PRÓTESES IMPLANTÁVEIS PARA REGENERAÇÃO DE TECIDO E MARCAÇÃO DE SÍTIOS CIRÚRGICOS
Patent Information
- Authority / Receiving Office
- BR · BR
- Patent Type
- Applications
- Current Assignee / Owner
- DAVOL INC
- Filing Date
- 2023-12-29
- Publication Date
- 2026-08-04
Smart Images
Figure 00000000_0000_ABST
Abstract
Description
1 / 77 “Implantable Prostheses for Tissue Regeneration and Marking of Surgical Sites” FIELD
[001] The disclosed modalities relate to tissue engineering devices and related methods and, more specifically, to implantable prostheses for soft tissue regeneration and identification of biopsy and lumpectomy sites. BACKGROUND
[002] Excision or resection of soft tissues has become an integral and important part of cancer treatment. Tissue may be removed as a biopsy sample to perform diagnostic examinations or tests to determine cytology, histology, the presence or absence of chemicals that act as indicators of disease states, or the presence of bacteria or other microbes. If the biopsy sample indicates malignant cells (e.g., diseased or cancerous), the surgeon may choose to remove a larger amount of tissue to limit the risk of cell spread and growth and to optimize surgical outcomes.
[003] The removal of a portion of diseased or cancerous cells from breast tissue may be called a lumpectomy, partial mastectomy, or mastectomy, which most commonly refers to the removal of all breast tissue. Resection or excision of tissue may result in an undesirable palpable and / or visible alteration in the tissue. Thus, patients may seek reconstructive options to fill the void left by the procedure, such as fat injections, autologous tissue, or natural material (e.g., collagen). Alternatively, synthetic materials such as silicone may be used. Petition 870250069888, dated 06 / 08 / 2025, p. 10 / 118 2 / 77 SUMMARY
[004] In some embodiments, an implantable prosthesis includes a plurality of substantially conical mesh bodies, wherein each of the plurality of substantially conical mesh bodies is connected to at least one other of the plurality of substantially conical mesh bodies, and wherein the substantially conical bodies are arranged to form an ellipsoid.
[005] 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 of the other substantially conical mesh bodies to form an ellipsoid.
[006] In other embodiments, an implantable prosthesis includes a plurality of substantially conical bodies, wherein each of the plurality of substantially conical bodies is connected to at least one other of the plurality of substantially conical bodies, and wherein the implantable prosthesis is substantially isotropic mechanically.
[007] In other embodiments, an implantable prosthesis includes a plurality of substantially conical bodies, each conical body including a lateral wall that defines a cone shape, wherein the lateral wall of each substantially conical body is connected to the lateral wall of at least one other adjacent substantially conical body.
[008] In other embodiments, a method of forming an implantable prosthesis involves forming a plurality of substantially conical bodies, each conical body including a lateral wall that defines a cone shape, and connecting the Petition 870250069888, dated 06 / 08 / 2025, p. 11 / 118 3 / 77 lateral wall of each substantially conical body to the lateral wall of at least one other substantially conical adjacent body.
[009] In other embodiments, an implantable prosthesis includes a plurality of mesh bodies, wherein each mesh body is connected to another mesh body, wherein at least some of the mesh bodies include a first mesh portion connected to a second mesh portion, wherein the first portion is disposed within a volume defined by the second mesh portion.
[010] In other embodiments, a method of forming an implantable prosthesis includes forming a plurality of mesh bodies, arranging a first mesh portion of at least some of the mesh bodies within a volume defined by a second mesh portion, connecting the first mesh portion to the second mesh portion, and connecting each of the mesh bodies to another mesh body.
[011] It should be understood that the preceding concepts and the additional concepts discussed below may be arranged in any suitable combination, as the present disclosure is not limited in this respect. Furthermore, other advantages and innovative attributes of the present disclosure will become apparent from the following detailed description of various non-limiting embodiments when considered in combination with the accompanying figures. BRIEF DESCRIPTION OF THE DRAWINGS
[012] The attached drawings are not intended to be drawn to scale. In the drawings, each identical or nearly identical component illustrated in various figures may be represented by a similar number. For clarity, not all components may be identified in all drawings. In the drawings: Petition 870250069888, dated 06 / 08 / 2025, p. 12 / 118 4 / 77
[013] Figures 1A-1B illustrate an implantable prosthesis according to some modalities;
[014] Figure 2A represents a top view of the conical subunit of an implantable prosthesis, according to some embodiments;
[015] Figure 2B represents an isometric view of the conical subunit of Figure 2A, according to some embodiments;
[016] Figure 3 illustrates a conical subunit of an implantable prosthesis according to some embodiments;
[017] Figures 4A-4D represent conical subunits of implantable prostheses according to other modalities;
[018] Figures 5A-5B illustrate various views of an implantable prosthesis according to some modalities;
[019] Figure 6A illustrates an implantable prosthesis according to other modalities;
[020] Figure 6B represents the implantable prosthesis of Figure 6A along line 6B-6B;
[021] Figures Figures 7A-7C illustrate three implantable prostheses according to other modalities still;
[022] Figures 8A-8B illustrate various views of an ellipsoidal implantable prosthesis according to some embodiments;
[023] Figures 9A-9F illustrate conical subunits of the implantable prosthesis of Figures 8A-8B, according to some embodiments;
[024] Figures 10A-10E illustrate an assembly process of a Petition 870250069888, dated 06 / 08 / 2025, page 13 / 118 5 / 77 implantable prosthesis according to some modalities;
[025] Figures 11A-11B illustrate a compression test system for implantable prostheses, according to some embodiments;
[026] Figure 12 illustrates a partial assembly process of an implantable prosthesis according to some modalities;
[027] Figures 13A-13D illustrate an assembly process for an implantable prosthesis according to some modalities;
[028] Figure 14 illustrates an implantable prosthesis according to other modalities;
[029] Figures 15A-15D illustrate an assembly process for an implantable prosthesis according to other modalities as well;
[030] Figures 16A-16B illustrate an implantable prosthesis according to other modalities;
[031] Figures 17A-17B illustrate an implantable prosthesis according to other modalities;
[032] Figures 18A-18B illustrate an implantable prosthesis according to other modalities as well;
[033] Figure 19 illustrates an implantable prosthesis according to other modalities as well;
[034] Figures 20A-20D illustrate an assembly process for an implantable prosthesis according to other modalities as well;
[035] Figure 21 shows exemplary data of local tissue response to experimental implantation of an implantable prosthesis according to some Petition 870250069888, dated 06 / 08 / 2025, p. 14 / 118 6 / 77 modalities; and
[036] Figure 22 shows exemplary data of cellular response to experimental implantation of an implantable prosthesis according to some modalities. DETAILED DESCRIPTION
[037] The removal of natural tissue at the removal site, which may occur during therapeutic treatment, can result in external rippling or disfigurement, which can affect both the appearance and palpability of the natural tissue. Conventional tissue reconstruction using autologous fat or soft natural material fillers can produce undesirable results due to the lack of mechanical rigidity of injectable materials, which are unable to support the tissue at the implant site. Furthermore, these materials can retard tissue growth at the removal site, prolonging the healing and reconstruction process. Alternative options, such as silicone, may be rigid enough to support the surrounding tissue, but may substantially limit the potential for tissue growth indefinitely. Additionally, synthetic fluid or filler materials may be incompatible with cancer treatments such as radiotherapy.Such treatments can result in material leaching. Thus, the inventors recognized the need for a soft tissue prosthesis that can simultaneously exhibit mechanical properties to support the anatomy of the implant site, while also allowing for rapid tissue growth.
[038] In addition, in cancer treatment, radiotherapy is often performed after the removal of a tumor to destroy any remaining cancer cells. Petition 870250069888, dated 06 / 08 / 2025, page 15 / 118 7 / 77 and reduce the risk of cancer recurrence. However, the inventors recognized that delineating the tissue margins of a tumor cavity after radiotherapy can be difficult. Traditionally, doctors rely on the location of the surgical scar or the presence of seroma to identify the radiotherapy site and the target radiation volume. However, these identification methods are not the most accurate and may not only reduce the effectiveness of radiotherapy but also increase the chances of damaging healthy tissue around the cavity. Correctly locating the margins of a tumor resection cavity can also be extremely difficult because the cavity may have an irregular shape, and in some tissues, the shape may change over time. For example, the tumor cavity may increase or decrease during breathing, or it may even change in size and shape as a result of continuous radiotherapy treatments.Markers are also used in cases where biopsy results are normal (e.g., benign) to provide information about the biopsy history in follow-up examinations (e.g., mammograms).
[039] In some cases, physicians often use marker devices to better define the location of the cavity and provide a clearer target for external beam radiation treatment. A marker device is a marker or set of markers placed in an imaging field as a reference point, conventionally made of surgical alloys such as titanium alloys, including shape memory alloys. Markers are typically small metal objects that are distinct from surrounding tissue through a variety of imaging modalities (e.g., X-rays), but may exhibit a tendency to migrate after imaging. Petition 870250069888, dated 06 / 08 / 2025, page 16 / 118 8 / 77 implantation, resulting in an accurate reading of the biopsy or lumpectomy site. Thus, the inventors also recognized the need for a biopsy or lumpectomy site marker to guide radiological targeting in therapeutic and imaging applications.
[040] In view of the foregoing, the inventors recognized the benefits of an implantable prosthesis for soft tissue reconstruction in applications such as surgically excised or resected tissue (e.g., in a lumpectomy procedure) and / or for natural soft tissue volume loss. The prosthesis may have mechanical and geometric properties similar to those of natural tissue to simulate the natural feel of the tissue. The prosthesis may additionally serve as a structure for tissue infiltration, to allow natural (or non-natural) tissue to grow within the prosthesis in order to retain mechanical properties similar to natural tissue without being significantly palpable externally. Tissue growth in the empty space of the resection or excision cavity may also have the added benefit of an improved cosmetic outcome as well as resistance to migration. The prosthesis may also serve as an indicator of biopsy and / or tissue resection site (e.g., lumpectomy).The prosthesis can be made visible using one or more medical imaging systems, allowing for external detection of the site for therapeutic and imaging applications. The prosthesis may offer the benefit of a reduced clinical target volume in radiotherapy and enhance aesthetic outcomes after lumpectomy. However, there are also possible cases where different benefits are offered by the systems and methods disclosed in this document.
[041] In some forms, an implantable prosthesis may be an implant Petition 870250069888, dated 06 / 08 / 2025, p. 17 / 118 9 / 77 three-dimensional formed by a set of subunits. Each subunit can be formed from a two-dimensional substrate, which can be shaped from a two-dimensional configuration to a three-dimensional configuration. In some embodiments, the two-dimensional substrate can be a substrate generally in the shape of a C with a cutout, as will be described in more detail below. The two-dimensional C-shaped substrate can be arranged into a three-dimensional form by fixing the two ends of the C-shaped substrate together. In this way, a cone shape (or truncated cone or frustum conical shape) can be formed which has side walls. It should be taken into account that the two-dimensional substrate can have any shape to facilitate its transformation into a three-dimensional subunit body.In some embodiments, the two ends of the C-shaped substrate can be fixed together using permanent means (e.g., welding), while in other embodiments, the two ends can be fixed together using temporary means (e.g., a fastener, such as a clamp). The side walls of the three-dimensional subunit can then be fixed to the side walls of one or more other subunits to form the three-dimensional implantable prosthesis. For example, twelve truncated cone subunits can be fixedly arranged together to form a generally ellipsoidal shape.
[042] The inventors recognized the benefits associated with implantable prostheses that balance mechanical properties to support surrounding anatomy with high rates of tissue infiltration. A highly rigid and dense implantable prosthesis would support surrounding tissue without providing natural palpability or facilitating tissue growth. On the other hand, the absence of a prosthesis may induce natural tissue growth, but may present a depression or disfigurement in the Petition 870250069888, dated 06 / 08 / 2025, page 18 / 118 10 / 77 site of tissue removal. Thus, the implantable prostheses of the present disclosure can exhibit both mechanical isotropy and large voids to allow for tissue growth. In this way, the prostheses can provide sufficient and isotropic mechanical support to the implant site while allowing for rapid tissue growth.
[043] The construction of implantable prostheses using subunits can allow greater tissue infiltration through the prosthesis when compared to a non-porous or solid prosthesis. In this way, implantable prostheses can exhibit palpability and / or other properties similar to natural tissue. In some embodiments, the prostheses can be formed from materials that allow fibroblast invasion to produce collagen, which can envelop the underlying material of the prosthesis. Thus, in some embodiments, the prostheses of the present disclosure can serve as a building block for the development of organs in vivo (engineering) or supplementation, providing a framework to induce vascularization.
[044] In some embodiments, an implantable prosthesis may be formed from an array of conical mesh subunits or bodies connected to at least one neighboring subunit. The prosthesis may have an assembled shape similar to an ellipsoid. In some embodiments, an implantable prosthesis may be constructed by first forming each conical mesh subunit or body, as will be described in greater detail below, and subsequently connecting each conical mesh subunit to a neighboring subunit to form an ellipsoidal prosthesis. An ellipsoidal (e.g., spherical) shape may have the benefit of fitting appropriately to a tissue resection site (e.g., biopsy site, lumpectomy site), which may Petition 870250069888, dated 06 / 08 / 2025, p. 19 / 118 11 / 77 helps maintain the natural palpability of the tissue, so that the prosthesis or resection site is not substantially palpable in the subject.
[045] In some embodiments, an implantable prosthesis may be formed from a set of subunits or conical mesh bodies connected to at least one neighboring subunit. The prosthesis may be substantially mechanically isotropic. In some embodiments, an implantable prosthesis may be constructed by first forming each subunit or conical mesh body, as will be described in greater detail below, and subsequently connecting each conical mesh subunit to a neighboring subunit to form a substantially mechanically isotropic prosthesis. As will be described in more detail below, substantially mechanical isotropic refers to the property of having similar compressive stiffness along more than one orientation of the prosthesis. A substantially mechanically isotropic implantable prosthesis may have the benefit of simulating natural tissue during palpation, in addition to providing uniform structural support to the anatomy.Consequently, the prosthesis may exhibit mechanical properties compatible with natural tissue, such that the prosthesis or the resection site is not substantially palpable in the subject.
[046] In some embodiments, an implantable prosthesis may be formed from a set of subunits or conical mesh bodies, each having a lateral wall that can be connected to a lateral wall of a neighboring or adjacent subunit or body. Such a prosthesis may be constructed by first forming each subunit or conical mesh body and connecting a lateral wall of each body to a lateral wall of an adjacent body. The connections between the various subunits or bodies Petition 870250069888, dated 06 / 08 / 2025, p. 20 / 118 12 / 77 can increase the mechanical robustness of the prosthesis. The connections formed between the lateral walls of the bodies can serve to unify the conical subunits in the final implantable prosthesis, so that the pressure from the surrounding anatomy can be distributed evenly within the prosthesis with a reduced risk of fraying.
