Microstructured soft tissue grafts

Abstract

The present disclosure includes micro-patterned fabrics, meshes, textiles, and implantable devices (300) that can include one substrate having a mesh (302), a second substrate having a microstructured surface (304), and a fibrous layer (308) disposed therebetween. The fibrous layer includes a plurality of randomly oriented fibers. The device having a microstructured surface can include a plurality of first-level microfeatures and a plurality of second-level microfeatures, wherein the plurality of second-level microfeatures are disposed in a hierarchical arrangement with the first-level microfeatures. Methods of manufacturing such micro-patterned fabrics, meshes, textiles, and implantable devices are also disclosed.

Description

Technical Field

[0001] This invention generally relates to micropatterned fabrics, meshes, textiles, etc. More specifically, this disclosure relates to apparatus and methods for producing a substrate having micropatterns thereon, wherein the substrate is capable of generating adhesion to a target surface. Background Technology

[0002] Implantable devices used to repair soft tissue defects often suffer from mobility problems. Therefore, such devices (such as prostheses) are typically sutured or stapled to the tissue surrounding the defect to restrict movement from the target location. While the mechanical means of sutures or staples are effective in restricting movement from the target location, attaching a prosthesis to healthy tissue results in tissue trauma. The cascade effect from this trauma can lead to postoperative adhesions, which can cause further complications and pain for the patient. The time required to position and attach the prosthesis significantly increases the time required to complete the procedure. These prostheses are generally not adhesive, and therefore may move during the time interval between initial positioning and fixation to the tissue. As an even further disadvantage, the lack of adhesive properties makes implantation via minimally invasive procedures such as laparoscopy particularly difficult, rendering them almost unusable for such procedures.

[0003] Therefore, there is a need for a soft tissue repair device that has adhesive properties, can be fixed without sutures or other trauma-causing mechanical devices, and provides postoperative prevention of complications such as adhesions or other trauma-related problems. Summary of the Invention

[0004] In some embodiments disclosed herein, an adhesive component may be added to the soft tissue repair fabric. In some embodiments, the soft tissue repair fabric may be a surgical mesh. The adhesive component may include an interwoven absorbable matrix applied to the mesh, wherein fibers protrude from the plane of the mesh. The added fibers can significantly increase the quality and stiffness of the implantable fabric. In some embodiments, implantable surgical meshes may generally rely on fibers to provide mesh strength. In some embodiments, the fibers may also be embellished with adhesive microstructures, which offer significant clinical advantages compared to composite structures. Composite soft tissue repair fabrics comprise a first reinforcing component and a second anti-slip component. For example, one type of composite soft tissue repair fabric may be an adhesive microstructure sheet bonded to a standard polypropylene mesh. This sheet component is typically quite rigid and compromises the flexibility of the woven mesh, making the tissue repair fabric stiffer and less flexible.

[0005] Therefore, there is a need for a soft, strong soft tissue repair fabric that contains minimal material weight.

[0006] A soft tissue repair fabric is also needed that self-adhedes to the target tissue surface and is sufficiently flexible to avoid creating gaps between the implantable fabric and the target tissue surface. The self-adhesive aspect of this disclosure can be described by capillary action or by establishing a Wenzel-Cassie interface between the implantable fabric and the target tissue surface.

[0007] There is a need for an implant with a micro-surface texture capable of generating immediate Wenzel-Cassie adhesion to secure the implant. In some embodiments, this same micro-surface texture can further facilitate healthy integration of the implant with surrounding tissue. Wenzel-Cassie adhesion can occur by forming a phase domain at the interface between the implant surface and the tissue surface. This type of adhesion can form an interfacial layer between the tissue and the implant. Unexpectedly, the applicant has discovered that the formation of the Wenzel-Cassie adhesion zone is stronger than that of the frictional interface.

[0008] In some embodiments, the hierarchical structures disclosed herein may include components with multi-scale morphologies and large, accessible surface areas. Recent advances in nanomaterials science have made it increasingly possible to design hierarchical microstructured surfaces with specific properties. Much of this work focuses on hierarchical single-walled carbon nanotube membranes achieved from aqueous dispersions via simple, rapid, repeatable, and inexpensive filtration methods. By varying the thickness of the random network of carbon nanotubes, their wettability can be adapted due to capillary phenomena in the porous membranes.

[0009] In some embodiments, a hierarchical microstructured surface can be a surface microstructure that includes high surface energy regions juxtaposed with lower surface energy regions. These high and low surface energy regions do not need to be stacked, but rather juxtaposed with each other. Typically, a higher Wenzel-Cassie positioning force is achieved when the microstructures span three-dimensional space and are stacked.

[0010] High surface energy microstructures are considered wettable, and in the case of water wetting, they are considered hydrophilic. Low surface energy microstructures are considered non-wetting, and in the case of water wetting, they are considered hydrophobic. The juxtaposition of wetting and non-wetting regions produces the so-called Wenzel-Cassie interface.

[0011] It will be understood that the Wenzel-Cassie interface does not require outward radial force to generate positioning force. To enable translation of the implantable surface relative to the target surface, additional energy is required to disrupt the low-energy state of the Wenzel-Cassie interface. In some embodiments, the hierarchical microstructured surface has a low contact area with the target surface, and in some embodiments, there is no contact at all.

[0012] Some embodiments of this disclosure may include a microstructured surface with periodicity. This periodicity can generate a secondary Wenzel-Cassie interface, which is referred to herein as a Wenzel-Cassie interface. The secondary Wenzel-Cassie interface is characterized by some type of mechanical deformation of the target surface and / or the microstructured surface, which creates interlocking conditions between the microstructured surface and the target surface, wherein the deformation is primarily caused by non-frictional forces.

