 10 mm.

15. The soft tissue repair graft according to claim 14, wherein the first filament and the second filament are bioabsorbable.

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