Implantable prosthesis for tissue regeneration and marking of surgical sites

Abstract

Implantable prostheses and related methods are generally described. In some embodiments, the prosthesis may be a generally ellipsoidal (e.g., spherical) shape formed from one or more subunits. The subunits may be tapered or frustoconical, formed by manipulating a two-dimensional substrate material. The sidewalls of the subunits may be secured to each other to enhance the stiffness of the prosthesis. In some embodiments, the markers may be used to assist in distinguishing prostheses in an implant site by medical imaging (e.g., x-ray imaging). In this manner, an implant site can be easily identified, which can also be a site of recent biopsy and / or resection of diseased tissue. The prosthesis may be formed from a porous material to induce tissue infiltration, which may promote natural tissue regeneration to achieve a more natural tissue appearance and feel. The tissue infiltration enables the prosthesis to have enhanced anti-migration ability after implantation.

Description

Technical Field

[0001] The disclosed embodiments relate to tissue engineering devices and related methods, and more particularly, to implantable prostheses for soft tissue regeneration and biopsy and tumor resection site identification. Background Art

[0002] Soft tissue removal or excision has become an essential and important part of cancer treatment. Tissue can be removed as a biopsy sample to perform diagnostic tests or examinations to determine cytology, histology, the presence or absence of chemicals that are indicators of disease state, or the presence of bacteria or other microorganisms. If the biopsy sample indicates malignant (e.g., diseased or cancerous) cells, the surgeon may choose to remove a larger body of tissue to limit the risk of cell spread and growth and optimize the surgical outcome.

[0003] Removing a portion of diseased or cancerous cells from breast tissue may be referred to as a lumpectomy, partial mastectomy, or mastectomy, which more commonly refers to the removal of the entire breast tissue. Tissue excision or removal may result in undesirable palpable and / or visible changes in the tissue. Therefore, patients may seek reconstructive options such as injections of fat, autologous tissue, or natural materials (e.g., collagen) to fill the space left by the surgery. Alternatively, synthetic materials such as silicone may be used. Summary of the Invention

[0004] In some embodiments, the implantable prosthesis includes a plurality of generally conical mesh bodies, wherein each generally conical mesh body of the plurality of generally conical mesh bodies is connected to at least another generally conical mesh body of the plurality of generally conical mesh bodies, and wherein the generally conical bodies are arranged to form an ellipsoid.

[0005] In some embodiments, a method of forming an implantable prosthesis includes forming a plurality of generally conical mesh bodies and connecting each of the conical mesh bodies to at least another of the other generally conical mesh bodies to form an ellipsoid.

[0006] In other embodiments, the implantable prosthesis includes a plurality of generally conical bodies, wherein each generally conical body of the plurality of generally conical bodies is connected to at least another generally conical body of the plurality of generally conical bodies, and wherein the implantable prosthesis is generally mechanically isotropic.

[0007] In other embodiments, the implantable prosthesis includes a plurality of generally conical bodies, each conical body including a sidewall defining a cone-like shape, wherein the sidewall of each generally conical body is connected to the sidewall of at least another adjacent generally conical body.

[0008] In other embodiments, a method of forming an implantable prosthesis includes forming a plurality of generally conical bodies, each conical body including a sidewall defining a conical shape and connecting the sidewall of each generally conical body to the sidewall of at least another adjacent generally conical body.

[0009] In other embodiments, the implantable prosthesis includes a plurality of mesh bodies, wherein each mesh body is connected to another mesh body, wherein at least some of the mesh bodies include a first mesh portion connected to a second mesh portion, wherein the first portion is arranged within a volume defined by the second mesh portion.

[0010] In other embodiments, a method of forming an implantable prosthesis includes forming a plurality of mesh bodies; arranging a first mesh portion of at least some of the mesh bodies within a volume defined by a second mesh portion; connecting the first mesh portion to the second mesh portion; and connecting each of the mesh bodies to another mesh body.

[0011] It should be understood that the aforementioned concepts and the additional concepts discussed below can be arranged in any suitable combination, as the present disclosure is not limited in this respect. In addition, other advantages and novel features of the present disclosure will become apparent from the following detailed description of various non-limiting embodiments when considered in conjunction with the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] The accompanying drawings are not intended to be drawn to scale. In the drawings, each identical or nearly identical component illustrated in various figures may be represented by a like reference numeral. For clarity, not every component may be labeled in every drawing. In the drawings:

[0013] Figure 1A to Figure 1B depicts an implantable prosthesis according to some embodiments;

[0014] Figure 2A depicts a top view of a tapered subunit of an implantable prosthesis according to some embodiments;

[0015] Figure 2B Depicted according to some embodiments Figure 2A Isometric view of the conical subunit;

[0016] Figure 3 depicts a tapered subunit of an implantable prosthesis according to some embodiments;

[0017] Figures 4A to 4D depicts a tapered subunit of an implantable prosthesis according to other embodiments;

[0018] Figures 5A to 5B depicts various views of an implantable prosthesis according to some embodiments;

[0019] Figure 6A Depicted are implantable prostheses according to other embodiments;

[0020] Figure 6B Depicted is a view taken along line 6B-6B. Figure 6A implantable prostheses;

[0021] 7A to 7C Still depicted are three implantable prostheses according to other embodiments;

[0022] Figures 8A to 8B depicts various views of an ellipsoidal implantable prosthesis according to some embodiments;

[0023] 9A to 9F Depicted according to some embodiments Figures 8A to 8B a tapered subunit of an implantable prosthesis;

[0024] Figures 10A to 10E depicts an assembly process for an implantable prosthesis according to some embodiments;

[0025] Figures 11A to 11B depicts a compression testing system for an implantable prosthesis according to some embodiments;

[0026] Figure 12 depicts a partial assembly process for an implantable prosthesis according to some embodiments;

[0027] 13A to 13D depicts an assembly process for an implantable prosthesis according to some embodiments;

[0028] Figure 14 Depicted are implantable prostheses according to other embodiments;

[0029] 15A to 15D Still depicted are assembly processes for implantable prostheses according to other embodiments;

[0030] 16A to 16B Still depicted are implantable prostheses according to other embodiments;

[0031] 17A to 17B Still depicted are implantable prostheses according to other embodiments;

[0032] 18A to 18B Still depicted are implantable prostheses according to other embodiments;

[0033] Figure 19 Still depicted are implantable prostheses according to other embodiments;

[0034] 20A to 20DStill depicted are assembly processes for implantable prostheses according to other embodiments;

[0035] Figure 21 shows exemplary local tissue reaction data from experimental implantation of an implantable prosthesis according to some embodiments; and

[0036] Figure 22 Shown are exemplary cellular response data from experimental implantation of an implantable prosthesis according to some embodiments. DETAILED DESCRIPTION

[0037] Removal of natural tissue at the tissue removal site, which may occur during therapeutic treatment, may result in external depressions or defects that may affect both the appearance and palpability of the natural tissue. Conventional tissue reconstruction using autologous fat or soft natural material fillers may produce undesirable results because the injectable materials lack mechanical rigidity and are unable to support the tissue at the implant site. In addition, such materials may slow the ingrowth of tissue within the tissue removal site, thereby prolonging the healing and reconstruction process. Alternative options such as silicone may be hard enough to support surrounding tissue, but may essentially limit the possibility of tissue ingrowth. In addition, fluids or materials and synthetic filling materials may be incompatible with cancer treatments, such as radiation therapy. Such treatment may result in material loss. Therefore, the inventors have recognized the need for a soft tissue prosthesis that can simultaneously exhibit the mechanical properties of supporting the anatomical structure of the implant site while also enabling rapid ingrowth of tissue.

[0038] Additionally, in cancer treatment, radiation therapy is often administered after tumor removal to destroy remaining cancer cells and reduce the risk of cancer recurrence. However, the inventors have recognized that delineating the tissue margins of the tumor cavity for radiation therapy after surgery can be difficult. Traditionally, clinicians rely on the presence of surgical scars or seroma to identify the site and radiation target volume for radiation therapy. However, these identification methods are not entirely accurate and not only reduce the effectiveness of radiation therapy, but also increase the chance that healthy tissue surrounding the cavity will be damaged. Correctly locating the margins of the tumor resection cavity can also be extremely difficult because the cavity can have an irregular shape, and in some tissues, the shape can change over time. For example, the tumor cavity can grow or shrink during respiration, or even change in size and shape due to ongoing radiation therapy treatment. Markers are also used in cases where the biopsy result is normal (e.g., benign) to provide information about the biopsy history in subsequent tests (e.g., mammograms).

[0039] In some cases, clinicians often use marker devices to better define the location of the cavity and provide a clearer target for external beam radiation therapy. A marker device is a marker or group of markers placed in the imaging field as a reference point, which is typically formed of a surgical alloy, such as a titanium alloy, including a shape memory alloy. The marker is typically a small metal object that is distinguished from surrounding tissue by various imaging modalities (e.g., x-rays), but may have a tendency to migrate after implantation, thereby affecting the accurate reading of the biopsy or tumor resection site. Therefore, the inventors also recognized the need for biopsy or tumor resection site markers to guide radiological targeting in treatment and imaging applications.

[0040] In view of the foregoing, the inventors have recognized the benefits of implantable prostheses for soft tissue reconstruction and / or for loss of natural soft tissue volume in applications such as surgical removal or excision of tissue (e.g., tumor resection surgery). The prosthesis can have mechanical and geometric properties similar to those of natural tissue to simulate the natural feel of the tissue. The prosthesis can also serve as a scaffold for tissue infiltration to allow natural (or other) tissue to grow within the prosthesis, thereby maintaining mechanical properties similar to those of natural tissue without being visibly palpable externally. Tissue ingrowth into the void space of the excision or removal cavity can also have the additional benefit of improved cosmetic results and resistance to migration. The prosthesis can also serve as an indicator of the site of biopsy and / or tissue resection (e.g., tumor resection). The prosthesis can be visible using one or more medical imaging systems to enable external detection of the site for treatment and imaging applications. The prosthesis can have the benefit of reducing the clinical target volume in radiotherapy and improving the cosmetic effect after tumor resection. However, it is also possible to provide different benefits through the systems and methods disclosed herein.

[0041] In some embodiments, the implantable prosthesis can be a three-dimensional implant formed by an assembly of subunits. Each subunit can be formed by a two-dimensional substrate that can be shaped from a two-dimensional configuration to a three-dimensional configuration. In some embodiments, the two-dimensional substrate can be a substrate with a roughly c-shaped shape having a cutout portion, as described in more detail below. The two-dimensional c-shaped substrate can be arranged into a three-dimensional shape by fixing the two ends of the c-shaped substrate together. In this way, a cone-shaped (or truncated cone or cone frustum) shape with side walls can be formed. It should be understood that the two-dimensional substrate can have any shape that facilitates its transformation into a three-dimensional subunit body. In some embodiments, the two ends of the c-shaped substrate can be fixed together using permanent means (e.g., welding), while in other embodiments, the two ends can be fixed together using temporary means (e.g., fasteners, such as staples). The sidewalls of the three-dimensional subunit can then be fixed to the sidewalls of one or more other subunits to form a three-dimensional implantable prosthesis. For example, twelve cone frustum subunits can be arranged to be fixed to each other to form a roughly ellipsoidal shape.

[0042] The inventors have recognized the benefits associated with an implantable prosthesis that balances mechanical properties to support the surrounding anatomical structures with a high rate of tissue infiltration. A highly rigid and dense implantable prosthesis would support the surrounding tissue without providing natural palpability or promoting tissue ingrowth. On the other hand, the absence of a prosthesis may induce natural tissue ingrowth, but may exhibit a depression or defect at the site of tissue removal. Therefore, the implantable prosthesis of the present disclosure can exhibit both mechanical isotropy and large void spaces to enable tissue ingrowth. In this way, the prosthesis can provide sufficient and isotropic mechanical support to the implant site while still enabling rapid tissue ingrowth.

[0043] When compared to non-porous or solid prostheses, the use of subunits to construct implantable prostheses can achieve greater tissue infiltration by the prosthesis. In this way, the implantable prosthesis can exhibit palpability and / or other properties similar to natural tissue. In some embodiments, the prosthesis can be formed of a material that allows fibroblasts to invade to produce collagen, which can be wrapped around the underlying material of the prosthesis. Therefore, in some embodiments, the prosthesis of the present disclosure can serve as a building block for organ development (engineering) or supplementation in vivo by providing a scaffold to induce vascularization.

