Devices and methods of making and use thereof

Abstract

Disclosed herein are devices and methods of making and use thereof.

Description

[0001] DEVICES AND METHODS OF MAKING AND USE THEREOF

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims the benefit of priority to U.S. Provisional Application No. 63 / 610,537 filed December 15, 2023, which is hereby incorporated herein by reference in its entirety.

[0004] BACKGROUND

[0005] 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.

[0006] Traditionally, silicone breast implants have been widely used for reconstruction. Among the options available, there are textured shaped implants designed to maintain their shape through a velcro-like texturing effect, preventing rotation. Tn contrast, round smooth implants, due to their smooth surface, may rotate freely and therefore need to maintain a round shape. However, recent advancements have raised concerns regarding the safety of textured implants.

[0007] In response to the growing concerns, the U.S. Food and Drug Administration (FDA) has implemented regulatory measures to address the safety issues associated with textured implants. Notably, 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.

[0008] In light of these safety concerns, it is crucial to develop innovative approaches that can overcome the limitations of textured implants. Strategic compression and / or elasticity offer promising avenues to address this challenge. By incorporating these techniques, alternative methods can be devised to support the tissue and / or implant effectively, while also allowing for the desired tear drop breast shape

[0009] Current solutions for providing support to an underlying organ and / or implant include ADM (acellular dermal matrix) and fabric / 2D mesh structures, all of which suffer from various limitations. With current technologies and techniques needing improvement, new methods and devices are necessary. The devices and methods discussed herein address these and other needs.

[0010] SUMMARY

[0011] In accordance with the purposes of the disclosed devices and methods as embodied and broadly described herein, the disclosed subject matter relates to devices and methods of making and use thereof.

[0012] For example, disclosed herein are devices configured to be inserted into an anatomical location of a subject. In some examples, the devices comprise 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. In some examples, the thickness of the mesh is 2 centimeters or less. In some examples, the thickness is from 0.4 centimeters to 2 centimeters, or from 0.5 to 2 centimeters.

[0013] In some examples, the mesh comprises a plurality of three-dimensional units, the plurality of three-dimensional units being interconnected to form the mesh.

[0014] Also disclosed herein are 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.

[0015] In some examples, the mesh is disposed on a membrane, such as a second mesh.

[0016] In some examples, 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.

[0017] In some examples, at least a portion of each of the plurality of three-dimensional units is configured to receive and hold adipose tissue.

[0018] In some examples, each of the three-dimensional units comprises a platform, a pillar, and one or more tubules.

[0019] In some examples, the pillar can provide a desired mechanical property and / or define a volume configured to receive and hold adipose tissue.

[0020] In some examples, the pillar is solid or hollow.

[0021] In some examples, the pillar is hollow, such that the pillar comprises a wall defining a lumen, the lumen being configured to receive and hold adipose tissue. In some examples, each of the one or more tubules extends from the platform to the pillar, thereby connecting the platform and the pillar.

[0022] In some examples, the one or more tubules can provide a desired mechanical property.

[0023] In some examples, each three-dimensional unit can have from 3 to 10 tubules.

[0024] In some examples, each tubule is solid or hollow.

[0025] In some examples, each tubule is hollow, such that each tubule comprises a wall defining a lumen, the lumen being configured to receive and hold adipose tissue.

[0026] In some examples, each tubule has an average diameter of 1.6 millimeters or less.

[0027] In some examples, the platform can have any suitable geometry, such as polygonal (e.g., triangular, rectangular, hexagonal, etc.) or circular.

[0028] In some examples, each three-dimensional unit further comprises a base, the pillar extending from the base to the platform.

[0029] In some examples, the base has any suitable geometry, such as polygonal (e.g., triangular, rectangular, hexagonal) or circular.

[0030] In some examples, the base and the platform are the same or different.

[0031] In some examples, the base (when present) and / or the platform each independently has a planar surface.

[0032] In some examples, 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.

[0033] In some examples, 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.

[0034] In some examples, 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.

[0035] In some examples, 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.

[0036] In some examples, the average height is from 0.4 centimeters to 2 centimeters, such as from 0.5 to 2 centimeters.

[0037] In some examples, the platform, the pillar, the base (when present), and the one or more tubules are integrally formed. In some examples, 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 cm3.

[0038] In some examples, neighboring three-dimensional units are connected to each other to form the mesh.

[0039] In some examples, the one or more tubules are configured to connect neighboring three- dimensional units to each other to form the mesh.

[0040] In some examples, the one of more tubules of neighboring three-dimensional units are interwoven to thereby connect neighboring three-dimensional units to each other.

[0041] In some examples, the mesh is integrally formed, for example by 3D printing.

[0042] In some examples, the mesh comprises a plurality of three-dimensional units as shown in one or more of Figure 36A-Figure 49.

[0043] In some examples, 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.

[0044] In some examples, 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.

[0045] In some examples, the mesh comprises a fat grafting zone having little to no elasticity.

[0046] In some examples, the fat grafting zone comprises adipose tissue.

[0047] In some examples, the adipose tissue comprises autologous adipose tissue.

[0048] In some examples, the mesh comprises a support zone, the support zone being elastic along one direction.

[0049] In some examples, the support zone has a non-auxetic geometry.

[0050] In some examples, the support zone comprises an anisotropic material, a non-auxetic material, or a combination thereof.

[0051] In some examples, the mesh comprises an elastic zone, the elastic zone having a high amount of elasticity in multiple directions.

[0052] In some examples, the elastic zone has an auxetic geometry.

[0053] In some examples, the elastic zone comprises an isotropic material, an auxetic material, or a combination thereof.

[0054] In some examples, the mesh comprises a transition zone, the transition zone being more elastic than the support zone and less elastic than the elastic zone. In some examples, 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.

[0055] In some examples, the plurality of zones and / or the plurality of three-dimensional units each have a different composition, a different geometry, or a combination thereof.

[0056] In some examples, 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.

[0057] In some examples, the plurality of zones and / or the plurality of three-dimensional units each have a different composition and a different geometry.

[0058] In some examples, 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.

[0059] In some examples, 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.

[0060] In some examples, 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-adhesive poly(ethylene glycol), MMP-sensitive poly(ethylene glycol), PEGylated fibrinogen, 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.

[0061] In some examples, 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), polyanhydrides, or a combination thereof.

[0062] In some examples, 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).

[0063] In some examples, 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).

[0064] In some examples, 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).

[0065] In some examples, the composition of each of the plurality of zones and / or each of the plurality of three-dimensional units comprises polydioxanone (PDO).

[0066] In some examples, 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.

[0067] In some examples, 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).

[0068] In some examples, 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.

[0069] In some examples, 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.

[0070] In some examples, the therapeutic agent is dispersed substantially homogeneously throughout the zone(s), the three-dimensional units, and / or device. In some examples, the therapeutic agent comprises an anticancer agent, antiinflammatory agent, analgesic agent, antimicrobial agent, or a combination thereof.

[0071] In some examples, the therapeutic agent comprises a chemotherapeutic agent, an immunotherapeutic agent, or a combination thereof.

[0072] In some examples, 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.

[0073] In some examples, the device comprises a support zone and an elastic zone.

[0074] In some examples, the device comprises a fat grafting zone, a support zone, a transition zone, and an elastic zone.

[0075] In some examples, the device comprises a first elastic zone and a second elastic zone, the first elastic zone being more elastic than the second elastic zone.

[0076] In some examples, the device has a periphery and the device further comprises a cuff extending from at least a portion of the periphery of the device.

[0077] In some examples, the cuff forms a pocket.

[0078] In some examples, 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.

[0079] In some examples, the device is configured to support and / or reshape an organ and / or an implant when inserted in the subject.

[0080] In some examples, the anatomical location comprises a breast of the subject.

[0081] In some examples, the device is configured to support at least a portion of a breast or at least a portion of a breast implant.

[0082] In some examples, the device is configured to support a breast or a breast implant.

[0083] In some examples, the device is formed from a model based on a tessellation of polyhedrons.

[0084] In some examples, the device is formed from a computational 3D space- filling model.

[0085] In some examples, the device is not flat.

[0086] In some examples, the device has a three dimensional shape.

[0087] In some examples, the device has a three-dimensional parametric teardrop shape.

[0088] In some examples, 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.

[0089] In some examples, the device has a three-dimensional parametric teardrop shape following the Fibonacci equation.

[0090] In some examples, the device is anatomically designed for the subject. In some examples, the device is produced by additive manufacturing (e.g., 3D printing).

[0091] In some examples, the device is a single piece of mesh (e.g., monolithic).

[0092] In some examples, the device is biocompatible.

[0093] Also disclosed herein are methods of manufacturing any of the devices disclosed herein. In some examples, the methods comprise making the device using additive manufacturing (e.g., 3D printing).

[0094] In some examples, the method comprises making the device based on a 3D model.

[0095] In some examples, the 3D model is based on the Fibonacci equation.

[0096] In some examples, the 3D model is based on an anatomical image of a subject.

[0097] In some examples, the method further comprises collecting the anatomical image of the subject.

[0098] Also disclosed herein are methods of treating a subject in need thereof, the methods comprising implanting any of the devices disclosed herein into the subject.

[0099] In some examples, the device is implanted into at least a portion of a breast of the subject.

[0100] In some examples, the method comprises breast reconstruction or augmentation (e.g., full or partial breast reconstruction or augmentation), such as after a lumpectomy or mastectomy.

[0101] In some examples, the device is implanted into a breast of the subject.

[0102] In some examples, the method comprises breast reconstruction or augmentation.

[0103] In some examples, the method further comprises anatomically designing the device for the subject.

[0104] Additional advantages of the disclosed devices and methods will be set forth in part in the description which follows, and in part will be obvious from the description. The advantages of the disclosed devices and methods will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the disclosed systems and methods, as claimed.

[0105] The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims.

[0106] BRIEF DESCRIPTION OF THE FIGURES

[0107] The accompanying figures, which are incorporated in and constitute a part of this specification, illustrate several aspects of the disclosure, and together with the description, serve to explain the principles of the disclosure. Figure 1. AP frontal view with legend.

[0108] Figure 2. AP frontal view.

[0109] Figure 3. Bottom up view (worm’s eye).

[0110] Figure 4. Lateral view.

[0111] Figure 5. Oblique Inferior view.

[0112] Figure 6. Oblique inferior view (zoomed out).

[0113] Figure 7. Superior view (bird’s eye).

[0114] Figure 8. Oblique view lateral.

[0115] Figure 9. Oblique view medial.

[0116] Figure 10. Additional design

[0117] Figure 11. Diagram of nonauxetic (honeycomb) structure deformation mechanism.

[0118] Figure 12. Diagram of auxetic (reentrant) structure deformation mechanism.

[0119] Figure 13. Deformation of auxetic and conventional materials.

[0120] Figure 14a- Figure 14b. Cell deformation by inclined cell member bending (Figure 14a) loaded in X-direction, (Figure 14b) loaded in Y direction.

[0121] Figure 15. Rigid rectangles connected together at their vertices through hinges and deforming by rotating.

[0122] Figure 16. Anatomical image of subject with Fibonacci curve overlaid.

[0123] Figure 17. Schematic view of an example device as disclosed herein according to one implementation.

[0124] Figure 18. Schematic cut away side view of an example device in use within a breast of a subject as disclosed herein according to one implementation.

[0125] Figure 19. Schematic view of an example device as disclosed herein according to one implementation.

[0126] Figure 20. Schematic view of an example device as disclosed herein according to one implementation.

[0127] Figure 21. Schematic view of an example device as disclosed herein according to one implementation.

[0128] Figure 22. Schematic cut away side view of an example device in use within a breast of a subject as disclosed herein according to one implementation.

[0129] Figure 23. Schematic cut away side view of an example device in use within a breast of a subject as disclosed herein according to one implementation.

[0130] Figure 24. Schematic view of an example device as disclosed herein according to one implementation. Figure 25. Schematic view of an example device as disclosed herein according to one implementation.

[0131] Figure 26. Schematic cut away side view of an example device in use within a breast of a subject as disclosed herein according to one implementation.

[0132] Figure 27. Schematic cut away side view of an example device in use within a breast of a subject as disclosed herein according to one implementation.

[0133] Figure 28. Schematic cut away side view of an example device in use within a breast of a subject as disclosed herein according to one implementation.

[0134] Figure 29. Schematic view of an example device as disclosed herein according to one implementation.

[0135] Figure 30. Schematic view of an example device as disclosed herein according to one implementation.

[0136] Figure 31. Schematic view of an example device as disclosed herein according to one implementation.

[0137] Figure 32. Schematic view of an example device as disclosed herein according to one implementation.

[0138] Figure 33. Schematic view of an example device as disclosed herein according to one implementation.

