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WO2025128946A1 - Dispositifs et leurs procédés de fabrication et d'utilisation - Google Patents

Dispositifs et leurs procédés de fabrication et d'utilisation Download PDF

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Publication number
WO2025128946A1
WO2025128946A1 PCT/US2024/059957 US2024059957W WO2025128946A1 WO 2025128946 A1 WO2025128946 A1 WO 2025128946A1 US 2024059957 W US2024059957 W US 2024059957W WO 2025128946 A1 WO2025128946 A1 WO 2025128946A1
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WO
WIPO (PCT)
Prior art keywords
examples
zone
dimensional units
mesh
poly
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2024/059957
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English (en)
Inventor
Aldona Jedrysiak SPIEGEL
Francesca TARABALLI
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Methodist Hospital
Original Assignee
Methodist Hospital
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Filing date
Publication date
Application filed by Methodist Hospital filed Critical Methodist Hospital
Publication of WO2025128946A1 publication Critical patent/WO2025128946A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y80/00—Products made by additive manufacturing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/0063—Implantable repair or support meshes, e.g. hernia meshes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/12—Mammary prostheses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24—Collagen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/0063—Implantable repair or support meshes, e.g. hernia meshes
    • A61F2002/0068—Implantable repair or support meshes, e.g. hernia meshes having a special mesh pattern
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2240/001—Designing or manufacturing processes
    • A61F2240/002—Designing or making customized prostheses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0014—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
    • A61F2250/0018—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis differing in elasticity, stiffness or compressibility
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/426—Immunomodulating agents, i.e. cytokines, interleukins, interferons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/04—Materials or treatment for tissue regeneration for mammary reconstruction

Definitions

  • Breast cancer is a complex disease that requires comprehensive treatment extending beyond the initial attainment of "Cancer-Free” status. Many breast cancer patients undergo mastectomy or lumpectomy procedures as part of their treatment, which often leads to significant anxiety and depression. In order to alleviate these emotional challenges, breast reconstruction has proven beneficial. However, the current state of breast reconstruction is far from perfect.
  • the U.S. Food and Drug Administration has implemented regulatory measures to address the safety issues associated with textured implants.
  • the FDA has issued a black box warning, specifically emphasizing the potential risks related to textured implants, particularly in relation to a rare form of BII-ALCL (anaplastic largecell lymphoma). Consequently, only round smooth implants are currently approved for clinical use, as textured implants have been linked to these complications.
  • This regulatory limitation necessitates the exploration of alternative methods to provide adequate support for the tissue and/or implant, while also enabling the achievement of a more natural tear drop breast shape.
  • the disclosed subject matter relates to devices and methods of making and use thereof.
  • the mesh comprises a plurality of three-dimensional units, the plurality of three-dimensional units being interconnected to form the mesh.
  • devices configured to be inserted into an anatomical location of a subject, the devices comprising a mesh with a plurality of zones having different elastic properties, each zone having a composition and a geometry, wherein the different elastic properties are based on the composition, the geometry, or combination thereof, wherein the mesh comprises a plurality of three-dimensional units, the plurality of three-dimensional units being interconnected to form the mesh.
  • each of the plurality of three-dimensional units is configured to receive and hold adipose tissue.
  • each tubule has an average diameter of 1.6 millimeters or less.
  • the platform can have any suitable geometry, such as polygonal (e.g., triangular, rectangular, hexagonal, etc.) or circular.
  • each three-dimensional unit further comprises a base, the pillar extending from the base to the platform.
  • the base has any suitable geometry, such as polygonal (e.g., triangular, rectangular, hexagonal) or circular.
  • the base and the platform are the same or different.
  • the base (when present) and/or the platform each independently has a planar surface.
  • the base (when present) and/or the platform each independently has an average characteristic dimension, wherein the average characteristic dimension is from 0.4 to 4 centimeters, such as from 0.5 to 4 centimeters.
  • the base (when present) and/or the platform are each triangular, the average characteristic dimension being the average length of the side of the triangle, the average characteristic dimension being from 0.4 to 4 centimeters.
  • each three dimensional unit has an average height, measured from the platform to the bottom of the pillar or measured from the platform to the base (when present), wherein the average height is 2 centimeters or less.
  • the average height is from 0.4 centimeters to 2 centimeters, such as from 0.5 to 2 centimeters.
  • each of the three-dimensional units has volume configured to receive and hold adipose tissue, the volume of each of the three-dimensional units independently being from 0.1 to 25 cm 3 .
  • neighboring three-dimensional units are connected to each other to form the mesh.
  • the one or more tubules are configured to connect neighboring three- dimensional units to each other to form the mesh.
  • the one of more tubules of neighboring three-dimensional units are interwoven to thereby connect neighboring three-dimensional units to each other.
  • the mesh is integrally formed, for example by 3D printing.
  • the mesh comprises a plurality of three-dimensional units as shown in one or more of Figure 36A- Figure 49.
  • composition of each of the plurality of zones and/or each of the plurality of three dimensional units comprises an isotropic material, an anisotropic material, an auxetic material, a non-auxetic material, or a combination thereof.
  • the geometry of each of the plurality of zones and/or each of the plurality of three dimensional units comprises an auxetic geometry, a non-auxetic geometry, or a combination thereof.
  • the mesh comprises a support zone, the support zone being elastic along one direction.
  • the composition of one or more of the plurality of zones, one or more of the plurality of three-dimensional units, at least a portion of each of the plurality of three- dimensional units, or a combination thereof independently comprises poly(ethylene glycol) diacrylate (PEGDA), poly(ethylene glycol) dimethacrylate (PEGDMA), poly(ethylene glycol) diacrylamide (PEGDAAm), gelatin methacrylate (GelMA), collagen methacrylate, silk methacrylate, hyaluronic acid methacrylate, chondroitin sulfate methacrylate, elastin methacrylate, cellulose acrylate, dextran methacrylate, heparin methacrylate, NIPAAm methacrylate, Chitosan methacrylate, polyethylene glycol norbomene, polyethylene glycol dithiol, thiolated gelatin, thiolated chitosan, thiolated silk, silk, PEG based peptide conjugates, cell-
  • composition of each of the plurality of zones and/or each of the plurality of three-dimensional units comprises polydioxanone (PDO).
  • the device comprises a support zone and an elastic zone.
  • the device is configured to support and/or reshape an organ and/or an implant when inserted in the subject.
  • the device is configured to support a breast or a breast implant.
  • the device is formed from a model based on a tessellation of polyhedrons.
  • the device is formed from a computational 3D space- filling model.
  • the device is not flat.
  • the device has a three dimensional shape.
  • the device has a three-dimensional parametric teardrop shape.
  • the device is substantially flat before insertion and can stretch to a three dimensional teardrop shape that conforms to support and/or reshape an organ and/or an implant when inserted in the subject.
  • the device is anatomically designed for the subject.
  • the device is produced by additive manufacturing (e.g., 3D printing).
  • the device is a single piece of mesh (e.g., monolithic).
  • the device is biocompatible.
  • the methods comprise making the device using additive manufacturing (e.g., 3D printing).
  • the method comprises making the device based on a 3D model.
