Implantable prosthesis for tissue regeneration and surgical site marking - Patent Application 20070122999

Abstract

Implantable prostheses and related methods are generally described. In one embodiment, the prosthesis may be generally ellipsoidal (spherical) in shape and formed from one or more subunits. The subunits may be conical or frustoconical and formed by processing a two-dimensional substrate material. The sidewalls of the subunits may be fixed to one another to increase the rigidity of the prosthesis. In one embodiment, markers may be used to aid in distinguishing the prosthesis within the implantation site using a medical imaging device (e.g., x-ray imaging). In this manner, implantation sites, which may also be the site of recent biopsies and / or resections of diseased tissue, may be easily identified. The prosthesis may be formed from a porous material to induce tissue infiltration, which may promote natural tissue regeneration and result in a more natural-looking and feeling tissue. Tissue infiltration may improve the resistance of the prosthesis to migration after implantation.

Description

[Technical Field]

[0001] FIELD OF THE INVENTION

[0001] The disclosed embodiments relate to tissue engineering devices and related methods, and more particularly to implantable prostheses for soft tissue regeneration and identification of biopsy and lumpectomy sites. [Background technology]

[0002]

[0002] The removal or resection of soft tissue has become an essential and important part of cancer treatment. Tissue may be taken as a biopsy specimen for cytology, histology, diagnostic tests or examinations to determine the presence of chemicals indicative of disease, or the presence of bacteria or other microorganisms. If the biopsy specimen shows malignant cells (e.g., diseased or cancerous cells), the surgeon may choose to remove more tissue to reduce the risk of cell spread or proliferation and optimize the surgical outcome.

[0003]

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

[0004]

[0004] In some embodiments, the implantable prosthesis includes a plurality of substantially conical mesh bodies, each of the plurality of substantially conical mesh bodies connected to at least one other of the plurality of substantially conical mesh bodies, and arranged so that the substantially conical bodies form an ellipsoid.

[0005]

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

[0006]

[0006] In another embodiment, the implantable prosthesis includes a plurality of substantially conical bodies, each of the plurality of substantially conical bodies being connected to at least one other of the plurality of substantially conical bodies, and the implantable prosthesis being substantially mechanically isotropic.

[0007]

[0007] In another embodiment, the implantable prosthesis includes a plurality of substantially conical bodies, each including a side wall defining a conical shape, the side wall of each substantially conical body being connected to the side wall of at least one other adjacent substantially conical body.

[0008]

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

[0009]

[0009] In another embodiment, the implantable prosthesis includes multiple mesh bodies, each mesh body connected to another mesh body, at least a portion of the mesh bodies including a first mesh portion connected to a second mesh portion, the first portion being disposed within a volume defined by the second mesh portion.

[0010]

[0010] In another embodiment, a method of forming an implantable prosthesis includes forming a plurality of mesh bodies, positioning a first mesh portion of at least a portion 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]

[0011] It should be understood that the foregoing concepts, and additional concepts discussed below, may be arranged in any suitable combination, as the disclosure is not limited in this respect. Furthermore, 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 explanation of the drawings]

[0012]

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

[0013] [Figure 1A-1B] 1 illustrates an implantable prosthesis according to some embodiments. [Figure 2A]

[0014] FIG. 10 shows a top view of a conical subunit of an implantable prosthesis according to some embodiments. [Figure 2B]

[0015] 2B illustrates an isometric view of the conical subunit of FIG. 2A, according to some embodiments. [Figure 3]

[0016] 10 illustrates a conical subunit of an implantable prosthesis according to some embodiments. [Figures 4A-4D]

[0017] 13 shows a conical subunit of an implantable prosthesis according to another embodiment. [Figure 5A-5B]

[0018] 1A-1D show various views of an implantable prosthesis according to some embodiments. [Figure 6A]

[0019] 1 shows an implantable prosthesis according to another embodiment. [Figure 6B]

[0020] The implantable prosthesis of Figure 6A is shown along line 6B-6B. [Figure 7A-7C]

[0021] 10 shows three implantable prostheses according to further embodiments. [Figure 8A-8B]

[0022] 1A-1D show various views of an ellipsoid implantable prosthesis according to some embodiments. [Figures 9A-9F]

[0023] 8C illustrates a conical subunit of the implantable prosthesis of FIGS. 8A-8B, according to some embodiments. [Figures 10A-10E]

[0024] 1 illustrates an assembly process for an implantable prosthesis according to some embodiments. [Figures 11A-11B]

[0025] 1 illustrates a compression testing system for an implantable prosthesis, according to some embodiments. [Figure 12]

[0026] 10 illustrates a partial assembly process of an implantable prosthesis according to some embodiments. [Figures 13A-13D]

[0027] 1 illustrates an assembly process for an implantable prosthesis according to some embodiments. [Figure 14]

[0028] 1 shows an implantable prosthesis according to another embodiment. [Figures 15A-15D]

[0029] 10 illustrates an assembly process for an implantable prosthesis according to yet another embodiment. [Figures 16A-16B]

[0030] 10 shows an implantable prosthesis according to yet another embodiment. [Figures 17A-17B]

[0031] 10 shows an implantable prosthesis according to yet another embodiment. [Figures 18A-18B]

[0032] 10 shows an implantable prosthesis according to yet another embodiment. [Figure 19]

[0033] 10 shows an implantable prosthesis according to yet another embodiment. [Figures 20A-20D]

[0034] 10 illustrates an assembly process for an implantable prosthesis according to yet another embodiment. [Figure 21]

[0035] 10 shows exemplary local tissue response data from experimental implantation of an implantable prosthesis according to some embodiments. [Figure 22]

[0036] 1 shows exemplary cellular response data from experimental implantation of an implantable prosthesis according to some embodiments. DETAILED DESCRIPTION OF THE INVENTION

[0014]

[0037] Removal of natural tissue at tissue removal sites during treatment can cause cosmetic indentations and deformations, affecting both the appearance and palpability of the natural tissue. Traditional tissue reconstruction using autologous fat or soft, natural-material fillers can lead to undesirable results, failing to support the tissue at the implantation site due to the lack of mechanical rigidity of the injected material. Furthermore, such materials can retard tissue ingrowth within the tissue removal site, prolonging the healing and remodeling process. Alternative options, such as silicone, may be sufficiently rigid to support the surrounding tissue, but can substantially limit the potential for tissue ingrowth indefinitely. Furthermore, fluids or substances and synthetic filler materials may be incompatible with cancer treatments, such as radiation therapy. Such treatments can result in leaching of the material. Therefore, the present inventors have recognized a need for a soft tissue prosthesis that can simultaneously exhibit mechanical properties that support the anatomical structures at the implantation site while also allowing for rapid tissue ingrowth.

[0015]

[0038] Radiation therapy is often used in cancer treatment to destroy remaining cancer cells after tumor removal and reduce the risk of cancer recurrence. However, the present inventors have recognized that it can be difficult to define the tissue boundaries of a tumor cavity for radiation therapy after surgery. Traditionally, clinicians have relied on the presence of surgical scars or seroma to identify the radiation therapy site and radiation target volume. However, these methods of definition are not the most accurate, potentially reducing the effectiveness of radiation therapy and increasing the likelihood of damage to healthy tissue surrounding the cavity. Accurately identifying the boundaries of a tumor resection cavity can also be extremely difficult because the cavity shape can be irregular and some tissues can change shape over time. For example, tumor cavities can grow or shrink with breathing, and they can also change size and shape as a result of ongoing radiation therapy treatments. Markers can also be used when biopsy results are normal (e.g., benign) to provide information about the biopsy history in follow-up tests (e.g., mammograms).

[0016]

[0039] In some cases, clinicians often use marker devices to more clearly define the location of the cavity and provide a clearer target for external radiation beam therapy. A marker device is a marker or set of markers placed as reference points within the imaging field of view, and is traditionally made of a surgical alloy such as a titanium alloy (including a shape-memory alloy). Markers are typically small metal objects that can be distinguished from surrounding tissue through various imaging modalities (e.g., x-rays), but they tend to migrate after implantation, which can make accurate reading of the biopsy or lumpectomy site difficult. Therefore, the present inventors have also recognized the need for biopsy or lumpectomy site markers to guide radiological targeting in treatment and imaging applications.

[0017]

[0040] In light of the above, the inventors have recognized the benefits of implantable prostheses for soft tissue reconstruction and / or volume reduction of natural soft tissue in applications such as surgically removed or excised tissue (e.g., in lumpectomy). The prosthesis may have mechanical and geometric properties similar to those of natural tissue to mimic the natural feel of the tissue. The prosthesis may also function as a scaffold for tissue infiltration, allowing natural (or other) tissue to grow within the prosthesis, maintaining mechanical properties similar to those of natural tissue without being significantly palpable externally. Tissue ingrowth into the resection or excision cavity void may also have the added benefits of improved cosmetic outcomes and resistance to migration. The prosthesis may also function as a marker for biopsy and / or tissue resection (e.g., lumpectomy) sites. The prosthesis may be visible using one or more medical imaging systems, allowing for external detection of the site in treatment and imaging applications. The prosthesis may have advantages such as reducing the clinical target volume in radiation therapy and improving cosmetic outcomes after lumpectomy. However, it is possible that the systems and methods disclosed herein may provide different advantages.

[0018]

[0041] In some embodiments, the implantable prosthesis may be a three-dimensional implant formed from an assembly of subunits. Each subunit may be formed from a two-dimensional substrate, which may be molded from the two-dimensional configuration into a three-dimensional configuration. In some embodiments, the two-dimensional substrate may be a generally C-shaped substrate with a notch, as described in more detail below. The two-dimensional C-shaped substrate may be configured into a three-dimensional shape by fastening two ends of the C-shaped substrate together. In this manner, a cone (or a truncated cone) with a sidewall may be formed. It should be understood that the two-dimensional substrate may have any shape to facilitate transformation into a three-dimensional subunit body. In some embodiments, the two ends of the C-shaped substrate may be fastened together using permanent means (e.g., welding), while in other embodiments, the two ends may be fastened together using temporary means (e.g., fasteners such as staples). The sidewalls of the three-dimensional subunit may then be fastened to the sidewalls of one or more other subunits to form the three-dimensional implantable prosthesis. For example, twelve frusto-conical subunits may be secured together to form a generally elliptical shape.