[0139] Figure 34. Schematic view of an example device as disclosed herein according to one implementation.

[0140] Figure 35. Schematic view of an example device as disclosed herein according to one implementation.

[0141] Figure 36A. Schematic view of an example single unit having a hexagonal geometry. Connectors indicated with stars. The unit can have a volume to contain fat.

[0142] Figure 36B. Alternative schematic view of the hexagonal unit of Figure 36A.

[0143] Figure 36C. Side view of the hexagonal unit of Figure 36A and Figure 36B.

[0144] Figure 36D. Schematic view of an example mesh / fabric comprising a plurality of the hexagonal units of Figure 36A-Figure 36C.

[0145] Figure 36E. Alternative schematic view of mesh / fabric of Figure 36D.

[0146] Figure 36F. Schematic view of an example single unit having a triangular geometry. Connectors indicated with stars. The unit can have a volume to contain fat.

[0147] Figure 36G. Alternative schematic view of the hexagonal unit of Figure 36E.

[0148] Figure 36H. Side view of the hexagonal unit of Figure 36E and Figure 36F. Figure 361. Schematic view of an example mesh / fabric comprising a plurality of the triangular units of Figure 36F-Figure 36H.

[0149] Figure 36J. Alternative schematic view of mesh / fabric of Figure 361.

[0150] Figure 37A-Figure 37C. Schematic diagram of different views of an example three- dimensional unit comprising a platform with a triangular geometry.

[0151] Figure 38A-Figure 38C. Schematic diagram of different views of an example three- dimensional unit comprising a platform with a triangular geometry.

[0152] Figure 39. Schematic diagrams of different views of an example three-dimensional unit comprising a platform with a triangular geometry.

[0153] Figure 40. Schematic diagram of an example mesh / fabric comprising a plurality of the triangular units.

[0154] Figure 41. Alternative schematic view of the mesh / fabric of Figure 40.

[0155] Figure 42. Magnified view of Figure 41 showing the interconnected tubules.

[0156] Figure 43A - Figure 43C. Schematic diagram of different views of an example three- dimensional unit comprising a platform with a hexagonal geometry.

[0157] Figure 44A - Figure 44C. Schematic diagram of different views of an example three- dimensional unit comprising a platform with a hexagonal geometry.

[0158] Figure 45. Schematic diagram of different views of an example three-dimensional unit comprising a platform with a hexagonal geometry.

[0159] Figure 46. Schematic diagram of an example mesh / fabric comprising a plurality of the hexagonal units.

[0160] Figure 47. Alternative schematic view of the mesh / fabric of Figure 46.

[0161] Figure 48. Magnified view of Figure 47 showing the interconnected tubules.

[0162] Figure 49. Schematic diagram of an example three-dimensional unit further comprising a base.

[0163] DETAILED DESCRIPTION

[0164] The devices and methods described herein may be understood more readily by reference to the following detailed description of specific aspects of the disclosed subject matter and the Examples included therein.

[0165] Before the present devices and methods are disclosed and described, it is to be understood that the aspects described below are not limited to specific synthetic methods or specific reagents, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. Also, throughout this specification, various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which the disclosed matter pertains. The references disclosed are also individually and specifically incorporated by reference herein for the material contained in them that is discussed in the sentence in which the reference is relied upon.

[0166] General Definitions

[0167] In this specification and in the claims that follow, reference will be made to a number of terms, which shall be defined to have the following meanings.

[0168] Throughout the description and claims of this specification, the word “comprise” and other forms of the word, such as “comprising” and “comprises,” means including but not limited to, and is not intended to exclude, for example, other additives, components, integers, or steps.

[0169] As used in the description and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a composition” includes mixtures of two or more such compositions, reference to “an agent” includes mixtures of two or more such agents, reference to “the component” includes mixtures of two or more such components, and the like.

[0170] “Optional” or “optionally” means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where the event or circumstance occurs and instances where it does not.

[0171] 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.

[0172] Values can be expressed herein as an “average” value. “Average” generally refers to the statistical mean value.

[0173] By “substantially” is meant within 5%, e.g., within 4%, 3%, 2%, or 1%.

[0174] “Exemplary” means “an example of’ and is not intended to convey an indication of a preferred or ideal embodiment. “Such as” is not used in a restrictive sense, but for explanatory purposes. It is understood that throughout this specification the identifiers “first” and “second” are used solely to aid in distinguishing the various components and steps of the disclosed subject matter. The identifiers “first” and “second” are not intended to imply any particular order, amount, preference, or importance to the components or steps modified by these terms.

[0175] References in the specification and concluding claims to parts by weight of a particular element or component in a composition denotes the weight relationship between the element or component and any other elements or components in the composition or article for which a part by weight is expressed. Thus, in a compound containing 2 parts by weight of component X and 5 parts by weight component Y, X and Y are present at a weight ratio of 2:5, and are present in such ratio regardless of whether additional components are contained in the compound.

[0176] A weight percent (wt. %) of a component, unless specifically stated to the contrary, is based on the total weight of the formulation or composition in which the component is included.

[0177] The term “or combinations thereof’ as used herein refers to all permutations and combinations of the listed items preceding the term. For example, “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. Continuing with this example, 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.

[0178] As used herein, by a “subject” is meant an individual. Thus, the “subject” can include domesticated animals (e.g., cats, dogs, etc.), livestock (e.g., cattle, horses, pigs, sheep, goats, etc.), laboratory animals (e.g., mouse, rabbit, rat, guinea pig, etc.), and birds. “Subject” can also include a mammal, such as a primate or a human. Thus, the subject can be a human or veterinary patient. The term “patient” refers to a subject under the treatment of a clinician, e.g., physician.

[0179] “Biocompatible” and “biologically compatible”, as used herein, generally refer to compounds and / or compositions that are, along with any metabolites or degradation products thereof, generally non-toxic to normal cells and tissues, and which do not cause any significant adverse effects to normal cells and tissues when cells and tissues are incubated e.g., cultured) in their presence.

[0180] The term “biodegradable” or “bioresorbable” as used herein refers to a material or substance wherein physical dissolution and / or chemical degradation is effected under physiological conditions. As used herein, “antimicrobial” refers to the ability to treat or control (e.g., reduce, prevent, treat, or eliminate) the growth of a microbe at any concentration. Similarly, the terms “antibacterial,” “antifungal,” and “antiviral” refer to the ability to treat or control the growth of bacteria, fungi, and viruses at any concentration, respectively.

[0181] As used herein, “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.

[0182] As used herein, “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.

[0183] As used herein, “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). The term “control” is used synonymously with the term “treat.”

[0184] The term “anticancer” refers to the ability to treat or control cellular proliferation and / or tumor growth at any concentration.

[0185] The term “therapeutically 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.

[0186] The term “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.

[0187] As used herein, “molecular weight” refers to the number average molecular weight as measured by1H NMR spectroscopy, unless indicated otherwise. Devices

[0188] Disclosed herein are devices 100 configured to be inserted into an anatomical location of a subject. In some examples, 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.

[0189] In some examples, 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). In some examples, 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. For example, 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). In some examples, the thickness of the mesh is from 0.5 to 2 centimeters.

[0190] In some examples, the mesh comprises a plurality of three-dimensional units 140, wherein the plurality of three-dimensional units 140 are interconnected to form the mesh.

[0191] Also disclosed herein are 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. Each of the plurality of three-dimensional units can be the same or different.

[0192] In some examples, the mesh is disposed on a membrane, such as a second mesh.

[0193] In some examples, 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. In some examples, 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.

[0194] 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.

[0195] 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. In some examples, 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.

[0196] In some examples, 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.

[0197] In some examples, the one or more tubules can provide a desired mechanical property (e.g., strength and / or elasticity). Each of the tubules can have any suitable geometry. Each of the tubules can be solid or hollow. In some examples, each tubule is hollow, such that each tubule comprises a wall defining a lumen, the lumen being configured to receive and hold adipose tissue, such as autologous adipose tissue.

[0198] Each of the three-dimensional units can have any suitable number of tubules. For example, each of the three-dimensional units can have one or more tubules (e.g., 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, or 10 or more). In some examples, each of the three-dimensional units can have from 3 to 10 tubules. In some examples, the number of tubules can be selected based on a desired mechanical property, the size of the three-dimensional unit, and / or the geometry of the platform.

[0199] The tubules can have any suitable dimensions. In some examples, wherein the tubules are configured to receive and hold adipose tissue, such as autologous adipose tissue, the tubules can have an average diameter of 1.6 millimeters (mm) or less (e.g., 1.5 mm or less, 1.4 mm or less, 1.3 mm or less, 1.2 mm or less, 1.1 mm or less, 1.0 mm or less, 0.9 mm or less, 0.8 mm or less, 0.7 mm or less, or 0.6 mm or less).

[0200] The platform can have any suitable geometry, such as polygonal (e.g., triangular, rectangular, hexagonal, etc.) or circular.

[0201] In some examples, each of the three-dimensional units 140 can further comprise a base 144, the pillar 142 extending from the base 144 to the platform 141. The base can have any suitable geometry, such as polygonal (e.g., triangular, rectangular, hexagonal, etc.) or circular. The base and the platform can be the same or different.

[0202] The base (when present) and / or the platform can each independently have an average characteristic dimension. “Average characteristic dimension” and “mean characteristic dimension” are used interchangeably herein, and generally refer to the statistical mean characteristic dimension of the base and / or platform in a population of bases and / or platforms. For example, the average characteristic dimension for a plurality of platforms with a substantially circular shape can comprise the average diameter of the plurality of platforms. For a triangular shaped platform, the average characteristic dimension can, for example, refer to the average length of the side of the triangle. For a hexagonal shaped platform, the average characteristic dimension can refer to the average diameter of the hexagon.

[0203] In some examples, the base (when present) and / or the platform can each independently have an average characteristic dimension of 0.4 centimeters 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,

[0204] 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, 1.9 cm or more, 2.0 cm or more, 2.1 cm or more, 2.2 cm or more, 2.3 cm or more, 2.4 cm or more, 2.5 cm or more, 2.6 cm or more, 2.7 cm or more, 2.8 cm or more, 2.9 cm or more, 3.0 cm or more, 3. 1 cm or more, 3.2 cm or more, 3.3 cm or more, 3.4 cm or more,

[0205] 3.5 cm or more, 3.6 cm or more, 3.7 cm or more, 3.8 cm or more, or 3.9 cm or more). In some examples, the base (when present) and / or the platform can each independently have an average characteristic dimension of 4 centimeters or less (e.g., 3.9 cm or less, 3.8 cm or less, 3.7 cm or less, 3.6 cm or less, 3.5 cm or less, 3.4 cm or less, 3.3 cm or less, 3.2 cm or less, 3.1 cm or less, 3.0 cm or less, 2.9 cm or less, 2.8 cm or less, 2.7 cm or less, 2.6 cm or less, 2.5 cm or less, 2.4 cm or less, 2.3 cm or less, 2.2 cm or less, 2.1 cm or less, 2.0 cm or less, 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 average characteristic dimension of the base (when present) and / or the platform can each independently range from any of the minimum values described above to any of the maximum values described above. For example, the base (when present) and / or the platform can each independently have an average characteristic dimension of from 0.4 to 4 centimeters (e.g., from 0.4 to 2 cm, from 2 to 4 cm, from 0.4 to 1 cm, from 1 to 2 cm, from 2 to 3 cm, from 3 to 4 cm, from 0.4 to 3.5 cm, from 0.4 to 3 cm, from 0.4 to 2.5 cm, from 0.4 to 1.5 cm, from 0.5 to 4 cm, from 1 to 4 cm, from 1.5 to 4 cm, from 2.5 to 4 cm, from 0.5 to 3.9 cm, or from 0.6 to 3.8 cm). In some examples, the base (when present) and / or the platform can each independently have an average characteristic dimension of from 0.5 to 4 centimeters. In some examples, 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. In some examples, 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.

[0206] Each of the three dimensional units can each independently have an average height, for example as measured from the platform to the bottom of the pillar or as measured from the platform to the base (when present). In some examples, the average height can be 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). In some examples, the average height can be 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 average height of each of the plurality of three dimensional units can independently range from any of the minimum values described above. For example, the average height of each of the three dimensional units 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). In some examples, the average height of each of the three-dimensional units can be from 0.5 to 2 centimeters.

[0207] In some examples, the platform, the pillar, the base (when present), and the one or more tubules can be integrally formed.

[0208] In some examples, each of the three dimensional units is monolithic.