  • the 3D model is based on the Fibonacci equation.
  • the 3D model is based on an anatomical image of a subject.
  • the method further comprises collecting the anatomical image of the subject.
  • the device is implanted into at least a portion of a breast of the subject.
  • the method comprises breast reconstruction or augmentation (e.g., full or partial breast reconstruction or augmentation), such as after a lumpectomy or mastectomy.
  • breast reconstruction or augmentation e.g., full or partial breast reconstruction or augmentation
  • the device is implanted into a breast of the subject.
  • the method comprises breast reconstruction or augmentation.
  • the method further comprises anatomically designing the device for the subject.
  • Figure 46 Schematic diagram of an example mesh/fabric comprising a plurality of the hexagonal units.
  • Figure 47 Alternative schematic view of the mesh/fabric of Figure 46.
  • Ranges can be expressed herein as from “about” one particular value, and/or to “about” another particular value. By “about” is meant within 5% of the value, e.g., within 4, 3, 2, or 1% of the value. When such a range is expressed, another aspect includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint.
  • Average generally refers to the statistical mean value.
  • A, B, C, or combinations thereof refers to all permutations and combinations of the listed items preceding the term.
  • “A, B, C, or combinations thereof’ is intended to include at least one of: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB.
  • expressly included are combinations that contain repeats of one or more item or term, such as BB, AAA, AB, BBC, AAABCCCC, CBBAAA, CAB ABB, and so forth.
  • the skilled artisan will understand that typically there is no limit on the number of items or terms in any combination, unless otherwise apparent from the context.
  • biodegradable or “bioresorbable” as used herein refers to a material or substance wherein physical dissolution and/or chemical degradation is effected under physiological conditions.
  • antimicrobial refers to the ability to treat or control (e.g., reduce, prevent, treat, or eliminate) the growth of a microbe at any concentration.
  • antibacterial refers to the ability to treat or control the growth of bacteria, fungi, and viruses at any concentration, respectively.
  • reduce or other forms of the word, such as “reducing” or “reduction,” refers to lowering of an event or characteristic e.g., microbe population/infection). It is understood that the reduction is typically in relation to some standard or expected value. For example, “reducing microbial infection” means reducing the spread of a microbial infection relative to a standard or a control.
  • prevent or other forms of the word, such as “preventing” or “prevention,” refers to stopping a particular event or characteristic, stabilizing or delaying the development or progression of a particular event or characteristic, or minimizing the chances that a particular event or characteristic will occur. “Prevent” does not require comparison to a control as it is typically more absolute than, for example, “reduce.” As used herein, something could be reduced but not prevented, but something that is reduced could also be prevented. Likewise, something could be prevented but not reduced, but something that is prevented could also be reduced.
  • treat or other forms of the word, such as “treated” or “treatment,” refers to administration of a composition or performing a method in order to reduce, prevent, inhibit, or eliminate a particular characteristic or event (e.g., microbe growth or survival).
  • control is used synonymously with the term “treat.”
  • anticancer refers to the ability to treat or control cellular proliferation and/or tumor growth at any concentration.
  • terapéuticaally effective refers to the amount of the composition used is of sufficient quantity to ameliorate one or more causes or symptoms of a disease or disorder. Such amelioration only requires a reduction or alteration, not necessarily elimination.
  • pharmaceutically acceptable refers to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problems or complications commensurate with a reasonable benefit/risk ratio.
  • molecular weight refers to the number average molecular weight as measured by 1 H NMR spectroscopy, unless indicated otherwise.
  • the device is a mesh with a plurality of zones having different elastic properties, each zone having a composition and a geometry, wherein the different elastic properties are based on the composition, the geometry, or combination thereof, wherein the mesh further has a thickness 130.
  • the thickness 130 can, for example, be configured to receive and hold adipose tissue, such as autologous adipose tissue.
  • the thickness of the mesh is 2 centimeters (cm) or less (e.g., 1.9 cm or less, 1.8 cm or less, 1.7 cm or less, 1.6 cm or less, 1.5 cm or less, 1.4 cm or less, 1.3 cm or less, 1.2 cm or less, 1.1 cm or less, 1.0 cm or less, 0.9 cm or less, 0.8 cm or less, 0.7 cm or less, 0.6 cm or less, or 0.5 cm or less).
  • the thickness of the mesh is 0.4 centimeters (cm) or more (e.g., 0.5 cm or more, 0.6 cm or more, 0.7 cm or more, 0.8 cm or more, 0.9 cm or more, 1.0 cm or more, 1.1 cm or more, 1.2 cm or more, 1.3 cm or more, 1.4 cm or more, 1.5 cm or more, 1.6 cm or more, 1.7 cm or more, 1.8 cm or more, or 1.9 cm or more).
  • the thickness of the mesh can range from any of the minimum values described above.
  • the thickness of the mesh can be from 0.4 to 2 centimeters (cm) (e.g., from 0.4 to 1.2 cm, from 1.2 to 2 cm, from 0.4 to 1 cm, from 1 cm to 1.5 cm, from 1.5 cm to 2 cm, from 0.4 to 1.8 cm, from 0.4 to 1.6 cm, from 0.4 to 1.4 cm, from 0.4 to 0.8 cm, from 0.5 to 2 cm, from 0.6 to 2 cm, from 0.8 to 2 cm, from 1 to 2 cm, from 1.4 to 2 cm, from 0.5 to 1.9 cm, or from 0.6 to 1.8 cm).
  • the thickness of the mesh is from 0.5 to 2 centimeters.
  • the mesh comprises a plurality of three-dimensional units 140, wherein the plurality of three-dimensional units 140 are interconnected to form the mesh.
  • devices 100 configured to be inserted into an anatomical location of a subject, the device 100 comprising a mesh with a plurality of zones having different elastic properties, each zone having a composition and a geometry, wherein the different elastic properties are based on the composition, the geometry, or combination thereof, wherein the mesh comprises a plurality of three-dimensional units 140, the plurality of three-dimensional units being interconnected to form the mesh.
  • the plurality of three-dimensional units can be the same or different.
  • the mesh is disposed on a membrane, such as a second mesh.
  • At least a portion of the mesh and/or at least a portion of a volume defined by the mesh and the membrane is configured to receive and hold adipose tissue, such as autologous adipose tissue.
  • at least a portion of each of the plurality of three-dimensional units is configured to receive and hold adipose tissue, such as autologous adipose tissue.
  • Each of the three-dimensional units 140 can, for example, comprise a platform 141, a pillar 142, and one or more tubules 143.
  • the pillar can, for example, extend from the platform.
  • the pillar can have any suitable shape and/or geometry.
  • the pillar can, for example, provide a desired mechanical property (e.g., strength and/or elasticity) and/or define a volume configured to receive and hold adipose tissue, such as autologous adipose tissue.
  • the pillar can be solid or hollow.
  • the pillar is hollow, such that the pillar comprises a wall defining a lumen, the lumen being configured to receive and hold adipose tissue, such as autologous adipose tissue.
  • each of the one or more tubules can extend from the platform to the pillar, thereby connecting the platform and the pillar. In some examples, each of the one or more tubules extends from a first portion of the pillar to a second portion of the pillar, thereby connecting the first portion of the pillar to the second portion of the pillar.