[0019]

[0042] The present inventors have recognized the benefits associated with an implantable prosthesis that balances mechanical properties for supporting surrounding anatomical structures with a high rate of tissue infiltration. A very stiff, dense implantable prosthesis would support surrounding tissue without providing natural tactility or promoting tissue ingrowth. On the other hand, the absence of a prosthesis may induce natural tissue ingrowth but may result in indentation or deformation at the tissue removal site. Thus, the implantable prosthesis of the present disclosure may exhibit both mechanical isotropy and large voids that allow tissue ingrowth. In this way, the prosthesis may allow rapid tissue ingrowth while providing sufficient isotropic mechanical support at the implantation site.

[0020]

[0043] The construction of an implantable prosthesis using subunits may allow for greater tissue infiltration through the prosthesis compared to non-porous or solid prostheses. In this manner, the implantable prosthesis may exhibit tactility and / or other properties similar to natural tissue. In some embodiments, the prosthesis may be formed from a material that allows fibroblast invasion to produce collagen, which may then envelop the prosthesis substrate. Thus, in some embodiments, the prostheses of the present disclosure may function as components for in vivo organ development (engineering) or replacement by providing a scaffold for inducing angiogenesis.

[0021]

[0044] In some embodiments, an implantable prosthesis may be formed of a collection of conical mesh subunits or bodies connected to at least one adjacent subunit. The prosthesis may have an assembled shape similar to an ellipsoid. In some embodiments, the implantable prosthesis may be constructed by first forming each conical mesh subunit or body, and then connecting each conical mesh subunit to an adjacent subunit to form an ellipsoidal prosthesis, as described in more detail below. An ellipsoidal shape (e.g., spherical) may have the advantage of fitting properly within a tissue resection site (e.g., biopsy site, lumpectomy site), which may help maintain the natural palpability of the tissue, such that the prosthesis or resection site is not substantially palpable on the subject.

[0022]

[0045] In some embodiments, an implantable prosthesis may be formed from a collection of conical mesh subunits or bodies connected to at least one adjacent subunit. The prosthesis may be substantially mechanically isotropic. In some embodiments, an implantable prosthesis may be constructed by first forming each conical mesh subunit or body, and then connecting each conical mesh subunit to an adjacent subunit to form a substantially mechanically isotropic prosthesis, as described in more detail below. As described in more detail below, "substantially mechanically isotropic" refers to the property of having similar compressive stiffness along two or more directions of the prosthesis. A substantially mechanically isotropic implantable prosthesis may have the advantage of mimicking natural tissue upon palpation and providing uniform structural support to an anatomical structure. Thus, the prosthesis may exhibit mechanical properties comparable to natural tissue, such that the prosthesis or resection site is substantially not palpable on the subject.

[0023]

[0046] In some embodiments, an implantable prosthesis may be formed from a collection of conical mesh subunits or bodies, each having a sidewall that can be connected to the sidewall of an adjacent subunit or body. Such a prosthesis may be constructed by first forming each conical mesh subunit or body and then connecting the sidewall of each body to the sidewall of an adjacent body. The connections between the various subunits or bodies may increase the mechanical robustness of the prosthesis. The connections formed between the sidewalls of the bodies may help integrate the conical subunits into the final implantable prosthesis so that pressure from surrounding anatomical structures can be evenly distributed within the prosthesis while reducing the risk of unraveling.

[0024]

[0047] In some embodiments, an implantable prosthesis may be formed from a collection of subunits or bodies, each connected to another subunit. The subunits may include a first portion connected to another portion of the subunit and disposed within a volume defined by the other portion of the subunit. Such a prosthesis may be constructed by first forming each of the subunits, disposing one portion of the subunit on the other portion of the subunit, connecting the two portions, and then connecting each subunit to the adjacent subunit. In this manner, the subunits of the prosthesis may benefit from a larger material volume, which may further strengthen the prosthesis and support natural tissue. As described in more detail below, each portion of the subunit may have a different geometry to encourage tissue ingrowth while optimizing the mechanical properties of the prosthesis.

[0025]

[0048] In some embodiments, the prosthesis of the present disclosure may facilitate tissue infiltration through its porosity, allowing cells to rapidly proliferate through the prosthesis. The prosthesis may have porosity on multiple length scales. For example, the interior volume of the conical subunit of the prosthesis may provide a large void space for tissue ingrowth. The subunit itself may be formed of a mesh-like or macroporous (large pore) material, which may allow the prosthesis to accommodate sufficient autologous fat, biological material, microphages, fibroblasts, collagen, hyaluronic acid, and / or bioactive agents to promote vascularization and tissue ingrowth within the prosthesis. In some embodiments, the prosthesis may be formed of a material with pores greater than 10 microns to limit the risk of rejection and scar tissue formation. As used herein, the terms "macroporous" or "mesh" refer to average pore sizes of 10 microns, 20 microns, 30 microns, 40 microns, 50 microns, 60 microns, 75 microns, 100 microns or greater, and / or any other suitable pore size.

[0026]

[0049] In some embodiments, the implantable prosthesis of the present disclosure may preferably have a generally ellipsoidal shape to mimic an anatomical cavity left behind from a tissue removal procedure (e.g., a lumpectomy) and / or any other natural or surgically created cavity. Specifically, in some embodiments, the prosthesis may have a spherical shape. However, it should be understood that the implantable prosthesis of the present disclosure 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 rectangular prism, a tetrahedron, a triangular or rectangular prism, a dodecahedron, combinations thereof, and / or customized geometric shapes. As used herein, it should be understood that the term "ellipsoid" refers to an ellipsoidal three-dimensional shape (which may have different average diameters in two or more directions), a spheroidal shape, and a spherical shape (which may have substantially the same average diameter in all directions).

[0027]

[0050] It should be understood that the prostheses of the present disclosure may have any suitable size corresponding to a given application. For example, the prosthesis may be sized to fit within a tissue removal (e.g., lumpectomy) site. Accordingly, the prosthesis may be any suitable size. The prosthesis may be characterized by an average diameter, which in some preferred embodiments may preferably be about 2 cm to 5 cm, although other sizes are contemplated, including prostheses with average diameters of 0.5 cm, 1 cm, 1.5 cm, 2 cm, 3 cm, 4 cm, 5 cm, 6 cm, 7 cm, 8 cm or greater, and / or any other suitable size. The average diameter of the prosthesis may also be 8 cm, 7 cm, 6 cm, 5 cm, 4 cm, 3 cm, 2 cm, 1.5 cm, 1 cm, 0.5 cm or less, and / or any other suitable size. Combinations of the above are also contemplated, e.g., prostheses with average diameters of 0.5 cm to 5 cm, 2 cm to 8 cm, as well as prostheses larger or smaller than the aforementioned ranges.

[0028]

[0051] In some embodiments, the prosthesis may have a first average diameter along a first direction of the prosthesis and a second average diameter along a second direction of the prosthesis. For example, the prosthesis may be generally ellipsoidal. Thus, it should be understood that the present disclosure is not limited by the geometry of the implantable prosthesis, and the foregoing average diameter ranges may apply to any suitable size of prosthesis.

[0029]

[0052] As mentioned above, in some embodiments, an implantable prosthesis may be formed with 12 connected subunits. However, it should be understood that any suitable number of subunits may be employed to form any suitable shape of implantable prosthesis. A prosthesis may have 1, 5, 10, 15, 20, 25, 30, 35, 40, 50 or more subunits, and / or any other suitable number of subunits. Also, a prosthesis may have 50, 40, 35, 30, 25, 20, 15, 10, 5, 1 or less subunits, and / or any other suitable number of subunits. Combinations of the above, including prostheses having 1 to 50 and 1 to 12 subunits, are also contemplated, along with numbers of subunits beyond the aforementioned ranges. As described in more detail below, in some embodiments, multiple subunits may be employed to enhance mechanical compressibility. Thus, the prostheses of the present disclosure are not limited by the number of subunits they comprise.

[0030]

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

[0031]

[0054] It should be understood that the term "conical" or "cone" as used herein refers to both conventional cones and cone-like shapes, as well as partial cone shapes, such as frustoconical shapes, which may not have a sharp tip.

[0032]

[0055] The subunits of the implantable prostheses described herein may be configured and secured in a three-dimensional configuration by any suitable means. In some embodiments, the subunits may be secured in a three-dimensional configuration by any suitable bonding, heat sealing, welding (e.g., ultrasonic, etc.), adhesive, combinations thereof, and / or other suitable techniques. In some embodiments, the subunits may be secured in a three-dimensional configuration by permanent or non-permanent devices. For example, fasteners such as staples or sutures may be used to non-permanently form the subunits and / or to join adjacent subunits together. It should be understood that any of the aforementioned securing techniques may be used to secure adjacent subunits together. The present disclosure is not limited thereto and any suitable combination of securing techniques may be employed to form the prosthesis.

[0033]

[0056] In some embodiments, as described in more detail below in connection with the figures, the subunits used in the implantable prostheses used herein may be fabricated from a two-dimensional substrate. The substrate itself may be formed from a two-dimensional sheet. The two-dimensional substrate may be formed using any suitable technique, including, but not limited to, trimming or cutting with scissors, blades, other sharp cutting tools, or thermal knives, laser cutting techniques, welding techniques, stamping techniques, combinations thereof, and / or any other suitable technique. In other embodiments, the substrate may be formed using additive manufacturing techniques, such as 3D printing.