[0209] In some examples, each of the three dimensional units has a volume configured to receive and hold adipose tissue, such as autologous adipose tissue. The volume of each of the three dimensional units can, for example, independently be 0.1 cm3or more (e.g., 0.25 cm3or more, 0.5 cm3or more, 0.75 cm3or more, 1 cm3or more, 1.25 cm3or more, 1.5 cm3or more, 2 cm3or more, 2.5 cm3or more, 3 cm3or more, 3.5 cm3or more, 4 cm3or more, 4.5 cm3or more, 5 cm3or more, 6 cm3or more, 7 cm3or more, 8 cm3or more, 9 cm3or more, 10 cm3or more, 11 cm3or more, 12 cm3or more, 13 cm3or more, 14 cm3or more, 15 cm3or more, 16 cm3or more, 17 cm3or more, 18 cm3or more, 19 cm3or more, 20 cm3or more, 21 cm3or more, 22 cm3or more, 23 cm3or more, or 24 cm3or more). In some examples, the volume of each of the three dimensional units can independently be 25 cm3or less (e.g., 24 cm3or less, 23 cm3or less, 22 cm3or less, 21 cm3or less, 20 cm3or less, 19 cm3or less, 18 cm3or less, 17 cm3or less, 16 cm3or less, 15 cm3or less, 14 cm3or less, 13 cm3or less, 12 cm3or less, 11 cm3or less, 10 cm3or less, 9 cm3or less, 8 cm3or less, 7 cm3or less, 6 cm3or less, 5 cm3or less, 4.5 cm3or less, 4 cm3or less, 3.5 cm3or less, 3 cm3or less, 2.5 cm3or less, 2 cm3or less, 1.5 cm3or less, 1.25 cm3or less, 1 cm3or less, 0.75 cm3or less, 0.5 cm3or less, or 0.25 cm3or less). The volume of each of the three dimensional units can each independently range from any of the minimum values described above to any of the maximum values described above. For example, the volume of each of the three dimensional units can independently be from 0.1 to 25 cm3(e.g., from 0.1 to 12.5 cm3, from 12.5 to 25 cm3, from 0.1 to 5 cm3, from 5 to 10 cm3, from 10 to 15 cm3, from 15 to 20 cm3, from 20 to 25 cm3, from 0.1 to 20 cm3, from 0.1 to 15 cm3, from 0.1 to 10 cm3, from 0.1 to 1 cm3, from 0.25 to 25 cm3, from 0.5 to 25 cm3, from 1 to 25 cm3, from 5 to 25 cm3, from 10 to 25 cm3, from 15 to 25 cm3, from 0.25 to 24 cm3, or from 0.5 to 23 cm3).

[0210] Neighboring three-dimensional units are connected to each other to form the mesh. The neighboring three-dimensional units can be connected to each other to form the mesh in any suitable way. In some examples, the one or more tubules are configured to connect neighboring three-dimensional units to each other to form the mesh. In some examples, the one of more tubules of neighboring three-dimensional units are interwoven to thereby connect neighboring three-dimensional units to each other. In some examples the mesh is integrally formed, for example by 3D printing.

[0211] In some examples, the mesh comprises a plurality of three-dimensional units as shown in one or more of Figure 36A-Figure 49.

[0212] In some examples, 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. In some examples, 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.

[0213] Non-auxetic materials and / or geometries have a positive Poisson’s ratio and become thinner in cross section when stretched. The transverse contraction strain to longitudinal extension strain in the direction of the stretching is positive.

[0214] Examples of a non-auxetic geometry include, but are not limited to, lattice structures based on a diamond, cube, truncated cube, rhombic dodecahedron, and truncated cuboctahedron unit cells. Auxetic materials and / or geometries have a negative Poisson's ratio; when stretched, they become thicker perpendicular to the applied force. This occurs due to their particular internal structure and the way this deforms when uniaxially loaded. Auxetics can be single molecules, crystals, or a particular structure of macroscopic matter. Examples of auxetics include, but are not limited to re-entrant structures, chiral structures, rotational (semi-)rigid structures, crumpled and perforated sheet models, and miscellaneous structure which includes arbitrary geometries (e.g., egg rack model, tethered nodule, hexa-truss model, and origami structure).

[0215] Re-entrant structures can, for example, include the re-entrant corner and re-entrant angle in an irregular polygon. The re-entrant angle in an irregular polygon is an interior angle that is greater than 180°, as seen in the ribs of the “bow-tie” honeycomb (Figure 12). Re-entrant structures can be formed by hexagonal face cells, which have the edges protruding outwardly. Along with re-alignment (hinging), deflection and axial deformation (stretching) of cell ribs can also be responsible for the deformation of re-entrant structures and auxetic behavior.

[0216] The plurality of zones and / or the plurality of three-dimensional units can, for example, each have a different composition, a different geometry, or a combination thereof. In some examples, 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. In some examples, the plurality of zones and / or the plurality of three-dimensional units each have a different composition and a different geometry.

[0217] In some examples, the mesh comprises a fat grafting zone having little to no elasticity. The fat grating zone can, for example, comprises adipose tissue, such as autologous adipose tissue.

[0218] In some examples, the mesh comprises a support zone, the support zone being elastic along one direction. The support zone can, for example, have a non-auxetic geometry. In some examples, the support zone comprises an anisotropic material, a non-auxetic material, or a combination thereof.

[0219] In some examples, the mesh comprises an elastic zone, the elastic zone having a high amount of elasticity in multiple directions. The elastic zone can, for example, have an auxetic geometry. In some examples, the elastic zone can comprise an isotropic material, an auxetic material, or a combination thereof.

[0220] In some examples, the mesh comprises a transition zone, the transition zone being more elastic than the support zone and less elastic than the elastic zone. In some examples, 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.

[0221] Each of the plurality of zones and / or each of the plurality of three-dimensional units can comprise any suitable composition. The composition of each of the plurality of zones and / or at least a portion of each of the plurality of three-dimensional units can, for example, independently comprise a polymer such as a bioresorbable polymer, collagen, adipose cellular stromal matrix, adipose tissue, or a combination thereof.

[0222] In some examples, 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 can each independently comprise 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 (e.g., from silkworms and / or spiders), PEG based peptide conjugates, cell-adhesive poly(ethylene glycol), MMP-sensitive poly (ethylene glycol), PEGylated fibrinogen, 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. In some examples, 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 can each independently comprise 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), polyanhydrides, or a combination thereof.

[0223] In some examples, 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 can each independently comprise a polyester, such as poly(glycerol- dodecanoate) (PGD). In some examples, 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 can each independently comprise a poly(ether-ester). In some examples, 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 can each independently comprise polydioxanone (PDO). In some examples, each of the plurality of zones and / or each of the plurality of three-dimensional units comprises polydioxanone (PDO).

[0224] In some examples, 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 can each independently comprise a polyolefin, such as polypropylene.

[0225] In some examples, 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 can each independently comprise poly glycolic acid (PGA).

[0226] In some examples, 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 can each independently comprise polyglycolic acid (PGA) or a copolymer thereof, polylactic acid (PLA) or a copolymer thereof, polycaprolactone (PCL) or a copolymer thereof, or a combination thereof.

[0227] In some examples, 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 can each independently comprise a bioink. Examples of bioinks include, but are not limited to, alginate-based bioinks, gelatin-based bioinks (e.g., GelMA - Gelatin Methacryloyl), collagen-based bioinks (e.g., Type I collagen, Type II collagen), fibrin-based bioinks, chitosan-based bioinks, hyaluronic acid-based bioinks, Matrigel-based bioinks, silk fibroin-based bioinks, cellulose-based bioinks, polyethylene glycol-based bioinks (PEG-based bioinks), polycaprolactone-based bioinks (PCL-based bioinks), poly(lactic-co-glycolic acid)- based bioinks (PLGA-based bioinks), polyvinyl alcohol-based bioinks (PVA-based bio inks), polyurethane-based bioinks, polydopamine-based bioinks, polypeptide-based bioinks, agarose- based bioinks, carboxymethyl cellulose-based bioinks, sodium alginate-gelatin-based bioinks, polyethylene oxide-based bioinks (PEO-based bioinks), and combinations thereof.

[0228] In some examples, 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 can each independently comprise collagen. In some examples, the composition of one of 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 can each independently be is porous. In some examples, the porous composition can comprise a plurality of pores. In some examples, the plurality of pores can have an average diameter of 0.5 mm or more. In some examples, the plurality of pores can have an average diameter of 0.5 mm or less.

[0229] In some examples, 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. In some examples, the therapeutic agent is dispersed inhomogeneously throughout the zone(s), the three-dimensional units, and / or device (e.g., randomly, along a concentration gradient, only in certain zones, etc.). In some examples, the therapeutic agent is dispersed substantially homogeneously throughout the zone(s), the three-dimensional units, and / or device.

[0230] The therapeutic agent can, for example, comprise an anticancer agent, anti-inflammatory agent, analgesic agent, antimicrobial agent, or a combination thereof. As used herein, antimicrobials include, for example, antibacterials, antifungals, and antivirals.

[0231] Examples of antimicrobial agents include, but are not limited to, alexidine, asphodelin A, atromentin, auranthine, austrocortilutein, austrocortirubin, azerizin, chlorbisan, chloroxine, cidex, cinoxacin, citreorosein, copper usnate, cupiennin, curvularin, DBNPA, dehydrocurvularin, desoxyfructo-serotonin, dichloroisocyanuric acid, elaiomycin, holtfreter's solution, malettinin, naphthomycin, neutrolin, niphimycin, nitrocefin, oxadiazoles, paenibacterin, proclin, ritiometan, ritipenem, silicone quaternary amine, stylisin, taurolidine, tirandamycin, trichloroisocyanuric acid, triclocarban, and combinations thereof.

[0232] Examples of 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, chromomycin A3, citromycin, clindamycin, clofazimine, clofoctol, clorobiocin, coprinol, coumermycin Al, cyclic lipopeptides, cycloheximide, cycloserine, dalfopristin, dapsone, daptomycin, debromomarinone, 17-dimethylaminoethylamino-17- demethoxygeldanamycin, echinomycin, endiandric acid C, enediyne, enviomycin, eravacycline, erythromycin, esperamicin, etamycin, ethambutol, ethionamide, (6S)-6-fluoroshikimic acid, fosfomycin, fosmidomycin, friulimicin, furazolidone, furonazide, fusidic acid, geldanamycin, gentamycin, gepotidacin, glycy ciclines, glycyrrhizol, gramicidin S, guanacastepene A, hachimycin, halocyamine, hedamycin, helquinoline, herbimycin, hexamethylenetetramine, hitachimycin, hydramacin- 1 , isoniazid, kanamycin, katanosin, kedarcidin, kendomycin, kettapeptin, kidamycin, lactivicin, lactocillin, landomycin, landomycinone, lasalocid, lenapenem, leptomycin, lincosamides, linopristin, lipiarmycins, macbecin, macrolides, macromomycin B, maduropeptin, mannopeptimycin glycopeptide, marinone, meclocycline, melafix, methylenomycin A, methylenomycin B, monensin, moromycin, mupirocin, mycosubtilin, myriocin, myxopyronin, naphthomycin A, narasin, neocarzinostatin, neopluramycin, neosalvarsan, neothramycin, netropsin, nifuroxazide, nifurquinazol, nigericin, nitrofural, nitrofurantoin, nocathiacin I, novobiocin, omadacycline, oxacephem, oxazolidinones, penicillins, peptaibol, phytoalexin, plantazolicin, platensimycin, plectasin, pluramycin A, polymixins, polyoxins, pristinamycin, pristinamycin IA, promin, prothionamide, pulvinone, puromycin, pyocyanase, pyocyanin, pyrenocine, questiomycin A, quinolones, quinupristin, ramoplanin, raphanin, resistome, reuterin, rifalazil, rifamycins, ristocetin, roseophilin, salinomycin, salinosporamide A, saptomycin, saquayamycin, seraticin, sideromycin, sodium sulfacetamide, solasulfone, solithromycin, sparassol, spectinomycin, staurosporine, streptazolin, streptogramin, streptogramin B, streptolydigin, streptonigrin, styelin A, sulfonamides, surfactin, surotomycin, tachyplesin, taksta, tanespimycin, telavancin, tetracyclines, thioacetazone, thiocarlide, thiolutin, thiostrepton, tobramycin, trichostatin A, triclosan, trimethoprim, trimethoprim, tunicamycin, tyrocidine, urauchimycin, validamycin, viridicatumtoxin B, vulgamycin, xanthomycin A, xibomol, amikacin, amoxicillin, ampicillin, atovaquone, azithromycin, aztreonam, bacitracin, carbenicillin, cefadroxil, cefazolin, cefdinir, cefditoren, cefepime, cefiderocol, cefoperazone, cefotetan, cefoxitin, cefotaxime, cefpodoxime, cefprozil, ceftaroline, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, chloramphenicol, colistimethate, cefuroxime, cephalexin, cephradine, cilastatin, cinoxacin, ciprofloxacin, clarithromycin, clindamycin, dalbavancin, dalfopristin, daptomycin, demeclocycline, dicloxacillin, doripenem, doxycycline, eravacycline, ertapenem, erythromycin, fidaxomicin, fosfomycin, gatifloxacin, gemifloxacin, gentamicin, imipenem, lefamulin, lincomycin, linezolid, lomefloxacin, loracarbef, meropenem, metronidazole, minocycline, moxifloxacin, nafcillin, nalidixic acid, neomycin, norfloxacin, ofloxacin, omadacycline, oritavancin, oxacillin, oxytetracycline, paromomycin, penicillin, pentamidine, piperacillin, plazomicin, quinupristin, rifaximin, sarecycline, secnidazole, sparfloxacin, spectinomycin, sulfamethoxazole, sulfisoxazole, tedizolid, telavancin, telithromycin, ticarcillin, tigecycline, tobramycin, trimethoprim, trovafloxacin, vancomycin, and combinations thereof.

