Implants assembled from skeleton polyhedral cells, coiled cells, or reticular cells

Abstract

Absorbable implants can be used to create volume and shape in soft tissue using regenerative tissue. The implant comprises a grid formed from a plurality of unit cells. The unit cells can be coils or springs, skeletal polyhedrons, foams, or structures derived from mesh and fibers. The implant can be coated or filled with cells and tissue, and is preferably coated or filled with an autologous fat graft. The implant is particularly suitable for use in plastic surgery procedures, for example, to regenerate or augment breast tissue after a mastectomy or during a mastopexy procedure, and can provide an alternative to the use of permanent breast implants in these procedures.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Application No. 62 / 855,835, filed May 31, 2019, entitled “IMPLANTS ASSEMBLED FROMSKELETAL POLYHEDRON UNIT CELLS, COILED UNIT CELLS OR MESH UNIT CELLS,” the entire contents of which are incorporated herein by reference in their entirety for all purposes. Technical Field

[0003] The present invention relates generally to implants and, more particularly, to absorbable implants formed from three-dimensional unit cells. Background Art

[0004] Breast reconstruction after mastectomy has become an integral and important part of breast cancer treatment, offering both aesthetic and psychosocial benefits to patients. In the United States, nearly 65% ​​of breast reconstruction procedures currently use a tissue expander to create a pocket for a permanent breast implant during the first step of the procedure. In some patients, a pocket for a breast implant can be created without the use of a tissue expander. Once the pocket is created, the tissue expander is removed and replaced with a permanent breast implant in a second step.

[0005] Breast implants can also be used in breast augmentation and mastopexy procedures to increase breast size. In the latter procedure, a breast lift is combined with a breast augmentation. Most commonly, breast implants are placed in a pocket beneath the breast tissue, but in some cases, they are implanted beneath the chest wall.

[0006] Breast implants vary in size, shape, and surface texture. A wide range of sizes are available, allowing surgeons and patients to choose from a range of projections, heights, widths, and overall volumes. In terms of shape, there are round and anatomically shaped implants, and the implant surface can be smooth, microtextured, or macrotextured. Generally speaking, round implants have a smooth surface, while anatomically shaped implants have a concave, microtextured, or macrotextured surface.

[0007] However, more and more patients considering breast reconstruction and breast augmentation are reluctant to have permanent breast implants in their breasts. This is especially true for women who have already undergone a mastectomy and are currently considering breast reconstruction. Some of these patients do not wish to have a permanent foreign body placed in their breasts and do not wish to risk the complications that may result from permanent breast implants. Complications include the risk of capsular contracture requiring reoperation, implant rupture or shrinkage, development of anaplastic large cell lymphoma (ALCL), infection, and implant migration leading to breast asymmetry.

[0008] Hutmacher's WO2016 / 038083 discloses an implant comprising a void that is filled with a space-occupying structure designed to prevent tissue or individual cells from invading the void. Six to eight weeks after implantation, the implant is removed, leaving a void space that can be filled with transplanted cells. The void space provides a preformed bed of connective tissue and vascular system to support the transplanted cells. The implant scaffold structure can be made of biodegradable materials.

[0009] US2018 / 0206978 to Rehnke discloses an inner bra device made of a pleated bra that can be used for breast augmentation patients.

[0010] WO2018 / 078489 by Danze discloses an implant for replacing or increasing the volume of soft tissue, the implant comprising a three-dimensional bioresorbable frame having two lateral openings, comprising two sheets of bioresorbable fabric stacked on top of each other inside the implant frame.

[0011] Significantly, there has been little innovation in the design of breast implants that, upon implantation, can produce new breast tissue with a specific and desired appearance. Thus, there remains a need for a breast implant that can not only serve as a scaffold for tissue ingrowth, but also as an implant that is soft to the touch, compressible, recovers from compression, and can regenerate tissue in the breast, thereby restoring normal breast feel. More specifically, there remains a need for an implant that can be used to form new breast tissue, preferably also having an elastic modulus similar to that of breast tissue, and preferably having a similar feel to that of breast tissue. Summary of the Invention

[0012] The implants described herein help surgeons reshape parts of the body, including the breasts, nipples, face, and buttocks, as well as fill voids, rebuild lost or missing tissue, support damaged tissue structures, enhance existing tissue structures, increase soft tissue volume, restore tissue or organ function, restore natural sensation to soft tissue, repair hernias, and deliver biologic and synthetic materials to aid in tissue regeneration, repair, reinforcement, and reconstruction.

[0013] In some embodiments, the absorbable implant comprises a framework or lattice formed from a plurality of unit cells. The unit cells can be skeletal polyhedrons with edges and vertices formed by polymer struts or fibers, coils or springs, or units formed from a knitted mesh or foam.

[0014] In some embodiments, the implant is porous, provides a scaffold for tissue ingrowth, and may also contain cells, collagen, autologous fat, lipoaspirate, or injectable fat.

[0015] In some embodiments, the implant is compressible and recovers its shape after being compressed.

[0016] In some embodiments, the implants are used for soft tissue repair, regeneration, and replacement. In fact, the implants described herein can be operated as any type of device selected from a wide range of devices, including, for example, plastic surgery devices, breast implants, breast lift devices, breast augmentation devices, nipple implants, facial reconstruction devices, buttock implants, zygomatic augmentation devices, cosmetic repair devices, soft tissue regeneration devices, hernia implants, hernia plugs, wound healing devices, tissue engineering scaffolds, scaffolds for delivering vascular pedicles, guided tissue repair / regeneration devices, expansion or filling devices, void fillers, devices for treating vesicoureteral reflux, cell seeding devices, or drug delivery devices.

[0017] In some embodiments, the polymer struts or fibers forming the unit cells of the skeleton polyhedron, or the coils or springs forming the unit cells of the skeleton polyhedron, have one or more of the following properties: (i) a diameter of 0.025 to 3 mm, more preferably 0.1 to 2 mm, even more preferably 0.15 to 1 mm; (ii) a breaking load of 0.1 to 200 N, more preferably 1 to 100 N, even more preferably 2 to 50 N; (iii) an elongation at break value of 22% to 1,000%, more preferably 100% to 700%; and (iv) an elastic modulus value of 0.05 to 10 GPa, more preferably 0.1 to 3 GPa, even more preferably 0.2 to 0.8 GPa.

[0018] In some embodiments, the implant has only one type of unit cell, wherein each unit cell is identical. Such an implant can be formed by a skeleton polyhedron, wherein all these characteristic values ​​are identical within the skeleton polyhedron. In other embodiments, the implant has more than one type of unit cell. Such an implant can be formed by a skeleton polyhedron in which polymer struts and fibers, or coils and springs have different characteristic values.

[0019] In some embodiments, the implant comprises resorbable polymer struts or fibers.

[0020] In some embodiments, the implant can be a scaffold of allograft or xenograft tissue and cells, but preferably a scaffold of autologous tissue and cells, including but not limited to autologous fat, fat lipoaspirate, lipo-filling, injectable fat, adipocytes, fibroblasts and stem cells. In some embodiments, the implant can be an adipose tissue engineering scaffold. In some embodiments, the implant can comprise collagen. In some embodiments, the implant can have one or more openings that allow insertion of a vascular pedicle or other tissue mass. The implant is designed to promote tissue ingrowth. The implant is designed to repair, replace, regenerate and increase soft tissue structure. After implantation, the implant is designed to be invaded by connective tissue and blood vessels and become well integrated. Preferably, the implant is porous, absorbable, degrades in a controlled manner and is replaced by the patient's tissue in vivo. The implant can be macroporous. The implant preferably comprises a polymer material with a predictable degradation rate and a predictable in vivo strength retention rate. The implants can allow tissue mass to be restored or augmented while restoring or maintaining tissue feel, which is particularly important for applications involving the breast, nipple, face, neck, buttocks, and skin.

[0021] In some embodiments, the implant comprises a lattice formed from a plurality of unit cells. The unit cells can be repeated to form the volume of the implant, and if desired, the surface of the unit cells can be trimmed to form the final shape of the implant. The repetitive unit cells of the implant make it possible to produce implants with predictable properties. The implant is preferably a three-dimensional shape. In some embodiments, the unit cells are skeletal polyhedrons with edges and vertices formed by polymer struts or fibers. In other embodiments, the unit cells are coils or springs formed from polymers. In yet other embodiments, the unit cells are knitted meshes formed from polymers. In yet other embodiments, the unit cells are foams formed from polymers. The unit cells are hollow or porous, making the lattice a space-occupying structure. In some embodiments, the unit cells of the lattice are joined to one or more different unit cells. The lattice can comprise two or more unit cells, and preferably 50 or more unit cells. The unit cells of the lattice are preferably colonized by cells before implantation or more preferably after implantation, and the pores of the lattice can be invaded by tissue, blood vessels, or a combination thereof. When the grating is absorbable, degradation of the grating can allow further invasion of the grating structure by tissue, blood vessels, or a combination thereof, and this process can continue until the grating is completely absorbed. In some embodiments, the grating can include one or more openings that allow, for example, insertion of a vascular pedicle or other tissue mass. In some embodiments, the one or more openings can form transverse channels within the grating.

[0022] In some embodiments, the implant can have anisotropic properties, meaning that the implant has different properties in different directions. The implant can have a first elastic modulus in one direction and a different second elastic modulus in a second direction. The implant can have a strength that is high relative to its bulk density.

[0023] In some embodiments, the implant is a soft tissue implant comprising a porous grating, wherein the grating further comprises connected unit cells, and wherein the unit cells are skeleton polyhedra, and the edges and vertices of the skeleton polyhedra are formed by polymer struts or fibers. In some embodiments, the implant is a soft tissue implant comprising a porous grating, wherein the grating further comprises connected unit cells, and wherein the unit cells are coils or springs, and the coils or springs are formed by polymer struts or fibers. In some further embodiments, the implant is a soft tissue implant comprising a porous grating, wherein the grating further comprises connected unit cells, and wherein the unit cells are knitted, and the top and bottom plates of the knitted mesh are connected by fibers, preferably wherein the unit cells are warp knitted. In some embodiments, the unit cells are foam, preferably compressible foam.

[0024] In some embodiments, the implant is a plastic surgery device, a breast implant, a breast lift device, a breast augmentation device, a nipple implant, a facial reconstruction device, a buttock implant, a zygomatic augmentation device, a cosmetic repair device, a soft tissue regeneration device, a hernia implant, a hernia plug, a wound healing device, a tissue engineering scaffold, a scaffold for a vascular pedicle or other tissue mass, a guided tissue repair / regeneration device, an expansion or filling device, a void filler, a device for treating vesicoureteral reflux, a cell seeding device, or a drug delivery device.

[0025] In a preferred embodiment, the implant is a resorbable breast implant and is optionally coated with autologous tissue from the patient before, during, or after implantation, or any combination thereof. The autologous tissue is preferably one or more of the following: autologous fat, lipoaspirate, injectable fat, adipocytes, fibroblasts, and stem cells. The breast implant is preferably macroporous. The macroporosity of the breast implant is designed to allow the implant to accommodate sufficient autologous fat, biomaterials, collagen, hyaluronic acid, and / or bioactive agents to promote vascularization and tissue ingrowth within the implant, which is a relatively large volume of breast tissue. Optionally, the breast implant may also contain one or more openings, including transverse channels, to allow for the insertion of a vascular pedicle or other tissue mass. The implant can be used for patients who: (i) have undergone a mastectomy, (ii) have undergone a breast lift and desire an enlargement, (iii) have undergone a breast reduction and require support and lift for a reduced breast, or (iv) have previously undergone breast surgery with silicone breast implants and desire to remove the silicone implants and subsequently undergo breast reconstruction to create a more youthful appearance but with fuller breasts and a larger size. Implants can also be used for patients who wish to restore the feel of natural breast tissue to their breasts after having their breast tissue removed. Implants can be used to increase the projection of the breast from the chest, as well as in combination with fat grafting to add volume to the breasts.

[0026] In some embodiments, the implant is a replacement or substitute for a breast lift device, a breast enlargement device, or a permanent breast implant. In some embodiments, the implant has a shape and size suitable for breast surgical procedures, including breast augmentation, breast reconstruction, and mastopexy.

[0027] In some embodiments, the implant is a breast implant, and even more preferably, can be compressed and recover from compression. In some embodiments, the implant is designed to have a shape that produces a specific and desired appearance of the breast. Ideally, the breast implant has an elastic modulus similar to that of breast tissue. In some embodiments, the implanted breast implant has a feel similar to that of breast tissue. After implantation of the breast implant, the breast does not feel hard, but rather feels soft to the touch and feels like a natural breast. Furthermore, in some embodiments, the breast implant allows for restoration of breast mass or increase in breast mass while maintaining or restoring tactile sensation.

[0028] In some embodiments, the implant maintains strength long enough to allow support at the implant site to transition from the implant to the new tissue. The implant needs to maintain its shape for an extended period of time to guide remodeling of the patient's tissue. When used as a breast implant, the implant provides support to the breast until support transitions from the implant to the new tissue. Preferably, there is minimal or no loss of support for the breast tissue during this transition period. The breast implant maintains its shape for an extended period of time to guide tissue ingrowth into the implant and create the desired breast shape.

[0029] In some embodiments, the implant has a predetermined three-dimensional shape. In the case of a breast implant, the implant has a predetermined three-dimensional shape that can be implanted subcutaneously between the skin of the breast and the breast mound or chest wall. The breast implant can be implanted in a pre-pectoral, sub-glandular, or sub-pectoral location. The implant allows the surgeon to easily control the volume ratio of the upper and lower breast poles, the degree to which the breast protrudes from the chest wall, and the curvature of the upper and lower breast poles. The surgeon can insert a vascular pedicle or other tissue mass into the implant prior to implantation.