[047] In some embodiments, an implantable prosthesis may be formed by a set of subunits or bodies, each connected to another subunit. The subunit may include a first portion connected to another portion of the subunit and arranged within a volume defined by the other portion of the subunit. Such a prosthesis may be constructed by first forming each of the subunits, arranging one portion of the subunit into another portion of the subunit, connecting the two portions, and connecting each subunit to a neighboring or adjacent subunit. In this way, the prosthesis subunits may benefit from a greater volume of material, which may further strengthen the prosthesis and provide support to the natural tissue. As will be described in more detail below, the subunit portions may differ in geometry to induce tissue growth and, at the same time, optimize the mechanical properties of the prosthesis.
[048] In some embodiments, the prostheses of the present disclosure can induce tissue infiltration through the porosity, which may allow cells to proliferate through the prostheses. The prosthesis may have porosity at multiple length scales. For example, the internal volume of the conical subunits of a prosthesis may provide large voids for tissue growth. The subunits themselves may be formed of a mesh-like or macroporous (with large pores) material, which may allow the prosthesis to accommodate sufficient autologous fat, Petition 870250069888, dated 06 / 08 / 2025, p. 21 / 118 13 / 77 Biological materials, microphages, fibroblasts, collagen, hyaluronic acid, and / or bioactive agents are used to facilitate vascularization and tissue growth within the prosthesis. In some embodiments, prostheses may be formed from materials with pores larger than 10 microns to limit the risk of rejection and scar tissue formation. The term “macroporous” or “mesh,” as used herein, refers to average pore diameters greater than or equal to 10 microns, 20 microns, 30 microns, 40 microns, 50 microns, 60 microns, 75 microns, 100 microns, and / or any other suitable pore size.
[049] In some embodiments, the implantable prostheses of the present disclosure may preferably have a generically ellipsoidal shape to simulate the anatomical cavity left by a tissue removal procedure (e.g., lumpectomy) and / or any other natural or surgically formed cavity. Specifically, in some embodiments, the prostheses may have a spherical shape. However, it should be understood that the implantable prostheses of the present disclosure may have any suitable three-dimensional shape, including, but not limited to, a sphere, ellipsoid, hemisphere, cylinder, cone, dome, cuboid, tetrahedron, triangular or square prism, dodecahedron, combinations thereof, and / or customized geometries.It should be understood that the term "ellipsoidal," as used in this document, refers to three-dimensional ellipsoidal shapes (which may have different average diameters in two or more directions), spheroidal shapes, and spherical shapes (which may have substantially similar average diameters in all directions).
[050] It should be understood that the prostheses of the present disclosure may be of any size suitable to accommodate a particular application. For example, Petition 870250069888, dated 06 / 08 / 2025, page 22 / 118 14 / 77 Prostheses can be sized to fit into a tissue removal site (e.g., lumpectomy). Thus, the prosthesis can be of any suitable size. The prosthesis can be characterized by an average diameter, which may preferably be between approximately 2 cm and 5 cm in some preferred embodiments, but other sizes are also contemplated, including prostheses with an average diameter greater than or equal to 0.5 cm, 1 cm, 1.5 cm, 2 cm, 3 cm, 4 cm, 5 cm, 6 cm, 7 cm, 8 cm and / or any other suitable size. Prostheses may also have an average diameter less than or equal to 8 cm, 7 cm, 6 cm, 5 cm, 4 cm, 3 cm, 2 cm, 1.5 cm, 1 cm, 0.5 cm and / or any other suitable size. Combinations of the above items, including prostheses with average diameters between 0.5 cm and 5 cm and between 2 cm and 8 cm, are also considered, including prostheses larger or smaller than the ranges mentioned.
[051] In some embodiments, a prosthesis may have a first mean diameter in one direction of the prosthesis and a second mean diameter in a second direction. For example, the prosthesis may be generically ellipsoidal. Thus, it should be understood that the aforementioned mean diameter ranges may be employed in relation to any suitable dimension of the prosthesis, since the present disclosure is not limited by the geometry of the implantable prosthesis.
[052] As described earlier, in some embodiments, implantable prostheses may be formed from twelve connected subunits. However, it should be understood that any suitable number of subunits may be employed to form any suitable shape of an implantable prosthesis. A prosthesis may have greater than or equal to 1, 5, 10, 15, 20, 25, 30, 35, 40, 50 and / or any other suitable number of subunits. A prosthesis may also have less than or equal to 50, 40, 35, 30, 25, 20, Petition 870250069888, dated 06 / 08 / 2025, page 23 / 118 15 / 77 15, 10, 5, 1 and / or any other suitable number of subunits. Combinations of the above, including prostheses with between 1 and 50 and between 1 and 12 subunits, are also contemplated, along with a number of subunits above the aforementioned ranges. As will be described in detail below, in some embodiments, multilayer subunits may be employed for greater mechanical compressibility. Consequently, the prostheses of the present disclosure are not limited by the number of constituent subunits.
[053] In some embodiments, the prosthetic subunits may also have a three-dimensional shape, such as the shapes mentioned above. In some embodiments, combinations of subunit geometries may be employed to achieve suitable mechanical behavior. For example, a prosthetic subunit may have a generally conical shape.
[054] It should be understood that the term “conical” or “cone”, as used in this document, refers to both conventional conical shapes and cone-like shapes, as well as partial conical shapes, such as a frustoconical shape, which may not have a sharp point.
[055] The subunits of the implantable prostheses described in this document can be arranged and fixed in a three-dimensional configuration by any suitable means. In some embodiments, the subunits can be fixed in their three-dimensional configuration by any suitable bonding, thermal sealing, welding (e.g., ultrasonic or other), adhesive bonding, combinations thereof, and / or any other suitable technique. In some embodiments, the subunits can be fixed in their three-dimensional configuration by a Petition 870250069888, dated 06 / 08 / 2025, page 24 / 118 16 / 77 permanent or non-permanent arrangement. For example, fasteners, such as staples or sutures, can be used to form the subunit in a non-permanent way and / or join neighboring subunits. It should be taken into account that any of the aforementioned fixation techniques can be used to fix neighboring subunits. Any suitable combination of fixation techniques to form the prosthesis can be employed, as the present disclosure is not so limited.
[056] In some embodiments, as described in greater detail below in relation to the figures, the subunits used in the implantable prostheses used in this document may be manufactured from two-dimensional substrates. The substrates themselves may be formed from two-dimensional sheets. The two-dimensional substrates may be formed using any suitable technique, including, but not limited to, trimming or cutting with scissors, blades, other sharp cutting instruments or thermal knives, laser cutting techniques, welding techniques, die-cutting techniques, combinations thereof and / or any other suitable technique. In other embodiments, the substrates may be formed using additive manufacturing techniques, such as 3D printing.
[057] The implantable prostheses of the present disclosure may be formed from a material that can promote the rapid growth of tissue or muscle within and around the prosthesis. In 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 used include BARD Mesh (available from CR Bard, Inc.), BARD Soft Mesh (available from CR Bard, Inc.), SOFT TISSUE PATCH (microporous ePTFE — available from WL Gore & Associates, Inc.); SURGIPRO (available Petition 870250069888, dated 06 / 08 / 2025, p. 25 / 118 17 / 77 near US Surgical, Inc.); TRELEX (available next to Meadox Medical); PROLENE and MERSILENE (available at Ethicon, Inc.); PHASIX Mesh (available from CR Bard, 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 materials (e.g., available from Atrium Medical Corporation). The implantable material may be formed from flat mesh substrates. In some embodiments, the mesh material may be formed from multifilament yarns, and any suitable method, such as knitting, weaving, braiding, molding, and the like, may be employed to form the mesh material.
[058] In some embodiments, prostheses may be formed from permanent materials such as non-degradable thermoplastic polymers, including ethylene and propylene polymers and copolymers, including ultra-high molecular weight polyethylene, ultra-high molecular weight polypropylene, nylon, polyesters such as poly(ethylene terephthalate), poly(tetrafluoroethylene), polyurethanes, poly(ether-urethanes), poly(methyl methacrylate), polyether ether ketone, polyolefins and poly(ethylene oxide). In other embodiments, prostheses may be formed from degradable materials, including, but not limited to, degradable thermoplastic or polymeric materials. Combinations of the above are also contemplated. In some embodiments, the prosthesis may be formed from one or more absorbable polymers or copolymers, absorbable thermoplastic polymers and copolymers and / or absorbable thermoplastic polyesters.Prostheses can be made from polymers including, but not limited to, glycolic acid, lactic acid, 1,4-dioxanone, trimethylene carbonate, 3-hydroxybutyric acid, 4. Petition 870250069888, dated 06 / 08 / 2025, p. 26 / 118 18 / 77 hydroxybutyrate, ε-caprolactone, including polyglycolic acid, polylactic acid, polydioxanone, polycaprolactone, glycolic and lactic acid copolymers, such as VICRYL®, MAXON® and MONOCRYL® polymers, and including poly(lactide-cocaprolactones); poly(orthoesters); polyanhydrides; poly(phosphazenes); polyhydroxyalkanoates; synthetically or biologically prepared polyesters; polycarbonates; tyrosine polycarbonates; polyamides (including synthetic and natural polyamides, polypeptides and poly(amino acids)); polyesteramides; poly(alkylene-alkylates); polyethers (such as polyethylene glycol, PEG, and polyethylene oxide, PEO); polyvinylpyrrolidones or PVP; polyurethanes; polyetheresters; polyacetals; polycyanoacrylates; poly(oxyethylene) / poly(oxypropylene) copolymers; polyacetals, polyketals; polyphosphates; phosphorus-containing polymers; polyphosphoesters; polyalkylene oxalates; polyalkylene succinates; poly(maleic acids);Silk (including recombinant silks and silk derivatives and analogues); 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, for example, poly(lactide), poly(lactide-co-glycolide) or polycaprolactone and their copolymers, including random copolymers and block copolymers.
[059] In some embodiments, the prostheses may be formed from mixtures of absorbable polymer materials, including, but not limited to, 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 Petition 870250069888, dated 06 / 08 / 2025, page 27 / 118 19 / 77 of these. In some embodiments, the prostheses may be made of poly-4-hydroxybutyrate or a copolymer thereof.
[060] In some embodiments, an implantable prosthesis may provide a means to deliver cells, stem cells, differentiated cells, fat cells, muscle cells, platelets, pedicles, vascular pedicles, tissue masses, extracellular adipose matrix proteins, gels, hydrogels, hyaluronic acid, collagen, bioactive agents, drugs, antibiotics, and other materials to the implant site. The cells and tissues that may be delivered and / or coated or injected into the prostheses may be autologous. Prostheses may be used for autologous fat transfer. The cells added, coated, or injected into the prosthesis may include pancreatic islet cells, liver cells, and stem cells genetically altered to contain genes for treating the patient's disease.Prostheses may comprise bioactive agents to stimulate internal cell growth, including growth factors, cell adhesion factors, cell differentiation factors, cell recruitment factors, cell receptors, cell binding factors, cell signaling molecules such as cytokines, and molecules to promote cell migration, cell division, cell proliferation, and extracellular matrix deposition. Prostheses may also be partially or fully coated and / or contain agents to prevent tissue adhesion, or agents to prevent cell proliferation, particularly to retard cell invasion into the prostheses.
[061] In some embodiments, implantable prostheses may be loaded, filled, coated, or otherwise incorporated with bioactive agents. Bioactive agents may be included in prostheses for various reasons. For example, agents Petition 870250069888, dated 06 / 08 / 2025, page 28 / 118 20 / 77 bioactive agents can be included to enhance tissue growth on the implant, improve tissue maturation, provide delivery of an active agent, enhance implant wettability, prevent infection, and enhance cell fixation. Bioactive agents can also be incorporated into the substrate material composition of the subunits.
[062] Prostheses may contain active agents designed to stimulate internal cell growth, 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 to promote cell migration, cell division, cell proliferation and extracellular matrix deposition.These 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-1-B (IL-1B), interleukin-8 (IL-8), and nerve growth factor (NGF), and combinations thereof. As used in this document, the term cell adhesion polypeptides refers to compounds that have at least two amino acids per molecule that are capable of binding to cells via cell surface molecules.Cell adhesion polypeptides include any extracellular matrix proteins known to play a role in cell adhesion, including fibronectin, vitronectin, laminin, elastin, fibrinogen, and collagen types I, II, and III. Petition 870250069888, dated 06 / 08 / 2025, page 29 / 118 21 / 77 V, as well as synthetic peptides with similar cell adhesion properties. Cell adhesion polypeptides also include peptides derived from any of the proteins mentioned above, including fragments or sequences containing the binding domains.
[063] In some embodiments, implantable prostheses may be loaded, filled, coated, or otherwise incorporated with wetting agents designed to enhance the wettability of the various surfaces of the prostheses to allow fluids to be readily adsorbed onto the prosthesis surfaces and to promote cell attachment and / or modify the contact angle of the prosthesis surface with water. Examples of wetting agents include ethylene oxide and propylene oxide polymers, such as polyethylene oxide, polypropylene oxide, or copolymers thereof, such as PLURONICS®. Other suitable wetting agents may include surfactants or emulsifiers.
[064] In some embodiments, implantable prostheses may be loaded, filled, coated, or otherwise incorporated with gels, hydrogels, or living hydrogel hybrids to further enhance wetting properties and promote cell growth throughout the prosthesis. Hydrogel hybrids consist of living cells encapsulated in a biocompatible hydrogel, such as gelatin, methacrylated gelatin (GelMa), silk gels, and hyaluronic acid (HA) gels.
[065] Other bioactive agents that can be incorporated into prostheses may include antimicrobial agents, in particular antibiotics, disinfectants, oncological agents, anti-scarring agents, anti-inflammatory agents, anesthetics, small molecule drugs, anti-adhesion agents, proliferation inhibitors Petition 870250069888, dated 06 / 08 / 2025, page 30 / 118 22 / 77 cellular, anti-angiogenic and pro-angiogenic factors, immunomodulatory agents, and blood coagulation agents. Bioactive agents may be proteins such as collagen and antibodies, peptides, polysaccharides such as chitosan, alginate, hyaluronic acid and derivatives thereof, 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, biguanide, triclosan, gentamicin, minocycline, rifampicin, vancomycin, cephalosporins, copper, zinc, silver, and gold. Nucleic acid molecules may include DNA, RNA, siRNA, miRNA, antisense, or aptamers.
[066] In some embodiments, implantable prostheses may be loaded, filled, coated, or otherwise incorporated with allograft material and xenograft materials, including acellular dermal matrix material and small bowel submucosa (SIS). In one embodiment, the prosthesis may contain a vascular pedicle or other tissue mass. In some embodiments, the prostheses may incorporate systems for the controlled release of therapeutic or prophylactic agents.
[067] In some embodiments, implantable prostheses may be loaded, filled, coated, or otherwise incorporated with allograft or xenograft tissue and cells before, during, or after implantation, or any combination thereof. In some embodiments, prostheses may be coated with autologous tissue and cells from the patient before, during, or after implantation, or any combination thereof. Autologous tissue and cells may include one or more of the following: autologous fat, fat liposuction, adipose tissue, injectable fat, tissue Petition 870250069888, dated 06 / 08 / 2025, page 31 / 118 23 / 77 adipose tissue, fat cells, fibroblast cells, and stem cells, including stem cells derived from human adipose tissue, also known as pre-adipocytes or adipose tissue-derived precursor cells, and fibroblast-like stem cells. In one embodiment, the prostheses may be coated with autologous tissue and cells, as described herein, and may also additionally comprise a vascular pedicle or other tissue mass. As will become evident herein, the prostheses are designed to create not only a shape for the implant, like a breast implant, but also a large surface area that can retain the autologous tissue and cells to stimulate tissue growth.