[0233] Examples of antifungals include, but are not limited to, abafungin, acibenzolar, acibenzolar-S-methyl, acrisorcin, allicin, aminocandin, amorolfine, amphotericin B, anidulafungin, azoxystrobin, bacillomycin, bacillus pumilus, barium borate, benomyl, binapacryl, boric acid, bromine monochloride, bromochlorosalicylanilide, bupirimate, butenafine, candicidin, caprylic acid, captafol, captan, carbendazim, caspofungin, cerulenin, chloranil, chlormidazole, chlorophetanol, chlorothalonil, chloroxylenol, chromated copper arsenate, ciclopirox, cilofungin, cinnamaldehyde, clioquinol, copper(I) cyanide, copper(II) arsenate, cruentaren, cycloheximide, davicil, dehydroacetic acid, dicarboximide fungicides, dichlofluanid, dimazole, diphenylamine, echinocandin, echinocandin B, epoxiconazole, ethonam, falcarindiol, falcarinol, famoxadone, fenamidone, fenarimol, fenpropimorph, fentin acetate, fenticlor, filipin, fhiazinam, fhiopicolide, flusilazole, fluxapyroxad, fuberidazole, griseofulvin, halicylindramide, haloprogin, hamycin, hexachlorobenzene, hexachlorocyclohexa- 2,5-dien-l-one, 5-hydroxy-2(5H)-furanone, iprodione, lime sulfur, mancozeb, maneb, melafix, metalaxyl, metam sodium, methylisothiazolone, methylparaben, micafungin, miltefosine, monosodium methyl arsenate, mycobacillin, myclobutanil, natamycin, beta-nitrostyrene, nystatin, paclobutrazol, papulacandin B, parietin, pecilocin, pencycuron, pentamidine, pentachloronitrobenzene, pentachlorophenol, perimycin, 2-phenylphenol, polyene antimycotic, propamocarb, propiconazole, pterulone, ptilomycalin A, pyrazophos, pyrimethanil, pyrrolnitrin, selenium disulfide, sparassol, strobilurin, sulbentine, tavaborole, tebuconazole, terbinafine, theonellamide F, thymol, tiabendazole, ticlatone, tolciclate, tolnaftate, triadimefon, triamiphos, tribromometacresol, 2,4,6-tribromophenol, tributyltin oxide, triclocarban, triclosan, tridemorph, trimetrexate, undecylenic acid, validamycin, venturicidin, vinclozolin, vinyldithiin, vusion, xanthene, zinc borate, zinc pyrithione, zineb, ziram, voriconazole, itraconazole, posaconazole, fluconazole, ketoconazole, clotrimazole, isavuconazonium, miconazole, caspofungin, anidulafungin, micafungin, griseofulvin, terbinafine, flucytosine, terbinafine, nystatin, amphotericin b., and combinations thereof.

[0234] Examples of antivirals 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, acyclovir, adefovir, amantadine, amprenavir, atazanavir, balavir, baloxavir marboxil, boceprevir, cidofovir, cobicistat, daclatasvir, darunavir, delavirdine, didanosine, docasanol, dolutegravir, doravirine, ecoliever, edoxudine, efavirenz, elvitegravir, emtricitabine, enfuvirtide, entecavir, etravirine, famciclovir, fomivirsen, fosamprenavir, forscamet, fosnonet, famciclovir, favipravir, fomivirsen, foscavir, ganciclovir, ibacitabine, idoxuridine, indinavir, inosine, inosine pranobex, interferon type I, interferon type II, interferon type III, lamivudine, letermovir, letermovir, lopinavir, loviride, maraviroc, methisazone, moroxydine, nelfinavir, nevirapine, nitazoxanide, oseltamivir, peginterferon alfa-2a, peginterferon alfa-2b, penciclovir, peramivir, pleconaril, podophyllotoxin, pyramidine, raltegravir, remdesevir, ribavirin, rilpivirine, rimantadine, rintatolimod, ritonavir, saquinavir, simeprevir, sofosbuvir, stavudine, tarabivirin, telaprevir, telbivudine, tenofovir alafenamide, tenofovir disoproxil, tenofovir, tipranavir, trifluridine, trizivir, tromantadine, umifenovir, valaciclovir, valganciclovir, vidarabine, zalcitabine, zanamivir, zidovudine, and combinations thereof.

[0235] In some examples, the therapeutic agent can comprise an anticancer agent. In some examples, the therapeutic agent comprises a chemotherapeutic agent, an immunotherapeutic agent, or a combination thereof.

[0236] In some examples, 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. Examples of 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, Bexarotene, Bicalutamide, BiCNU, Blenoxane, Bleomycin, Bortezomib, Busulfan, Busulfex, C225, Calcium Leucovorin, Campath, Camptosar, Camptothecin- 11, Capecitabine, Carac, Carboplatin, Carmustine, Carmustine wafer, Casodex, CCNU, CDDP, CeeNU, Cerubidine, cetuximab, Chlorambucil, Cisplatin, Citrovorum Factor, Cladribine, Cortisone, Cosmegen, CPT-11, Cyclophosphamide, Cytadren, Cytarabine, Cytarabine liposomal, Cytosar-U, Cytoxan, Dacarbazine, Dactinomycin, Darbepoetin alfa, Daunomycin, Daunorubicin, Daunorubicin hydrochloride, Daunorubicin liposomal, DaunoXome, Decadron, Delta-Cortef, Deltasone, Denileukin diftitox, DepoCyt, Dexamethasone, Dexamethasone acetate, Dexamethasone sodium phosphate, Dexasone, Dexrazoxane, DHAD, DIC, Diodex, Docetaxel, Doxil, Doxorubicin, Doxorubicin liposomal, Droxia, DTIC, DTIC-Dome, Duralone, Efudex, Eligard, Ellence, Eloxatin, Elspar, Emcyt, Epirubicin, Epoetin alfa, Erbitux, Erwinia L-asparaginase, Estramustine, Ethyol, Etopophos, Etoposide, Etoposide phosphate, Eulexin, Evista, Exemestane, Fareston, Faslodex, Femara, Filgrastim, Floxuridine, Fludara, Fludarabine, Fluoroplex, Fluorouracil, Fluorouracil (cream), Fluoxymesterone, Flutamide, Folinic Acid, FUDR, Fulvestrant, G-CSF, Gefitinib, Gemcitabine, Gemtuzumab ozogamicin, Gemzar, Gleevec, Lupron, Lupron Depot, Matulane, Maxidex, Mechlorethamine, -Mechlorethamine Hydrochlorine, Medralone, Medrol, Megace, Megestrol, Megestrol Acetate, Melphalan, Mercaptopurine, Mesna, Mesnex, Methotrexate, Methotrexate Sodium, Methylprednisolone, Mylocel, Letrozole, Neosar, Neulasta, Neumega, Neupogen, Nilandron, Nilutamide, Nitrogen Mustard, Novaldex, Novantrone, Octreotide, Octreotide acetate, Oncospar, Oncovin, Ontak, Onxal, Oprevelkin, Orapred, Orasone, Oxaliplatin, Paclitaxel, Pamidronate, Panretin, Paraplatin, Pediapred, PEG Interferon, Pegaspargase, Pegfilgrastim, PEG-INTRON, PEG-L-asparaginase, Phenylalanine Mustard, Platinol, Platinol- AQ, Prednisolone, Prednisone, Prelone, Procarbazine, PROCRIT, Proleukin, Prolifeprospan 20 with Carmustine implant, Purinethol, Raloxifene, Rheumatrex, Rituxan, Rituximab, Roveron-A (interferon alfa-2a), Rubex, Rubidomycin hydrochloride, Sandostatin, Sandostatin LAR, Sargramostim, Solu-Cortef, Solu-Medrol, STI-571, Streptozocin, Tamoxifen, Targretin, Taxol, Taxotere, Temodar, Temozolomide, Teniposide, TESPA, Thalidomide, Thalomid, TheraCys, Thioguanine, Thioguanine Tabloid, Thiophosphoamide, Thioplex, Thiotepa, TICE, Toposar, Topotecan, Toremifene, Trastuzumab, Tretinoin, Trexall, Trisenox, TSPA, VCR, Velban, Velcade, VePesid, Vesanoid, Viadur, Vinblastine, Vinblastine Sulfate, Vincasar Pfs, Vincristine, Vinorelbine, Vinorelbine tartrate, VLB, VP-16, Vumon, Xeloda, Zanosar, Zevalin, Zinecard, Zoladex, Zoledronic acid, Zometa, Gliadel wafer, Glivec, GM-CSF, Goserelin, granulocyte colony stimulating factor, Halotestin, Herceptin, Hexadrol, Hexalen, Hexamethylmelamine, HMM, Hycamtin, Hydrea, Hydrocort Acetate, Hydrocortisone, Hydrocortisone sodium phosphate, Hydrocortisone sodium succinate, Hydrocortone phosphate, Hydroxyurea, Ibritumomab, Ibritumomab Tiuxetan, Idamycin, Idarubicin, Ifex, IFN-alpha, Ifosfamide, IL 2, IL-11, Imatinib mesylate, Imidazole Carboxamide, Interferon alfa, Interferon Alfa-2b (PEG conjugate), Interleukin 2, Interleukin-11, Intron A (interferon alfa-2b), Leucovorin, Leukeran, Leukine, Leuprolide, Leurocristine, Leustatin, Liposomal Ara-C, Liquid Pred, Lomustine, L- PAM, L-Sarcolysin, Meticorten, Mitomycin, Mitomycin-C, Mitoxantrone, M-Prednisol, MTC, MTX, Mustargen, Mustine, Mutamycin, Myleran, Iressa, Irinotecan, Isotretinoin, Kidrolase, Lanacort, L-asparaginase, LCR, FAM-HYD-1, Marizomib (NPI-0052), Lenalidomide, Carfilzomib, Panobinostat, Quisinostat, Selinexor, Oprozomib, and combinations thereof. The anticancer agent can also include biopharmaceuticals such as, for example, antibodies.

[0237] Examples of suitable immunotherapeutic agents include, but are not limited to, alemtuzumab, cetuximab (ERBITUX), gemtuzumab, iodine 131 tositumomab, rituximab, trastuzamab (HERCEPTIN), and combinations thereof.

[0238] In some examples, the therapeutic agent can comprise an anti-inflammatory agent, such as steroidal and / or non-steroidal anti-inflammatory agents. Examples of steroidal antiinflammatory agents include, but are not limited to, hydrocortisone, dexamethasone, prednisolone, prednisone, triamcinolone, methylprednisolone, budesonide, betamethasone, cortisone, and deflazacort. Examples of non-steroidal anti-inflammatory drugs include acetaminophen, aspirin, ibuprofen, naproxen, Celebrex, ketoprofen, tolmetin, etodolac, fenoprofen, flurbiprofen, diclofenac, piroxicam, indomethacin, sulindax, meloxicam, nabumetone, oxaprozin, mefenamic acid, and diflunisal.

