Implant assembled by skeleton polyhedral unit cells, coiled unit cells or reticular unit cells

Abstract

The invention relates to an implant assembled from skeleton polyhedral unit cells, coiled unit cells or mesh unit cells. The resorbable implants may be used to create volumes and shapes with regenerated tissue in soft tissue. The implant includes a grid formed from a plurality of unit cells. The unit cells may be coils or springs, skeleton polyhedrons, foams, or structures from webs and fibers. The implants may be coated or filled with cells and tissues, and preferably coated or filled with autologous fat grafts. The implants are particularly suitable for plastic surgical procedures, for example, regenerating or enlarging breast tissue after breast resection or in breast fixation procedures, and may provide an alternative to the use of permanent breast implants in these procedures.

Description

[0001] This application is a divisional application of Chinese patent application filed on April 27, 2020, with application number 202080039486.3 and invention title "Implant assembled from skeletal polyhedral unit cells, coiled unit cells or mesh unit cells".

[0002] Cross-references to related applications

[0003] 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 for all purposes. Technical Field

[0004] This invention generally relates to implants, and more particularly to absorbable implants formed from three-dimensional unit cells. Background Technology

[0005] Breast reconstruction after mastectomy has become an integral and important part of breast cancer treatment, offering patients both aesthetic and psychosocial benefits. In the United States, nearly 65% ​​of breast reconstruction procedures currently use a tissue expander to create a pocket for the permanent breast implant in the first step of the procedure. In some patients, a pocket for the 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 the second step.

[0006] Breast implants can also be used in breast augmentation and mastectomy procedures to increase breast size. In the latter, breast lift is combined with breast enlargement. Most commonly, the breast implant is placed in a pocket beneath the breast tissue, but in some cases, it is implanted below the chest wall.

[0007] Breast implants vary in size, shape, and surface texture. A variety of sizes are available, allowing surgeons and patients to choose from a range of projections, heights, widths, and overall volumes. In terms of shape, implants exist in both round and anatomical shapes, and their surfaces can be smooth, microtextured, or macrotextured. Generally, round implants have a smooth surface, while anatomically shaped implants have a recessed microtextured or macrotextured surface.

[0008] However, a growing number of patients considering breast reconstruction and breast augmentation are reluctant to have permanent breast implants in their breasts. This is particularly true for women who have undergone mastectomy and are currently considering breast reconstruction. Some of these patients do not want a permanent foreign body in their breasts and do not want to take the risks of complications associated with permanent breast implants. Complications include the following risks: capsular contracture requiring further surgery, implant rupture or shrinkage, anaplastic large cell lymphoma (ALCL), infection, and implant displacement leading to breast asymmetry.

[0009] Hutmacher's WO2016 / 038083 discloses an implant containing voids filled with space-occupying structures designed to prevent tissue or individual cells from intruding into the voids. Six to eight weeks after implantation, the implant is removed, leaving void spaces that can be filled by transplanted cells. These void spaces provide a pre-formed bed of connective tissue and the vascular system to support the transplanted cells. The implant scaffold structure can be made of biodegradable materials.

[0010] Rehnke’s US2018 / 0206978 discloses an internal bra device made of a pleated support that can be used by patients with breast augmentation.

[0011] Danze's WO2018 / 078489 discloses an implant for replacing or increasing the volume of soft tissue, the implant comprising a three-dimensional bioresorbable frame with two lateral openings, containing two pieces of bioresorbable fabric stacked on top of each other inside the implant frame.

[0012] It is worth noting that there has been little innovation in the design of breast implants, which can generate new breast tissue with a specific and desired appearance upon implantation. Therefore, there remains a need for a breast implant that not only serves as a scaffold for tissue ingrowth but also as one that is soft to the touch, compressible, recoverable from compression, and capable of regenerating tissue within the breast to restore normal breast sensation. More specifically, there remains a need for implants that can be used to form new breast tissue, preferably also having an elastic modulus similar to that of breast tissue, and preferably possessing a similar sensation. Summary of the Invention

[0013] The implants described in this article help surgeons reshape parts of the body, including the breasts, nipples, face, and buttocks, as well as fill gaps, 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 tissues, repair hernias, and deliver biological and synthetic materials to aid in tissue regeneration, repair, strengthening, and reconstruction.