  • the base (when present) and/or the platform can each independently have an average characteristic dimension of from 0.5 to 4 centimeters.
  • the base (when present) and/or the platform are each triangular, the average characteristic dimension being the average length of the side of the triangle, the average characteristic dimension being from 0.4 to 4 centimeters.
  • the base (when present) and/or the platform are each hexagonal, the average characteristic dimension being the average diameter of the hexagon, the average characteristic dimension being from 0.5 to 4 centimeters.
  • antibacterials include, but are not limited to, acetoxycycloheximide, aciduliprofundum, actaplanin, actinorhodin, alazopeptin, albomycin, allicin, allistatin, allyl isothiocyanate, ambazone, aminocoumarin, aminoglycosides, 4- aminosalicylic acid, ampicillin, ansamycin, anthramycin, antimycin A, aphidicolin, aplasmomycin, archaeocin, arenicin, arsphenamine, arylomycin A2, ascofuranone, aspergillic acid, avenanthramide, avibactam, azelaic acid, bafilomycin, bambermycin, beauvericin, benzoyl peroxide, blasticidin S, bottromycin, brilacidin, caprazamycin, carbomycin, cathelicidin, cephalosporins, ceragenin, chartreusin, chrom
  • antivirals examples include, but are not limited to, afovirsen, alisporivir, angustific acid, angustifodilactone, alovudine, beclabuvir, 2,3-bis(acetylmercaptomethyl)quinoxaline, brincidofovir, dasabuvir, docosanol, fialuridine, ibacitabine, imiquimod, inosine, inosine pranobex, interferon, metisazone, miltefosine, neokadsuranin, neotripterifordin, ombitasvir, oragen, oseltamivir, pegylated interferon, podophyllotoxin, radalbuvir, semapimod, tecovirimat, telbivudine, theaflavin, tilorone, triptofordin C-2, variecolol, ZMapp, abacavir,
  • the therapeutic agent can comprise an anticancer agent.
  • the therapeutic agent comprises a chemotherapeutic agent, an immunotherapeutic agent, or a combination thereof.
  • the therapeutic agent can comprise a chemotherapeutic agent.
  • Chemotherapy is the treatment of cancer with one or more cytotoxic anti-neoplastic drugs (e.g., chemotherapeutic agents) as part of a standardized regimen. Chemotherapy may be given with a curative intent or it may aim to prolong life or to palliate symptoms. In some cases, it can be used in conjunction with other cancer treatments, such as radiation therapy, surgery, hyperthermia therapy, or a combination thereof.
  • chemotherapeutic agents include, but are not limited to, 13-cis-Retinoic Acid, 2-Amino-6-Mercaptopurine, 2-CdA, 2- Chlorodeoxyadenosine, 5 -fluorouracil, 6-Thioguanine, 6-Mercaptopurine, Accutane, Actinomycin-D, Adriamycin, Adrucil, Agrylin, Ala-Cort, Aldesleukin, Alemtuzumab, Alitretinoin, Alkaban-AQ, Alkeran, All-transretinoic acid, Alpha interferon, Altretamine, Amethopterin, Amifostine, Aminoglutethimide, Anagrelide, Anandron, Anastrozole, Arabinosylcytosine, Aranesp, Aredia, Arimidex, Aromasin, Arsenic trioxide, Asparaginase, ATRA, Avastin, BCG, BCNU, Bevacizumab, Be
  • the therapeutic agent can comprise an anti-inflammatory agent, such as steroidal and/or non-steroidal anti-inflammatory agents.
  • steroidal antiinflammatory agents include, but are not limited to, hydrocortisone, dexamethasone, prednisolone, prednisone, triamcinolone, methylprednisolone, budesonide, betamethasone, cortisone, and deflazacort.
  • the therapeutic agent can comprise an analgesic.
  • analgesics include, but are not limited to, 1-Iodomorphine; 3-Hydroxymorphinan; 4- Methylpregabalin; A-366,833; ABT-202; Aceburic acid; Acefurtiamine; Acetaminosalol; Acetyldihydrocodeine; Acetylmethadol; Adrenorphin; Alazocine; Algifen; Alimadol; Alletorphine; Alphacetylmethadol; Alphamethadol; Amidorphin; Aminophenazone ; Ampyrone; Amrutanjan (balm); Anacin; Anadin; Analgecine; Anazocine; Anileridine; Anilopam; Anodyne; Askit Powders; Aspergum; Aspirin; Axomadol; AZD0328; BC Powder; Befiradol; Benorilate; Betacetylmethadol; Beta
  • the therapeutic agent can comprise an analgesic, such as an opioid.
  • opioids include, but are not limited to, (a/P)-Meprodine; (a/P)-Prodine; l-(4- Nitrophenylethyl)piperidylidene-2-(4-chlorophenyl)sulfonamide (W-l 8); 14- Cinnamoyloxycodeinone; 14-Ethoxymetopon; 14-Hydroxydihydrocodeine; 14- Hydroxy morphine; 14-Methoxymetopon; 14-Phenylpropoxymetopon; 18,19- Dehydrobuprenorphine (HS-599); 18-Methoxycoronaridine; 1 -Bromocodeine; 1 -Chlorocodeine; 1-Iodomorphine Codeine-6-glucuronide; 1 -Nitrocodeine; 2,4-Dinitrophenylmorphine; 3-(3- Methoxyphenyl
  • Chlomaltrexamine Chlorodihydrocodide; Chloromorphide; Chloroxymorphamine; Ciprefadol; Ciramadol; Clonitazene; Codeine; Codeine methylbromide; Codeine-N-oxide; Codeine-N- oxide (genocodeine); Codeinone; Codide; Codoxime; Cogazocine; Conorfone (codorphone); Coronaridine; Cyclazocine; Cyclorphan; Cyprenorphine; Cyprodime; Cyproterone acetate; Desmethylclozapine; Desmethylmoramide; Desmethylprodine (MPPP); Desocodeine Desomorphine (dihydrodesoxymorphine); Dextromethadone; Dextromoramide;
  • Heroin diacetylmorphine
  • Heroin-7 8-oxide
  • Heterocodeine Hodgkinsine
  • Homprenorphine a member of Heroin (diacetylmorphine); Heroin-7, 8-oxide; Heterocodeine; Hodgkinsine; Homprenorphine;
  • Hydrocodone Hydrocodone; Hydromorphinol; Hydromorphone; Hydroxycodeine; Hydroxypethidine (bemidone); HZ-2; Ibazocine; IBNtxA; Ibogaine; IC-26; ICI-199,441; ICI-204,448; Isoaminile; Isocodeine; Isomethadol; Isomethadone; Isotonitazene; Ketamine; Ketazocine; Ketobemidone; Ketorfanol; KNT-42; Kolokol-1; Lefetamine; Levacetylmethadol; Levargorphan;
  • Methyldihydromorphine (dihydroheterocodeine) ; Methyldihy dromorphinone; Methylketobemidone; Metofoline; Metonitazene; Metopon; Mirfentanil; Mitragynine; Mitragynine pseudoindoxyl; Morphanol (racemorphanol); Morphenol; Morpheridine; Morphine; Morphine methylbromide; Morphine-6-glucuronide; Morphine-N-oxide; Morphine-N- oxide (genomorphine); Morphinone; Morphol; Moxazocine; MT-45; MT-7716; Myrophine; Nalbuphine; Nalbuphone; Nalfurafine; Nalorphine; Nalorphine dinicotinate; Naltrexol; N- cyclopropylmethylnoretorphine; Nepenthone; Nexeridine; Nicocodeine; Nicodicodeine
  • Racemoramide Racemoramide; RAM-378; Remifentanil; Ro-1539; Ro4-1539; Ro64-6198; Ro65-6570; RWJ- 394,674; Salvinorin A; Salvinorin B ethoxymethyl ether; Salvinorin B methoxymethyl ether; Sameridine; SB-612,111 ; SC-17599; Semorphone; SKF-10047; SNC-80; SoRI-9409;
  • the device can, for example, be configured to support and/or reshape at least a portion of an organ and/or at least a portion of an implant when inserted in the subject.