[0044] In some embodiments, the implantable prosthesis can be formed by an assembly of tapered mesh subunits or tapered mesh bodies connected to at least one adjacent subunit. The prosthesis can have an assembled shape similar to an ellipsoid. In some embodiments, the implantable prosthesis can be constructed by the following process: first, each tapered mesh subunit or tapered mesh body is formed as will be described in more detail below, and then each tapered mesh subunit is connected to an adjacent subunit to form an ellipsoidal prosthesis. The ellipsoidal shape (e.g., a sphere) can have the benefit of being appropriately fitted within a tissue resection site (e.g., a biopsy site, a tumor resection site), which can help maintain the natural palpability of the tissue so that the prosthesis or resection site is substantially impalpable on the subject.

[0045] In some embodiments, an implantable prosthesis can be formed from an assembly of tapered mesh subunits or a tapered mesh body connected to at least one adjacent subunit. The prosthesis can be mechanically substantially isotropic. In some embodiments, an implantable prosthesis can be constructed by first forming each tapered mesh subunit or tapered mesh body as will be described in more detail below, and then connecting each tapered mesh subunit to adjacent subunits to form a prosthesis that is mechanically substantially isotropic. As will be described in more detail below, being mechanically substantially isotropic refers to the property of having similar compressive stiffness along more than one orientation of the prosthesis. An implantable prosthesis that is mechanically substantially isotropic can have the benefit of mimicking natural tissue during palpation and providing uniform structural support to anatomical structures. Thus, the prosthesis can exhibit mechanical properties commensurate with natural tissue, such that the prosthesis or resection site is substantially untouchable on the subject.

[0046] In some embodiments, an implantable prosthesis can be formed from an assembly of tapered mesh subunits or tapered mesh bodies, each of which has a sidewall that can be connected to the sidewalls of an adjacent or neighboring subunit or body. Such a prosthesis can be constructed by the following process: first, each tapered mesh subunit or tapered mesh body is formed, and the sidewall of each body is connected to the sidewall of an adjacent body. The connection between the various subunits or bodies can enhance the mechanical robustness of the prosthesis. The connection formed between the sidewalls of the body can be used to integrate the tapered subunits into a final implantable prosthesis so that pressure from the surrounding anatomical structures can be evenly distributed within the prosthesis while reducing the risk of dispersal.

[0047] In some embodiments, an implantable prosthesis can be formed by an assembly of subunits or bodies, each of which is connected to another subunit in the subunit. A subunit can include a first portion that is connected to another portion of the subunit and is arranged inside a volume defined by another portion of the subunit. Such a prosthesis can be constructed by the following process: first, each subunit in the subunit is formed, a portion of the subunit is arranged to another portion of the subunit, the two portions are connected, and each subunit is connected to an adjacent or neighboring subunit. In this way, the subunits of the prosthesis can benefit from a larger volume of material, which can further strengthen the prosthesis and support natural tissue. As will be described in more detail below, the various portions of the subunit can be different in geometry to induce tissue ingrowth while optimizing the mechanical properties of the prosthesis.

[0048] In some embodiments, the prosthesis of the present invention can induce tissue infiltration through the pores, which can enable cells to proliferate through the prosthesis. The prosthesis can have porosity on multiple length scales. For example, the internal volume of the conical subunit of the prosthesis can provide large gaps for tissue ingrowth. The subunit itself can be formed by a reticular or macroporous (having large holes) material, which can allow the prosthesis to accommodate enough autologous fat, biomaterials, microphages, fibroblasts, collagen, hyaluronic acid and / or bioactive agents to promote angiogenesis and tissue ingrowth in the prosthesis. In some embodiments, the prosthesis can be formed by a material with pores greater than 10 microns to limit the risk of rejection and scar tissue formation. As used herein, the term "macroporous" or "reticular" refers to an average pore diameter greater than or equal to 10 microns, 20 microns, 30 microns, 40 microns, 50 microns, 60 microns, 75 microns, 100 microns and / or any other suitable pore size.

[0049] In some embodiments, the implantable prosthesis of the present invention may preferably have a roughly ellipsoidal shape to simulate the anatomical cavity left by tissue removal surgery (e.g., tumor resection) and / or any other natural or surgically formed cavity. Specifically, in some embodiments, the prosthesis may have a spherical shape. However, it should be understood that the implantable prosthesis of the present invention may have any suitable three-dimensional shape, including but not limited to a sphere, an ellipsoid, a hemisphere, a cylinder, a cone, a dome, a cuboid, a tetrahedron, a triangular or square prism, a dodecahedron, a combination thereof, and / or a customized geometry. It should be understood that the term "ellipsoidal" as used herein refers to an ellipsoidal three-dimensional shape (which can have different average diameters in two or more directions), a spherical shape, and a spherical shape (which can have substantially similar average diameters in all directions).

[0050] It should be understood that the prosthesis of the present disclosure can have any suitable size to adapt to a given application. For example, the prosthesis can be sized to fit within a tissue removal (e.g., tumor resection) site. Therefore, the prosthesis can have any suitable size. The prosthesis can be characterized by an average diameter, which in some preferred embodiments can preferably be between about 2 cm and 5 cm, but other sizes can also be envisioned, including prostheses with an average diameter greater than or equal to 0.5 cm, 1 cm, 1.5 cm, 2 cm, 3 cm, 4 cm, 5 cm, 6 cm, 7 cm, 8 cm, and / or any other suitable size. The prosthesis can also have an average diameter less than or equal to 8 cm, 7 cm, 6 cm, 5 cm, 4 cm, 3 cm, 2 cm, 1.5 cm, 1 cm, 0.5 cm, and / or any other suitable size. Combinations of the foregoing can also be envisioned, including prostheses with an average diameter between 0.5 cm and 5 cm and between 2 cm and 8 cm, including prostheses greater than or less than the previously mentioned ranges.

[0051] In some embodiments, the prosthesis can have a first average diameter across a first direction of the prosthesis and a second average diameter across a second direction. For example, the prosthesis can be generally ellipsoidal. Thus, it should be understood that the aforementioned average diameter ranges can be employed with respect to any suitable size of the prosthesis, as the present disclosure is not limited by the geometry of the implantable prosthesis.

[0052] As previously described, in some embodiments, the implantable prosthesis can be formed by twelve connected subunits. However, it should be understood that any suitable number of subunits can be used to form an implantable prosthesis of any suitable shape. The prosthesis can have more than or equal to 1, 5, 10, 15, 20, 25, 30, 35, 40, 50, and / or any other suitable number of subunits. The prosthesis can also have less than or equal to 50, 40, 35, 30, 25, 20, 15, 10, 5, 1, and / or any other suitable number of subunits. Combinations of the foregoing are also contemplated, including prostheses with between 1 and 50 and between 1 and 12 subunits, as well as prostheses with the number of subunits above the previously mentioned ranges. As will be described in detail below, in some embodiments, multiple layers of subunits can be used to enhance mechanical compressibility. Therefore, the prosthesis of the present disclosure is not limited by the number of subunits.

[0053] In some embodiments, the subunits of the prosthesis may also have three-dimensional shapes, such as those mentioned previously. In some embodiments, a combination of subunit geometries may be employed to achieve suitable mechanical behavior. For example, a subunit of the prosthesis may have a generally conical shape.

[0054] It should be understood that the terms "conical" or "tapered" as used herein refer to conventional cones and cone-like shapes, as well as partial cone shapes, such as a frustum of a cone, which may not have a sharp tip.

[0055] The subunits of the implantable prosthesis described herein can be arranged and fixed in a three-dimensional configuration by any suitable means. In some embodiments, the subunits can be fixed in their three-dimensional configuration by any suitable combination, heat sealing, welding (e.g., ultrasonic or other means), adhesive bonding, combinations thereof, and / or any other suitable technology. In some embodiments, the subunits can be fixed in their three-dimensional configuration by a permanent or non-permanent arrangement. For example, fasteners such as staples or sutures can be used to form subunits and / or link adjacent subunits together in a non-permanent manner. It should be understood that any of the aforementioned fixing techniques can be used to fix adjacent subunits together. Any suitable combination of fixing techniques can be used to form the prosthesis, as the present disclosure is not limited thereto.

[0056] In some embodiments, as described in more detail below with respect to the accompanying drawings, the subunits used in the implantable prosthesis used in this article can be made of a two-dimensional substrate. The substrate itself can be formed from a two-dimensional sheet. The two-dimensional substrate can be formed using any suitable technology, including but not limited to trimming or cutting with scissors, blades, other sharp cutting instruments or hot knives, laser cutting techniques, welding techniques, die-cutting techniques, combinations thereof, and / or any other suitable technology. In other embodiments, the substrate can be formed using additive manufacturing techniques, such as 3D printing.

[0057] The implantable prosthesis of the present disclosure can be formed of a material that can promote rapid ingrowth of tissue or muscle into and around the prosthesis.In some embodiments, the prosthesis can be formed of one or more layers of knitted mesh fabric. Non-limiting examples of surgical materials that can be used include BARD Mesh (available from CRBard), BARD SoftMesh (available from CRBard), SOFT TISSUE PATCH (microporous ePTFE - available from WL Gore & Associates), SURGIPRO (available from US Surgical), TRELEX (available from Meadox Medical), PROLENE and MERSILENE (available from Ethicon), PHASIX Mesh (available from CRBard), polylactose (VICRYL - available from Ethicon) and polyglycolic acid (DEXON - available from US Surgical), collagen materials such as COOK SURGISIS (available from Cook Biomedical), combinations thereof, and / or any other mesh material (e.g., available from Atrium Medical Corporation). The implantable material can be formed from a planar mesh substrate. In some embodiments, the mesh material may be formed from multifilament yarns, and any suitable method may be used to form the mesh material, such as knitting, braiding, plaiting, molding, and the like.

[0058] In some embodiments, the prosthesis can be made of permanent materials, such as non-degradable thermoplastic polymers, including polymers and copolymers of ethylene and propylene, including ultra-high molecular weight polyethylene, ultra-high molecular weight polypropylene, nylon, polyesters such as poly(ethylene terephthalate), poly(tetrafluoroethylene), polyurethanes, poly(ether-urethane), poly(methyl methacrylate), polyetheretherketone, polyolefins, and poly(ethylene oxide). In other embodiments, the prosthesis can be formed of degradable materials, including but not limited to thermoplastic or polymeric degradable materials. Combinations of the foregoing are also contemplated. In some embodiments, the prosthesis can be formed of one or more absorbable polymers or copolymers, absorbable thermoplastic polymers and copolymers, and / or absorbable thermoplastic polyesters. The prosthesis can be formed from polymers including, but not limited to, polymers formed from glycolic acid, lactic acid, 1,4-dioxanone, trimethylene carbonate, 3-hydroxybutyric acid, 4-hydroxybutyric acid, e-caprolactone, including polyglycolic acid, polylactic acid, polydioxanone, polycaprolactone, copolymers of glycolic acid and lactic acid such as polymer, and Polymers, and include poly(lactide-co-caprolactone); poly(orthoesters); polyanhydrides; poly(phosphazenes); polyhydroxyalkanoates; synthetically or biologically prepared polyesters; polycarbonates; tyrosine polycarbonate; polyamides (including synthetic and natural polyamides, polypeptides and poly(amino acids)); polyesteramides; poly(alkylene alkylates); polyethers (such as polyethylene glycol, PEG and polyethylene oxide, PEO); polyvinylpyrrolidone or PVP; polyurethanes; polyetheresters; polyacetals; polycyanoacrylates; poly(oxyethylene) / poly(oxypropylene) copolymers; poly Acetals, polyketals; polyphosphates; (phosphorus-containing) polymers; polyphosphate esters; polyalkylene oxalates; polyalkylene succinates; poly(maleic acid); silk (including recombinant silk and silk derivatives and analogs); chitin; chitosan; modified chitosan; biocompatible polysaccharides; hydrophilic or water-soluble polymers, such as polyethylene glycol (PEG) or polyvinylpyrrolidone (PVP), and blocks of other biocompatible or biodegradable polymers, such as poly(lactide), poly(lactide-co-glycolide) or polycaprolactone and copolymers thereof, including random copolymers and block copolymers thereof.

[0059] In some embodiments, the prosthesis can be formed from a material blend of absorbable polymers, including but not limited to polymers formed from glycolic acid, lactic acid, 1,4-dioxanone, trimethylene carbonate, 3-hydroxybutyric acid, 4-hydroxybutyric acid, e-caprolactone, 1,4-butanediol, 1,3-propylene glycol, ethylene glycol, glutaric acid, malonic acid, oxalic acid, succinic acid, adipic acid, or copolymers thereof. In some embodiments, the prosthesis can be formed from poly-4-hydroxybutyrate or a copolymer thereof.