[0014] In some implementations, the absorbable implant comprises a framework or lattice formed of multiple unit cells. The unit cell may be a skeletal polyhedron with edges and vertices formed of polymer struts or fibers, coils or springs, or a unit cell formed of knitted mesh or foam.

[0015] In some implementations, the implant is porous, providing a scaffold for tissue growth, and may also contain cells, collagen, autologous fat, liposuction material, or injectable fat.

[0016] In some implementations, the implant is compressible and returns to its shape after being compressed.

[0017] In some implementations, the implant is used for soft tissue repair, regeneration, and replacement. In fact, the implants described herein can function as any type of device selected from a wide range of devices, including, for example, orthopedic devices, breast implants, breast lift devices, breast enlargement devices, nipple implants, facial reconstruction devices, buttock implants, cheekbone enlargement devices, cosmetic repair devices, soft tissue regeneration devices, hernia implants, hernia plugs, wound healing devices, tissue-engineered 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.

[0018] In some embodiments, the polymer struts or fibers forming the unit cell of the skeletal polyhedron, or the coils or springs forming the unit cell of the skeletal polyhedron, have one or more of the following characteristics: (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.

[0019] In some embodiments, the implant has only one type of unit cell, where each unit cell is identical. Such implants can be formed from a scaffold polyhedron, where all these property values ​​are identical within the scaffold polyhedron. In other embodiments, the implant has more than one type of unit cell. Such implants can be formed from a scaffold polyhedron in which polymer struts and fibers, or coils and springs, have different property values.

[0020] In some implementations, the implant comprises reabsorbable polymer struts or fibers.

[0021] In some embodiments, the implant may be an allogeneic graft or a scaffold of xenograft tissue and cells, but preferably an autologous tissue and cell scaffold, including but not limited to autologous fat, fat aspirate, lipo-filling, injectable fat, adipocytes, fibroblasts, and stem cells. In some embodiments, the implant may be a fat tissue-engineered scaffold. In some embodiments, the implant may contain collagen. In some embodiments, the implant may have one or more openings allowing insertion of a vascular pedicle or other tissue block. The implant is designed to promote inward tissue growth. The implant is designed to repair, replace, regenerate, and enlarge soft tissue structures. After implantation, the implant is designed to be penetrated by connective tissue and blood vessels and become well integrated. Preferably, the implant is porous, absorbable, degrades in a controlled manner, and is replaced in vivo by the patient's tissue. The implant may be macroporous. The implant preferably comprises a polymer material with a predictable degradation rate and predictable in vivo strength retention. Implants can allow tissue blocks to recover or increase in size while restoring or maintaining the tactile sensation of the tissue, which is particularly important for applications involving the breast, nipple, face, neck, buttocks, and skin.

[0022] In some embodiments, the implant comprises a grid formed by multiple unit cells. Unit cells can be repeated to form the volume of the implant, and the surfaces of the unit cells can be trimmed to form the final shape of the implant, if desired. The repeated unit cells of the implant enable the production of implants with predictable properties. The implant is preferably a 3D shape. In some embodiments, the unit cell is a skeletal polyhedron with edges and vertices formed of polymer struts or fibers. In other embodiments, the unit cell is a coil or spring formed of polymer. In still other embodiments, the unit cell is a knitted mesh formed of polymer. In yet another embodiment, the unit cell is a foam formed of polymer. The unit cell is hollow or porous, making the grid a space-occupying structure. In some embodiments, the unit cells of the grid are joined with one or more different unit cells. The grid can contain two or more unit cells, and preferably 50 or more unit cells. The unit cells of the grid are preferably colonized before implantation or more preferably after implantation, and the pores of the grid can be invaded by tissue, blood vessels, or a combination thereof. When the grating is absorbable, its degradation allows for further invasion by tissue, blood vessels, or a combination thereof, and this process can continue until the grating is completely absorbed. In some embodiments, the grating may include one or more openings that allow, for example, insertion of a vascular pedicle or other tissue block. In some embodiments, one or more openings may form transverse channels within the grating.