[0239] In some examples, the therapeutic agent can comprise an analgesic. Examples of 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; Betahydroxyfentanyl; Betamethadol; Bicifadine; Biphalin; Brorphine; Bucetin; Bucinnazine; Butalbital; Butinazocine; Butonitazine; Butorphanol; Cannabidiol; Carbazocine; Cebranopadol; Chlorodyne; Chlorproethazine; Cinchophen; Cogazocine; Conolidine; Conorfone; CR-4056; CR665; Dasolampanel; Deltorphin; Deltorphin I; DepoDur; Desmetramadol; Desomorphine; Dezocine; Diacetylnalorphine; Dichloralphenazone; Difenamizole; Dimenoxadol; Dimepheptanol; Dimethylheptylpyran; Dinalbuphine sebacate; Dipipanone; Diproqualone; Dipyrocetyl; Dosulepin; DSP-2230; Embutramide; Enkephalinase nhibitor; Epibatidine; Epiboxidine; Eptazocine; Esterom; Etazocine; Ethylketazocine; Etodesnitazene; Etonitazepipne; Etonitazepyne; Etorphine; Famotidine; Faxeladol; Fedotozine; Fentanyl; Filenadol; Flumexadol; Flumizole; Fluproquazone; Frakefamide; Funapide; Gabapentin; Gabapentin enacarbil; Gabapentinoid; Glafenine; Homofentanyl; Homprenorphine; Ibazocine; Ibuprofen; Incarvillateine; Indantadol; Isomethadone; Isotonitazene; Isovaline; Kavalactone; Kelatorphan; Ketamine; Ketobemidone; Ketorfanol; Ketorolac; Lactucarium; Leconotide; Levallorphan; Levomepromazine; Levomethadone; Lufuradom; Magnesium alicylate; Mavatrep; Meconopsis horridula; Menabitan; Menthol; Menthoxypropanediol; Meprobamate; Meseclazone; Metacetamol; Metamizole; Methoxyflurane; Metkefamide; Metodesnitazene; Metonitazene; Mexiletine; Migraleve; Mirogabalin; Mitragyna speciosa; Moffett’s solution; Moramide intermediate; Morpheridine; Morphiceptin; Morphine; Moxazocine; MP-2001; N-2'-Indolylnaltrexamine; Nabilone; Nafoxadol; Nalbuphine; Nalmexone; Naproxen; Nefopam; Nexeridine; NFEPP; Nimesulide; Noracymethadol; Norlevorphanol; Normethadone; Norpipanone; NS- 11394; Oliceridine; Opiorphin; Opiranserin; Opium; Otenaproxesul; Oxilorphan; Paracetamol; Pethidine; PF-05089771; Phenacetin; Phenazone; derivatives thereof; and combinations thereof.

[0240] In some examples, the therapeutic agent can comprise an analgesic, such as an opioid. Examples of 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)-3-ethoxycarbonyltropane; 3-(dimethylamino)-2,2-dimethyl-l-phenylpropan-l- one; 3,14-Diacetyloxymorphone; 3,6-Dibutanoylmorphine; 3-Acetyloxymorphone; 3- Allylfentanyl; 3 -Hydroxy morphinan; 3 -Methylfentanyl; 3-Methylthiofentanyl; 3- Monoacetylmorphine; 4-Chlorophenylpyridomorphinan; 4-Fluoropethidine; 4-Phenylfentanyl; 5,6-Dihydronorsalutaridine; 5,9 alpha-diethyl-2-hydroxybenzomorphan (5,9-DEHB); 6- Acetyldihydromorphine; 6-Keto Nalbuphine; 6-Methyldihydromorphine; 6- Methylenedihydrodesoxymorphine; 6-Monoacetylcodeine; 6-Monoacetylmorphine; 6- Nicotinoyldihydromorphine; 7- Acetoxymitragynine; 7-Hydroxymitragynine; 7-PET; 7- Spiroindanyloxymorphone; 8,14-Dihydroxydihydromorphinone; 8-Carboxamidocyclazocine (8- CAC); Acetorphine; Acetoxy ketobemidone; Acetylcodone; Acetyldihydrocodeine; Acetylmethadol; Acetylmorphone; Acetylpropionylmorphine; AD- 1211; ADL-5859; AH-7921; Aknadinine; Akuammidine; Akuammine; Alazocine; Alfentanil; Alimadol; Alletorphine (N- allyl-noretorphine); Allylnorpethidine; Allylprodine; Alphaacetylmethadol; Alphamethadol; Alvimopan; Amentoflavone; Anazocine; Anileridine; Anilopam +HC1; Asimadoline; Axomadol; Azaprocin; AZD-2327; Azidomorphine; BDPC; Benzethidine; Benzhydrocodone; Benzylfentanyl; Benzylmorphine; Betacetylmethadol; Betamethadol; Bezitramide; Bisnortilidine; Bremazocine; Brifentanil; BRL-52537; Bromadol; Bromadoline; Bromocodide; Bromoisopropropyldihydromorphinone; Bromomorphide; BU-48; Buprenorphine; Buprenorphine-3-glucuronide; Butinazocine; Butorphanol; Butyrfentanyl; BW373U86; Carbazocine; Carfentanil; Carperidine; Cephakicine; Cephasamine;

[0241] 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;

[0242] Dextropropoxyphene (propoxyphene); Dezocine; Diacetyldihydromorphine (dihydroheroin, acetylmorphinol); Diampromide; Dibenzoylmorphine; Dibutyrylmorphine; Diethylthiambutene; Difenoxin; Diformylmorphine; Dihydrocodeine; Dihydrocodeine; Dihydrodesoxycodeine (desocodeine); Dihydroetorphine; Dihydroisocodeine; Dihydromorphine; Dimenoxadol; Dimepheptanol (racemethadol); Dimethylmorphine (6-O-Methylcodeine);

[0243] Dimethylthiambutene; Dioxaphetyl butyrate; Diphenoxylate; Dipipanone;

[0244] Dipropanoylmorphine; Doxpicomine; DPI-221; DPI-287; DPI-3290; Drotebanol; Droxypropine; Embutramide; Enadoline; Eptazocine; Eseroline; Etazocine; Ethoheptazine;

[0245] Ethyldihydromorphine; Ethylketazocine; Ethylmethylthiambutene; Ethylmorphine (dionine); Etonitazene; Etorphine; Etoxeridine (carbetidine); Faxeladol; FE 200665; Fedotozine; Fenfangjine G; Fentanyl; Fluorophen; Furethidine; Gemazocine; GR-89696; Herkinorin;

[0246] Heroin (diacetylmorphine); Heroin-7, 8-oxide; Heterocodeine; Hodgkinsine; Homprenorphine;

[0247] 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;

[0248] Levoisomethadone; Levomethadone; Levomethorphan; Levomoramide; Levophenacylmorphan; Levopropoxyphene; Levorphanol; Lofentanil; Loperamide; LPK-26; LS- 115509; Lufuradom; Matrine; MCOPPB; Menthol; Meperidine-N-oxide; Meptazinol; Metazocine; Metethoheptazine; Methadone; Metheptazine; Methorphan (racemethorphan); Methyldesorphine;

[0249] 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; Nicomorphine; N-Methylcarfentanil; N-Methylmorphinan; NNC 63-0532; Noracymethadol; Norbuprenorphine; Norbuprenorphine-3-glucuronide; Norcodeine; Noribogaine; Norlevorphanol; Normethadone; Normorphine; Noroxymorphone; Norpipanone;

[0250] Norpropoxyphene; Nortilidine; N-Phenethyl-14-ethoxymetopon; N-Phenethyl-14- ethoxymetopon; N-Phenethylnordesomorphine; N-Phenethylnormorphine; Ocfentanil; O- Desmethyltramadol; Ohmefentanyl; Opium; Oripavine; Oxilorphan; Oxpheneridine (carbamethidine); Oxycodone; Oxymorphazone; Oxymorphol; Oxymorphone; Pantopon; Papaveretum (Omnopon); Parafluorofentanyl; Pentamorphone; Pentazocine; PEPAP; Pericine; Pethidine (meperidine); Phenadone; Phenadoxone (heptazone); Phenampromide; Phenaridine; Phenazocine; Phencyclidine; Pheneridine; Phenomorphan; Phenoperidine; Pholcodine (morpholinylethylmorphine); Picenadol; Piminodine; Piperidylthiambutene; Piritramide; Prodilidine; Profadol; Proglumide; Proheptazine; Properidine (ipropethidine); Propiram; Propylketobemidone; Prosidol; Proxorphan; Pseudoakuammigine; Pseudomorphine;

[0251] Pyrrolidinylthiambutene; Pyrroliphene; PZM21; Quadazocine; R-30490; R-4066;

[0252] 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;

[0253] Spiradoline; SR- 16435; SR-8993; Sufentanil; TAN-67; Tannagine; Tapentadol; Tetrapon; Thebacon; Thebacon (acetyldihydrocodeinone, dihydrocodeinone enol acetate); Thebaine; Thenylfentanyl; Thevinone; Thiambutene; Thiazocine; Thienorphine; Thiobromadol (C-8813); Thiofentanyl; Tifluadom; Tilidine; Tonazocine; Tramadol; Transisocodeine; Trefentanil;

[0254] Trimebutine; Trimeperidine (promedol); U-47700; U-50,488; U-69,593; Viminol; Volazocine; Zenazocine; a-Chlorocodide; a-Chloromorphide; a-hydrocodol; a-Methylacetylfentanyl; a- Methylfentanyl; a-Methylthiofentanyl; 0-Chlorocodide; P-hydroxy fentanyl; P- hydroxythiofentanyl; P-Methylfentanyl; \| / -Akuammigine; derivatives thereof; and combinations thereof.

[0255] 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. In some examples, the anatomical location comprises a breast of the subject. In some examples, the device is configured to support at least a portion of a breast or at least a portion of a breast implant. In some examples, the device is configured to support a breast or a breast implant.

[0256] In some examples, the device is formed from a model based on a tessellation of polyhedrons. For example, the device can be formed from a computational 3D space-filling model.

[0257] In some examples, the device is not flat. For example, the device can have a three dimensional shape, such as a three-dimensional parametric teardrop shape. In some examples, 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. In some examples, the device has a three-dimensional parametric teardrop shape following the Fibonacci equation.

[0258] In some examples, the device is a single piece of mesh (e.g., monolithic).

[0259] In some examples, 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.

[0260] In some examples, the device is configured to be stable for an amount of time after the device is implanted in the subject. As used herein, “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.

[0261] In some examples, 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 more, 33 months or more, 34 months or more, 35 months or more, 36 months or more, 3.5 years or more, 4 years or more, or 4.5 years or more). In some examples, 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 weeks or less, 13 weeks or less, 12 weeks or less, 11 weeks or less, 10 weeks or less, 9 weeks or less, 8 weeks or less, or 7 weeks or less). 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. For example, 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).

[0262] In some examples, the device is produced by additive manufacturing (e.g., 3D printing).

[0263] Referring now to Figure 17 and Figure 18, in some examples 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. In some examples, the mesh further has a thickness 130, for example as shown in Figure 18.

[0264] Referring now to Figure 19, in some examples 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. Referring now to Figure 20-Figure 23, in some examples 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.

[0265] Referring now to Figure 21, in some examples, when in use, the device 100 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.

[0266] Referring now to Figure 24, in some examples the device 100 can further comprise a skin defect zone 110, the skin defect zone 110 being aligned with skin-growth promoting stroma such that the skin defect zone 110 facilitates epithelization and skin coverage when implanted in the subject.

[0267] Referring now to Figure 25 and Figure 26, in some examples the device 100 can further comprise a cuff 112 extending from at least a portion of the periphery 114 of the device 100. In some examples, the cuff 112 can comprise the same composition and / or geometry as the support zone 104. In some examples, the cuff 112 can comprise a substantially non-elastic material. The cuff 112 can, for example, lay flat or be folded under the device 100 when inserted in the subject. In some examples, the cuff 112 can provide a surface area for contact with the chest wall when inserted in the subject. For example, the cuff 112 can allow for anchoring the device to the chest wall of the subject, for example by securing (e.g., suturing) at least a portion of the cuff 112 to the chest wall of the subject.

[0268] Referring now to Figure 27 and Figure 28, in some examples the cuff 112 can form a pocket.

[0269] Referring now to Figure 29 - Figure 31, in some examples, the device 100 can include one or more slots 116 around the periphery 114, and the cuff 112 can include one or more tabs 118 configured to be inserted into the slots 116 to thereby form a pocket. In some examples, the implant can be placed into the pocket, for example as shown in Figure 30.

[0270] Referring now to Figure 32 - Figure 33, in some examples, 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. In some examples, the device 100 and / or the slit 120 can be secured, for example using sutures 122.

[0271] In some examples, the device 100 including the pocket can have an overall teardrop or egg shape, where the cuff portion of the pocket is flat and non-stretchable.

[0272] Referring now to Figure 34 - Figure 35, in some examples, the device can include one or more tabs that can lay flat and provide a surface for anchoring the device to the subject, for example by securing (e.g., suturing) the tabs to the chest wall of the subject. In some examples, the device can include a posterior patch such that the device can form a pocket. In some examples, the device can include a slit configured to receive the implant.

[0273] In some examples, 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.

[0274] In some examples, the device can minimize the subject’s foreign body response to the implant.

[0275] In some examples, the device can be simply sutured into the subject, for example into a mastectomy or lumpectomy defect, and the implant inserted into it as a means of support and / or minimize foreign body response to the implant.

[0276] In some examples, 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.

[0277] In some examples, the device has a surface area which can be selected in view of the anatomical location and dimensions thereof. For example, 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. For example, 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.