[0030] In some embodiments, implants are used to provide a device for delivering cells, stem cells, differentiated cells, adipocytes, muscle cells, platelets, pedicles, vascular pedicles, tissue blocks, extracellular fat matrix proteins, gels, hydrogels, hyaluronic acid, collagen, bioactive agents, drugs, antibiotics and other materials to the implant site for the surgeon. Preferably, the cells and tissues delivered by the implant or coated or injected into the implant are autologous. Implants can be used for autologous fat transfer. The cells added, coated or injected into the implant can include pancreatic islet cells, hepatocytes and stem cells that are genetically modified to include genes for treating patient diseases. Implants can include bioactive agents that stimulate cell ingrowth, including growth factors, cell adhesion factors, cell differentiation factors, cell recruitment factors, cell receptors, cell binding factors, cell signaling molecules, such as cytokines and molecules that promote cell migration, cell division, cell proliferation and extracellular matrix deposition. Implants can also be coated with or include reagents that prevent tissue adhesion or reagents that prevent cell proliferation, especially reagents that delay cell invasion into the implant structure. Such agents may be present on or throughout the grid, or only on or in one or more specific areas of the grid.

[0031] In some embodiments, an implant can be implanted to replace and or increase soft tissue volume or tissue mass. In some embodiments, the implant can also include a growth chamber for cells and tissue. In some embodiments, the implant can include one, two, or more openings that allow a vascular pedicle or other tissue mass to be inserted into the implant or that allow the implant to clamp a vascular pedicle or other tissue mass.

[0032] In some embodiments, the elastic modulus of the implant is 0.01 kPa to 290 MPa, more preferably 0.1 kPa to 10 MPa, even more preferably 0.1 kPa to 1 MPa or 0.1 kPa to 100 kPa. When the implant is a breast implant, the elastic modulus is preferably 0.01 kPa to 1 MPa, more preferably 0.1 kPa to 100 kPa.

[0033] In some embodiments, the implant can be temporarily deformed for implantation, for example, to allow for minimally invasive delivery procedures. The lattice of the implant can be filled after implantation by injecting one or more of the following: cells, tissue, and / or lipoaspirate. A vascular pedicle or other tissue mass can be inserted before or after the lattice has been filled with cells, tissue, and / or lipoaspirate.

[0034] In some embodiments, the implant can be made of poly-4-hydroxybutyrate (P4HB) and its copolymers, or of poly(butylene succinate) (PBS) and its copolymers. PBS polymers and copolymers may further comprise one or more of the following: a branching agent, a cross-linking agent, a chain extender, and a reactive blending agent. PBS and P4HB polymers and copolymers may be isotopically enriched. In some preferred embodiments, the lattice unit cells of the implant can be made of P4HB, PBS, or a copolymer of P4HB and PBS by injection molding, extrusion, knitting, weaving, foaming, or 3D printing. In some embodiments, the lattice is made of a material that can hold the microspheres of liposuctioned fat in place and prevent fat accumulation that can cause necrosis.

[0035] In some embodiments, the polymer used to prepare the implant has a weight average molecular weight of 50 kDa to 1,000 kDa, more preferably 90 kDa to 600 kDa, and even more preferably 200 kDa to 450 kDa.

[0036] In some embodiments, the endotoxin content of the implant is less than 20 endotoxin units per implant. In some embodiments, the implant has been sterilized by ethylene oxide, electron beam, or gamma-irradiation.

[0037] In some embodiments, an implant is manufactured by forming a plurality of first type unit cells into a grid, wherein (i) the unit cells are formed by injection molding a polymer composition to form struts or fibers of the unit cells, and the unit cells are assembled to form a grid, (ii) the unit cells are formed by warp knitting the fibers, and the unit cells are assembled to form a grid, (iii) the grid is formed directly from the polymer composition by 3D printing the polymer struts or fibers of the grid, or (iv) the unit cells are formed by foaming, and the foamed unit cells are assembled to form the grid. The grid thus formed may: (i) have an elastic modulus of 0.01 kPa to 1 MPa, (ii) be trimmed after molding or printing, and or (iii) include one or more tabs or anchors for fixing the implant. The grid thus formed by injection molding may also include fasteners that allow the unit cells to be attached to each other to form a grid.

[0038] In some embodiments, the implant can be temporarily deformed during implantation or delivery via minimally invasive techniques.

[0039] In some embodiments, the cell of the implant is formed with a surface roughness (Ra). Surface roughness promotes cell attachment and tissue formation on the implant. Surface roughness also promotes attachment of the implant to adjacent tissues, promotes tissue ingrowth, and helps prevent the device from moving after implantation. In some embodiments, the surface roughness of the struts or fibers of the implant cell is 0.02 to 75 microns, more preferably 0.1 to 50 microns or 0.5 to 30 microns, even more preferably 5 to 30 microns. In some embodiments, the cell of the implant is 3D printed with these surface roughness values. Preferably, the cell of the implant is 3D printed by selective laser melting (SLM) of polymer powder or melt extrusion deposition (MED) of polymer pellets. In some embodiments, the cell is formed by extruded fibers with surface roughness. In some embodiments, extruded fibers having surface roughness can be formed by inducing melt fracture during fiber extrusion, using textured nip rolls to create roughness on the fiber surface after extrusion, extruding the fiber through a feature die orifice (e.g., a sawtooth orifice) and treating the extruded fiber with a solvent vapor mist (e.g., using micron-sized solvent droplets) to produce dimples on the fiber surface. In some embodiments, the implant is formed from a unit cell comprising struts or fibers having a surface roughness of 0.02 to 75 microns, more preferably 0.1 to 50 microns, and the struts or fibers having one or more of the following properties: (i) a diameter of 0.025 to 3 mm, more preferably 0.1 to 2 mm, even more preferably 0.15 to 1 mm; (ii) a breaking load of 0.1 to 200 N, more preferably 1 to 100 N, even more preferably 2 to 50 N; (iii) an elongation at break value of 22% to 1,000%, more preferably 100% to 700%; and (iv) an elastic modulus value of 0.05 to 10 GPa, more preferably 0.1 to 3 GPa, even more preferably 0.2 to 0.8 GPa. In some embodiments, the implant is formed from a single cell comprising struts or fibers having a surface roughness of 0.02 to 75 microns, more preferably 0.1 to 50 microns, and the implant has an elastic modulus of 0.01 kPa to 290 MPa, more preferably 0.1 kPa to 10 MPa. In some embodiments, the implant having a surface roughness is a breast implant.

[0040] In some embodiments, the implant is not permanent, but rather degrades at a predictable rate and with a predictable strength retention that allows for the transition of support from the implant to the new tissue.

[0041] In some embodiments, the implant has a scaffold structure that can be coated with or serve as a reservoir for autologous tissue, including but not limited to autologous fat, lipoaspirate, injectable fat, adipocytes, fibroblasts, and stem cells.

[0042] In some embodiments, the implant contains one or more openings that allow for the insertion of a vascular pedicle or other tissue mass to augment or replace tissue volume.

[0043] In some embodiments, the implant can be readily designed into any shape, for example, a shape that provides a specific and desired appearance of the breast.

[0044] These and other objects and advantages of the present invention will become apparent from the following detailed description and accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Figure 1 is a perspective view of an implant comprising a plurality of connected skeletal polyhedral unit cells according to one embodiment of the present invention;

[0046] Figures 2A to 2D They are Figure 1 bottom, isometric, front, and left views of a skeleton polyhedral unit cell of the implant shown;

[0047] Figure 3 yes Figure 1 Schematic diagram of the implant shown being compressed by the fingers;

[0048] Figure 4 is a perspective view of a coiled cylindrical unit cell according to one embodiment of the present invention;

[0049] Figure 5 is a perspective view of a coiled unit cell including fasteners for assembling the unit cells together according to one embodiment of the present invention;

[0050] Figure 6 is a perspective view of a coiled unit cell made of a thermoplastic polymer by 3D printing according to one embodiment of the present invention;

[0051] Figure 7 According to one embodiment of the present invention, a plurality of Figure 5 A perspective view of the lattice structure of the implant formed by coiled unit cells shown in FIG;

[0052] Figure 8 According to one embodiment of the present invention, multiple Figure 4 An upper perspective view of a lattice structure of an implant is shown formed by coiling cylindrical unit cells to form the lattice structure of the implant;

[0053] Figure 9A is a side view of an absorbable breast implant comprising a skeleton polyhedral unit cell and a porous shell according to one embodiment of the present invention;

[0054] Figure 9B yes Figure 9A a top view of the illustrated implant showing the porous shell;

[0055] Figure 10A is an upper perspective view of another breast implant comprising a skeleton polyhedral unit cell according to an embodiment of the present invention;

[0056] Figure 10B yes Figure 10A a cross-section of the illustrated implant showing a polyhedral unit cell of the implant's skeleton;

[0057] Figure 11 is a superior perspective view of another implant according to an embodiment of the present invention;

[0058] Figure 12 is a diagram of a reticulated unit cell according to one embodiment of the present invention;

[0059] Figure 13 is a top view of a cuboid-shaped compressible unit cell according to one embodiment of the present invention;

[0060] Figure 14 yes Figure 13 A side perspective view of a cuboid-shaped compressible unit cell is shown;

[0061] Figure 15 is a side perspective view of four cuboid-shaped compressible unit cells stitched together to form a compressible assembly unit according to one embodiment of the present invention; and

[0062] Figures 16A to 16C is a diagram illustrating a method for forming porous compressible foam cells according to one embodiment of the present invention. DETAILED DESCRIPTION

[0063] Before describing the present invention in detail, it should be understood that the present invention is not limited to the specific changes set forth herein, because various changes or modifications can be made to the described invention and equivalents can be replaced without departing from the spirit and scope of the present invention. It will be apparent to those skilled in the art after reading this disclosure that each individual embodiment described and illustrated herein has discrete components and features that can be easily separated or combined with the features of any one of the other several embodiments without departing from the scope or spirit of the present invention. In addition, many modifications can be made to adapt specific circumstances, materials, composition of matter, processes, process behavior or steps to the purpose, spirit or scope of the present invention. All such modifications are intended to fall within the scope of the claims set forth herein.

[0064] The methods recited herein can be performed in any order of the recited events that is logically possible, as well as in the order in which the events are recited. In addition, where a range of values ​​is provided, it is understood that each intervening value between the upper and lower limits of the range, as well as any other specified value or intervening value within the specified range, is encompassed within the present invention. Furthermore, it is contemplated that any optional feature of the described inventive variations may be set forth and claimed independently or in combination with any one or more of the features described herein.

[0065] All prior subject matter (eg, publications, patents, patent applications, and articles) mentioned herein is incorporated by reference in its entirety, except to the extent that the subject matter may conflict with the subject matter of the present invention, in which case the subject matter presented herein controls.

[0066] A noun without a quantifier means one, one or more. More specifically, unless the context clearly indicates otherwise, a noun without a quantifier used herein and in the appended claims means one, one or more. It is further noted that the claims can be drafted to exclude any optional element. Similarly, this statement is intended to serve as an antecedent basis for the use of exclusive terminology such as "only," "only," etc., in connection with the recitation of claim elements, or for the use of a "negative" limitation.

[0067] To further aid understanding, the following definitions are set forth below. However, it should also be understood that unless otherwise defined as described herein, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0068] I. Definition

[0069] As generally used herein, "absorbable" means that the material degrades in the body and the degradation products are eliminated or excreted from the body. The terms "absorbable," "resorbable," "degradable," and "erodible," whether or not prefixed with "bio," and whether the degradation is primarily due to hydrolysis or mediated by metabolic processes, are used interchangeably herein to describe materials that break down and are gradually absorbed, excreted, or eliminated by the body.

[0070] As generally used herein, "biologically active agent" refers to a therapeutic agent, a prophylactic agent, or a diagnostic agent, preferably an agent that promotes healing and regeneration of host tissue, and also a therapeutic agent that prevents, inhibits, or eliminates infection. An "agent" without a quantifier modifier means one or more "agents."

[0071] As generally used herein, "biocompatible" means that the biological response to a material or device is appropriate for the device's intended in vivo application. Any metabolites of these materials should also be biocompatible.

[0072] "Blend" as generally used herein means a physical combination of different polymers, as opposed to a copolymer formed from two or more different monomers.

[0073] As generally used herein, "copolymer of poly-4-hydroxybutyrate" means any polymer containing 4-hydroxybutyrate with one or more different hydroxy acid units. The copolymer may be isotopically enriched.

[0074] As generally used herein, "copolymer of poly(butylene succinate)" means any polymer containing 1,4-butanediol and succinic acid units and one or more different diol or diacid units. The copolymer may contain one or more of the following: a branching agent, a crosslinking agent, a chain extender, and a reactive blending agent. The copolymer may be isotopically enriched.

[0075] "Endotoxin content" as generally used herein refers to the amount of endotoxin present in an implant or sample and is determined by the limulus amebocyte lysate (LAL) test.

[0076] Unless otherwise indicated, "molecular weight" as generally used herein refers to weight average molecular weight (Mw), not number average molecular weight (Mn), and is measured by GPC relative to polystyrene.

[0077] "Pitch," as generally used herein to describe coils or springs, means the distance between the wires of adjacent coils, and is measured from the center of a wire to the center of an adjacent wire.

[0078] "Poly(butylene succinate)" means a polymer containing 1,4-butanediol units and succinic acid units. The polymer may contain one or more of the following: a branching agent, a crosslinking agent, a chain extender, and a reactive blending agent. The polymer may be isotopically enriched.

[0079] "Poly(butylene succinate) and copolymers" include polymers and copolymers prepared with one or more of the following: chain extenders, coupling agents, cross-linking agents, and branching agents.

[0080] As generally used herein, "poly-4-hydroxybutyrate" means a homopolymer containing 4-hydroxybutyrate units. It may be referred to herein as P4HB or Biomaterial (manufactured by Tepha, Inc., Lexington, MA) The polymer may be isotopically enriched.