[0034]

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

[0035]

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

[0036]

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

[0037]

[0060] In some embodiments, an implantable prosthesis may provide a means for delivering cells, stem cells, differentiated cells, adipocytes, muscle cells, platelets, stalks, vascular stalks, tissue mass, extracellular adipose matrix proteins, gels, hydrogels, hyaluronic acid, collagen, bioactive agents, drugs, antibiotics, and other materials to the implantation site. The cells and tissues that may be delivered to and / or coated or injected into the prosthesis may be autologous. The prosthesis may be used for autologous fat transplantation. Cells added to, coated on, or injected into the prosthesis may include pancreatic islet cells, hepatocytes, and stem cells genetically modified to contain genes for the treatment of a patient's disease. The prosthesis may contain bioactive agents that stimulate cellular ingrowth, including cell signaling molecules such as growth factors, cell adhesion factors, cell differentiation factors, cell recruitment factors, cell receptors, cell binding factors, and cytokines, as well as molecules that promote cell migration, cell division, cell proliferation, and extracellular matrix deposition. The prosthesis may also be partially or entirely coated with and / or contain agents that inhibit tissue adhesion or that inhibit cell proliferation, particularly agents that retard cell invasion into the prosthesis.

[0038]

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

[0039]

[0062] The prosthesis may contain active agents 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 active 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-1B (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 and capable of binding cells via cell surface molecules. Cell adhesion polypeptides include any of the extracellular matrix proteins known to be involved in cell adhesion, such as fibronectin, vitronectin, laminin, elastin, fibrinogen, collagen types I, II, and V, as well as synthetic peptides with similar cell adhesion properties. Cell adhesion polypeptides also include peptides derived from any of the foregoing proteins, including fragments or sequences that contain the binding domain.

[0040]

[0063] In some embodiments, implantable prostheses may be loaded, filled, coated, or otherwise incorporated with wetting agents designed to improve the wettability of various surfaces of the prosthesis, allowing fluids to more easily adsorb onto the prosthesis surface, promoting cell attachment, and / or modifying 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 thereof, such as PLURONICS®. Other suitable wetting agents may include surfactants or emulsifiers.

[0041]

[0064] In some embodiments, implantable prostheses may be loaded, filled, coated, or otherwise incorporated with gels, hydrogels, or biohydrogel hybrids to further improve wettability and promote cell growth throughout the prosthesis. Hydrogel hybrids consist of biological cells encapsulated in a biocompatible hydrogel, such as gelatin, gelatin methacryloyl (GelMa), silk gel, or hyaluronic acid (HA) gel.

[0042]

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

[0043]

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

[0044]

[0067] In some embodiments, the implantable prosthesis may be loaded, filled, coated, or otherwise incorporated with allograft or xenograft tissue and cells before, during, after, or any combination thereof. In some embodiments, the implantable prosthesis may be coated with autologous patient-derived tissue and cells before, during, after, or any combination thereof. The autologous tissue and cells may include one or more of the following: autologous fat, lipoaspirate, adipose tissue, injectable fat, adipose tissue, adipocytes, fibroblasts, and stem cells (including human adipose tissue-derived stem cells, also known as preadipocytes or adipose tissue-derived progenitor cells, and fibroblast-like stem cells). In one embodiment, the prosthesis may be coated with autologous tissue and cells as described herein and may further include a vascular pedicle or other tissue mass. As noted herein, the prosthesis is designed to create not only the shape of an implant, such as a breast implant, but also a large surface area that may retain autologous tissue and cells to promote tissue ingrowth.

[0045]

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

[0046]

[0069] In some embodiments, the polymer and copolymer compositions of the prosthesis may have a low water content to ensure the production of a prosthesis with stiffness comparable to that of natural tissue, long-term strength retention, and a good shelf life. In some embodiments, the polymers and copolymers used to manufacture the prosthesis have a water content of less than 1,000 ppm (0.1% by weight), less than 500 ppm (0.05% by weight), less than 300 ppm (0.03% by weight), less than 100 ppm (0.01% by weight), and / or less than 50 ppm (0.005% by weight).

[0047]

[0070] It should be understood that the compositions used to manufacture the prostheses may have low endotoxin content. In some embodiments, the endotoxin content may be sufficiently low so that a prosthesis manufactured from the polymer composition has an endotoxin content of less than 20 endotoxin units per prosthesis, as measured by the Limulus Amebocyte Extract (LAL) test. For example, the polymer composition used to manufacture the prosthesis may have an endotoxin content of less than 2.5 EU per gram of polymer or copolymer. In another example, a P4HB polymer or copolymer or a PBS polymer or copolymer has an endotoxin content of less than 2.5 EU per gram of polymer or copolymer.

[0048]

[0071] In some embodiments, the prosthesis of the present disclosure may include one or more markers for externally detecting the position of the prosthesis. For example, the prosthesis may include radiopaque markers (e.g., metal staples) that are visible during x-ray imaging and distinguishable from adjacent anatomical structures. The markers may be formed of any suitable medical material approved for long-term use that can be medically imaged. Medical imaging methods include, for example, radiographic imaging devices (e.g., x-rays), magnetic resonance imaging (MRI), ultrasonography, fluoroscopy, or computed tomography. Thus, the markers may 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 over the patient's lifetime. Non-absorbable biocompatible materials include, but are not limited to, metal-containing materials, polymeric materials, ceramic materials, or composite materials containing 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, and alloys thereof, combinations thereof, etc. Suitable polymers include, but are not limited to, polyvinyl alcohol, polyurethane, polyolefin, polyester, polypropylene, polyimide, polyetherimide, fluoropolymers, liquid thermoplastic polymers (LCPs) such as Celanese's Vectra®, polyethyl ether ketone such as Vitrex's PEEK®, polyamides, polycarbonates such as Bayer Polymers' Makrolon®, polysulfone, polyethersulfone, polyphenylsulfone such as Rowland Technologies' Radel®, nylon, nylon copolymers, combinations thereof, etc. In some embodiments, the marker may comprise a shape memory material, including, but not limited to, nitinol, titanium, or any shape memory polymer.

[0049]

[0072] In some embodiments, the subunit substrate may include one or more visual and / or tactile fiducial markers to facilitate assembly. In some embodiments, the fiducial markers may indicate the location of fixation spots (e.g., welding spots). The fiducial markers may be visually / optically or otherwise apparent to an operator for assembly. In some embodiments, the fiducial markers may be a different color than the prosthesis substrate or may be distinguished from the underlying prosthesis substrate. In some embodiments, the fiducial markers may be a different color than the underlying substrate. In some embodiments, the prosthesis may include multiple fiducial markers in multiple colors to distinguish them from one another. For example, a first group of fiducial markers may be used to indicate fixation points within a single subunit substrate in a first color, and a second group of fiducial markers may be used to indicate fixation points between adjacent subunit substrates. It should be understood that any combination of fiducial marker types may be employed in any prosthetic subunit of the present disclosure.

[0050]

[0073] The implantable prostheses of the present disclosure may exhibit any suitable mechanical properties to mimic natural anatomical structures. In some embodiments, the prosthesis may exhibit compressive stiffness to mimic the mechanics of natural tissue while still supporting the surrounding anatomical structures after implantation. As used herein, and as described in more detail below, compressive stiffness is defined as the normalized compressive load applied to a subject during compression testing divided by its relative strain.

[0051]

[0074] The prostheses of the present disclosure may have any suitable compression stiffness, including, but not limited to, 0.5 psi, 1 psi, 1.5 psi, 1.8 psi, 2 psi, 3 psi, 4 psi, 5 psi, 6 psi, 6.8 psi, 7 psi, 8 psi, 9 psi, 10 psi, 12 psi, 15 psi or greater, and / or any other suitable stiffness. The prostheses may also exhibit compression stiffnesses of 15 psi, 12 psi, 10 psi, 9 psi, 8 psi, 7 psi, 6.8 psi, 6 psi, 5 psi, 4 psi, 3 psi, 2 psi, 1.8 psi, 1.5 psi, 1 psi, 0.5 psi or less, and / or any other suitable stiffness. Combinations of the above, including prostheses having compression stiffnesses of 0.5 psi to 15 psi and 1.8 psi to 6.8 psi, as well as compression stiffnesses above and below the aforementioned ranges, are also contemplated. It should be understood that the stiffness may be designed to mimic or support the tissue at the implantation site. Thus, the prosthesis may have any suitable stiffness above or below the aforementioned ranges.

[0052]

[0075] It should be understood that in some embodiments, an implantable prosthesis of the present disclosure may have substantially mechanical isotropy, which may refer to isotropy of the compressive stiffness (and / or any other mechanical property) of the prosthesis. The prosthesis may 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, where the magnitudes of the first compressive stiffness and the second compressive stiffness are within 30% of each other, although first and second compressive stiffnesses within other ranges (e.g., within 25%, 15%, 10%, 5%) are also contemplated. The first and second directions may refer to the major / minor axes of the structure (e.g., if the prosthesis is elliptically shaped) or any other suitable direction. For example, a substantially mechanically isotropic prosthesis may refer to a prosthesis having a horizontal compressive stiffness of 3 psi and a vertical compressive stiffness of 2.6 to 3.4 psi. Thus, the first and second directions may be orthogonal to one another, although other configurations are contemplated.

[0053]

[0076] In other embodiments, the mechanical properties of the implantable prosthesis may be anisotropic (e.g., orientation-dependent). Thus, it should be understood that one or more orientations of the implantable prosthesis may exhibit any of the aforementioned mechanical properties. It should also be understood that the mechanical properties of the prosthesis may be selected to mimic the natural tissue properties of the implantation site. Thus, depending on the implantation site, the mechanical properties of the prosthesis may be any suitable value above or below the aforementioned ranges.

[0054]

[0077] In some embodiments, the implantable prosthesis of the present disclosure may be compressible enough to fit through an incision smaller than the prosthesis. For example, an implantable prosthesis with an average diameter of 2 cm may be compressed up to 0.5 cm to fit through a 1.5 cm incision. Note that the compressibility of the prosthesis may be temporary, and that the prosthesis may return to within 10% of its original size after compression.

[0055]

[0078] In some embodiments, implantable prostheses of the present disclosure may include features that significantly reduce the risk of prosthesis migration. For example, markers may have the added benefit of generating friction within the implantation site, limiting prosthesis migration. In other embodiments, the prosthesis may include other features to limit marker migration and / or reorientation after implantation. It should be appreciated that in embodiments in which the prosthesis is formed of a generally resorbable material, tissue infiltration through the prosthesis may secure or engage the prosthesis relative to adjacent tissue. Thus, in some embodiments, the prosthesis may reduce the risk of migration through its material properties.