  • the device can, for example, be configured to support and/or reshape an organ and/or an implant when inserted in the subject.
  • the anatomical location comprises a breast of the subject.
  • the device is configured to support at least a portion of a breast or at least a portion of a breast implant.
  • the device is configured to support a breast or a breast implant.
  • the device is formed from a model based on a tessellation of polyhedrons.
  • the device can be formed from a computational 3D space-filling model.
  • the device is not flat.
  • the device can have a three dimensional shape, such as a three-dimensional parametric teardrop shape.
  • the device is substantially flat before insertion and can stretch to a three dimensional teardrop shape that conforms to support and/or reshape an organ and/or an implant when inserted in the subject.
  • the device has a three-dimensional parametric teardrop shape following the Fibonacci equation.
  • the device is a single piece of mesh (e.g., monolithic).
  • the device is implantable in a subject. In some examples, the device is biocompatible. In some examples, the device is anatomically designed for the subject. In some examples, the anatomical location comprises at least a portion of a breast of the subject. In some examples, the anatomical location comprises a breast of the subject.
  • the device is configured to be stable for an amount of time after the device is implanted in the subject.
  • stable means that 10 wt% or less (e.g., 9% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4% or less, 3% or less, 2% or less, or 1% or less) of the device biodegrades over the selected time period after the device is implanted in the subject.
  • the device is configured to be stable for an amount of time of 6 weeks or more after the device is implanted in the subject (e.g., 7 weeks or more, 8 weeks or more, 9 weeks or more, 10 weeks or more, 11 weeks or more, 12 weeks or more, 13 weeks or more, 14 weeks or more, 15 weeks or more, 16 weeks or more, 17 weeks or more, 18 weeks or more, 19 weeks or more, 20 weeks or more, 21 weeks or more, 22 weeks or more, 23 weeks or more, 6 months or more, 7 months or more, 8 months or more, 9 months or more, 10 months or more, 11 months or more, 12 months or more, 13 months or more, 14 months or more, 15 months or more, 16 months or more, 17 months or more, 18 months or more, 19 months or more, 20 months or more, 21 months or more, 22 months or more, 23 months or more, 24 months or more, 25 months or more, 26 months or more, 27 months or more, 28 months or more, 29 months or more, 30 months or more, 31 months or more, 32 months or
  • the device is configured to be stable for an amount of time of 5 years or less after the device is implanted in the subject (e.g., 4.5 years or less, 4 years or less, 3.5 years or less, 36 months or less, 35 months or less, 34 months or less, 33 months or less, 32 months or less, 31 months or less, 30 months or less, 29 months or less, 28 months or less, 27 months or less, 26 months or less, 25 months or less, 24 months or less, 23 months or less, 22 months or less, 21 months or less, 20 months or less, 19 months or less, 18 months or less, 17 months or less, 16 months or less, 15 months or less, 14 months or less, 13 months or less, 12 months or less, 11 months or less, 10 months or less, 9 months or less, 8 months or less, 7 months or less, 6 months or less, 23 weeks or less, 22 weeks or less, 21 weeks or less, 20 weeks or less, 19 weeks or less, 18 weeks or less, 17 weeks or less, 16 weeks or less, 15 weeks or less, 14
  • the amount of time for which the device is configured to be stable can range from any of the minimum values described above to any of the maximum values described above.
  • the device can be configured to be stable for an amount of time of from 6 weeks to 5 years after the device is implanted in the subject (e.g., from 6 weeks to 6 months, from 6 months to 5 years, from 6 weeks to 12 weeks, from 12 weeks to 18 weeks, from 18 weeks to 6 months, from 6 months to 12 months, from 12 months to 18 months, from 18 months to 24 months, from 24 months to 30 months, from 30 months to 36 months, from 36 months to 5 years, from 7 weeks to 5 years, from 6 weeks to 4.5 years, from 7 weeks to 4.5 years, from 8 weeks to 5 years, from 10 weeks to 5 years, from 12 weeks to 5 years, from 16 weeks to 5 years, from 20 weeks to 5 years, from 6 months to 5 years, from 8 months to 5 years, from 10 months to 5 years, from 12 months to 5 years, from 18 months to 5 years, from 24 months to 5 years, or from 30 months to 5 years
  • the device is produced by additive manufacturing (e.g., 3D printing).
  • the device 100 comprises a mesh with a plurality of zones, such as a support zone 104 and an elastic zone 108.
  • the support zone 104 is elastic along one direction.
  • the mesh further has a thickness 130, for example as shown in Figure 18.
  • the device 100 comprises a mesh with a plurality of zones, such as a fat grafting zone 102, a support zone 104, a transition zone 106, and an elastic zone 108.
  • the fat grafting zone 102 has little to no elasticity.
  • the support zone 104 is elastic along one direction.
  • the elastic zone 108 has a high amount of elasticity in multiple directions.
  • the transition zone 106 is more elastic than the support zone 104 and less elastic than the elastic zone 108.
  • the device 100 can comprise a first elastic zone 108a and a second elastic zone 108b, the first elastic zone 108a being more elastic than the second elastic zone 108b.
  • the device 100 when in use, can be anchored to the chest wall of the subject, for example by securing (e.g., suturing) at least a portion of the device 100 to the chest wall of the subject.
  • securing e.g., suturing
  • the device 100 can include a slit 120 configured to receive the implant after the pocket is formed.
  • the slit can have a width selected in view of the size of the implant.
  • the slit 120 can, for example, can be 5 centimeters wide to accommodate receiving the implant.
  • the device 100 and/or the slit 120 can be secured, for example using sutures 122.
  • the pocket can be specifically designed for the shape of the patient and the shape of the implant inserted into it as a means of support.
  • the plurality of zones and/or the plurality of three-dimensional units are specifically designed to optimize the device for long term shape support of the implant and/or to minimize gravitational effects on the tissue.
  • the device has a surface area which can be selected in view of the anatomical location and dimensions thereof.
  • the surface area of the device can be selected to be comparable to the surface area of the anatomical location where the device is to be inserted.