[0023] In some implementations, the implant may be anisotropic, meaning that the implant has different properties in different directions. The implant may have a first elastic modulus in one direction and a different second elastic modulus in a second direction. The implant may have high strength relative to its bulk density.

[0024] In some embodiments, the implant is a soft tissue implant comprising a porous grid, wherein the grid further comprises connected unit cells, and wherein the unit cells are skeletal polyhedra, the edges and vertices of which are formed by polymer struts or fibers. In some embodiments, the implant is a soft tissue implant comprising a porous grid, wherein the grid further comprises connected unit cells, and wherein the unit cells are coils or springs, and which are formed by polymer struts or fibers. In still other embodiments, the implant is a soft tissue implant comprising a porous grid, wherein the grid 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.

[0025] In some implementations, the implant is a plastic surgery device, a breast implant, a breast lift device, a breast enlargement device, a nipple implant, a facial reconstruction device, a buttock implant, a cheekbone enlargement 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 block, 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.

[0026] In a preferred embodiment, the implant is an absorbable breast implant and 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, liposuction, injectable fat, adipocytes, fibroblasts, and stem cells. The breast implant is preferably macroporous. The macropority of the breast implant is designed to allow the implant to contain sufficient autologous fat, biomaterials, collagen, hyaluronic acid, and / or bioactive agents to promote angiogenesis and inward tissue growth within the relatively large volume of breast tissue. Optionally, the breast implant may also include one or more openings allowing insertion of a vascular pedicle or other tissue block, comprising transverse channels. The implant can be used for patients who: (i) have undergone mastectomy, (ii) have undergone breast lift and have a need for enlargement, (iii) have undergone breast reduction and require support and lift for the reduced breast, or (iv) have previously undergone breast surgery with silicone breast implants and wish to remove the silicone implants and subsequently undergo breast reconstruction to produce a youthful appearance but with fuller breasts and larger size. Implants can also be used for patients who wish to restore the feel of natural breast tissue after its removal. Implants can be used to increase the projection of the breast from the chest, and in combination with fat grafts to increase breast volume.

[0027] In some embodiments, the implant is a replacement or alternative to a breast lift device, breast enlargement device, or permanent breast implant. In some embodiments, the implant has a shape and size suitable for breast surgical procedures, including breast enlargement, breast reconstruction, and breast fixation.

[0028] In some embodiments, the implant is a breast implant, and even more preferably, it 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 sensation similar to that of breast tissue. After the breast implant is implanted, the breast does not feel hard but rather soft to the touch and feels like a natural breast. Furthermore, in some embodiments, the breast implant allows for the restoration or increase of breast mass while maintaining or restoring touch.

[0029] In some implementations, the implant retains strength long enough to allow support at the implantation site to transition from the implant to new tissue. The implant needs to maintain its shape for an extended period to guide tissue remodeling. When used as a breast implant, it provides support to the breast until that support transitions from the implant to new tissue. Preferably, no loss of support to the breast tissue occurs or minimal loss of support occurs during this transition period. Maintaining the shape of the breast implant for an extended period guides tissue to grow inward into the implant and achieves the desired breast shape.

[0030] In some implementations, the implant has a predetermined three-dimensional shape. In the case of a breast implant, the implant has a predetermined three-dimensional shape between the skin of the breast and the breast mound or chest wall, which can be subcutaneously implanted. The breast implant can be implanted in anterior, subglandular, or subchest location. The implant allows the surgeon to easily control the volume ratio of the upper and lower poles of the breast, the degree of breast protrusion from the chest wall, and the curvature of the upper and lower poles of the breast. The surgeon can insert a vascular pedicle or other tissue block into the implant prior to implantation.