[0081] As used herein, "pre-chest" means below the skin and above or on the pectoral muscles.

[0082] As used herein, "skeleton polyhedron" means a perimeter framework consisting of the edges and vertices of the polyhedron, and its interior is hollow unless filled.

[0083] As used herein, "soft tissue" refers to body tissue that is not hardened or calcified. Soft tissue does not include hard tissue, such as bone and tooth enamel.

[0084] "Strength retention" refers to the amount of time a material retains specific mechanical properties after being implanted in a human or animal. For example, if the tensile strength of a resorbable fiber or strut decreases by half within 3 months of implantation in an animal, the fiber or strut's strength retention at 3 months would be 50%.

[0085] As used herein, "subglandular" means below the breast tissue and above the pectoral muscle.

[0086] As used herein, "subpectoral" means at least partially beneath the pectoral muscle.

[0087] "Surface roughness" (Ra) as used herein is the arithmetic mean of the absolute values ​​of the deviations of the profile heights from the mean line recorded within the evaluation length.

[0088] As used herein, "bulk density" refers to the ratio of the volume of material forming a unit cell of an implant lattice divided by the volume of the void space within the implant lattice. For example, an implant lattice with a bulk density of 20% would contain 20% material by volume and 80% void space by volume. Bulk density is measured before any additives, bioactive agents, cells, and tissues are applied to the lattice.

[0089] II. Materials used to make implants

[0090] In some embodiments, implants can be used to reshape parts of the body, including the breasts, nipples, face, and buttocks, as well as fill voids, repair hernias, and deliver biological and synthetic materials to help regenerate, augment, repair, strengthen, and rebuild tissue. Implants are soft tissue implants, meaning they can be used to regenerate, augment, repair, strengthen, and rebuild soft tissue. Implants can eliminate the need for permanent breast implants during mastectomy, mastopexy, and breast augmentation procedures, as well as the need for permanent implants in other surgical procedures. Implants are biocompatible and, as the implant degrades, are preferably replaced in vivo by the patient's tissue. Implants are particularly suitable for filling voids or augmenting tissue, particularly soft tissue. Implants can have a range of properties, from hard, rigid structures to soft structures that temporarily deform when force is applied. These properties can be designed to resemble soft tissue. Implants manufactured for the breast can be compressed and can recover their shape after being compressed. Optionally, the implant can be coated with autologous tissue, autologous fat, lipoaspirate, injectable fat, adipocytes, fibroblasts, and stem cells before, during, or after implantation. The implant may also contain one or more openings or channels (including transverse channels) to allow insertion into a vascular pedicle or other tissue mass.

[0091] A. Polymers used to make implants

[0092] In some embodiments, the implant comprises a grid formed by a plurality of unit cells. The shape or type of the unit cells can vary. The shape of the unit cell can be a skeleton polyhedron with edges and vertices formed by polymer struts or fibers. Alternatively, the unit cell can be a coil or spring formed by a polymer. A third type of unit cell is a mesh unit cell in which the top and bottom of the unit cell are formed by a mesh and the top and bottom meshes are connected together with struts or fibers to form the unit cell. A fourth type of unit cell is a foam unit cell, preferably a porous compressible unit cell. The grid structure of the implant is formed by joining two or more unit cells together. The unit cells joined together can be the same or different. The grid can comprise 2 or more unit cells, and preferably 50 or more unit cells. The grid can optionally comprise other features, such as one or more openings or one or more channels (including one or more transverse channels).

[0093] The lattice of the implant can comprise permanent materials, such as non-degradable thermoplastic polymers, including polymers and copolymers of ethylene and propylene, including ultra-high molecular weight polyethylene, ultra-high molecular weight polypropylene, nylon, polyesters such as poly(ethylene terephthalate), poly(tetrafluoroethylene), polyurethanes, poly(ether-urethanes), poly(methyl methacrylate), polyetheretherketones, polyolefins, and poly(ethylene oxide). However, the lattice of the implant preferably comprises a degradable material, more preferably a thermoplastic or polymeric degradable material, and even more preferably the lattice of the implant is made entirely of a degradable material.

[0094] In a preferred embodiment, the lattice of the implant is made of one or more absorbable polymers or copolymers, preferably absorbable thermoplastic polymers and copolymers, and even more preferably absorbable thermoplastic polyesters. The lattice of the implant can be made, for example, from polymers including but not limited to glycolic acid, lactic acid, 1,4-diol, Polymers of alkyl ketone, trimethylene carbonate, 3-hydroxybutyric acid, 4-hydroxybutyric acid, ε-caprolactone, including polyglycolic acid, polylactic acid, polydimethylsiloxane, polyvinyl alcohol ... copolymers of alkanone, polycaprolactone, glycolic acid and lactic acid, e.g. polymer, and Polymers, and include poly(lactide-co-caprolactone); poly(orthoesters); polyanhydrides; poly(phosphazenes); polyhydroxyalkanoates; synthetic or biologically produced polyesters; polycarbonates; tyrosine polycarbonate; polyamides (including synthetic and natural polyamides, polypeptides and poly(amino acids)); polyesteramides; poly(alkylene alkylates); polyethers (e.g., polyethylene glycol PEG and polyethylene oxide PEO); polyvinyl pyrrolidone or PVP; polyurethanes; polyetheresters; polyacetals; polycyanoacrylates; poly(oxyethylene) / poly(oxypropylene) copolymers; polyacetals, polyketals; polyphosphates (polyphosph ate); (phosphorus-containing) polymers; polyphosphoesters; polyalkylene oxalates; polyalkylene succinates; poly(maleic acid); silk (including recombinant silk and silk derivatives and analogs); chitin; chitosan; modified chitosan; biocompatible polysaccharides; hydrophilic or water-soluble polymers, such as polyethylene glycol (PEG) or polyvinylpyrrolidone (PVP), and blocks of other biocompatible or biodegradable polymers, such as poly(lactide), poly(lactide-co-glycolide) or polycaprolactone and copolymers thereof, including random copolymers and block copolymers thereof.

[0095] Preferably, the lattice of the implant is made of a resorbable polymer or copolymer that will be substantially resorbed within a timeframe of 1 month to 24 months, more preferably 3 months to 18 months after implantation, and retain some residual strength for at least 2 weeks to 6 months.

[0096] The lattice of the implant can also be prepared using blends of polymers and copolymers, preferably absorbable polymers. Particularly preferred blends of absorbable polymers are prepared from absorbable polymers including, but not limited to, glycolic acid, lactic acid, 1,4-dimethoxybenzyl alcohol, and 1,4-dimethoxybenzyl alcohol. polymers of alkyl ketone, trimethylene carbonate, 3-hydroxybutyric acid, 4-hydroxybutyric acid ester, ε-caprolactone, 1,4-butanediol, 1,3-propylene glycol, ethylene glycol, glutaric acid, malonic acid, oxalic acid, succinic acid, adipic acid, or copolymers thereof.

[0097] In a particularly preferred embodiment, the lattice of the implant is made using poly-4-hydroxybutyrate (P4HB™ polymer from Tepha, Lexington, MA) or its copolymers. Copolymers include P4HB with other hydroxy acids (e.g., 3-hydroxybutyrate), as well as P4HB with glycolic or lactic acid monomers. Poly-4-hydroxybutyrate is a strong, flexible thermoplastic polyester that is biocompatible and resorbable (Williams et al., Poly-4-hydroxybutyrate (P4HB): a new generation of resorbable medical devices for tissue repair and regeneration, Biomed. Tech. 58(5): 439-452 (2013)). Upon implantation, P4HB is hydrolyzed into its monomers, and the monomers are metabolized to carbon dioxide and water via the Krebs cycle. In a preferred embodiment, the weight average molecular weight Mw of the P4HB homopolymer and its copolymers is in the range of 50 kDa to 1,200 kDa (by GPC relative to polystyrene), more preferably 100 kDa to 600 kDa, even more preferably 200 kDa to 450 kDa. A weight average molecular weight of 50 kDa or higher is preferred for processing and mechanical properties.

[0098] In another preferred embodiment, the lattice of the implant is prepared from a polymer comprising at least a diol and a diacid. In a particularly preferred embodiment, the polymer used to prepare the lattice is poly(butylene succinate) (PBS), wherein the diol is 1,4-butanediol and the diacid is succinic acid. The poly(butylene succinate) polymer can be a copolymer with other diols, other diacids, or combinations thereof. For example, the polymer can be a poly(butylene succinate) copolymer further comprising one or more of: 1,3-propylene glycol, ethylene glycol, 1,5-pentanediol, glutaric acid, adipic acid, terephthalic acid, malonic acid, methylsuccinic acid, dimethylsuccinic acid, and oxalic acid. Examples of preferred copolymers are poly(butylene succinate-co-adipate), poly(butylene succinate-co-terephthalate), poly(butylene succinate-co-butylene methyl succinate), poly(butylene succinate-co-butylene dimethyl succinate), poly(butylene succinate-co-ethylene succinate), and poly(butylene succinate-co-propylene succinate). The poly(butylene succinate) polymer or copolymer may further comprise one or more of the following: a chain extender, a coupling agent, a cross-linking agent, and a branching agent. For example, the poly(butylene succinate) or copolymer thereof may be branched or cross-linked by adding one or more of the following agents: malic acid, trimethylolpropane, trimesic acid, citric acid, glycerol propoxylate, and tartaric acid. Particularly preferred agents for branching or crosslinking poly(butylene succinate) polymers or copolymers thereof are hydroxycarboxylic acid units. Preferably, the hydroxycarboxylic acid units have two carboxyl groups and one hydroxyl group, two hydroxyls and one carboxyl group, three carboxyl groups and one hydroxyl group, or two hydroxyls and two carboxyl groups. In a preferred embodiment, the lattice of the implant is prepared from poly(butylene succinate) containing malic acid as a branching or crosslinking agent. This polymer may be referred to as poly(butylene succinate) crosslinked with malic acid, succinic acid-1,4-butylene glycol-malic acid copolyester, or poly(1,4-butylene glycol-co-succinic acid) crosslinked with malic acid. It should be understood that references to malic acid and other crosslinking agents, coupling agents, branching agents, and chain extenders include polymers prepared with these agents, wherein the agents have undergone further reactions during processing. For example, the agents may undergo dehydration during polymerization. Thus, poly(butylene succinate)-malic acid copolymer refers to a copolymer prepared from succinic acid, 1,4-butylene glycol, and malic acid. In another preferred embodiment, malic acid can be used as a branching agent or crosslinking agent to prepare a copolymer of poly(butylene succinate) and adipate, which copolymer can be referred to as poly[(butylene succinate)-co-adipate crosslinked with malic acid]. As used herein, "poly(butylene succinate) and copolymers" include polymers and copolymers prepared with one or more of the following: chain extenders, coupling agents, crosslinking agents, and branching agents.In a particularly preferred embodiment, poly(butylene succinate) and copolymers thereof comprise at least 70% by weight, more preferably 80% by weight, and even more preferably 90% by weight of succinic acid and 1,4-butanediol units. The polymers comprising a diacid and a diol, including poly(butylene succinate) and copolymers thereof and other polymers comprising a diacid and a diol described herein, preferably have a weight average molecular weight (Mw) of 10,000 to 400,000, more preferably 50,000 to 300,000, and even more preferably 100,000 to 200,000, based on gel permeation chromatography (GPC) relative to a polystyrene standard. In a particularly preferred embodiment, the polymers and copolymers have a weight average molecular weight of 50,000 to 300,000, more preferably 75,000 to 300,000. In a preferred embodiment, the poly(butylene succinate) or copolymers thereof used to make the grid have one or more, or all, of the following properties: 1.23 g / cm 3 to 1.26g / cm 3 density, a glass transition temperature of -31°C to -35°C, a melting point of 113°C to 117°C, a melt flow rate (MFR) at 190°C / 2.16kgf of 2g / 10min to 10g / 10min, and a tensile strength of 30 to 60MPa.

[0099] In another embodiment, the polymers and copolymers described herein (including P4HB and its copolymers and PBS and its copolymers) used to prepare the lattice of the implant include polymers and copolymers in which isotopic enrichment of hydrogen, carbon and or oxygen is known. Hydrogen has three naturally occurring isotopes, including 1 H (hydrogen), 2 H (deuterium) and 3 H (tritium), the most common of which is 1 H isotope. The isotopic content of the polymer or copolymer can be enriched, for example, so that the polymer or copolymer contains a specific one or more isotopes above the natural proportion. The carbon and oxygen content of the polymer or copolymer can also be enriched to contain carbon and oxygen isotopes above the natural proportion, including but not limited to 13 C. 14 C. 17 O or 18 O. Other isotopes of carbon, hydrogen, and oxygen are known to those skilled in the art. A preferred hydrogen isotope to be enriched in P4HB or its copolymers or PBS or its copolymers is deuterium, i.e., deuterated P4HB or its copolymers or deuterated PBS or its copolymers. The deuteration percentage may be as high as at least 1% and as high as 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80% or 85% or more.

[0100] In a preferred embodiment, the polymers and copolymers used to prepare the lattice, including P4HB and its copolymers and PBS and its copolymers, have a low moisture content. This is preferred to ensure that implants with high tensile strength, extended strength retention, and good shelf life can be produced. In a preferred embodiment, the polymers and copolymers used to prepare the implant have a moisture content of less than 1,000 ppm (0.1 wt%), less than 500 ppm (0.05 wt%), less than 300 ppm (0.03 wt%), more preferably less than 100 ppm (0.01 wt%), and even more preferably less than 50 ppm (0.005 wt%).

[0101] The composition used to prepare the implant desirably has a low endotoxin content. In some preferred embodiments, the endotoxin content is sufficiently low that the endotoxin content of the implant produced from the polymer composition is less than 20 endotoxin units / device as determined by the Limulus Amebocyte Lysate (LAL) test. In one embodiment, the polymer composition used to prepare the lattice of the implant has an endotoxin content of <2.5 EU / g polymer or copolymer. For example, the endotoxin content of the P4HB polymer or copolymer or the PBS polymer or copolymer is <2.5 EU / g polymer or copolymer.