[0278] When the device is used to support at least a portion of a breast or breast implant, the surface area of the device can be selected in view of the surface area of said portion of the breast or breast implant. For example, if the surface area of the device is too large relative to the portion of the breast or breast implant, the device will be too loose and can lead to undesirable rippling. Alternatively, if the surface area of the device is, for example, too small relative to the portion of the breast or breast implant, the device will be too tight, which can lead to undesirable effects.

[0279] Methods

[0280] Also disclosed herein are methods of manufacturing any of the devices disclosed herein. For example, the methods can comprise making the device using additive manufacturing (e.g., 3D printing).

[0281] In some examples, the method comprises making the device based on a 3D model. In some examples, the 3D model is based on the Fibonacci equation.

[0282] In some examples, the 3D model is based on an anatomical image of a subject. In some examples, 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.

[0283] In some examples, the device is implanted into at least a portion breast of the subject. For example, the method can comprise breast reconstruction or augmentation (e.g., full or partial breast reconstruction or augmentation), for example after a lumpectomy or mastectomy.

[0284] In some examples, the device is implanted into a breast of the subject. For example, the method can comprise breast reconstruction or augmentation (e.g., full or partial breast reconstruction or augmentation), for example after a lumpectomy or mastectomy.

[0285] In some examples, the method further comprises anatomically designing the device for the subject.

[0286] In some examples, the methods can comprise breast reconstruction (e.g., full or partial breast reconstruction) and treatment of an oncological disorder, such as breast cancer. In some examples, the devices can further include a therapeutic agent, for example for treatment of the oncological disorder.

[0287] For the treatment of oncological disorders, 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. For example, 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.

[0288] A number of embodiments of the invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims.

[0289] The examples below are intended to further illustrate certain aspects of the systems and methods described herein and are not intended to limit the scope of the claims.

[0290] EXAMPLES

[0291] The following examples are set forth below to illustrate the methods and results according to the disclosed subject matter. These examples are not intended to be inclusive of all aspects of the subject matter disclosed herein, but rather to illustrate representative methods and results. These examples are not intended to exclude equivalents and variations of the present invention, which are apparent to one skilled in the art.

[0292] Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.) but some errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, temperature is in °C or is at ambient temperature, and pressure is at or near atmospheric. There are numerous variations and combinations of measurement conditions, e.g., component concentrations, temperatures, pressures and other measurement ranges and conditions that can be used to optimize the described process.

[0293] Example 1 - 3D Matrix Mesh Printing

[0294] Currently, breast implants made out of silicone are traditionally used, but recently received a black box warning by the FDA, due to risk of implant failure, a rare form of ALCL (anaplastic large-cell lymphoma) that is associated with some textured implants, and Breast implant illness. Because of the association of shaped and / or textured implants with the above complications, only round smooth implants are currently approved for clinical use. Therefore, additional means are needed to help support the tissue and / or implant as well as adjust the shape of the spherical implant (e.g., by strategic compression and / or elasticity) to provide a more natural tear drop breast shape.

[0295] Current solutions for providing support to an underlying organ and / or implant include ADM (acellular dermal matrix) and fabric / 2D mesh structures, all of which suffer from various limitations.

[0296] Acellular Dermal Matrix (ADM), a type of surgical mesh, is developed from skin, in which the cells are removed and the support structure is left in place. ADMs vary significantly in their source, processing, level of sterility, biomechanical properties, thickness, final product state, and preparation methods prior to clinical application.

[0297] ADMs have, for example, traditionally been used for control of mastectomy pocket for creating a footprint for placement of implant; long term support of the implant and / or prevention of capsular contracture by mitigating the inflammatory reaction that occurs due to implant surface. Further, shaped ADM can improve the breast shape to be more natural (tear drop) when using round implant devices. Currently, surgeons are limited with pre-determined ADM sizes, resulting the inability to match the proper breast size to the patient. Also the ADM material is cadaveric which is expensive and has a limited supply. Moreover, the FDA has not cleared or approved any ADM product for use in breast reconstruction and has further issues statements that certain acellular dermal matrix (ADM) products used in implant-based breast reconstruction may have a higher chance for complications or problems.

[0298] Currently there are some companies working in this space to create a replacement for ADM with a 2D mesh. These 2D mesh products are almost like fabric and lack the ability to conform to a convex implant surface and further lack any control or differentiation in the elasticity of the mesh for different zones of the breast.

[0299] The technology described herein relates to a 3D Matrix Mesh, which is a 3D printed soft tissue scaffold designed to recreate a natural breast shape that restores support for the overlying mastectomy skin and can, for example, have auxetic properties for differential isotropic and anisotropic control. To optimize soft tissue support, certain parts of the mesh would expand for projection and other parts of the mesh would have no expansion for improved support. Further, the devices described herein can rely on compositions such as bioresorbable polymers, collagen, bioinks, etc.

[0300] Combining both a computational breast analysis model with the 3D Matrix Mesh printing technology would have the ability to mimic a natural breast shape customized to the patient.

[0301] An advantage of the 3D Matrix Mesh would be the ability to customize to the patient’s natural breast shape. Currently, surgeons are limited with pre-determined ADM sizes, resulting the inability to match the proper breast size to the patient. Also the ADM material is cadaveric which is expensive and has a limited supply. Utilizing a computational breast analysis model to match the patient by scanning their natural breast shape permits a customized designed for breast reconstruction.

[0302] The 3D Matrix Mesh can contain the following materials to create a self-regenerating and biodegradable device: 1. Bioresorbable Polymer; 2. Recombinant Human Collagen; and 3. Adipose Cellular Stromal Matrix. In some examples, the 3D matrix mesh can include a bioink.

[0303] The 3D Matrix Mesh can be structured to support the soft breast tissue. In addition, the mesh can provide support for a traditional implant or other implantable devices. The matrix mesh can have different properties in various locations of the breast envelope to provide support and encourage fat-in growth in specific breast regions. For example, the lower part of the breast, which supports the weight of the implant, can have a tighter, less elastic pattern of the mesh, whereas over the top part of the breast above the nipple area, the mesh can have a more stretching design to allow maximum projection of the underlining implant and to improve breast shape.

[0304] At the present time, surgeons do not have the ability to replicate the original breast shape of a patient with the current ADM products or current mesh products. However, combining the computational breast analysis model with the 3D Matrix Mesh technology would revolutionize breast reconstruction and customize the patients' anatomical breast size maintaining a natural breast complementing the original breast shape.

[0305] As shown in the Figure 1 -Figure 9, the matrix mesh can be a 3D printed construct with various patterns at specific locations that can provide isotropic and anisotropic breast support. Due to the ability to be printed as a 3D structure, the mesh can be customized to the specific size and anatomy of the patient. The 3D Bio Matrix Mesh can be used with various types and sizes of implants. The 3D Matrix Mesh can combine recombinant human collagen, bioresorbable polymer, and adipose cellular stromal matrix materials that promote fat in growth.

[0306] This can allow the Matrix Mesh to have better inherited qualitative properties, including, for example, to support soft breast tissue; to provide support for traditional implants and other implantable devices; and to take advantage of the ability to control 3D printing properties for different material property location that can support and encourage isolated fat-in growth to specific regions of the breast.

[0307] By specifically designing the printing pattern at various parts of the breast, the amount of elasticity can be controlled. As such, the lower part of the breast, which supports the weight of the implant, can have a tighter less elastic pattern of the mesh. The mesh in the area surrounding the nipple areola complex can have the most elasticity to allow maximum projection of the underlying implant and to improve breast shape.

[0308] For example, the 3D Matrix Mesh can be designed and shaped according to the patient's structural needs as shown, for example, in Figure 1 - Figure 10. To optimize breast support, a less elastic mesh pattern ring would extend from the bottom of the breast to the superior pectoral fascia where it would be anchored by sutures, thereby forming a suspension effect for the underlying implant. Prior to surgery, a 3D computational breast model can be obtained to customize the patient's breast via scan, and the 3D Matrix Mesh would be printed for the patient. Additionally, a variety of predetermined sizes can be available if a scan is not possible.

[0309] To accomplish a natural breast shape, the 3D Matrix Mesh can be printed into a similar proportion to the Fibonacci sequence (Figure 16) and an auxetic structure maintaining the integrity of the patient's natural geometric breast shape.

[0310] Microscopic characteristics

[0311] 3D Printing Pattern. Auxetic materials have specific properties when compared to non- auxetic materials based on their structure and deformation behavior (Figure 1 1-Figure 13). Unlike traditional materials that elongate when stretched, auxetic materials and patterns expand laterally when stretched longitudinally. Poisson ratio (v) = lateral contractile strain / longitudinal tensile strain

[0312] Pattern 1: Honeycomb hexagonal pattern - Positive v ratio: cells elongate along the y axis and close up along the x axis when stretched along the y axis (Figure 11, Figure 13).

[0313] Pattern 2 Modified Reentrant honeycomb pattern - Negative v ratio: cells undergo elongation in both x and y axis when stretched (Figure 12, Figure 13).

[0314] Nonauxetic and auxetic structure. The auxetic portion of the mesh can be printed around the nipple because there is stretching one direction, but also elastically in the second direction (Figure 13). As it is stretched it is not contracting in the perpendicular direction, which is also stretching, especially in the area where there is more projection needed (Figure 13). The non-auxetic portion would be 3D printed to provide support superior to the inframammary fold (Figure 13).

[0315] Auxetic and nonauxetic materials. The material used can also be adjusted to be auxetic or non-auxetic. For example, an auxetic material printed in an auxetic pattern can amplify the auxetic properties, which can be exploited to maximize control of the support and / or shape of the underlying implant / organ.

[0316] Isotropic and Anisotropic Material. The material used can also be adjusted to be isotropic or anisotropic, allowing an additional degree of control of the stretch / support in the different zones of the mesh (Figure 14a-Figure 15). The properties of an isotropic material are identical in all directions. Meanwhile, the properties of an anisotropic depend on / vary based on the direction.

[0317] 3D Printing Zones. The mesh can include different zones, such as, for example, those illustrated in Figure 1 - Figure 9. Referring now to Figure 1 -Figure 9, the mesh can include a Fat Grafting Zone (Solid yellow), which can maximize adipose tissue and has little to no elasticity. The mesh can further, for example, include a support zone (pattern 1, purple), which can maximize support (purple) and stretch in one direction (e.g., non-auxetic honeycomb), such that when elongated horizontally, vertical shortening occurs, maximizing breast support. The mesh can further include an Elastic Zone (Pattern 2, light pink), which can maximize projection (light pink) and can be auxetic, allowing elongation in both directions. The mesh can further include a Transition zone (Mix of Pattern 1 & 2, mixed yellow and purple), which can transition between a zone of support and a zone of maximal projection.

[0318] The materials can be used to maximize properties of each zone. The materials used to print each zone can be selected based on maximizing the properties of each zone. For example, the materials used to print each zone can be selected based on the properties of the following materials: a. Bioresorbable Polymer; b. Recombinant Human Collagen; and c. Adipose Cellular Stromal Matrix.

[0319] The mesh can, in some examples, include an additional feature for cases where there is a skin defect. For these cases, there can also be a solid component of the mesh that can be aligned with skin growth-promoting stroma to facilitate epithelization and skin coverage. There is potential to customize a solid patch of the matrix for skin replacement option, which is aligned with skin keratinocyte promoting factors for skin epithelization.

[0320] Macroscopic characteristics. Macroscopic characteristics of the zone include the location of the different zones and proportion of the entire construct (Figure 16).

[0321] With the current ADM technology, surgeons are not able to replicate a natural-looking breast compared to an original breast shape. However, with the computational breast analysis model combined with the 3D Matrix Mesh technology, surgeons can reconstruct a breast to complement the original breast shape surgically. In addition, the 3D Matrix Mesh cellular makeup can allow faster healing and cellular regeneration to support fat-in growth.

[0322] The 3D Matrix Mesh can allow customization and allow surgeons to control the implant position and prevent the need for submuscular implant placement.

[0323] The Matrix Mesh can have better inherited qualitative qualities, such as support of soft breast tissue, support for traditional implants and other implantable devices, and the ability to control 3D printing properties for different material property location that can support and encouraging isolated fat-in growth to specific regions of the breast. As such, at the lower part of the breast, which supports the weight of the implant, the mesh can have a tighter less elastic pattern, but over the top part of the breast above the nipple area, the mesh can have a more stretchable design to allow maximum projection of the underlining implant and to improve breast shape.

[0324] Incorporating computational breast analysis model combined with the 3D Matrix Mesh technology can incorporate a more natural breast when compared to the original breast shape for the patient. In addition to providing mechanical stability in the breast, the 3D Matrix Mesh can facilitate cellular wound healing and fat-growth regeneration.

[0325] The technology can be extended to other medical field that would need a customized 3D Matrix mesh related surgery.