[068] In some embodiments, the prosthesis may be made of an absorbable material (e.g., polymer or copolymer) that may be substantially reabsorbed after implantation within a period of 1 to 24 months, or 3 to 18 months, and retain some residual strength for at least 2 weeks to 6 months.
[069] In some embodiments, the polymer and copolymer composition of the prostheses may have a low moisture content to ensure that the prostheses can be produced with stiffness comparable to natural tissue, prolonged strength retention, and satisfactory shelf life. In some embodiments, the polymers and copolymers used to prepare the prostheses have a moisture 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).
[070] It should be taken into consideration that the compositions used to prepare the prostheses may have a low endotoxin content. In some embodiments, the endotoxin content may be low enough that the prostheses produced from the Petition 870250069888, dated 06 / 08 / 2025, page 32 / 118 24 / 77 polymer compositions have an endotoxin content of less than 20 endotoxin units per prosthesis, as determined by the Limulus amebocyte lysate (LAL) assay. For example, the polymer compositions used to prepare the prosthesis may have an endotoxin content <2.5 EU / g of polymer or copolymer. In another example, the P4HB polymer or copolymer, or the PBS polymer or copolymer have an endotoxin content <2.5 EU / g of polymer or copolymer.
[071] In some embodiments, the prostheses of the present disclosure may include one or more markers for external detection of the prosthesis location. For example, a prosthesis may include a radiopaque marker (e.g., metallic clip), which may be visible and distinct over the nearby anatomy during X-ray imaging. The markers may be formed from any medical materials approved for long-term use that can be used in medical imaging. Medical imaging means include, for example, radiographic imaging modalities (e.g., X-ray imaging), magnetic resonance imaging (MRI), ultrasound, fluoroscopy, or computed tomography. The marker may therefore be formed from any non-absorbable and biocompatible material, which refers to a material that does not cause any adverse health reaction in the patient and that does not disintegrate over the patient's lifetime.Non-absorbable and biocompatible materials include, but are not limited to, materials containing metal, polymeric materials, ceramic materials, or composite materials that include 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, and / or others. Suitable polymers include, but are not limited to... Petition 870250069888, dated 06 / 08 / 2025, page 33 / 118 25 / 77 polyvinyl alcohol, polyurethanes, polyolefins, polyesters, polypropylenes, polyimides, polyetherimides, fluoropolymers, liquid thermoplastic polymers (LCPs) such as, for example, Celanese's Vectra®, polyethylene ether ketones such as, for example, Vitrex's PEEK™, polyamides, polycarbonates such as, for example, Bayer Polymers' Makrolon®, polysulfones, polyethersulfones, polyphenylsulfones such as, for example, Rowland Technologies' Radel®, nylon, nylon copolymers, combinations thereof and / or others. In some embodiments, the marker may include a shape memory material, including, but not limited to, nitinol, titanium or any shape memory polymers.
[072] In some modalities, the present disclosure prostheses may include one or more brachytherapy seeds that release low levels of radiation for therapy. The seeds may be physically attached to the prostheses and, in some cases, may be embedded within the conical mesh body assembly. The number and location of the brachytherapy seeds may be customized to the targeted radiotherapy location. For example, the prostheses may include between six and thirty-six seeds. In some cases, the seeds are arranged in a pattern as directed by a radiation oncologist and / or nuclear medicine physician. In general, the seeds may comprise suitable radioactive agents (e.g., I-125, Ir-192, Pd-103) and may have a metallic outer casing (e.g., stainless steel, titanium-aluminum-vanadium). The brachytherapy seeds may be radiopaque. In modalities where the implanted prostheses are reabsorbed, the seeds may remain in the body.In some embodiments, the subunit substrate may include one or more visual and / or tactile fiducial markers to facilitate assembly. In some... Petition 870250069888, dated 06 / 08 / 2025, p. 34 / 118 In 26 / 77 embodiments, fiducial markers can indicate the location of an attachment point (e.g., solder point). Fiducial markers may be visually / optically or otherwise apparent to an operator for fitting purposes. In some embodiments, fiducial markers may be colored differently from the prosthesis substrate or otherwise distinct from the underlying prosthesis substrate. In some embodiments, the prosthesis may include multiple fiducial markers colored with more than one color to differentiate the fiducial markers from each other. For example, a first group of fiducial markers may be used to indicate attachment points within a single subunit substrate with a first color, and a second group of fiducial markers may be used to indicate attachment points between neighboring subunit substrates.It should be understood that any combination of fiducial marker types can be employed in any of the prosthetic subunits of the present disclosure.
[073] In some embodiments, the prosthesis itself may be colored. For example, coloring may be used to enhance visualization and / or provide visual cues to assist surgeons intraoperatively. The prosthesis may be colored in several different ways. In some embodiments, a dye / pigment (e.g., medical-grade dye) may be incorporated (e.g., impregnated) into the prosthesis. In some embodiments, a colored coating may be applied to an outer surface of the prosthesis.
[074] The implantable prostheses of the present disclosure may exhibit any Petition 870250069888, dated 06 / 08 / 2025, page 35 / 118 27 / 77 adequate mechanical property to simulate natural anatomy. In some embodiments, prostheses may exhibit compressive stiffness to simulate the mechanics of natural tissue and still provide support to the surrounding anatomy after implantation. As used in this document and as will be expanded upon in more detail below, compressive stiffness is defined as the normalized compressive load applied to a subject divided by its relative deformation during a compression test.
[075] The prostheses of this disclosure may have any adequate compressive stiffness, including, but not limited to, values equal to or greater than 3.45 kPa (0.5 psi), 6.89 kPa (1 psi), 10.34 kPa (1.5 psi), 12.41 kPa (1.8 psi), 13.79 kPa (2 psi), 20.68 kPa (3 psi), 27.58 kPa (4 psi), 34.47 kPa (5 psi), 41.37 kPa (6 psi), 46.89 kPa (6.8 psi), 48.26 kPa (7 psi), 55.16 kPa (8 psi), 62.06 kPa (9 psi), 68.95 kPa (10 psi), 82.74 kPa (12 psi), 103.42 kPa (15 psi) and / or any other adequate stiffness value. Prostheses may also exhibit compressive stiffness less than or equal to 103.42 kPa (15 psi), 82.74 kPa (12 psi), 68.95 kPa (10 psi), 62.06 kPa (9 psi), 55.16 kPa (8 psi), 48.26 kPa (7 psi), 46.89 kPa (6.8 psi), 41.37 kPa (6 psi), 34.47 kPa (5 psi), 27.58 kPa (4 psi), 20.68 kPa (3 psi), 13.79 kPa (2 psi), 12.41 kPa (1.8 psi), 10.34 kPa (1.5 psi), 6.89 kPa (1 psi), 3.45 kPa (0.5 psi) and / or any other suitable stiffness values.Combinations of the aforementioned values are also considered, including prostheses with compressive stiffness between 3.45 kPa and 103.42 kPa (0.5 psi and 15 psi) and between 12.41 kPa and 46.89 kPa (1.8 psi and 6.8 psi), as well as compressive stiffnesses above and below the cited ranges. It should be understood that stiffness can be designed to simulate or support the tissue at the implantation site. Thus, the prosthesis can have any... Petition 870250069888, dated 06 / 08 / 2025, page 36 / 118 28 / 77 adequate stiffness above or below the mentioned ranges.
[076] It should be understood that, in some embodiments, the implantable prostheses of the present disclosure may have substantial mechanical isotropy, which may refer to the isotropic nature of the compressive stiffness of the prosthesis (and / or any other mechanical property). The prosthesis may exhibit similar mechanical properties in multiple orientations. In some embodiments, a prosthesis with substantially isotropic compressive stiffness refers to a prosthesis that has a first compressive stiffness along a first direction and a second compressive stiffness along a second direction, such that the magnitude of the first and second compressive stiffness is 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 primary / secondary geometric axes of the structure (for example, when the prosthesis is formed in an ellipsoidal shape) or may refer to any other suitable direction. For example, a substantially mechanically isotropic prosthesis may refer to a prosthesis with a compressive stiffness of 20.68 kPa (3 psi) in the horizontal direction and a compressive stiffness between 17.93 kPa and 23.44 kPa (2.6 and 3.4 psi) in the vertical direction. Thus, the first and second directions may be perpendicular to each other, although other arrangements are also contemplated.
[077] In other embodiments, the mechanical properties of implantable prostheses may be anisotropic (i.e., orientation-dependent). Therefore, 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 Petition 870250069888, dated 06 / 08 / 2025, p. 37 / 118 29 / 77 taking into account that the mechanical properties of the prosthesis can be selected to simulate the natural properties of the implant site tissue. Therefore, depending on the implant site, the mechanical properties of the prosthesis may have any suitable value above or below the aforementioned ranges.
[078] In some embodiments, the implantable prostheses of the present disclosure may be sufficiently compressible to pass through an incision smaller than the prosthesis. For example, an implantable prosthesis with an average diameter of 2 cm may be compressed to 0.5 cm so that it can pass through a 1.5 cm incision. It should be noted that the compressibility of the prosthesis may be temporary and that it may return to up to 10% of its original size after compression.
[079] In some embodiments, the implantable prostheses of the present disclosure may include features to significantly reduce the risk of prosthesis migration. For example, markers may have the added benefit of generating friction at the implant site to limit prosthesis migration. In other embodiments, the prostheses may include other features to limit migration and / or reorientation of the marker after implantation. It should be understood that, in embodiments where the prosthesis is formed from a generally resorbable material, tissue infiltration through the prosthesis may fix or relatively envelop the prosthesis with the surrounding tissue. Thus, in some embodiments, the prostheses may reduce the risk of migration through the material properties.
[080] The implantable prostheses of the present disclosure can be used in any suitable application. In some embodiments, the prostheses can be implanted into soft tissue after a biopsy (and / or any other procedure, such as Petition 870250069888, dated 06 / 08 / 2025, p. 38 / 118 30 / 77 a lumpectomy) during the treatment of cancers such as breast, abdominal, liver, muscle, kidney, lung, and prostate cancer.In some embodiments, the prosthesis can be used in soft tissue reconstruction applications, so it can serve as a breast implant, breast lift device, breast augmentation device, nipple implant, facial reconstruction device, buttock implant, cheek augmentation device, cosmetic repair device, soft tissue regeneration device, hernia implant, hernia tampon, wound healing device, tissue engineering scaffold, scaffold for a vascular pedicle or other tissue mass, guided tissue repair / regeneration device, volume or filling device, void filler, device for treatment of vesicoureteral reflux, cell seeding device, drug delivery device, combinations thereof and / or any other suitable application.
[081] Returning to the figures, specific non-limiting modalities are described in more detail. It should be understood that the various systems, components, attributes and methods described in relation to these modalities may be used individually and / or in any desired combination, since the disclosure is not limited only to the specific modalities described in this document.
[082] Figures 1A-1B show two isometric views of an implantable prosthesis 100 according to some embodiments. The prosthesis 100 may be formed by conical subunits 20, which may be arranged to form a generally ellipsoidal shape. Specifically, as shown in Figures 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 tissue growth, which may, in some Petition 870250069888, dated 06 / 08 / 2025, page 39 / 118 31 / 77 modalities, resulting in a more natural feel after tissue infiltration into the implant. In some modalities, the prosthesis may include one or more markers 30, which may have radiopaque properties. As described earlier, the markers 30 can facilitate precise visualization of the prosthesis's position after implantation within the anatomy.
[083] It should be noted that although the prosthesis 100 shown in Figures 1A-1B is shown as having a generally spherical shape, prostheses of any shape suitable for filling a biopsy or lumpectomy cavity or serving other prosthetic purposes may also be employed. It should also be understood that although the prosthesis 100 shown in Figures 1A-1B is formed by a set of twelve conical subunits 20, any suitable number of subunits (conical or not) may be employed to form any of the implantable prostheses described herein. Consequently, the prostheses of the present disclosure are not limited by shape, size, number of subunits, shape of the subunits, arrangement of the subunits and / or any other factor.
[084] Figures 2A-2B show various views of a conical subunit 20 according to some embodiments. Figure 2A illustrates a top view of a substantially two-dimensional substrate 22, which can be manipulated (e.g., rolled) to form the conical subunit 20 shown in the isometric view of Figure 2B. In some embodiments, the substrate can be formed from a porous biocompatible mesh material. In some embodiments, the end portions of the substrate 22 can be overlapped to form an overlapping region 24, where the end portions can be subsequently fixed together. In some Petition 870250069888, dated 06 / 08 / 2025, page 40 / 118 In 32 / 77 embodiments, a welding point 29 can fix the end portions of the substrate 22 together, as shown in Figure 2B, although other fastening methods, both temporary and permanent, are also contemplated. This manipulation process can transform the substrate 22 from a substantially two-dimensional arrangement, as shown in Figure 2A, into a three-dimensional arrangement with side walls, as shown in Figure 2B. In some embodiments, the subunit may have a truncated cone shape (or “conical”), while in other embodiments, the subunit may form a different three-dimensional shape.
[085] The overlap region 24 of each conical subunit 20, as shown in Figure 2B, can contribute to the overall mechanical properties of the subunit and the prosthesis. For example, a large overlap region can produce a stiffer subunit compared to a smaller overlap region. In part, this increase in stiffness may be due to the change in the thickness of the subunit, which now has two layers instead of one. The overlap region 24 can be defined by an overlap degree O1, as shown in Figure 2B, which can be added to a non-overlap degree O2 to sum approximately 360°. The overlap degree O1 can be any value suitable to achieve the desired stiffness of the subunit.The degree of overlap can be greater than or equal to 5°, 10°, 15°, 20°, 25°, 30°, 35°, 40°, 45°, 50°, 55°, 60°, 65°, 70°, 75°, 80°, 85°, 90°, 100° and / or less than or equal to 100°, 95°, 90°, 85°, 80°, 75°, 70°, 65°, 60°, 55°, 50°, 45°, 40°, 35°, 30°, 25°, 20°, 15°, 10°, 5° and / or combinations thereof.
[086] It should be noted that although the fastening points (e.g., weld points) 29 are represented as substantially circular, the fastening points Petition 870250069888, dated 06 / 08 / 2025, p. 41 / 118 33 / 77 non-circular options are also contemplated. In some embodiments, an oblong or elongated attachment point can be employed to produce an improved fixation between substrate portions and / or between neighboring subunits. In some embodiments, an oblong or elongated attachment point can help fix the various elements in more than one direction. In some embodiments, an oblong or elongated attachment point can replace several circular attachment points. For example, a series of three weld points can be replaced by one elongated attachment point. This substitution can speed up assembly processes. In some embodiments, the elongated attachment point can increase the rigidity of the subunit.