[0056]

[0079] The implantable prostheses of the present disclosure may be used in any suitable application. In some embodiments, the prosthesis may be implanted into soft tissue after a biopsy (and / or other surgery, such as a lumpectomy) 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 may be used in soft tissue reconstruction applications and may function as a breast implant, a breast lift device, a breast augmentation device, a nipple implant, a facial reconstruction device, a buttocks implant, a cheekbone 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 augmentation or filling device, a void filler, a device for treating vesicoureteral reflux, a cell seeding device, a drug delivery device, combinations thereof, and / or any other suitable application.

[0057]

[0080] Specific non-limiting embodiments will now be described in more detail with reference to the figures. It will be understood that the various systems, components, functions, and methods described in connection with these embodiments can be used individually and / or in any desired combination, as the disclosure is not limited to only the specific embodiments described herein.

[0058]

[0081] 1A-1B show two isometric views of an implantable prosthesis 100 according to some embodiments. The prosthesis 100 may be formed with conical subunits 20, which may be configured to form a generally elliptical shape. Specifically, as shown in FIGS. 1A-1B, the prosthesis may have a generally spherical shape. The central portion of the prosthesis 100 may include a hollow core 60 to allow for tissue ingrowth, which may, in some embodiments, provide a more natural feel upon tissue infiltration of the implant. In some embodiments, the prosthesis may include one or more markers 30, which may be radiopaque. As previously described, the markers 30 may facilitate accurate visualization of the position of the prosthesis after implantation within the anatomy.

[0059]

[0082] 1A-1B is shown as having a generally spherical shape, it should be understood that any suitable shape of prosthesis for filling a biopsy or lumpectomy cavity or for other prosthetic purposes may be employed. Also, it should be understood that while the prosthesis 100 shown in FIGS. 1A-1B is formed from an assembly of 12 conical subunits 20, any suitable number of subunits (conical 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 other factors.

[0060]

[0083] 2A-2B show various views of a conical subunit 20 according to some embodiments. FIG. 2A shows a top view of a substantially two-dimensional substrate 22, which may be machined (e.g., rolled) to form the conical subunit 20 shown in the isometric view of FIG. 2B. In some embodiments, the substrate may be formed of a porous biocompatible mesh material. In some embodiments, the ends of the substrate 22 may be overlapped to form an overlapping region 24, and then the ends may be secured together. In some embodiments, the ends of the substrate 22 may be secured together by weld spots 29, as shown in FIG. 2B, although other temporary and permanent securing methods are contemplated. This fabrication process may transform the substrate 22 from the substantially two-dimensional configuration shown in FIG. 2A to a three-dimensional configuration with sidewalls, as shown in FIG. 2B. In some embodiments, the subunit may have a frustum (or "cone") shape, while in other embodiments, the subunit may form a different three-dimensional shape.

[0061]

[0084] The overlapping area 24 of each conical subunit 20, shown in FIG. 2B, may contribute to the overall mechanical properties of the subunit and the prosthesis. For example, a larger overlapping area may result in a stiffer subunit compared to a smaller overlapping area. In part, this increased stiffness may be due to the change in thickness of the subunit to two layers instead of one. The overlapping area 24 may be defined by an overlapping degree O1, as shown in FIG. 2B, which may be added to a non-overlapping degree O2 to total approximately 360°. The overlapping degree O1 may be any appropriate value to achieve the desired stiffness of the subunit. The degree of overlap may be 5°, 10°, 15°, 20°, 25°, 30°, 35°, 40°, 45°, 50°, 55°, 60°, 65°, 70°, 75°, 80°, 85°, 90°, 100° or more, and / or 100°, 95°, 90°, 85°, 80°, 75°, 70°, 65°, 60°, 55°, 50°, 45°, 40°, 35°, 30°, 25°, 20°, 15°, 10°, 5° or less, and / or combinations thereof.

[0062]

[0085] While the fastening points (e.g., weld spots) 29 are depicted as substantially circular, it should be understood that non-circular fastening points are also contemplated. In some embodiments, elongated or narrow fastening points may be employed to enhance fastening between substrate portions and / or adjacent subunits. In some embodiments, the elongated or narrow fastening points may be useful for fastening various elements in multiple directions. In some embodiments, the elongated or narrow fastening points may replace multiple circular fastening points. For example, a series of three weld spots may be replaced with one elongated fastening point. Such a replacement may facilitate the assembly process. In some embodiments, the elongated fastening points may increase the rigidity of the subunits.

[0063]

[0086] In some embodiments, the substrate 22 may be formed in a generally C-shaped configuration, as shown in FIG. 2A. A central portion 26 of the substrate 22 may be removed to allow tissue ingrowth through the implantable prosthesis, as shown in FIGS. 1A-1B. The substrate 22 may also include a notch around the periphery of the substrate 22 spanning a notch angle A1, as shown in FIG. 2A. Such a notch may allow the substrate 22 to be machined to form a three-dimensional conical sidewall. In some exemplary embodiments, the subunit 20 shown in FIG. 2B may have a sidewall angle of approximately 63°, and 12 identical subunits may collectively enable the formation of a generally spherical implantable prosthesis. In some embodiments, the sidewall angle of the subunits may be greater than or less than 63°, for example, between 50° and 70°, between 60° and 65°, and / or any other suitable sidewall angle range. Of course, prostheses employing different numbers of subunits with different geometries to form spherical or non-spherical prostheses are also contemplated.

[0064]

[0087] The notch angle A1 shown in FIG. 2A can be any suitable angle that enables the formation of a truncated cone. In some embodiments, the substrate may include a notch, rather than a notch, with the angle A1 approximately equal to 0°. In some embodiments, the notch angle A1 can be 0°, 5°, 10°, 15°, 20°, 30°, 40°, 50°, 65°, 80°, 90°, 100°, 120°, 135°, 150°, 180° or greater, and / or any other suitable angle. The notch angle A1 can also be 180°, 150°, 135°, 120°, 100°, 90°, 80°, 65°, 50°, 40°, 30°, 20°, 15°, 10°, 5°, 0° or less, and / or any other suitable angle. Combinations of the foregoing angles are also contemplated, including notch angles from 0° to 180°. In some embodiments, the notch angle A1 may be 40°. In other embodiments, the notch angle A1 may be 65°. In yet other embodiments, the notch angle A1 may be 135°. Of course, notch angles above and below the aforementioned ranges are also contemplated. It should be understood that any implantable prosthesis of the present disclosure may be formed with two or more conical (or other) subunits having the same or different notch angles.

[0065]

[0088] In some embodiments, the substrate 22 may be characterized by an average diameter D1. The average substrate diameter D1 may be any suitable size to adequately fit the implantation site and / or accommodate other suitable applications. In some exemplary embodiments, the average diameter D1 of the substrate 22 may be 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 or greater, and / or other suitable sizes. The average diameter D1 of the substrate 22 may also be 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 or less, and / or other suitable sizes. Combinations of the above ranges, including average substrate diameters between 1 cm and 8 cm, as well as sizes above and below the aforementioned ranges, are also contemplated.

[0066]

[0089] In some embodiments, the central portion 26 of the substrate 22 may 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 may be any suitable value that allows for sufficient tissue ingrowth in the implantable prosthesis while still maintaining sufficient mechanical rigidity to support surrounding tissue after implantation. The core percentage may be any suitable value equal to or greater than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 50%, and / or any other suitable percentage. The core percentage may also be equal to or less than 50%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, and / or any other suitable percentage. Combinations of the foregoing ranges, including core percentages of 10% to 35% and 5% to 50%, as well as the ranges above and the ranges above, are also contemplated.

[0067]

[0090] In some embodiments, the core percentages of the subunits may result in a total hollow core percentage of the implantable prosthesis, which may represent the ratio of the hollow central volume of the prosthesis to the total volume of the prosthesis. The hollow core percentage of the prosthesis may be greater than, less than, or equal to the core percentage of a given subunit of the prosthesis.

[0068]

[0091] In some embodiments, substrate 22 may include one or more fiducial markers 28, shown in Figure 2A, to facilitate assembly of the conical subunits, shown in Figure 2B. The ends of substrate 22 may be folded over to align fiducial markers 28 and then secured together (e.g., using welding techniques) to form the sidewalls of the three-dimensional subunits. Of course, embodiments without fiducial markers are also contemplated.

[0069]

[0092] In some embodiments, as shown in FIG. 2A , the fiducial markers, and therefore the welds (or other fastening techniques), may be spaced a distance D3 from the outer edge. This distance may be sized sufficiently to allow a practitioner to fasten the implantable prosthesis to tissue with fasteners. Thus, the welds may be spaced from the edge to provide clearance for the fasteners. In some embodiments, this distance may also provide sufficient space for other fastening processes, such as fastening between adjacent subunits. Distance D3 may be any suitable value, such as 2 mm, 2.5 mm, 3 mm, 5 mm, or more, and / or any other suitable distance from the edge of the substrate. This distance may also be 5 mm, 3 mm, 2.5 mm, 2 mm, or less, and / or any other suitable distance from the edge of the substrate. While FIGS. 2A-2B show one fiducial marker 28 and weld spot 29, subunits having two or more fiducial markers and weld spots are also contemplated. In some embodiments, two weld spots may increase the rigidity of the subunit.

[0070]

[0093] Figure 3 illustrates a conical subunit according to some embodiments. As shown, the substrates 22 of the subunits may overlap in region 24 to allow for a three-dimensional configuration. Figure 3 also illustrates weld spots 29 formed in overlap region 24. As shown, weld spots 29 may physically and permanently change substrate 22 to secure the subunits in a three-dimensional configuration. However, embodiments are also contemplated in which fasteners, such as staples, are used to temporarily position the subunits in a three-dimensional configuration.