[0013] For example, in some embodiments, the target surface may have an eigenwrinkle mode that causes wrinkling of the target surface without causing mechanical damage. These wrinkles may match one or more periodicities of the microstructured surface, allowing the target surface and the microstructured surface to interlock with minimal mechanical contact. Alternatively, the microstructured surface may also have an eigenwrinkle mode that achieves the same second-order Wenzel-Cassie effect. Essentially, shear forces can be translated into wrinkling of the implantable or tissue surface without displacement of the implant.

[0014] In some embodiments, related but distinct second-order Wenzel-Cassie effects may be associated with Schallamach waves. These waves are generated in microstructured or target surfaces and include multiple folding components, some of which may not be eigenmodes. The periodicity of the microstructured surface can “traps” some components of the Schallamach wave while allowing others to “pass through.” This type of second-order Wenzel-Cassie interface is referred to herein as a “sliding clamping” interface.

[0015] Other second- and third-order Wenzel-Cassie interfaces can also be employed, where the periodicity of the Wenzel-Cassie interface and the microstructured surface works synergistically to position the implant on a dynamically changing target surface. The spatial periodicity of the microstructure can be combined synergistically with other mechanical properties of the microstructured surface, such as the Young's modulus of the material containing the microstructured surface. Furthermore, the geometry of the microstructured surface and how it adheres to the implant can enhance or diminish these second-order Wenzel-Cassie effects.

[0016] The soft tissue repair device of the present invention is characterized by its mechanical properties, which differ from any implant / prosthesis currently disclosed in the prior art. Microstructured surfaces employing hydrophobic and hydrophilic regions can produce a device that exhibits increased displacement force when the target contact surface / lumen becomes wet, when oil is applied, when a surfactant is applied, or when a lubricant is applied. This physical property of enhancing gripping force under conditions that typically reduce gripping force is the opposite of implants / prostheses in the prior art that typically have mechanically frictional surface textures. A problem with prior art implants / prostheses is that the in vivo environment typically tends to lubricate the device's surface and avoid frictional resistance to movement.

[0017] For existing friction treatments (such as those involving barbs, raised pillars, surface cylinders, pyramids, etc.) to be effective, large radial forces must be provided to enable effective interpenetration between the tissue and surface friction geometry. Conversely, in the embodiments of this disclosure, the Wenzel-Cassie regions generated by the microstructure when wetted prevent movement through various non-contact effects, broadly termed van der Waals forces. These positioning forces can be characterized primarily by electronic and quantum mechanics, rather than mechanical and classical mechanics.

[0018] In some embodiments, the Wenzel-Cassie effect can create a "downward suction" effect between the target surface and the implanted device. Therefore, an inward (suction) radial force can be applied instead of an outward radial force to the tissue.

[0019] While these novel effects detail some aspects of various embodiments of this disclosure, the combination of the Wenzel-Cassie effect and the mechanical friction effect should not be excluded, particularly in applications where one is superior to the other on discrete parts of the same device.

[0020] In some other embodiments, viscous and lubricating microsurface textures can be used in combination. Fluid thinning and thickening are common effects due to the disorder or order of water molecules. This disorder or order is caused by the influence of the surface energy pattern of the spatial distribution of the microstructured surface on the electric dipoles in the interfacial fluid. In particular, high surface energy regions can be juxtaposed with low surface energy regions to allow tissue dynamics to pass through the implantation device without displacing it. These and other effects will be described in detail below.

[0021] A soft tissue repair fabric is also needed that can be repositioned before and after surgery without damaging the tissue in contact with the prosthesis.

[0022] There is also a need for a soft tissue repair fabric with improved anti-migration properties, and in particular, a soft tissue repair fabric that does not require sutures, staples or other mechanical mechanisms between the fabric and the target surface to prevent postoperative device displacement.

[0023] Soft tissue repair fabrics with minimum areal density (mass per unit area) and maximum tensile strength are also required.

[0024] In addition, various methods for texturing or creating patterned effects in fabrics are generally known. Texturing methods include chemical methods (such as chemical etching, local shrinkage techniques) and physical methods (such as mechanical cutting, compression, or compaction of fabric areas).

[0025] In some embodiments, the soft tissue repair fabric may include a mesh, an interface mesh structure, and an imprinted microstructure. The microstructure may be imprinted onto a prepolymer layer on the interface mesh or directly imprinted onto the interface mesh by heating.

[0026] In a third embodiment, a standard polymeric mesh can be internally heated to a deformable state, and then microstructures are subsequently imprinted onto it. The polymeric mesh material is heated uniformly and non-destructively, such that the original tensile strength of the mesh is maintained after the microstructures are imprinted on the fibers comprising the mesh.

[0027] This disclosure enables the achievement of high adhesion and layered patterning effects on medical prostheses at a relatively low processing cost. Attached Figure Description

[0028] Figure 1 This is an illustration of a method for creating embodiments of the present disclosure.

[0029] Figure 2 This is a flowchart of a method for creating embodiments of the present disclosure.

[0030] Figure 3 This is an illustration of one embodiment of a microstructured soft tissue device.

[0031] Figure 4 This is an illustration of a heating method used to heat and imprint microstructures onto a soft tissue device.