  • the device and the anatomical location can each have an average lateral dimension, and the average lateral dimension of the device can be selected to be comparable to the average lateral dimension of the anatomical location where the device is to be inserted.
  • the methods can comprise making the device using additive manufacturing (e.g., 3D printing).
  • additive manufacturing e.g., 3D printing
  • the 3D model is based on an anatomical image of a subject.
  • the method further comprises collecting the anatomical image of the subject. Also disclosed herein are methods of treating a subject in need thereof, the methods comprising implanting the device into the subject.
  • the device is implanted into at least a portion breast of the subject.
  • the method can comprise breast reconstruction or augmentation (e.g., full or partial breast reconstruction or augmentation), for example after a lumpectomy or mastectomy.
  • the device is implanted into a breast of the subject.
  • the method can comprise breast reconstruction or augmentation (e.g., full or partial breast reconstruction or augmentation), for example after a lumpectomy or mastectomy.
  • the method further comprises anatomically designing the device for the subject.
  • the methods can comprise breast reconstruction (e.g., full or partial breast reconstruction) and treatment of an oncological disorder, such as breast cancer.
  • the devices can further include a therapeutic agent, for example for treatment of the oncological disorder.
  • the devices disclosed herein can be administered to a patient in need of treatment in combination with other antitumor or anti-cancer substances and/or with radiation and/or photodynamic therapy and/or with surgical treatment to remove a tumor.
  • these other substances or treatments can be given at the same as or at different times from the devices disclosed herein.
  • the devices disclosed herein can be used in combination with mitotic inhibitors such as taxol or vinblastine, alkylating agents such as cyclophosamide or ifosfamide, antimetabolites such as 5 -fluorouracil or hydroxyurea, DNA intercalators such as adriamycin or bleomycin, topoisomerase inhibitors such as etoposide or camptothecin, antiangiogenic agents such as angiostatin, antiestrogens such as tamoxifen, and/or other anti-cancer drugs or antibodies, such as, for example, GLEEVEC (Novartis Pharmaceuticals Corporation) and HERCEPTIN (Genentech, Inc.), respectively, or an immunotherapeutic such as ipilimumab and bortezomib.
  • mitotic inhibitors such as taxol or vinblastine
  • alkylating agents such as cyclophosamide or ifosfamide
  • antimetabolites such as 5 -fluorouracil
  • the 3D Matrix Mesh can allow customization and allow surgeons to control the implant position and prevent the need for submuscular implant placement.
  • Zone 1 primarily located at the superior part of the breast, is predominantly solid with minimal elasticity. This zone provides upper pole fullness and facilitates support to the implant, thereby enhancing the breast's natural shape.
  • a prototype of the 4D-printed matrix can be fabricated, incorporating distinct zones and materials. This prototype can allow mechanical properties and auxetic behaviors to be tested, verifying the interplay between zones, material compositions, and the overall structure of the interlocked fabric.
  • Integrating computational breast analysis with the 4D Bio Matrix technology can surgically achieve a breast reconstruction that mirrors the original breast shape.
  • the structure of the 4D Bio Matrix also has the capacity to support fat integration.
  • the approach herein involves a 4D-printed matrix constructed from bioresorbable polymers. This design isn't confined to two dimensions but has the capacity to house specific quantities of fat in each unit, adjustable based on the desired volume and design parameters.
  • the 3D printing method allows for customization based on the patient's scan, resulting in a personalized implant. It offers straightforward and reproducible fabrication, ensuring defect- free production and a faster manufacturing process. Additionally, the matrix’s compatibility with viable fat enhances its applicability in breast reconstruction.
  • the invention is the concept of a four-dimensional (4D) Bio Matrix for breast reconstruction, to provide support to the overlying skin post-mastectomy and which will be tailored to a patient's natural breast shape.
  • the 4D Bio Matrix can also support traditional implants.
  • the 4D Bio Matrix has promise to reduce the risk of implant rupture or displacement relative to current solutions.
  • the 4D Bio Matrix uses a computational breast analysis model to scan and match the patient's natural breast shape, and is a three-dimensional (3D) printed fabric-like matrix specifically designed to adapt to and enhance the natural properties of biological tissues, such as skin and muscle. Although physically three-dimensional the 4D Bio Matrix exhibits 4D behavior due to its ability to change and adapt over time.
  • This matrix is designed to encapsulate a breast implant, creating a three-dimensional shape that is both aesthetically pleasing and structurally robust.
  • the elasticity of the matrix also permits contraction and adaptation to fluctuations in the shape and size of the implant over time, consequently maintaining a natural appearance and feel. According to the inventors, it represents a significant advancement in the application of materials science and 3D printing technology in the field of medical implants.
  • the 4D Bio Matrix design will feature distinct regions with different mechanical properties to allow for tailored levels of elasticity and flexibility, ultimately providing an adaptable and custom fit for each patient’s unique needs. Distinct from traditional mesh technologies that rely on layered materials, the invention is constructed from bioresorbable polymers. This design isn't confined to two dimensions but has the capacity to house specific quantities of fat in each unit, adjustable based on the desired volume and design parameters.
  • the 3D matrix can use existing 3D printing technology.
  • the 3D printing method allows for customization based on the patient’s scan and it offers straightforward and reproducible fabrication, ensuring defect-free production and a faster manufacturing process.
  • the 4D Bio Matrix is characterized by auxetic properties allowing it to differentially control isotropic and anisotropic expansion. Auxetic materials exhibit counterintuitive behavior when subjected to tensile forces, such that the material expands perpendicularly to the applied force.
  • the matrix features properties strategically distributed across the breast envelope to ensure support and encourage fat in-growth in specific regions using the 3D segment units. For instance, the lower part of the breast that bears the implant’s weight would have a tighter, less elastic matrix pattern. Conversely, the matrix over the superior aspect of the breast, particularly above the nipple area, would possess a more stretchable design. This design allows maximum projection of the underlying implant and improves the overall breast shape. In its relaxed state, the matrix exhibits a relatively flat, compact structure.
  • Zone 1 primarily located at the superior part of the breast, is predominantly solid with minimal elasticity. This zone provides upper pole fullness and facilitates support to the implant, thereby enhancing the breast’s natural shape.
  • Zone 3 the auxetic zone, is placed on the anterior part of the breast. This zone is specifically designed to stretch and expand in all directions, thereby maximizing the breast's forward projection and enhancing the implant's aesthetic appearance.
  • the composition of the 4D Bio Matrix can be tailored to achieve optimal performance by utilizing a single polymer, multiple polymers, or a combination of materials designed to support and maintain the viability of fat-grafted cells within the wall of the construct.
  • the selection of materials can be based on various factors such as biocompatibility, elasticity, mechanical strength, and the ability to create an environment conducive to the survival and proliferation of the grafted fat cells.
  • the construct can potentially facilitate the integration of fat grafts into the surrounding tissue, thereby promoting improved aesthetic outcomes.
  • each material can be strategically selected and distributed throughout the zones or segments of the construct to optimize the desired mechanical, auxetic, and biological properties. For example, a more rigid polymer may be used in Zone 1 to provide support, while a more elastic or auxetic material could be implemented in Zones 2 and 3 to ensure proper contouring and projection.