[0071]

[0094] 4A through 4D illustrate various embodiments of conical subunits having different cutout angles A1. As shown, in some embodiments, the cutout angle may determine the extent of the overlap region 24. FIGS. 4B and 4D illustrate subunits with similar sidewall angles. However, given that the cutout angle A1 (see FIG. 4A) of the subunit in FIG. 4B is significantly larger than the cutout angle A1 (see FIG. 4C) of the subunit in FIG. 4D, the overlap region 24 of the subunit in FIG. 4D is significantly larger. In some embodiments, extending the overlap region may improve stiffness. It should be understood that extending the overlap region may be selected independently of the cutout angle, depending on the final desired sidewall angle of the subunit.

[0072]

[0095] 5A-5B show two exemplary embodiments of an implantable prosthesis 100. Both embodiments include twelve conical subunits formed in a generally spherical configuration. As illustrated in FIG. 5A, in some embodiments, each cone may be secured to an adjacent cone via one weld spot 29. As illustrated in FIG. 5B, in other embodiments, each cone may be secured to an adjacent cone via two weld spots 29. In some embodiments, increasing the number of weld spots (between cones or within a single cone) may increase the overall stiffness of the implantable prosthesis.

[0073]

[0096] 6A-6B illustrate an implantable prosthesis 100 according to some embodiments. The prosthesis 100 may be formed of 12 subunits 20, each having a generally frustoconical shape, as shown in FIG. 6A. Each subunit 20 may include one or more weld spots 29A resulting from the formation of the subunit itself and one or more weld spots 29B resulting from assembly of the prosthesis. In other words, the weld spots 29A may be applied during intra-subunit formation, and the weld spots 29B may be applied during inter-subunit assembly to secure adjacent subunits to one another. The prosthesis may also include one or more markers 30 to facilitate external visualization of the prosthesis using various medical imaging devices (e.g., x-ray, MRI).

[0074]

[0097] Figure 6B shows a cross-section of the prosthesis 100 of Figure 6A taken along line 6B-6B. As shown, the core 60 of the prosthesis may have an average core diameter D5, which may be formed in response to the frustoconical shape of the subunits 20. As explained in more detail above, the prosthesis may have a hollow core percentage proportional to the ratio of the average core diameter D5 to the average prosthesis diameter D4, as shown in Figure 6B. The average prosthesis diameter D4 in Figure 6B may be approximately 3 cm, although diameters greater or less than 3 cm are contemplated, as explained in more detail above.

[0075]

[0098] The mean core diameter D5 can be any suitable value for inducing tissue ingrowth while maintaining adequate mechanical rigidity to support adjacent tissue. The mean core diameter D5 can be 0.05 cm, 0.1 cm, 0.2 cm, 0.5 cm, 1 cm, 2 cm or more, and / or any other suitable size. The mean core diameter D5 can also be 2 cm, 1 cm, 0.5 cm, 0.2 cm, 0.1 cm, 0.05 cm or less, and / or any other suitable size. Combinations of the foregoing ranges, including mean core diameters D5 of 0.05 cm to 2 cm, as well as diameters above and below the foregoing ranges, are also contemplated. The mean core diameter D5 can also be any suitable percentage of the mean prosthesis diameter D4. In some embodiments, the average core diameter D5 may be 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 50%, 60%, 75% or more of the average prosthesis diameter, and / or any other suitable percentage. The average core diameter D5 may also be 75%, 60%, 50%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 2% or less of the average prosthesis diameter, and / or any other suitable percentage. Combinations of the foregoing ranges, including average core diameters D5 of 10% to 35% and 2% to 75% of the average prosthesis diameter, as well as the ranges above and the foregoing ranges, are also contemplated. It should be understood that the present disclosure is not limited to the geometry of the core, and therefore any suitable sizes of average core diameter and prosthesis diameter (and any suitable ratio thereof) may be employed.

[0076]

[0099] Figures 7A through 7C show three embodiments of spherical prostheses formed with 12 conical subunits 20 each. All three prostheses have similarly sized cores 60 (e.g., similar core diameters). However, the three prostheses differ in average diameter. The prosthesis in Figure 7A has an average diameter D4 of approximately 2 cm, Figure 7B has an average diameter D4 of approximately 4 cm, and Figure 7C has an average diameter D4 of approximately 5 cm. Therefore, the hollow core percentage of the prosthesis shown in Figure 7C may be smaller than the hollow core percentage of the prosthesis shown in Figure 7A.

[0077]

[0100] In some embodiments, the number of fixation points (e.g., markers and weld spots) may depend on the size of the prosthesis. For example, Figure 7A shows a prosthesis in which each subunit 20 has five intra-subunit weld spots 29A to increase the rigidity of each subunit and five inter-subunit weld spots 29B, where a subunit is fixed once to each adjacent subunit. Figures 7B-7C both show prostheses in which 12 subunits each include six intra-subunit weld spots 29A and 12 inter-subunit weld spots 29B. However, the arrangement and absolute positions of the weld spots in Figures 7B and 7C differ due to differences in the average prosthesis diameter D4.

[0078]

[0101] It should be understood that prostheses having different subunits, each having a different number and / or arrangement of subunits, are also contemplated. It should also be understood that any of the implantable prostheses of the present disclosure may be formed with any combination of subunits. In some embodiments, a prosthesis may be formed with multiple similar subunits, as shown in FIGS. 5A through 7C. In other embodiments, a prosthesis may be formed with different subunits. For example, an implantable prosthesis may include a first group of subunits having a first core percentage, a first average substrate diameter, and a first notch angle, and a second group of subunits having a second core percentage, a second average substrate diameter, and a second notch angle. Thus, it should be understood that the implantable prostheses of the present disclosure may employ any number of subunits to form any combination of geometric, structural, and / or mechanical properties.

[0079]

[0102] 8A-8B show various views of an implantable prosthesis 200 having a generally oval shape. In some embodiments, the oval shape of the prosthesis 200 may be achieved by combining three types of subunits: a side cone 240, a peak cone 250, and a middle cone 260. The different types of subunits allow an implantable prosthesis having an elongated oval shape to accommodate similarly shaped implantation sites (e.g., biopsy sites or lumpectomy sites).

[0080]

[0103] 9A-9F illustrate the substrate geometries of the three subunits forming the prosthesis 200 of FIGS. 8A-8B. In some embodiments, the side cone 240 may include a generally C-shaped substrate with a notch that may be characterized by a notch angle A1. It should be appreciated that the side cone substrate 242 may include an extension 243 that may partially distort the C-shape of the side cone 240. This change in geometry allows the side cone, when used with the peak and middle cones, to form a rounded, oval prosthesis. Similar to the embodiment described above in connection with FIG. 2A, the side cone 240 may include one or more fiducial markers 248 indicating intra-subunit welds and one or more fiducial markers 247 indicating inter-cone (or inter-subunit) welds. As previously discussed, any number of subunits and / or welds between subunits and adjacent subunits may be employed to achieve desired mechanical properties. In some embodiments, fiducial markers may not be employed.

[0081]

[0104] FIG. 9B illustrates a peak cone according to some embodiments, and FIG. 9C illustrates a middle cone 260. Similar to the embodiment shown in FIG. 2A, the peak cone and middle cone may include substrates 252, 262, along which notches may be formed. The peak cone notch angle A1 may be greater than the middle cone notch angle A1, allowing for the formation of three-dimensional cones of different sizes. For example, the peak cone notch angle A1 may be 191.25° as shown in FIG. 9B. However, other peak cone notch angles are contemplated, including those between 100° and 250° and between 135° and 210°. It should be understood that the peak cone notch angle may vary depending on the size of the implantable prosthesis. Thus, any suitable peak cone notch angle may be employed. While FIG. 9C illustrates a middle cone notch angle A1 of 135°, as discussed in connection with the peak cone notch angle, any suitable notch angle, such as 40° to 140°, may be employed. Of course, the notch angle of any subunit of the present disclosure may be any suitable size that allows for the formation of suitable three-dimensional subunit sidewalls. Both the peak cone and the middle cone may include one or more fiducial markers 258, 268 indicating intra-subunit welds and one or more fiducial markers 257, 267 indicating inter-cone (or inter-subunit) welds. As previously discussed, any number of subunits and / or welds between subunits and adjacent subunits may be employed to achieve desired mechanical properties. In some embodiments, fiducial markers may not be employed.

[0082]

[0105] As previously mentioned, in some embodiments, the implantable prosthesis may be ellipsoidal and non-spherical. In some embodiments, the ellipsoidal prosthesis may have an average height and an average width. Table 1 below summarizes an exemplary list of geometric characteristics of ellipsoidal implantable prostheses. Each of the prostheses listed in Table 1 is formed with a total of 14 conical subunits, including two peak cones, eight side cones, and four middle cones, as previously described.

[0083] [Table 1]

[0084]

[0106] In some embodiments, an ellipsoidal prosthesis may utilize the peak cone, side cone, and middle cone shown in and described in connection with FIGS. 9A-9C. In other embodiments, an ellipsoidal prosthesis may employ a peak cone that may differ from the cone 250 shown in FIG. 9B. For example, an ellipsoidal prosthesis may be formed with three conical subunits, including a side cone 240 shown in FIG. 9D, which may be similar to the side cone 240 of FIG. 9A; a middle cone 260 shown in FIG. 9F, which may be similar to the middle cone 260 of FIG. 9C; and a peak cone 2050 shown in FIG. 9E, which may differ from the peak cone 250 of FIG. 9B. Specifically, the peak cone 2050 may be formed with a base material 2052 having two extensions 2053 that may partially distort the C-shaped formation of the peak cone 2050. The peak cone 2050 may also include one or more fiducial markers 2058 indicating intra-subunit welds and one or more fiducial markers 2057 indicating inter-cone (or inter-subunit) welds. As previously mentioned, any number of subunits and / or welds between subunits and adjacent subunits may be employed to achieve desired mechanical properties. In some embodiments, fiducial markers may not be employed.

[0085]

[0107] It should be understood that the peak cone of Figure 9E may be used 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.