[0032] Figure 5A and Figure 5B This is an illustration of one embodiment of a microstructured soft tissue device; Figure 5B This is a detailed illustration of the groove microstructure. Detailed Implementation

[0033] refer to Figure 2A method for preparing a substrate having micropatterns thereon is disclosed. In some embodiments, the method may include providing a substrate. The substrate may include a material suitable for coating. In some embodiments, the substrate may be a material type such as fabric, plastic, polymer, etc. In some embodiments, the material may be biocompatible, bioabsorbable, biostable, non-reabsorbable, etc., and may be a combination thereof. In some embodiments, the substrate may include at least one bioabsorbable portion and a second non-reabsorbable portion. In other embodiments, the substrate may be biocompatible and include a bioabsorbable portion and a second non-reabsorbable portion. In some embodiments, the substrate may include more than one material combined together, wherein each component may be fabric, plastic, polymer, etc., and may be biocompatible, bioabsorbable, biostable, non-reabsorbable, etc., and may be a combination thereof.

[0034] In some embodiments, a coating of polymeric adhesive or binder may be applied to a substrate. The coated substrate may then be embossed. In some embodiments, a die or embossing surface may be applied to the coated substrate via a physical embossing structure, such as a cylindrical roller or a stamping press. In some embodiments, the embossed coated substrate may be cured.

[0035] In some embodiments, the coating may be liquid during the imprinting step. In some embodiments, the coating may be semi-liquid / semi-solid during the imprinting step. In some embodiments, the coating is liquid during imprinting and can be transferred for imprinting using a rotating cylindrical die. In some embodiments, the die for the imprinting process may be implemented in a cylindrical screen that can rotate simultaneously with the movement of the substrate beneath it.

[0036] refer to Figure 1A method for preparing a substrate having micropatterns thereon may include a roller 102 for substrate material. In some embodiments, roller 102 may provide a continuous source of substrate material as it unfolds. The substrate material may be transferred to a second region where a coating may be applied. In some embodiments, the coating may be a polymeric adhesive or binder. In some embodiments, the coating may be applied via an impregnation station 104. In other embodiments, the coating may be applied by spraying or via electrostatic discharge. In some embodiments, after coating, the coated substrate may be passed through a cylindrical impression roller 106. In some embodiments, the cylindrical impression roller 106 may include a die with a microstructured pattern that can be transferred onto the coating. In some embodiments, the die may be a male die. In some embodiments, the die may be a female die. In some embodiments, the die may include a male portion and a female portion of the die. In some embodiments, the impression process may include a contact pressure roller 108 for applying pressure to the coated substrate in contact with the cylindrical impression roller 106. In some embodiments, gas pressure may be applied instead of the contact pressure roller 108.

[0037] In embodiments utilizing gas pressure, gas can be directed onto the surface of the mold to press the mold against the coated substrate, or gas can be directed onto the coated substrate to press the coated substrate against the mold.

[0038] After the coating is imprinted with a microstructured pattern, the microstructured substrate can be cured using a curing process 110. The curing process can be one of the conventional types known in the art, in which the coating is solidified or cured. In some embodiments, the microstructured substrate can then be collected for storage or for further processing. In some embodiments, the microstructured substrate can be wound into a roll of material 112.

[0039] In some embodiments disclosed herein, coatings disposed on a substrate are generally classified as water-based and / or solvent-based coatings. In some embodiments, water-based coatings may consist of one or more of the following: binders, emulsion polymers, and / or tackifiers, or any combination thereof. In some embodiments, water-based coatings may include binders, emulsion polymers, and tackifiers together. In other embodiments, they may also contain one or more of the following: plasticizers, thermosetting resins, curing catalysts, stabilizers, and / or other additives.

[0040] The emulsion polymer can be selected from the following: acrylic, vinyl-acrylic, vinyl, polyurethane, and / or styrene-butadiene latex, and combinations thereof. In embodiments of cured coatings, it is typically necessary to increase the viscosity of the coating to approximately 30,000-100,000 MPa-s (mPa-s) immediately after imprinting so that the microstructure maintains the desired geometry between imprinting and curing. In some embodiments, the viscosity can be determined at least in part by the properties of the substrate and / or the method of contacting the microstructure with the coating.

[0041] Suitable thickeners for increasing viscosity may include water-soluble polymers (such as carboxymethyl cellulose, hydroxyethyl cellulose, polyoxymethylene, and natural gums) and alkali-swellable polymers (such as highly carboxylated acrylic emulsion polymers and poloxamer prepolymers).

[0042] In some embodiments, plasticizers may be added to alter the feel of the finished product or improve the flow and leveling properties of the coating. When the goal is to improve leveling properties, short-acting plasticizers, such as phthalates, may be used. If the goal is to alter the feel of the finished device or at least a portion of the finished device, more permanent plasticizers, such as low molecular weight polyesters, may be used.

[0043] In some embodiments, thermosetting resins (such as hydroxymethyl-melamine, urea-formaldehyde condensate, or phenol-formaldehyde condensate) may be incorporated to improve the durability or abrasion resistance of the finished device.

[0044] In some embodiments that include a catalyst, oxalic acid or diammonium phosphate may be used. In some embodiments, the use of a catalyst can increase the curing rate of the adhesive. More specialized additives may be used, which may include UV absorbers (where the backing material, such as polyurethane foam, is subject to photodegradation) and dyes or pigments to impart color to the adhesive layer. When a breathable membrane is required, the coating may be chemically or mechanically foamed. Solvent coatings may include fully reacted soluble polymers, such as acrylic homopolymers and copolymers, polyesters, polyamides, or polyurethanes.

[0045] Solvent coatings may also include fully reacted soluble polymers (such as acrylic homopolymers and copolymers, polyesters, polyamides, or polyurethanes) and two-part systems (such as polyester polyols with diisocyanates or isocyanate prepolymers and epoxy resins with polyamines).