[0060] In some embodiments, implantable prostheses can provide a device for delivering cells, stem cells, differentiated cells, adipocytes, muscle cells, platelets, pedicles, vascular pedicles, tissue blocks, extracellular fat matrix proteins, gels, hydrogels, hyaluronic acid, collagen, bioactive agents, drugs, antibiotics and other materials to the implant site. The cells and tissues that can be delivered and / or coated or injected into the prosthesis can be autologous. The prosthesis can be used for autologous fat transfer. The cells added, coated or injected into the prosthesis can include pancreatic islet cells, hepatocytes and stem cells that have been genetically modified to contain genes for treating patient diseases. The prosthesis can include bioactive agents to stimulate cell ingrowth, including growth factors, cell adhesion factors, cell differentiation factors, cell recruitment factors, cell receptors, cell binding factors, cell signaling molecules such as cytokines and molecules to promote cell migration, cell division, cell proliferation and extracellular matrix deposition. The prosthesis can also be partially or completely coated and / or include reagents to prevent tissue adhesion or to prevent cell proliferation, particularly delaying cell invasion into the prosthesis.

[0061] In some embodiments, the implantable prosthesis can be loaded, filled, coated, or otherwise incorporated with a bioactive agent. Bioactive agents can be included in the prosthesis for a variety of reasons. For example, a bioactive agent can be included to improve tissue ingrowth into the implant, improve tissue maturation, provide for delivery of an active agent, improve wettability of the implant, prevent infection, and improve cell attachment. The bioactive agent can also be incorporated into the material composition of the substrate of the subunit.

[0062] The prosthesis can include an agent designed to stimulate cell ingrowth, including growth factors, cell adhesion factors including cell adhesion polypeptides, cell differentiation factors, cell recruitment factors, cell receptors, cell binding factors, cell signaling molecules such as cytokines, and molecules that promote cell migration, cell division, cell proliferation, and extracellular matrix deposition. Such agents include fibroblast growth factor (FGF), transforming growth factor (TGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), granulocyte-macrophage colony stimulating factor (GMCSF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), hepatocyte growth factor (HGF), interleukin-1-B (IL-1B), interleukin-8 (IL-8), and nerve growth factor (NGF), and combinations thereof. As used herein, the term "cell adhesion polypeptide" refers to a compound having at least two amino acids per molecule that is capable of binding to cells via cell surface molecules. Cell adhesion polypeptides include any of the proteins of the extracellular matrix known to play a role in cell adhesion, including fibronectin, vitronectin, laminin, elastin, fibrinogen, collagen type I, collagen type II, and collagen type V, as well as synthetic peptides with similar cell adhesion properties. Cell adhesion polypeptides also include peptides derived from any of the aforementioned proteins, including fragments or sequences containing binding domains.

[0063] In some embodiments, the implantable prosthesis can be loaded, filled, coated, or otherwise combined with a wetting agent designed to improve the wettability of various surfaces of the prosthesis to allow fluids to readily adsorb onto the prosthesis surface and promote cell attachment and / or alter the water contact angle of the prosthesis surface. Examples of wetting agents include polymers of ethylene oxide and propylene oxide such as polyethylene oxide, polypropylene oxide, or copolymers of ethylene oxide and propylene oxide such as Other suitable wetting agents may include surfactants or emulsifiers.

[0064] In some embodiments, implantable prostheses can be loaded, filled, coated, or otherwise incorporated with gels, hydrogels, or active hydrogel hybrids to further improve wetting properties and promote cell growth throughout the prosthesis. Hydrogel hybrids consist of living cells encapsulated in biocompatible hydrogels such as gelatin, methacrylated gelatin (GelMa), silk gels, and hyaluronic acid (HA) gels.

[0065] Other bioactive agents that can be incorporated into the prosthesis can include antimicrobials, particularly antibiotics, disinfectants, tumor agents, anti-scarring agents, anti-inflammatory agents, anesthetics, small molecule drugs, anti-adhesives, cell proliferation inhibitors, anti-angiogenic factors and pro-angiogenic factors, immunomodulators and coagulants. Bioactive agents can be proteins such as collagen and antibodies, peptides, polysaccharides such as chitosan, alginate, hyaluronic acid and derivatives thereof, nucleic acid molecules, small molecular weight compounds such as steroids, inorganic materials such as hydroxyapatite and ceramics or complex mixtures such as platelet-rich plasma. Suitable antimicrobials include: bacitracin, biguanide, triclosan, gentamicin, minocycline, rifampicin, vancomycin, cephalosporins, copper, zinc, silver and gold. Nucleic acid molecules can include DNA, RNA, siRNA, miRNA, antisense molecules or aptamers.

[0066] In some embodiments, the implantable prosthesis can be loaded, filled, coated or otherwise combined with allograft material and xenograft material, including acellular dermal matrix material and small intestinal submucosa (SIS). In embodiments, the prosthesis can include a vascular pedicle or other tissue mass. In some embodiments, the prosthesis can be combined with a system for controlled release of a therapeutic or prophylactic agent.

[0067] In some embodiments, implantable prosthesis can be loaded, filled, coated or otherwise combined with allograft or xenograft tissue and cells before, during or after implantation or in any combination thereof. In some embodiments, prosthesis can be coated with autologous tissue and cells from the patient before, during or after implantation or in any combination thereof. Autologous tissue and cells can include one or more of the following: autologous fat, lipoaspirate, adipose tissue, injectable fat, adipose tissue, adipose cells, fibroblasts and stem cells, stem cells including human adipose tissue-derived stem cells, also referred to as precursor adipocytes or adipose tissue-derived precursor cells and fibroblast-like stem cells. In one embodiment, prosthesis can be coated with autologous tissue and cells as described herein, and can further include vascular pedicles or other tissue blocks. As will be apparent herein, prosthesis is designed to not only produce the shape of an implant, such as a breast implant, but also produces a large surface area that can retain autologous tissue and cells to promote tissue ingrowth.

[0068] In some embodiments, the prosthesis can be formed of an absorbable material (e.g., a polymer or copolymer) that can be substantially resorbed within a timeframe of 1 month to 24 months, or within a timeframe of 3 months to 18 months after implantation, and retain some residual strength for at least 2 weeks to 6 months.

[0069] In some embodiments, the polymer and copolymer compositions of the prosthesis can have a low moisture content to ensure that the prosthesis can be produced with stiffness comparable to natural tissue, extended strength retention, and good shelf life. In some embodiments, the polymers and copolymers used to prepare the prosthesis have a moisture content of less than 1,000 ppm (0.1 wt%), less than 500 ppm (0.05 wt%), less than 300 ppm (0.03 wt%), less than 100 ppm (0.01 wt%), and / or less than 50 ppm (0.005 wt%).

[0070] It should be understood that the composition used to prepare the prosthesis can have a low endotoxin content. In some embodiments, the endotoxin content can be low enough so that the prosthesis produced from the polymer composition has an endotoxin content of less than 20 endotoxin units per prosthesis as determined by the Limulus Amebocyte Lysate (LAL) assay. For example, the polymer composition used to prepare the prosthesis can have an endotoxin content of <2.5 EU / g polymer or copolymer. In another example, the P4HB polymer or copolymer or the PBS polymer or copolymer has an endotoxin content of <2.5 EU / g polymer or copolymer.

[0071] In some embodiments, the prosthesis of the present disclosure may include one or more markers for external detection of the position of the prosthesis. For example, the prosthesis may include a radiopaque marker (e.g., a metal staple) that can be visible and conspicuous on nearby anatomical structures during x-ray imaging. The marker can be formed of any suitable medical material that can be used for medical imaging and is approved for long-term use. Medical imaging methods include, for example, radiographic imaging modalities (e.g., x-ray imaging), magnetic resonance imaging (MRI), ultrasound, fluoroscopy, or computed tomography. The marker can therefore be formed of any non-absorbable biocompatible material, which refers to a material that does not cause any adverse reactions to the patient's health and does not decompose during the patient's lifetime. Non-absorbable biocompatible materials include, but are not limited to, metal-containing materials, polymeric materials, ceramic materials, or composite materials including metals, polymers, or combinations of metals and polymers. Suitable metals include, but are not limited to, gold, iridium, nickel, rhodium, silver, tantalum, titanium, stainless steel, alloys thereof, combinations thereof, and / or other metals. Suitable polymers include, but are not limited to, polyvinyl alcohol, polyurethane, polyolefin, polyester, polypropylene, polyimide, polyetherimide, fluoropolymers, thermoplastic liquid polymers (LCP) such as Celanese, Polyvinyl ether ketone, such as Vitrex PEEK TM , polyamide, polycarbonate such as Bayer Polymers Polysulfone, polyethersulfone, polyphenylsulfone, such as Rowland Technologies Nylon, nylon copolymers, combinations thereof, and / or other polymers. In some embodiments, a marker may comprise a shape memory material including, but not limited to, nitinol, titanium, or any shape memory polymer.

[0072] In some embodiments, the prosthesis of the present disclosure may include one or more brachytherapy particles that release low-level radiation for treatment. The particles can be physically attached to the prosthesis and, in some cases, can be embedded in components of the tapered mesh body. The number and position of the brachytherapy particles can be customized to target the radiation therapy. For example, the prosthesis can include between six and thirty-six particles. In some cases, the particles are arranged in a pattern directed by a radiation oncologist and / or nuclear medicine physician. Typically, the particles can include a suitable radioactive agent (e.g., I-125, Ir-192, Pd-103) and can have a metal shell (e.g., stainless steel, titanium-aluminum-vanadium). The brachytherapy particles can be radiopaque. In embodiments where the implanted prosthesis resorbs, the particles can remain in the body. In some embodiments, the subunit substrate can include one or more visual and / or tactile fiducial markers to facilitate assembly. In some embodiments, the fiducial markers can indicate the location of fixation points (e.g., welding points). For assembly purposes, the fiducial markers can be visually / optically or otherwise apparent to the operator. In some embodiments, the fiducial markers can be colored differently from the prosthesis substrate or otherwise distinguishable from the underlying prosthesis substrate. In some embodiments, the fiducial markers can be colored differently relative to the underlying substrate. In some embodiments, a prosthesis can include multiple fiducial markers that are colored with more than one color to distinguish the fiducial markers from each other. For example, a first set of fiducial markers can be used to indicate fixation points within a single subunit substrate in a first color, and a second set of fiducial markers can be used to indicate fixation points between adjacent subunit substrates. It should be understood that any combination of fiducial marker types can be employed on any prosthesis subunit of the present disclosure.

[0073] In some embodiments, the prosthesis itself can be colored. For example, coloring can be used to enhance visualization and / or provide visual alignment to help surgeons during surgery. The prosthesis can be colored in various ways. In some embodiments, dyes / pigments (e.g., medical grade colorants) can be incorporated (e.g., impregnated) into the prosthesis. In some embodiments, a colored coating can be applied to the outer surface of the prosthesis.

[0074] The implantable prostheses of the present disclosure can exhibit any suitable mechanical properties to simulate natural anatomical structures. In some embodiments, the prosthesis can exhibit compressive stiffness to simulate the mechanics of natural tissue while still providing support to the surrounding anatomical structures after implantation. As used herein and described in further detail below, compressive stiffness is defined as the normalized compressive load applied to a subject during a compression test divided by its relative strain.

[0075] The prosthesis of the present disclosure can have any suitable compression stiffness, including but not limited to being greater than or equal to 0.5psi, 1psi, 1.5psi, 1.8psi, 2psi, 3psi, 4psi, 5psi, 6psi, 6.8psi, 7psi, 8psi, 9psi, 10psi, 12psi, 15psi, and / or any other suitable stiffness. The prosthesis can also exhibit a compression stiffness less than or equal to 15psi, 12psi, 10psi, 9psi, 8psi, 7psi, 6.8psi, 6psi, 5psi, 4psi, 3psi, 2psi, 1.8psi, 1.5psi, 1psi, 0.5psi, and / or any other suitable stiffness. Combinations of the foregoing are also contemplated, including prostheses having a compression stiffness between 0.5psi and 15psi and between 1.8psi and 6.8psi, as well as prostheses having a compression stiffness above and below the above ranges. It should be understood that the stiffness can be designed to simulate or support tissue at the implant site. Thus, the prosthesis may have any suitable stiffness above or below the aforementioned ranges.

