Design and fabrication methods of radially arrayed lattice architectures for controlled properties of medical devices

Abstract

A method of producing a structure, as well as the structure produced according to the method. The method includes steps of defining an outer surface of the structure, an internal volume of the structure being defined within the outer surface; defining, within the internal volume of the structure, one or more cores; selecting a unit cell geometry; and radially arraying unit cells around a perimeter of and / or within the internal volume of the structure to form a plurality of such unit cells that extend between the one or more cores and the perimeter, within the internal volume of the structure. The structures can be produced via additive manufacturing and loaded with one or more therapeutic compounds for use as medical devices. An example of such a medical device is an intravaginal ring (IVR) or a subcutaneous rod-shaped implant device.

Description

Attorney Docket No. 4210.0466WODesign and Fabrication Methods of Radially Arrayed Lattice Architectures for Controlled Properties of Medical DevicesCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims priority to U.S. Provisional Patent Application Serial No. 63 / 762,296, which was filed February 24, 2025, the disclosure of which is incorporated herein by reference in its entirety.GOVERNMENT LICENSE RIGHTSThis invention was made with government support under Grant Numbers AI136002 and TR001109 awarded by the National Institutes of Health. The government has certain rights in the invention.BACKGROUND

[0001] There is at present an ongoing unmet need for systems that provide controlled delivery of therapeutic compound(s) (e.g., pharmaceutical drugs). It has been shown that precise dosing and delivery of therapeutic compounds can improve patient outcomes while minimizing adverse events. The modality for the controlled delivery of the therapeutic compound (e.g., topical, parenteral, oral, etc.) often dictates the type of materials, manufacturing, and release mechanism selected for use. For medical devices specifically, it is well understood that the application impacts device design, which in turn dictates appropriate materials and fabrication methods. For devices aimed at sustained delivery of such therapeutic compounds, either through drug diffusion or matrix degradation, device design is a critical parameter to optimize therapeutic performance. Common methods utilized to control device design include foaming, extrusion, injection molding, and polymer gelation. Each of these methods, however, are known to have disadvantages associated with the use thereof, for example, regarding material selection, fabrication parameters, and / or drug compatibility. The overarching disadvantage to these common methods is the lack of precise control over the physical macro and micro dimensions of the resultant medical device.Attorney Docket No. 4210.0466WO

[0002] Recent advancements in additive manufacturing (AM), more commonly referred to as “3D printing,” have harnessed the power of computationally aided design (CAD) to precisely fabricate medical devices. The fields currently being explored include, for example, bespoke prosthetics, implants, and bioprinting organs. The design approach in CAD is dictated by the parameters of each application. The use of 3D printed lattices to control drug delivery is a nascent area of study and there is an as yet unmet need for new methods and devices for controlling the delivery of therapeutic compounds.

[0003] An area that is of particular interest and importance to the presently disclosed subject matter is controlling the delivery of therapeutic compounds through the design of the device itself. According to the presently disclosed subject matter, 3D printed lattice structures have been evaluated for controlling performance parameters of therapeutic compound delivery. The incorporation of complex geometries in circular devices has far reaching applications. This has largely been addressed for devices that are hollow, such as, for example, stents (e.g., those that both permanent and biodegradable). However, a challenge remains for designing devices that are intended to have structural complexity throughout, an example of which includes a radially arrayed lattice. This can largely be attributed to the way conventionally used CAD software imparts geometric complexity, as well as the computational cost associated therewith.

[0004] For mesh-based systems, geometric complexity is achieved through the arraying of a unit cell to generate a lattice structure. Unit cells are defined by XYZ dimensions and are inherently a polygon, usually 4-sided. For medical devices that are also polygonal in nature, the lattice can be adjusted to fit the boundaries. However, for circular medical devices, the resulting structure resembles a “punch-out” and thus has rough edges that either need to be sealed in CAD or post-fabrication to enable patient usability. There are other non-mesh-based CAD systems that can generate a lattice for circular device. A lattice that conforms radially can be generated for simple cylinders however the thickness of the struts is limited, as the center of the lattice is the focal point of the circle and resulting in the lattice collapsing in on itself. TheAttorney Docket No. 4210.0466WOlarger the device and more precise the lattice, the more tessellation is required to define the structure and, thus, the computational space increases for both design and fabrication. The known non-mesh-based CAD systems, however, cannot be extended to more complex circular devices, such as a torus, for both of the above stated reasons. Therefore, there remains a need to develop a method to enable lattices and subsequent geometric complexity for circular medical devices for precise and controlled delivery of therapeutic compounds through the design of the medical device itself.SUMMARY

[0005] The presently disclosed subject matter now will be described more fully hereinafter, in which some, but not all embodiments of the presently disclosed subject matter are described. Indeed, the presently disclosed subject matter can be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements.

[0006] A method of producing a structure, the method comprising defining an outer surface of the structure, an internal volume of the structure being defined within the outer surface; defining, within the internal volume of the structure, one or more cores; selecting a unit cell geometry; and radially arraying unit cells around a perimeter of and / or within the internal volume of the structure to form a plurality of such unit cells that extend between the one or more cores and the perimeter, within the internal volume of the structure.

[0007] According to any of the example methods disclosed herein, the unit cells are each formed by a plurality of struts.

[0008] According to any of the example methods disclosed herein, at least a subset of the plurality of struts extend between the one or more cores and the perimeter of the structure.

[0009] According to any of the example methods disclosed herein, the one or more cores is a plurality of cores.Attorney Docket No. 4210.0466WO

[0010] According to any of the example methods disclosed herein, the plurality of cores have a cross-sectional shape that is the same as or different from each other.

[0011] According to any of the example methods disclosed herein, the one or more cores have a cross-sectional shape that is circular.

[0012] According to any of the example methods disclosed herein, the one or more cores have a cross-sectional shape that is non-circular.

[0013] According to any of the example methods disclosed herein, the noncircular shape is ellipsoidal or triangular.

[0014] According to any of the example methods disclosed herein, the one or more cores is centered, relative to a cross-section of the internal volume of the structure, within the internal volume of the structure.

[0015] According to any of the example methods disclosed herein, the one or more cores is offset, relative to the cross-section of the internal volume of the structure, from a center of the internal volume of the structure.

[0016] According to any of the example methods disclosed herein, the internal volume of the structure is subdivided in a circumferential direction into a plurality of circumferential portions; in a first subset of the plurality of circumferential portions, the unit cells are formed therein; and in a second subset of the plurality of circumferential portions, the internal volume within each of the second subset is entirely solid.

[0017] According to any of the example methods disclosed herein, the structure has a shape of a torus.

[0018] According to any of the example methods disclosed herein, the method further comprises forming, on a portion of the perimeter of the structure, an outer cover.

[0019] According to any of the example methods disclosed herein, the structure has a shape of a U, a Y, a V, a T, or a rod.

[0020] According to any of the example methods disclosed herein, the unit cell geometry comprises one or more of X, star, cross, tesseract, vintiles, octet, diamond, honeycomb, and grid.

[0021] According to any of the example methods methods disclosed herein, the method comprises immersing the structure in a solution comprisingAttorney Docket No. 4210.0466WOone or more therapeutic compounds for storage of the one or more therapeutic compounds in at least the struts of the unit cells and release of the one or more therapeutic compounds in vivo.

[0022] According to any of the example methods disclosed herein, the one or more cores are solid structures comprising one or more therapeutic compounds within the structure; and optionally, the unit cells define a hollow void and act as a rate-controlling membrane for the release of the one or more therapeutic compounds in vivo.

[0023] According to any of the example methods disclosed herein, the core is solid

[0024] According to any of the example methods disclosed herein, the core is hollow.

[0025] According to any of the example methods disclosed herein, a medical device, such as an implant device, can be produced using any of the example methods disclosed herein.

[0026] According to any of the example methods disclosed herein, the medical device is an intravaginal ring (IVR).

[0027] According to any of the example methods disclosed herein, the medical device is a rod-shaped implant device.

[0028] According to another example, a medical device is disclosed herein, the medical device comprising an outer surface that delimits an internal volume of the medical device; one or more cores defined within the internal volume of the medical device; and a plurality of unit cells radially arrayed around a perimeter of and / or within the internal volume of the structure, such that the plurality of such unit cells that extend between the one or more cores and the perimeter, within the internal volume of the structure.

[0029] According to any of the example medical devices disclosed herein, the unit cells are each formed by a plurality of struts.

[0030] According to any of the example medical devices disclosed herein, at least a subset of the plurality of struts extend between the one or more cores and the perimeter of the structure.

[0031] According to any of the example medical devices disclosed herein, the one or more cores is a plurality of cores.Attorney Docket No. 4210.0466WO

[0032] According to any of the example medical devices disclosed herein, the plurality of cores are a same or a different cross-sectional shape from each other.

[0033] According to any of the example medical devices disclosed herein, the one or more cores have a cross-sectional shape that is circular.

[0034] According to any of the example medical devices disclosed herein, the one or more cores have a cross-sectional shape that is non-circular.

[0035] According to any of the example medical devices disclosed herein, the non-circular shape is ellipsoidal or triangular.

[0036] According to any of the example medical devices disclosed herein, the one or more cores is centered, relative to a cross-section of the internal volume of the structure, within the internal volume of the structure.

[0037] According to any of the example medical devices disclosed herein, the one or more cores is offset, relative to the cross-section of the internal volume of the structure, from a center of the internal volume of the structure.

[0038] According to any of the example medical devices disclosed herein, the internal volume of the structure is subdivided into a plurality of circumferential portions; in a first subset of the plurality of circumferential portions, the unit cells are formed therein; and in a second subset of the plurality of circumferential portions, the internal volume is a solid structure.