[0046] The polymer or prepolymer can be dissolved in a suitable solvent, preferably with a low boiling point, and then thickened to a suitable viscosity in a manner similar to that used for water-based adhesives. In some embodiments of solvent-based coatings, catalysts, crosslinking agents, stabilizers, pigments, or dyes may also be incorporated.

[0047] Some embodiments disclosed herein may incorporate a cylindrical die for imprinting a pattern onto a substrate or onto a coating of the substrate. As previously described, some embodiments may incorporate a contact pressure cylinder for applying pressure to the coated substrate in contact with the cylindrical impression roller, and some embodiments may incorporate gas pressure instead of a contact pressure cylinder. In embodiments using gas pressure, a range of gas pressures may exist that provide acceptable results. In some embodiments, the gas pressure may be in the range of about 30 psi to about 100 psi. In some embodiments, the gas pressure may be in the range of about 60 psi to 100 psi.

[0048] Embodiments of a cylindrical mold may include a substrate or coated substrate resting on and transported by a conveyor belt or similar transport system. In some embodiments, the conveyor belt may include positioning retainers projecting upward therefrom, intended to maintain the substrate's positioning on the conveyor belt and to hold the substrate in a substantially flat position against the conveyor belt. Typically, the conveyor belt may be a tenter frame or a conventional type of conveyor belt, or a rubber blanket, vacuum belt, etc., adapted to maintain the substrate in a flat form. The conveyor may be wider than the substrate, such that a boundary region may exist on either side of the substrate between the outer edge of the substrate and the outer edge of the belt. In some embodiments, the cylindrical mold may be a rotary mold that rotates at the same speed or substantially the same speed as the conveyor system. In some embodiments, the conveyor system and the rotary mold may include wheels resting on the edge region of the belt. The wheels may be any type of suitable material, such as plastic, metal, rubber, etc. The cylindrical mold may include an extension that protrudes beyond the wheels and rests on a support bracket adapted to rotatably support the mold.

[0049] Therefore, with the help of the support bracket, most of the weight of the cylindrical mold can be supported by the bracket. Then, the wheels can rest gently on the boundary portion, so that the movement of the conveyor causes the cylindrical mold to rotate in the same direction as the base, while the axis of the cylindrical mold remains in a position substantially perpendicular to the direction of conveyor movement. In other embodiments, the cylindrical mold may include a support bracket comprising an integral or external rotating device for rotating the cylindrical mold. The rotation of the cylindrical mold can be synchronized with the speed of the conveyor system.

[0050] Some embodiments disclosed herein may include implantable devices for repairing soft tissue defects. In one embodiment, the device may include a surgical mesh having laminated layers comprising microstructures. In some embodiments, the laminated structure may include a region of a soft, absorbent central core with a relatively low fiber concentration, which may be disposed between two highly abrasion-resistant surface regions.

[0051] Now for reference Figure 3The implantable device 300 may include a mesh structure 302 and a substrate having a microstructured surface 304. In some embodiments, the microstructured surface may include a region 306 capable of generating capillary action. In some embodiments, the capillary action region 306 may be in communication with a fiber layer 308 located between the microstructured surface 304 and the mesh surface 302. In some cases, capillary action may draw moisture into the fibers of the fiber layer 308. The relatively low fiber concentration within the central core region 310 provides space to increase the amount of moisture that can be absorbed by the fiber layer.

[0052] In some embodiments, within the central core region 310, a network of fibers 312 typically bonds the two surface regions together without the use of an adhesive material or bonding agent. In some embodiments, an adhesive material or bonding agent may be used, but may not be applied throughout the entire central core region 310. In some embodiments, the adhesive material in at least one surface region is arranged in a finely spaced pattern, and the adhesive portions in that surface region are finely modeled to soften them. In other embodiments, the adhesive material or bonding agent may be used throughout the entire central core region. Typically, an adhesive material or bonding agent may be used to connect two surface regions within an implantable device.

[0053] In some embodiments, as disclosed herein, the fiber layer 308 can be formed in a variety of ways. In some embodiments, the fiber layer 308 can preferably be formed of randomly oriented short fibers 314, 316. In some embodiments, the fiber layer 308 may include a first side 318 to which a first adhesive material or binder permeable to the fiber layer is applied. In some embodiments, permeation may occur through the following thicknesses of the fiber layer: from about 10 micrometers to about 60 micrometers, or from about 10 micrometers to about 50 micrometers, from about 10 micrometers to about 40 micrometers, from about 10 micrometers to about 30 micrometers, from about 10 micrometers to about 20 micrometers, or from about 10 micrometers to about 15 micrometers. In other embodiments, permeation of the first adhesive material may occur from about 20 micrometers to about 50 micrometers, from about 30 micrometers to about 40 micrometers, or about 35 micrometers. In still other embodiments, permeation may occur from about 20 micrometers to about 60 micrometers, from about 30 micrometers to about 60 micrometers, from about 40 micrometers to about 60 micrometers, or from about 50 micrometers to about 60 micrometers.