[087] In some embodiments, as shown in Figure 2A, the substrate 22 may be formed in a generally C-shaped arrangement. A central portion 26 of the substrate 22 may be removed to allow tissue growth through the implantable prosthesis, as shown in Figures 1A-1B. The substrate 22 may also include a cutout encompassing a cutout angle A1 around the substrate 22, as shown in Figure 2A. This cutout may allow the substrate 22 to be manipulated to form the side walls of a three-dimensional cone. In some exemplary embodiments, the subunit 20, shown in Figure 2B, may have a side wall angle of approximately 63°, so that twelve identical subunits together may allow the formation of a generally spherical implantable prosthesis.In some embodiments, the lateral wall angle of the subunits may be greater or less than 63°, including between 50° and 70°, between 60° and 65°, and / or any other suitable range of lateral wall angles. Obviously, prostheses employing different numbers of subunits with different geometries to form prostheses. Petition 870250069888, dated 06 / 08 / 2025, p. 42 / 118 34 / 77 spherical or non-spherical shapes are also considered.
[088] The clipping angle A1 shown in Figure 2A can be any angle suitable to allow the formation of a truncated cone. In some embodiments, the substrate may include a cut, instead of a clipping, spanning an angle A1 approximately equal to 0°. In some embodiments, the clipping angle A1 may be greater than or equal to 0°, 5°, 10°, 15°, 20°, 30°, 40°, 50°, 65°, 80°, 90°, 100°, 120°, 135°, 150°, 180° and / or any other suitable angle. The A1 cutting angle can also be less than or equal to 180°, 150°, 135°, 120°, 100°, 90°, 80°, 65°, 50°, 40°, 30°, 20°, 15°, 10°, 5°, 0°, and / or any other suitable angle. Combinations of the above, including cutting angles between 0° and 180°, are also contemplated. In some modalities, the A1 cutting angle may be 40°. In other modalities, the A1 cutting angle may be 65°. In still other modalities, the A1 cutting angle may be 135°.Obviously, cutting angles above and below the aforementioned ranges are also contemplated. It should be understood that any of the implantable prostheses of the present disclosure may be formed by more than one conical (or non-conical) subunit with equal or different cutting angles.
[089] In some embodiments, substrate 22 may be characterized by an average diameter D1. The average diameter of substrate D1 may be any size suitable to properly fit the implant site and / or accommodate any other suitable application. In some exemplary embodiments, the average diameter D1 of substrate 22 may be greater than or equal to 1 cm, 1.5 cm, 2 cm, 2.2 cm, 2.5 cm, 2.8 cm, 3 cm, 3.2 cm, 3.5 cm, 3.8 cm, 4 cm, 4.5 cm, 5 cm, 6 cm, 7 cm, 8 cm and / or any other suitable size. The average diameter D1 of substrate 22 may also be smaller or Petition 870250069888, dated 06 / 08 / 2025, page 43 / 118 35 / 77 equals 8 cm, 7 cm, 6 cm, 5 cm, 4.5 cm, 4 cm, 3.8 cm, 3.5 cm, 3.2 cm, 3 cm, 2.8 cm, 2.5 cm, 2.2 cm, 2 cm, 1.5 cm, 1 cm and / or any other suitable size. Combinations of the above ranges, including average substrate diameters between 1 cm and 8 cm, are also contemplated, as well as sizes above and below the ranges mentioned above.
[090] In some embodiments, the central portion 26 of the substrate 22 can be characterized with a core percentage value, representing the ratio between the average diameter D2 of the central portion 26 and the average diameter D1 of the substrate 22. The core percentage can be any suitable value to allow sufficient tissue growth in the implantable prosthesis while still maintaining sufficient mechanical rigidity to support the surrounding tissue after implantation. The core percentage can be any suitable value greater than or equal to 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 50% and / or any other percentage. The core percentage can also be less than or equal to 50%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5% and / or any other suitable percentage. Combinations of the previous ranges, including basic percentages between 10% and 35% and between 5% and 50%, are also contemplated, as well as ranges above and the ranges mentioned previously.
[091] In some embodiments, the percentage of the core of the subunits may result in a total percentage of the hollow core of the implantable prosthesis, which may represent the ratio between the hollow core volume of the prosthesis and the total volume of the prosthesis. The percentage of the hollow core of the prosthesis may be greater than, equal to, or less than the percentage of the core of any subunit of the prosthesis.
[092] In some embodiments, substrate 22 may include one or more Petition 870250069888, dated 06 / 08 / 2025, page 44 / 118 36 / 77 fiducial markers 28, shown in Figure 2A, facilitate the assembly of the conical subunit, shown in Figure 2B. The end portions of the substrate 22 can be folded together to align the fiducial markers 28 and subsequently fastened together (e.g., using a welding technique) to form the side walls of the three-dimensional subunit. Obviously, embodiments without fiducial markers are also contemplated.
[093] In some embodiments, the fiducial marker and subsequently the weld (or other fixation technique) may be spaced from the outer edge by a distance D3, as shown in Figure 2A. This distance may be large enough to allow the practitioner to fix the implantable prosthesis to the tissue with a fixator. The weld may therefore be moved away from the edge to provide space for the fixator. In some embodiments, the distance may also provide ample space for other fixation processes, such as fixation between adjacent subunits. The distance D3 may be any suitable value greater than or equal to 2 mm, 2.5 mm, 3 mm, 5 mm, and / or any other suitable distance from the edge of the substrate. The distance may also be less than or equal to 5 mm, 3 mm, 25 mm, 2 mm, and / or any other suitable distance from the edge of the substrate.It should be noted that although a single fiducial marker 28 and a weld point 29 are shown in Figures 2A-2B, subunits with more than one fiducial marker and weld points are also contemplated. In some embodiments, two weld points can increase the rigidity of the subunit.
[094] Figure 3 illustrates a conical subunit according to some embodiments. As shown, the substrate 22 of the subunit can be superimposed within a region 24 to allow for the three-dimensional configuration. Figure 3 also Petition 870250069888, dated 06 / 08 / 2025, page 45 / 118 37 / 77 represents a weld point 29 formed in the overlap region 24. As shown, the weld point 29 can physically and permanently alter the substrate 22 to fix the subunit in its three-dimensional configuration. However, embodiments are also contemplated in which the subunit is temporarily arranged in its three-dimensional configuration, using, for example, fasteners such as clamps.
[095] Figures 4A-4D illustrate various embodiments of conical subunits with different clipping angles A1. As shown, in some embodiments, the clipping angle can determine the extent of the overlap region 24. Figures 4B and 4D show subunits with similar side wall angles. However, given that the clipping angle A1 of the subunit in Figure 4B (see Figure 4A) is significantly larger than the clipping angle A1 of the subunit in Figure 4D (see Figure 4C), the overlap region 24 of the subunit in Figure 4D is significantly larger. In some embodiments, an extended overlap region can result in greater stiffness. It should be understood that, depending on the desired final angle of the subunit side wall, the extent of the overlap region can be selected independently of the clipping angle.
[096] Figures 5A-5B illustrate two exemplary embodiments of implantable prostheses 100. Both embodiments include twelve conical subunits formed in a generally spherical arrangement. In some embodiments, as exemplified by Figure 5A, each cone can be fixed to a neighboring cone by means of a single weld point 29. In other embodiments, as exemplified by Figure 5B, each cone can be fixed to a neighboring cone by means of two weld points 29. In some embodiments, the increase in weld points (between cones or within a single cone) Petition 870250069888, dated 06 / 08 / 2025, page 46 / 118 38 / 77 cone) can increase the overall rigidity of the implantable prosthesis.
[097] Figures 6A-6B depict an implantable prosthesis 100 according to some embodiments. The prosthesis 100 may be formed from twelve subunits 20, which generally have a conical trunk shape, as shown in Figure 6A. Each subunit 20 may include one or more weld points 29A from the formation of the subunit itself and one or more weld points 29B from the assembly of the prosthesis. In other words, weld points 29A may be applied in the intra-subunit formation, and weld points 29B may be applied in the inter-subunit assembly to fix neighboring subunits to each other. The prosthesis may also include one or more markers 30 to facilitate external visualization of the prosthesis using various medical imaging modalities (e.g., X-ray, magnetic resonance imaging).
[098] Figure 6B represents a cross-section of 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 as a result of the trunk shape of the subunits 20. As described in greater detail above, the prosthesis may have a percentage of hollow core proportional to the ratio between the average core diameter D5 and the average prosthesis diameter D4, as shown in Figure 6B. The average prosthesis diameter D4 of Figure 6B may be approximately 3 cm, but diameters larger and smaller than 3 cm are also contemplated, as described in greater detail above.
[099] The average diameter of the D5 core can be any value suitable for inducing tissue growth while maintaining adequate mechanical rigidity to support nearby tissue. The average diameter of the D5 core can be greater than or equal to 0.05 cm, Petition 870250069888, dated 06 / 08 / 2025, page 47 / 118 39 / 77 0.1 cm, 0.2 cm, 0.5 cm, 1 cm, 2 cm, and / or any other suitable size. The average diameter of the D5 core may also be less than or equal to 2 cm, 1 cm, 0.5 cm, 0.2 cm, 0.1 cm, 0.05 cm, and / or any other suitable size. Combinations of the preceding ranges, including average D5 core diameters between 0.05 cm and 2 cm, are also contemplated, as well as diameters above and below the ranges mentioned above. The average diameter of the D5 core may also be any suitable percentage of the average D4 prosthesis diameter. In some embodiments, the average diameter of the D5 core may be greater than or equal to 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 50%, 60%, 75%, and / or any other percentage of the average prosthesis diameter. The average diameter of the D5 core may also be less than or equal to 75%, 60%, 50%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 2%, and / or any other suitable percentage of the average diameter of the prosthesis.Combinations of the preceding ranges, including average D5 core diameters between 10% and 35% and between 2% and 75% of the average prosthesis diameter, are also contemplated, as well as the ranges above and the ranges mentioned previously. It should be understood that any suitable size of the average core and prosthesis diameters (and any suitable ratio thereof) may be employed, since the present disclosure is not limited by core geometry.
[0100] Figures 7A-7C show three embodiments of spherical prostheses formed by twelve conical subunits each. All three prostheses have cores of similar size (i.e., similar core diameters). However, the three prostheses differ in their average diameter. The prosthesis in Figure 7A has an average diameter D4 of approximately 2 cm, the one in Figure 7B has an average diameter D4 of approximately 4 cm, and the one in Figure 7C has an average diameter D4 of approximately Petition 870250069888, dated 06 / 08 / 2025, page 48 / 118 40 / 77 cm. Therefore, the percentage of hollow core of the prosthesis shown in Figure 7C may be less than the percentage of hollow core of the prosthesis shown in Figure 7A.
[0101] In some embodiments, the number of attachment points (e.g., markers and weld points) may depend on the size of the prosthesis. For example, Figure 7A shows a prosthesis where each subunit 20 has 5 intra-subunit weld points 29A to increase the rigidity of each subunit, and 5 inter-subunit weld points 29B, where the subunit is attached to each of its neighboring subunits once. Figures 7B-7C show prostheses where each of their twelve subunits includes 6 intra-subunit weld points 29A and twelve inter-subunit weld points 29B. However, the arrangement and absolute positions of the weld points in Figures 7B and 7C differ due to the difference in the average diameter of the prosthesis D4.
[0102] It should be taken into account that prostheses with different subunits, each with a different number and / or arrangement of subunits, are also contemplated. It should also be noted that any of the implantable prostheses of the present disclosure may be formed by any combination of subunits. In some embodiments, the prosthesis may be formed by a series of similar subunits, as shown in Figures 5A-7C. In other embodiments, the prosthesis may be formed by 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 trim angle, and a second group of subunits having a second core percentage, a second average substrate diameter, and a second trim angle. Thus, it should be understood that the implantable prostheses of the present disclosure may employ Petition 870250069888, dated 06 / 08 / 2025, page 49 / 118 41 / 77 any number of subunits to form any combination of geometric, structural and / or mechanical properties.
[0103] Figures 8A-8B depict various views of an implantable prosthesis 200 with a generally ellipsoidal shape. In some embodiments, the ellipsoidal shape of the prosthesis 200 can be obtained by combining three types of subunits: lateral cones 240, peak cones 250, and middle cones 260. Variation in the type of subunit allows for an implantable prosthesis with an elongated ellipse to accommodate similarly shaped implant sites (e.g., biopsy or lumpectomy sites).
[0104] Figures 9A-9F show substrate geometries for the three subunits that form the prosthesis 200 in Figures 8A-8B. In some embodiments, the lateral cone 240 may include a generally C-shaped substrate with a notch, which can be characterized by a notch angle A1. It should be noted that the substrate of the lateral cone 242 may include an extended portion 243, which may partially distort the C-shape of the lateral cone 240. The variation in geometry allows the lateral cone to form a rounded ellipsoidal-shaped prosthesis when used together with the peak and mid-cones. Similar to the embodiments described earlier in relation to Figure 2A, the lateral cone 240 may include one or more fiducial markers 248 to indicate intra-subunit weld points, as well as one or more fiducial markers 247 for cone-to-cone (or inter-subunit) weld points.As previously described, any number of weld points to the subunit and / or between the subunit and its neighboring subunits can be employed to achieve the desired mechanical properties. In some embodiments, no marker is used. Petition 870250069888, dated 06 / 08 / 2025, page 50 / 118 42 / 77 fiducial can be employed.
[0105] Figure 9B illustrates a peak cone and Figure 9C illustrates a mean cone 260 according to some embodiments. Similar to the embodiment shown in FIG 2A, the peak and mean cones may include substrates 252, 262, along which cutouts may be formed. The cutout angle of the peak cone A1 may be greater than the cutout angle of the mean cone A1 to allow the formation of a three-dimensional cone of different sizes. For example, the cutout angle of the peak cone A1 may be 191.25°, as shown in Figure 9B. However, other peak cone cutout angles are also contemplated, including between 100°-250° and between 135°-210°. It should be taken into consideration that the peak cone cutout angle may vary depending on the size of the implantable prosthesis. Consequently, any suitable peak cone cutout angle may be employed.Figure 9C shows a clipping angle of the exemplary middle cone A1 of 135°, but, as noted with respect to the peak cone clipping angle, any suitable clipping angle may be employed, such as between 40° and 140°. Obviously, the clipping angles of any of the subunits of the present disclosure may have any magnitude suitable to permit the formation of sidewalls for a suitable three-dimensional subunit. The peak and middle cones may include one or more fiducial markers 258, 268 to indicate intra-subunit weld points, as well as one or more fiducial markers 257, 267 for cone-to-cone (or inter-subunit) weld points. As described above, any number of weld points to the subunit and / or between the subunit and its neighboring subunits may be employed to achieve the desired mechanical properties. In some embodiments, none. Petition 870250069888, dated 06 / 08 / 2025, page 51 / 118 43 / 77 fiducial marker can be used.
[0106] As described earlier, in some embodiments, an implantable prosthesis may be ellipsoidal rather than 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 properties of ellipsoidal implantable prostheses. Each of the prostheses listed in Table 1 is formed by fourteen total conical subunits, which include 2 peak cones, 8 lateral cones, and 4 median cones, as described earlier. Ellipsoidal prosthesis size (width x height) Cone type Percentage of hollow core (%) Overlap (degrees of circle removed) (°) 2 cm x 3 cm Peak: 25 200 Lateral 20 120 Middle 25 125 3 cm x 4 cm Peak: 24.5 218 Lateral 13 120 Middle 10 120 4 cm x 5 cm Peak: 10 120 Lateral 10 55 Middle 10 35 Table 1 - Tabulated illustrative geometric properties of non-spherical ellipsoidal prostheses.