[0102] B. Additives

[0103] Certain additives can be incorporated into the implant, preferably into the polymer composition used to make the grid. In one embodiment, these additives are incorporated into the polymer or copolymer described herein during the compounding process to produce a pellet that can then be processed to produce a grid. For example, the pellet can be injection molded, extruded, or printed to form a grid or a unit cell of a grid. In another embodiment, the pellet can be ground to produce a powder suitable for further processing, such as by 3D printing. Alternatively, a powder suitable for further processing, such as by 3D printing, can be directly formed by blending the additive and the polymer or copolymer. If desired, the powder for processing can be sieved to select the optimal particle size range. In another embodiment, the additive can be incorporated into the polymer composition used to prepare the grid of the implant using a solution-based method.

[0104] In a preferred embodiment, the additive is biocompatible, and even more preferably, the additive is biocompatible and resorbable.

[0105] In one embodiment, the additive can be a nucleating agent and or a plasticizer. These additives can be added to the polymer composition of the grid for the preparation of the implant in an amount sufficient to produce the desired result. Generally speaking, these additives can be added in an amount of 1% by weight to 20% by weight. Nucleating agents can be incorporated to increase the crystallization rate of polymers, copolymers or blends. Such agents can be used, for example, to promote the manufacture of the grid and improve the mechanical properties of the grid. Preferred nucleating agents include, but are not limited to, salts of organic acids such as calcium citrate, polymers or oligomers of PHA polymers and copolymers, high melting point polymers such as PGA, talc, micronized mica, calcium carbonate, ammonium chloride and aromatic amino acids such as tyrosine and phenylalanine.

[0106] Plasticizers that can be incorporated into the polymer composition used to prepare the implant lattice include, but are not limited to, di-n-butyl maleate, methyl laurate, dibutyl fumarate, di(2-ethylhexyl)(dioctyl)maleate, paraffin wax, dodecanol, olive oil, soybean oil, polytetramethylene glycol, methyl oleate, n-propyl oleate, tetrahydrofurfuryl oleate, epoxidized linseed oil, 2-ethylhexyl epoxy talloleate, triacetin, methyl linoleate, dibutyl fumarate, methyl acetyl ricinoleate, acetyl tri(n-butyl oleate), ... The plasticizers include bis(2-hydroxyethyl)dimer, butyl ricinoleate, glyceryl tri(acetyl ricinoleate), methyl ricinoleate, n-butyl acetyl ricinoleate, propylene glycol ricinoleate, diethyl succinate, diisobutyl adipate, dimethyl azelaic acid, di(n-hexyl) azelaic acid, tributyl phosphate, and mixtures thereof. Particularly preferred plasticizers are citric acid esters.

[0107] C. Bioactive Agents, Cells, and Tissues

[0108] Implants can be loaded, filled, coated, or otherwise incorporated with bioactive agents. Bioactive agents can be included in implants for a variety of reasons. For example, bioactive agents can be included to improve tissue ingrowth into the implant, to improve tissue maturation, to provide delivery of active agents, to improve the wettability of the implant, to prevent infection, and to improve cell attachment. Bioactive agents can also be incorporated into the lattice structure of the implant.

[0109] Implants can include agents designed to stimulate cell ingrowth, including growth factors, cell adhesion factors (including cell adhesion polypeptides), cell differentiation factors, cell recruitment factors, cell receptors, cell binding factors, cell signaling molecules, such as cell factors and molecules that promote cell migration, cell division, cell proliferation, and extracellular matrix deposition. Such agents include fibroblast growth factor (FGF), transforming growth factor (TGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), granulocyte-macrophage colony stimulating factor (GMCSF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), hepatocyte growth factor (HGF), interleukin-1-B (IL-1B), interleukin-8 (IL-8) and nerve growth factor (NGF), and combinations thereof. As used herein, the term "cell adhesion polypeptide" refers to a compound having at least two amino acids per molecule that is capable of binding to cells via cell surface molecules. Cell adhesion polypeptides include any extracellular matrix protein known to play a role in cell adhesion, including fibronectin, vitronectin, laminin, elastin, fibrinogen, collagen type I, II and V, and synthetic peptides with similar cell adhesion properties. Cell adhesion polypeptides also include peptides from any of the aforementioned proteins, including fragments or sequences containing binding domains.

[0110] The implant may incorporate a wetting agent designed to improve the wettability of the lattice structure surface to allow fluids to readily adsorb onto the implant surface and to promote cell attachment and / or modify the water contact angle of the implant surface. Examples of wetting agents include polymers of ethylene oxide and propylene oxide, such as polyethylene oxide, polypropylene oxide, or copolymers of these, such as Additional suitable wetting agents include surfactants or emulsifiers.

[0111] Implants can contain gels, hydrogels, or living hydrogel blends to further improve wetting properties and promote cell growth throughout the implant's lattice structure. Hydrogel blends consist of living cells encapsulated in biocompatible hydrogels such as gelatin, methacrylated gelatin (GelMa), silk gel, and hyaluronic acid (HA) gel.

[0112] Other bioactive agents that can be incorporated into the implant include antimicrobials, particularly antibiotics, disinfectants, tumor agents, anti-scarring agents, anti-inflammatory agents, anesthetics, small molecule drugs, anti-adhesion agents, cell proliferation inhibitors, anti-angiogenic factors and pro-angiogenic factors, immunomodulators and coagulants. The bioactive agent can be a protein such as collagen and an antibody, a peptide, a polysaccharide such as chitosan, alginate, hyaluronic acid and its derivatives, a nucleic acid molecule, a small molecular weight compound such as a steroid, an inorganic material such as hydroxyapatite and ceramics, or a complex mixture such as platelet-rich plasma. Suitable antimicrobials include: bacitracin, biguanides, triclosan, gentamicin, minocycline, rifampicin, vancomycin, cephalosporins, copper, zinc, silver and gold. The nucleic acid molecule can include DNA, RNA, siRNA, miRNA, antisense or aptamers.

[0113] Implants can also include allograft materials and xenograft materials, including acellular dermal matrix materials and small intestinal submucosa (SIS). In one embodiment, the implant can include a vascular pedicle or other tissue block. The vascular pedicle or other tissue block is preferably autologous tissue.

[0114] In another embodiment, the implant may incorporate a system for controlled release of the therapeutic or prophylactic agent.

[0115] In one embodiment, implant is coated with allograft or xenograft and cell before implanting, during implantation or after implantation or its arbitrary combination.In a particularly preferred embodiment, implant is coated with autologous tissue and cell from patient before implanting, during implantation or after implantation or its arbitrary combination.Autologous tissue and cell are preferably one or more of the following: autologous fat, lipoaspirate, adipose tissue, injectable fat, adipose tissue, adipocyte, fibroblast and stem cell, comprise people's adipose tissue derived stem cell (also referred to as preadipocyte or adipose tissue derived precursor cell) and fibroblast-like stem cell.In a preferred embodiment, implant can be coated with autologous tissue and cell as described herein, and can further comprise vascular pedicle or other tissue blocks.As obvious in this article, the lattice structure of implant is designed to not only produce the shape of implant (for example breast implant), and produces and can retain autologous tissue and cell to promote the large surface area of ​​tissue ingrowth.

[0116] III. Methods for preparing implants from skeleton polyhedral cells, coiled cells, reticular cells, and foam cells

[0117] There are a variety of methods that can be used to manufacture implants.

[0118] A. Implant shape

[0119] In one embodiment, the implants are designed such that they are three-dimensional when manufactured.

[0120] Their shape allows surgeons to increase tissue volume, fill voids, reconstruct lost or missing tissue or tissue structures, outline tissue, augment tissue, restore tissue or organ function, support or repair damaged tissue structures, enhance existing tissue structures, increase soft tissue volume, and reshape body parts. For example, implants can be used to reshape, replace, or repair breasts, nipples, face, and buttocks. In one embodiment, implants allow the shape of soft tissue structures to be changed or sculpted without the use of permanent implants.

[0121] Within the scope described herein, it should be understood that there are a variety of implant shapes and sizes, and except for the circumstances listed in the appended claims, the present invention has no restrictions on the three-dimensional shape and size of the implant. The implant can be assembled or printed into any size and shape suitable for use as an implant. For example, implants with the following three-dimensional shapes can be easily prepared, for example: sphere, hemisphere, cylinder, cone, dome, cuboid, tetrahedron, triangular prism or quadrangular prism, dodecahedron, torus and ellipsoid, and custom shapes can optionally be produced with the help of computer-aided design. For example, people can produce cylindrical shaped implants for nipple reconstruction, or dome shaped implants for breast reconstruction. The size of the implant can be sized to increase tissue volume, replace previous tissue volume, change the volume distribution of tissue, change the appearance of tissue, or replace existing tissue volume with a smaller volume.

[0122] In a preferred embodiment, the shape of the implant is provided so that it can be used to change the soft tissue volume of the breast without the use of permanent breast implants, such as silicone breast implants. In some embodiments, the implant can be prepared in a shape and size that is used to increase breast size, replace the tissue volume and shape of the breast after a mastectomy procedure, and create a specific breast appearance. For example, the implant can be prepared so that when implanted in the breast, it creates a breast with a specific upper pole volume (UPV) to lower pole volume (LPV) ratio. In some embodiments, the implant is a breast implant with a volumetric size such that implantation of the implant creates a breast with a UPV of 25% to 35% of the total breast volume and an LPV of 65% to 75% of the total breast volume. In addition to sculpting the breast to a specific upper and lower pole tissue volume ratio, the size and shape of the implant can also be selected to provide a highly desired lower pole and upper pole shape and the degree of breast protrusion from the chest wall. In some embodiments, the implant is a breast implant designed so that: (a) the lower pole of the breast has a very attractive lower pole curvature, particularly an attractive convex shape, (b) the upper pole of the breast has a straight or slightly concave curvature, and (c) the distance the breast projects from the chest wall is defined. It will therefore be apparent that the implant of the present invention can be used to create a very attractive reconstructed breast by having the following specific shapes: (i) a defined ratio of UPV to LPV; (ii) a defined curvature of the upper and lower poles; (iii) a defined extent of breast projection from the chest wall; and (iv) a defined angle of the nipple on the breast.

[0123] Additional shapes for the implant are described in U.S. patent application Ser. No. 16 / 262,018, filed on Jan. 30, 2019, and entitled “FULL CONTOUR BREAST IMPLANT.”

[0124] Implants designed for the breast can be made to a size large enough to allow them to be used for mastopexy and breast reconstruction. These implants are wide enough to span the width of the breast. In one embodiment, four sizes and shapes of implants are used in breast surgery, namely small, medium, large and extra large. The four sizes of these implants are shown in Table 1, where IMF-UP is the longitudinal distance between the lowest point of the implant in the breast (closest to the inferior fold (IMF) of the breast after implantation) and the highest point in the breast (closest to the intersection between the breast and the chest wall in the upper pole after implantation), MD-LT is the width of the implant measured from the inside to the outside of the implant, CHST-NAC is the maximum projection distance of the implant when implanted on the chest wall, and LP radius is the radius of curvature of the implant in the lower pole. As is apparent from Table 1, implants for breast surgery may have an IMF-UP distance of 12 cm to 20.8 cm, an MD-LT size of 10.8 cm to 19.2 cm, a CHST-NAC size of 5 cm to 11.9 cm, and an LP radius of 4.2 cm to 7.6 cm. The dimensions of the implant that imparts the upper pole shape in the region may vary. In this region, the implant shape is preferably slightly concave or straight.

[0125] Table 1

[0126] Breast implant size

[0127]

[0128] In some embodiments, the implant can be prepared with a porous shell. For example, Figure 9A and 9B Shows how a breast implant can be constructed with a skeleton polyhedral unit cell and a porous outer shell. Figure 9A shows a cross section of an implant 480, wherein a unit cell 482 is visible inside the porous shell 490 of the implant, and Figure 9B Shown is the top of a porous outer membrane 490 covering the implant.The implant has a large surface area that can be coated with, for example, autologous fat, cells, collagen or bioactive agents.

[0129] B. Single cell

[0130] Implants containing grids having different shapes can be produced using the same or different types of unit cells. The unit cells can be assembled to form the grid, or 3D printed to form the grid. The grid can contain 2 or more unit cells, but more preferably 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 100, 1,000, 10,000 or more unit cells. The unit cells of the grid are joined to one or more unit cells that can be of the same or different types. The unit cells are hollow or porous so that the grid formed by the unit cells fills a defined volume and creates a space-occupying structure. In one embodiment, the unit cells have pores with a width or diameter of 100 μm to 1 mm, more preferably 250 μm to 750 μm. In another embodiment, the unit cells incorporated into the grid can have pores of the same size, or a mixture of pore sizes. The grid of the implant made of unit cells has a low bulk density that provides a large surface area and void volume. The size of the unit cells allows for the formation of a low-volume density lattice that can be colonized by cells and invaded by tissues, blood vessels, or a combination thereof. The size of the unit cells also allows for the implant lattice to be coated with allograft or xenograft tissue and cells, preferably autologous tissue and cells, including but not limited to autologous fat, lipoaspirate, lipofiller, injectable fat, adipocytes, fibroblasts, and stem cells. In a preferred embodiment, the size of the unit cells allows for the interior of the lattice formed from the unit cells to be coated with fat, lipoaspirate, injectable fat, adipocytes, fibroblasts, and stem cells. The unit cell size is also designed to allow for the coating of the lattice with collagen and / or hyaluronic acid or its derivatives. Cells and other compositions, such as collagen and hyaluronic acid, can be applied to the lattice before, after, or both before and after implantation. Preferably, the unit cells are large enough to allow for the insertion of a needle into the lattice structure for the delivery of bioactive agents, cells, fat, and other compositions by injection. In some embodiments, the lattice is constructed from unit cells that allow a needle with a gauge of 12 to 21 to be inserted into a unit cell of the lattice. This property allows the use of a syringe and the loading of the grid with cells, tissue, collagen, bioactive agents and additives, including fat, without damaging the grid.Preferably, the grid allows the insertion of a needle with an outer diameter of 0.5 to 3 mm.