[0054] In some embodiments, the fiber layer 308 may include a second side 320 onto which a second adhesive material is applied in a fine, spaced pattern, penetrating through the fiber layer to the following thicknesses: from about 10 micrometers to about 60 micrometers, from about 10 micrometers to about 50 micrometers, from about 10 micrometers to about 40 micrometers, from about 10 micrometers to about 30 micrometers, from about 10 micrometers to about 20 micrometers, or from about 10 micrometers to about 15 micrometers. In other embodiments, penetration of the first adhesive material may occur from about 20 micrometers to about 50 micrometers, from about 30 micrometers to about 40 micrometers, or about 35 micrometers. In other embodiments, penetration may occur from about 20 micrometers to about 60 micrometers, from about 30 micrometers to about 60 micrometers, from about 40 micrometers to about 60 micrometers, or from about 50 micrometers to about 60 micrometers. In some embodiments, the first adhesive material and the second adhesive material do not contact each other within the thickness of the fiber layer. In some embodiments, the first adhesive material and the second adhesive material are substantially not in contact with or connected to each other, wherein substantially no contact or connection includes a contact area of ​​10% or less, 15% or less, 20% or less, 25% or less, 30% or less, 35% or less, 40% or less, 45% or less, or 50% or less.

[0055] In some embodiments, the implantable device may include applying an adhesive material to one side of a fiber layer in a fine, spaced pattern, wherein the adhesive material bonds a first side of the fiber to a microstructured surface, and then repeating these steps on a second side of the fiber layer and bonding the second side to a surgical mesh.

[0056] In some embodiments using a surgical mesh, the implantable device may include a fibrous layer comprising randomly oriented short fibers 314, 316. In some embodiments, the fibrous layer 308 may include a first side 318 to which a first adhesive material or binder permeable to the fibrous layer is applied. In some embodiments, permeation may occur through the following thicknesses of the fibrous layer: from about 10 micrometers to about 60 micrometers, or from about 10 micrometers to about 50 micrometers, from about 10 micrometers to about 40 micrometers, or from about 10 micrometers to about 30 micrometers, or from about 10 micrometers to about 20 micrometers, or from about 10 micrometers to about 15 micrometers. In other embodiments, permeation of the first adhesive material may occur from about 20 micrometers to about 50 micrometers, from about 30 micrometers to about 40 micrometers, or about 35 micrometers. In still other embodiments, permeation may occur from about 20 micrometers to about 60 micrometers, from about 30 micrometers to about 60 micrometers, from about 40 micrometers to about 60 micrometers, or from about 50 micrometers to about 60 micrometers.

[0057] In some embodiments, the fiber layer 308 may include a second side 320 onto which a second adhesive material is applied in a fine, spaced pattern, penetrating through the fiber layer to the following thicknesses: from about 10 micrometers to about 60 micrometers, or from about 10 micrometers to about 50 micrometers, from about 10 micrometers to about 40 micrometers, from about 10 micrometers to about 30 micrometers, from about 10 micrometers to about 20 micrometers, or from about 10 micrometers to about 15 micrometers. In other embodiments, penetration of the first adhesive material may occur from about 20 micrometers to about 50 micrometers, from about 30 micrometers to about 40 micrometers, or about 35 micrometers. In still other embodiments, penetration may occur from about 20 micrometers to about 60 micrometers, from about 30 micrometers to about 60 micrometers, from about 40 micrometers to about 60 micrometers, or from about 50 micrometers to about 60 micrometers. In some embodiments, the first adhesive material and the second adhesive material do not contact each other across the thickness of the fiber layer. In some embodiments, the first and second adhesive materials are substantially not in contact with or connected to each other, wherein substantially not in contact with or connected to each other includes contact of 10% or less, 15% or less, 20% or less, 25% or less, 30% or less, 35% or less, 40% or less, 45% or less, or 50% or less. In some embodiments, the second side 320 can then be adhered to the surgical mesh with the second adhesive material. In some embodiments, the first side 318 can be adhered to the microstructured surface.

[0058] In some embodiments, the substrate may include a plurality of first-level microfeatures. The first-level microfeatures may have a height of 10 to 1000 micrometers, a diameter of 10 to 1000 micrometers, and a center-to-center spacing of 25 to 10000 micrometers between adjacent microfeatures. In some embodiments, the substrate may further include a plurality of second-level microfeatures layered around the first-level microfeatures. In some embodiments, the second-level microfeatures may include a height of 5 to 200 micrometers, a diameter of 5 to 200 micrometers, and a center-to-center spacing of 10 to 1000 micrometers between adjacent microfeatures. In some embodiments, the substrate may further include a plurality of third-level microfeatures layered around the second-level microfeatures. In some embodiments, the third-level microfeatures may include a height of 1 to 5 micrometers, a diameter of 5 to 200 micrometers, and a center-to-center spacing of 10 to 1000 micrometers.

[0059] In some embodiments, the substrate may include a plurality of first-level microfeatures. The first-level microfeatures may have a height of 50 to 1000 micrometers, a diameter of 50 to 1000 micrometers, and a center-to-center spacing of 100 to 10000 micrometers between adjacent microfeatures. In some embodiments, the substrate may further include a plurality of second-level microfeatures layered around the first-level microfeatures. In some embodiments, the second-level microfeatures may include a height of 10 to 200 micrometers, a diameter of 10 to 200 micrometers, and a center-to-center spacing of 50 to 1000 micrometers between adjacent microfeatures. In some embodiments, the substrate may further include a plurality of third-level microfeatures layered around the second-level microfeatures. In some embodiments, the third-level microfeatures may include a height of 1 to 5 micrometers, a diameter of 10 to 200 micrometers, and a center-to-center spacing of 100 to 1000 micrometers.