[0107] In some embodiments, an ellipsoidal prosthesis may utilize peak, lateral, and mid-cones, as shown and described in relation to Figures 9A-9C. In other embodiments, an ellipsoidal prosthesis may employ a peak cone that may be different from the 250 cone shown in Figure 9B. For example, an ellipsoidal prosthesis may be formed by three conical subunits, including a 240 lateral cone, as Petition 870250069888, dated 06 / 08 / 2025, page 52 / 118 44ΓΠ shown in Figure 9D, which may be similar to the side cone 240 of Figure 9A, a middle cone 260, as shown in Figure 9F, which may be similar to the middle cone 260 of Figure 9C, and a peak cone 2050, as shown in Figure 9E, which may be different from the peak cone 250 of Figure 9B. Specifically, the peak cone 2050 may be formed from a substrate 2052 having two extended portions 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 to indicate intra-subunit weld points, as well as one or more fiducial markers 2057 for cone-to-cone (or inter-subunit) weld points. As previously described, numerous welding points to the subunit and / or between the subunit and its neighboring subunits can be employed to achieve the desired mechanical properties. In some embodiments, no fiducial marker may be employed.
[0108] It should be noted that the peak cone in Figure 9E can be used with ellipsoidal prostheses with a height of 5 cm and an average width of 4 cm to accommodate the larger geometry of the prostheses.
[0109] Figures 10A-10E illustrate a process for assembling an ellipsoidal implantable prosthesis, such as that shown in Figures 8A-8B. The exemplary prosthesis can be formed by two peak cones, eight lateral cones, and four middle cones. However, it should be considered that any suitable number of any subunit can be employed. Initially, each subunit can be assembled from its two-dimensional substrate into a three-dimensional configuration, as described previously. Subsequently, as shown in Figure 10A, a peak cone 250 can be aligned with a lateral cone 240 so that the edges Petition 870250069888, dated 06 / 08 / 2025, page 53 / 118 45 / 77 tops should be aligned. The side walls of the two cones can be fixed together for alignment and subsequently fixed to each other (e.g., by welding). Three other side cones 240 can then be fixed to the central peak cone 250, aided by fiducial markers 249, 259 on the side and peak cones, respectively, as shown in Figure 10B. It should be noted that each side cone can be welded one or more times to the peak cone and, additionally, welded one or more times to each of its neighboring cones.
[0110] The subset of the peak cone 250 and four lateral cones 240 can be repeated to form two partial halves of the prosthesis. When the partial halves are aligned, as shown in Figure 10C, four lateral cones from each partial half can be fixed together, connecting the two partial halves. However, as shown in Figure 10C, there may be gaps 290 between the lateral cones in the central portion of the prosthesis. These gaps can be filled with middle cones 260, as shown in Figure 10D. Each central cone 260 can be welded at least once to four neighboring lateral cones 240. The final prosthesis formed by fourteen subunits in total may appear generically ellipsoidal, as shown in Figure 10E. It should be understood that the assembly processes described in relation to Figures 10A-10E are not limiting, and any other assembly process may be employed to form the implantable prostheses of the present disclosure.
[0111] As described in greater detail above, implantable prostheses can exhibit substantially isotropic mechanical properties, such as compressive stiffness. In some embodiments, the implantable prostheses of the present disclosure can be subjected to compression tests to evaluate stiffness and palpability. Petition 870250069888, dated 06 / 08 / 2025, page 54 / 118 46 / 77 of the prostheses and determine the compressive stiffness of the prostheses. The test can be performed by compressing the prostheses up to 30% at a rate of 0.2 mm / s, which may be slow enough to achieve a near-static test condition. To evaluate a prosthesis, the prosthesis can first be measured and then positioned within a compression testing system (e.g., Instron), as shown in Figure 11A. In some non-limiting embodiments, a 100 N load cell can be used to compress the prosthesis. The system can then compress the prosthesis to 30% of its original height (e.g., a point of interest) and collect force displacement data.
[0112] The various geometric measurements of the prosthesis, such as precompression height, displacement, and force, can be used to calculate the compressive stiffness of the prosthesis. Specifically, the compressive stiffness of the prosthesis can be derived as follows: Compressive stiffness (psi) = Normalized Force Compressive displacement (mm) Force Measurement (lbf) Cross-sectional Area (in2) Displacement (mm) Prosthesis Height (mm)
[0113] In the equation above, the normalized force and compressive displacement are measured during the test, and the dimensions of the prosthesis are measured before the test. It should be understood that, in some embodiments, given the non-linear slope of the compression curve, the term “compressive stiffness”, as used in this document, refers to a secant compressive stiffness, defined by the linear slope between the origin and the point of interest. Petition 870250069888, dated 06 / 08 / 2025, page 55 / 118 47 / 77
[0114] Figure 11B shows the various dimensions related to an implantable prosthesis. The cross-sectional area of the prosthesis can be calculated as follows: Cross-sectional Area (in2) Width of Prosthesis #1 (mm) Width of Prosthesis #2 (mm) = π *--------------------:---------------* --------------------:--------------2*25.4 2 * 25.4
[0115] The force measurement of the test system can be converted into a normalized force as follows: Normalized Force zlbf· Vin2. Force Measurement (lbf) Cross-sectional Area (in2)
[0116] In one exemplary embodiment, an ellipsoidal implantable prosthesis with total dimensions of approximately 2 cm by 2 cm by 3 cm, having a hollow core percentage of 25%, may exhibit an average compressive stiffness of approximately 31.03 kPa (4.05 psi) in the horizontal orientation and an average compressive stiffness of 32.13 kPa (4.66 psi) in the vertical direction. In another exemplary embodiment, an ellipsoidal implantable prosthesis with total dimensions of approximately 3 cm by 3 cm by 4 cm, having a hollow core percentage of 10%, may exhibit an average compressive stiffness of approximately 24.48 kPa (3.55 psi) in the horizontal orientation and an average compressive stiffness of 24.27 kPa (3.52 psi) in the vertical direction.In another illustrative embodiment, an ellipsoidal implantable prosthesis with total dimensions of approximately 4 cm by 4 cm by 5 cm, having a hollow core percentage of 10%, may exhibit an average compressive stiffness of approximately 16.55 kPa (2.40 psi) in the horizontal orientation and an average compressive stiffness of 19.44 kPa (2.82 psi) in the vertical direction.
[0117] The rigidity of the implantable prostheses of the present disclosure can be adjusted by a variety of means, including, but not limited to, size. Petition 870250069888, dated 06 / 08 / 2025, page 56 / 118 48 / 77 of the prosthesis, composition of the prosthesis material, type and number of fixation sites, percentage of hollow core, among many others. In some embodiments, the rigidity of the implantable prosthesis can be increased by increasing the wall thickness of the subunits. The wall thickness can be increased through the use of thicker substrate material (e.g., mesh-like repair tissue). In some embodiments, the wall thickness of the subunits can be increased through the use of multiple overlapping subunits.
[0118] Figure 12 illustrates an exemplary partial assembly process for a double-cone subunit 310. The subunit 310 may include a first conical subunit 301, similar to those described in relation to Figures 2A-2B, having a first central portion 361, connected to a second conical subunit 302 with a second central portion 362. In some embodiments, the second conical subunit may be arranged within a volume defined by the first conical subunit, so that they may overlap. In some embodiments, as shown in Figure 12, the central portions of the first and second conical subunits may differ (e.g., the central portion 362 may be smaller than the central portion 361).Thus, the core of the implantable prosthesis formed by such a 310 subunit may have less material, which can induce a higher rate of tissue infiltration to improve the repair process, while maintaining compressive stiffness comparable to natural tissue to support the surrounding anatomy. Obviously, double-cone subunits having two substantially similar conical subunits (e.g., similar central portions) are also contemplated.
[0119] It should be understood that any of the implantable prostheses of Petition 870250069888, dated 06 / 08 / 2025, page 57 / 118 49 / 77 present disclosure may employ a double-layer subunit. In some embodiments, depending on the application, the prosthesis subunit may employ more than two layers (e.g., three, four, five) to enhance the mechanical properties of the prosthesis and better simulate the surrounding anatomy.
[0120] Figures 13A-13D show an exemplary assembly process for forming a spherical implantable prosthesis 300 formed from double-layer subunits. Figure 13A illustrates two substantially two-dimensional substrates 301 and 302, which can be manipulated to form the side walls of a three-dimensional subunit, as shown in Figure 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 central portion than the second substrate 302. Each substrate may have an overlapping portion, which can be formed when the substrates are manipulated into the side walls of conical subunits. When arranged together, as shown in Figure 13C, the overlapping portions 314 and 324 of each subunit 301 and 302, respectively, can be arranged opposite each other.Depending on the arrangement of the subunits, as well as the cutting angles, the maximum thickness of the assembled double-layer subunit can be two, three, or four layers. Obviously, embodiments in which the overlapping regions overlap or are arranged differently are also contemplated. Figure 13D illustrates an exemplary spherical prosthesis 300 formed by twelve double-cone subunits. Thus, the prosthesis 300 includes twenty-four subunits. Compared to a prosthesis formed by single-cone subunits with similar geometries, material compositions, and weld point arrangements, the configuration... Petition 870250069888, dated 06 / 08 / 2025, page 58 / 118 A 50 / 77 double cone design can offer greater compressive stiffness while allowing tissue growth through its central core. As previously described, the difference in size between the central portions of the two cones can reduce the volume of material in the prosthesis core and increase tissue growth. Obviously, arrangements of double cones (or other subunits) formed using similar cones are also contemplated.
[0121] Table 2 below shows the exemplary geometric and mechanical characterization of six implantable spherical prostheses formed with double-layer subunits. Each prosthesis is designed to generally measure 5 cm x 5 cm x 5 cm, with its double-layer conical subunits including a first conical subunit with a core percentage of 10% and a second conical subunit with a core percentage of 22.5%. Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 Prosthesis Height (mm) 44.68 46.61 45.75 46.45 46.52 45.6 Prosthesis Diameter #1 (mm) 49.85 50.74 50.13 49.41 48.88 52.5 Prosthesis Diameter #2 (mm) 50.29 50.88 49.35 50.83 49.6 52.3 Force Measurement (lbf) 3.07 2.66 3.02 2.84 3.23 3.21 Displacement (mm) 13.41 13.99 13.73 13.94 13.96 13.68 Compressive Displacement 0.3 0.3 0.3 0.3 0.3 0.3 Cross-sectional area (in²) 3.05 3.14 3.01 3.06 2.95 3.34 Normalized force (lbf / in²) 1.01 0.85 1 0.93 1.09 0.96 Petition 870250069888, dated 06 / 08 / 2025, page 59 / 118 51 / 77 Stiffness (psi) 3.35 2.82 3.34 3.1 3.65 3.2 Table 2 - Exemplary tabulated geometric and mechanical characterization of five implantable spherical prostheses formed by double-layer conical subunits.
[0122] Figure 14 illustrates an exemplary ellipsoidal implantable prosthesis 400 formed by two sets of double-layer subunits 410 and 415. As shown, subunits 415 can be larger than subunits 410, to help form the generically ellipsoidal shape. Obviously, any suitable combination of subunits can be employed to form any suitable prosthesis shape, as the present disclosure is not so limited. Table 3 below shows the exemplary geometric and mechanical characterization of an ellipsoidal implantable prosthesis formed with double-layer subunits. Vertical Orientation Horizontal Orientation Prosthesis Height (mm) 52.6 42.3 Prosthesis Width #1 (mm) 45.8 52.5 Prosthesis Width #2 (mm) 42.8 46.2 Force Measurement (lbf) 1.17 1.97 Displacement (mm) 15.78 12.69 Compressive Displacement 0.3 0.3 Cross-sectional Area (in²) 2.39 2.95 Normalized Force (lbf / in²) 0.49 0.67 Stiffness (psi) 1.63 2.22 Table 3 - Exemplary tabulated geometric and mechanical characterization of Petition 870250069888, dated 06 / 08 / 2025, page 60 / 118 52 / 77 is an ellipsoidal implantable prosthesis formed by double-layered conical subunits.
[0123] Figures 15A-15D illustrate an assembly process for an implantable prosthesis 500 formed by a conical subunit 503 and a corrugated subunit 502. The combination of the conical and corrugated shapes, when superimposed (as shown in Figures 15C-15D), can provide larger void volumes between the subunits, allowing for higher rates of tissue infiltration through the implantable prosthesis while maintaining sufficient mechanical compressibility after implantation. In some embodiments, the corrugated subunit 502 can take the form of a star-shaped cone, as shown in Figure 15B. The corrugated subunit 502 can be formed from a substrate 501 (see Figure 15A) that can be folded or otherwise manipulated to form radial corrugations.It should be considered that any suitable number of radial corrugations, ranging from three (so that the subunit assumes a generally convex triangular prismatic shape) to six (so that the subunit assumes a generally hexagonal convex prismatic shape) to any other suitable number of corrugations. The substrate can then be manipulated (e.g., rolled) to form the side walls of a three-dimensional subunit. In some embodiments, the corrugated subunit 502 can be arranged within a conical subunit 503, as shown in subunit 504 of Figure 15C. In other embodiments, the conical subunit can be arranged within a corrugated subunit. It should be understood that any combination of various subunits (conical, corrugated, etc.) can be employed in any of the prostheses of the present disclosure. Figure 15D illustrates a partially assembled prosthesis 500 formed by six subunits, each of which... Petition 870250069888, dated 06 / 08 / 2025, page 61 / 118 53 / 77 which includes at least one conical subunit and at least one corrugated subunit.
[0124] Table 4 below shows the exemplary geometric and mechanical characterization of two spherical implantable prostheses with double-layer subunits formed by a conical subunit and a corrugated subunit. In the table below, sample 1 was designed to generally measure 4 cm x 4 cm x 4 cm, and sample 2 was designed to generally measure 5 cm x 5 cm x 5 cm. Sample 1 Sample 2 Prosthesis Height (mm) 37.5 46.3 Prosthesis Width #1 (mm) 42.5 50.5 Prosthesis Width #2 (mm) 38.9 50.4 Force Measurement (lbf) 2.99 2.25 Displacement (mm) 11.25 13.89 Compressive Displacement 0.3 0.3 Cross-sectional Area (in²) 2.01 3.1 Normalized Force (lbf / in²) 1.49 0.73 Stiffness (psi) 4.95 2.42 Table 4 - provides an exemplary geometric and mechanical characterization of two implantable spherical prostheses formed by double-layer subunits, including a conical subunit and a corrugated subunit.
[0125] Figures 16A-16B depict an implantable prosthesis 600 according to some embodiments. The 600 prosthesis may be formed by two-dimensional substrates fixed to each other to form radiating fins emanating from a central portion. Petition 870250069888, dated 06 / 08 / 2025, p. 62 / 118 54 / 77 hollow 620. The central portion 620 can serve as a void volume for tissue infiltration. In some modalities, the prosthesis 600 may include one or more markers 630, which may exhibit properties that allow external detection of the prosthesis location. For example, the markers 630 may be metallic clips, which may be radiopaque and therefore distinguishable during X-ray imaging.