[0076] It should be understood that, in some embodiments, the implantable prosthesis of the present disclosure can be mechanically substantially isotropic, which can refer to the isotropic nature of the prosthesis's compressive stiffness (and / or any other mechanical properties). A prosthesis can exhibit similar mechanical properties in multiple orientations. In some embodiments, a prosthesis having substantially isotropic compressive stiffness refers to a prosthesis having a first compressive stiffness along a first direction and a second compressive stiffness along a second direction, such that the first and second compressive stiffnesses are within 30% of each other, but first and second compressive stiffnesses within other ranges (e.g., within 25%, 15%, 10%, 5%) are also contemplated. The first and second directions can refer to the major / minor axes of the structure (e.g., when the prosthesis is formed into an ellipsoidal shape), or can refer to any other suitable directions. For example, a prosthesis that is mechanically substantially isotropic can refer to a prosthesis having a compressive stiffness of 3 psi in the horizontal direction and a compressive stiffness between 2.6 psi and 3.4 psi in the vertical direction. Thus, the first direction and the second direction may be perpendicular to each other, although other arrangements are also contemplated.

[0077] In other embodiments, the mechanical properties of the implantable prosthesis can be anisotropic (e.g., orientation-dependent). Thus, it should be understood that one or more orientations of the implantable prosthesis can exhibit any of the aforementioned mechanical properties. It should also be understood that the mechanical properties of the prosthesis can be selected to mimic the natural tissue properties of the implant site. Thus, depending on the implant site, the mechanical properties of the prosthesis can be any suitable value above or below the above-mentioned ranges.

[0078] In some embodiments, the implantable prosthesis of the present disclosure can be sufficiently compressed to fit through an incision smaller than the prosthesis itself. For example, an implantable prosthesis having an average diameter of 2 cm can be compressed to 0.5 cm so that it can fit through a 1.5 cm incision. It should be understood that the compressibility of the prosthesis can be temporary, and after compression, the prosthesis can recover to within 10% of its original size.

[0079] In some embodiments, the implantable prostheses of the present disclosure may include features to significantly reduce the risk of prosthesis migration. For example, the markers may have the additional benefit of creating friction within the implant site to limit migration of the prosthesis. In other embodiments, the prosthesis may include other features to limit migration and / or reorientation of the markers after implantation. It should be understood that in embodiments where the prosthesis is formed from a generally resorbable material, the prosthesis may be secured or engaged relative to nearby tissue by tissue infiltration of the prosthesis. Thus, in some embodiments, the prosthesis may reduce the risk of migration through material properties.

[0080] The implantable prosthesis of the present disclosure can be used in any suitable application. In some embodiments, the prosthesis can be implanted in soft tissue after biopsy (and / or any other surgery, such as tumor resection) during the treatment of cancers such as breast cancer, abdominal cancer, liver cancer, muscle cancer, kidney cancer, lung cancer and prostate cancer. In some embodiments, the prosthesis can be used in soft tissue reconstruction applications, so that the prosthesis can be used as a breast implant, a breast lift device, a breast enlargement device, a nipple implant, a facial reconstruction device, a buttocks implant, a zygomatic augmentation device, a cosmetic repair device, a soft tissue regeneration device, a hernia implant, a hernia plug, a wound healing device, a tissue engineering scaffold, a scaffold for a vascular pedicle or other tissue mass, a guided tissue repair / regeneration device, an expansion or filling device, a void filler, a device for treating vesicoureteral reflux, a cell seeding device, a drug delivery device, a combination thereof, and / or any other suitable application.

[0081] Turning to the drawings, specific non-limiting embodiments are described in further detail. It should be understood that the various systems, components, features, and methods described with respect to these embodiments can be used alone and / or in any desired combination, as the present disclosure is not limited to the specific embodiments described herein.

[0082] Figure 1A to Figure 1B Two isometric views of an implantable prosthesis 100 according to some embodiments are shown. The prosthesis 100 can be formed from tapered subunits 20 that can be arranged to form a generally ellipsoidal shape. Specifically, as Figure 1A to Figure 1BAs shown in , the prosthesis can have a generally spherical shape. The central portion of the prosthesis 100 can include a hollow core 60 to allow for tissue ingrowth, which in some embodiments can create a more natural feel during tissue infiltration of the implant. In some embodiments, the prosthesis can include one or more markers 30, which can have radiopaque properties. As previously described, the markers 30 can aid in accurate visualization of the position of the prosthesis after implantation within the anatomical structure.

[0083] It should be understood that although Figure 1A to Figure 1B The prosthesis 100 shown in FIG is shown as having a generally spherical shape, but any suitable shape of prosthesis may be used to fill a biopsy or tumor resection cavity or for other prosthetic purposes. It should also be understood that although Figure 1A to Figure 1B The prosthesis 100 shown in FIG is formed from an assembly of twelve tapered subunits 20, but any suitable number of subunits (tapered or otherwise) may be employed to form any of the implantable prostheses described herein. Thus, the prostheses of the present disclosure are not limited by shape, size, number of subunits, shape of subunits, arrangement of subunits, and / or any other factors.

[0084] Figures 2A to 2B Various views of a tapered subunit 20 are shown, according to some embodiments. Figure 2A Depicted is a top view of a generally two-dimensional substrate 22 that can be manipulated (e.g., rolled) into a Figure 2B 20. In some embodiments, the substrate can be formed of a porous biocompatible mesh material. In some embodiments, the end portions of the substrate 22 can overlap to form an overlap region 24, wherein the end portions can then be secured to each other. In some embodiments, welds 29 can secure the end portions of the substrate 22 together, such as Figure 2B As shown in FIG, but other temporary and permanent fixing methods are also contemplated. Figure 2A The roughly two-dimensional arrangement shown in is transformed into Figure 2B In some embodiments, the subunits can have a conical frustum (or "cone") shape, while in other embodiments, the subunits can form different three-dimensional shapes.

[0085] like Figure 2B As shown in FIG, the overlap region 24 of each tapered subunit 20 can contribute to the overall mechanical properties of the subunit and the prosthesis. For example, a larger overlap region can produce a stiffer subunit when compared to a smaller overlap region. In part, this increase in stiffness can be due to the change in thickness of the subunit, being two layers instead of one. The overlap region 24 can be defined by the degree of overlap O1, as shown in FIG. Figure 2B As shown in , the overlap O1 can be added to the non-overlap O2 to add up to approximately 360°. The overlap O1 can be any suitable value to achieve the desired stiffness of the subunit. The overlap can be greater than or equal to 5°, 10°, 15°, 20°, 25°, 30°, 35°, 40°, 45°, 50°, 55°, 60°, 65°, 70°, 75°, 80°, 85°, 90°, 100°, and / or less than or equal to 100°, 95°, 90°, 85°, 80°, 75°, 70°, 65°, 60°, 55°, 50°, 45°, 40°, 35°, 30°, 25°, 20°, 15°, 10°, 5°, and / or combinations thereof.

[0086] It should be understood that although the fixing points (e.g., welds) 29 are depicted as being generally circular, non-circular fixing points are also contemplated. In some embodiments, rectangular or elongated fixing points may be employed to provide enhanced fixation between substrate portions and / or between adjacent subunits. In some embodiments, rectangular or elongated fixing points may help to secure various components in more than one direction. In some embodiments, rectangular or elongated fixing points may replace multiple circular fixing points. For example, a series of three welds may be replaced by a single elongated fixing point. This substitution may speed up the assembly process. In some embodiments, elongated fixing points may enhance the rigidity of the subunits.

[0087] In some embodiments, as Figure 2A As shown in FIG, the substrate 22 can be formed into a generally C-shaped arrangement. A central portion 26 of the substrate 22 can be removed to allow tissue to grow inward through the implantable prosthesis, such as Figure 1A to Figure 1B The substrate 22 may also include a cutout around the substrate 22 spanning a cutout angle A1, as shown in FIG. Figure 2A This cutout allows the substrate 22 to be manipulated to form the sidewalls of a three-dimensional cone. In some exemplary embodiments, Figure 2B The subunits 20 shown in the figure can have a sidewall angle of approximately 63°, so that twelve identical subunits can together form a generally spherical implantable prosthesis. In some embodiments, the sidewall angles of the subunits can be greater than or less than 63°, including between 50° and 70°, between 60° and 65°, and / or any other suitable sidewall angle range. Of course, it is also contemplated that prostheses with different numbers of subunits having different geometries can be used to form spherical or non-spherical prostheses.

[0088] Figure 2AThe cutout angle A1 shown in FIG can be any suitable angle that enables the formation of a conical frustum. In some embodiments, the substrate can include a cutout spanning an angle A1 approximately equal to 0° instead of a cutout. In some embodiments, the cutout angle A1 can be greater than or equal to 0°, 5°, 10°, 15°, 20°, 30°, 40°, 50°, 65°, 80°, 90°, 100°, 120°, 135°, 150°, 180°, and / or any other suitable angle. The cutout angle A1 can also be less than or equal to 180°, 150°, 135°, 120°, 100°, 90°, 80°, 65°, 50°, 40°, 30°, 20°, 15°, 10°, 5°, 0°, and / or any other suitable angle. Combinations of the foregoing are also contemplated, including cutout angles between 0° and 180°. In some embodiments, the resection angle A1 can be 40°. In other embodiments, the resection angle A1 can be 65°. In still other embodiments, the resection angle A1 can be 135°. Of course, resection angles above and below the aforementioned ranges can also be envisioned. It should be understood that any implantable prosthesis disclosed herein can be formed by more than one tapered (or other shaped) subunit having the same or different resection angles.

[0089] In some embodiments, the substrate 22 can be characterized by an average diameter D1. The average substrate diameter D1 can be any suitable size to properly fit within the implant site and / or accommodate any other suitable application. In some exemplary embodiments, the average diameter D1 of the substrate 22 can be greater than or equal to 1 cm, 1.5 cm, 2 cm, 2.2 cm, 2.5 cm, 2.8 cm, 3 cm, 3.2 cm, 3.5 cm, 3.8 cm, 4 cm, 4.5 cm, 5 cm, 6 cm, 7 cm, 8 cm, and / or any other suitable size. The average diameter D1 of the substrate 22 can also be less than or equal to 8 cm, 7 cm, 6 cm, 5 cm, 4.5 cm, 4 cm, 3.8 cm, 3.5 cm, 3.2 cm, 3 cm, 2.8 cm, 2.5 cm, 2.2 cm, 2 cm, 1.5 cm, 1 cm, and / or any other suitable size. Combinations of the foregoing ranges are also contemplated, including average substrate diameters between 1 cm and 8 cm, as well as sizes above and below the aforementioned ranges.

[0090] In some embodiments, the central portion 26 of the substrate 22 can be characterized by a core percentage value representing the ratio of the average diameter D2 of the central portion 26 to the average diameter D1 of the substrate 22. The core percentage can be any suitable value that allows sufficient tissue ingrowth in the implantable prosthesis while still maintaining sufficient mechanical rigidity to support surrounding tissue after implantation. The core percentage can be any suitable value greater than or equal to 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 50%, and / or any other percentage. The core percentage can also be less than or equal to 50%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, and / or any other suitable percentage. Combinations of the foregoing ranges are also contemplated, including core percentages between 10% and 35% and between 5% and 50%, as well as ranges above the aforementioned ranges.

[0091] In some embodiments, the core percentage of a subunit can yield a total hollow core percentage of an implantable prosthesis, which can represent the ratio of the hollow central volume of the prosthesis to the total volume of the prosthesis. The hollow core percentage of a prosthesis can be greater than, equal to, or less than the core percentage of any given subunit of the prosthesis.

[0092] In some embodiments, substrate 22 may include one or more fiducial markers 28. Figure 2A As shown in Figure 2B . The end portions of substrate 22 can be folded together to align fiducial markers 28 and then secured together (e.g., using welding techniques) to form the sidewalls of the three-dimensional subunit. Of course, embodiments without fiducial markers are also contemplated.

[0093] In some embodiments, the fiducial mark and subsequent weld (or other fixing technique) may be spaced a distance D3 from the outer edge, as shown in FIG. Figure 2A . The distance can be sufficiently sized to enable a practitioner to secure the implantable prosthesis to tissue using fasteners. Thus, the weld can be spaced apart from the edge to provide clearance for the fasteners. In some embodiments, the distance can also provide ample space for other securing processes, such as securing between adjacent subunits. The distance D3 can be any suitable value greater than or equal to 2 mm, 2.5 mm, 3 mm, 5 mm and / or any other suitable distance away from the edge of the substrate. The distance can also be less than or equal to 5 mm, 3 mm, 25 mm, 2 mm and / or any other suitable distance away from the edge of the substrate. It should be understood that although in Figures 2A to 2BA single fiducial marker 28 and weld point 29 is shown in FIG, but subunits having more than one fiducial marker and weld point are also contemplated. In some embodiments, two weld points may enhance the rigidity of the subunit.