[0060] In some embodiments, the substrate may include a plurality of first-level microfeatures having a height of 100 to 750 micrometers, a diameter of 50 to 500 micrometers, and a center-to-center spacing of 100 to 1000 micrometers between adjacent microfeatures. In some embodiments, the substrate may further include a plurality of second-level microfeatures layered around the first-level microfeatures, the second-level microfeatures having a height of 25 to 100 micrometers, a diameter of 25 to 100 micrometers, and a center-to-center spacing of 50 to 500 micrometers between adjacent microfeatures. In some embodiments, the substrate may further include a plurality of third-level microfeatures layered around the second-level microfeatures. In some embodiments, the third-level microfeatures may include a height of 1 to 5 micrometers, a diameter of 10 to 100 micrometers, and a center-to-center spacing of 10 to 100 micrometers.

[0061] In some embodiments, the substrate may include a plurality of first-level microfeatures having a height of 100 to 500 micrometers, a diameter of 100 to 500 micrometers, and a center-to-center spacing of 100 to 750 micrometers between adjacent microfeatures. In some embodiments, the substrate may further include a plurality of second-level microfeatures arranged in layers around the first-level microfeatures, the second-level microfeatures having a height of 25 to 100 micrometers, a diameter of 25 to 100 micrometers, and a center-to-center spacing of 50 to 500 micrometers between adjacent microfeatures. In some embodiments, the substrate may further include a plurality of third-level microfeatures arranged in layers around the second-level microfeatures. In some embodiments, the third-level microfeatures may include a height of 1 to 5 micrometers, a diameter of 10 to 100 micrometers, and a center-to-center spacing of 10 to 100 micrometers.

[0062] In some embodiments disclosed herein, the microstructured surface may be a microstructured pattern embossed in a first adhesive material located on one side of the fiber layer. In some embodiments, the implantable device may include applying adhesive material to one side of the fiber layer in a fine, spaced pattern and adhering a surgical mesh, and embossing a microstructured pattern on the opposite side of the fiber.

[0063] In some embodiments, each surface region may include an adhesive material. In some embodiments, the adhesive material may be elastomer. In some embodiments, the elastomer adhesive material may be disposed throughout the entire fiber layer or at least a portion thereof to bond the fibers into a robust network and impart abrasion resistance to both sides of the fiber layer. In some embodiments, one side may be formed or bonded to a mesh, while the other side may be formed or bonded to a microstructured surface.

[0064] In some embodiments, one side of the fiber layer with the bonding material may be arranged in a fine, spaced pattern, with a substantial portion of the surface free of the bonding material. In some embodiments, this substantial portion of the surface free of the bonding material may be at least 40% or more, more preferably 50% or more. In such embodiments where a substantial portion of the surface is free of the bonding material, the fiber layer thus provides a highly absorbent region through which moisture can easily penetrate into the interior of the fiber layer. In some embodiments, both sides of the fiber layer may include a bonding material arranged in a fine, spaced pattern, with a substantial portion of both sides of the fiber layer free of the bonding material. In some embodiments, this substantial portion of the surface free of the bonding material may be at least 40% or more, more preferably 50% or more. In such embodiments where a substantial portion of the surface is free of the bonding material, the fiber layer thus provides a highly absorbent region through which moisture can easily penetrate into the interior of the fiber layer.

[0065] In some embodiments disclosed herein, the central core region 310 may include a soft, relatively low-density fiber network loosely held together by electrospinning or deposited during electrospinning. In some embodiments, additional strength may be imparted to the central region by entanglement of relatively long fibers (synthetic or natural, added to the fiber blend of relatively short fibers disclosed above). Longer fibers may be provided such that the total density of the fiber blend is 50% or greater, 60% or greater, 70% or greater, 80% or greater, 90% or greater, 95% or greater, 96% or greater, 97% or greater, 98% or greater, or 99% or greater. In some embodiments, including relatively long fibers may be the sole source of strength for the central region. For clarity, when referring to relatively long fibers, it means that the longer fibers are at least 1.5 times, or at least 2.0 times, or at least 2.5 times, or at least 3.0 times, or at least 3.5 times, or at least 4.0 times, or at least 4.5 times, or at least 5.0 times, or at least 10.0 times, or at least 20.0 times, or at least 30.0 times, or at least 4.0 times, or at least 50.0 times, or at least 100.0 times the length of the shorter fibers.

[0066] In some embodiments, the central core region may include distinct regions or portions comprising cavities positioned along the entire core region. In some embodiments, these distinct regions or portions of the cavities may provide additional properties to the core region. For example, additional properties may include greater volume, softness, and absorbency of the fiber layers. In some embodiments, separating the distinct regions from each other may include a fiber network connecting the microstructured surfaces and the mesh together. This embodiment may allow for the construction of implantable devices without using the undesirable rigid adhesives used in the prior art.

[0067] In some embodiments, the fiber layer can have an undulating appearance due to the patterning of the fiber layer by using a patterned adhesive material. The controlled patterning of the fiber layer can increase its volume and absorbency, as well as its softness and compressibility.

[0068] Another embodiment of this disclosure may include heating a surgical mesh and imprinting a microstructure pattern into the fibers of the surgical mesh. Heating the mesh fibers by a heated mandrel is unsatisfactory because if the mandrel is too hot or applied for longer than necessary, the tensile strength of the mesh may be reduced. In extreme cases, excessively hot iron may melt or otherwise damage the mesh, rendering it unusable for implantation or general use.

[0069] Therefore, one object of this disclosure is to provide an improved method and apparatus for continuously embossing patterns on a material, which does not have the defects and disadvantages mentioned above. In some embodiments, an improved method and apparatus is disclosed, wherein the heat used to soften the material and the duration of heat application can be adequately controlled, and material deterioration is prevented.