[0039] According to any of the example medical devices disclosed herein, the structure has a shape of a torus.

[0040] According to any of the example medical devices disclosed herein, the medical device comprises an outer cover that is formed on at least a portion of the perimeter of the structure.

[0041] According to any of the example medical devices disclosed herein, the structure has a shape of a U, a Y, a V, a T, or a rod.

[0042] According to any of the example medical devices disclosed herein, the unit cell geometry comprises one or more of X, star, cross, tesseract, vintiles, octet, diamond, honeycomb, and grid.

[0043] According to any of the example medical devices disclosed herein, the struts of the unit cells comprise one or more therapeutic compounds storedAttorney Docket No. 4210.0466WOtherein; and the struts of the unit cells are configured to release the one or more therapeutic compounds in vivo.

[0044] According to any of the example medical devices disclosed herein, the medical device is an intravaginal ring (IVR).

[0045] According to any of the example medical devices disclosed herein, the medical device is a rod-shaped implant device.

[0046] According to any of the example medical devices disclosed herein, the medical device is an insert or a housing.

[0047] According to any of the example medical devices disclosed herein, the insert or the housing contains one or more therapeutic compounds.

[0048] According to any of the example medical devices disclosed herein, the insert or the housing is therapeutically inert.

[0049] According to another example, a method of producing a structure is disclosed herein, the method comprising: defining an outer surface of the structure, an internal volume of the structure being defined within the outer surface; defining, within the internal volume of the structure, one or more cores; selecting a unit cell geometry; and radially arraying unit cells around a perimeter of and / or within the internal volume of the structure to form a plurality of such unit cells that extend between the one or more cores and the perimeter, within the internal volume of the structure; optionally, wherein the unit cells are each formed by a plurality of struts; optionally, wherein at least a subset of the plurality of struts extend between the one or more cores and the perimeter of the structure; optionally, wherein the one or more cores is a plurality of cores; optionally, wherein the plurality of cores have a cross-sectional shape that is the same as or different from each other; optionally, wherein the one or more cores have a cross-sectional shape that is circular; optionally, wherein the one or more cores have a cross-sectional shape that is non-circular, the non-circular shape optionally being ellipsoidal or triangular; optionally, wherein the one or more cores is: centered, relative to a crosssection of the internal volume of the structure, within the internal volume of the structure; and / or offset, relative to the cross-section of the internal volume of the structure, from a center of the internal volume of the structure; optionally, wherein: the internal volume of the structure is subdivided in a circumferentialAttorney Docket No. 4210.0466WOdirection into a plurality of circumferential portions; and / or in a first subset of the plurality of circumferential portions, the unit cells are formed therein; and / or in a second subset of the plurality of circumferential portions, the internal volume within each of the second subset is entirely solid; and / or optionally, wherein the structure has a shape of a torus or, further optionally, a shape of a II, a Y, a V, a T, or a rod; optionally, wherein an outer cover is formed on at least a portion of the perimeter of the structure; optionally, wherein the unit cell geometry comprises one or more of X, star, cross, tesseract, vintiles, octet, diamond, honeycomb, and grid; optionally, the method comprising immersing the structure in a solution comprising one or more therapeutic compounds for storage of the one or more therapeutic compounds in at least the struts of the unit cells and release of the one or more therapeutic compounds in vivo\ optionally, wherein: the one or more cores are solid structures comprising one or more therapeutic compounds within the structure; and the unit cells define a hollow void and act as a ratecontrolling membrane for the release of the one or more therapeutic compounds in vivo optionally, wherein the core is solid or hollow.

[0050] According to another example, a medical device is disclosed herein, the medical device being produced using the any of the methods disclosed herein.

[0051] According to any of the example medical devices disclosed herein, the medical device is an intravaginal ring (IVR).

[0052] According to any of the example medical devices disclosed herein, the medical device is a rod-shaped implant device.

[0053] According to another example, a medical device is disclosed herein, the medical device comprising: an outer surface that delimits an internal volume of the medical device; one or more cores defined within the internal volume of the medical device; and a plurality of unit cells radially arrayed around a perimeter of and / or within the internal volume of the structure, such that the plurality of such unit cells that extend between the one or more cores and the perimeter, within the internal volume of the structure; optionally, wherein the unit cells are each formed by a plurality of struts; optionally, wherein at least a subset of the plurality of struts extend between the one orAttorney Docket No. 4210.0466WOmore cores and the perimeter of the structure; optionally, wherein the one or more cores is a plurality of cores; optionally, wherein the plurality of cores are a same or a different cross-sectional shape from each other; optionally, wherein the one or more cores have a cross-sectional shape that is circular; optionally, wherein the one or more cores have a cross-sectional shape that is non-circular, the non-circular shape optionally being ellipsoidal or triangular; optionally, wherein the one or more cores is: centered, relative to a crosssection of the internal volume of the structure, within the internal volume of the structure; and / or offset, relative to the cross-section of the internal volume of the structure, from a center of the internal volume of the structure; optionally, wherein: the internal volume of the structure is subdivided into a plurality of circumferential portions; and / or in a first subset of the plurality of circumferential portions, the unit cells are formed therein; and / or in a second subset of the plurality of circumferential portions, the internal volume is a solid structure; optionally, wherein the structure has a shape of a torus or, further optionally, a shape of a II, a Y, a V, a T, or a rod; optionally, wherein an outer cover is formed on at least a portion of the perimeter of the structure; optionally, wherein the unit cell geometry comprises one or more of X, star, cross, tesseract, vintiles, octet, diamond, honeycomb, and grid; optionally, wherein: the struts of the unit cells comprise one or more therapeutic compounds stored therein; and / or the struts of the unit cells are configured to release the one or more therapeutic compounds in vivo optionally, wherein the medical device is an intravaginal ring (IVR); optionally, wherein the medical device is an insert or a housing; and optionally, wherein the insert or the housing contains one or more therapeutic compounds therein or is therapeutically inert.BRIEF DESCRIPTION OF THE DRAWINGS

[0054] The accompanying figures illustrate a number of exemplary embodiments and are a part of the specification. Together with the following description, these figures demonstrate and explain various principles of the instant disclosure.Attorney Docket No. 4210.0466WO

[0055] FIGS. 1 A and 1 B show, respectively, method for imparting geometric complexity within a torus structure (or toroid) using computationally aided design (CAD) software. In FIG. 1A, the method is performed using a linear array, utilizing meshes. In FIG. 1 B, the method is performed using a radial array, utilizing non-uniform rational basis spline (NURBS).

[0056] FIGS. 2A and 2B show the effect of the presence of a core on the geometric complexity of the torus structure produced using the method shown in FIG. 1 B, as the torus structure shown in FIG. 2A does not have a core and the torus structure shown in FIG. 2B does have a core. Without a core (FIG.2A) geometric complexity can only be achieved around the circular device whereas, with a core (FIG. 2B) geometric complexity can be achieved throughout the circular device.

[0057] FIG. 3 shows and defines surfaces within the design space in CAD software.

[0058] FIG. 4A is a schematic illustration of a torus structure produced with a radially arrayed architecture, with the inner core having a negligible diameter of 0.001 mm.

[0059] FIG. 4B is a schematic illustration of a torus structure produced with a radially arrayed architecture, with the inner core having a diameter of 1 .0 mm, such that the torus structure has a solid core.

[0060] FIGS. 5A-5I show example torus structures using the radially arrayed design method of FIG. 1 B using 9 different unit cell designs.

[0061] FIGS. 6A-6C each show top and cross-sectional views of banded radially arrayed torus structures, produced using a tesseract unit cell (FIG.6A), a star unit cell (FIG. 6B), and a diamond unit cell (FIG. 60).

[0062] FIGS. 7A-7I show cross-sectional views of example CAD renderings and 3D printed banded torus structures produced with a radially arrayed architecture, using a plurality of different unit cell shapes.

[0063] FIGS. 8A-8I show perspective and magnified views of example torus structures produced with a radially arrayed architecture, using a plurality of different unit cell shapes, these figures showing the internal structure of each of the torus structures.Attorney Docket No. 4210.0466WO

[0064] FIGS. 9A-9C each show perspective and magnified views of radially arrayed torus structures, produced using a tesseract unit cell (FIG. 6A), a star unit cell (FIG. 6B), and a diamond unit cell (FIG. 6C).

[0065] FIG. 10A shows perspective and top views of example torus structures produced with a linearly arrayed architecture (left half of images) and a radially arrayed architecture (right half of images).

[0066] FIG. 10B is a table showing theoretical and empirical metrics / values for each of the linearly arraying and radially arraying methods.

[0067] FIGS. 11A-11C show images of example CAD renderings and a fabricated torus structures, each of which is produced with a different radially arrayed architecture.

[0068] FIG. 12 shows images of example torus structures produced with a radially arrayed architecture, as well as tabulated theoretical and empirical metrics / values for the example torus structures shown therein.

[0069] FIG. 13A shows images of compression testing of commercially available intravaginal rings (IVRs) compared to a torus structure according to the present disclosure, produced with a radially arrayed architecture.

[0070] FIG. 13B is a graphical plot of load at 50% compression for several of the torus structures, plotted by band type.

[0071] FIG. 14A shows perspective views of a solid torus structure (left) and a torus structure (right) produced with a radially arrayed architecture, according to the subject matter disclosed herein.

[0072] FIG. 14B is a table showing metrics / values for the example torus structures shown in FIG. 14A.