[0131] The size and shape of the unit cells can be selected to provide different types of grids with different volume densities. The properties of an implant grid formed from repeating unit cells are highly predictable and can be predicted based on the size of the unit cells and the materials used to make the unit cells. Unit cells with different physical properties can be prepared by selecting the size of the unit cells, the geometry of the unit cells, and the materials used to make the unit cells. Selecting specific unit cell sizes and materials can produce grids with properties ranging from hard, stiff, or rigid to elastic, soft, or compressible from the unit cells. In some embodiments, the mechanical properties of the grid can be changed without changing the shape of the unit cells, but rather by changing the diameter or width of the struts or fibers of the unit cells. For example, if the desired mechanical properties, such as the elastic modulus or compressive strength, are known, the strut thickness or diameter required for a given unit cell made from a given polymer can be calculated. In a preferred embodiment, the size and material of the unit cells are selected so that the implant grid prepared from the unit cells has properties similar to those of the soft tissue into which the implant is implanted. For example, the size and material of the unit cells can be selected to provide an implant grid with mechanical properties similar to those of breast tissue. In another preferred embodiment, the unit cell can be compressed and, optionally, recover its original shape when the compressive force is released.

[0132] i. Skeleton polyhedron unit cell

[0133] In some embodiments, the unit cell is a skeleton polyhedron with edges and vertices formed by polymer struts or fibers. The edges and vertices or struts / fibers of the skeleton unit cell can have different sizes, thicknesses, lengths, angles, and can be hard, rigid, flexible, elastic, spring-like, and can be made of oriented or non-oriented polymers. In one embodiment, the grid can be prepared by skeleton unit cells having one or more of the following shapes: tetrahedron, cuboid, pentahedron, hexahedron, heptahedron, octahedron, icosahedron, decahedron, dodecahedron, tetradecahedron, and prisms, anti-prisms and truncated polyhedrons thereof. Examples of unit cells in the shape of prisms, anti-prisms and truncated polyhedrons are hexagonal prisms, octagonal anti-prisms and truncated dodecahedrons. In one embodiment, the skeleton unit cell is formed by an elongated polyhedron. In a preferred embodiment, the skeleton unit cell has 4, 6, 8, 12 or 20 faces. In a particularly preferred embodiment, the skeleton unit cell is a dodecahedron, even more preferably a rhombic dodecahedron. Thus, for example, a unit cell having a rhombic dodecahedron shape can be formed into a grid for an implant, and the implant can be implanted, for example, in the breast, nipple, face, or buttocks. Alternatively, the grid can be formed from unit cells having an octagonal shape. In other embodiments, the grid can be made from a combination of two or more different skeleton unit cells, such as dodecahedron and octagonal shapes.

[0134] In some embodiments, the implant is formed from a skeleton polyhedron, wherein the diameter or width of the edges and vertices of the unit cells forming the skeleton polyhedron is 0.025 to 3 mm, more preferably 0.1 to 2 mm, and even more preferably 0.15 to 1 mm. In some embodiments, the breaking load of the edges and vertices of the unit cells forming the skeleton polyhedron is 0.1 to 200 N, more preferably 1 to 100 N, and even more preferably 2 to 50 N. In some embodiments, the elongation at break of the edges and vertices of the unit cells forming the skeleton polyhedron is 22% to 1,000%, more preferably 100% to 700%. In some embodiments, the elastic modulus of the edges and vertices of the unit cells forming the skeleton polyhedron is 0.05 to 10 GPa, more preferably 0.1 to 3 GPa, and even more preferably 0.2 to 0.8 GPa. The diameter, width, breaking load, elongation at break, and elastic modulus of the unit cells' edges and vertices can be the same across the skeleton polyhedron or unit cell, or these values ​​can vary across the skeleton polyhedron or unit cell. The polymer struts forming the edges and vertices of the unit cell preferably have one or more of the following properties: (i) a breaking load of 0.1 to 200 N, (ii) an elongation at break of 22% to 1,000%, and (iii) an elastic modulus of 0.05 to 10 GPa.

[0135] In some embodiments, the elastic modulus of the implant formed by the skeleton polyhedron is 0.01 kPa to 290 MPa, more preferably 0.1 kPa to 10 MPa, even more preferably 0.1 kPa to 1 MPa or 0.1 kPa to 100 kPa, and the polymer struts or fibers forming the unit cells of the skeleton polyhedron have one or more of the following properties: (i) a diameter of 0.025 to 3 mm, more preferably 0.1 to 2 mm, even more preferably 0.15 to 1 mm; (ii) an initial breaking load of 0.1 to 200 N, more preferably 1 to 100 N, even more preferably 2 to 50 N; (iii) an elongation at break value of 22% to 1,000%, more preferably 100% to 700%; and (iv) an elastic modulus value of 0.05 to 10 GPa, more preferably 0.1 to 3 GPa, even more preferably 0.2 to 0.8 GPa.

[0136] In some embodiments, the implant is a breast implant formed from a skeleton polyhedron, and the elastic modulus of the implant is 0.01 kPa to 290 MPa, more preferably 0.1 kPa to 10 MPa, even more preferably 0.1 kPa to 1 MPa or 0.1 kPa to 100 kPa, and the polymer struts or fibers forming the unit cells of the skeleton polyhedron have one or more of the following properties: (i) a diameter of 0.025 to 3 mm, more preferably 0.1 to 2 mm, even more preferably 0.15 to 1 mm; (ii) an initial breaking load of 0.1 to 200 N, more preferably 1 to 100 N, even more preferably 2 to 50 N; (iii) an elongation at break value of 22% to 1,000%, more preferably 100% to 700%; and (iv) an elastic modulus value of 0.05 to 10 GPa, more preferably 0.1 to 3 GPa, even more preferably 0.2 to 0.8 GPa.

[0137] Reference Figure 1 , breast implant 10 is shown comprising a lattice made of connected unit cells of rhombic dodecahedrons that are the backbone. Implant 10 has a low bulk density that provides a large surface area and void volume.

[0138] Figures 2A to 2D Shown for generating Figure 1 Different views of the backbone rhombic dodecahedron unit cell 20 of the lattice implant 10 are shown. The backbone rhombic dodecahedron unit cell 20 has 12 open faces / spaces formed by the edges and vertices of the unit cell made of polymer struts 22. The interior of the unit cell is hollow.

[0139] Figure 3 It is shown that by preparing unit cells of specific dimensions and with specific polymer materials, a grid with desired properties can be formed. Figure 3 In the example shown, a breast implant 30 is shown that includes a lattice, wherein it is apparent that the lattice can be compressed by relatively light pressure from a finger 32 that is sufficient to compress the lattice structure. When the finger is removed, the lattice recovers. Figure 1 Original shape shown. Implants containing compressible gratings are particularly suitable for breast applications because the compressibility of the gratings can be designed to mimic the properties of breast tissue. Therefore, when the breast is massaged, the patient will not feel the hard implant in the breast.

[0140] Refer again Figures 2A to 2D The length (L) of the struts or fibers in the skeleton polyhedral unit cell is preferably 1 to 300 mm, more preferably 2 to 10 mm, and even more preferably 3 to 8 mm. In some embodiments, the struts or fibers are long enough to form a unit cell that allows a needle having an outer diameter (OD) of 0.5 to 3 mm to be inserted into a grid made of the unit cell.

[0141] The height (H) of the unit cell may vary. In some embodiments, the height (H) is 1 to 500 mm, more preferably 5 to 20 mm, and even more preferably 12 to 18 mm.

[0142] The width (W) of the struts or the diameter of the fibers in the skeleton polyhedron unit cell is preferably 50 μm to 5 mm, more preferably 150 μm to 2 mm, and even more preferably 200 μm to 1.5 mm or 500 μm to 1 mm. One advantage of implant design is that the strut width or fiber diameter and strut or fiber length required to produce a lattice with a specific elastic modulus or other mechanical properties can be calculated for a given material.

[0143] In a particularly preferred embodiment, the scaffold unit cells are compressible, and even more preferably can return to their original size after being compressed. A particularly preferred embodiment is a compressible breast implant comprising scaffold unit cells that can return to their original size after being compressed. Implants having different shapes can also be produced using the same or different unit cells, wherein the unit cells are scaffold unit cells.

[0144] ii. Unit cells with coils or springs

[0145] In other embodiments, the unit cells used to form the lattice of the implant are coils, springs, or helices formed from a polymer. An example of a unit cell having coils and springs is Figure 4 In this example, the unit cell is a coiled cylindrical unit cell 40 consisting of three helical struts or wires 42, 44, 46 supporting a top ring 48 and a bottom ring 50. Figure 4 The top and bottom rings of the unit cell shown have an outer diameter of 10 mm, an inner diameter of 8 mm and a circular cross-section of 2 mm. The helical struts or wires are at an angle of 120 degrees to each other with a constant spacing of 0.75 per centimeter. In one embodiment, the outer diameter of the unit cell as a coil and or spring is 2 to 30 mm, more preferably 5 to 15 mm. In one embodiment, the outer diameter of the helical struts or wires can be 0.2 to 3 mm. In one embodiment, the helical struts of these unit cells can be at an angle of 10 to 180 degrees to each other, and the spacing of the helical struts can be 0.5 to 5 per cm. The number of helical struts of the unit cell is preferably 1 to 20, but more preferably 2 to 5.

[0146] The required dimensions of the unit cells comprising coils or springs can be calculated for a given material to provide a grid with specific mechanical properties, such as a specific elastic modulus or compressive strength. In a particularly preferred embodiment, the unit cells made of coils and / or springs are compressible, and even more preferably can recover their original dimensions after being compressed. Implants with different shapes can also be produced using the same or different unit cells, where the unit cells are coils and / or springs.

[0147] In some embodiments, the implant is formed from a unit cell comprising a coil or spring, and the diameter or width of the coil or spring is 0.025 to 3 mm, more preferably 0.1 to 2 mm, and even more preferably 0.15 to 1 mm. In some embodiments, the coil or spring forming a unit cell of the skeleton polyhedron has a breaking load of 0.1 to 200 N, more preferably 1 to 100 N, and even more preferably 2 to 50 N. In some embodiments, the coil or spring forming a unit cell of the skeleton polyhedron has an elongation at break of 22% to 1,000%, more preferably 100% to 700%. In some embodiments, the coil or spring forming a unit cell of the skeleton polyhedron has an elastic modulus of 0.05 to 10 GPa, more preferably 0.1 to 3 GPa, and even more preferably 0.2 to 0.8 GPa. The diameter, width, breaking load, elongation at break, and elastic modulus of the coil or spring of a unit cell can be the same across the entire skeleton polyhedron or unit cell, or these values ​​can vary across the entire skeleton polyhedron or unit cell. The coil or spring of the unit cell preferably has one or more of the following properties: (i) a breaking load of 0.1 to 200 N; (ii) an elongation at break of 22% to 1,000%; and (iii) an elastic modulus of 0.05 to 10 GPa.

[0148] In some embodiments, the elastic modulus of the implant formed by the lattice of coils or springs is 0.01 kPa to 290 MPa, more preferably 0.1 kPa to 10 MPa, even more preferably 0.1 kPa to 1 MPa or 0.1 kPa to 100 kPa, and the coils or springs forming the lattice have one or more of the following properties: (i) a diameter of 0.025 to 3 mm, more preferably 0.1 to 2 mm, even more preferably 0.15 to 1 mm; (ii) an initial breaking load of 0.1 to 200 N, more preferably 1 to 100 N, even more preferably 2 to 50 N; (iii) an elongation at break value of 22% to 1,000%, more preferably 100% to 700%; and (iv) an elastic modulus value of 0.05 to 10 GPa, more preferably 0.1 to 3 GPa, even more preferably 0.2 to 0.8 GPa.

[0149] In some embodiments, the implant is a breast implant formed from a grid of coils or springs, and the breast implant has an elastic modulus of 0.01 kPa to 290 MPa, more preferably 0.1 kPa to 10 MPa, even more preferably 0.1 kPa to 1 MPa or 0.1 kPa to 100 kPa, and the coils or springs forming the grid have one or more of the following properties: (i) a diameter of 0.025 to 3 mm, more preferably 0.1 to 2 mm, even more preferably 0.15 to 1 mm; (ii) an initial breaking load of 0.1 to 200 N, more preferably 1 to 100 N, even more preferably 2 to 50 N; (iii) an elongation at break value of 22% to 1,000%, more preferably 100% to 700%; and (iv) an elastic modulus value of 0.05 to 10 GPa, more preferably 0.1 to 3 GPa, even more preferably 0.2 to 0.8 GPa.

[0150] In a preferred embodiment, the cells made of coils and or springs also contain fasteners that can be used to assemble the cells into a grid. Figure 5 An example of a cell 60 made of coils and springs that also includes fasteners is shown in FIG. In this example, the top ring 62 and the bottom ring 64 of the cell include fasteners. The fasteners may use any suitable mechanism that allows the cells to be joined together. Figure 5 In the example shown, the cells include male connectors 66 and female connectors 68 that can be joined together to assemble the cells into a grid. Figure 5 In the example shown in FIG, male and female fasteners are visible in both the upper and lower rings of the unit cell, which are spaced at 90 degrees apart. Figure 5 Although not visible in the figure, the illustrated cell contains two male connectors and two female connectors in each of the top and bottom rings of the cell, with the male and female connectors alternating and positioned at 90-degree intervals. The number of fasteners used to connect the cell can be more or less than four on the top and bottom rings of the cell, but preferably, the top and bottom rings each contain two male connectors and two female connectors alternating at 90-degree intervals. If desired, fasteners can also be positioned on the helical struts of the cell.