  • the 3D mesh is fabricated using various bioresorbable polymers, including single polymers, copolymers, and other suitable materials. The goal is for the device to eventually biodegrade and be absorbed by the surrounding tissue. Different designs are being developed using the 3D printer, incorporating various unit geometries such as triangles, squares, hexagons, and other polygons. Circular base designs may also be explored.
  • the connectors between the units play a mechanical role, with a minimum of three and a maximum of ten connectors, providing different levels of mechanical resistance throughout the mesh.
  • silica theoretical model has been developed of the matrix, segmented into three zones with unique auxetic properties.
  • the model also considers biocompatibility, mechanical strength and cell survival support.
  • the model predicts favorable outcomes in stress distribution, implant rupture risk mitigation, and maintaining a natural appearance.
  • a prototype of the 4D-printed matrix can be fabricated with the following zones:
  • Fat Grafting Zone/Solid solid zone with no elasticity designed to maximize adipose tissue.
  • Support Zone/Pattern 1 designed to provide maximum support with a non-auxetic honeycomb structure that stretches in one direction. When elongated horizontally, vertical shortening occurs, maximizing breast support.
  • Transition Zone/Mix of Patterns 1 & 2 transitions between zones 1&2.
  • the fabrication will allow testing of mechanical properties and auxetic behaviors, verifying the interplay between zones, material compositions, and the overall structure of the interlocked fabric.
  • Bioresorbable Polymer to create structures that can safely degrade in the body over time.
  • Adipose Cellular Stromal Matrix to support the viability and integration of fat cells within the Matrix.
  • a feature for cases with a skin defect can be prototyped using a solid Matrix component that would align with skin growth-promoting stroma to facilitate epithelization and skin coverage.
  • Customizing a solid matrix patch for skin replacement is possible, which aligns with skin keratinocyte-promoting factors for skin epithelization.
  • Example 1 A device configured to be inserted into an anatomical location of a subject, the device comprising a mesh with a plurality of zones having different elastic properties, each zone having a composition and a geometry, wherein the different elastic properties are based on the composition, the geometry, or combination thereof, wherein the mesh further has a thickness configured to receive and hold adipose tissue.
  • Example 2 The device of any examples herein, particularly example 1, wherein the thickness of the mesh is 2 centimeters or less.
  • Example 3 The device of any examples herein, particularly example 1 or example 2, wherein the thickness is from 0.4 centimeters to 2 centimeters, or from 0.5 to 2 centimeters.
  • Example 4 The device of any examples herein, particularly examples 1-3, wherein the mesh comprises a plurality of three-dimensional units, the plurality of three-dimensional units being interconnected to form the mesh.
  • Example 5 A device configured to be inserted into an anatomical location of a subject, the device comprising a mesh with a plurality of zones having different elastic properties, each zone having a composition and a geometry, wherein the different elastic properties are based on the composition, the geometry, or combination thereof, wherein the mesh comprises a plurality of three-dimensional units, the plurality of three-dimensional units being interconnected to form the mesh.
  • Example 6 The device of any examples herein, particularly examples 1-5, wherein the mesh is disposed on a membrane, such as a second mesh.
  • Example 7 The device of any examples herein, particularly examples 1 -6, wherein at least a portion of the mesh and/or at least a portion of a volume defined by the mesh and the membrane is configured to receive and hold adipose tissue.
  • Example 8 The device of any examples herein, particularly examples 4-7, wherein at least a portion of each of the plurality of three-dimensional units is configured to receive and hold adipose tissue.
  • Example 9 The device of any examples herein, particularly examples 4-8, wherein each of the three-dimensional units comprises a platform, a pillar, and one or more tubules.
  • Example 10 The device of any examples herein, particularly examples 4-9, wherein the pillar can provide a desired mechanical property and/or define a volume configured to receive and hold adipose tissue.
  • Example 11 The device of any examples herein, particularly examples 4-10, wherein the pillar is solid or hollow.
  • Example 16 The device of any examples herein, particularly examples 4-15, wherein each tubule is solid or hollow.
  • Example 18 The device of any examples herein, particularly examples 4-17, wherein each tubule has an average diameter of 1.6 millimeters or less.
  • Example 19 The device of any examples herein, particularly examples 4-18, wherein the platform can have any suitable geometry, such as polygonal (e.g., triangular, rectangular, hexagonal, etc.) or circular.
  • Example 20 The device of any examples herein, particularly examples 4-19, wherein each three-dimensional unit further comprises a base, the pillar extending from the base to the platform.
  • Example 21 The device of any examples herein, particularly example 20, wherein the base has any suitable geometry, such as polygonal (e.g., triangular, rectangular, hexagonal) or circular.
  • Example 22 The device of any examples herein, particularly example 20 or example 21, wherein the base and the platform are the same or different.
  • Example 23 The device of any examples herein, particularly examples 4-22, wherein the base (when present) and/or the platform each independently has a planar surface.
  • Example 24 The device of any examples herein, particularly examples 4-23, wherein the base (when present) and/or the platform each independently has an average characteristic dimension, wherein the average characteristic dimension is from 0.4 to 4 centimeters, such as from 0.5 to 4 centimeters.
  • Example 25 The device of any examples herein, particularly examples 4-24, wherein the base (when present) and/or the platform are each triangular, the average characteristic dimension being the average length of the side of the triangle, the average characteristic dimension being from 0.4 to 4 centimeters.
  • Example 26 The device of any examples herein, particularly examples 4-25, wherein the base (when present) and/or the platform are each hexagonal, the average characteristic dimension being the average diameter of the hexagon, the average characteristic dimension being from 0.5 to 4 centimeters.
  • Example 27 The device of any examples herein, particularly examples 4-26, wherein each three dimensional unit has an average height, measured from the platform to the bottom of the pillar or measured from the platform to the base (when present), wherein the average height is 2 centimeters or less.
  • Example 28 The device of any examples herein, particularly examples 4-27, wherein the average height is from 0.4 centimeters to 2 centimeters, such as from 0.5 to 2 centimeters.
  • Example 29 The device of any examples herein, particularly examples 4-28, wherein the platform, the pillar, the base (when present), and the one or more tubules are integrally formed.
  • Example 30 The device of any examples herein, particularly examples 4-29, wherein each of the three-dimensional units has volume configured to receive and hold adipose tissue, the volume of each of the three-dimensional units independently being from 0.1 to 25 cm 3 .
  • Example 31 The device of any examples herein, particularly examples 4-30, wherein neighboring three-dimensional units are connected to each other to form the mesh.
  • Example 32 The device of any examples herein, particularly examples 4-31, wherein the one or more tubules are configured to connect neighboring three-dimensional units to each other to form the mesh.
  • Example 34 The device of any examples herein, particularly examples 4-33, wherein the mesh is integrally formed, for example by 3D printing.
  • Example 35 The device of any examples herein, particularly examples 4-34, wherein the mesh comprises a plurality of three-dimensional units as shown in one or more of Figure 36A- Figure 49.