[0073] FIG. 14C is a graphical plot of cumulative in vitro release of progesterone (pg) as a function of time (days) from the torus structures shown in FIG. 14A.

[0074] FIG. 14D is a graphical plot of cumulative in vitro release of progesterone (%) as a function of time (days) from the torus structures shown in FIG. 14A.

[0075] FIG. 15A shows various graphical plots of pharmacokinetic efficacy as a function of time (days), comparing the performance of a solid torusAttorney Docket No. 4210.0466WOstructure against a torus structure produced with a radially arrayed architecture, according to the subject matter disclosed herein.

[0076] FIG. 15B is a table showing metrics / values for the torus structures, on which the graphical plots shown in FIG. 15A were based and from which the graphical plots shown in FIG. 15A were produced.

[0077] FIG. 16 shows graphical plots for example embodiments of torus structures produced with a radially arrayed architecture, the left plot showing theoretical surface area (mm2) as a function of theoretical volume (mm3) for torus structures produced with a radially arrayed architecture and the right plot showing specific surface area (mm'1) as a function of strut thickness (pm) for torus structures produced using linearly arrayed and radially arrayed architectures.

[0078] FIG. 17A shows examples of rod-shaped (e.g., axially-extending) structures produced with a radially arrayed architecture and having different unit cell geometries.

[0079] FIG. 17B shows graphical plots of pharmacokinetic efficacy as a function of time (days), comparing the performance of a solid rod-shaped structure to the performance of the rod-shaped structures shown in FIG. 17A.

[0080] FIGS. 18A-18D show images of a torus structure produced with a radially arrayed architecture with a core structure of several different diameters.

[0081] FIG. 19 shows images of a torus structure produced with a radially arrayed architecture and having a non-circular core structure, specifically two inner cores, each with a half-moon or semicircular cross-sectional shape.

[0082] FIG. 20A shows a torus structure produced with a radially arrayed architecture and having a core structure located at the innermost circumferential surface or edge of the torus structure.

[0083] FIG. 20B shows a torus structure produced with a radially arrayed architecture and having a core structure located at the outermost circumferential surface or edge of the torus structure.

[0084] FIG. 21 shows images of a torus structure produced with a radially arrayed architecture and having offsetting core structures, specifically two circular core structures that are radially adjacent to each other.Attorney Docket No. 4210.0466WO

[0085] FIG. 22A shows features of a torus structure produced with a radially arrayed architecture and having a solid core structure.

[0086] FIG. 22B shows features of a torus structure produced with a radially arrayed architecture and having a hollow core structure.

[0087] FIGS. 23A-23I show example torus structures using the radially arrayed design method of FIG. 1 B using 9 different unit cell designs.

[0088] FIGS. 24A-24C show examples of a lattice design in a section of a torus structure containing multiple strut thicknesses (FIG. 24A), a bisected section of the torus structure (FIG. 24B), and a section of a 3D printed torus structure (FIG. 24C).

[0089] FIG. 25 shows an example torus structure having both solid portions (e.g., segments of the torus structure that extend circumferentially) and also lattice portions (e.g., segments of the torus structure that extend circumferentially), the lattice portions being produced with a radially arrayed architecture.

[0090] FIGS. 26A-26C show images of an unbanded torus structure (FIG.26A, outer surface open), a first example banded torus structure (FIG. 26B, partially closed / covered outer surface), and a second example banded torus structure (FIG. 26C, partiall closed / covered outer surface).

[0091] FIG. 27 shows absorption of a pharmaceutical compound within a torus structure produced with a radially arrayed architecture, the size of which increases as a function of time and absorption of the pharmaceutical compound.

[0092] FIGS. 28A and 28B show, respectively, method for imparting geometric complexity within a torus structure (or toroid) using computationally aided design (CAD) software. In FIG. 28A, the method is performed using a linear array, utilizing meshes. In FIG. 28B, the method is performed using a radial array, utilizing non-uniform rational basis spline (NURBS). Without a core (FIG. 2A) geometric complexity can only be achieved around the circular device whereas, with a core (FIG. 2B) geometric complexity can be achieved throughout the circular device.

[0093] FIG. 29A is an illustration of preparation of a rod-shaped device (see FIG. 17A) to house multiple drug / polymer solid implants.Attorney Docket No. 4210.0466WO

[0094] FIG. 29B shows hollow rod-shaped devices on a build platform.

[0095] FIG. 29C shows a drug / polymer solid implant within a silicone 3D printed hollow rod-shaped device.

[0096] FIG. 29D shows a plurality of 3D printed hollow rod-shaped devices in silicone-urethane resin using CLIP 3D printing.

[0097] FIG. 30 schematically shows example design options and variations for radially-arrayed rod-shaped devices.

[0098] FIG. 31 A shows torus structures that have a radially arrayed architecture on a build platform with vertical supports.

[0099] FIG. 31 B is a side view of one of the torus structures shown in FIG.31 A without vertical supports.

[0100] FIG. 32 is a graphical plot of a cumulative percentage released from the torus structure as a function of time (days) for different amounts of a pharmaceutical compound in / on the torus structure.

[0101] FIG. 33A is a graphical plot comparing efficacy (cumulative percent release) of a solid torus structure vs a torus structure having a radially arrayed architecture, as a function of time (days), with both torus structures loaded with 30 mg dapirivine (DPV).

[0102] FIG. 33B is a graphical plot comparing efficacy (cumulative percent release) of a solid torus structure vs a torus structure having a radially arrayed architecture, as a function of time (days), with both torus structures loaded with 150 mg dapirivine (DPV).

[0103] FIG. 34 is a graphical plot comparing efficacy (cumulative percent release) of a torus structure having a radially arrayed architecture, releasing three different pharmaceutical compounds that are loaded in / or the torus structure, as a function of time (days).

[0104] FIG. 35A is a graphical plot comparing efficacy (cumulative percent release) of a solid torus structure vs a torus structure having a radially arrayed architecture, as a function of time (days), each of the solid torus structure and the radially arrayed torus structure being loaded with 150 mg of three different pharmaceutical compounds.

[0105] FIG. 35B is a graphical plot comparing efficacy (cumulative release, measured in pg) of a torus structure having an internal honeycomb structure,Attorney Docket No. 4210.0466WOsuch as is produced using a linear array methodology shown in FIG. 1 A, vs a torus structure having a radially arrayed architecture, as a function of time (days), each of the linearly arrayed torus structure and the radially arrayed torus structure being loaded with 30 mg of three different pharmaceutical compounds.DETAILED DESCRIPTION

[0106] The presently disclosed subject matter now will be described more fully hereinafter, in which some, but not all embodiments of the presently disclosed subject matter are described. Indeed, the presently disclosed subject matter can be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements.

[0107] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the presently disclosed subject matter.

[0108] All technical and scientific terms used herein, unless otherwise defined below, are intended to have the same meaning as commonly understood by one of ordinary skill in the art. References to techniques employed herein are intended to refer to the techniques as commonly understood in the art, including variations on those techniques or substitutions of equivalent techniques that would be apparent to one of skill in the art. While the following terms are believed to be well understood by one of ordinary skill in the art, the following definitions are set forth to facilitate explanation of the presently disclosed subject matter.

[0109] In describing the presently disclosed subject matter, it will be understood that a number of techniques and steps are disclosed. Each of these has individual benefit and each can also be used in conjunction with one or more, or in some cases all, of the other disclosed techniques.

[0110] Accordingly, for the sake of clarity, this description will refrain from repeating every possible combination of the individual steps in an unnecessary fashion. Nevertheless, the specification and claims should beAttorney Docket No. 4210.0466WOread with the understanding that such combinations are entirely within the scope of the invention and the claims.

[0111] Following long-standing patent law convention, the terms “a”, “an”, and “the” refer to “one or more” when used in this application, including the claims. Thus, for example, reference to "a unit cell" includes a plurality of such unit cells, and so forth.

[0112] Unless otherwise indicated, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about”. Accordingly, unless indicated to the contrary, the numerical parameters set forth in this specification and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by the presently disclosed subject matter.

[0113] As used herein, the term “about,” when referring to a value or to an amount of a composition, mass, weight, temperature, time, volume, concentration, percentage, etc., is meant to encompass variations of in some embodiments ±20%, in some embodiments ±10%, in some embodiments ±5%, in some embodiments ±1%, in some embodiments ±0.5%, and in some embodiments ±0.1% from the specified amount, as such variations are appropriate to perform the disclosed methods or employ the disclosed compositions.

[0114] The term “comprising”, which is synonymous with “including” “containing” or “characterized by” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. “Comprising” is a term of art used in claim language which means that the named elements are essential, but other elements can be added and still form a construct within the scope of the claim.

[0115] As used herein, the phrase “consisting of” excludes any element, step, or ingredient not specified in the claim. When the phrase “consists of” appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole.Attorney Docket No. 4210.0466WO

[0116] As used herein, the phrase “consisting essentially of” limits the scope of a claim to the specified materials or steps, plus those that do not materially affect the basic and novel characteristic(s) of the claimed subject matter.

[0117] With respect to the terms “comprising”, “consisting of”, and “consisting essentially of”, where one of these three terms is used herein, the presently disclosed and claimed subject matter can include the use of either of the other two terms.

[0118] As used herein, the term “and / or” when used in the context of a listing of entities, refers to the entities being present singly or in combination. Thus, for example, the phrase “A, B, C, and / or D” includes A, B, C, and D individually, but also includes any and all combinations and subcombinations of A, B, C, and D.