[0070] According to some embodiments of this disclosure, the conveying system or similar system (which supplies the substrate between a cylindrical impression roller and a pressure roller or gas pressure) may further include one or more pairs of electrodes connected to a high-frequency power supply. Due to dielectric loss, the substrate or a portion thereof can be heated uniformly, rather than simply heating the surface to the temperature required to imprint the microstructure onto the polymer layer. Applying slight pressure completes the microstructure transfer process from the mold to the fabric.

[0071] This method and apparatus enable operators to maintain a level of control far superior to any that can be achieved by methods known in the prior art, namely convection heating, radiation heating, and / or contact heating.

[0072] Now for reference Figure 4 The substrate material 402 is fed between a pair of rotating circular electrodes 404, 406 along a conveying system or similar transport / manufacturing system. In some embodiments, the pair of rotating circular electrodes 404, 406 may be powered by an RF source 408. The electrodes may be mechanically biased by a spring 410 that biases the electrodes toward each other, thereby applying pressure to the substrate as it passes between them.

[0073] The electrodes can be located near where the substrate enters the transport system, or as close as possible to the start of the manufacturing process. In some embodiments, there will be two pairs of electrodes, each pair adapted to receive one side of the transported substrate sheet.

[0074] In such Figure 4 In one embodiment shown, one of the electrodes 404 may be rotated by a motor 412 connected via a reduction gear, a universal joint, and / or an insulating coupling. In some embodiments, the second electrode 406 of the electrode pair may also be connected via an insulating coupling, a universal joint, and / or a reversing gear (which is connected to the motor 412 via a gearbox).

[0075] It will be understood that embodiments with two electrodes must rotate in opposite directions. In some embodiments, the electrode system may also include insulating strips 414, 416. Strips 414, 416 can be used as drive devices for supplying the material to be treated. However, in some embodiments, the electrodes may be stationary or freely rotating, and other motor drive units may drive the substrate relative to the electric field.

[0076] like Figure 4 As further shown, each pair of electrodes may include a pair of associated strips 414, 416. In some embodiments, these strips may be made of Teflon or other insulating materials. They may be held on an idler roller. Strips 414, 416 may be interposed between each surface of the electrodes 404, 406 of the substrate 402. The strips insulate the electrodes so that the electrode temperature does not rise excessively when the substrate is heated. In some embodiments, if the strips are omitted, the electrodes will gradually become overheated due to contact with the heated substrate.

[0077] When the temperature of the electrode rises too high, the substrate may become sticky and may adhere to the electrode without a tape. It is this surface heat transfer that can create a layer on the substrate that damages the polymer material and reduces its tensile strength.

[0078] To prevent the power applied through the strip from heating it, they can preferably be made of materials with very low dielectric loss. Materials chosen for the buffer layer can be dielectrics such as PTFE, polypropylene, silicone, and / or polyamide. These materials all have low dielectric loss, which prevents them from heating in the RF field, and these dielectrics also tend to have high breakdown voltage limits.

[0079] A belt in contact with a uniformly heated substrate can be heated through this contact. If the belt is manufactured to be relatively long and exposed, it can quickly begin to radiate this heat, making the heat unrestricted. If shorter belts are required due to space constraints, their radiation can be increased by guiding airflow or other coolants across the belt.

[0080] It should be understood that the tape can include any desired microstructure pattern that can be imprinted onto the heated target material. Due to uniform heating, the microstructure pattern is faithfully transferred without surface effects.

[0081] In some embodiments, the electrodes may be connected to an oscillator or other high-frequency electrical energy source. Frequencies from 200 to 300 MHz have been found to be practical for this application, but operation is not limited to these frequencies. However, if such frequencies are used, the voltage applied to the electrodes can be kept within convenient limits, thereby eliminating the possibility of voltage breakdown.

[0082] High-frequency electrical energy from the oscillator can establish an electric field between the electrodes. Due to the dielectric loss of the material, the substrate passing between the electrodes becomes uniformly and rapidly heated.

[0083] The following are examples of materials and patterns that can be used to implement the disclosures presented herein, but are not intended to be limiting.

[0084] Example 1. Microstructured surface

[0085] Referring to Figure 5, a microstructured surface 500 is disclosed, which may include a substrate 502. The substrate 502 may include a first sinusoidal microstructure 504, a second pillar microstructure 506 disposed on the sinusoidal microstructure, and a third groove microstructure 508 disposed on the second pillar microstructure. Each of the three different microstructures is arranged in layers. The diameter, pitch, and height suitable for each microstructure can be defined as follows: the size of the first sinusoidal microstructure is 1.1 to 10 times the size of the second pillar microstructure, and the size of the second pillar microstructure may be 1.1 to 10 times the size of the third groove microstructure. The second pillar microstructure may have any elliptical or polygonal cross-section.

[0086] Example 2. A mesh coated with a microstructured prepolymer.

[0087] In some embodiments, microstructures can be formed in polymers that are cross-linked into a fixed shape or that are swellable. When the microstructures swell, the swelled microstructures may have the additional advantage of actively engaging target surfaces, such as tissues.

[0088] Poloxamer and polylactic acid-based hydrogel

[0089] Pluronic 31R1 (molecular weight 3250) (BASF, Mt. Olive, NJ) was dried under vacuum at 85 °C for 12 hours in a spherical flask. The final water content was less than 300 ppm. One equivalent of Pluronic 31R1 was added to 1 / 5 equivalent of (1)-lactide and 0.18 g of catalyst (stannous 2-ethylhexanoate) (0.43%). The reaction was carried out in a sealed flask at 145 °C for 2.5 hours under dry nitrogen saturation.