  • Example 36 The device of any examples herein, particularly examples 1-35, wherein the composition of each of the plurality of zones and/or each of the plurality of three dimensional units comprises an isotropic material, an anisotropic material, an auxetic material, a non-auxetic material, or a combination thereof.
  • Example 37 The device of any examples herein, particularly examples 1-36, wherein the geometry of each of the plurality of zones and/or each of the plurality of three dimensional units comprises an auxetic geometry, a non-auxetic geometry, or a combination thereof.
  • Example 38 The device of any examples herein, particularly examples 1-37, wherein the mesh comprises a fat grafting zone having little to no elasticity.
  • Example 39 The device of any examples herein, particularly example 38, wherein the fat grafting zone comprises adipose tissue.
  • Example 40 The device of any examples herein, particularly examples 1-39, wherein the adipose tissue comprises autologous adipose tissue.
  • Example 41 The device of any examples herein, particularly examples 1-40, wherein the mesh comprises a support zone, the support zone being elastic along one direction.
  • Example 42 The device of any examples herein, particularly example 41, wherein the support zone has a non-auxetic geometry.
  • Example 43 The device of any examples herein, particularly example 41 or example 42, wherein the support zone comprises an anisotropic material, a non-auxetic material, or a combination thereof.
  • Example 44 The device of any examples herein, particularly examples 1-43, wherein the mesh comprises an elastic zone, the elastic zone having a high amount of elasticity in multiple directions.
  • Example 45 The device of any examples herein, particularly example 44, wherein the elastic zone has an auxetic geometry.
  • Example 46 The device of any examples herein, particularly example 44 or example 45, wherein the elastic zone comprises an isotropic material, an auxetic material, or a combination thereof.
  • Example 47 The device of any examples herein, particularly examples 1-46, wherein the mesh comprises a transition zone, the transition zone being more elastic than the support zone and less elastic than the elastic zone.
  • Example 48 The device of any examples herein, particularly examples 1-47, wherein the mesh comprises a skin defect zone, the skin defect zone being aligned with skin-growth promoting stroma such that the skin defect zone facilitates epithelization and skin coverage when implanted in the subject.
  • Example 49 The device of any examples herein, particularly examples 1-48, wherein the plurality of zones and/or the plurality of three-dimensional units each have a different composition, a different geometry, or a combination thereof.
  • Example 50 The device of any examples herein, particularly examples 1-49, wherein the plurality of zones and/or the plurality of three-dimensional units have the same composition and different geometries, such that the different properties are based on the geometry of each zone and/or unit.
  • Example 51 The device of any examples herein, particularly examples 1-50, wherein the plurality of zones and/or the plurality of three-dimensional units each have a different composition and a different geometry.
  • Example 52 The device of any examples herein, particularly examples 1-51, wherein the composition of each of the plurality of zones and/or at least a portion of each of the plurality of three-dimensional units independently comprises a polymer such as a bioresorbable polymer, collagen, adipose cellular stromal matrix, adipose tissue, or a combination thereof.
  • a polymer such as a bioresorbable polymer, collagen, adipose cellular stromal matrix, adipose tissue, or a combination thereof.
  • Example 53 The device of any examples herein, particularly examples 1-52, wherein one or more of the plurality of zones, one or more of the plurality of three-dimensional units, at least a portion of each of the plurality of three-dimensional units, or a combination thereof independently is porous.
  • Example 54 The device of any examples herein, particularly examples 1-53, wherein the composition of one or more of the plurality of zones, one or more of the plurality of three- dimensional units, at least a portion of each of the plurality of three-dimensional units, or a combination thereof independently comprises poly(ethylene glycol) diacrylate (PEGDA), poly (ethylene glycol) dimethacrylate (PEGDMA), poly (ethylene glycol) diacrylamide (PEGDAAm), gelatin methacrylate (GelMA), collagen methacrylate, silk methacrylate, hyaluronic acid methacrylate, chondroitin sulfate methacrylate, elastin methacrylate, cellulose acrylate, dextran methacrylate, heparin methacrylate, NIPAAm methacrylate, Chitosan methacrylate, polyethylene glycol norbornene, polyethylene glycol dithiol, thiolated gelatin, thiolated chitosan, thiolated silk, silk
  • Example 55 The device of any examples herein, particularly examples 1-54, wherein the composition of one or more of the plurality of zones, one or more of the plurality of three- dimensional units, at least a portion of each of the plurality of three-dimensional units, or a combination thereof independently comprises aliphatic poly-isocyanate, poly-aliphatic isocyanates, poly-4-hudroxybutyrate, poly(l-lactide) (PLLA), bioceramic particles, L-lactide (LLA), sub-dermal explant comprising polycaprolactone (PCL), polyurethane, poly(D) lactide, poly(lactic-co-glycolic) acid, poly(a-hydroxy acids), cross-linked polyester hydrogels, poly(orthoesters), poly anhydrides, or a combination thereof.
  • aliphatic poly-isocyanate poly-aliphatic isocyanates
  • poly-4-hudroxybutyrate poly(l-lactide) (PLLA), biocera
  • Example 56 The device of any examples herein, particularly examples 1-55, wherein the composition of one or more of the plurality of zones, one or more of the plurality of three- dimensional units, at least a portion of each of the plurality of three-dimensional units, or a combination thereof independently comprises a polyester, such as poly(glycerol-dodecanoate) (PGD).
  • PWD poly(glycerol-dodecanoate)
  • Example 57 The device of any examples herein, particularly examples 1-56, wherein the composition of one or more of the plurality of zones, one or more of the plurality of three- dimensional units, at least a portion of each of the plurality of three-dimensional units, or a combination thereof independently comprises a poly(ether-ester).
  • Example 58 The device of any examples herein, particularly examples 1-57, wherein the composition of one or more of the plurality of zones, one or more of the plurality of three- dimensional units, at least a portion of each of the plurality of three-dimensional units, or a combination thereof independently comprises polydioxanone (PDO).
  • PDO polydioxanone
  • Example 59 The device of any examples herein, particularly examples 1-58, wherein the composition of each of the plurality of zones and/or each of the plurality of three-dimensional units comprises polydioxanone (PDO).
  • PDO polydioxanone
  • Example 60 The device of any examples herein, particularly examples 1-59, wherein the composition of one or more of the plurality of zones, one or more of the plurality of three- dimensional units, at least a portion of each of the plurality of three-dimensional units, or a combination thereof independently comprises a polyolefin, such as polypropylene.
  • a polyolefin such as polypropylene
  • Example 61 The device of any examples herein, particularly examples 1-60, wherein the composition of each of the one or more of the plurality of zones, one or more of the plurality of three-dimensional units, at least a portion of each of the plurality of three-dimensional units, or a combination thereof independently comprises polyglycolic acid (PGA).
  • PGA polyglycolic acid
  • Example 62 The device of any examples herein, particularly examples 1-61, wherein the composition of each of the one or more of the plurality of zones, one or more of the plurality of three-dimensional units, at least a portion of each of the plurality of three-dimensional units, or a combination thereof independently comprises a bioink.
  • Example 63 The device of any examples herein, particularly examples 1-62, wherein the device further comprises a therapeutic agent dispersed within the composition of one or more of the plurality of zones, one or more of the plurality of three-dimensional units, at least a portion of each of the plurality of three-dimensional units, or a combination thereof.