[0119] As will be shown herein, the ability and necessity of including geometric complexity within the architecture of medical devices is herein established. The illustrative examples disclosed herein are shown in relation to an intravaginal ring (IVR) and rod-shaped implant devices; however, the methods and systems disclosed herein are not limited to the design of an IVR or rod-shaped implant device and, in fact, can be used to design any medical device that has a substantially circular or nonpolygonal shape. The terms IVR and torus structure should be regarded as having the same meaning and can be used interchangeably with each other herein. The terms rod-shape implant, RSI, RSD, and rod-shaped structure should be regarded as having the same meaning and can be used interchangeably with each other herein.

[0120] The example methods and systems disclosed herein are shown herein to control key performance metrics of the medical device produced, such as burst release and release kinetics of an active pharmaceutical ingredient (API). Known medical device design techniques have utilized what are termed as ‘linear arrays’ in computationally aided design (CAD) software. For a torus shaped device such as an IVR, the use of such known design techniques involves defining a unit cell of a given dimension then a geometry of these unit cells is laid out linearly along the X-axis, then the Y-axis, and then the Z-axis within a solid volumetric envelope of the IVR, referred to as a template. Next, the void material is essentially “stamped” out of the solidAttorney Docket No. 4210.0466WOvolumetric envelope to form each of the unit cells and, ultimately, the IVR is formed of and / or contains a plurality of these unit cells. This is essentially a “cookie cut” approach and results in the unit cells fitting as a grid-like pattern internal to a torus structure, an example of such LA torus structure 10 being schematically shown in FIG. 1A.

[0121] Radial arrays, however, take a fundamentally different approach to generating a lattice structure within a torus structure 100, 101 or circular medical device. Rather than “punching” material out to define the cells of the torus structure 100, 101, radial arrays employ a secondary surface within the torus or circular device to serve as a nucleation point from, which a lattice structure can be rendered. This second structure is referred to as a core 200, which can also be referred to herein as an “inner surface.” In some embodiments, a different form of CAD, referred to using the acronym NURBS (Non-Uniform Rational Basis Spline), to define points in space that can form a lattice once rendered. These points in space are arranged radially around a central point, both within the torus cross-section and also within three-dimensional space. According to the methods and systems disclosed herein, a second torus is embedded within the CAD structure to enable the formation of this internal radial array of cells 220. The structure produced using the methods and systems disclosed herein is better suited for torus or cylindrical devices (i.e. , forming a round lattice into a round region rather than a square unit cell into a round region). An example of how a torus structure 100, 101 can be formed in shown in FIG. 1 B. The examples disclosed herein are specific to torus IVRs; however, these methods and systems can be extended and adapted to use in forming other cylindrical devices such as subcutaneous, intraperitoneal, intravaginal, intrauterine, intratracheal, subdermal, and dental implants, without limitation.

[0122] The embedded inner core 200 serves as a reference point enabling the internal lattice structures to intercalate within the interior of the torus structure 100 (or cylindrical structure) rather than just on the outer surface 210, as is the case for the example torus structure 101 shown in FIG. 2A, which does not have a core 200 internal to the torus structure 101 and, thus, as shown in FIG. 2A, the lattice unit cells 220 are only on the outer surfaceAttorney Docket No. 4210.0466WO210 of the torus structure 101. Additionally, the incorporation of the core 200 enables access to a wider range of critical performance values or metrics, such as volume, surface area, specific surface area, and mechanical properties.

[0123] In the example method of designing IVRs with controlled internal architectures to impart geometric complexity shown in FIG. 1 A, a template IVR of a given outer diameter and cross-sectional diameter was generated using CAD software. A unit cell of a given type, size and orientation was arrayed into the template, resulting in the internal architecture of the IVR. A band of specified outer diameter, height, and thickness is generated and placed over the internal architecture, at the outer surface 210. The purpose of the band is two-fold. First, the use of such a unit cell is known, as shown, to result in the formation of partial unit cells and, thus, rough edges on the outer surface of the resultant device. Thus, the band is used to seal and encase the internal architecture. Second, the band can be used to dictate the mechanical properties of the IVR. This design approach enabled the interchanging and optimization of the internal architecture without altering the macro-mechanical properties of the ring, namely compressive force. The combination of the internal architecture and the band in CAD results in the final, geometrically complex IVR. Using the method shown in FIG. 1 A, the unit cell array is limited to linear (X-Y) arraying and leaves hanging struts and rough edges for non-cubic structures (such as the torus IVR or other cylindrical shapes). For such structures, the use of the radial arraying method shown in FIG. 1 B would be more appropriate. Additionally, when rendering structures using a complex mesh using the linear arraying method of FIG. 1A, more complex unit cells, either in terms of intricacy, roundness, or smallness, are rendered with increasingly more computationally costly meshes. This limits the geometry and size of arrayed unit cells.

[0124] To overcome the limitations associated with the use of linear arraybased design, in some embodiments, a CAD software that uses NURBS was used to develop a novel method for designing lattice architectures that are radially arrayed within a specified design space. To demonstrate the utility of this novel radial array design method in the context of an IVR, the designAttorney Docket No. 4210.0466WOspace was defined as a torus for the outer surface 210 of the structure being formed. Within this torus-shaped space, a second, internal torus was generated. This inner torus-shaped volume defines the inner surface 200 of the structure. The inner surface 200 serves as an embedded reference surface, around which the lattice is arrayed to produce a radially-arrayed architecture for the structure. An example torus structure 100 is shown in FIG.3, in which the inner surface 200 and the outer surface 210 are shown.

[0125] This novel method of forming a radially arrayed torus structure 100 using NURBS-based CAD software offers several advantages over the known method using a mesh-based CAD software with a linear array architecture. These advantages include, for example, that NURBS-based CAD software is significantly less computationally expensive than mesh rendering used in linear array-based architectures; unit cells 220 are defined in terms of points in three-dimensional space (to accommodate the NURBS rendering) and the thickness of the struts 230 is defined in a later step. This enables the arraying of more complex structures with fine control over strut thickness. Another advantage provided by the novel methods disclosed herein is that the outer surface 210, the core 200, the band, and the internal radial array can be constructed within a single CAD platform or software package, limiting the number of steps necessary to form such structures and also minimizing accumulated tessellation error that is known to occur when the .STL file is transferred from one CAD platform to another.

[0126] The inner core 200 can be specified to have any dimensions so long as it is contained within the design space of the outer surface 210. This is described in the following equation:XIC< Xos- 0.001 mm (Equation 1)

[0127] Thus, according to Equation 1 , the cross-sectional diameter of the inner core 200 (Xie) is less than or equal to the cross-sectional diameter of the outer surface 210 (Xos) minus 0.001 mm. An example dimension for Xos is 10 mm for a structure with an Xie value in the range of 0.001-9.999 mm. Another example dimension for Xos is 10.1 mm for a structure with an Xie value in the range of 0.001-10 mm.Attorney Docket No. 4210.0466WO

[0128] In the context of IVRs and to demonstrate the utility of this relationship of Equation 1 , the diameter of the inner surface 200 was varied, as shown in FIGS. 4A and 4B. In FIG. 4A, the inner surface 200 has a negligible diameter of only 0.001 mm, such that it will only serve as a reference surface for the resulting radial array. However, once rendered, this embedded inner surface 200 is suppressed, so that it does not appear within the design space and resulting structure. In FIG. 4B, the inner surface 200 is defined with tangible dimensions, such that the inner surface 200 (or core, or inner torus) has a diameter of 1.0 mm. The lattice architecture is formed to be arrayed radially between the inner and outer surfaces 200, 210; unlike in the example shown in FIG. 4A, however, once rendered, the embedded inner surface 200 is produced as a solid core structure.

[0129] It should be noted that, just as was shown in the example for the core 200 of negligible thickness shown in FIG. 4A, the inner surface 200 can be suppressed (e.g., hidden, or rendered to be invisible) regardless of the thickness defined prior to rendering the structure, such that this inner surface 200 would essentially be rendered to be invisible. For example, by suppressing the 1.0 mm diameter core 200 in the example shown in FIG. 4B, the resulting torus structure 100 would have a 1.0 mm generally annularly-, ellipsoidal-, rod-, Y-, U-shaped void space inside the radially arrayed lattice structure. This method of radially arraying a lattice architecture between inner and outer surfaces 200, 210 within a design space allows structures to be generated with precise features. The examples shown in FIGS. 4A and 4B contain lattice features (e.g., struts 230) with a diameter of 0.5 mm. Particularly advantageously, the distribution, size, and / or density of these radially arrayed features can be controlled (e.g., changed) without disrupting (e.g., changing) the rendered lattice structure.

[0130] In the illustrative example of the toroidally-shaped (torus) structure 100, 101 or design space, the design space was defined to mimic the dimensions of commercially available intravaginal rings (IVRs). Using this novel design method, it is now possible to design and fabricate IVRs using additive manufacturing (AM) or other manufacturing processes compatible with CAD-based design packages. The example design method disclosedAttorney Docket No. 4210.0466WOherein advantageously enables the use of CAD to define the construction of the interior lattice (e.g., struts 230), which has been found to play a pivotal role in determining uptake and release kinetics of therapeutic compounds on and / or in the medical device being produced. Conventionally fabricated IVRs do not contain interior lattices and, thus, their ability to control therapeutic loading and release is dramatically limited over the devices produced using the example method disclosed herein. IVRs designed with geometric complexity define release properties by theoretical values, rather than tangible values associated with the dimensions of the lattice. The example method disclosed herein, however, can be applied to any round structure for controlled device properties, particularly pertaining to the release of therapeutic compounds. FIGS. 5A-5I shows examples of radial designs suitable for use in producing a variety of torus structures 100 with internal lattice structures (e.g., struts 230), which define unit cells 220. The lattice unit cell designs used to produce the example structures shown in FIGS. 5A-5I include X (FIG. 5A), Star (FIG. 5B), Cross (FIG. 5C), Tesseract (FIG. 5D), Vintiles (FIG. 5E), Octet (FIG. 5F), Diamond (FIG. 5F), Honeycomb (FIG. 5G), and Grid (FIG. 5I). These lattice unit cells were radially arrayed uniformly around the torus shape of the IVR using NURBS-based CAD software.