[0031] In some embodiments, the implant serves as a means for providing a surgeon with a means of delivering cells, stem cells, differentiated cells, adipocytes, muscle cells, platelets, pedicles, vascular pedicles, tissue blocks, extracellular matrix proteins, gels, hydrogels, hyaluronic acid, collagen, bioactive agents, drugs, antibiotics, and other materials to the implantation site. Preferably, the cells and tissues delivered by the implant or coated or injected into the implant are autologous. The implant can be used for autologous fat transfer. Cells added, coated, or injected onto the implant may include pancreatic islet cells, hepatocytes, and genetically modified stem cells containing genes for treating a patient's disease. The implant may contain bioactive agents that stimulate inward cell growth, including growth factors, cell adhesion factors, cell differentiation factors, cell recruitment factors, cell receptors, cell binding factors, and cell signaling molecules, such as cytokines and molecules that promote cell migration, cell division, cell proliferation, and extracellular matrix deposition. The implant may also be coated with or contain agents that prevent tissue adhesion or cell proliferation, particularly agents that delay cell invasion into the implant structure. Such reagents may be present on or in the entire grid, or may be present only in one or more specific regions of the grid.

[0032] In some embodiments, an implant may be implanted to replace and / or increase the volume or size of soft tissue. In some embodiments, the implant may also include a growth chamber for cells and tissue. In some embodiments, the implant may include one, two, or more openings that allow insertion of a vascular pedicle or other tissue block into the implant or cause the implant to clamp onto a vascular pedicle or other tissue block.

[0033] In some embodiments, the elastic modulus of the implant is from 0.01 kPa to 290 MPa, more preferably from 0.1 kPa to 10 MPa, and even more preferably from 0.1 kPa to 1 MPa or from 0.1 kPa to 100 kPa. When the implant is a breast implant, the elastic modulus is preferably from 0.01 kPa to 1 MPa, more preferably from 0.1 kPa to 100 kPa.

[0034] In some implementations, the implant can be temporarily deformed for implantation, for example, to allow for minimally invasive delivery procedures. The implant's grid can be filled after implantation by injecting one or more of the following: cells, tissue, and / or fat aspirate. A vascular pedicle or other tissue block can be inserted before or after the grid has been filled with cells, tissue, and / or fat aspirate.

[0035] In some embodiments, the implant may be made of poly-4-hydroxybutyrate (P4HB) and its copolymers, or of poly(butylene succinate) (PBS) and its copolymers. The PBS polymers and copolymers may further comprise one or more of the following: branching agents, crosslinking agents, chain extenders, and reactive blending agents. The PBS and P4HB polymers and copolymers may be isotopically enriched. In some preferred embodiments, the grid cells of the implant may be made from P4HB, PBS, or copolymers of P4HB and PBS by injection molding, extrusion, knitting, weaving, foaming, or 3D printing. In some embodiments, the grid is made of a material that can hold the liposuction fat microspheres in place and prevent the accumulation of fat that could lead to necrosis.

[0036] 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.

[0037] 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 radiation.

[0038] In some embodiments, the implant is manufactured by forming a grid of multiple first-type unit cells, wherein (i) unit cells are formed by injection molding a polymer composition to form the struts or fibers of the unit cells and assembling the unit cells to form the grid, (ii) unit cells are formed by warp knitting the fibers and assembling the unit cells to form the grid, (iii) the grid is formed directly from the polymer composition by 3D printing the polymer struts or fibers of the grid, or (iv) unit cells are formed by foaming and assembling the foam unit cells 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 (iii) contain one or more tabs or anchors for securing the implant. The grid thus formed by injection molding may also contain fasteners that allow the unit cells to attach to each other to form the grid.

[0039] In some implementations, the implant can be temporarily deformed during implantation or delivery via minimally invasive techniques.