[0151] iii. Reticulate unit cells

[0152] In yet another embodiment, the unit cell is formed from a mesh and fibers. The unit cell may have a top plate formed from the mesh and a bottom plate formed from the mesh. The top plate and bottom plate are joined together by fibers to form a mesh-like unit cell. Preferably, the top plate and bottom plate are joined by interweaving the fibers, more preferably by interweaving the top plate and bottom plate with monofilament fibers.

[0153] Figure 121 is a diagram of a mesh unit cell 100 showing a top plate 110 and a bottom plate 120, and struts 130 connecting the top and bottom plates. The top and bottom plates are formed from mesh. Fiber inlays 140 from the mesh are shown on the top and bottom plates, and interwoven loops 142 of the mesh are also shown. Figure 12 The struts shown in are preferably formed of fibers, more preferably of monofilament fibers. The reticular cells have a low bulk density that provides a large surface area and void volume. The top and bottom plates and the struts can have different sizes, angles, and lengths, and can be hard, rigid, flexible, elastic, spring-like, and can be made of oriented or non-oriented polymers. The reticular cells can be formed into any suitable shape. In one embodiment, the reticular cells have a polyhedral shape, including an elongated polyhedral shape. In a preferred embodiment, the reticular cells have six faces. In a particularly preferred embodiment, the reticular cells are cuboids. The interior of the reticular cells can be hollow or can contain additional fibers. For example, the reticular cells can contain additional fibers that join the top and bottom plates. The reticular cells can also contain additional fibers between the top and bottom plates that increase the surface area of ​​the cells. The latter may result in an increase in the binding ability of the cells, such as an increase in the ability to bind fat.

[0154] In a preferred embodiment, the mesh cells are compressible, and in an even more preferred embodiment, the mesh cells are compressible and recover after being compressed. Implants having a lattice formed from compressible mesh cells are particularly suitable for use in the breast because the lattice so formed is compressible and can be designed to mimic the properties of breast tissue.

[0155] The length of the struts or fibers of the reticular unit cells is preferably 1 to 300 mm, more preferably 2 to 10 mm, and even more preferably 3 to 8 mm. In some embodiments, the struts or fibers are long enough to form a unit cell that allows a needle having an outer diameter of 0.5 to 3 mm to be inserted into the grid made of the unit cells.

[0156] The diameter of the fibers used to prepare the reticulated unit cells is preferably 20 μm to 2 mm, more preferably 50 μm to 1 mm, even more preferably 80 μm to 500 μm or 100 μm to 250 μm.

[0157] In some embodiments, the implant is formed from a mesh-like unit cell having fibers, and the fibers have a breaking load of 0.1 to 200 N, more preferably 1 to 100 N, and even more preferably 2 to 50 N. In some embodiments, the implant is formed from a mesh-like unit cell having fibers, and the fibers have an elongation at break of 22% to 1,000%, more preferably 100% to 700%. In some embodiments, the implant is formed from a mesh-like unit cell having fibers, and the fibers have an elastic modulus value of 0.05 to 10 GPa, more preferably 0.1 to 3 GPa, and even more preferably 0.2 to 0.8 GPa. The fibers forming the mesh-like unit cell preferably have one or more of the following properties: (i) a breaking load of 0.1 to 200 N; (ii) an elongation at break of 22% to 1,000%; and (iii) an elastic modulus of 0.05 to 10 GPa.

[0158] In some embodiments, the elastic modulus of the implant formed by the reticular cells having fibers is 0.01 kPa to 290 MPa, more preferably 0.1 kPa to 10 MPa, even more preferably 0.1 kPa to 1 MPa or 0.1 kPa to 100 kPa, and the fibers of the reticular cells have one or more of the following properties: (i) a diameter of 0.025 to 3 mm, more preferably 0.1 to 2 mm, even more preferably 0.15 to 1 mm; (ii) an initial breaking load of 0.1 to 200 N, more preferably 1 to 100 N, even more preferably 2 to 50 N; (iii) an elongation at break value of 22% to 1,000%, more preferably 100% to 700%; and (iv) an elastic modulus value of 0.05 to 10 GPa, more preferably 0.1 to 3 GPa, even more preferably 0.2 to 0.8 GPa.

[0159] In some embodiments, the implant is a breast implant formed from reticulum cells, and the elastic modulus of the implant is from 0.01 kPa to 290 MPa, more preferably from 0.1 kPa to 10 MPa, even more preferably from 0.1 kPa to 1 MPa or from 0.1 kPa to 100 kPa, and the fibers of the reticulum cells have one or more of the following properties: (i) a diameter of from 0.025 to 3 mm, more preferably from 0.1 to 2 mm, even more preferably from 0.15 to 1 mm; (ii) an initial breaking load of from 0.1 to 200 N, more preferably from 1 to 100 N, even more preferably from 2 to 50 N; (iii) an elongation at break value of from 22% to 1,000%, more preferably from 100% to 700%; and (iv) an elastic modulus value of from 0.05 to 10 GPa, more preferably from 0.1 to 3 GPa, even more preferably from 0.2 to 0.8 GPa.

[0160] iv. Foam cells

[0161] In another embodiment, the unit cell is formed of foam, preferably compressible foam. The foam unit cell preferably comprises interconnected pores. The pores can be of uniform size (i.e., each pore has equal size) or different sizes. The foam unit cell has a low bulk density that provides a large surface area and void volume. The foam unit cell can be formed into any suitable shape. In one embodiment, the foam unit cell has a polyhedral shape, including an elongated polyhedral shape. In a preferred embodiment, the foam unit cell has six faces. In a particularly preferred embodiment, the foam unit cell is a cuboid.

[0162] In one embodiment, the foam cell further comprises male and female anchors. The anchors allow multiple cells to be joined together to form a lattice of implants.

[0163] Reference Figure 16C , a cross-sectional view of a compressible foam cell 300 having a convex anchor 310 and a concave anchor 320 showing a hole 330 in the foam 340. The foam 340 is preferably formed of a polymer, more preferably an absorbable polymer.

[0164] Figure 16A 、 16B 16C and 16D illustrate a method for forming a foam cell according to one embodiment of the present invention. In particular, Figure 16A Mold cavity 336 is shown filled with leachable porogen beads 340. Optionally, the mold cavity can feature concave shaped anchor sites 344 and convex shaped anchor sites 346 as further described herein.

[0165] Reference Figure 16B , the beads 340 are covered with a solution 350 of polymer in a volatile solvent. The solvent is allowed to evaporate, leaving the porogen beads trapped in the polymer. Figure 16C As shown, open foam cells 300 are formed by leaching porogen beads trapped in a polymer, leaving an array of pores 330 in the foam 354. Optionally, as described herein, male and female anchors 310, 320 are created to assemble the foam cells together.

[0166] Implants having a lattice formed from compressible foam cells are particularly suitable for use in the breast because the lattice so formed is compressible and can be designed to mimic the properties of breast tissue.

[0167] C. Implant Construction

[0168] A variety of methods can be used to make the implant. The implant comprises a lattice formed from two or more unit cells, but more preferably from a plurality of unit cells or a plurality of unit cells. The unit cells are repeated within the volume of the lattice. In some embodiments, the lattice of the implant can provide one or more of the following: (i) structural support, (ii) a scaffold for tissue ingrowth, (iii) a scaffold for the delivery of cells, tissues, collagen, hyaluronic acid and bioactive agents (including fat, lipoaspirate, adipocytes, fibroblasts and stem cells) (iv) a structure that can provide mechanical spacing, (v) a structure that can allow the graft to be incorporated into the lattice structure, such as a vascular pedicle, (vi) a structure that can be coated on the interior of the lattice by injection using a needle with cells, tissues, collagen, hyaluronic acid and bioactive agents. (vii) structures that are compatible with agents (including fat, lipoaspirate, adipocytes, fibroblasts, and stem cells), (vii) structures that have properties similar (meaning within ±50% of the property value) or the same as soft tissue, (viii) structures that have an elastic modulus that is within ±50%, more preferably within ±25% of the elastic modulus value of breast tissue, (viii) structures that have high strength relative to their bulk density, (ix) structures that have a compression design and or spring design (meaning that the grating can be deformed by a force and return to its original shape when the force is removed), and (x) structures that have anisotropic mechanical properties.

[0169] In one embodiment, the implant is formed by making a grid of a single cell, wherein the single cell is a coil and a spring. In another embodiment, the implant is formed by making a grid of a single cell, wherein the single cell is a skeleton polyhedron with edges and vertices formed by pillars or fibers and with a hollow or porous interior. Preferably, the skeleton polyhedron single cell meets with adjacent skeleton polyhedron single cells at its corner to form a grid. In yet another embodiment, the implant is formed by making a grid of a reticular single cell, wherein the reticular single cell comprises a net on two opposite sides of the single cell, and the net is engaged by pillars or fibers. In another embodiment, the implant is formed by making a grid of a foam single cell.

[0170] In a preferred embodiment, the lattice of the implant is formed from unit cells, wherein the unit cells are formed from a polymer. The unit cells can be polymer coils and springs, skeleton polyhedra, wherein the edges and vertices of the skeleton polyhedra are formed from polymer struts or fibers, or the unit cells can be a polymer mesh connected by polymer fibers, or the unit cells can be a polymer foam.

[0171] In a preferred embodiment, the implant is formed from a grid of unit cells wherein the unit cells have a low volume density that provides a network of open pores through the grid and such that when a unit cell is placed in the center of the grid it will be surrounded by other unit cells. For example, if the unit cells of the grid all have the shape of a dodecahedron with 12 faces, each face of the dodecahedron will be connected to 12 adjacent unit cells. Connecting the unit cells in this manner creates a grid network in which there is a continuous path through the grid that promotes and allows tissue to grow inwardly into the grid structure. The continuous path also allows the entire grid structure to be coated with one or more of the following: bioactive agents, collagen, hyaluronic acid, additives, cells and tissues, including fat and adipocytes. The number of unit cells that form the grid will depend in part on the volume of the grid desired and the unit volume of the unit cells. For example, a grid having a volume of 1 cm 3 The volume of the same unit cell is 500 cm 3 The grid will contain at most 500 cells.

[0172] The implant's lattice can be defined by its volume density. In a preferred embodiment, the implant lattice has a volume density, i.e., the ratio of the volume of material used to make the lattice to the volume of the void space within the lattice, of 1% to 50%. In a more preferred embodiment, the lattice has a volume density of 1% to 25%, and in an even more preferred embodiment, the lattice has a volume density of 1% to 17%. For clarity of definition only, a lattice with a volume density of 25% has 25% material and 75% void space by volume. The volume density of the lattice refers to the volume density before cells or other substances are added. lattices with low volume densities (e.g., less than 50%) are preferred because they provide large void spaces that can be occupied by, for example, cells, tissue, collagen, and bioactive agents (including fat, lipoaspirate, adipocytes, fibroblasts, and stem cells). In one embodiment, 25% to 100%, more preferably 75% to 100%, of the void space is filled with one or more of the following: cells, tissue, collagen, and bioactive agents, including fat, lipoaspirate, adipocytes, fibroblasts, and stem cells.

[0173] The struts, fibers, coils and springs of the unit cells can be manufactured by any suitable method. A preferred method for manufacturing the unit cells is 3D printing. 3D printing is a computer-controlled program by which three-dimensional objects can be manufactured from 3D CAD (computer-aided design) models using additive manufacturing methods. Objects can be manufactured by depositing, joining or solidifying materials (typically plastic or metal). 3D printing can be used to manufacture unit cells, and can also be used to manufacture grid structures. The latter method is particularly preferred when the grid of the implant comprises unit cells that are skeletal polyhedrons, but can also be used to manufacture unit cells containing coils or springs. Suitable 3D printing technologies include selective laser melting (SLM), melt extrusion deposition (MED), fused pellet deposition (FPD), filament fabrication, printing of slurries and solutions using a coagulation bath, and printing using a binding solution and powder particles. In one embodiment, the lattice of the implant is formed by 3D printing an absorbable polymer, more preferably by 3D printing one or more of: poly-4-hydroxybutyrate and copolymers, and poly(butylene succinate) or copolymers, optionally wherein these polymers and copolymers have been cross-linked. In a particularly preferred embodiment, the implant is a breast implant, and the cells and or lattice of the implant are formed by 3D printing one or more of: poly-4-hydroxybutyrate and copolymers, and poly(butylene succinate) or copolymers, optionally wherein these polymers and copolymers have been cross-linked.

[0174] A particularly preferred method of 3D printing unit cells is selective laser melting (SLM). Figure 6

[0045] An example of a coiled cylindrical unit cell 400 fabricated by SLM is shown. The coiled unit cell is formed with three helical struts supporting a top ring and a bottom ring, and has a total height of 7.5 mm, with the helical struts angled 120 degrees from each other at a constant spacing of 0.75 per centimeter. The outer and inner diameters of the top and bottom rings are 10 mm and 8 mm, respectively, and the rings are formed with a 2 mm circular cross-section. Coiled cylindrical unit cells formed by 3D printing can be assembled into a grid by fusing the unit cells together. The unit cells can be fused, for example, by applying heat, pressure, and / or solvents.

[0175] 3D printing can also be used to form Figure 5 After printing, the coiled cylindrical unit cell (e.g., a unit cell having built-in fasteners 66, 68) can be connected by connecting the male and female connectors on the top and bottom rings of the unit cell. Figure 5 As shown) are assembled together to form Figure 7The lattice structure 410 of the implant is shown. In a preferred embodiment, coiled cylindrical cells containing fasteners are assembled into a lattice, wherein the lattice is compressible and returns to its original shape after being compressed. In an even more preferred embodiment, coiled cylindrical cells containing fasteners are assembled into a lattice of a breast implant, wherein the lattice is compressible and optionally returns to its original shape after being compressed.