  • Example 64 The device of any examples herein, particularly example 63, wherein the therapeutic agent is dispersed substantially homogeneously throughout the zone(s), the three- dimensional units, and/or device.
  • Example 65 The device of any examples herein, particularly example 63 or example 64, wherein the therapeutic agent comprises an anticancer agent, anti-inflammatory agent, analgesic agent, antimicrobial agent, or a combination thereof.
  • Example 66 The device of any examples herein, particularly examples 63-65, wherein the therapeutic agent comprises a chemotherapeutic agent, an immunotherapeutic agent, or a combination thereof.
  • Example 67 The device of any examples herein, particularly examples 1-66, wherein the device is configured to be stable for an amount of time of from 6 weeks to 5 years weeks after the device is implanted in the subject.
  • Example 68 The device of any examples herein, particularly examples 1-67, wherein the device comprises a support zone and an elastic zone.
  • Example 69 The device of any examples herein, particularly examples 1-68, wherein the device comprises a fat grafting zone, a support zone, a transition zone, and an elastic zone.
  • Example 40 The device of any examples herein, particularly examples 1-69, wherein the device comprises a first elastic zone and a second elastic zone, the first elastic zone being more elastic than the second elastic zone.
  • Example 71 The device of any examples herein, particularly examples 1-70, wherein the device has a periphery and the device further comprises a cuff extending from at least a portion of the periphery of the device.
  • Example 72 The device of any examples herein, particularly example 71, wherein the cuff forms a pocket.
  • Example 73 The device of any examples herein, particularly examples 1-72, wherein the device is configured to support and/or reshape at least a portion of an organ and/or at least a portion of an implant when inserted in the subject.
  • Example 74 The device of any examples herein, particularly examples 1-73, wherein the device is configured to support and/or reshape an organ and/or an implant when inserted in the subject.
  • Example 75 The device of any examples herein, particularly examples 1-74, wherein the anatomical location comprises a breast of the subject.
  • Example 76 The device of any examples herein, particularly example 75, wherein the device is configured to support at least a portion of a breast or at least a portion of a breast implant.
  • Example 77 The device of any examples herein, particularly example 75 or example 76, wherein the device is configured to support a breast or a breast implant.
  • Example 78 The device of any examples herein, particularly examples 1-77, wherein the device is formed from a model based on a tessellation of polyhedrons.
  • Example 79 The device of any examples herein, particularly examples 1-78, wherein the device is formed from a computational 3D space-filling model.
  • Example 80 The device of any examples herein, particularly examples 1-79, wherein the device is not flat.
  • Example 81 The device of any examples herein, particularly examples 1-80, wherein the device has a three dimensional shape.
  • Example 82 The device of any examples herein, particularly examples 1-81, wherein the device has a three-dimensional parametric teardrop shape.
  • Example 83 The device of any examples herein, particularly examples 1-82, wherein the device is substantially flat before insertion and can stretch to a three dimensional teardrop shape that conforms to support and/or reshape an organ and/or an implant when inserted in the subject.
  • Example 84 The device of any examples herein, particularly examples 1-83, wherein the device has a three-dimensional parametric teardrop shape following the Fibonacci equation.
  • Example 85 The device of any examples herein, particularly examples 1-84, wherein the device is anatomically designed for the subject.
  • Example 86 The device of any examples herein, particularly examples 1-85, wherein the device is produced by additive manufacturing (e.g., 3D printing).
  • additive manufacturing e.g., 3D printing
  • Example 87 The device of any examples herein, particularly examples 1-86, wherein the device is a single piece of mesh (e.g., monolithic).
  • Example 88 The device of any examples herein, particularly examples 1-87, wherein the device is biocompatible.
  • Example 89 A method of manufacturing the device of any examples herein, particularly examples 1-88, the method comprising making the device using additive manufacturing (e.g., 3D printing).
  • additive manufacturing e.g., 3D printing
  • Example 90 The method of any examples herein, particularly example 89, wherein the method comprises making the device based on a 3D model.
  • Example 91 The method of any examples herein, particularly example 90, wherein the 3D model is based on the Fibonacci equation.
  • Example 92 The method of any examples herein, particularly example 90 or example 91, wherein the 3D model is based on an anatomical image of a subject.
  • Example 93 The method of any examples herein, particularly example 92, wherein the method further comprises collecting the anatomical image of the subject.
  • Example 94 A method of treating a subject in need thereof, the method comprising implanting the device of any examples herein, particularly examples 1-88 into the subject.
  • Example 95 The method of any examples herein, particularly example 94, wherein the device is implanted into at least a portion of a breast of the subject.
  • Example 96 The method of any examples herein, particularly example 95, wherein the method comprises breast reconstruction or augmentation (e.g., full or partial breast reconstruction or augmentation), such as after a lumpectomy or mastectomy.
  • Example 97 The method of any examples herein, particularly example 94, wherein the device is implanted into a breast of the subject.
  • Example 98 The method of any examples herein, particularly example 97, wherein the method comprises breast reconstruction or augmentation.
  • Example 99 The method of any examples herein, particularly examples 94-98, wherein the method further comprises anatomically designing the device for the subject.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Vascular Medicine (AREA)
  • Molecular Biology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Zoology (AREA)
  • Urology & Nephrology (AREA)
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  • Dispersion Chemistry (AREA)
  • Manufacturing & Machinery (AREA)
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Abstract

La présente invention concerne des dispositifs et leurs procédés de fabrication et d'utilisation.
PCT/US2024/059957 2023-12-15 2024-12-13 Dispositifs et leurs procédés de fabrication et d'utilisation Pending WO2025128946A1 (fr)

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US63/610,537 2023-12-15

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090082864A1 (en) * 2007-09-19 2009-03-26 Gaoyuan Gavin Chen Naturally contoured, preformed, three dimensional mesh device for breast implant support
US20210022848A1 (en) * 2018-09-07 2021-01-28 Musculoskeletal Transplant Foundation Soft tissue repair grafts and processes for preparing and using same
US20210052367A1 (en) * 2018-02-06 2021-02-25 The Trustees Of The University Of Pennsylvania The kirigami modification of biomedical tissue reinforcing meshes and matrices for expansile two-to-three dimensional conversion
US20230119855A1 (en) * 2021-10-14 2023-04-20 The Methodist Hospital System Hydrogel devices and methods of making and use thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090082864A1 (en) * 2007-09-19 2009-03-26 Gaoyuan Gavin Chen Naturally contoured, preformed, three dimensional mesh device for breast implant support
US20210052367A1 (en) * 2018-02-06 2021-02-25 The Trustees Of The University Of Pennsylvania The kirigami modification of biomedical tissue reinforcing meshes and matrices for expansile two-to-three dimensional conversion
US20210022848A1 (en) * 2018-09-07 2021-01-28 Musculoskeletal Transplant Foundation Soft tissue repair grafts and processes for preparing and using same
US20230119855A1 (en) * 2021-10-14 2023-04-20 The Methodist Hospital System Hydrogel devices and methods of making and use thereof

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