[0040] In some embodiments, the implant unit cells are 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 tissue, promotes tissue inward growth, and helps prevent device migration after implantation. In some embodiments, the surface roughness of the struts or fibers of the implant unit cells is 0.02 to 75 micrometers, more preferably 0.1 to 50 micrometers or 0.5 to 30 micrometers, and even more preferably 5 to 30 micrometers. In some embodiments, the implant unit cells are 3D printed with these surface roughness values. Preferably, the implant unit cells are 3D printed by selective laser melting (SLM) of polymer powder or melt extrusion deposition (MED) of polymer granules. In some embodiments, the unit cells are formed from extruded fibers with a surface roughness. In some embodiments, extruded fibers with surface roughness can be formed by inducing melt fracture during fiber extrusion, forming roughness on the fiber surface using textured rollers after extrusion, extruding the fiber through a characteristic die orifice (e.g., a serrated orifice) and treating the extruded fiber with a solvent vapor mist (e.g., using micron-sized solvent droplets) to create pits on the fiber surface. In some embodiments, the implant is formed from a single cell comprising a strut or fiber with a surface roughness of 0.02 to 75 micrometers, more preferably 0.1 to 50 micrometers, and the strut or fiber 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 of 22% to 1,000%, more preferably 100% to 700%; and (iv) an elastic modulus 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 with a surface roughness of 0.02 to 75 micrometers, more preferably 0.1 to 50 micrometers, 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 with surface roughness is a breast implant.

[0041] In some implementations, the implant is not permanent, but degrades at a predictable rate and has a predictable strength retention rate that allows support to transition from the implant to new tissue.

[0042] In some implementations, the implant has a scaffold structure that can be coated with autologous tissue or serve as a reservoir of autologous tissue, including but not limited to autologous fat, liposuction, injectable fat, adipocytes, fibroblasts, and stem cells.

[0043] In some implementations, the implant includes one or more openings that allow insertion of a vascular pedicle or other tissue block to increase or replace tissue volume.

[0044] In some implementations, the implant can be easily designed into any shape, for example, a shape that provides a specific and desired appearance for the breast.

[0045] These advantages, as well as other objects and advantages of the present invention, will become apparent from the following detailed embodiments and accompanying drawings. Attached Figure Description

[0046] Figure 1 This is a perspective view of an implant comprising multiple connected skeletal polyhedral cells according to an embodiment of the present invention;

[0047] Figure 2A , Figure 2B , Figure 2C and 2D They are Figure 1 The bottom view, isometric view, front view, and left view of a skeletal polyhedral unit cell of the implant shown.

[0048] Figure 3 yes Figure 1 A schematic diagram showing the implant being compressed by a finger;

[0049] Figure 4 This is a perspective view of a coiled cylindrical unit cell according to one embodiment of the present invention;

[0050] Figure 5 This is a perspective view of a coiled unit cell including fasteners for assembling unit cells together, according to one embodiment of the present invention;

[0051] Figure 6 This is a perspective view of a coiled unit cell made of thermoplastic polymer by 3D printing according to one embodiment of the present invention;

[0052] Figure 7 It is a plurality of embodiments according to the present invention. Figure 5 A perspective view of the lattice structure of the implant formed by coiled unit cells, as shown in the image.

[0053] Figure 8 According to one embodiment of the present invention, multiple [items] are produced by 3D printing. Figure 4The upper perspective view of the lattice structure of the implant formed by coiling a cylindrical unit cell to form the lattice structure of the implant;

[0054] Figure 9A This is a side view of an absorbable breast implant comprising a skeletal polyhedral unit cell and a porous shell according to an embodiment of the present invention.

[0055] Figure 9B yes Figure 9A The implant shown is a top view of its porous outer shell;

[0056] Figure 10A This is a top perspective view of another breast implant comprising a skeletal polyhedral unit cell according to one embodiment of the present invention;

[0057] Figure 10B yes Figure 10A The implant shown is a cross-section of the implant's skeletal polyhedral unit cell;

[0058] Figure 11 This is a top perspective view of another implant according to one embodiment of the present invention;

[0059] Figure 12 This is a diagram of a network unit cell according to one embodiment of the present invention;

[0060] Figure 13 This is a top view of a cuboid-shaped compressible unit cell according to an embodiment of the present invention;

[0061] Figure 14 yes Figure 13 The side perspective view of the compressible unit cell shown in the figure;