[0086]

[0108] FIGS. 10A through 10E illustrate the process of assembling an ellipsoidal implantable prosthesis, such as that shown in FIGS. 8A through 8B. The exemplary prosthesis may be formed with two peak cones, eight side cones, and four middle cones. However, it should be understood that any suitable number of subunits may be employed. First, each subunit may be assembled into a three-dimensional configuration from its two-dimensional base material, as described above. Next, as shown in FIG. 10A, the peak cone 250 may be aligned with the side cone 240 so that their upper edges are aligned. The side walls of the two cones may be clamped together for alignment and then secured to each other (e.g., by welding). Next, the other three side cones 240 may be secured to the central peak cone 250, aided by fiducial markers 249, 259 on the side cones and peak cone, as shown in FIG. 10B. It should be understood that each side cone may be welded to the peak cone one or more times, and may also be welded to each of the adjacent cones one or more times.

[0087]

[0109] The partial assembly of the peak cone 250 and the four side cones 240 may be repeated to form the two halves of the prosthesis. Once the halves are aligned, the four side cones of each half may be secured to one another, connecting the two halves, as shown in FIG. 10C. However, as shown in FIG. 10C, gaps 290 may exist between the side cones in the center of the prosthesis. These gaps may be filled with middle cones 260, as shown in FIG. 10D. Each middle cone 260 may be welded at least once to the four adjacent side cones 240. The final prosthesis, formed with a total of 14 subunits, may appear roughly ellipsoidal, as shown in FIG. 10E. It should be understood that the assembly process described in connection with FIGS. 10A through 10E is not limiting, and that any other assembly process may be employed to form the implantable prosthesis of the present disclosure.

[0088]

[0110] As described in more detail above, an implantable prosthesis may exhibit substantially isotropic mechanical properties, such as compressive stiffness. In some embodiments, an implantable prosthesis of the present disclosure may be subjected to a compression test to evaluate the stiffness and tactility of the prosthesis and to determine the compressive stiffness of the prosthesis. The test may be performed by compressing the prosthesis up to 30% at a rate of 0.2 mm / s, which may be slow enough to achieve quasi-static testing conditions. To evaluate the prosthesis, the prosthesis 100 may first be measured and then placed in a compression testing system (e.g., an Instron product) as shown in FIG. 11A. In some non-limiting embodiments, a 100 N load cell may be used to compress the prosthesis. The system may then compress the prosthesis up to 30% of its original height (e.g., to the point of interest) and collect force-displacement data.

[0089]

[0111] Various geometric measurements of the prosthesis, such as pre-compression height, displacement, and force, may be used to calculate the compressive stiffness of the prosthesis. Specifically, the compressive stiffness of the prosthesis may be derived as follows:

number

[0090]

[0112] In the above equations, the normalized force and compression displacement are measured throughout the test, and the dimensions of the prosthesis are measured before the test. Note that in some embodiments, given that the slope of the compression curve is non-linear, the term "compression stiffness" as used herein refers to the compression secant stiffness, which is defined by the linear slope between the origin and the point of interest.

[0091]

[0113] Figure 11B shows various dimensions associated with an implantable prosthesis. The cross-sectional area of ​​the prosthesis can be calculated as follows:

number

[0092]

[0114] The force measurements from the test system may be converted to a normalized force as follows:

number

[0093]

[0115] In one exemplary embodiment, an ellipsoidal implantable prosthesis having overall dimensions of approximately 2 cm x 2 cm x 3 cm and a 25% hollow core percentage may exhibit an average compressive stiffness in the horizontal orientation of approximately 4.05 psi and an average compressive stiffness in the vertical orientation of 4.66 psi. In another exemplary embodiment, an ellipsoidal implantable prosthesis having overall dimensions of approximately 3 cm x 3 cm x 4 cm and a 10% hollow core percentage may exhibit an average compressive stiffness in the horizontal orientation of approximately 3.55 psi and an average compressive stiffness in the vertical orientation of 3.52 psi. In yet another exemplary embodiment, an ellipsoidal implantable prosthesis having overall dimensions of approximately 4 cm x 4 cm x 5 cm and a 10% hollow core percentage may exhibit an average compressive stiffness in the horizontal orientation of approximately 2.40 psi and an average compressive stiffness in the vertical orientation of approximately 2.82 psi.

[0094]

[0116] The stiffness of the implantable prostheses of the present disclosure may be adjusted by various 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 hollow core percentage, etc. In some embodiments, the stiffness of the implantable prosthesis may be increased by increasing the wall thickness of the subunits. Wall thickness may be increased by using a thicker substrate material (e.g., a mesh-like repair fabric). In some embodiments, the wall thickness of the subunits may be increased by using multiple overlapping subunits.

[0095]

[0117] FIG. 12 illustrates an exemplary partial assembly process for a double conical subunit 310. The subunit 310 includes a first conical subunit 301, similar to that described in connection with FIGS. 2A-2B, having a first central portion 361, connected to a second conical subunit 302 having a second central portion 362. In some embodiments, the second conical subunit may be positioned so as to overlap within a volume defined by the first conical subunit. In some embodiments, as shown in FIG. 12, the central portions of the first and second conical subunits may be different (e.g., central portion 362 may be smaller than central portion 361). In this manner, the core of an implantable prosthesis formed with such subunits 310 may require less material, which may increase tissue infiltration rates and facilitate the repair process, while maintaining compressive stiffness comparable to that of natural tissue to support adjacent anatomical structures. Of course, biconical subunits having two substantially similar conical subunits (eg, similar central portions) are also contemplated.

[0096]

[0118] It should be understood that any of the implantable prostheses of the present disclosure may employ double-layered subunits. In some embodiments, depending on the application, the prosthesis subunits may employ three or more layers (e.g., three, four, five layers) to improve the mechanical properties of the prosthesis and better mimic the surrounding anatomy.

[0097]

[0119] 13A through 13D illustrate an exemplary assembly process for forming a spherical implantable prosthesis 300 formed from bilayer subunits. FIG. 13A illustrates two substantially two-dimensional substrates 301 and 302, each of which may be processed to form the sidewalls of a three-dimensional subunit, as shown in FIG. 13B. In some embodiments, the substrates may be formed from a porous biocompatible mesh material. As shown, the first substrate 301 may have a smaller center than the second substrate 302. Each substrate may have an overlapping portion that may be formed when the substrates are processed into the sidewalls of the conical subunit. As shown in FIG. 13C, when placed together, the overlapping portions 314 and 324 of each subunit 301 and 302, respectively, may be positioned opposite each other. Depending on the arrangement and notch angles of the subunits, the maximum thickness of the assembled bilayer subunits may be two, three, or four layers. Of course, embodiments in which the overlapping regions overlap or have different arrangements are also contemplated. 13D shows an exemplary spherical prosthesis 300 formed with 12 double-cone subunits. Thus, the prosthesis 300 includes 24 subunits. Compared to a prosthesis formed with single-cone subunits having a similar geometry, material composition, and weld point placement, the double-cone configuration may exhibit greater compressive stiffness while still allowing tissue ingrowth through a central core. As previously explained, the difference in size of the central portions of the two cones may reduce the material volume in the center of the prosthesis, promoting tissue ingrowth. Of course, double-cone (or other subunit) configurations formed using similar cones are also contemplated.

[0098]

[0120] Table 2 below shows exemplary geometric and mechanical properties of six spherical implantable prostheses formed with double-layered subunits. Each prosthesis was designed to be approximately 5 cm x 5 cm x 5 cm and its double-layered conical subunits included a first conical subunit with a core percentage of 10% and a second conical subunit with a core percentage of 22.5%.

[0099] [Table 2]

[0100]

[0121] 14 illustrates an exemplary ellipsoidal implantable prosthesis 400 formed from two pairs of bilayered subunits 410 and 415. As shown, subunit 415 may be larger than subunit 410, which helps achieve the generally ellipsoidal shape. Of course, the present disclosure is not limited in this respect, and any suitable combination of subunits may be employed to achieve any suitable prosthesis shape. Table 3 below illustrates exemplary geometric and mechanical properties of an ellipsoidal implantable prosthesis formed from bilayered subunits.

[0101] [Table 3]

[0102]

[0122] 15A-15D illustrate the process of assembly of an implantable prosthesis 500 formed of conical subunits 503 and wavy subunits 502. The combination of conical and wavy shapes, when stacked (as shown in FIGS. 15C-15D), may increase the void volume between the subunits and increase the rate of tissue infiltration through the implantable prosthesis while still maintaining sufficient mechanical compressibility after implantation. In some embodiments, the wavy subunits 502 may be in the shape of a star-shaped cone, as shown in FIG. 15B. The wavy subunits 502 may be formed from a substrate 501 (see FIG. 15A) that may be folded or otherwise processed to form radial corrugations. It should be understood that the number of radial corrugations may be any suitable number from three (so that the subunits assume a generally convex triangular prism shape) to six (so that the subunits assume a generally convex hexagonal prism shape), or any other suitable number. The substrate may then be processed (e.g., rolled) to form the sidewalls of the three-dimensional subunits. In some embodiments, the wavy subunit 502 may be disposed within the conical subunit 503, as shown in subunit 504 in FIG. 15C. In other embodiments, the conical subunit may be disposed within the wavy subunit. It should be understood that any combination of various subunits (conical, wavy, etc.) may be employed in any of the prostheses of the present disclosure. FIG. 15D shows a partially assembled prosthesis 500 formed of six subunits, each including at least one conical subunit and at least one wavy subunit.

[0103]

[0123] Table 4 below shows exemplary geometric and mechanical properties of two spherical implantable prostheses having a double-layer subunit formed with a conical subunit and a wavy subunit. 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.

[0104] [Table 4]

[0105]

[0124] 16A-16B illustrate an implantable prosthesis 600 according to some embodiments. The prosthesis 600 may be formed of two-dimensional substrates secured together to form radiating fins emanating from a hollow central portion 620. The central portion 620 may serve as a void volume for tissue infiltration. In some embodiments, the prosthesis 600 may include one or more markers 630 that may exhibit characteristics that may allow for external detection of the position of the prosthesis. For example, the markers 630 may be metal staples that are radiopaque and therefore identifiable during imaging using x-ray imaging.