[0094] Figure 3 Depicted are tapered subunits according to some embodiments. As shown, the substrates 22 of the subunits can overlap within regions 24 to achieve a three-dimensional configuration. Figure 3 Also depicted are welds 29 formed in overlap regions 24. As shown, welds 29 can physically and permanently alter substrate 22 to secure the subunits in their three-dimensional configurations. However, embodiments are also contemplated in which fasteners, such as staples, are used to temporarily arrange the subunits in their three-dimensional configurations.

[0095] Figures 4A to 4D Various embodiments of tapered subunits having different cut-away angles A1 are depicted. As shown, in some embodiments, the cut-away angle can determine the extent of the overlap region 24. Figure 4B and Figure 4D shows subunits with similar sidewall angles. However, considering Figure 4B The cut-off angle A1 of the subunit (see Figure 4A ) is significantly greater than Figure 4D The cut-off angle A1 of the subunit (see Figure 4C ),but Figure 4D The overlap area 24 of the subunits is significantly larger. In some embodiments, the expanded overlap area can result in enhanced stiffness. It should be understood that the overlap area extension range can be selected depending on the final desired sidewall angle of the subunits, regardless of the cutout angle.

[0096] Figures 5A to 5B Two exemplary embodiments of an implantable prosthesis 100 are depicted. Both embodiments include twelve tapered subunits formed in a generally spherical arrangement. In some embodiments, as Figure 5A As illustrated, each cone may be secured to an adjacent cone by a weld 29. In other embodiments, such as Figure 5B As illustrated, each cone can be secured to an adjacent cone by two welds 29. In some embodiments, the addition of welds (between cones or within a single cone) can increase the overall stiffness of the implantable prosthesis.

[0097] Figures 6A to 6B Depicted is an implantable prosthesis 100 according to some embodiments. The prosthesis 100 may be formed from twelve subunits 20 having a generally conical truncated shape, such as Figure 6A. Each subunit 20 may include one or more welds 29A from the formation of the subunit itself and one or more welds 29B from the assembly of the prosthesis. In other words, welds 29A may be applied in the intra-subunit formation, and welds 29B may be applied in the inter-subunit assembly to secure adjacent subunits to each other. The prosthesis may also include one or more markers 30 to facilitate external visualization of the prosthesis using various medical imaging modalities (e.g., x-ray, MRI).

[0098] Figure 6B Depicted is a view taken along line 6B-6B. Figure 6A As shown, the core 60 of the prosthesis can have an average core diameter D5, which can be formed as a result of the truncated shape of the subunit 20. As described in more detail above, the prosthesis can have a hollow core percentage that is proportional to the ratio of the average core diameter D5 to the average prosthesis diameter D4, as shown in FIG. Figure 6B As shown in . Figure 6B The average prosthesis diameter D4 may be approximately 3 cm, although diameters greater than 3 cm and less than 3 cm are also contemplated, as described in more detail above.

[0099] The average core diameter D5 can be any suitable value to induce tissue ingrowth while maintaining suitable mechanical stiffness to support nearby tissue. The average core diameter D5 can be greater than or equal to 0.05 cm, 0.1 cm, 0.2 cm, 0.5 cm, 1 cm, 2 cm, and / or any other suitable size. The average core diameter D5 can also be less than or equal to 2 cm, 1 cm, 0.5 cm, 0.2 cm, 0.1 cm, 0.05 cm, and / or any other suitable size. Combinations of the foregoing ranges, including average core diameters D5 between 0.05 cm and 2 cm, as well as diameters above and below the foregoing ranges, are also contemplated. The average core diameter D5 can also be any suitable percentage of the average prosthesis diameter D4. In some embodiments, the average core diameter D5 can be greater than or equal to 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 50%, 60%, 75%, and / or any other percentage of the average prosthesis diameter. The average core diameter D5 may also be less than or equal to 75%, 60%, 50%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 2%, and / or any other suitable percentage of the average prosthesis diameter. Combinations of the aforementioned ranges, including average core diameters D5 between 10% and 35% and between 2% and 75% of the average prosthesis diameter, as well as the aforementioned ranges and the aforementioned ranges, are also contemplated. It should be understood that any suitable size of average core diameter and average prosthesis diameter (and any suitable ratio of average core diameter to average prosthesis diameter) may be employed, as the present disclosure is not limited by the geometry of the core.

[0100] 7A to 7C Three embodiments of spherical prostheses are shown, each formed from twelve conical subunits 20. All three prostheses have similarly sized cores 60 (eg, similar core diameters). However, the three prostheses differ in their average diameter. Figure 7A The average diameter D4 of the prosthesis is about 2 cm, Figure 7B The average diameter D4 is about 4 cm, and Figure 7C The average diameter D4 is about 5 cm. Figure 7C The hollow core percentage of the prosthesis shown in can be less than Figure 7A The percentage of hollow core of the prosthesis shown in .

[0101] In some embodiments, the number of fixation points (e.g., markings and welding points) may depend on the size of the prosthesis. Figure 7AA prosthesis is shown in which each subunit 20 has five intra-subunit welds 29A to enhance the rigidity of each subunit, and each subunit 20 has five inter-subunit welds 29B, in which a subunit is secured once to each of its adjacent subunits. Figures 7B to 7C Both show prostheses in which each of their twelve subunits includes six intra-subunit welds 29A and twelve inter-subunit welds 29B. However, due to the difference in average prosthesis diameter D4, Figure 7B and Figure 7C The arrangement structure and absolute position of the welding points are different.

[0102] It should be understood that prostheses with different subunits can also be envisioned, each having a different number and / or arrangement of subunits. It should also be understood that any implantable prosthesis of the presently disclosed implantable prostheses can be formed from any combination of subunits. In some embodiments, a prosthesis can be formed from multiple similar subunits, such as Figures 5A to 7C . In other embodiments, the prosthesis can be formed from different subunits. For example, the implantable prosthesis can include a first set of subunits having a first core percentage, a first average base material diameter, and a first cut-away angle, and a second set of subunits having a second core percentage, a second average base material diameter, and a second cut-away angle. Therefore, it should be understood that the implantable prosthesis of the present disclosure can utilize any number of subunits to form any combination of geometric, structural, and / or mechanical properties.

[0103] Figures 8A to 8B Various views of an implantable prosthesis 200 having a generally ellipsoidal shape are depicted. In some embodiments, the ellipsoidal shape of the prosthesis 200 can be achieved through a combination of three types of subunits: side cones 240, peak cones 250, and medial cones 260. Variations in subunit types enable an implantable prosthesis having an elongated ellipsoidal shape to accommodate similarly shaped implantation sites (e.g., a biopsy site or a tumor resection site).

[0104] 9A to 9F Shows the formation Figures 8A to 8B The substrate geometry of the three subunits of the prosthesis 200. In some embodiments, the side cone 240 can include a generally c-shaped substrate having a cutout that can be characterized by a cutout angle A1. It should be understood that the side cone substrate 242 can include an extension 243 that can partially deflect the c-shape of the side cone 240. The change in geometry enables the side cones to form a rounded ellipsoidal shaped prosthesis when used in conjunction with the peak cone and the middle cone. Similar to the previous discussion of Figure 2AIn the depicted embodiment, the side cone 240 may include one or more fiducial marks 248 to indicate weld points within a subunit, and one or more fiducial marks 247 for cone-to-cone (or inter-subunit) weld points. As previously described, any number of weld points for a subunit and / or between a subunit and its adjacent subunits may be employed to achieve the desired mechanical properties. In some embodiments, no fiducial marks may be employed.

[0105] Figure 9B depicts a peak cone according to some embodiments and Figure 9C An intermediate cone 260 is depicted according to some embodiments. Figure 2A In the embodiment shown in , the peak cone and the middle cone may include substrates 252, 262, and the cutout portion may be formed along the substrates 252, 262. The peak cone cutout angle A1 may be greater than the middle cone cutout angle A1, so that three-dimensional cones of different sizes can be formed. For example, Figure 9B As shown in FIG, the peak cone resection angle A1 can be 191.25°. However, other peak cone resection angles are also contemplated, including between 100° and 250° and between 135° and 210°. It should be understood that the peak cone resection angle can vary depending on the size of the implantable prosthesis. Thus, any suitable peak cone resection angle can be employed. Figure 9C An exemplary mid-cone cut-away angle A1 of 135° is shown, but as noted relative to the peak cone cut-away angle, any suitable cut-away angle, such as a cut-away angle between 40° and 140°, may be employed. Of course, the cut-away angle of any of the subunits of the present disclosure may be of any suitable size to enable the formation of sidewalls for suitable three-dimensional subunits. Both the peak cone and the mid-cone may include one or more fiducial marks 258, 268 to indicate weld points within the subunit, and one or more fiducial marks 257, 267 for cone-to-cone (or inter-subunit) welds. As previously described, any number of welds for a subunit and / or between a subunit and its adjacent subunits may be employed to achieve the desired mechanical properties. In some embodiments, no fiducial marks may be employed.

[0106] As previously described, in some embodiments, the implantable prosthesis can be ellipsoidal and non-spherical. In some embodiments, the ellipsoidal prosthesis can have an average height and an average width. Table 1 below summarizes an exemplary list of geometric properties of ellipsoidal implantable prostheses. Each of the prostheses listed in Table 1 is formed by a total of fourteen conical subunits, including two peak cones, eight side cones, and four intermediate cones, as previously described.

[0107]

[0108]

[0109] Table 1 - Lists exemplary geometrical properties of ellipsoidal and non-spherical prostheses.

[0110] In some embodiments, the ellipsoidal prosthesis can be used as compared to Figures 9A to 9C In other embodiments, the ellipsoidal prosthesis may be formed in a manner that can be combined with Figure 9B The cone 250 shown in FIG has different peak cones. For example, the ellipsoidal prosthesis can be formed by three cone subunits, the three cone subunits including: Figure 9D The side cone 240 shown in FIG. 1 may be similar to Figure 9A Side cone 240; Figure 9F The intermediate cone 260 shown in FIG. 1 may be similar to Figure 9C The middle cone 260; and Figure 9E The peak cone 2050 shown in FIG, which may be different from Figure 9B 2050. Specifically, the peak cone 2050 can be formed from a substrate 2052 having two extended portions 2053 that can partially bias the c-shaped configuration of the peak cone 2050. The peak cone 2050 can also include one or more fiducial marks 2058 to indicate welds within a subunit, and one or more fiducial marks 2057 for cone-to-cone (or inter-subunit) welds. As previously described, any number of welds for a subunit and / or between a subunit and its adjacent subunits can be used to achieve the desired mechanical properties. In some embodiments, no fiducial marks may be used.

[0111] It should be understood that Figure 9E A peak cone of 5 cm can be employed with an ellipsoidal prosthesis having a height of 5 cm and an average width of 4 cm to accommodate the larger geometry of the prosthesis.

[0112] Figures 10A to 10E Describes a method for assembling an ellipsoidal implantable prosthesis, such as Figures 8A to 8B The process of making an ellipsoidal implantable prosthesis as shown in FIG. The exemplary prosthesis can be formed from two peak cones, eight side cones and four middle cones. However, it should be understood that any suitable number of any subunits can be used. Initially, each subunit can be assembled from its two-dimensional substrate into a three-dimensional configuration as previously described. Subsequently, as Figure 10AAs shown in FIG, the peak cone 250 can be aligned with the side cone 240 so that the top edges are aligned. The side walls of the two cones can be clamped together to align and then fixed to each other (e.g., by welding). Then, the three other side cones 240 can be fixed to the central peak cone 250 with the help of the reference marks 249, 259 on the side cones and peak cones, respectively, as shown in FIG. Figure 10B It will be appreciated that each side cone may be welded to the peak cone one or more times, and additionally welded to each of its adjacent cones one or more times.

[0113] The subassembly of the peak cone 250 and the four side cones 240 can be repeated to form the two partial halves of the prosthesis. Figure 10C As shown in , the four side cones from each segment half can be fixed to each other, thereby connecting the two segment halves. However, as Figure 10C As shown in FIG, there may be gaps 290 between the side cones in the central portion of the prosthesis. These gaps may be filled with the middle cone 260, as shown in FIG. Figure 10D As shown in . Each middle cone 260 can be welded to four adjacent side cones 240 at least once. Figure 10E As shown in FIG, the final prosthesis formed by a total of fourteen subunits may appear to be roughly ellipsoidal. It should be understood that Figures 10A to 10E The assembly process described is non-limiting, and any other assembly process may be employed to form the implantable prosthesis of the present disclosure.