[0090] Two equivalents of toluene diisocyanate were added to the above-mentioned compound, and the reaction was carried out at 60°C for 8 hours. Half an equivalent of a biofunctional molecule, such as frankincense extract, was then added to the product, and the reaction was carried out at 75°C for 8 hours.

[0091] A hydrogel of the desired viscosity is formed by adding an appropriate amount of water. For example, 1 g of water can be added for a high-viscosity gel, and 100 g of water can be added for a low-viscosity gel.

[0092] The mesh coated with the above prepolymer can be cured in a high humidity chamber or by lightly spraying water.

[0093] Example 3. Polyethylene glycol and polylactic acid hydrogel.

[0094] Polyethylene glycol (“PEG”) (molecular weight 3000) was vacuum dried overnight at 85°C. The PEG was then cooled to room temperature and the product was end-capped with dry nitrogen. One equivalent of PEG was added to one-fifth equivalent of (1)-lactide and 0.18 g of catalyst (stannous 2-ethylhexanoate). The mixture of PEG and lactide was placed in an oil bath under flowing nitrogen at 140°C and mixed for 3 hours.

[0095] Two equivalents of toluene diisocyanate were added to the above synthesis, and the reaction was carried out at 60°C for 8 hours. Half an equivalent of a biofunctional molecule, such as frankincense extract, was added to the product, and the reaction was carried out at 75°C for 8 hours.

[0096] A hydrogel of the desired viscosity is formed by adding an appropriate amount of water. For example, 1g of water can be added for a high-viscosity gel, and 100g of water can be added for a low-viscosity gel.

[0097] Example 4

[0098] Healing hydrogel based on poloxamer and polylactic acid

[0099] In a reactor equipped with a stir bar, 2 moles of diisocyanate are provided under nitrogen atmosphere. The reactor can be heated to 60°C, and 1 mole of poloxamer diol is slowly added. The poloxamer should be added at a sufficiently slow rate so that the volumetric temperature does not exceed 65°C. If the poloxamer is solid at 60°C, a solvent can be used. Once all the poloxamer has been added to the reaction volume, the mixture should react until the isocyanate content corresponds to two available NCO groups per poloxamer molecule. The slow addition of poloxamer ensures that each poloxamer molecule is terminally capped by two diisocyanate molecules, as most of the reaction occurs in excess diisocyanate, and chain extension of the poloxamer is unlikely. If preventing chain extension is important, a large excess of diisocyanate can be used, and the excess diisocyanate evaporates upon termination of the reaction.

[0100] Once poloxamer diisocyanate has been prepared as described above, 1 mole can be added to the reactor under nitrogen atmosphere, heated to 85°C, and 2 moles of dilactide (A) or a more common ester can be slowly added, while preventing excessive exothermic reaction as previously described.

[0101] Half an equivalent of a biofunctional molecule, such as frankincense extract, was added to the product, and the mixture was reacted at 75°C for 8 hours.

[0102] A hydrogel of the desired viscosity is formed by adding an appropriate amount of water; for example, 1 g of water is added for a high-viscosity gel, and 100 g of water is added for a low-viscosity gel.

[0103] 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, unless set forth in the appended claims.

Claims

1. An implantable device for repairing soft tissue, comprising: The first substrate includes a mesh; The second substrate has a microstructured surface comprising a plurality of first-level microfeatures and a plurality of second-level microfeatures, wherein at least a portion of the plurality of second-level microfeatures is layered on at least a portion of the first-level microfeatures, wherein the microstructured surface is capable of generating Wenzel-Cassie adhesion forces to secure an implantable device to a target tissue surface. as well as A fiber layer is disposed between a first substrate and a second substrate, wherein the fiber layer comprises a plurality of randomly oriented fibers, the fiber layer has a first side and an opposing second side, a first adhesive material is disposed on the first side and permeates the fiber layer, and a second adhesive material is disposed on the opposing second side and permeates the fiber layer, wherein the first adhesive material and the second adhesive material bond the first substrate and the second substrate together via the fiber layer, wherein the first adhesive material and the second adhesive material do not contact each other within the fiber layer.

2. The implantable device according to claim 1, characterized in that, The plurality of first-level micro-features have a height of 10 to 1000 micrometers, a diameter of 10 to 1000 micrometers, and a center-to-center spacing of 25 to 10000 micrometers between adjacent micro-features.

3. The implantable device according to claim 1, characterized in that, The plurality of second-level micro-features have a height of 5 to 200 micrometers, a diameter of 5 to 200 micrometers, and a center-to-center spacing of 10 to 1000 micrometers between adjacent micro-features.

4. The implantable device according to claim 2, characterized in that, The plurality of first-level micro-features include sinusoidal waveforms.

5. The implantable device according to claim 1, characterized in that, The microstructured surface also includes a plurality of third-level micro-features, wherein at least a portion of the plurality of third-level micro-features are layered on at least a portion of the second-level micro-features.

6. The implantable device according to claim 5, characterized in that, The plurality of third-level micro-features include a height of 1 to 5 micrometers, a diameter of 5 to 200 micrometers, and a center-to-center spacing of 10 to 1000 micrometers.

7. The implantable device according to claim 1, characterized in that, The second substrate is bioavailable, while the first substrate is not bioavailable.

8. The implantable device according to claim 7, characterized in that, The mesh of the first substrate contains polypropylene.

9. The implantable device according to claim 1, characterized in that, The first adhesive material permeates the fiber layer from the first side by 10 to 60 micrometers, and the second adhesive material permeates the fiber layer from the opposite second side by 10 to 60 micrometers.

Images