[0106]

[0125] 17A-17B illustrate another embodiment of an implantable prosthesis 700. This 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 a ring-shaped substrate, which may form a hollow core 720 after assembly of the prosthesis. As described in connection with other embodiments, the hollow core may serve as a void volume to allow tissue ingrowth within the prosthesis after implantation.

[0107]

[0126] 18A-18B illustrate yet another embodiment of an implantable prosthesis 800. The prosthesis 800 may be generally cubic in shape and formed of four subunits, as shown in FIG. 18A. Each subunit may be formed of various panels 810, 815, 825 that may be folded and welded together to form the quadrants of the prosthesis. The four subunits may then be welded together at weld spots 890 to form the prosthesis. The prosthesis may also include one or more markers 830 that may enable the prosthesis to be visible within the implantation site during medical imaging.

[0108]

[0127] 19 illustrates yet another embodiment of an implantable prosthesis 900. The prosthesis 900 may be formed of at least two generally cubic shapes, one contained within the other. In some embodiments, the prosthesis 900 may be accompanied by a marker 930 for external detection. As shown in FIG. 19, the marker may be metallic and thus radiopaque.

[0109]

[0128] 20A-20D illustrate the process of assembling the prosthesis 900 of FIG. 19. Each cube subassembly (see cubes 960 and 970 in FIG. 20D) may be formed by fastening six two-dimensional substrates 950 together, as shown in FIGS. 20A-20B. As previously described, the substrates 950 may be secured together using welds 959, which may strengthen the prosthesis and significantly reduce the risk of disassembly. Once both cubes are partially assembled, the smaller inner cube 960 may be placed within the larger outer cube 970, as shown in FIG. 20D. The outer cube may then be closed, and one or more markers may be added to the prosthesis in preparation for implantation, as shown in FIG. 19.

[0110]

[0129] It should be understood that any of the prostheses described herein may have any suitable shape or geometry depending on the application (e.g., the shape and size of the biopsy). The prosthesis may also be formed of any suitable number, size, and arrangement of subunits.

[0111]

[0130] Example 1

[0131] In some embodiments, the prostheses of the present disclosure may exhibit a degradation profile comparable to conventional prostheses known in the art. As previously discussed, such a degradation profile may promote tissue ingrowth into the prosthesis as it degrades, ultimately allowing the prosthesis to be replaced by natural tissue. Of course, the prostheses described herein may exhibit a conventional degradation profile, but may also improve stiffness transfer between the implant and natural tissue to promote controlled tissue ingrowth.

[0112]

[0132] In one example, the degradation profile of a prosthesis is evaluated over a 12-week period using a porcine preclinical lumpectomy model. 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 for three spherical prostheses formed of 12 conical subunits with an overall average diameter of approximately 3 cm, and Sample 2 represents the average data for three conventional prostheses (e.g., PHASIX plug and patch).

[0113] [Table 5]

[0114]

[0133] As shown in Table 5 above, molecular weight analysis of Samples 1 and 2 showed statistically significant reductions at 4 and 12 weeks compared to the pre-implantation state. Molecular weight analysis also showed statistically significant reductions at 12 weeks compared to 4 weeks after implantation. However, there was no statistically significant difference in molecular weight at the center compared to the periphery for the two samples at either 4 or 12 weeks after implantation, suggesting that the molecular weight reduction caused by these devices was uniform.

[0115]

[0134] The molecular weight analysis presented in Table 5 above may suggest that the implantable prostheses described herein may exhibit the same molecular weight reduction as conventional implantable devices. However, it should be noted that the prostheses described herein may result in a different biological response compared to conventional prostheses, as discussed below in connection with Example 2.

[0116]

[0135] Example 2

[0136] In some embodiments, the local tissue response after implantation of the prosthesis may be characterized histologically by assessing the presence of angiogenesis, fibrosis, collagen deposition, vascular integration, collagen morphology (by PSR staining), myofibroblast proliferation (by SMA or smooth muscle actin staining), and angiogenesis (by VWF or von Willebrand factor staining).

[0117]

[0137] FIG. 21 shows exemplary data of the aforementioned local tissue reactions for various prostheses, including the commercially available BioZorb prosthesis, represented by Group 3 (week 4) and Group 8 (week 12), the commercially available PHASIX Plug prosthesis, represented by Group 4 (week 4) and Group 9 (week 12), sham-treated controls, represented by Group 5 (week 4) and Group 10 (week 12), and spherical prostheses formed of 12 conical subunits according to the present disclosure, having an overall average diameter of approximately 3 cm, represented by Group 11 (week 4) and Group 12 (week 12).

[0118]

[0138] Tissue reaction data are scored as shown in Table 6 below.

[0119] [Table 6]

[0120]

[0139] The exemplary data in Figure 21 are also presented below in Table 7 (week 4) and Table 8 (week 12).

[0121] [Table 7]

[0122] [Table 8]

[0123]

[0140] The data presented in Figure 21 and Tables 7 and 8 show several statistically significant differences for angiogenesis (n=2), fibrosis (n=1), and collagen deposition (n=1) at 4 weeks, and one statistically significant difference for fibrosis at 12 weeks. At 4 weeks, the PHASIX™ plugs (Group 4) had statistically significantly higher mean angiogenesis than the sham sites (Group 5) (probably due to the expected minimal inflammation / tissue reaction at the sham sites), and the sham sites (Group 5) had statistically significantly lower mean angiogenesis than the prosthesis of the present disclosure (Group 11) (probably due to the expected minimal inflammation / tissue reaction at the sham sites). At 4 weeks, the sham sites (Group 5) had statistically significantly lower mean fibrosis than the prosthesis of the present disclosure (Group 11) (probably due to the expected minimal inflammation / tissue reaction at the sham sites). At 4 weeks, the sham site (Group 5) had a statistically significantly lower mean collagen deposition compared to the disclosed prosthesis (Group 11) (probably due to the expected minimal inflammation / tissue reaction at the sham site). Furthermore, at 12 weeks, the PHASIX™ Plug (Group 9) had a statistically significantly higher mean fibrosis compared to the sham site (Group 10) (probably due to the expected minimal inflammation / tissue reaction at the sham site). These statistically significant differences may be interpreted as not being biologically significant and likely the result of a comparison between the device-present group and the sham site group, where the expected minimal inflammation / tissue reaction was present.

[0124]

[0141] In some embodiments, the cellular response after implantation of the prosthesis may be characterized by histological observation of inflammation and inflammatory cell types. Figure 22 shows exemplary data of the aforementioned inflammatory response for various prostheses, including the commercially available BioZorb prosthesis, represented by Group 3 (week 4) and Group 8 (week 12), the commercially available PHASIX Plug prosthesis, represented by Group 4 (week 4) and Group 9 (week 12), sham-treated controls, represented by Group 5 (week 4) and Group 10 (week 12), and spherical prostheses formed of 12 conical subunits according to the present disclosure, with an overall mean diameter of approximately 3 cm, represented by Group 11 (week 4) and Group 12 (week 12). The inflammation data is scored as shown in Table 6.

[0125]

[0142] The exemplary data in Figure 22 are also presented below in Table 9 (week 4) and Table 10 (week 12).

[0126] [Table 9]

[0127] [Table 10]

[0128]

[0143] As shown in Figure 22 and Tables 9 and 10, histologically, in the implanted test and control sites, overall inflammation was similar between the prosthesis and control implanted sites at both time points (4 and 12 weeks), and overall inflammation decreased over time in all groups except for the sham-treated sites, where overall inflammation was (as expected) lower than the test and control-treated sites at both time points. The inflammatory infiltrate was heterogeneous at both time points; at 4 weeks, it consisted of neutrophils (absent in the sham-treated and sites associated with the disclosed prosthesis), eosinophils (absent in the sham-treated and BioZorb® sites), macrophages, lymphocytes, and multinucleated giant cells. At 12 weeks, the inflammatory infiltrate consisted of neutrophils (seen in small numbers only in the BioZorb® and PHASIX™ plug sites), eosinophils (absent in the BioZorb® sites), macrophages, lymphocytes, and multinucleated giant cells. Two statistically significant differences were observed for eosinophils at 4 weeks (BioZorb® and sham vs. the prosthesis of the present disclosure) and one statistically significant difference was observed for lymphocytes at 12 weeks (PHASIX™ Plug vs. sham). All three statistically significant differences were interpreted as not being biologically significant and likely the result of comparing groups with two different materials comprising the device and comparing the group with the device present vs. the group containing a sham site where, as expected, there was little inflammation / tissue reaction.

[0129]

[0144] Example 3

[0145] As previously mentioned, in some embodiments, implantable prostheses may be formed from porous, two-dimensional substrates that can be cut and assembled into three-dimensional prostheses. In some embodiments, the substrate may be a porous mesh-like sheet. For example, the substrate may be formed from a PHASIX porous material having at least two pore size distributions: large and small pore sizes. The porosity of the prostheses may be evaluated using a statistical Six Sigma system, as shown in Table 11 below. This table summarizes porosity data from 15 exemplary mesh substrates used to form implantable prostheses, including the number of samples (N), mean pore size, standard error of the mean (SE), standard deviation (SD), minimum size of the distribution, first quartile porosity (Q1), median porosity, third quartile porosity (Q3), and maximum size. The porosity of the substrates shown in Table 11 below was measured by optical characterization.

[0130] [Table 11]

[0131]

[0146] In some embodiments, the implantable prosthesis may be sutured to the implantation site. In some embodiments, adjacent conical subunits may be sutured to one another during assembly. Thus, the mesh sheet may have sufficient suture pull-out strength to withstand this force during implantation and / or assembly. The suture pull-out strength of the mesh substrate may be evaluated using a statistical Six Sigma system, as shown in Table 12 below. This table summarizes suture pull-out strength data in both the machine direction (MD) and cross direction (CD) from 15 exemplary mesh substrates used to form implantable prostheses. The data in Table 12 include the sample size (N), mean strength, standard error of the mean (SE), standard deviation (SD), minimum strength of the distribution, 1st quartile strength (Q1), median strength, 3rd quartile strength (Q3), and maximum strength. The strength of the substrates shown in Table 12 below was measured by conventional tensile techniques using a mechanical testing machine.