[0131] FIGS. 6A-6C show examples of three (3) IVRs produced with tesseract-shaped (FIG. 6A), star-shaped (FIG. 6B), and diamond-shaped (FIG. 6C) lattice unit cells. In these examples, the IVRs are designed as banded IVRs and cross-sectional views of the core and internal lattice structure are shown for each of the example IVRs to illustrate the internal architecture generated using each of these three (3) example lattice unit cell designs. FIGS. 7A-7I show, respectively, example embodiments of bisected CAD representations of radial array (RA) IVRs and physical models of each of the examples produced via a 3D printing process. CAD and 3D printed radially arrayed IVRs were generated and bisected (e.g., to produce the cross-sectional views shown in FIGS. 7A-7I) to demonstrate the interior design architecture generated by arraying each different unit cell design around the torus structure 100 (e.g., IVR). Example embodiments of 3D printed radially arrayed IVRs were produced using 3D printing in a functional resin. Nine (9)Attorney Docket No. 4210.0466WOexamples of radial array IVRs that were produced via 3D printing are shown in FIG. 8. These examples were produced using the nine (9) unit cell designs shown in FIGS. 5A-7I in a biocompatible silicone-urethane resin (SIL 30, Carbon) with continuous liquid interface production (CLIP™, Carbon) using an M1 3D printer. These example IVRs were 3D printed vertically to generate 16 rings per print. The resulting RA IVRs shown in FIGS. 8A-8I demonstrate the ability to successfully manufacture such RA IVRs using CLIP 3D printing.

[0132] FIGS. 9A-9C show three (3) example embodiments of RA IVRs produced using three (3) of the lattice unit cell designs shown in FIGS. 6A-6C. Specifically, the example embodiments of the RA IVRs shown in FIGS. 9A were produced using a tesseract lattice unit cell design (FIG. 9A), a star lattice unit cell design (FIG. 9B), and a diamond lattice unit cell design (FIG. 9C). These example RA IVRs were fabricated in a functional resin (SIL 30) using CLIP 3D printing. Closeup images of the lattice unit cell design obtained from stereomicroscopy are also shown in FIGS. 9A-9C.

[0133] To demonstrate the main differences in the design outcomes between the linear array (LA) design method and the radial array (RA) design method, FIG. 10A shows an IVR 10 designed and fabricated using the LA design method and an IVR 100 designed and fabricated using the novel RA design method disclosed herein. Because the respective LA and RA design methods are so different from each other, the designs were optimized to have similar performance outcomes, such as strut thickness, to generate directly comparable devices / structures. The results shown in FIG. 10B demonstrate the key differences between the LA and RA design methods, with the RA design method being capable of building an array of lattice unit cells uniformly around the torus shape of the IVR, unlike in the LA design method, which is shown in FIG. 10A to produce a combination of complete and incomplete unit cells across the cross section of the toroidally-shaped IVR. Furthermore, the performance metrics of the devices produced using the LA design method, such as strut thickness, are dictated by the input dimensions of the unit cell (which has, in the example shown in FIG. 10, a honeycomb shape). In contrast, the performance metrics for devices designed and produced according to the RA design method can be set directly, thus enablingAttorney Docket No. 4210.0466WOequivalency. The table shown in FIG. 10B compares critical theoretical and experimental metrics for each of the devices (10, 100) shown in FIG. 10A produced using the LA and RA design methods, respectively.

[0134] It is possible also to design, as shown in FIGS. 11A-11C, a torus structure 100 that has a surrounding band incorporated into the outer surface 210 of the torus structure 100 during the design process using the RA design method disclosed herein. In the context of IVRs, this band on and over at least a portion of the outer surface 210 serves to provide a smooth contact surface between the vaginal wall and the device. Therefore, the design of the band can take several forms and / or dimensions, as shown in FIGS. 11 A-11 C.

[0135] The internal architecture of the devices produced using the radial array design methods disclosed herein enables a wide range of band types over the outer surface 210 of the torus structure 100. Devices fabricated with the standard band have been previously described for linear arrays (LA) and were therefore used as a basis for comparison to demonstrate efficacy of the devices produced using the RA design methods disclosed herein. Examples of such banded IVRs that were produced using a 3D printing technique (Carbon, M1) are shown in FIG. 12. These devices were fabricated in a silicone-urethane resin and the critical performance metrics were collected, as shown in FIG. 12. Calculated performance metrics include cross-sectional ratio (XS ratio) which is used to represent how “round” the device is. Volume fraction was also collected and is a measure of how much void space is contained within the device. In the example devices shown in FIG. 12, varying band types were integrally produced for devices having a star lattice unit cell and produced using the RA design method. The band descriptions included in FIG. 12 are based on orientation relative to the X-Y plane. Standard bands have been previously published for devices produced using a LA design method and were used as a basis for comparison to the devices shown in FIG.12. As can be seen in reviewing the data shown in the table of FIG. 12, the effect of the different band types is minimal on critical performance metrics such as dimension. However, it is noted that the band is intended to mechanically support the IVR during insertion and device use. Therefore, devices were tested at 50% compression, as shown in FIG. 13A. The effect ofAttorney Docket No. 4210.0466WOthe band on the load at 50% compression is shown in the graph of FIG. 13B. FIG. 13A also shows images of commercially available IVRs (Estring® and NuvaRing®) along with IVRs designed using the RA design methods disclosed herein and produced via a 3D printing process. In the graphical data shown in FIG. 13B, the bars represent mean values of n=4 per sample type and the error bars represent standard deviation of the mean. Statistical analysis found significance at p < 0.01 (B).

[0136] To demonstrate efficacy of the IVRs designed according to the RA design method disclosed herein, in vitro release of an example hormone, progesterone, for an RA IVR (equivalent to torus structure 100) was compared to that of a solid IVR 1. To investigate the effect of the increase in surface area of an RA IVR, progesterone was loaded at equivalent wt.% (12.6 wt.%) on a Star RA IVR (-563 mg progesterone) and a solid IVR (-888 mg progesterone). In vitro release studies showed that the Star RA IVR elicited a greater burst release of progesterone in the first 24 hr (22%, 126 mg progesterone) and overall higher release rates over 28 days compared to the solid IVR (7.8% burst at 24 hr, 70 mg progesterone). The IVRs were incubated in SVF (pH 4.2)+2% Solutol at 37 °C and sample aliquots were collected at predetermined timepoints to quantify progesterone release by HPLC analysis. All experiments were done in triplicate (n=3). The solid and RA IVRs, as well as these results are shown in FIG. 14. These results demonstrate the ability to fine-tune release kinetics by changing the surface area of the IVR using the RA design method.

[0137] As a further demonstration of sustained drug delivery using RA IVRs, in vitro release of a combination drug (Dapivirine, Pritelivir, Levonorgestrel) was evaluated for both solid and RA IVRs. Similarly to the first example (progesterone, see FIG. 14) discussed elsewhere herein, the effect of ring design was evaluated using solid and RA IVRs loaded with a triple-drug combination (Dapivirine, Pritelivir, Levonorgestrel). The effect of ring design was evaluated based on in vitro release kinetics. In the example shown in FIG.15, the RA IVR and the solid IVR had similar specific surface area (SSA, 0.57 mm’1for the RA IVR vs 0.53 mm'1for the solid IVR) and, as such elicited similar in vitro release kinetics for all three active pharmaceutical ingredients (APIs).Attorney Docket No. 4210.0466WO

[0138] A method for designing a structure (e.g., a medical device) for delivery of a therapeutic compound is disclosed herein. The design architecture includes an internal core and is formed using a plurality of radially arrayed lattice unit cells to form the structure. Thus, the method can include steps of defining an internal core, defining an outer surface of the structure, and forming internal unit cells to define the internal geometry of the structure. The internal core can have a diameter within a range of about 0.001mm to about 10.00 mm, inclusive. The internal unit cells are defined / created using a radially arrayed (RA) design methodology, which allows predictability for critical metrics for the structure, including, for example and without limitation, surface area, volume, and specific surface area, which have been shown to directly impact release of a therapeutic compound (e.g., a pharmaceutical drug) from a device having the structure produced according to any of the methods presently disclosed herein. The therapeutic compound can be one or more (e.g., a plurality) of small molecules (e.g., antivirals, antibacterials, contraceptive hormones, chemotherapeutics, analgesics, etc.}, large molecules (e.g., dendrimers, polymers, etc.), and / or biologies (e.g., peptides, antibodies, proteins, etc.).

[0139] Graphical plots showing the relationship between several key performance metrics, and the predictability thereof that is afforded by using a radial array design methodology, are shown in FIG. 16. In the left plot, theoretical surface area (mm2) is plotted as a function of theoretical volume (mm3) for Nv values of 3, 5, 7, and 10 illustrating the number of spokes around the central core (Nv) using a radial array design methodology. In the right plot, specific surface area (mm'1) is plotted as a function of strut thickness (pm) for radial array- and linear array-derived structures. As shown in the right plot, the relationship between specific surface area and strut thickness is much more closely correlated (e.g., linear, at least over a significant portion of the plot above about 250 pm) for radial array-derived structures than for linear array-derived structures, which are largely scattered in this plot.