[0114] As described in more detail above, the implantable prosthesis can exhibit substantially isotropic mechanical properties, such as compressive stiffness. In some embodiments, the implantable prosthesis of the present disclosure can undergo compression testing to evaluate the stiffness and palpability of the prosthesis and determine the compressive stiffness of the prosthesis. Testing can be accomplished by compressing the prosthesis up to 30% at a rate of 0.2 mm / s, which can be slow enough to achieve quasi-static test conditions. To evaluate the prosthesis, the prosthesis 100 can first be measured and then positioned within a compression testing system (e.g., an Instron), such as Figure 11A In some non-limiting embodiments, a 100N load cell can be used to compress the prosthesis. The system can then compress the prosthesis until 30% of the original height of the prosthesis (e.g., a point of interest) and collect force-displacement data.

[0115] Various geometric measurements of the prosthesis, such as pre-compression height, displacement, and force, can be used to calculate the compression stiffness of the prosthesis. Specifically, the compression stiffness of the prosthesis can be derived as follows:

[0116]

[0117] In the above equations, the normalized force and compressive displacement are measured by the test, and the prosthesis dimensions are measured prior to the test. It should be understood that in some embodiments, given the nonlinear slope of the compression curve, the term "compression stiffness" as used herein refers to the compression secant stiffness defined by the linear slope between the origin and the point of interest.

[0118] Figure 11B Various dimensions associated with an implantable prosthesis are shown. The cross-sectional area of ​​the prosthesis can be calculated as follows:

[0119]

[0120] Force measurements from a test system can be converted to normalized forces as follows:

[0121]

[0122] In one exemplary embodiment, an ellipsoidal implantable prosthesis having an overall dimension of approximately 2 cm by 2 cm by 3 cm with a 25% hollow core percentage can exhibit an average compressive stiffness of approximately 4.05 psi in the horizontal orientation and an average compressive stiffness of 4.66 psi in the vertical direction. In another exemplary embodiment, an ellipsoidal implantable prosthesis having an overall dimension of approximately 3 cm by 3 cm by 4 cm with a 10% hollow core percentage can exhibit an average compressive stiffness of approximately 3.55 psi in the horizontal orientation and an average compressive stiffness of 3.52 psi in the vertical direction. In yet another exemplary embodiment, an ellipsoidal implantable prosthesis having an overall dimension of approximately 4 cm by 4 cm by 5 cm with a 10% hollow core percentage can exhibit an average compressive stiffness of approximately 2.40 psi in the horizontal orientation and an average compressive stiffness of 2.82 psi in the vertical direction.

[0123] The stiffness of the implantable prosthesis of the present disclosure can be adjusted by a variety of means, including but not limited to the size of the prosthesis, the material composition of the prosthesis, the type and number of fixation sites, the percentage of hollow core, etc. In some embodiments, the stiffness of the implantable prosthesis can be increased by increasing the wall thickness of the subunits. The wall thickness can be increased by using a thicker substrate material (e.g., a mesh repair fabric). In some embodiments, the wall thickness of the subunits can be increased by using multiple overlapping subunits.

[0124] Figure 12 An exemplary partial assembly process for a bi-conical subunit 310 is depicted. The subunit 310 may include a first conical subunit 301 similar to the first conical subunit 302 with respect to the Figures 2A to 2BIn the tapered subunits described above, the first tapered subunit 301 has a first central portion 361 connected to the second tapered subunit 302 having a second central portion 362. In some embodiments, the second tapered subunit can be arranged inside the volume defined by the first tapered subunit so that the second tapered subunit and the first tapered subunit can overlap. In some embodiments, as Figure 12 As shown in , the central portion of the first tapered subunit and the central portion of the second tapered subunit can be different (e.g., central portion 362 can be smaller than central portion 361). In this way, the core of the implantable prosthesis formed by such subunits 310 can have less material, which can induce a greater tissue infiltration rate to enhance the repair process while maintaining a compressive stiffness comparable to that of native tissue to support nearby anatomical structures. Of course, a dual-tapered subunit having two substantially similar tapered subunits (e.g., similar central portions) is also contemplated.

[0125] It should be understood that any implantable prosthesis of the present invention can be provided with a double-layer subunit. In some embodiments, depending on the application, the prosthesis subunit can be provided with more than two layers (e.g., three, four, five layers) to enhance the mechanical properties of the prosthesis and to better simulate the surrounding anatomical structure.

[0126] 13A to 13D An exemplary assembly process for forming a spherical implantable prosthesis 300 formed from bi-layered subunits is shown. Figure 13A Depicted are two substantially two-dimensional substrates 301 and 302, each of which can be manipulated to form the sidewalls of a three-dimensional subunit, such as Figure 13B In some embodiments, the substrates can be formed of a porous biocompatible mesh material. As shown, the first substrate 301 can have a smaller central portion than the second substrate 302. Each substrate can have an overlapping portion that can be formed into the sidewalls of the tapered subunits when the substrates are manipulated. When arranged together, as shown Figure 13C As shown in FIG, the overlapping portions 314 and 324 of each subunit 301 and 302 can be arranged opposite to each other. Depending on the arrangement of the subunits and the angle of the cutouts, the maximum thickness of the assembled double-layer subunit can be two layers, three layers, or four layers. Of course, embodiments in which the overlapping regions overlap or are arranged differently are also contemplated. Figure 13DAn exemplary spherical prosthesis 300 is depicted as being formed from twelve bi-conical subunits. Thus, prosthesis 300 includes twenty-four subunits. Compared to a prosthesis formed from single-conical subunits having similar geometry, material composition, and weld point arrangement, the bi-conical configuration can exhibit greater compressive stiffness while still allowing tissue ingrowth through the central core of the bi-conical configuration. As previously discussed, the difference in size between the central portions of the two cones can reduce the material volume at the core of the prosthesis and enhance tissue ingrowth. Of course, arrangements of bi-conical (or other subunits) using similar cone formations are also contemplated.

[0127] Table 2 below shows exemplary geometric and mechanical characteristics of six spherical implantable prostheses formed with double-layer subunits. Each prosthesis is designed to be approximately 5 cm×5 cm×5 cm, wherein the double-layer conical subunits of each prosthesis include a first conical subunit with a core percentage of 10% and a second conical subunit with a core percentage of 22.5%.

[0128]

[0129]

[0130] Table 2 - Lists exemplary geometric and mechanical characteristics of five spherical implantable prostheses formed from double-layered tapered subunits.

[0131] Figure 14 An exemplary ellipsoidal implantable prosthesis 400 is depicted, formed from two sets of double-layered subunits 410 and 415. As shown, subunit 415 can be larger than subunit 410 to help form a generally ellipsoidal shape. Of course, any suitable combination of subunits can be employed to form any suitable prosthesis shape, as the present disclosure is not limited thereto. Table 3 below shows exemplary geometric and mechanical characteristics of an ellipsoidal implantable prosthesis formed using double-layered subunits.

[0132] Vertical orientation Horizontal orientation Prosthesis height (mm) 52.6 42.3 Prosthesis width #1 (mm) 45.8 52.5 Prosthesis width #2 (mm) 42.8 46.2 Force measurement (lbf) 1.17 1.97 Displacement (mm) 15.78 12.69 Compression displacement 0.3 0.3 <![CDATA[Cross-sectional area (in 2 )]]> 2.39 2.95 <![CDATA[Normalized force (lbf / in 2 )]]> 0.49 0.67 Stiffness (psi) 1.63 2.22

[0133] Table 3 - Lists exemplary geometric and mechanical features of an elliptical implantable prosthesis formed from double-layered tapered subunits.

[0134] 15A to 15D Depicted is an assembly process for an implantable prosthesis 500 formed from a tapered subunit 503 and a corrugated subunit 502. The combination of the tapered and corrugated shapes is achieved by overlapping (e.g. Figures 15C to 15D ) can provide a larger void volume between the subunits, thereby allowing a greater tissue infiltration rate through the implantable prosthesis while still maintaining sufficient mechanical compressibility after implantation. In some embodiments, the corrugated subunits 502 can take the form of star-shaped cones, such as Figure 15BThe corrugated subunit 502 can be made of a substrate 501 (see Figure 15A ) is formed, the substrate 501 can be folded or otherwise manipulated to form radial corrugations. It should be understood that any suitable number of radial corrugations can range from three (so that the subunits have a generally convex triangular prism shape) to six (so that the subunits have a generally hexagonal convex prism shape) to any other suitable number of corrugations. The substrate can then be manipulated (e.g., rolled) to form the sidewalls of the three-dimensional subunits. In some embodiments, the corrugated subunits 502 can be arranged within the tapered subunits 503, such as Figure 15C 504. In other embodiments, a tapered subunit can be arranged within a corrugated subunit. It should be understood that any combination of various subunits (tapered, corrugated, etc.) can be used in any of the prostheses of the present disclosure. Figure 15D A partially assembled prosthesis 500 is depicted, formed from six subunits, each of which includes at least one tapered subunit and at least one corrugated subunit.

[0135] Table 4 below shows exemplary geometric and mechanical characteristics of two spherical implantable prostheses having double-layer subunits formed of tapered subunits and corrugated subunits. In the table below, Sample 1 is designed to be approximately 4 cm x 4 cm x 4 cm, and Sample 2 is designed to be approximately 5 cm x 5 cm x 5 cm.

[0136] Sample 1 Sample 2 Prosthesis height (mm) 37.5 46.3 Prosthesis width #1 (mm) 42.5 50.5 Prosthesis width #2 (mm) 38.9 50.4 Force measurement (lbf) 2.99 2.25 Displacement (mm) 11.25 13.89 Compression displacement 0.3 0.3 <![CDATA[Cross-sectional area (in 2 )]]> 2.01 3.1 <![CDATA[Normalized force (lbf / in 2 )]]> 1.49 0.73 Stiffness (psi) 4.95 2.42

[0137] Table 4 - Lists exemplary geometric and mechanical characteristics of two spherical implantable prostheses formed from a double layer of subunits including tapered subunits and corrugated subunits.

[0138] 16A to 16B An implantable prosthesis 600 is depicted in accordance with some embodiments. Prosthesis 600 can be formed from two-dimensional substrates secured to one another to form radiating fins emanating from a hollow central portion 620. Central portion 620 can serve as a void volume for tissue infiltration. In some embodiments, prosthesis 600 can include one or more markers 630 that can exhibit properties that enable external detection of the prosthesis' position. For example, markers 630 can be metal staples that can be radiopaque and thus distinguishable during imaging using x-ray imaging.

[0139] 17A to 17BAnother embodiment of an implantable prosthesis 700 is depicted. The prosthesis may also include a series of radial fins formed from a two-dimensional substrate. In some embodiments, the fins of the prosthesis 700 may be formed from an annular substrate that may form a hollow core 720 after assembly of the prosthesis. As described with respect to other embodiments, the hollow core may serve as a void volume to enable tissue ingrowth within the prosthesis after implantation.

[0140] 18A to 18B Another embodiment of an implantable prosthesis 800 is depicted. The prosthesis 800 may be generally cubic in shape, formed from four subunits, such as Figure 18A Each subunit can be formed from various panels 810, 815, 825 that can be folded and welded together to form a quadrant of the prosthesis. The four subunits can then be welded together at weld points 890 to form the prosthesis. The prosthesis can also include one or more markers 830 that can make the prosthesis visible within the implant site during medical imaging.

[0141] Figure 19 Another embodiment of an implantable prosthesis 900 is depicted. The prosthesis 900 can be formed of at least two generally cubic shapes, one within the other. In some embodiments, the prosthesis 900 can be provided with markings 930 for external detection. Figure 19 As shown in , the markers can be metallic and then radiopaque.

[0142] 20A to 20D Depicts the assembly Figure 19 The process of prosthesis 900. Each cubic subassembly (see Figure 20D The cubes 960 and 970 in FIG. 1 can be formed by fixing six two-dimensional substrates 950 together, as shown in FIG. FIG. 20A to FIG. 20B As previously mentioned, the substrates 950 can be secured to each other using welds 959, which can strengthen the prosthesis and significantly reduce the risk of deconstruction. Once the two cubes are partially assembled, the smaller inner cube 960 can be arranged within the larger outer cube 970, as shown in FIG. Figure 20D The outer cube can then be closed and one or more markers can be added to the prosthesis in preparation for implantation, such as Figure 19 As shown in .