[0132] [Table 12]

[0133]

[0147] Example 4

[0148] In some embodiments, an implantable prosthesis may be sufficiently compressible so that it can be inserted into an implantation site through an incision smaller than its average size. For example, a generally spherical implantable prosthesis with an average diameter of 2 cm may need to be inserted through an incision of about 1.5 cm (to minimize scarring and incision formation), but may be larger than the incision because the majority of the prosthesis' size is maintained at the implantation site.

[0134]

[0149] The size recovery of an implantable prosthesis may be assessed along one or more directions through measurements of the pre-insertion and post-insertion dimension D, with the differential percentage calculated as follows:

[0135]

number

[0136]

[0150] The differential percentage may be calculated for any suitable dimension, such as the height and first and second widths of the prosthesis (see FIG. 11B). Table 13 below summarizes the differential percentages for height and first and second widths for 15 exemplary spherical implantable prostheses formed with 12 conical subunits using the statistical Six Sigma system described above. The exemplary prostheses measured in Table 13 below have an average diameter of 2 cm and are inserted through a 1.5 cm incision.

[0137] [Table 13]

[0138]

[0151] In some embodiments, the recoverability of an implantable prosthesis may be evaluated using a compression test. For example, an implantable prosthesis may be subjected to a 30% compression and return to its pre-compression state. In some embodiments, a design requirement for such compression may be that the prosthesis return to within 10% of its original dimensions after compression. Table 14 below summarizes the percentage difference in height and first and second widths for 15 exemplary spherical implantable prostheses that meet such requirements. These prostheses are formed from 12 conical subunits, and the values ​​shown in Table 14 were evaluated using a statistical Six Sigma system as described above.

[0139] [Table 14]

[0140]

[0152] Example 5

[0153] In some embodiments, an implantable prosthesis may have sufficient mechanical stiffness to provide strength to adjacent tissue during implantation, while transferring loads to natural tissue during the regeneration process. In some embodiments, the stiffness of the prosthesis may better match natural tissue, allowing for smoother and more controllable load transfer during prosthesis degradation. Thus, in some embodiments, prostheses may be designed to have stiffness requirements, such as a support stiffness of 1.8 psi or greater at 30% compression and a compression stiffness of 6.1 psi or less, because a high-stiffness prosthesis may induce undesirable cellular responses. Table 15 below summarizes the stiffness of 15 exemplary spherical implantable prostheses formed from 12 conical subunits, each with a different average diameter, as shown in the table. The prostheses in Table 15 met the aforementioned design requirements using a statistical Six Sigma system, as described above.

[0141] [Table 15]

[0142]

[0154] Similar stiffness characterization may be performed on non-spherical implantable prostheses described herein, such as the ellipsoidal prostheses, as described in connection with Figures 8A through 10E. Table 16 below summarizes the stiffness of two exemplary sets of ellipsoidal implantable prostheses, each comprised of 14 subunits of different sizes, as shown in the table. The stiffness values ​​shown in the table were evaluated using a statistical Six Sigma system, as previously described. The specific geometries of the various ellipsoidal prostheses evaluated in Table 16 are set forth in Table 1 above.

[0143] [Table 16]

[0144]

[0155] Example 6

[0156] In some embodiments, the prostheses described herein may be tissue infiltrative, which may allow the prosthesis to be fixed in place after implantation. Natural tissue ingrowth may serve to limit prosthesis migration. Prosthesis migration may be verified by tracking radiopaque markers associated with the prosthesis, which may allow the prosthesis to be observed and tracked by an external imaging system without the need for an invasive procedure. As previously mentioned, markers may be used to mark specific physiological locations within the patient (e.g., the location of the tumor bed) for follow-up imaging to monitor recovery and potential recurrence. In some cases, it may be desirable to limit marker migration to within 1 cm of the initial device attachment site after five months of implantation. Table 17 below summarizes radiopaque marker migration for 30 exemplary markers from initial implantation to five months post-implantation using a statistical six-sigma system, as previously described. The data shown in Table 17 reflect measurements at two different locations for each marker between the aforementioned time points.

[0145] [Table 17]

[0146]

[0157] Example 7

[0158] In some embodiments, the stiffness of an implantable prosthesis may be determined by various factors, such as the hollow core percentage, the number of connections between and within each conical subunit, the distance between connections (e.g., welds), and the overall geometric shape of each conical subunit. In one exemplary experiment, a Pareto analysis of the various factors that may determine stiffness was performed to determine which factors were most influential in achieving a desired stiffness. This analysis revealed that a hollow core percentage of 10% and an overlap of about 65° could achieve a target stiffness of about 3.75 psi for a spherical prosthesis with an average diameter of about 4 cm.

[0147]

[0159] The embodiments described herein may be embodied as methods, examples of which are shown. The actions performed as part of the method may be ordered in any suitable manner. Thus, embodiments may be constructed in which actions are performed in an order different from that described, and may include performing some actions simultaneously despite being shown as sequential actions in the described embodiments.

[0148]

[0160] Additionally, some actions are described as being performed by a "user." It should be understood that a "user" need not necessarily be a single individual, and that in some embodiments, actions attributed to a "user" may be performed by a team of individuals and / or an individual in combination with computer-assisted tools or other mechanisms.

[0149]

[0161] While the present teachings have been described in conjunction with various embodiments and examples, it is not intended that the present teachings be limited to such embodiments or examples. On the contrary, the present teachings encompass various alternatives, modifications, and equivalents, as will be appreciated by those skilled in the art. Accordingly, the foregoing description and drawings are by way of example only.

[0150]

[0162] While several embodiments of the present invention have been described and illustrated herein, those skilled in the art will readily envision various other mechanisms and / or structures that perform the functions and / or obtain the results and / or one or more advantages described herein, and each such variation and / or modification is deemed to be within the scope of the present invention. More generally, those skilled in the art will readily recognize that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary, and that the actual parameters, dimensions, materials, and / or configurations will depend on the particular application or applications for which the teachings of the present invention are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. It is therefore understood that the above-described embodiments are presented by way of example only, and that, within the scope of the appended claims and their equivalents, the invention may be practiced otherwise than as specifically described and claimed. The present invention relates to each individual mechanism, system, article, material, kit, and / or method described herein. Also, any combination of two or more such features, systems, articles, materials, kits, and / or methods is included within the scope of the present invention, provided that such features, systems, articles, materials, kits, and / or methods are not mutually inconsistent.

Claims

1. An implantable prosthesis comprising multiple substantially conical mesh bodies, Each of the plurality of substantially conical mesh bodies is connected to at least one other mesh body among the plurality of substantially conical mesh bodies, An implantable prosthesis in which the substantially conical body is arranged to form an ellipsoid.

2. A method for forming a transplantable prosthesis, Forming multiple substantially conical mesh bodies, Each of the aforementioned conical mesh bodies is connected to at least one other mesh body from among the other substantially conical mesh bodies to form an ellipsoid, Methods that include...

3. An implantable prosthesis comprising multiple substantially conical bodies, Each of the plurality of substantially conical bodies is connected to at least one of the plurality of substantially conical bodies, An implantable prosthesis wherein the implantable prosthesis is substantially mechanically isotropic.

4. An implantable prosthesis comprising a plurality of substantially conical bodies, each including a side wall defining a conical shape, An implantable prosthesis in which the side walls of each substantially conical body are connected to the side walls of at least one other adjacent substantially conical body.

5. A method for forming a transplantable prosthesis, Each of these forms a plurality of substantially conical bodies, each including side walls that define a conical shape, Connecting the side walls of each substantially conical body to the side walls of at least one other adjacent substantially conical body, Methods that include...

6. The implantable prosthesis according to claim 1, 3, or 4, wherein the implantable prosthesis comprises a hollow core.

7. The implantable prosthesis according to claim 1, 3, or 4, wherein the prosthesis is configured to be sized and shaped so as to be positioned at the site of tumor removal.

8. The implantable prosthesis according to claim 1, 3, or 4, wherein the implantable prosthesis is formed at least partially of an absorbable material.

9. An implantable prosthesis according to claim 1, 3, or 4, further comprising one or more radiopaque markers.

10. The implantable prosthesis according to claim 1, 3, or 4, wherein the compressive rigidity of the implantable prosthesis is 1 psi or more and 10 psi or less.

11. The implantable prosthesis of claim 4, wherein a first portion of the side wall of each substantially conical body is connected to a second portion of the side wall of the same substantially conical body.

12. The implantable prosthesis of claim 4, wherein a first portion of the side wall of each substantially conical body is welded to a second portion of the side wall of the same substantially conical body.

13. Each substantially conical body has side walls, An implantable prosthesis according to claim 1 or 3, wherein a first portion of the side wall of each substantially conical body is welded to a second portion of the side wall of the same substantially conical body.

14. Each substantially conical body has side walls, The implantable prosthesis according to claim 1 or 3, wherein the side walls of each substantially conical body are welded to the side walls of at least one other adjacent substantially conical body.

15. The implantable prosthesis according to claim 1, 3, or 4, wherein the average diameter of at least one of the implantable prostheses is 2 cm to 5 cm.

16. The implantable prosthesis according to claim 3 or 4, wherein the substantially conical body is arranged to form an ellipsoid.

17. The implantable prosthesis according to claim 1 or 4, wherein the implantable prosthesis is substantially mechanically isotropic.

18. The implantable prosthesis according to claim 1, 3, or 4, wherein the substantially conical body is arranged to form a sphere.

19. The implantable prosthesis of claim 1, 3, or 4, further comprising a second plurality of substantially conical mesh bodies geometrically distinct from the first plurality of substantially conical mesh bodies.

20. The implantable prosthesis according to claim 6, wherein the volume of the hollow core is 10% to 35% of the total volume of the implantable prosthesis.

Images