[0140] All designs disclosed herein can be fabricated with 3D printing in either a prototyping or functional resin (e.g., silicone-based), but are not necessarily limited to being fabricated from such materials. Silicone, urethane,Attorney Docket No. 4210.0466WOand similar resin-based devices can then be loaded using the approach outlined in International Pat. App. No. PCT / US21 / 50949, the entire contents of which are incorporated herein.

[0141] The radial array design methodologies disclosed herein can be used to form a medical device of any suitable shape, including, for example and without limitation, torus (IVR), derivative of a cylinder (implant), U-shape, Y-shape, T-shape (IUD), V-shape, efc. FIG. 17 shows examples of rodshaped implant devices 300 having, in this example, a 4 mm cross-sectional diameter. These examples can be loaded with, for example, a contraceptive (ENG) according to International Pat. App. No. PCT / US21 / 50949. This contraceptive can be released under physiological conditions. The rodshaped implant devices 300 can have, for example and without limitation, unit cells that are star, diamond, or tesseract shaped, these unit cells being formed according to the radial array design methodology.

[0142] The rod-shaped or other shaped (Y, U, T, V, etc.) devices can also have a hollow internal structure to house solid implants containing, for example, an antiretroviral drug (ARV) according to International Pat. App. No. PCT / US20 / 16061. In this case, the rod-shaped or other shaped devices can act as a housing device for delivery of drug-loaded solid implants (FIGS. 29A-29D and FIG. 30).

[0143] The core 200 (also referred to herein as the inner core, or IC, the embedded core, and the inner surface) can be designed to have varying cross-sectional diameter ranging from 0.001 mm to 9.999 mm, inclusive or ranging from 0.001 -10 mm, inclusive. CAD examples of IC sizes ranging from 1 mm to 4 mm cross sectional diameter and their resulting hollow volume and volume fraction are illustrated in FIGS. 18A-18D. The hollow volume is determined by the volume of the inner core (torus) in CAD. The volume fraction was calculated by dividing the inner core volume (mm3) by the outer torus volume (mm3); thus, the volume fraction is a unitless value between 0 and 1 that describes the extent of the void space within the device; stated differently, there is a proportional relationship between the size of the core, the hollow volume, and the volume fraction.Attorney Docket No. 4210.0466WO

[0144] The shape of the core 200 has also been investigated. Example shapes for the core 200 include, for example and without limitation, cylindrical, ellipsoidal, triangular etc. The core 200 can also be designed with shapes other than cylindrical (e.g. ellipsoidal, shown in the example of FIG. 19). The example shown in FIG. 19 also has two cores 200, both of which have respective half-moon or semicircular cross-sectional shapes and are spaced apart from each other by a gap 202.

[0145] The core 200 can be centered (see, e.g., FIGS. 18A-18D), or off-centered, which is shown in FIGS. 20A and 20B. In FIG. 20A, the core 200 is interior facing (e.g., radially biased towards the center of the torus structure 100). In FIG. 20B, the core 200 is exterior facing, meaning radially biased away from the center of the torus structure 100. The position of the core 200 within the volume defined by the outer surface of the torus structure 100 is not limited to the examples described herein; indeed, the core can be at any location within the volume defined by the outer surface of the torus structure 100.

[0146] In some embodiments, the torus structure 100 can have more than one (e.g., a plurality of) cores 200, examples of which are shown in FIGS. 19 and 21. Thus, the torus structures 100 that can be derived using the radial array design methodologies disclosed herein can have one, two, or multiple (e.g., more than two) cores 200. For torus structures 100 having more than one core 200, the cores 200 can have a different shape from each other. The core 200 can be defined as a single or multiple cores 200 within the outer torus cross-section. An example of a CAD mesh and CAD render of two cores 200 centered within the torus structure 100 and outer surface 210 is shown in FIG. 21. The cores 200 can have the same or different diameters as each other and can be located in the center, interior facing (see, e.g., FIG. 20A), exterior facing (see, e.g., FIG. 20B), or a combination thereof within the torus structure 100.

[0147] In some embodiments, the torus structure 100 can have a core 200 that is solid or a core 200 that is hollow. Thus, the core 200 can be a solid core, an example of which is shown in FIG. 22A, or a hollow core, an example of which is shown in FIG. 22B. The resulting structure (e.g., ring or other atAttorney Docket No. 4210.0466WOleast generally annular structure) with solid vs. hollow core 200 will have varying specific surface area depending on whether the core is a solid core or a hollow core. In embodiments in which the torus structure 100 has multiple cores (such as is shown in FIGS 19 and 21), it is possible for at least one of the cores 200 to be in the form of a hollow core (such as is shown in FIG. 22B) and at least one of the cores 200 to be in the form of a solid core (such as is shown in FIG. 22A). The images shown in FIGS. 22A and 22B show, respectively, a torus structure 100 with a solid core 200 and a torus structure 100 with a hollow core 200.

[0148] The material surrounding the core 200 can be solid or a lattice-like structure. The design surrounding the core can be a complete solid crosssection, a lattice-based design, or combinations thereof in a single torus structure 100. Introducing lattice designs around the core 200 results in higher specific surface area, which is a key parameter to how drug diffusion and release kinetics are controlled. Illustrations of example torus structures 100 formed with different example lattice structures are shown in FIGS. 23A-23I. The lattice type and dimensions (e.g., strut thickness and density) can be selected for a torus structure 100 to control key performance metrics of the torus structure 100, including surface area (mm2), volume (mm3), and specific surface area (mm'1, derived from surface area divided by volume), which have been shown to control the rate of drug diffusion from a medical device in the form of such a torus structure 100.

[0149] Mixed lattice types can be used in a single torus structure 100, in some embodiments. By way of nonlimiting example, half of the torus structure 100 (e.g, a segment extending over 180°) can have a lattice structure formed using a differently-shaped and / or sized unit cell from the unit cell used to form the lattice structure of the other half of the torus structure 100. Lattice structures with different strut thicknesses, dimensions, and density, for example, can be designed around the core 200. Examples are shown in FIGS.24A-24C. In some embodiments, the structures can have different lattice types (e.g., tesseract and start) in the same structure. These designs dictate the overall specific surface area of the device, as well as drug diffusion and release kinetics therefrom. FIGS. 24A-24C show examples of lattice design inAttorney Docket No. 4210.0466WOCAD ring section, bisected CAD ring section, and 3D printed ring section in silicone-urethane resin.

[0150] Mixed types of material can be used in a single structure. By way of nonlimiting example, the structures can contain both lattice portion(s) and solid portion(s). By way of nonlimiting example, a first quarter (90°) of the torus structure 100 can have a lattice structure formed using a first unit cell, a second quarter (90°) of the torus structure 100 can be formed as a solid section (e.g., devoid of any internal lattice structure), a third quarter (90°) of the torus structure 100 can have a lattice structure that is formed using a second unit cell, which is differently-shaped and / or sized from the first unit cell used to form the lattice structure of the first quarter of the torus structure 100, and a fourth quarter (90°) of the torus structure can have any suitable design, including a solid construction (e.g., substantially identical to the second quarter), a lattice structure that is the same as the lattice structure of either the lattice structure of the first or third quarters, or a lattice structure that is different from the lattice structure of both of the first and third quarters. The design of the structure surrounding the core can be a combination of solid and lattice designs, an example of which is shown in FIG. 25. These designs can have the same or different proportions within the overall torus shape (e.g., equal solid and lattice portions or unequal solid and lattice portions, meaning that there are more solid portions than lattice portions or that there are more lattice portions than solid portions).

[0151] In some embodiments, it is advantageous to provide, such as in the case of a medical implant device, the outer surface of the torus structure 100 with an outer banding or sheath-like structure (which can also be considered as a cover element). The radially arrayed lattice design internal structure (shown without the cover in FIG. 26A) that defines the torus structure 100 can be, as shown in FIGS. 26B and 260, wrapped with an outer band or cover that can have a range of dimensions ranging from equal height for both sides (Type 1 , see FIG. 26B) to unequal height (Type 2, see FIG. 26C). As shown in FIG.26B, a gap is provided in the cover on the top edge of the torus structure, whereas in the example shown in FIG. 26C, the gap is inset radially inwardly, such that the innermost diameter of the gap in the example of FIG. 26C isAttorney Docket No. 4210.0466WOsmaller than the innermost diameter o fhte gap in the example of FIG. 26B. The dimensions of the cover (e.g., thickness of the cover, as well as the quantity, size, width, construction, circumferential continuity, and positioning of the one or more gaps formed in the cover) dictate the overall performance of the torus structure, namely, the mechanical compression thereof, in addition to the pharmacokinetics of an implant device having such a shape.

[0152] Medical devices for applications in fertility treatment, HIV prevention / treatment, STI prevention / treatment, contraception, gynecology oncology, gynecological disorders (e.g. urinary incontinence, heavy menstrual bleeding, pelvic pain, endometriosis) etc. can be designed using the example radial array design methods disclosed herein. Radially arrayed medical devices can be in any shape, including the rod-shaped implant devices 300 and the torus structures 100. Such radially arrayed medical devices can also be compatible with a range of APIs for various indications (e.g., treatments) and can be designed to be administered topically (e.g., vaginal ring, Y-shape, U-shape, V-shape, T-shape), subdermally or subcutaneously (e.g. rodshaped implant), intraperitoneally (e.g. cylindrical, star-shape, etc.), and the like, without limitation.