[0126] Figures 17A-17B illustrate another embodiment of an implantable prosthesis 700. The prosthesis may also include a series of radial fins formed from two-dimensional substrates. In some embodiments, the fins of the prosthesis 700 may be formed from ring-shaped substrates, which may form a hollow core 720 after the prosthesis is assembled. As described in relation to other embodiments, the hollow core may serve as an empty volume to allow tissue growth within the prosthesis after implantation.
[0127] Figures 18A-18B illustrate yet another embodiment of an implantable prosthesis 800. The prosthesis 800 may have a generally cubic shape, formed by four subunits, shown in Figure 18A. Each subunit may be formed by several panels 810, 815, 825, which may be folded and welded together to form a quadrant of the prosthesis. Four subunits may then be welded together at the weld points 890 to form the prosthesis. The prosthesis may also include one or more markers 830, which may make the prosthesis visible within the implant site during medical imaging.
[0128] Figure 19 illustrates yet another embodiment of an implantable prosthesis 900. The 900 prosthesis can be formed by at least two generally cubic shapes, Petition 870250069888, dated 06 / 08 / 2025, page 63 / 118 55 / 77 one inside the other. In some modalities, the 900 prosthesis may be accompanied by 930 markers for external detection. As shown in Figure 19, the markers may be metallic and subsequently radiopaque.
[0129] Figures 20A-20D illustrate the assembly process of the 900 prosthesis of Figure 19. Each cubic subassembly (see cubes 960 and 970 in Figure 20D) can be formed by fixing six two-dimensional substrates 950 together, as shown in Figures 20A-20B. As described earlier, the substrates 950 can be fixed to each other using welds 959, which can strengthen the prosthesis and significantly reduce the risk of deconstruction. Once both cubes are partially assembled, the smaller inner cube 960 can be placed inside the larger outer cube 970, as shown in Figure 20D. The outer cube can then be closed and one or more markers can be added to the prosthesis in preparation for implantation, as shown in Figure 19.
[0130] It should be understood that any of the prostheses described in this document may have any suitable shape or geometry, depending on the application (e.g., biopsy shape and size). The prostheses may also be formed from any suitable number, size, and arrangement of subunits. EXAMPLE 1
[0131] In some embodiments, the prostheses of the present disclosure may exhibit degradation profiles compatible with conventional prostheses known in the art. As previously described, such degradation profiles may facilitate tissue growth on the prosthesis as it degrades, allowing it to be replaced by natural tissue. Obviously, although the prostheses described in the present disclosure... Petition 870250069888, dated 06 / 08 / 2025, page 64 / 118 56 / 77 documents may exhibit conventional degradation profiles, but they may also exhibit improved stiffness transfer between the implant and natural tissue to facilitate controlled tissue growth.
[0132] In one example, the degradation profiles of a prosthesis are evaluated using a porcine preclinical lumpectomy model over twelve weeks. Table 5 below shows the molecular weight retention for a prosthesis according to the present disclosure and a prosthesis known in the art. In Table 5 below, sample 1 represents mean data from three spherical prostheses formed by 12 conical subunits, with an overall mean diameter of approximately 3 cm, and sample 2 represents mean data from three conventional prostheses (e.g., PHASIX Plug and Patch). Time (week) Location Sample 1 Sample 2 pre-implementation N / A 100 100 4 Center 87 89 Periphery 87 89 12 Center 66 65 Periphery 67 64 Table 5 - Tabulated illustrative molecular weight analysis of an implantable spherical prosthesis (sample 1) and a conventional prosthesis (sample 2).
[0133] As shown in Table 5 above, molecular weight analysis for samples 1 and 2 demonstrated a statistically significant reduction at 4 and 12 weeks, respectively, compared to the pre-implantation state. Molecular weight analysis also demonstrated a statistically significant reduction at 12 weeks, compared to Petition 870250069888, dated 06 / 08 / 2025, page 65 / 118 57 / 77 at 4 weeks post-implantation. However, the molecular weight of the central location was not statistically different from that of the peripheral portion for the two samples at 4 or 12 weeks post-implantation, suggesting a uniform degradation of molecular weight by these devices.
[0134] The molecular weight analysis represented by Table 5 above may suggest that the implantable prostheses described in this document may exhibit the same molecular weight degradation as conventional implantable devices. However, it should be understood that the prostheses described in this document may produce different biological responses compared to conventional prostheses, as described below in relation to Example 2. EXAMPLE 2
[0135] In some modalities, local tissue responses after prosthesis implantation can be characterized by histological means. Specifically, local tissue responses can be characterized by the presence of neovascularization, fibrosis, collagen deposition, vascular integration, collagen morphology (by means of PSR staining), myofibroblast proliferation (by means of SMA or smooth muscle actin staining) and neovascularization (by means of VWF or von Willebrand factor staining), evaluated histologically.
[0136] Figure 21 shows exemplary data of the aforementioned local tissue responses for a variety of prostheses, including a commercial BioZorb prosthesis, represented by group 3 (week 4) and group 8 (week 12), a commercial PHASIX plug prosthesis, represented by group 4 (week 4) and group 9 (week 12), a control group with a sham treatment, represented by group 5 (week 4) and group 10 Petition 870250069888, dated 06 / 08 / 2025, page 66 / 118 58 / 77 (week 12), and a spherical prosthesis according to the present disclosure, formed by 12 conical subunits, having an overall average diameter of approximately 3 cm, represented by group 11 (week 4) and group 12 (week 12).
[0137] The tissue response data are scored as tabulated in Table 6 below. Scoring Matrix of observations Collagen morphology scoring matrix Smooth muscle actin (SMA) staining scoring matrix 0 No response None 1 Minimal / focal / almost imperceptible Predominant green (thin) Minimal and subtle scattered spots 2 Light / focal or rarely multifocal / slightly detectable Mixed Light, noticeable, scattered or locally extensive staining 3 Moderate / multifocal to confluent / easily detectable Predominant orange-red (thick) Moderate, multifocal to regionally extensive staining 4 Marked presence / diffuse / overwhelming Marked and diffuse staining. Table 6 - observations associated with the scores shown in Figures 21- 22.
[0138] The example data in Figure 21 are also presented below in Table 7 (week 4) and Table 8 (week 12) below. Parameter Group 3 Group 4 Group 5 Group 11 BioZorb® (n=3) PHASIX™ Plug (n=3) Sham Treatment (n=3) Spherical Prosthesis (n=3) Petition 870250069888, dated 06 / 08 / 2025, p. 67 / 118 59 / 77 Neovascularization 0 2.0 (0.00, 0 - 0.00) sp 0s O o 3.0 (0.00, 0 - 0.00) sp 0s O o 0.3 (0.58, 3 - 0.33) 33% 3.0 (0.00, 0 - 0.00) 100% 2.00 T” 3.00 T” 0.00 3.00 Fibroplasia 0.0 (0.00, 0 “ 0.00) sp 0s o 0.0 (0.00, 0 - 0.00) sp 0s o 0.0 (0.00, 0 “ 0.00) sp 0s o 0.0 (0.00, 0 - 0.00) 0% 0.00 0.00 0.00 0.00 Hemorrhage 0.0 (0.00, 0 - 0.00) 3% 0.0 (0.00, 0 - 0.00) 3% 0.0 (0.00, 0 - 0.00) 3% 0.0 (0.00, 0 - 0.00) 0% 0.00 0.00 0.00 0.00 Necrosis 0.0 (0.00, 0 - 0.00) sp 0s o 0.0 (0.00, 0 - 0.00) sp 0s o 0.0 (0.00, 0 - 0.00) sp 0s o 0.0 (0.00, 0 - 0.00) 0% 0.00 0.00 0.00 0.00 Fibrosis 2.3 (0.58, 3 - 0.33) sp 0s O o 2.6 (0.58, 7 - 0.33) sp 0s O o 0.6 (0.58, 7 - 0.33) 67% I 3.0 (0.00, 0 - 0.00) 100% 2.00 T” 3.00 T” 1.00 3.00 Collagen deposition 2.3 (0.58, 3 “ 0.33) sp 0s O o 2.6 (0.58, 7 “ 0.33) sp 0s O o 0.6 (0.58, 7 “ 0.33) 67% I 3.0 (0.00, 0 - 0.00) 100% 2.00 T” 3.00 T” 1.00 3.00 Vascular Integration 2.0 (0.00, 0 0.00) sp 0s O o 3.0 (0.00, 0 0.00) sp 0s O o 0.0 (NA, 0 NA) sp 0s o 3.0 (0.00, 0 - 0,00) 100% 2.00 T” 3.00 T” 0.00 3.00 Collagen Morphology NA + (NA' NA1 NA) NA 3.0 (0.00, 0 - 0.00) sp 0s O o 3.0 (0.00, 0 - 0.00) sp 0s O o 3.0 (0.00, 0 - 0.00) 100% NA 3.00 T” 3.00 T” 3.00 Myofibroblast Proliferation / S MA NA + (NA' “ NA) NA 3.0 (1.00, 0 0.58) sp 0s O o NA + (NA' “ NA) NA 3.6 (0.58, 7 0.33) 100% NA 3.00 T” NA 4.00 Neovascularization o / VWF NA + (NA' NA1 NA) NA 2.0 (1.73, 0 “ 1.00) I 67% I 0.0 (NA, 0 “ NA) sp 0s o 2.0 (1.73, 0 “ 1.00) 67% NA 3.00 0.00 3.00, Table 7 - observations of local tissue responses represented in Figure 21 at week 4. Data presented as mean ± (SD, SEM), median and incidence (%). NA = not applicable. Parameter Group 8 Group 9 Group 10 Group 12 BioZorb® (n=3) PHASIX™ Plug (n=3) Sham Treatment (n=3) Spherical Prosthesis (n=3) Petition 870250069888, dated 06 / 08 / 2025, page 68 / 118 60 / 77 Neovascularization 1.3 (0.58, 3 - 0.33) sp 0s O o 3.0 (0.00, 0 - 0.00) sp 0s O o 0.3 (0.58, 3 - 0.33) 33% 3.0 (0.00, 0 - 0.00) 100% 1.00 3.00 0.00 3.00 Fibroplasia 0.0 (0.00, 0 0.00) sp 0s o 0.0 (0.00, 0 0.00) sp 0s o 0.0 (0.00, 0 0.00) sp 0s o 0.0 (0.00, 0 - 0.00) 0% 0.00 0.00 0.00 0.00 Hemorrhage 0.0 (0.00, 0 - 0.00) 3% 0.0 (0.00, 0 - 0.00) 3% 0.0 (0.00, 0 - 0.00) 3% 0.0 (0.00, 0 - 0.00) 0% 0.00 0.00 0.00 0.00 Necrosis 0.0 (0.00, 0 - 0.00) sp 0s o 0.0 (0.00, 0 - 0.00) sp 0s o 0.0 (0.00, 0 - 0.00) sp 0s o 0.0 (0.00, 0 - 0.00) 0% 0.00 0.00 0.00 0.00 Fibrosis 2.0 (0.00, 0 - 0.00) sp Collagen Deposition 2.0 (0.00, 0 - 0.00) sp 0s O o 2.6 (0.58, 7 0.33) sp 0s O o 1.0 (1.00, 0 - 0.58) 67% 2.0 (0.00, 0 - 0.00) 100% 2.00 3.00 1.00 2.00 Vascular Integration 1.3 (0.58, 3 0.33) sp 0s O o 3.0 (0.00, 0 0.00) sp 0s O o ±(NA, NA) sp 0s o 3.0 (0.00, 0 - 0.00) 100% 1.00 3.00 0.00 3.00 Collagen Morphology NA±(NA, NA) NA 3.0 (0.00, 0 – 0.00) sp 0s O o 3 0 θ ±(NA, NA) sp 0s O o 3.0 (0.00, 0 - 0.00) 100% NA 3.00 3.00 3.00 Myofibroblast Proliferation / SMA NA ±(NA, NA) NA 2.6 (0.58, 7 0.33) sp 0s O o NA ±(NA, NA) NA 3.0 (0.00, 0 - 0.00) 100% NA 3.00 NA 3.00 Neovascularization / VWF NA ±(NA, NA) NA 2.0 (1.73, 0 – 1.00) 67% 0.0 (0.00, 0 “ 0.00) sp 0s o 1.0 (1.73, 0 “ 1.00) 33% NA 3.00 0.00 0.00, Table 8 - observations of local tissue responses represented in Figure 21 at week 12. Data presented as mean ± (SD, SEM), median and incidence (%). NA = not applicable.
[0139] The data presented in Figure 21 and in Tables 7 and 8 indicate some statistically significant differences at 4 weeks for neovascularization (n=2), Petition 870250069888, dated 06 / 08 / 2025, page 69 / 118 61 / 77 fibrosis (n=1) and collagen deposition (n=1) and a statistically significant difference for fibrosis at 12 weeks. At week 4, mean neovascularization was statistically significantly higher (likely due to the low presence of inflammation / tissue responses at sham sites, as expected) in the PHASIX™ Plug (group 4) compared to sham sites (group 5) and statistically significantly lower (likely due to the low presence of inflammation / tissue responses at sham sites, as expected) at sham sites (group 5) compared to the present disclosure prosthesis (group 11). At week 4, mean fibrosis was statistically significantly lower (likely due to the low presence of inflammation / tissue responses at sham sites, as expected) at sham sites (group 5) compared to the present disclosure prosthesis (group 11).In week 4, mean collagen deposition was statistically significantly lower (likely due to the low presence of inflammation / tissue responses at sham sites, as expected) in sham sites (Group 5) when compared to the present disclosure prosthesis (Group 11). Furthermore, in Week 12, mean fibrosis was statistically significantly higher (likely due to the low presence of inflammatory / tissue responses at sham sites, as expected) in the PHASIX™ Plug (Group 9) when compared to sham sites (Group 10). These statistically significant differences can be interpreted as biologically insignificant and likely due to the comparison of groups with devices and groups with sham sites showing low levels of inflammatory / tissue responses, as expected. Petition 870250069888, dated 06 / 08 / 2025, page 70 / 118 62 / 77
[0140] In some modalities, cellular responses after prosthesis implantation can be characterized by observing inflammation and the types of inflammatory cells through histology. Figure 22 shows exemplary data of the aforementioned inflammatory responses for a variety of prostheses, including a commercial BioZorb prosthesis, represented by group 3 (week 4) and group 8 (week 12), a commercial PHASIX plug prosthesis, represented by group 4 (week 4) and group 9 (week 12), a sham treatment control group, represented by group 5 (week 4) and group 10 (week 12), and a spherical prosthesis according to the present disclosure, formed by 12 conical subunits, having an overall average diameter of approximately 3 cm, represented by group 11 (week 4) and group 12 (week 12). Inflammatory data are scored as observed in Table 6.