[0176] 3D printing can also be used to directly form the lattice structure of an implant, without having to assemble the lattice from individual cells. Figure 8 It is achieved by 3D printing multiple coiled cylindrical unit cells 440 (similar to Figure 4 FIG4 is an image of a lattice structure 430 of an implant formed by 3D printing a lattice structure 430 of a 3D printed breast implant (using a plurality of unit cells as shown), wherein the unit cells are connected to each other during printing of the lattice. In a preferred embodiment, the lattice thus formed is compressible and recovers its original shape after being compressed. In an even more preferred embodiment, the 3D printed lattice is a lattice for a breast implant, wherein the lattice is compressible and recovers its original shape after being compressed.

[0177] In other preferred embodiments, a lattice having a skeleton polyhedral unit cell can be directly formed by 3D printing. An example of a 3D printed implant lattice 10 made of a skeleton polyhedral unit cell is shown in FIG. Figure 1 In a preferred embodiment, as shown in Figure 3 As shown, the lattice of the 3D-printed implant is compressible and can return to its original shape after being compressed. In a particularly preferred embodiment, the lattice of the breast implant is formed by 3D printing a lattice of skeleton polyhedrons, wherein the lattice is compressible. Even more preferably, the lattice returns to its original shape after being compressed. In some embodiments, the 3D-printed lattice (including the lattice of the 3D-printed breast implant) comprises skeleton polyhedral unit cells, wherein the unit cells are shaped as tetrahedrons, cuboids, pentahedrons, hexahedrons, heptahedrons, octahedrons, icosahedrons, decahedrons, dodecahedrons, tetradecahedrons, and prisms, anti-prisms, and truncated polyhedrons thereof. In a preferred embodiment, these skeleton unit cells have 4, 6, 8, 12, or 20 faces. In another embodiment, these skeleton unit cells are formed from elongated polyhedrons. In a particularly preferred embodiment, the skeleton unit cells of the 3D-printed implant (including breast, nipple, facial, or buttock implants) are dodecahedrons, and even more preferably, rhombic dodecahedrons. In other embodiments, the grid can be 3D printed from two or more different types of skeleton unit cells. For example, the grid can be printed from a combination of dodecahedron and octagonal shapes.

[0178] In other embodiments, the grid cells can be prepared by injection molding. Figure 4 and Figure 5 The unit cells 40, 60 shown in FIG. 4 are assembled to form a grid. Figure 4 Injection molded cells 40 of the type shown may be formed into a grid by fusing the cells together, for example, using heat, pressure, and or solvents. Figure 5 Injection-molded cells 60 of the type shown can be formed into a grid by connecting male and female connectors. In a preferred embodiment, the injection-molded cells are formed into a grid that is compressible and, optionally, recovers its original shape after being compressed. In a particularly preferred embodiment, the injection-molded cells are formed into grids for compressible breast, nipple, facial, and buttock implants. Preferably, these grids recover their shape after being compressed.

[0179] The mesh unit cell can be prepared by preparing two meshes and connecting them with struts or fibers to form a unit cell. In a preferred embodiment, the mesh unit cell is prepared using a double needle bed knitter. Figures 12 to 15 , the top plate 110 of the mesh cell 100 can be knitted on the front bed of a double needle bed knitting machine, and the bottom plate 120 of the mesh cell 100 can be knitted on the back bed of the double needle bed knitting machine. Fibers, preferably monofilament fibers, can be interwoven between the front bed and the back bed to form the mesh cell. Preferably, the mesh in the mesh cell is a warp knit and can be prepared using a double needle bed knitting machine. In a particularly preferred embodiment, the mesh cell comprises a warp knit mesh on opposite sides of the cell that is interwoven with the monofilament fibers to form the mesh cell. In a particularly preferred embodiment, the mesh cell comprises a warp knit mesh interwoven with the monofilament fibers and is compressible.

[0180] In a preferred embodiment, the reticulated cells are prepared from fibers (preferably monofilament fibers) and one or more of the following polymers or copolymers: poly-4-hydroxybutyrate and copolymers, and poly(butylene succinate) or copolymers. These polymers and copolymers may also contain one or more of the following: branching agents, crosslinking agents, chain extenders, and reactive blending agents. Particularly preferred implants made from reticulated cells using these polymer compositions can be used as breast implants.

[0181] The mesh cells can be assembled into an implant using any suitable method. For example, the mesh cells can be fused to form a grid for the implant. For example, by applying heat, pressure, and / or solvents. More preferably, the mesh cells can be connected together using fibers. In one embodiment, the mesh cells can be sewn together using fibers.

[0182] In one embodiment, the cells are made of foam and the foam cells can be assembled into an implant. For example, the foam cells can be fused to form a grid of the implant. For example, by applying heat, pressure, and / or solvents. More preferably, the grid of the implant comprising the foam cells can be formed from the foam cells comprising the convex anchors and the concave anchors by connecting the convex anchors and the concave anchors together.

[0183] D. Physical Properties of the Implant's Grid

[0184] In one embodiment, the mechanical properties of the grating are designed so that they approximate the mechanical properties of tissue. In one embodiment, the elastic modulus of the grating of the implant is between 0.01 kPa and 290 MPa, more preferably between 0.1 kPa and 10 MPa, even more preferably between 0.1 kPa and 1 MPa or between 0.1 kPa and 100 kPa. In a particularly preferred embodiment, the implant is a breast implant and the elastic modulus of the grating of the breast implant is between 0.01 kPa and 1 MPa, more preferably between 0.01 kPa and 100 kPa. In another embodiment, the implant is a breast implant and the elastic modulus of the grating of the breast implant is ±50% of the elastic modulus of breast tissue. In other embodiments, the elastic modulus of the grating of the implant is ±50%, more preferably ±25%, of the elastic modulus of glandular tissue, adipose tissue, skin, pectoral fascia, or breast tissue. For reference, the elastic modulus values ​​for glandular tissue, adipose tissue, skin, pectoral fascia, and breast tissue are reported to be 7.5 kPa to 66 kPa, 0.5 kPa to 25 kPa, 200 kPa to 3,000 kPa, 100 kPa to 2,000 kPa, and 0.167 kPa to 29 kPa, respectively. In a particularly preferred embodiment, the elastic modulus of the lattice of a breast implant comprising skeleton polyhedral unit cells, spiral or coiled unit cells, or reticular unit cells is 0.167 kPa ± 50% to 66 kPa ± 50%.

[0185] Figure 10A An example of a breast implant 500 is shown having a spring design that provides the implant with a compression modulus similar to that of breast tissue.The implant 500 comprises segments 502 that define gaps 504 between adjacent segments. Figure 10B A cross section of a breast implant is shown in . In this example, the lattice of the implant is made of stacked rhombus-shaped cells 510. The implant has a large surface area that can be coated with, for example, autologous fat, cells, collagen or bioactive agents.

[0186] Figure 11 is a diagram illustrating an alternative embodiment of a breast implant 530 designed to have an elastic modulus similar to that of breast tissue.

[0187] In another embodiment, the grating of the implant can have anisotropic properties. That is, the grating can have different properties in different directions. For example, the grating can have a first elastic modulus in one direction, and a second elastic modulus in a second direction. In one embodiment, the implant can be a breast implant, and the grating of the breast implant can have a first elastic modulus in one direction, and a second, different elastic modulus in a second direction. The grating of the breast implant can have different properties in the up-down direction of the breast compared to the properties in the outside-to-inside direction of the breast. In one embodiment, the unit cells of the grating can be elongated in one direction to provide a grating with anisotropic properties. For example, the unit cells of the grating can be elongated in a first direction to provide a grating with an increased elastic modulus in the first direction.

[0188] To allow tissue ingrowth into the implant's lattice, the lattice should retain strength long enough to allow cells and blood vessels to invade the implant and proliferate. In some embodiments, the implant's lattice retains strength of at least 25% at 2 weeks, more preferably at least 50% at 2 weeks, and even more preferably at least 50% at 4 weeks. In other embodiments, the implant's lattice is designed to support mechanical forces acting on the implant and allow for a stable transition of mechanical forces from the lattice to the regenerated host tissue. In particular, the breast implant's lattice is designed to support mechanical forces acting on the breast implant and allow for a stable transition of mechanical forces from the lattice to the new host tissue.

[0189] E. Other features of the implant

[0190] Can use scissors, blades, other sharp cutting tools or hot knife to trim or cut implant or the grid of implant, to provide the implant of expectation or grid shape.Can also utilize laser cutting technology that implant or grid are cut into desired shape.This makes aspect the implant shaping based on fiber, based on net and based on pillar, may be particularly advantageous, because this technology is universal, and importantly it can provide shaped implant and the grid without sharp edge.

[0191] In some embodiments, the implant may also include a column to reinforce the implant or facilitate implantation. The column may, for example, help reshape the implant after implantation. Preferably, the column is incorporated into the grid structure to reinforce the implant or facilitate implantation of the implant. The column may be incorporated into the implant by any suitable method, including fusion, molding, weaving, knitting, or printing. In a preferred embodiment, the column is incorporated by fusing absorbable polymer fibers or struts into the grid of the implant. In some embodiments, the diameter or width of the column may be 0.1 to 5 mm, more preferably 0.5 to 3 mm. The absorbable polymer fibers or struts may be oriented or non-oriented, but are preferably non-oriented, and more preferably non-oriented poly-4-hydroxybutyrate fibers or struts. In another embodiment, the flexible column may be printed directly onto the grid of the implant, or incorporated into the grid during printing of the grid.

[0192] The implant may include retainers, such as barbs or spikes, that allow the implant to be anchored in the body without the use of sutures. The implant preferably includes retainers within the implant's peripheral border or within the implant's lattice structure. When the implant is a breast implant, retainers are preferably located on the implant to allow the implant to be anchored to the chest wall.

[0193] The implant may comprise suture tabs so that the implant can be anchored in the body using, for example, sutures and or staples. The number of tabs may vary. In one embodiment, the number of tabs will depend on the load applied to the implant. When the implant is heavy or bulky, a large number of tabs may be required. In some embodiments, the implant comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 tabs or more, but preferably 4 to 12. When the implant is a breast implant, the implant preferably comprises 4 or more tabs, preferably 4 to 12 tabs, to anchor the breast implant to the chest wall. The tab size is preferably 0.5 cm x 0.5 cm to 5 cm x 4 cm, preferably 2 cm x 2.5 cm. The sheet attached to the implant must have sufficient strength retention in vivo to resist mechanical loads and allow sufficient ingrowth of tissue into the implant to prevent subsequent migration of the implant after implantation. In a preferred embodiment, the suture pull-out strength of the sheet attached to the implant is greater than 10N, more preferably greater than 20N.

[0194] F. Implant Coating and Filling

[0195] In some embodiments, the implant is manufactured with a coating and / or some or all of the grating is used as a carrier. For example, the grating can be manufactured by filling some or all of the void spaces of the grating with cells or tissues (including autologous grafts, allografts or xenograft tissues and cells, and vascular pedicles). Examples of cells that can be inserted into the void spaces of the implant and coated on its surface include adipocytes, fibroblasts, and stem cells. In a preferred embodiment, autologous fat, lipoaspirate, or injectable fat is coated on the implant and inserted into the void spaces of the implant. In another preferred embodiment, the vascular pedicle can be inserted into the void spaces of the implant. In yet another preferred embodiment, the implant can be coated with or partially or completely filled with one or more bioactive agents. Particularly preferred bioactive agents that can be coated on the implant or used to partially or completely fill the implant include collagen and hyaluronic acid. In other embodiments, the implant can be coated with one or more antibiotics.

[0196] Any suitable method can be used to coat the implant and fill its void space with cells, tissues, bioactive agents and other additives. In some embodiments, the implant is filled or coated with cells, tissues, bioactive agents and other additives by injection, spraying or dipping. Collagen can be applied to the implant by coating and freeze drying. In a particularly preferred embodiment, the implant can be coated with or partially or completely filled with cells, tissues, bioactive agents and or other additives by injection using a needle that can be inserted into the grid of the implant without damaging the grid. In one embodiment, the outer diameter of the needle used to inject cells, tissues, fat, lipoaspirate, bioactive agents, collagen, hyaluronic acid and other additives is 0.5 mm to 5 mm.

[0197] IV Methods for Implantation

[0198] In some embodiments, the implant is implanted in vivo. Preferably, the implant is implanted at a site of reconstruction, remodeling, repair, and / or regeneration. In a preferred embodiment, connective tissue and / or vasculature will invade the lattice of the implant after implantation. In a particularly preferred embodiment, the implant comprises an absorbable material, and connective tissue and / or vasculature will also invade the space where the absorbable material has degraded. The cells of the lattice can be colonized by cells before or, more preferably, after implantation, and the pores of the lattice can be invaded by tissue, blood vessels, or a combination thereof.

[0199] The implant can be coated or filled with transplanted cells, stem cells, fibroblasts, adipocytes and or tissue before or after implantation. In some embodiments, the implant is coated or filled with differentiated cells before or after implantation. Differentiated cells have specific forms and functions. Examples include adipocytes and muscle cells. Preferably, the implant is filled with cells before or after implantation by injection and more preferably by using a needle that does not damage the grid of the implant. The implant can also be coated or filled with platelets, extracellular fat matrix proteins, gels, hydrogels and bioactive agents before implantation. In one embodiment, the implant can be coated with antibiotics before implantation, for example, by immersing the implant in an antibiotic solution.

[0200] Implants can be used to deliver autologous cells and tissues to specific locations in a patient, such as the breast, nipple, face, and buttocks. The autologous tissue is preferably one or more of the following: autologous fat, lipoaspirate, injectable fat, adipocytes, fibroblasts, and stem cells.