[0153] The structures produced by the example radial array design method disclosed herein are compatible with the absorption-based drug loading process described in International Pat. App. No. PCT / US21 / 50949 and / or as housing systems for drug delivery of solid implants made with the process described in International Pat. App. No. PCT / US20 / 16061 . FIG. 27 shows how the shape of an example torus structure formed using the radially arrayed methods disclosed herein changes as a function of the duration of exposure (e.g., soaking) of the torus structure to a liquid solution comprising the API(s). As shown in FIG. 27, a radial array IVR in the form of a torus structure was fabricated in silicone-urethane resin using CLIP 3D printing and was incubated in a rhodamine-B solution in ethanol for a period of 8 hours. As shown in FIG.27, the dimensions of the torus structure increase over time (e.g., the IVR swells as the API is absorbed), allowing homogenous distribution and incorporation of rhodamine-B throughout the ring matrix (e.g., struts of the unit cells) of the torus structure.Attorney Docket No. 4210.0466WO

[0154] The radial array lattice designs, as well as the methods of making the same, examples of which are disclosed herein, can be used for designing structures with predictable, tuned, and controlled therapeutic delivery performance characteristics. Unlike structures created using conventional linear array design methodologies, in which designs are incorporated from the outside-in, designs created using the radial array design methods disclosed herein are incorporated from the inside-out, preferably using an internal core structure that is positioned internal to (or at least not outside of) the design envelope or outer perimeter of the structure being designed to have such a radial array architecture, for creating structures using the radial array design methods disclosed herein. This is shown in FIGS. 28A and 28B, in which a comparison is shown between the two methods (linear array in FIG. 28A, radial array in FIG. 28B) of imparting geometric complexity onto a medical device in the context of an IVR. In a linear array design methodology (FIG.28A), a unit cell is arrayed following an X-Y path and material is essentially subtracted from a “solid” starting, or base structure; this can, as shown, result in the formation of open, or partially formed, unit cells around the perimeter of the structure. In contrast, for a structure formed using a radial array design methodology (FIG. 28B), a core is defined as being embedded within an outer volume that defines the outer contours and shape of the finished structure; a lattice structure is then arrayed within the volume, radiating outward from the embedded core structure, filling in the toroidal space to form a plurality of unit cells within the structure. Advantageously, the structure formed using the radial array design methodology has no partial, or open, unit cells. The core is defined as being internal to the device and having a diameter within a range of from about 0.001 mm to 9.999 mm, inclusive or from about 0.001 mm to 10 mm, inclusive. In instances in which a solid IVR is desired, the diameter of the core can be set to be the same as the diameter of the cross-section of the outer surface of the volume, such that the resultant structure is essentially defined as being a single large core structure. The core can be solid or hollow, as desired and based on the particular application, and the structure that surrounds the internal core can be solid, a lattice structure, or combination(s) of solid and lattice portions or regions. A structure formed using the radialAttorney Docket No. 4210.0466WOarray design methods disclosed herein can have multiple internal cores, which can be spaced apart of in contact with each other, and the shapes of such cores can be any combination of, for example, cylindrical, ellipsoidal, triangular, etc. In some examples, the core can have an irregular (e.g., nongeometric) or polygonal cross-sectional shape. There is a distinct relationship between the critical performance metrics of surface area, volume, and specific surface area to the design parameters of the radial arrays and, therefore, the use of radial array design methodologies has been found to be a more precise method to achieve targeted performance characteristics.

[0155] FIG. 29A is an illustration of preparation of a rod-shaped implant device that is configured to house multiple drug / polymer solid implants (PSIs). In this example, one end of the rod-shaped implant device is sealed (e.g., with a heat-sealer or by applying a melted polymer thereto). Next the desired quantity of PSIs are added into the rod-shaped implant device and, finally, the open end of the rod-shaped implant device is sealed (e.g., with a heat-sealer or by applying a melted polymer thereto). FIG. 29B is an illustration of a plurality of such rod-shaped implant devices on a build platform, as may be the case when multiple such rod-shaped implant devices are constructed simultaneously, as is the case during additive manufacturing (also commonly referred to as 3D printing). FIG. 290 shows PSI housed within a silicone-based rod-shaped implant device that is internally hollow (e.g., before the PSI is added therein) and produced using additive manufacturing. FIG. 29D shows a plurality of such hollow rod-shaped implant devices produced using additive manufacturing, each of the rod-shaped implant devices shown in FIG. 29D being produced using a silicone-urethane resin, using CLIP 3D printing technique.

[0156] FIG. 30 shows example dimensions for a housing, which can either be drug-loaded (e.g., contain one or more therapeutic compounds) or therapeutically inert (e.g., not containing any therapeutic compounds in the structure of the housing itself). Ranges of example dimensions of such a housing are shown in FIG. 30. By way of nonlimiting example, the example housings for the rod-shaped implant devices shown in FIG. 30 have a length between about 10 mm to about 40 mm, inclusive. Within each length (or rangeAttorney Docket No. 4210.0466WOof lengths), the outer diameter can be within a range of about 2.0 mm to about 4.0 mm, inclusive. Still further, the inner diameter can be adjusted, resulting in and / or producing wall thicknesses ranging from about 0.05 mm to about 0.25 mm, inclusive. These housings shown in FIG. 30 can be designed with internal radial array architectures within the walls and can be either inert or release an active compound (e.g., a pharmacological compound).

[0157] FIG. 31A shows a plurality of the torus structures 100 on a build plate 3, such as will be the case when a plurality of such torus structures 100 are produced simultaneously using an additive manufacturing process. FIG.31 B shows one of the torus structure 100 of FIG. 31 separated from the build plate 3. Using the radial array design methodologies disclosed herein, it is now possible to introduce geometric complexity, both inside or and on the outer surface of such torus structures 100 (e.g., IVRs). Also, using the radial array design methodologies disclosed herein, it has been discovered that the total surface area of the implant device (e.g., torus structure 100, rod-shaped implant device 300) can be increased over known implant devices; increasing the total surface area of such implant devices is advantageous for promoting the efficient and steady release of APIs, such as Dapirivine (DPV), Pritelivir (PTV), and / or Levonorgestrel (LNG). Implant devices produced according to the example radial array design methods disclosed herein can be used for a period of at least 1 -month, preferably at least 3 months.

[0158] FIG. 32 is a graphical plot of cumulative release (measured as a percentage) of an API (in the example shown, DPV) loaded in / on the implant device shown in FIG. 31 B in different quantities, the cumulative release being plotted as a function of time, measured in days. The effect of the DPV dose on in vitro release kinetics is shown in FIG. 32, with the cumulative release percentage decreasing with increased API loading (e.g., the percentage cumulative release for 25 mg DPV is consistently greater than for 30 mg DPV, which is in turn consistently greater than the percentage cumulative release for 150 mg DPV). It should be noted that, while the percentage of API release decreased as a function of the quantity of the API loaded in / on the implant device, the quantity of the API actually released (e.g., as measured in mg)Attorney Docket No. 4210.0466WOfrom the implant device generally increased as a function of the quantity of the API loaded in / on the implant device.

[0159] FIGS. 33 and 33B are graphical plots comparing solid vs grid (e.g., lattice) radial array implant devices. FIG. 33A is a graphical plot of cumulative percentage release of an API (30 mg DPV) as a function of time, measured in days. FIG. 33B is a graphical plot of cumulative percentage release of an API (150 mg DPV) as a function of time, measured in days. In each of FIGS. 33A and 33B, the cumulative release percentage of the API is compared for a radial array implant device vs a solid implant device of the same outer shape. These results show that an implant device (here, an IVR) with higher total surface area (i.e., the radial array implant device) produces a higher percentage release of DPV in vitro as compared to the solid implant device.

[0160] FIG. 34 is a graphical plot of cumulative percentage release of three APIs from a radial array implant device, as a function of time, measured in days. In producing this graphical plot, the implant device was loaded with 30 mg each of DPV, PTV, and LNG. The cumulative release percentage was plotted for each of the APIs and it is shown in FIG. 34 that harmonious release kinetics were provided using the radial array design methodologies disclosed herein to produce such an API-laden implant device.

[0161] FIGS. 35A and 35B are respective graphical plots, comparing cumulative percentage release as a function of time, measured in days, for three (3) APIs (DPV, PTV, LNG) loaded onto different implant devices. In FIG.35A, 150 mg of each of DPV, PTV, and LNG are loaded in / on a solid implant device and an implant device with a radial array internal architecture; these implant devices have the same shape and size (e.g., the volume of the outer shape is the same). As shown, the cumulative percentage released was consistently higher in vitro for each of the APIs in the implant device produced with the radial array design methods disclosed herein, as compared to a solid implant device of the same size and shape. In FIG. 35B, 30 mg of each of DPV, PTV, and LNG are loaded in / on an implant device with a radial array internal architecture and also an implant device with a honeycomb architecture; these implant devices have the same shape and size (e.g., the volume of the outer shape is the same). As shown, the cumulative percentageAttorney Docket No. 4210.0466WOreleased was somewhat higher but largely similar in vitro for each of the APIs in the implant device produced with the radial array design methods disclosed herein, as compared to the implant device that is of the same size and shape but has the honeycomb internal architecture.

[0162] It will be understood that various details of the presently disclosed subject matter may be changed without departing from the scope of the presently disclosed subject matter. Furthermore, the foregoing description is for the purpose of illustration only, and not for the purpose of limitation.

Claims

Attorney Docket No. 4210.0466WOCLAIMS1 . A method of producing a structure, the method comprising:defining an outer surface of the structure, an internal volume of the structure being defined within the outer surface;defining, within the internal volume of the structure, one or more cores; selecting a unit cell geometry; andradially arraying unit cells around a perimeter of and / or within the internal volume of the structure to form a plurality of such unit cells that extend between the one or more cores and the perimeter, within the internal volume of the structure.