[0141] The example data in Figure 22 are also presented below in Table 9 (week 4) and Table 10 (week 12) below. Parameter Group 3 Group 4 Group 5 Group 11 BioZorb® (n=3) PHASIX™ Plug (n=3) Sham Treatment (n=3) Spherical Prosthesis (n=3) Inflammation 2.3 (0.58, 3 “ 0.33) sp 0s O 2.3 (0.58, 3 “ 0.33) sp 0s O 0.6 (0.58, 7 “ 0.33) 67% 2.3 (0.58, 3 “ 0.33) 100% 2.00 X” 2.00 X- 1.00 2.00 Neutrophils 0.3 (0.58, 3 0.33) 33% 1.0 (0.00, 0 0.00) sp 0s o 0.0 (0.00, 0 0.00) sp 0s 0.0 (0.00, 0 0.00) 0% 0.00 1.00 X” 0.00 0.00 Eosinophils 0.0 (0.00, 0 “ 0.00) sp 0s 0.6 (0.58, 7 “ 0.33) 67% 0.0 (0.00, 0 - 0.00) sp 0s 2.0 (0.00, 0 “ 0.00) 100% 0.00 1.00 0.00 2.00 Macrophages 2.3 ± (0.58, 3 - 0.33) 100 2.3 ± (0.58, 3 - 0.33) 100 0.6 ± (0.58, 7 - 0.33) 67% 2.0 ± (0.00, 0 - 0.00) 100 Petition 870250069888, dated 06 / 08 / 2025, page 71 / 118 63 / 77 2.00 2.00 1.00 2.00 Lymphocytes 1.0 (0.00, 0 – 0.00) sp 0s O 1.0 (0.00, 0 - 0.00) sp 0s O 0.6 (0.58, 7 - 0.33) 67% 1.0 (0.00, 0 - 0.00) 100% 1.00 1.00 1.00 1.00 Multinucleated giant cells 0.6 (0.58, 7 0.33) 67% 1.6 (0.58, 7 0.33) sp 0s 0.6 (0.58, 7 - 0.33) 67% 1.0 (0.00, 0 - 0.00) 100% 1.00 2.00 10( 1.00 1.00 Plasma cells 0.0 (0.00, 0 “ 0.00) sp 0s 0.0 (0.00, 0 “ 0.00) sp 0s 0.0 (0.00, 0 - 0.00) sp 0s 0.0 (0.00, 0 - 0.00) 0% 0.00 0.00 0.00 0.00 Table 9 - Inflammation observations depicted in Figure 22 at week 4. Data presented as mean ± (SD, SEM), median, and incidence (%). Parameter Group 8 Group 9 Group 10 Group 12 BioZorb® (n=3) PHASIX™ Plug (n=3) Sham Treatment (n=3) Spherical Prosthesis (n=3) Inflammation 2.0 (0.00, 0 - 0.00) sp 0s O 2.0 (0.00, 0 - 0.00) sp 0s O 0.6 (1.15, 7 - 0.66) 33% 1.6 (0.58, 7 - 0.33) 100% 2.00 2.00 0.00 2.00 Neutrophils 0.3 (0.58, 3 - 0.33) 33% 0.3 (0.58, 3 - 0.33) 33% 0.0 (0.00, 0 - Eosinophils 0.0 (0.00, 0 0.00) sp 0s 0.6 (0.58, 7 0.33) 67% 0.3 (0.58, 3 0.33) 33% 0.6 (0.58, 7 0.33) 67% 0.00 1.00 0.00 1.00 Macrophages 2.0 (0.00, 0 0.00) sp 0s 0 1.0 (0.00, 0 0.00) sp 0s 0.6 (1.15, 7 0.66) 33% 1.3 (0.58, 3 “ 0.33) 100% 2.00 1.00 0.00 1.00 Lymphocytes 1.0 (0.00, 0 - 0.00) sp 0s O 1.6 (0.58, 7 0.33) sp 0s o 0.3 (0.58, 3 0.33) 33% 1.0 (0.00, 0 0.00) 100% 1.00 2.00 0.00 1.00 Giant cells 0.6 ± (0.58, 7 ± 0.33) 67% 1.0 ± (0.00, 0 ± 0.00) 100 0.3 ± (0.58, 3 ± 0.33) 33% 1.0 ± (0.00, 0 ± 0.00) 100 Petition 870250069888, dated 06 / 08 / 2025, page 72 / 118 64 / 77 Multinucleated plasma cells 1.00 1.00 0 ... Table 10 - Inflammation observations depicted in Figure 22 at week 12. Data presented as mean ± (SD, SEM), median, and incidence (%).
[0142] As shown in Figure 22 and Tables 9 and 10, histologically, at the implanted test and control sites, overall inflammation was similar between the implanted prosthesis and control sites at both time points (4 weeks and 12 weeks), with overall inflammation decreasing over time in all groups except at the sham-treated sites, where overall inflammation was lower (as expected) than at the test and control treated sites at both time points. The inflammatory infiltrate was heterogeneous at both time points and at 4 weeks consisted of neutrophils (not observed at the sham treatment sites and at the sites associated with the prostheses of the present disclosure), eosinophils (not observed at the sham treatment sites and at the BioZorb® sites), macrophages, lymphocytes, and multinucleated giant cells.At 12 weeks, the inflammatory infiltrate consisted of neutrophils (only observed in small numbers at BioZorb® and PHASIX™ Plug sites), eosinophils (not observed at BioZorb® sites), macrophages, lymphocytes, and multinucleated giant cells. Two statistically significant differences were observed for eosinophils at 4 weeks (BioZorb® and Sham when compared to the present disclosure prosthesis) and one statistically significant difference was observed for lymphocytes at 12 weeks (PHASIX™ Plug when compared to Sham). All three statistically significant differences were interpreted as... Petition 870250069888, dated 06 / 08 / 2025, page 73 / 118 65 / 77 biologically insignificant and likely resulting from the comparison of groups with two different materials composing the devices and the comparison of groups with devices and groups with sham sites with scarce inflammatory / tissue responses, as expected. EXAMPLE 3
[0143] As described earlier, in some embodiments, implantable prostheses can be formed from two-dimensional porous substrates, which can be cut and assembled into three-dimensional prostheses. In some embodiments, the substrates can be mesh-like sheets with porosity. For example, the substrates can be formed from PHASIX porous material, having at least two pore size distributions, a larger pore size and a smaller pore size. The porosity of the prostheses can be evaluated using a six-sigma statistical system, as tabulated in Table 11 below. The table summarizes the porosity data of fifteen exemplary mesh substrates used to form implantable prostheses, including sample number N, mean pore size, standard error SE of the mean, standard deviation SD, minimum distribution size, Q1 porosity of the first quartile, median porosity, Q3 porosity of the third quartile, and maximum size.The porosity of the substrates listed in Table 11 below is measured using optical characterization methods. Variable N Mean SE SD Min Q1 Median Q3 Max Smallest pore size (microns) 15 355.51 5.27 20.41 326.10 333.30 354.60 374.90 384.20 Petition 870250069888, dated 06 / 08 / 2025, page 74 / 118 66 / 77 Main pore size (microns) 15 777.37 7.50 29.06 736.80 754.00 770.90 810.50 830.70 Table 11 - Tabulated exemplary porosity properties of mesh-like substrates used to form implantable prostheses.
[0144] In some embodiments, implantable prostheses can be sutured to the implant site. In some embodiments, adjacent conical subunits can be sutured together during assembly. Consequently, mesh-like sheets may have sufficient suture pull-out resistance to withstand these forces during implantation and / or assembly. The suture pull-out resistance of mesh-like substrates can be evaluated using a six sigma statistical system, as tabulated in Table 12 below. The table summarizes the suture pull-out resistance data of fifteen exemplary mesh substrates used to form implantable prostheses in both the machine direction (MD) and the transverse direction (CD).The data in Table 12 include the number of samples N, mean strength, standard error SE of the mean, standard deviation SD, minimum strength distribution, strength in the first quartile Q1, median strength, strength in the third quartile Q3, and maximum strength. The strength of the substrates tabulated in Table 12 below is measured by conventional tensile techniques using mechanical testing machines. variable 1.250 7.79 0 7.910 8.530 9.630 12.040 Petition 870250069888, dated 06 / 08 / 2025, page 75 / 118 67 / 77 CD suture (lbf) Table 12 - Exemplary tabulated suture pull-out resistance properties of mesh-like substrates used to form implantable prostheses, in the machine direction (MD) and in the transverse direction (CD). EXAMPLE 4
[0145] In some embodiments, an implantable prosthesis may be compressible enough that it can be inserted into an implant site through an incision smaller than the average size of the prosthesis. For example, a typically spherical implantable prosthesis with an average diameter of 2 cm may need to be inserted through an incision site of approximately 1.5 cm (to minimize scarring and incision formation), retaining most of its size at the implant site, which may be larger than the incision site.
[0146] The recovery of the size of an implantable prosthesis can be evaluated along one or more directions, where the percentage difference is calculated by measuring a dimension D before and after insertion, as follows: n / J ρ..ρ / DpremeditationDpostmeditation3 . % Difference = I---------------------I * 100 \ Dpremedição /
[0147] The percentage difference can be calculated for any suitable dimension, such as the height of a prosthesis and the first and second widths (see Figure 11B). Table 13 below summarizes the percentage difference in heights and widths of the first and second widths for fifteen exemplary implantable spherical prostheses formed by 12 conical subunits, using a six sigma statistical system, as per Petition 870250069888, dated 06 / 08 / 2025, page 76 / 118 68 / 77 described previously. The exemplary prostheses measured in Table 13 below have an average diameter of 2 cm and are inserted through a 1.5 cm incision. Variable N Mean SE SD Min Q1 Median Q3 Max Height difference 15 1.074 0.247 0.956 0.797 0.507 0.971 1.835 2.935 Width difference 1 15 0.685 0.278 1.077 1.050 0.112 0.508 1.247 3.413 Width difference 2 15 0.167 0.340 1.318 2.509 0.324 0.122 0.725 2.595 Table 13 - Tabulated illustrative effect of insertion in implantable prostheses, determined by geometric changes in prosthesis size.
[0148] In some embodiments, the recoverability of an implantable prosthesis can be evaluated using a compression test. For example, the implantable prosthesis can be subjected to 30% compression and returned to its uncompressed state. In some embodiments, a design requirement for such compression may be that the prosthesis returns to 10% of its original dimension after compression. Table 14 below summarizes the percentage difference in heights and widths of the first and second for fifteen exemplary spherical implantable prostheses to meet such requirements. The prostheses are formed by 12 conical subunits, and the values tabulated in Table 14 are evaluated using a six sigma statistical system, as described previously. Variable N Mean SE SD Min Q1 Median Q3 Max Spherical prostheses with an average diameter of 2 cm Petition 870250069888, dated 06 / 08 / 2025, page 77 / 118 69 / 77 Difference in height 15 1.087 0.158 0.613 0.000 0.65 9 1.131 1.597 2.008 Difference in width 1 15 -0.061 0.303 1.174 -1.800 0.75 8 -0.261 0.184 3.185 Difference in width 2 15 0.044 0.353 1.365 -2.601 0.43 8 -0.220 0.618 2.683 Spherical prostheses with an average diameter of 3 cm Difference in height 15 0.342 0.354 1.370 -0.690 0.07 7 0.038 0.231 5.162 Difference in width 1 15 -0.072 0.176 0.682 -1.301 0.63 0 -0.006 0.325 1.377 Difference in width 2 15 -0.161 0.366 1.416 -2.076 1.21 9 -0.020 0.223 4.004 Spherical prostheses with an average diameter of 4 cm Difference in height 15 0.483 3 0.097 5 0.377 7 0.057 4 0.28 53 0.4313 0.538 7 1.552 8 Difference in width 1 15 0.376 0.496 1.919 -1.659 1.13 3 0.220 1.417 5.783 Difference in width 2 15 -1.015 0.497 1.927 -3.837 3.11 5 -0.521 0.104 2.592 Spherical prostheses with an average diameter of 5 cm Petition 870250069888, dated 06 / 08 / 2025, p. 78 / 118 70 / 77 Difference in height 15 0.628 0.126 0.488 0.024 0.25 4 0.478 0.832 1.654 Difference in width 1 15 0.044 4 0.061 3 0.237 4 0.217 7 0.13 71 -0.0330 0.190 8 0.604 5 Difference in width 2 15 0.056 2 0.045 1 0.174 6 0.178 0 0.08 63 0.0785 0.177 7 0.462 2 Table 14 - Tabulated exemplary recoverability after 30% compression for spherical implantable prostheses with average diameters of 2, 3, 4 and 5 cm, as indicated. EXAMPLE 5
[0149] In some embodiments, an implantable prosthesis may be sufficiently mechanically rigid to impart strength to the surrounding tissue during implantation, but may transfer the load to the natural tissue during the regrowth process. In some embodiments, the prosthesis stiffness may be better matched to the 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 bearing stiffness greater than or equal to 12.41 kPa (1.8 psi) at 30% compression and a compressive stiffness less than or equal to 42.06 kPa (6.1 psi), as a highly rigid prosthesis may elicit undesirable cellular responses. Table 15 below summarizes the stiffness of fifteen sets of exemplary spherical implantable prostheses formed by 12 conical subunits, each with a different mean diameter, as indicated.The prostheses in Table 15 meet the aforementioned design requirements using a... Petition 870250069888, dated 06 / 08 / 2025, page 79 / 118 71 / 77 six sigma statistical system, as described previously. Variable N Mean SE SD Min Q1 Median Q3 Max Rigidity (psi) Spherical prosthesis, 2 cm diameter 15 4.083 0.12 6 0.48 8 3.28 0 3.64 0 4.030 4.52 0 4.84 0 Rigidity (psi) Spherical prosthesis, 3 cm diameter 15 3.2427 0.05 62 0.21 77 2.85 00 3.07 00 3.3200 3.40 00 3.57 00 Rigidity (psi) Spherical prosthesis, 4 cm diameter 15 4.0567 0.06 43 0.24 92 3.63 00 3.88 00 3.9700 4.32 00 4.46 00 Rigidity (psi) Spherical prosthesis, 5 cm in diameter 15 3.0973 0.06 05 0.23 44 2.81 00 2.90 00 3.0600 3.20 00 3.66 00 Table 15 - Tabulated exemplary stiffness of implantable spherical prostheses with different average diameters.