[0143] It should be understood that any of the prostheses described herein can have any suitable shape or geometry depending on the application (eg, biopsy shape and size). The prosthesis can also be formed from subunits of any suitable number, size, and arrangement.

[0144] Example 1

[0145] In some embodiments, the prostheses disclosed herein can exhibit a degradation profile comparable to conventional prostheses known in the art. As previously described, such a degradation profile can promote tissue ingrowth into the prosthesis as the prosthesis degrades, thereby allowing the prosthesis to eventually be replaced by natural tissue. Of course, while the prostheses described herein can exhibit a conventional degradation profile, the prostheses described herein can exhibit an improved stiffness transfer between the implant and the natural tissue to promote controlled tissue ingrowth.

[0146] In one example, a porcine preclinical tumor resection model was used to evaluate the degradation profile of the prosthesis over a twelve-week period. Table 5 below shows the molecular weight retention of prostheses according to the present disclosure and prostheses known in the art. In Table 5 below, Sample 1 represents the average data of three spherical prostheses formed of 12 conical subunits with an overall average diameter of approximately 3 cm, and Sample 2 represents the average data of three conventional prostheses (e.g., PHASIX Plug and Patch).

[0147]

[0148] Table 5 - Lists exemplary molecular weight analyses of a spherical implantable prosthesis (Sample 1) and a conventional prosthesis (Sample 2).

[0149] As shown in Table 5 above, molecular weight analysis of Samples 1 and 2 showed statistically significant decreases at 4 and 12 weeks compared to the pre-implantation state. Molecular weight analysis also showed a statistically significant decrease at 12 weeks post-implantation compared to 4 weeks post-implantation. However, there was no statistically significant difference in molecular weight between the central and peripheral portions of either sample at 4 or 12 weeks post-implantation, indicating that molecular weight degradation was uniform across the devices.

[0150] The molecular weight analysis presented in Table 5 above can indicate that the implantable prostheses described herein can exhibit the same molecular weight degradation as conventional implantable devices. However, it should be understood that the prostheses described herein can produce different biological responses compared to conventional prostheses, as described below with respect to Example 2.

[0151] Example 2

[0152] In some embodiments, the local tissue reaction after implantation of the prosthesis can be characterized by histological means. Specifically, the local tissue reaction can be characterized by the presence of neovascularization, fibrosis, collagen deposition, vascular integration, collagen morphology (via PSR staining), myofibroblast proliferation (via SMA or smooth muscle actin staining), and neovascularization (via VWF or von Willebrand factor staining) assessed histologically.

[0153] Figure 21 Exemplary data of the aforementioned local tissue reactions for various prostheses are shown, including the commercial prosthesis BioZorb represented by Group 3 (4 weeks) and Group 8 (12 weeks), the commercial prosthesis PHASIXplug represented by Group 4 (4 weeks) and Group 9 (12 weeks), a control group of sham therapy represented by Group 5 (4 weeks) and Group 10 (12 weeks), and a spherical prosthesis according to the present disclosure, which is formed of 12 conical subunits and has an overall average diameter of approximately 3 cm, represented by Group 11 (4 weeks) and Group 12 (12 weeks).

[0154] Tissue response data were scored as listed in Table 6 below.

[0155]

[0156] Table 6-with Figures 21 to 22 The score-related observations shown in .

[0157] Figure 21 Exemplary data are also presented in Table 7 below (4 weeks) and Table 8 below (12 weeks).

[0158]

[0159]

[0160] Table 7 - At 4 weeks Figure 21 Observations of local tissue reactions are depicted in . Data are presented as mean ± (SD, SEM), median, and incidence (%). NA = not applicable.

[0161]

[0162]

[0163] Table 8 - At 12 weeks Figure 21 The observation results of local tissue reaction are depicted in Figure 2. Data are presented as mean ±

[0164] The data are presented as mean ±SD, mean ±SEM, median and incidence (%). NA = not applicable.

[0165] Figure 21 The data presented in Tables 7 and 8 indicate that at 4 weeks there were several statistically significant differences in neovascularization (n=2), fibrosis (n=1), and collagen deposition (n=1), and at 12 weeks there was one statistically significant difference in fibrosis. At 4 weeks, PHASIX was significantly different when compared to the sham site (Group 5). TMThe mean neovascularization was statistically significantly higher in the Plug (Group 4) (likely due to the minimal inflammation / tissue response in the sham site as expected), and the mean neovascularization was statistically significantly lower in the sham site (Group 5) when compared to the Prosthesis of the Present Disclosure (Group 11) (likely due to the minimal inflammation / tissue response in the sham site as expected). At 4 weeks, the mean fibrosis was statistically significantly lower in the sham site (Group 5) when compared to the Prosthesis of the Present Disclosure (Group 11) (likely due to the minimal inflammation / tissue response in the sham site as expected). At 4 weeks, the mean collagen deposition was statistically significantly lower in the sham site (Group 5) when compared to the Prosthesis of the Present Disclosure (Group 11) (likely due to the minimal inflammation / tissue response in the sham site as expected). In addition, at 12 weeks, the PHASIX® was significantly lower in the sham site (Group 10) when compared to the sham site (Group 10). TM The mean fibrosis was statistically significantly higher in the Plug (Group 9) (likely due to minimal inflammation / tissue reaction in the sham site, as expected). These statistically significant differences can be interpreted as biologically insignificant and likely due to the comparison of the device group with a sham site that had minimal inflammation / tissue reaction, as expected.

[0166] In some embodiments, the cellular response following implantation of the prosthesis can be characterized by observing inflammation and inflammatory cell types histologically. Figure 22 Exemplary data for the aforementioned inflammatory response of various prostheses are shown, including the commercial prosthesis BioZorb represented by Group 3 (4 weeks) and Group 8 (12 weeks), the commercial prosthesis PHASIX plug represented by Group 4 (4 weeks) and Group 9 (12 weeks), a control group of sham therapy represented by Group 5 (4 weeks) and Group 10 (12 weeks), and a spherical prosthesis according to the present disclosure, which is formed of 12 conical subunits and has an overall average diameter of approximately 3 cm, represented by Group 11 (4 weeks) and Group 12 (12 weeks). The inflammatory data were scored as described in Table 6.

[0167] Figure 22 Exemplary data are also presented in Table 9 below (4 weeks) and Table 10 below (12 weeks).

[0168]

[0169] Table 9 - At 4 weeks Figure 22 The observation results of inflammation are depicted in Figure 2. Data are expressed as mean ± (SD, SEM), median and incidence (%).

[0170]

[0171] Table 10 - At 12 weeks Figure 22 The data are presented as mean ± (SD,

[0172] SEM), median and incidence (%).

[0173] like Figure 22 As shown in Tables 9 and 10, histologically, overall inflammation was similar between the prosthesis and control implant sites at both time points (4 and 12 weeks) within the implanted test and control sites, with overall inflammation decreasing over time in all groups except the sham-treated sites, where overall inflammation was lower than that of the test and control-treated sites at both time points (as expected). The inflammatory infiltrate was heterogeneous at both time points, and at 4 weeks, the inflammatory infiltrate consisted of neutrophils (not seen in the sham-treated sites and sites associated with the disclosed prostheses), eosinophils (not seen in the sham-treated sites and sites associated with the disclosed prostheses), and eosinophils (not seen in the sham-treated sites and sites associated with the disclosed prostheses). At 12 weeks, the inflammatory infiltrate consisted of neutrophils (only in the Parts and PHASIX TM A small number of eosinophils were observed in the plug site. Two statistically significant differences in eosinophils were noted at 4 weeks ( and sham surgery when compared to the disclosed prosthesis), and a statistically significant difference in lymphocytes was noted at 12 weeks (PHASIX TM Plug when compared to sham surgery). All 3 statistically significant differences were interpreted as biologically insignificant and likely due to the comparison of groups with two devices composed of different materials, as well as the comparison of the group with the device present and a group with a sham surgery site that had minimal inflammatory / tissue response, as expected.

[0174] Example 3

[0175] As previously mentioned, in some embodiments, the implantable prosthesis can be formed from a porous two-dimensional substrate that can be cut and assembled into a three-dimensional prosthesis. In some embodiments, the substrate can be a mesh sheet with pores. For example, the substrate can be formed from a PHASIX porous material having at least two pore size distributions: a primary pore size and a secondary pore size. The porosity of the prosthesis can be evaluated using a statistical six sigma system, as listed in Table 11 below. This table summarizes the porosity data from fifteen exemplary mesh substrates used to form implantable prostheses, the porosity data including the number of samples N, the average pore size, the standard error of the mean SE, the standard deviation SD, the minimum size of the distribution, the first quartile Q1 porosity, the median porosity, the third quartile Q3 porosity, and the maximum size. The porosity of the substrates listed in Table 11 below was measured by an optical characterization method.

[0176] variable N average value SE SD Minimum Q1 median Q3 Maximum Secondary pore size (micrometers) 15 355.51 5.27 20.41 326.10 333.30 354.60 374.90 384.20 Main pore size (micrometers) 15 777.37 7.50 29.06 736.80 754.00 770.90 810.50 830.70

[0177] Table 11 - Lists exemplary porosity properties of mesh substrates useful in forming implantable prostheses.

[0178] In some embodiments, implantable prosthesis can be sutured to implantation site. In some embodiments, nearby tapered subunit can be sutured to each other during assembly. Therefore, mesh sheet can have the suture pull-out strength that is enough to bear described force during implantation and / or assembly. The suture pull-out strength of mesh substrate can be evaluated using statistical six sigma system, as listed in following table 12. This table summarizes the suture pull-out strength data in machine direction (MD) and cross direction (CD) of 15 exemplary mesh substrates for forming implantable prosthesis. The data in table 12 include sample number N, mean strength, standard error SE of mean value, standard deviation SD, minimum distribution strength, first quartile Q1 strength, median strength, third quartile Q3 strength and maximum strength. The strength of the substrate listed in following table 12 is measured by the conventional tensile technique using a mechanical testing machine.

[0179]

[0180] Table 12 - Lists exemplary suture pull-out strength properties in the machine direction (MD) and cross direction (CD) of mesh substrates used to form implantable prostheses.

[0181] Example 4

[0182] In some embodiments, the implantable prosthesis can be sufficiently compressible that the implantable prosthesis can be inserted into the implantation site through an incision that is smaller than the average size of the prosthesis. For example, a generally spherical implantable prosthesis having an average diameter of 2 cm may need to be inserted through an incision site of approximately 1.5 cm (to minimize scarring and incision formation) while retaining the majority of the size of the implantable prosthesis at the implantation site, which may be larger than the incision site.

[0183] The dimensional recovery of the implantable prosthesis can be assessed along one or more directions in which the percentage difference is calculated from the measurements of dimension D before and after insertion as follows:

[0184]

[0185] The percentage difference can be calculated for any suitable dimension, such as the height of the prosthesis and the first and second widths (see Figure 11B Table 13 below summarizes the heights and the percentage differences between the first width and the second width for fifteen exemplary spherical implantable prostheses formed from 12 tapered subunits using the statistical six sigma system described above. The exemplary prostheses measured in Table 13 below had an average diameter of 2 cm and were inserted through a 1.5 cm incision.

[0186] variable N average value SE SD Minimum Q1 median Q3 Maximum Height difference 15 1.074 0.247 0.956 -0.797 0.507 0.971 1.835 2.935 Width 1 Difference 15 0.685 0.278 1.077 -1.050 0.112 0.508 1.247 3.413 Width 2 Difference 15 0.167 0.340 1.318 -2.509 -0.324 0.122 0.725 2.595

[0187] Table 13 - Lists exemplary effects of insertion on implantable prostheses as determined by geometric changes in prosthesis size.

[0188] In some embodiments, a compression test can be used to evaluate the recoverability of an implantable prosthesis. For example, an implantable prosthesis can withstand 30% compression and recover to the uncompressed state of the implantable prosthesis. In some embodiments, the design requirement for such compression can be that the prosthesis recovers to within 10% of the original size of the prosthesis after compression. Table 14 below summarizes the height and the percentage difference between the first width and the second width of fifteen exemplary spherical implantable prostheses that meet such requirements. The prosthesis is formed from 12 tapered subunits, and the values ​​listed in Table 14 are evaluated using the statistical six sigma system as described above.

[0189]

[0190] Table 14 - Lists exemplary recoverability after 30% compression for spherical implantable prostheses having average diameters of 2 cm, 3 cm, 4 cm, and 5 cm, as shown.