2. The method of claim 1 , wherein the unit cells are each formed by a plurality of struts.

3. The method of claim 2, wherein at least a subset of the plurality of struts extend between the one or more cores and the perimeter of the structure.

4. The method of claim 1 , wherein the one or more cores is a plurality of cores.

5. The method of claim 4, wherein the plurality of cores have a cross-sectional shape that is the same as or different from each other.

6. The method of any of claims 1 -5, wherein the one or more cores have a cross-sectional shape that is circular.

7. The method of any of claims 1 -5, wherein the one or more cores have a cross-sectional shape that is non-circular.

8. The method of claim 7, wherein the non-circular shape is ellipsoidal or triangular.

9. The method of claim 1 , wherein the one or more cores is:Attorney Docket No. 4210.0466WOcentered, relative to a cross-section of the internal volume of the structure, within the internal volume of the structure; oroffset, relative to the cross-section of the internal volume of the structure, from a center of the internal volume of the structure.

10. The method of claim 1 , wherein:the internal volume of the structure is subdivided in a circumferential direction into a plurality of circumferential portions;in a first subset of the plurality of circumferential portions, the unit cells are formed therein; andin a second subset of the plurality of circumferential portions, the internal volume within each of the second subset is entirely solid.

11. The method of any of claims 1 -10, wherein the structure has a shape of a torus.

12. The method of claim 11 , comprising forming, on a portion of the perimeter of the structure, an outer cover.

13. The method of any claims 1 -10, wherein the structure has a shape of a U, a Y, a V, a T, or a rod.

14. The method of any of claims 1-13, wherein the unit cell geometry comprises one or more of X, star, cross, tesseract, vintiles, octet, diamond, honeycomb, and grid.

15. The method of any of claims 1-14, comprising immersing the structure in a solution comprising one or more therapeutic compounds for storage of the one or more therapeutic compounds in at least the struts of the unit cells and release of the one or more therapeutic compounds in vivo.

16. The method of any of claims 1-15, wherein:Attorney Docket No. 4210.0466WOthe one or more cores are solid structures comprising one or more therapeutic compounds within the structure; andthe unit cells define a hollow void and act as a rate-controlling membrane for the release of the one or more therapeutic compounds in vivo.

17. The method of any of claims 1-16, wherein the core is solid or hollow.

18. A medical device produced using the method of claim 1 .

19. The medical device of claim 18, wherein the medical device is an intravaginal ring (IVR).

20. A medical device comprising:an outer surface that delimits an internal volume of the medical device; one or more cores defined within the internal volume of the medical device; anda plurality of unit cells radially arrayed around a perimeter of and / or within the internal volume of the structure, such that the plurality of such unit cells that extend between the one or more cores and the perimeter, within the internal volume of the structure.21 . The medical device of claim 20, wherein the unit cells are each formed by a plurality of struts.

22. The medical device of claim 21 , wherein at least a subset of the plurality of struts extend between the one or more cores and the perimeter of the structure.

23. The medical device of claim 20, wherein the one or more cores is a plurality of cores.

24. The medical device of claim 23, wherein the plurality of cores are a same or a different cross-sectional shape from each other.Attorney Docket No. 4210.0466WO25. The medical device of any of claims 20-24, wherein the one or more cores have a cross-sectional shape that is circular.

26. The medical device of any of claims 20-24, wherein the one or more cores have a cross-sectional shape that is non-circular.

27. The medical device of claim 26, wherein the non-circular shape is ellipsoidal or triangular.

28. The medical device of claim 20, wherein the one or more cores is: centered, relative to a cross-section of the internal volume of the structure, within the internal volume of the structure; oroffset, relative to the cross-section of the internal volume of the structure, from a center of the internal volume of the structure.

29. The medical device of claim 20, wherein:the internal volume of the structure is subdivided into a plurality of circumferential portions;in a first subset of the plurality of circumferential portions, the unit cells are formed therein; andin a second subset of the plurality of circumferential portions, the internal volume is a solid structure.

30. The medical device of any of claims 20-29, wherein the structure has a shape of a torus.

31. The medical device of claim 30, comprising an outer cover that is formed on at least a portion of the perimeter of the structure.

32. The medical device of any claims 20-31, wherein the structure has a shape of a U, a Y, a V, a T, or a rod.Attorney Docket No. 4210.0466WO33. The medical device of any of claims 20-32, wherein the unit cell geometry comprises one or more of X, star, cross, tesseract, vintiles, octet, diamond, honeycomb, and grid.

34. The medical device of any of claims 20-33, wherein:the struts of the unit cells comprise one or more therapeutic compounds stored therein; andthe struts of the unit cells are configured to release the one or more therapeutic compounds in vivo.

35. The medical device of any of claims 20-34, wherein the medical device is an intravaginal ring (IVR).

36. The medical device of any of claims 20-35, wherein the medical device is an insert or a housing.

37. The medical device of claim 36, wherein the insert or the housing contains one or more therapeutic compounds.

38. The medical device of claim 36, wherein the insert or the housing is therapeutically inert.

39. A method of producing a structure, the method comprising:defining an outer surface of the structure, an internal volume of the structure being defined within the outer surface;defining, within the internal volume of the structure, one or more cores; selecting a unit cell geometry; andradially arraying unit cells around a perimeter of and / or within the internal volume of the structure to form a plurality of such unit cells that extend between the one or more cores and the perimeter, within the internal volume of the structure;optionally, wherein the unit cells are each formed by a plurality of struts;Attorney Docket No. 4210.0466WOoptionally, wherein at least a subset of the plurality of struts extend between the one or more cores and the perimeter of the structure;optionally, wherein the one or more cores is a plurality of cores; optionally, wherein the plurality of cores have a cross-sectional shape that is the same as or different from each other;optionally, wherein the one or more cores have a cross-sectional shape that is circular;optionally, wherein the one or more cores have a cross-sectional shape that is non-circular, the non-circular shape optionally being ellipsoidal or triangular;optionally, wherein the one or more cores is:centered, relative to a cross-section of the internal volume of the structure, within the internal volume of the structure; and / or offset, relative to the cross-section of the internal volume of the structure, from a center of the internal volume of the structure; optionally, wherein:the internal volume of the structure is subdivided in a circumferential direction into a plurality of circumferential portions; and / orin a first subset of the plurality of circumferential portions, the unit cells are formed therein; and / orin a second subset of the plurality of circumferential portions, the internal volume within each of the second subset is entirely solid; and / oroptionally, wherein the structure has a shape of a torus or, further optionally, a shape of a U, a Y, a V, a T, or a rod;optionally, wherein an outer cover is formed on at least a portion of the perimeter of the structure;optionally, wherein the unit cell geometry comprises one or more of X, star, cross, tesseract, vintiles, octet, diamond, honeycomb, and grid;optionally, the method comprising immersing the structure in a solution comprising one or more therapeutic compounds for storage of the one or moreAttorney Docket No. 4210.0466WOtherapeutic compounds in at least the struts of the unit cells and release of the one or more therapeutic compounds in vivo;optionally, wherein:the one or more cores are solid structures comprising one or more therapeutic compounds within the structure; andthe unit cells define a hollow void and act as a rate-controlling membrane for the release of the one or more therapeutic compounds in vivo;optionally, wherein the core is solid or hollow.

40. A medical device produced using the method of claim 39.

41. The medical device of claim 40, wherein the medical device is an intravaginal ring (IVR).

42. A medical device comprising:an outer surface that delimits an internal volume of the medical device; one or more cores defined within the internal volume of the medical device; anda plurality of unit cells radially arrayed around a perimeter of and / or within the internal volume of the structure, such that the plurality of such unit cells that extend between the one or more cores and the perimeter, within the internal volume of the structure;optionally, wherein the unit cells are each formed by a plurality of struts; optionally, wherein at least a subset of the plurality of struts extend between the one or more cores and the perimeter of the structure;optionally, wherein the one or more cores is a plurality of cores; optionally, wherein the plurality of cores are a same or a different cross-sectional shape from each other;optionally, wherein the one or more cores have a cross-sectional shape that is circular;Attorney Docket No. 4210.0466WOoptionally, wherein the one or more cores have a cross-sectional shape that is non-circular, the non-circular shape optionally being ellipsoidal or triangular;optionally, wherein the one or more cores is:centered, relative to a cross-section of the internal volume of the structure, within the internal volume of the structure; and / or offset, relative to the cross-section of the internal volume of the structure, from a center of the internal volume of the structure; optionally, wherein:the internal volume of the structure is subdivided into a plurality of circumferential portions; and / orin a first subset of the plurality of circumferential portions, the unit cells are formed therein; and / orin a second subset of the plurality of circumferential portions, the internal volume is a solid structure;optionally, wherein the structure has a shape of a torus or, further optionally, a shape of a U, a Y, a V, a T, or a rod;optionally, wherein an outer cover is formed on at least a portion of the perimeter of the structure;optionally, wherein the unit cell geometry comprises one or more of X, star, cross, tesseract, vintiles, octet, diamond, honeycomb, and grid;optionally, wherein:the struts of the unit cells comprise one or more therapeutic compounds stored therein; and / orthe struts of the unit cells are configured to release the one or more therapeutic compounds in viva,optionally, wherein the medical device is an intravaginal ring (IVR); optionally, wherein the medical device is an insert or a housing; and optionally, wherein the insert or the housing contains one or more therapeutic compounds therein or is therapeutically inert.

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