[0326] Example 2

[0327] The technology disclosed herein envisions replacing the ADM using a computer breast analysis model to create a 3D matrix printed mesh customized to the patient's anatomical breast shape. Also, allowing the mesh material to be customized to support the implant's weight and allow more elasticity in areas that are needed while providing support for the underlying implant and finally, it would contain materials that can promote and encourage isolated fat-in growth. The 3D Matrix Mesh can promote fat-in growth regeneration and quicker healing time.

[0328] Example 3

[0329] The 4D Bio Matrix is a 3D-printed soft tissue multi-layered 3-dimensional unit matrix. Its primary function is to recreate a natural breast shape, providing critical support to the overlying skin post-mastectomy. Its auxetic properties characterize the matrix, allowing it to differentially control isotropic and anisotropic expansion. Some matrix sections are designed to expand for projection, while others resist expansion to provide improved support. Utilizing a computational breast analysis model with the 4D Bio Matrix printing technology enables the recreation of a patient-customized natural breast shape.

[0330] An advantage of the 4D Bio Matrix lies in its capability to be tailored to a patient’s natural breast shape. Using a computational breast analysis model to scan and match the patient's natural breast shape presents a promising advancement in breast reconstruction, enabling a patient-specific design.

[0331] Designed to support soft breast tissue, the 4D Bio Matrix can also support traditional implants or BioBreasts. 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.

[0332] The combination of a computational breast analysis model with the 4D Matrix segment unit technology holds the potential to revolutionize breast reconstruction.

[0333] Described herein 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. The matrix comprises multiple units, each fabricated with distinct material compositions and geometric structures, thereby providing unique auxetic properties. The matrix construct is characterized by a collection of three-dimensional units, each specifically designed with distinct auxetic structures that contribute to the overall functionality of the Matrix. This results in a structure that, although physically three-dimensional, exhibits four-dimensional behavior due to its ability to change and adapt over time.

[0334] Auxetic materials exhibit counterintuitive behavior when subjected to tensile forces, such that the material expands perpendicularly to the applied force. The multiplanar Matrix described herein is designed in zones which is composed of 3D Segments, wherein each zone possesses a specific set of auxetic properties, including varying degrees of elasticity and distinctive expansion and contraction characteristics when subjected to stress. This zoning enables the Matrix to contour around a breast implant, thereby facilitating a more natural, tear-drop shape.

[0335] In its relaxed state, the matrix exhibits a relatively flat, compact structure. However, upon the application of an external load, such as the placement of a breast implant, the distinct auxetic characteristics of the matrix facilitate its expansion and elongation in a controlled and precise manner.

[0336] The units situated at the anterior aspect of the implant are engineered for superior flexibility and extendibility, allowing them to maximize forward projection and conform to the implant's contour. Conversely, the segment at the implant's base functions as a supportive sling, thereby ensuring the stable positioning of the implant.

[0337] The upper segment of the matrix, featuring minimal elasticity, plays a pivotal role in providing support, thereby contributing to the formation of the upper pole of the breast. This variance facilitates a differential expansion that yields the desired tear-drop shape.

[0338] Described herein is a 3D-printed, biocompatible matrix with distinctive auxetic properties. The strategic segmentation of this Matrix, each with unique auxetic characteristics, allows for a controlled deformation that mimics the natural contour of a human breast, thereby mitigating the risk of implant rupture or displacement. This matrix is designed to encapsulate a breast implant, creating a three-dimensional tear-drop 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. It represents a significant advancement in the application of materials science and 3D printing technology in the field of medical implants.

[0339] Described herein is a sophisticated three-dimensional (3D) printed fabric-like matrix configured with distinct 3D units or segments, each possessing unique properties based on their designated roles in supporting and contouring a breast implant.

[0340] The matrix is arranged into three distinct zones.

[0341] 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.

[0342] Zone 2, positioned at the inferior part of the breast, is characterized by its ability to stretch uniaxially. This zone exhibits a unique property wherein the segments can stretch in one direction while simultaneously contracting in the opposite direction. This behavior enables Zone 2 to function as a sling, effectively supporting the weight of the implant and maintaining its position.

[0343] 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.

[0344] These 3D units are interconnected to form a comprehensive Matrix structure that, once expanded and contoured around the breast implant, results in a natural, three-dimensional teardrop breast shape. Given that the matrix dynamically adjusts over time to changes in the shape and size of the implant, it effectively functions as a four-dimensional (4D) structure.

[0345] In summary, the disclosed 3D printed fabric-like matrix represents an innovative solution that leverages the advancements in materials science and 3D printing technology, along with strategic design principles, to develop a more effective, natural-looking, and supportive structure for breast implants.

[0346] The composition of the disclosed construct 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.

[0347] 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. By incorporating materials that encourage cellular adhesion, the construct can potentially facilitate the integration of fat grafts into the surrounding tissue, thereby promoting improved aesthetic outcomes.

[0348] In instances where multiple polymers or a combination of materials are employed, 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.

[0349] Furthermore, the construct can be designed with specific porosities or microstructures to enable nutrient and oxygen exchange, which are crucial for the viability of the fat-grafted cells. These features can also promote vascularization and integration with the surrounding tissue, ultimately enhancing the long-term success of the fat grafting procedure.

[0350] In conclusion, the composition of the 3D printed fabric-like matrix can be customized using a single polymer, multiple polymers, or a combination of materials in order to optimize the construct's performance and support the viability of fat-grafted cells. This innovative approach has the potential to improve the overall aesthetic results and long-term success of breast augmentation procedures.

[0351] Described herein is a three-dimensional (4D) matrix, for surgical applications, specifically for breast implant support. This matrix design features 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.

[0352] An in silico theoretical model has been developed of the matrix, segmented into three zones with unique auxetic properties to contour a breast implant for a natural, tear-drop shape. The model also considers biocompatibility, mechanical strength, and cell survival support. It predicts favorable outcomes in stress distribution, implant rupture risk mitigation, and maintaining a natural appearance.

[0353] 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.

[0354] Described herein is a customized 4D printed matrix for breast reconstruction, with distinct zones designed to maximize functionality and adaptability:

[0355] 1. Fat Grafting Zone / Solid: This region, marked in yellow, is designed to maximize adipose tissue. It is a solid zone with no elasticity.

[0356] 2. Support Zone / Pattern 1: Indicated in purple, this zone is designed to provide maximum support. It features a non-auxetic honeycomb structure that stretches in one direction. When elongated horizontally, vertical shortening occurs, maximizing breast support.

[0357] 3. Elastic Zone / Pattern 2: Colored in light pink, this zone is designed to maximize projection. It features an auxetic structure that allows for elongation in both directions.

[0358] 4. Transition Zone / Mix of Patterns 1 & 2: This zone transitions between the support zone and the zone of maximal projection.

[0359] To maximize the properties of each zone, specific materials can be used based on their characteristics:

[0360] 1. Bioresorbable Polymer: Suitable for creating structures that can safely degrade in the body over time.

[0361] 2. Adipose Cellular Stromal Matrix: This could be used to support the viability and integration of fat cells within the Matrix.

[0362] Additionally, the devices can further include a feature for cases with a skin defect. A solid Matrix component 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.

[0363] Macroscopic Characteristics:

[0364] 1. The location of the different zones has been strategically determined.

[0365] 2. The ideal proportions of the entire construct can be established based on individual patient characteristics and surgical requirements.

[0366] A 3D biomatrix print of the prototype can allow biocompatibility and the Matrix’s effectiveness for commercialization to be assessed. Successful outcomes in these stages can pave the way for clinical trials to refine the matrix design and truly personalize the breast reconstruction process. The 3D-printed matrix can revolutionize the field, providing patients with a more effective, natural-looking solution.

[0367] The design aims to create a highly flexible, effective, and natural-looking solution for breast reconstruction by strategically using various materials' unique properties in specific matrix zones.

[0368] 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.

[0369] Distinct from traditional mash technologies that rely on layered materials, 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.

[0370] 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.

[0371] 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.

[0372] Different designs are being developed using the 3D printer, incorporating various unit geometries such as triangles, squares, hexagons, and other polygons (See Figure 36A-Figure 49). 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.

[0373] Example 4

[0374] 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.

[0375] 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.

[0376] 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.

[0377] 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.

[0378] Matrix properties. 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.

[0379] However, upon the application of an external load, such as the placement of a breast implant, the distinct auxetic characteristics of the matrix facilitate its expansion and elongation in a controlled and precise manner.

[0380] Matrix regions. The matrix comprises multiple 3D units, designed in at least 3 distinct zones, with each fabricated with distinct material compositions and geometric structures, thereby providing unique auxetic properties. Some zones are designed to expand for projection, while others resist expansion to provide improved support. These 3D units are interconnected to form a comprehensive Matrix structure that, once expanded and contoured around the breast implant, results in a natural, three-dimensional tear-drop breast shape. Given that the matrix dynamically adjusts over time to changes in the shape and size of the implant, it effectively functions as a 4D structure.

[0381] 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.

[0382] Zone 2, positioned at the inferior part of the breast, is characterized by its ability to stretch uniaxially. This zone exhibits a unique property wherein the segments can stretch in one direction while simultaneously contracting in the opposite direction. This behavior enables Zone 2 to function as a sling, effectively supporting the weight of the implant and maintaining its position.

[0383] 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.

[0384] Materials. 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. By incorporating materials that encourage cellular adhesion, the construct can potentially facilitate the integration of fat grafts into the surrounding tissue, thereby promoting improved aesthetic outcomes. In instances where multiple polymers or a combination of materials are employed, 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.

[0385] 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.

[0386] Potential Products include, but are not limited to, a 4D Bio Matrix for breast reconstruction and a 4D Bio Matrix for breast augmentation.

[0387] An in 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.

[0388] A prototype of the 4D-printed matrix can be fabricated with the following zones:

[0389] 1. Fat Grafting Zone / Solid: solid zone with no elasticity designed to maximize adipose tissue.

[0390] 2. 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.

[0391] 3. Elastic Zone / Pattern 2: designed to maximize projection with an auxetic structure that allows for elongation in both directions.

[0392] 4. Transition Zone / Mix of Patterns 1 & 2: transitions between zones 1&2.

[0393] 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.

[0394] The following materials can be used for the prototype:

[0395] 1. Bioresorbable Polymer to create structures that can safely degrade in the body over time. 2. Adipose Cellular Stromal Matrix to support the viability and integration of fat cells within the Matrix.

[0396] In addition, 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.

[0397] EXEMPLARY ASPECTS

[0398] In view of the described compositions and methods, herein below are described certain more particularly described aspects of the inventions. The particularly recited aspects should not, however, be interpreted to have any limiting effect on any different claims containing different or more general teaching described herein or that the “particular” aspects are somehow limited in some way other than the inherent meanings of the language and formulas literally used therein.

[0399] 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.

[0400] Example 2: The device of any examples herein, particularly example 1, wherein the thickness of the mesh is 2 centimeters or less.

[0401] 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.

[0402] 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.

[0403] 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.

[0404] 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.

[0405] 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.

[0406] 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.

[0407] 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.

[0408] Example 11 : The device of any examples herein, particularly examples 4-10, wherein the pillar is solid or hollow.

[0409] Example 12: The device of any examples herein, particularly examples 4-11, wherein the pillar is hollow, such that the pillar comprises a wall defining a lumen, the lumen being configured to receive and hold adipose tissue.

[0410] Example 13: The device of any examples herein, particularly examples 4-12, wherein each of the one or more tubules extends from the platform to the pillar, thereby connecting the platform and the pillar.

[0411] Example 14: The device of any examples herein, particularly examples 4-13, wherein the one or more tubules can provide a desired mechanical property.

[0412] Example 15: The device of any examples herein, particularly examples 4-14, wherein each three-dimensional unit can have from 3 to 10 tubules.

[0413] Example 16: The device of any examples herein, particularly examples 4-15, wherein each tubule is solid or hollow.

[0414] Example 17: The device of any examples herein, particularly examples 4-16, wherein each tubule is hollow, such that each tubule comprises a wall defining a lumen, the lumen being configured to receive and hold adipose tissue.

[0415] 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.

[0416] 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.

[0417] 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.

[0418] 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.

[0419] 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.

[0420] 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.

[0421] 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.

[0422] 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.

[0423] 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.

[0424] 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.

[0425] 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.

[0426] 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 cm3. 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.

[0427] 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.

[0428] Example 33: The device of any examples herein, particularly examples 4-32, wherein the one of more tubules of neighboring three-dimensional units are interwoven to thereby connect neighboring three-dimensional units to each other.

[0429] Example 34: The device of any examples herein, particularly examples 4-33, wherein the mesh is integrally formed, for example by 3D printing.

[0430] 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.

[0431] 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.

[0432] 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.