[0150] Similar stiffness characterizations can be made for the non-spherical implantable prostheses described in this document, such as ellipsoidal prostheses, as described in relation to Figures 8A-10E. Table 16 below summarizes the stiffnesses of two sets of exemplary ellipsoidal implantable prostheses formed by 14 subunits, each with a different size, as indicated. The tabulated stiffnesses were evaluated using a six-sigma statistical system, as Petition 870250069888, dated 06 / 08 / 2025, pages 80 / 118 72 / 77 described previously. The specific geometries of the various ellipsoidal prostheses evaluated in Table 16 are shown in Table 1 above. Variable N Mean SE SD Min Q1 Median Q3 Max Ellipsoidal prostheses with an average height of 3 cm and an average width of 2 cm Horizontal stiffness (psi) 3 4.003 0.147 0.254 3.710 3.710 4.140 4.160 4.160 Vertical stiffness (psi) 3 3.827 0.140 0.242 3.640 3.640 3.740 4.100 4.100 Ellipsoidal prostheses with an average height of 4 cm and an average width of 3 cm Horizontal stiffness (psi) 5 3.622 0.127 0.284 3.140 3.400 3.670 3.820 3.880 Vertical stiffness (psi) 5 3,640 0,106 0,237 3,280 3,440 3,660 3,830 3,930 Ellipsoidal prostheses with an average height of 5 cm and an average width of 4 cm Horizontal stiffness (psi) 3 3,780 0,189 0,327 3,410 3,410 3,900 4,030 4,030 Vertical stiffness (psi) 3 3,457 0,185 0,320 3,110 3,110 3,520 3,740 3,740 Table 16 - Tabulated exemplary stiffness of ellipsoidal implantable prostheses with different average diameters. EXAMPLE 6
[0151] In some embodiments, the prostheses described in this document may be infiltrated into the tissue, which may allow the prostheses to be fixed in place after implantation. The growth of natural tissue may serve to limit prosthesis migration. Prosthesis migration can be verified by means of Petition 870250069888, dated 06 / 08 / 2025, page 81 / 118 73 / 77 tracking of a radiopaque marker associated with the prosthesis, allowing an external imaging system to visualize and track the prosthesis without the need for an invasive procedure. As previously described, markers can be used to mark specific physiological locations (e.g., tumor bed locations) in the patient for follow-up imaging to monitor recovery and potential recurrences. In some cases, it may be desirable to limit marker migration to 1 cm from its original fixation site on the device after 5 months post-implantation. Table 17 below summarizes the migration of radiopaque markers for thirty exemplary markers between their initial implantation and five months post-implantation, using a six-sigma statistical system as previously described. The data presented in Table 17 reflect measurements at two different locations for each marker between the time points mentioned above. Variable N Mean SE SD Min Q1 Mean in Q3 Max Measurement Difference Location 1 (cm) 3 0 0.0315 0 0.0032 5 0.0177 9 0.0058 0 0.0170 6 0.0298 3 0.0450 7 0.0659 1 Measurement Difference Location 2 (cm) 3 0 0.0295 9 0.0033 8 0.0185 1 0.0008 1 0.0125 6 0.0252 9 0.0434 7 0.0667 4 Table 17 - Tabulated exemplary stiffness of implantable spherical prostheses. EXAMPLE 7
[0152] In some modalities, the rigidity of an implantable prosthesis may be Petition 870250069888, dated 06 / 08 / 2025, page 82 / 118 74 / 77 is determined by a variety of factors, such as the percentage of hollow core, the number of connections between and within each conical subunit, the distance between connections (e.g., welds), and the overall geometry of each conical subunit. In an exemplary experiment, a Pareto analysis of the variety of factors that can determine stiffness was performed to determine which elements were most influential in achieving the desired stiffness. The analysis revealed that a hollow core percentage of 10% and an overlap degree of approximately 65° can achieve a desired stiffness of approximately 25.86 kPa (3.75 psi) for a spherical prosthesis with an average diameter of approximately 4 cm. EXAMPLE 8
[0153] In some embodiments, the stiffness (e.g., horizontal stiffness and vertical stiffness) of an ellipsoidal implantable prosthesis can be determined by a variety of factors, such as the percentage of hollow core, the number of connections (e.g., welds) between and within each conical subunit, the distance between the connections (e.g., welds) from the edge, and the overall geometry of each conical subunit. In an exemplary experiment, a series of different ellipsoidal prostheses (2 cm x 3 cm; 3 cm x 4 cm; 4 cm x 5 cm) were evaluated. Each prosthesis included a set of lateral, peak, and intermediate conical subunits with different design characteristics (e.g., degree of overlap (cutout); percentage of hollow core (HC); number of welds and distance from the edge), as summarized in the table below. Side Peak Size: Medium 2 x 3 120° Cutout 200° Cutout 125° Cutout Petition 870250069888, dated 06 / 08 / 2025, p. 83 / 118 75 / 77 20% HC 1 weld of 3 mm 25% HC 1 weld of 3 mm 25% HC 1 weld of 3 mm 3x4 120° cut 13% HC 2 welds of 3 and 7 mm 218° cut 24.5% HC 2 welds of 3 and 7 mm 120° cut 10% HC 3 and 7 mm welds 4 x 5 55° cut 10% HC 2 welds of 3 and 7 mm 120° cut 10% HC 2 welds of 3 and 7 mm 35° cut 10% HC 2 welds of 3 and 7 mm Table 18 - Design attributes of the evaluated ellipsoidal implantable prostheses.
[0154] The evaluation showed the following: for the 2 cm x 3 cm ellipsoid-shaped prosthesis, a horizontal stiffness of 27.58 kPa (4.00 psi) and a vertical stiffness of 26.40 kPa (3.83 psi) were obtained; for the 3 cm x 4 cm ellipsoid-shaped prosthesis, a horizontal stiffness of 24.96 kPa (3.62 psi) and a vertical stiffness of 25.10 kPa (3.64 psi) were obtained; and, for the 4 cm x 5 cm ellipsoid-shaped prosthesis, a horizontal stiffness of 23.85 kPa (3.46 psi) and a vertical stiffness of 26.06 kPa (3.78 psi) were obtained.
[0155] The modalities described in this document can be incorporated as a method, of which an example has been provided. The actions performed as part of the method can be ordered in any suitable way. Therefore, modalities can be constructed in which the actions are performed in a different order than illustrated, which may include performing some actions simultaneously, although shown as sequential actions in illustrative modalities.
[0156] In addition, some actions are described as being performed by a “user”. It should be understood that a “user” does not need to be a single individual and that, Petition 870250069888, dated 06 / 08 / 2025, page 84 / 118 76 / 77 In some modalities, actions attributable to a “user” may be performed by a team of individuals and / or an individual in combination with computer-assisted tools or other mechanisms.
[0157] Although the present teachings have been described in conjunction with various modalities and examples, it is not intended that the present teachings be limited to these modalities or examples. On the contrary, the present teachings encompass various alternatives, modifications, and equivalents, as will be understood by those skilled in the art. Therefore, the preceding description and drawings are only by way of example.
[0158] Although various embodiments of the present invention have been described and illustrated herein, those skilled in the art will readily imagine a variety of other means and / or structures for performing the functions and / or obtaining the results and / or one or more of the advantages described herein, and each of these variations and / or modifications is considered to be encompassed within the scope of the present invention. More generally, those skilled in the art will readily understand that all parameters, dimensions, materials, and configurations described herein are intended to be illustrative and that the actual parameters, dimensions, materials, and / or configurations will depend on the specific application or applications for which the teachings of the present invention are used.Those skilled in the art will recognize, or be able to determine, using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. It should therefore be understood that the foregoing embodiments are presented only as examples and that, within the scope... Petition 870250069888, dated 06 / 08 / 2025, p. 85 / 118 77 / 77 of the appended and equivalent claims, the invention may be practiced in a manner other than that specifically described and claimed. The present invention is directed to each individual attribute, system, item, material, kit and / or method described in this document. Furthermore, any combination of two or more of these attributes, systems, articles, materials, kits and / or methods, provided that such attributes, systems, articles, materials, kits and / or methods are not mutually inconsistent, is included within the scope of the present invention. Petition 870250069888, dated 06 / 08 / 2025, p. 86 / 118
Claims
1 / 7 CLAIMS 1. Implantable prosthesis CHARACTERIZED in that it comprises: a plurality of substantially conical mesh bodies, wherein each of the plurality of substantially conical mesh bodies is connected to at least one other of the plurality of substantially conical mesh bodies, and wherein the substantially conical bodies are arranged to form an ellipsoid.
2. A method for forming an implantable prosthesis, the method being characterized by the fact that it comprises: forming a plurality of substantially conical mesh bodies; and connecting each of the conical mesh bodies to at least one other substantially conical mesh body to form an ellipsoid.
3. Implantable prosthesis CHARACTERIZED by the fact that it comprises: a plurality of substantially conical bodies, wherein each of the plurality of substantially conical bodies is connected to at least one other of the plurality of substantially conical bodies, and wherein the implantable prosthesis is substantially isotropic mechanically.
4. Implantable prosthesis CHARACTERIZED by the fact that it comprises: a plurality of substantially conical bodies, each conical body including a lateral wall that defines a cone shape, wherein the lateral wall of each substantially conical body is connected to the lateral wall of at least one other adjacent substantially conical body. Petition 870250069888, dated 06 / 08 / 2025, page 87 / 118 2 / 7 5. A method for forming an implantable prosthesis, the method being characterized by the fact that it comprises: forming a plurality of substantially conical bodies, each conical body including a lateral wall that defines a cone shape; and connecting the lateral wall of each substantially conical body to the lateral wall of at least one other adjacent substantially conical body.
6. Implantable prosthesis or method, according to any one of claims 1 to 5, wherein the implantable prosthesis is CHARACTERIZED in that it comprises a hollow core.
7. Implantable prosthesis or method, according to any one of claims 1 to 6, wherein the prosthesis is CHARACTERIZED in that it is configured to be sized and shaped to be placed in a lumpectomy site.
8. Implantable prosthesis or method, according to any one of claims 1 to 7, wherein the implantable prosthesis is CHARACTERIZED in that it is formed at least partially of a resorbable material.
9. Implantable prosthesis or method, according to any one of claims 1 to 8, CHARACTERIZED in that it additionally comprises one or more radiopaque markers.
10. Implantable prosthesis or method, according to any one of claims 1 to 9, CHARACTERIZED in that the compressive stiffness of the implantable prosthesis is between 6.89 kPa and 68.95 kPa (1 psi and 10 psi), inclusive.
11. Implantable prosthesis or method, according to any of claims 4 and 5, CHARACTERIZED in that a first portion of the lateral wall of each substantially conical body is connected to a second portion of the lateral wall of the same substantially conical body.
12. Implantable prosthesis or method, according to any one of claims 4 and 5, CHARACTERIZED in that a first portion of the lateral wall of each substantially conical body is welded to a second portion of the lateral wall of the same substantially conical body.
13. Implantable prosthesis or method, according to any one of claims 1 to 3 and 6 to 10, CHARACTERIZED in that each substantially conical body comprises a lateral wall, and in that a first portion of the lateral wall of each substantially conical body is welded to a second portion of the lateral wall of the same substantially conical body.
14. Implantable prosthesis or method, according to any one of claims 1 to 3 and 6 to 10, CHARACTERIZED in that each substantially conical body comprises a lateral wall, and in that the lateral wall of each substantially conical body is welded to a lateral wall of at least one other adjacent substantially conical body.
15. Implantable prosthesis or method, according to any one of claims 1 to 14, CHARACTERIZED in that at least one average diameter of the implantable prosthesis is between 2 cm and 5 cm.
16. Implantable prosthesis or method, according to any one of claims 3 to 5, CHARACTERIZED in that the substantially conical bodies are arranged to form an ellipsoid. Petition 870250069888, dated 06 / 08 / 2025, p. 89 / 118 4 / 7 17. Implantable prosthesis or method, according to any one of claims 1 and 2 and 4 and 5, wherein the implantable prosthesis is CHARACTERIZED by the fact that it is substantially mechanically isotropic.
18. Implantable prosthesis or method, according to any one of claims 1 to 17, CHARACTERIZED in that the substantially conical bodies are arranged to form a sphere.
19. Implantable prosthesis or method, according to any one of claims 1 to 18, CHARACTERIZED in that it further comprises a second plurality of substantially conical mesh bodies geometrically distinct from the first plurality of substantially conical mesh bodies.
20. Implantable prosthesis or method, according to claim 6, CHARACTERIZED in that the volume of the hollow core is between 10% and 35% of the total volume of the implantable prosthesis.
21. Implantable prosthesis CHARACTERIZED by the fact that it comprises: a plurality of mesh bodies, wherein each mesh body is connected to another mesh body; wherein at least some of the mesh bodies include a first mesh portion connected to a second mesh portion, wherein the first portion is disposed within a volume defined by the second mesh portion.
22. Method for forming an implantable prosthesis, the method being CHARACTERIZED by the fact that it comprises: forming a plurality of mesh bodies; Petition 870250069888, dated 06 / 08 / 2025, p. 90 / 118 5 / 7 arranging a first mesh portion of at least some of the mesh bodies within a volume defined by a second mesh portion; connecting the first mesh portion to the second mesh portion; and connecting each of the mesh bodies to another mesh body.
23. Implantable prosthesis or method, according to any one of claims 21 and 22, wherein the implantable prosthesis is CHARACTERIZED in that it comprises a hollow core.
24. Implantable prosthesis or method, according to any one of claims 21 to 23, wherein the prosthesis is CHARACTERIZED in that it is configured to be sized and shaped to be placed in a lumpectomy site.
25. Implantable prosthesis or method, according to any one of claims 21 to 24, wherein the implantable prosthesis is CHARACTERIZED in that it is formed at least partially of a resorbable material.
26. Implantable prosthesis or method, according to any one of claims 21 to 25, CHARACTERIZED in that it additionally comprises one or more radiopaque markers.
27. Implantable prosthesis or method, according to any one of claims 1 to 26, CHARACTERIZED in that the compressive stiffness of the implantable prosthesis is between 6.89 kPa and 68.95 kPa (21 psi and 10 psi), inclusive.
28. Implantable prosthesis or method, according to any one of claims 21 to 27, CHARACTERIZED in that the first portion is welded to the second portion. Petition 870250069888, dated 06 / 08 / 2025, p. 91 / 118 6 / 7 29. Implantable prosthesis or method, according to any one of claims 21 to 28, CHARACTERIZED in that each mesh body comprises a side wall, and in that a first portion of the side wall of each mesh body is welded to a second portion of the side wall of the same mesh body.
30. Implantable prosthesis or method, according to any one of claims 21 to 29, CHARACTERIZED in that at least one average diameter of the implantable prosthesis is between 2 cm and 5 cm.
31. Implantable prosthesis or method, according to any one of claims 21 to 30, CHARACTERIZED in that the mesh bodies are arranged to form an ellipsoid.
32. Implantable prosthesis or method, according to any one of claims 21 to 31, CHARACTERIZED in that the implantable prosthesis is substantially mechanically isotropic.
33. Implantable prosthesis or method, according to any one of claims 21 to 32, CHARACTERIZED in that the mesh bodies are arranged to form a sphere.
34. Implantable prosthesis or method, according to any one of claims 21 to 33, CHARACTERIZED by the suit additionally comprising a second plurality of mesh bodies geometrically distinct from the first plurality of mesh bodies.
35. Implantable prosthesis or method, according to claim 23, CHARACTERIZED in that the volume of the hollow core is between 10% and 35% of the total volume of the implantable prosthesis.
36. Implantable prosthesis or method, according to any one of claims 21 to 35, CHARACTERIZED in that each of the plurality of mesh bodies is substantially conical.
37. Implantable prosthesis or method, according to any one of claims 21 to 36, CHARACTERIZED in that at least some of the plurality of mesh bodies are corrugated.
38. Implantable prosthesis or method, according to claim 37, CHARACTERIZED in that the corrugated mesh bodies comprise at least 5 corrugations. Petition 870250069888, dated 06 / 08 / 2025, p. 93 / 118