[0191] Example 5

[0192] In some embodiments, the implantable prosthesis can be mechanically rigid enough to impart strength to nearby tissue during implantation, but may transfer loads to the native tissue during the regrowth process. In some embodiments, the prosthesis stiffness can be better matched to the native tissue, allowing for smoother and more controlled load transfer during prosthesis degradation. Therefore, in some embodiments, the prosthesis can be designed with stiffness requirements, such as a bearing stiffness greater than or equal to 1.8 psi at 30% compression, and a compression stiffness less than or equal to 6.1 psi, as high stiffness prostheses may cause undesirable cellular reactions. Table 15 below summarizes the stiffness of fifteen sets of exemplary spherical implantable prostheses formed from 12 conical subunits, each having a different average diameter, as shown. The prostheses of Table 15 met the above design requirements using the statistical six sigma system as described above.

[0193]

[0194] Table 15 - Lists exemplary stiffness of spherical implantable prostheses having different average diameters.

[0195] Similar stiffness characterization can be used for the non-spherical implantable prostheses described herein, such as, for example, 8A to 10E Table 16 below summarizes the stiffness of two sets of exemplary ellipsoidal implantable prostheses formed from 14 subunits, each having different sizes, as shown. The listed stiffnesses were evaluated using the statistical six sigma system described above. The specific geometries of the various ellipsoidal prostheses evaluated in Table 16 are shown in Table 1 above.

[0196]

[0197]

[0198] Table 16 - Lists exemplary stiffness of ellipsoidal implantable prostheses having different average diameters.

[0199] Example 6

[0200] In some embodiments, the prosthesis described herein can be tissue infiltrated, which can allow the prosthesis to be fixed in place after implantation. The ingrowth of natural tissue can be used to limit the migration of the prosthesis. Prosthesis migration can be verified by tracking the radiopaque markers associated with the prosthesis, thereby allowing an external imaging system to view and track the prosthesis without the need for invasive surgery. As previously mentioned, a marker can be used to mark a specific physiological position (e.g., tumor bed position) in the patient's body for subsequent imaging to monitor recovery and potential recurrence. In some cases, it may be desirable to limit the migration of the marker to within 1 cm of the original attachment site marked on the device after 5 months after implantation. Table 17 below uses the statistical six sigma system as previously described to summarize the migration of 30 exemplary markers between their initial implantation and implantation five months later. The data presented in Table 17 reflect the measurement results at two different positions of each marker between the above-mentioned time points.

[0201]

[0202] Table 17 - Lists exemplary stiffnesses of spherical implantable prostheses.

[0203] Example 7

[0204] In some embodiments, the stiffness of an implantable prosthesis can be determined by a variety of factors, such as the percentage of hollow core, the number of connections between and within each tapered subunit, the distance between connections (e.g., welds), and the overall geometry of each tapered subunit. In one exemplary experiment, a Pareto analysis of the various factors that can determine stiffness was performed to determine which elements had the greatest impact on achieving the desired stiffness. The analysis showed that for a spherical prosthesis having an average diameter of approximately 4 cm, a 10% hollow core percentage and an overlap of approximately 65° could achieve a target stiffness of approximately 3.75 psi.

[0205] Example 8

[0206] In some embodiments, the stiffness (e.g., horizontal stiffness and vertical stiffness) of an implantable ellipsoidal implantable prosthesis can be determined by a variety of factors, such as the percentage of hollow core, the number of connections (e.g., welds) between and within each conical subunit, the distance between the connections (e.g., welds) and the edge, and the overall geometry of each conical subunit. In an exemplary experiment, a series of different ellipsoidal prostheses (2 cm×3 cm; 3 cm×4 cm; 4 cm×5 cm) were evaluated. Each prosthesis included an assembly of side conical subunits, peak conical subunits, and intermediate conical subunits with different design features (e.g., overlap (cutout), percentage of hollow core (HC), number of welds, and distance of welds from the edge), as summarized in the table below.

[0207]

[0208] Table 18 - Design features of evaluated ellipsoidal implantable prostheses.

[0209] The evaluation showed the following: for the 2 cm × 3 cm ellipsoidal prosthesis, a horizontal stiffness of 4.00 psi and a vertical stiffness of 3.83 psi were obtained; for the 3 cm × 4 cm ellipsoidal prosthesis, a horizontal stiffness of 3.62 psi and a vertical stiffness of 3.64 psi were obtained; and for the 4 cm × 5 cm ellipsoidal prosthesis, a horizontal stiffness of 3.46 psi and a vertical stiffness of 3.78 psi were obtained.

[0210] The embodiments described herein can be implemented as methods for which examples have been provided. The actions performed as part of the method can be ordered in any suitable manner. Thus, embodiments can be constructed in which the actions are performed in an order different from the illustrated order, which can include performing some actions simultaneously, even though these actions are shown as sequential actions in the illustrative embodiments.

[0211] Additionally, some actions are described as being taken by a “user.” It should be understood that a “user” need not be a single individual, and in some embodiments, actions attributable to a “user” may be performed by a team of individuals and / or an individual in conjunction with a computer-assisted tool or other mechanism.

[0212] Although the present teachings have been described in conjunction with various embodiments and examples, it is not intended that the present teachings be limited to these embodiments or examples. On the contrary, as will be appreciated by those skilled in the art, the present teachings encompass various alternatives, modifications, and equivalents. Therefore, the foregoing description and accompanying drawings are intended to be examples only.

[0213] Although several embodiments of the present invention have been described and illustrated herein, a person of ordinary skill in the art will readily conceive of various other devices and / or structures for performing the functions and / or obtaining one or more of the results and / or advantages described herein, and each of such variations and / or modifications is considered to be within the scope of the present invention. More generally, a person skilled in the art will readily understand that all parameters, dimensions, materials, and configurations described herein are intended to be exemplary, and that the actual parameters, dimensions, materials, and / or configurations will depend on the specific application or applications in which the teachings of the present invention are used. A person skilled in the art will recognize or be able to determine, using only routine experimentation, many equivalents to the specific embodiments of the invention described herein. Therefore, it should be understood that the foregoing embodiments are presented by way of example only, and that, within the scope of the appended claims and their equivalents, the present invention may be implemented in ways other than those specifically described and claimed. The present invention relates to each individual feature, system, article, material, kit, and / or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and / or methods is included within the scope of the present invention if they are not mutually inconsistent.

Claims

1. An implantable prosthesis comprising: a plurality of generally conical mesh bodies, wherein each of the plurality of generally conical reticulate bodies is connected to at least another generally conical reticulate body of the plurality of generally conical reticulate bodies, and wherein the generally conical bodies are arranged to form an ellipsoid.

2. A method of forming an implantable prosthesis, the method comprising: forming a plurality of generally conical mesh bodies; as well as Each of the conical mesh bodies is connected to at least one other of the other substantially conical mesh bodies to form an ellipsoid.

3. An implantable prosthesis comprising: a plurality of generally conical bodies, wherein each of the plurality of generally conical bodies is connected to at least one other generally conical body of the plurality of generally conical bodies, and Wherein, the implantable prosthesis is substantially mechanically isotropic.

4. An implantable prosthesis comprising: a plurality of generally conical bodies, each conical body including a sidewall defining a conical shape, wherein the sidewall of each generally conical body is connected to the sidewall of at least another adjacent generally conical body.

5. A method of forming an implantable prosthesis, the method comprising: forming a plurality of generally conical bodies, each conical body including a sidewall defining a conical shape; as well as The sidewall of each generally conical body is connected to the sidewall of at least another adjacent generally conical body.

6. The implantable prosthesis or method according to any one of claims 1 to 5, wherein: The implantable prosthesis includes a hollow core.

7. The implantable prosthesis or method according to any one of claims 1 to 6, wherein: The prosthesis is configured to be sized and shaped for placement in a tumor resection site.

8. The implantable prosthesis or method according to any one of claims 1 to 7, wherein: The implantable prosthesis is formed at least in part from a resorbable material.

9. The implantable prosthesis or method of any one of claims 1 to 8, further comprising one or more radiopaque markers.

10. The implantable prosthesis or method according to any one of claims 1 to 9, wherein: The implantable prosthesis has a compressive stiffness between 1 psi and 10 psi, inclusive.

11. The implantable prosthesis or method according to any one of claims 4 to 5, wherein: The first portion of the side wall of each generally conical body is connected to the second portion of the side wall of the same generally conical body.

12. The implantable prosthesis or method according to any one of claims 4 to 5, wherein: The first portion of the side wall of each generally conical body is welded to the second portion of the side wall of the same generally conical body.

13. The implantable prosthesis or method of any one of claims 1 to 3 and 6 to 10, wherein: Each generally conical body includes a sidewall, and wherein a first portion of the sidewall of each generally conical body is welded to a second portion of the sidewall of the same generally conical body.

14. The implantable prosthesis or method of any one of claims 1 to 3 and 6 to 10, wherein: Each generally conical body includes a sidewall, and wherein the sidewall of each generally conical body is welded to the sidewall of at least another adjacent generally conical body.

15. The implantable prosthesis or method of any one of claims 1 to 14, wherein: At least one average diameter of the implantable prosthesis is between 2 cm and 5 cm.

16. The implantable prosthesis or method of any one of claims 3 to 5, wherein: The generally conical bodies are arranged to form an ellipsoid.

17. The implantable prosthesis or method of any one of claims 1 to 2 and 4 to 5, wherein: The implantable prosthesis is substantially mechanically isotropic.

18. The implantable prosthesis or method of any one of claims 1 to 17, wherein: The generally conical bodies are arranged to form a sphere.

19. The implantable prosthesis or method of any one of claims 1 to 18, further comprising a second plurality of generally conical mesh bodies that are geometrically different from the first plurality of generally conical mesh bodies.

20. The implantable prosthesis or method of claim 6, wherein: The volume of the hollow core is between 10% and 35% of the total volume of the implantable prosthesis.

21. An implantable prosthesis comprising: a plurality of mesh bodies, wherein each mesh body is connected to another mesh body; Wherein at least some of the mesh bodies comprise a first mesh portion connected to a second mesh portion, wherein the first portion is arranged inside a volume defined by the second mesh portion.

22. A method of forming an implantable prosthesis, the method comprising: forming a plurality of mesh bodies; arranging the first mesh portions of at least some of the mesh bodies within a volume defined by the second mesh portions; connecting the first mesh portion to the second mesh portion; as well as Each of the mesh bodies is connected to another mesh body.

23. The implantable prosthesis or method of any one of claims 21 to 22, wherein: The implantable prosthesis includes a hollow core.

24. The implantable prosthesis or method of any one of claims 21 to 23, wherein: The prosthesis is configured to be sized and shaped for placement in a tumor resection site.

25. The implantable prosthesis or method of any one of claims 21 to 24, wherein: The implantable prosthesis is formed at least in part from a resorbable material.

26. The implantable prosthesis or method of any one of claims 21 to 25, further comprising one or more radiopaque markers.

27. The implantable prosthesis or method of any one of claims 21 to 26, wherein: The implantable prosthesis has a compressive stiffness between 1 psi and 10 psi, inclusive.

28. The implantable prosthesis or method of any one of claims 21 to 27, wherein: The first portion is welded to the second portion.

29. The implantable prosthesis or method of any one of claims 21 to 28, wherein: Each mesh body comprises a side wall, and wherein a first portion of the side wall of each mesh body is welded to a second portion of the side wall of the same mesh body.

30. The implantable prosthesis or method of any one of claims 21 to 29, wherein: At least one average diameter of the implantable prosthesis is between 2 cm and 5 cm.

31. The implantable prosthesis or method of any one of claims 21 to 30, wherein: The mesh body is arranged to form an ellipsoid.

32. The implantable prosthesis or method of any one of claims 21 to 31, wherein: The implantable prosthesis is substantially mechanically isotropic.

33. The implantable prosthesis or method of any one of claims 21 to 32, wherein: The mesh body is arranged to form a sphere.

34. The implantable prosthesis or method of any one of claims 21 to 33, further comprising a second plurality of mesh bodies that are geometrically different from the first plurality of mesh bodies.

35. The implantable prosthesis or method of claim 23, wherein: The volume of the hollow core is between 10% and 35% of the total volume of the implantable prosthesis.

36. The implantable prosthesis or method of any one of claims 21 to 35, wherein: Each of the plurality of mesh bodies is generally conical.

37. The implantable prosthesis or method of any one of claims 21 to 36, wherein: At least some of the plurality of mesh bodies are corrugated.

38. The implantable prosthesis or method of claim 37, wherein: The corrugated mesh body comprises at least 5 corrugations.

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