[0433] 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.

[0434] Example 39: The device of any examples herein, particularly example 38, wherein the fat grafting zone comprises adipose tissue.

[0435] Example 40: The device of any examples herein, particularly examples 1-39, wherein the adipose tissue comprises autologous adipose tissue.

[0436] 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.

[0437] Example 42: The device of any examples herein, particularly example 41, wherein the support zone has a non-auxetic geometry.

[0438] 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.

[0439] Example 45: The device of any examples herein, particularly example 44, wherein the elastic zone has an auxetic geometry.

[0440] 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.

[0441] 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.

[0442] 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.

[0443] 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.

[0444] 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.

[0445] 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.

[0446] 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.

[0447] 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, PEG based peptide conjugates, cell-adhesive poly(ethylene glycol), MMP-sensitive poly(ethylene glycol), PEGylated fibrinogen, 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), polyanhydrides, or a combination thereof.

[0448] 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.

[0449] 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).

[0450] 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).

[0451] 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).

[0452] 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).

[0453] 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.

[0454] 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).

[0455] 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.

[0456] 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.

[0457] 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.

[0458] 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.

[0459] 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.

[0460] 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.

[0461] 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.

[0462] 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.

[0463] 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.

[0464] Example 72: The device of any examples herein, particularly example 71, wherein the cuff forms a pocket.

[0465] 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.

[0466] 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.

[0467] Example 75: The device of any examples herein, particularly examples 1-74, wherein the anatomical location comprises a breast of the subject.

[0468] 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.

[0469] 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.

[0470] 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.

[0471] Example 79: The device of any examples herein, particularly examples 1-78, wherein the device is formed from a computational 3D space-filling model.

[0472] Example 80: The device of any examples herein, particularly examples 1-79, wherein the device is not flat.

[0473] 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.

[0474] 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.

[0475] 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.

[0476] Example 85: The device of any examples herein, particularly examples 1-84, wherein the device is anatomically designed for the subject.

[0477] Example 86: The device of any examples herein, particularly examples 1-85, wherein the device is produced by additive manufacturing (e.g., 3D printing).

[0478] Example 87: The device of any examples herein, particularly examples 1-86, wherein the device is a single piece of mesh (e.g., monolithic).

[0479] Example 88: The device of any examples herein, particularly examples 1-87, wherein the device is biocompatible.

[0480] 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).

[0481] Example 90: The method of any examples herein, particularly example 89, wherein the method comprises making the device based on a 3D model.

[0482] Example 91 : The method of any examples herein, particularly example 90, wherein the 3D model is based on the Fibonacci equation.

[0483] 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.

[0484] Example 93: The method of any examples herein, particularly example 92, wherein the method further comprises collecting the anatomical image of the subject.

[0485] 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.

[0486] 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.

[0487] 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.

[0488] Example 98: The method of any examples herein, particularly example 97, wherein the method comprises breast reconstruction or augmentation.

[0489] Example 99: The method of any examples herein, particularly examples 94-98, wherein the method further comprises anatomically designing the device for the subject.

[0490] Other advantages which are obvious and which are inherent to the invention will be evident to one skilled in the art. It will be understood that certain features and sub-combinations are of utility and may be employed without reference to other features and sub-combinations. This is contemplated by and is within the scope of the claims. Since many possible embodiments may be made of the invention without departing from the scope thereof, it is to be understood that all matter herein set forth or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense.

[0491] The methods of the appended claims are not limited in scope by the specific methods described herein, which are intended as illustrations of a few aspects of the claims and any methods that are functionally equivalent are intended to fall within the scope of the claims. Various modifications of the methods in addition to those shown and described herein are intended to fall within the scope of the appended claims. Further, while only certain representative method steps disclosed herein are specifically described, other combinations of the method steps also are intended to fall within the scope of the appended claims, even if not specifically recited. Thus, a combination of steps, elements, components, or constituents may be explicitly mentioned herein or less, however, other combinations of steps, elements, components, and constituents are included, even though not explicitly stated.

Claims

CLAIMSWhat is claimed is:

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.

2. The device of claim 1, wherein the thickness of the mesh is 2 centimeters or less.

3. The device of claim 1 or claim 2, wherein the thickness is from 0.4 centimeters to 2 centimeters, or from 0.5 to 2 centimeters.

4. The device of any one of claims 1-3, wherein the mesh comprises a plurality of three- dimensional units, the plurality of three-dimensional units being interconnected to form the mesh.

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.

6. The device of any one of claims 1-5, wherein the mesh is disposed on a membrane, such as a second mesh.

7. The device of any one of claims 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.

8. The device of any one of claims 4-7, wherein at least a portion of each of the plurality of three-dimensional units is configured to receive and hold adipose tissue.

9. The device of any one of claims 4-8, wherein each of the three-dimensional units comprises a platform, a pillar, and one or more tubules.

10. The device of any one of claims 4-9, wherein the pillar can provide a desired mechanical property and / or define a volume configured to receive and hold adipose tissue.

11. The device of any one of claims 4-10, wherein the pillar is solid or hollow.

12. The device of any one of claims 4-11, wherein the pillar is hollow, such that the pillar comprises a wall defining a lumen, the lumen being configured to receive and hold adipose tissue.

13. The device of any one of claims 4-12, wherein each of the one or more tubules extends from the platform to the pillar, thereby connecting the platform and the pillar.

14. The device of any one of claims 4-13, wherein the one or more tubules can provide a desired mechanical property.

15. The device of any one of claims 4-14, wherein each three-dimensional unit can have from 3 to 10 tubules.

16. The device of any one of claims 4-15, wherein each tubule is solid or hollow.

17. The device of any one of claims 4-16, wherein each tubule is hollow, such that each tubule comprises a wall defining a lumen, the lumen being configured to receive and hold adipose tissue.

18. The device of any one of claims 4-17, wherein each tubule has an average diameter of 1 .6 millimeters or less.

19. The device of any one of claims 4-18, wherein the platform can have any suitable geometry, such as polygonal (e.g., triangular, rectangular, hexagonal, etc.) or circular.

20. The device of any one of claims 4-19, wherein each three-dimensional unit further comprises a base, the pillar extending from the base to the platform.

21. The device of claim 20, wherein the base has any suitable geometry, such as polygonal (e.g., triangular, rectangular, hexagonal) or circular.

22. The device of claim 20 or claim 21 , wherein the base and the platform are the same or different.

23. The device of any one of claims 4-22, wherein the base (when present) and / or the platform each independently has a planar surface.

24. The device of any one of claims 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.

25. The device of any one of claims 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.

26. The device of any one of claims 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.

27. The device of any one of claims 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.

28. The device of any one of claims 4-27, wherein the average height is from 0.4 centimeters to 2 centimeters, such as from 0.5 to 2 centimeters.

29. The device of any one of claims 4-28, wherein the platform, the pillar, the base (when present), and the one or more tubules are integrally formed.

30. The device of any one of claims 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 cm3.

31. The device of any one of claims 4-30, wherein neighboring three-dimensional units are connected to each other to form the mesh.

32. The device of any one of claims 4-31 , wherein the one or more tubules are configured to connect neighboring three-dimensional units to each other to form the mesh.

33. The device of any one of claims 4-32, wherein the one of more tubules of neighboring three-dimensional units are interwoven to thereby connect neighboring three-dimensional units to each other.

34. The device of any one of claims 4-33, wherein the mesh is integrally formed, for example by 3D printing.

35. The device of any one of claims 4-34, wherein the mesh comprises a plurality of three- dimensional units as shown in one or more of Figure 36A-Figure 49.

36. The device of any one of claims 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.

37. The device of any one of claims 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.

38. The device of any one of claims 1-37, wherein the mesh comprises a fat grafting zone having little to no elasticity.

39. The device of claim 38, wherein the fat grafting zone comprises adipose tissue.

40. The device of any one of claims 1-39, wherein the adipose tissue comprises autologous adipose tissue.

41. The device of any one of claims 1-40, wherein the mesh comprises a support zone, the support zone being elastic along one direction.

42. The device of claim 41 , wherein the support zone has a non-auxetic geometry.

43. The device of claim 41 or claim 42, wherein the support zone comprises an anisotropic material, a non-auxetic material, or a combination thereof.

44. The device of any one of claims 1-43, wherein the mesh comprises an elastic zone, the elastic zone having a high amount of elasticity in multiple directions.

45. The device of claim 44, wherein the elastic zone has an auxetic geometry.

46. The device of claim 44 or claim 45, wherein the elastic zone comprises an isotropic material, an auxetic material, or a combination thereof.

47. The device of any one of claims 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.

48. The device of any one of claims 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.

49. The device of any one of claims 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.

50. The device of any one of claims 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.

51. The device of any one of claims 1-50, wherein the plurality of zones and / or the plurality of three-dimensional units each have a different composition and a different geometry.

52. The device of any one of claims 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.

53. The device of any one of claims 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.

54. The device of any one of claims 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 norbomene, polyethylene glycol dithiol, thiolated gelatin, thiolated chitosan, thiolated silk, silk, PEG based peptide conjugates, cell-adhesive poly(ethylene glycol), MMP-sensitive poly(ethylene glycol), PEGylated fibrinogen, 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), polyanhydrides, or a combination thereof.

55. The device of any one of claims 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.

56. The device of any one of claims 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).

57. The device of any one of claims 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).

58. The device of any one of claims 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).

59. The device of any one of claims 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).

60. The device of any one of claims 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.

61. The device of any one of claims 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 aportion of each of the plurality of three-dimensional units, or a combination thereof independently comprises polyglycolic acid (PGA).

62. The device of any one of claims 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.

63. The device of any one of claims 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.

64. The device of claim 63, wherein the therapeutic agent is dispersed substantially homogeneously throughout the zone(s), the three-dimensional units, and / or device.

65. The device of claim 63 or claim 64, wherein the therapeutic agent comprises an anticancer agent, anti-inflammatory agent, analgesic agent, antimicrobial agent, or a combination thereof.

66. The device of any one of claims 63-65, wherein the therapeutic agent comprises a chemotherapeutic agent, an immunotherapeutic agent, or a combination thereof.

67. The device of any one of claims 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.

68. The device of any one of claims 1-67, wherein the device comprises a support zone and an elastic zone.

69. The device of any one of claims 1-68, wherein the device comprises a fat grafting zone, a support zone, a transition zone, and an elastic zone.

70. The device of any one of claims 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.

71. The device of any one of claims 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.

72. The device of claim 71 , wherein the cuff forms a pocket.

73. The device of any one of claims 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.

74. The device of any one of claims 1-73, wherein the device is configured to support and / or reshape an organ and / or an implant when inserted in the subject.

75. The device of any one of claims 1-74, wherein the anatomical location comprises a breast of the subject.

76. The device of claim 75, wherein the device is configured to support at least a portion of a breast or at least a portion of a breast implant.

77. The device of claim 75 or claim 76, wherein the device is configured to support a breast or a breast implant.

78. The device of any one of claims 1-77, wherein the device is formed from a model based on a tessellation of polyhedrons.

79. The device of any one of claims 1-78, wherein the device is formed from a computational 3D space-filling model.

80. The device of any one of claims 1-79, wherein the device is not flat.

81. The device of any one of claims 1-80, wherein the device has a three dimensional shape.

82. The device of any one of claims 1-81, wherein the device has a three-dimensional parametric teardrop shape.

83. The device of any one of claims 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.

84. The device of any one of claims 1-83, wherein the device has a three-dimensional parametric teardrop shape following the Fibonacci equation.

85. The device of any one of claims 1-84, wherein the device is anatomically designed for the subject.

86. The device of any one of claims 1-85, wherein the device is produced by additive manufacturing (e.g., 3D printing).

87. The device of any one of claims 1-86, wherein the device is a single piece of mesh (e.g., monolithic).

88. The device of any one of claims 1-87, wherein the device is biocompatible.

89. A method of manufacturing the device of any one of claims 1-88, the method comprising making the device using additive manufacturing (e.g., 3D printing).

90. The method of claim 89, wherein the method comprises making the device based on a 3D model.

91. The method of claim 90, wherein the 3D model is based on the Fibonacci equation.

92. The method of claim 90 or claim 91, wherein the 3D model is based on an anatomical image of a subject.

93. The method of claim 92, wherein the method further comprises collecting the anatomical image of the subject.

94. A method of treating a subject in need thereof, the method comprising implanting the device of any one of claims 1-88 into the subject.

95. The method of claim 94, wherein the device is implanted into at least a portion of a breast of the subject.

96. The method of claim 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.

97. The method of claim 94, wherein the device is implanted into a breast of the subject.

98. The method of claim 97, wherein the method comprises breast reconstruction or augmentation.

99. The method of any one of claims 94-98, wherein the method further comprises anatomically designing the device for the subject.

Images