[0201] The implant can be used to fill and deliver fat to the patient. In a particularly preferred embodiment, autologous adipose tissue is prepared before or after implantation of the implant and is injected or otherwise inserted into or coated onto the implant before or after implantation of the implant. The autologous adipose tissue is preferably prepared by liposuction at a donor site on the patient's body. After centrifugation, the lipid phase containing the adipocytes is separated from the blood components and combined with the implant before implantation, or injected or otherwise inserted into the implant after implantation. In one embodiment, the implant is injected or filled with a volume of lipoaspirate that accounts for 1% to 50% of the total volume of the grid, more preferably 1% to 20% of the total volume of the grid.

[0202] In another embodiment, lipoaspirate adipose tissue removed from the patient can be mixed with a biological or synthetic scaffold matrix (e.g., very small fibers or particles) before the lipoaspirate is added to the implant. In this embodiment, the added matrix serves to hold or bind the fat microspheres and disperse and retain them within the implant's lattice. In some embodiments, the use of an added matrix can help prevent fat accumulation that can lead to necrosis and / or help enhance vascularization of the implant.

[0203] In another embodiment, a vascular pedicle or other tissue mass is harvested from the patient and inserted into the implant. The pedicle or other tissue mass can be inserted into the implant before the implant is implanted, and the implant with the pedicle or other tissue mass is then implanted into the patient, or the pedicle or other tissue mass can be inserted into the implant after the implant has been implanted in the patient.

[0204] In a preferred embodiment, the implant is implanted in the patient's breast. In another embodiment, the implant is implanted and secured in both breasts. In some embodiments, the implant is implanted in the patient during the mastopexy and augmentation procedures, including revision procedures. In a particularly preferred embodiment, the implant is implanted in a patient who has undergone: (i) a mastectomy, (ii) a breast lift with a desire for augmentation, (iii) a breast reduction with a desire for support, lift, or reshaping of the reduced breast, or (iv) a previous silicone or saline breast implant procedure and desires removal of the silicone or saline implants and subsequent breast reconstruction that will provide a fuller or larger breast. Implants can also be implanted in breast surgery patients to increase the projection of the breast away from the chest, and additional fat graft volume can optionally be added to the implant after implantation to increase the projection. Additional fat graft volume can be added to the implant immediately after implantation, but can also be added during a subsequent examination. For example, additional fat graft volume can be added to the implant at one or more occasions, days, weeks, or months after implantation. The procedures described herein can also be performed by removing, excising, and redistributing breast tissue.

[0205] In one embodiment, a method for implanting an implant in a breast comprises at least the following steps: (i) making at least one incision to access the patient's breast tissue, (ii) separating the skin and subcutaneous fascia of the breast from the breast mound, (iii) positioning the implant on the breast mound of the breast, (iv) securing the implant to the tissue surrounding the breast mound of the breast, and (v) closing the incision in the breast. Preferably, the method further comprises one or more of the following steps: (a) preparing a lipoaspirate sample and coating or filling the implant with the sample before implanting the implant, (b) preparing a lipoaspirate sample and coating or filling the implant with the sample after implanting the implant, preferably by injecting the sample into the implant, (c) inserting a vascular pedicle into the implant before or after implanting the implant, and (d) suturing or stapling the implant in place. In a preferred embodiment, the implant is implanted in a subglandular, subpectoral, or pre-pectoral location. In some embodiments, the implant is sutured to the tissue surrounding the breast mound, and even more preferably to the fascia surrounding the pectoral muscle below the breast mound. In another embodiment, the implant comprises a sheet, and the sheet is sutured to the tissue surrounding the breast mound.

[0206] Implants can also be coated or filled with cells and tissues other than fat grafts before or after implantation, as well as cytokines, platelets, and extracellular adipose matrix proteins. For example, implants can be coated or filled with cartilage or dermal grafts. Implants can also be coated or filled with other tissue cells, such as pancreatic islet cells, hepatocytes, or stem cells genetically modified to contain genes for treating a patient's disease.

[0207] In some embodiments, the implant is implanted in vivo. Preferably, the implant is implanted in a site of reconstruction, remodeling, repair and or regeneration. In a preferred embodiment, connective tissue and or vascular system will invade the lattice of the implant after implantation.

[0208] In one embodiment, implant has the characteristic that allows it to send via small incision by minimally invasive manner.Implant can for example be designed so that it can roll up or fold to allow to send via small incision.This minimally invasive method can reduce patient morbidity rate, cicatrix and infection probability.In an even more preferred embodiment, implant has three-dimensional shape and allows it to send via incision and enter the anatomical tissue plane of appropriate size after recovering its original three-dimensional shape under unassisted shape memory characteristics.For example, implant can be temporarily deformed by being rolled into small diameter cylindrical shape, uses inserter to send, then allows to recover its original three-dimensional shape without auxiliary in vivo.

[0209] Example

[0210] The present invention will be further understood by reference to the following non-limiting examples.

[0211] Example 1: Implant with a porous lattice of connected skeleton polyhedral cells formed by SLS printing

[0212] Prepared as described herein Figure 1The implant shown. P4HB pellets (Tepha, Inc., Mw480kDa) were subjected to cryogenic grinding and then continuously sieved to produce P4HB powder with a particle size of 40 to 60 microns. The P4HB powder was made from P4HB pellets with an average size of 2mm×2mm×3mm that were cooled to -70°C and injected in a high-speed cross-collision path in a cryogenic grinder. The resulting powder was sieved using a 60-micron shaker followed by a 40-micron shaker to remove particles larger than 60 microns and smaller than 40 microns. The sieved P4HB powder (40 to 60 micron particles) was then dried, flushed with nitrogen, and wrapped in foil. The moisture content of the P4HB powder was less than 650ppm. The P4HB powder was loaded into the powder bed of a 3D selective laser sintering (SLS) printer. The thickness of the powder layer was set to 100 microns, the laser power was set to 0.3 watts, and the speed of the laser beam was set to 20cm / second. Under these conditions, the energy used per unit area was 1J / cm 2 The 3D printer is loaded with the STL file to print Figure 1 The open porous scaffold structure of the implant is shown.

[0213] The resulting structure has a dome or spherical cap shape with a base diameter of 12 cm and a protrusion of 5.5 cm (height from base to apex). The implant is formed with a fully interconnected porous structure with open porosity. The open porosity design of the implant provides a morphology that allows cells to invade the scaffold and proliferate after implantation. The diameter of the struts of the skeleton unit cell is 1.5 mm, and the distance between the nodes or intersections (i.e., the length (L) of the struts in the unit cell) is 10 mm. The implant has an elastic modulus value of 16 kPa, shape memory, and as Figure 3 As shown, it can be compressed by light pressure of the fingers.

Claims

1. A breast implant comprising a porous lattice, wherein the lattice further comprises a plurality of connected unit cells, wherein the unit cells are of a structural type of skeleton polyhedron, wherein the skeleton polyhedron includes edges and vertices formed by polymer struts or polymer fibers, wherein the polymer struts or polymer fibers have two or more of the following properties: (i) a breaking load of 0.1 to 200 N; (ii) an elongation at break of 22% to 1,000%; and (iii) an elastic modulus of 0.05 to 10 GPa.

2. The implant of claim 1, wherein the unit cell is compressible.

3. The implant of claim 1, wherein the polymer struts or polymer fibers have a length extending along an edge from a first apex to a second apex, wherein the length is 3 mm to 3 cm.

4. The implant of claim 1, wherein the polymer struts or polymer fibers have a length extending along an edge from a first apex to a second apex, wherein the length is 3 mm to 8 mm.

5. The implant of claim 1, wherein the unit cells in the lattice are identical to one another.

6. The implant of claim 1, wherein the polymer struts or polymer fibers have a thickness or diameter of 50 μm to 5 mm.

7. The implant of claim 1, wherein the grid comprises a plurality of holes, and the holes of the grid have a width or diameter of at least 0.5 mm.

8. The implant of claim 1, wherein the lattice has an elastic modulus of 0.01 kPa to 1 MPa, such that the implant is compressible and can recover its shape after being compressed.

9. The implant of claim 1, wherein the polymer struts or polymer fibers have a breaking load of 1 to 100 N.

10. The implant of claim 1, wherein the polymer struts or polymer fibers have a breaking load of 2 to 50 N.

11. The implant of claim 1 , wherein the polymer struts or polymer fibers have an elongation at break of 100% to 700%.

12. The implant of claim 1, wherein the polymer struts or polymer fibers have an elastic modulus of 0.1 to 3 GPa.

13. The implant of claim 1, wherein the polymer struts or polymer fibers have an elastic modulus of 0.2 to 0.8 GPa.

14. The implant of claim 1, wherein the lattice is resorbable.

15. The implant of claim 1, wherein the polymer struts or polymer fibers are made from a polymer formed from one or more of the following monomers: 4-hydroxybutyric acid, 3-hydroxybutyric acid, glycolic acid, lactic acid, 1,4-diol Alkanone, trimethylene carbonate, ε-caprolactone, succinic acid, adipic acid, 1,4-butanediol and ethylene glycol.

16. The implant of claim 15, wherein the polymer has been cross-linked.

17. The implant of claim 15, wherein the polymer struts or polymer fibers are made of poly-4-hydroxybutyrate or a copolymer thereof.

18. The implant of claim 15, wherein the polymer struts or polymer fibers are made of polybutylene succinate or a copolymer thereof.

19. The implant of claim 1 , further comprising (i) one or more of: adipocytes, fibroblasts, stem cells, gel, hyaluronic acid, collagen, a bioactive agent, and a diagnostic device; (ii) one or more fasteners that secure the implant; or (iii) one or more openings for inserting a vascular pedicle.

20. The implant of claim 1 further comprising autologous fat.

21. The implant of claim 1 further comprising lipoaspirate.

22. The implant of claim 1 further comprising injectable fat.

23. The implant of claim 1 further comprising a hydrogel.

24. The implant of claim 1 further comprising an antibiotic.

25. The implant of claim 1 further comprising an antimicrobial agent.

26. The implant of claim 1, further comprising one or more plates that secure the implant.

27. The implant of claim 1, further comprising one or more anchors that secure the implant.

28. An implant according to claim 1, wherein the implant is manufactured by a process selected from the following: (i) forming the polymer struts or polymer fibers of the unit cells by injection molding a polymer composition and assembling the unit cells to form the lattice of the implant, and (ii) forming the lattice of the implant by 3D printing the polymer struts or polymer fibers of the unit cells.

29. The implant of claim 28, wherein forming the lattice of the implant by 3D printing the polymer struts or polymer fibers of the unit cells comprises forming the lattice of the implant by melt extrusion deposition printing.

30. The implant of claim 1, wherein the grating has a dome-like shape.

31. A method of manufacturing a breast implant, comprising forming a porous lattice of the breast implant, the porous lattice comprising a plurality of connected unit cells, the unit cells being of a structural type of skeleton polyhedron, the skeleton polyhedron including edges and vertices formed by polymer struts or polymer fibers, by one of the following: (i) forming a plurality of the unit cells by injection molding a polymer composition to form the polymer struts or polymer fibers of the unit cells, and assembling the unit cells to form the lattice, and (ii) directly forming the lattice from a polymer composition by 3D printing the polymer struts or polymer fibers of the lattice, wherein the polymer struts or polymer fibers of the skeleton polyhedron have two or more of the following properties: (i) a breaking load of 0.1 to 200 N; (ii) an elongation at break of 22% to 1,000%; and (iii) an elastic modulus of 0.05 to 10 GPa.

32. The method of claim 31 , wherein directly forming the grating from a polymer composition by 3D printing polymer struts or polymer fibers of the grating comprises forming the grating by melt extrusion deposition printing.

33. The method of claim 31, wherein the polymer composition is selected from polymers formed from one or more of the following monomers: 4-hydroxybutyric acid, 3-hydroxybutyric acid, glycolic acid, lactic acid, 1,4-diol Alkanone, trimethylene carbonate, ε-caprolactone, succinic acid, adipic acid, 1,4-butanediol and ethylene glycol.

34. The method of claim 33, wherein the polymer composition has been cross-linked.

35. The method of claim 33, wherein the polymer composition comprises poly-4-hydroxybutyrate or a copolymer thereof.

36. The method of claim 33, wherein the polymer composition comprises polybutylene succinate or a copolymer thereof.

37. The method of claim 31 , wherein the polymer struts or polymer fibers have a thickness or diameter of 50 μm to 5 mm.

38. The method of claim 37, wherein the polymer struts or polymer fibers have a thickness or diameter of 150 μm to 2 mm.

39. The method of claim 37, wherein the polymer struts or polymer fibers have a thickness or diameter of 200 μm to 1.5 mm.

40. The method of claim 37, wherein the polymer struts or polymer fibers have a breaking load of 1 to 100 N.

41. The method of claim 37, wherein the polymer struts or polymer fibers have a breaking load of 2 to 50N.

42. The method of claim 37, wherein the polymeric struts or polymeric fibers have an elongation at break of 100% to 700%.

43. The method of claim 37, wherein the polymer struts or polymer fibers have an elastic modulus of 0.1 to 3 GPa.

44. The method of claim 37, wherein the polymer struts or polymer fibers have an elastic modulus of 0.2 to 0.8 GPa.

45. The method of claim 31 , wherein the implant further comprises one or more of: adipocytes, fibroblasts, stem cells, gel, hyaluronic acid, collagen, a bioactive agent, and a diagnostic device.

46. ​​The method of claim 31 , wherein the implant further comprises autologous fat.

47. The method of claim 31 , wherein the implant further comprises lipoaspirate.

48. The method of claim 31 , wherein the implant further comprises injectable fat.

49. The method of claim 31 , wherein the implant further comprises a hydrogel.

50. The method of claim 31 , wherein the implant further comprises an antibiotic.

51. The method of claim 31 , wherein the implant further comprises an antimicrobial agent.

52. The method of claim 31, wherein the grid has an elastic modulus of 0.01 KPa to 1 MPa.

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