[0062] Figure 15 A side perspective view of four cuboid-shaped compressible unit cells sewn together to form a compressible assembly unit according to an embodiment of the present invention; and

[0063] Figure 16A , Figure 16B and 16C This is a diagram illustrating a method for forming porous compressible foam unit cells according to an embodiment of the present invention. Detailed Implementation

[0064] Before describing the invention in detail, it should be understood that the invention is not limited to the specific variations set forth herein, as various changes or modifications can be made to the described invention and equivalent alternatives can be substituted without departing from the spirit and scope of the invention. It will be apparent to those skilled in the art, upon reading this disclosure, that each individual embodiment described and illustrated herein has discrete components and features that can be readily separated from or combined with features of any of the other several embodiments without departing from the scope or spirit of the invention. Furthermore, numerous modifications can be made to adapt particular circumstances, materials, composition, processes, process behaviors, or steps to the purpose, spirit, or scope of the invention. All such modifications are intended to fall within the scope of the claims set forth herein.

[0065] The methods listed herein can be performed in any logically possible order of the listed events, as well as in the order in which the events are listed. Furthermore, where a range of values ​​is provided, it should be understood that every intermediate value between the upper and lower limits of the range, and any other specified value or intermediate value within that range, is covered within the scope of this invention. Additionally, any optional features of the inventive variations contemplated herein may be set forth and claimed independently or in combination with any one or more of the features described herein.

[0066] All existing subjects mentioned herein (e.g., publications, patents, patent applications, and physical objects) are incorporated herein by reference in their entirety, unless the subject matter may conflict with the subject matter of this invention (in which case the subject matter presented herein shall prevail).

[0067] Nouns without quantifiers indicate one or more types. More specifically, unless the context clearly indicates otherwise, nouns without quantifiers used herein and in the appended claims indicate one or more types. It should be further noted that claims may be drafted to exclude any optional elements. Similarly, this statement is intended to serve as a prior basis for the use of exclusive terms such as “merely,” “only,” etc., or the use of “negative” limiting terms associated with the recitation of elements of the claims.

[0068] To further aid understanding, the following definitions are set forth below. However, it should also be understood that, unless otherwise defined 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 pertains.

[0069] I. Definition

[0070] As is commonly used in this article, “absorbable” means that a material degrades in the body and that the degradation products are eliminated or excreted from the body. The terms “absorbable,” “reabsorbable,” “degradable,” and “biodegradable,” whether or not they are prefixed with “bio”, and whether the degradation is primarily due to hydrolysis or mediated by metabolic processes, are used interchangeably in this article to describe materials that decompose and are gradually absorbed, excreted, or eliminated by the body.

[0071] As is commonly used in this text, "bioactive agent" refers to therapeutic agents, preventative agents, or diagnostic agents, preferably agents that promote the healing and regeneration of host tissues, as well as therapeutic agents that prevent, inhibit, or eliminate infection. "Reagent" without a quantifier indicates one or more "reagents".

[0072] As is commonly used in this article, "biocompatibility" means that the biological response of a material or device is suitable for its intended in vivo application. Any metabolites of these materials should also be biocompatible.

[0073] As is commonly used in this article, “blend” refers to a physical combination of different polymers, as opposed to a copolymer formed from two or more different monomers.

[0074] As is commonly used in this document, "polymer of poly-4-hydroxybutyrate" refers to any polymer containing 4-hydroxybutyrates having one or more distinct hydroxy acid units. The copolymer may be isotopically enriched.

[0075] As is commonly used herein, "polymer of poly(butylene succinate)" refers to any polymer containing 1,4-butanediol and succinic acid units, as well as one or more different diol or diacid units. The copolymer may contain one or more of the following: branching agents, crosslinking agents, chain extenders, and reactive blending agents. The copolymer may be isotopically enriched.

[0076] As is commonly used in this article, “endotoxin content” refers to the amount of endotoxin present in the implant or sample, and is determined by the limulus amebocyte lysate (LAL) assay.

[0077] Unless otherwise stated, “molecular weight” as commonly used herein refers to weight-average molecular weight (Mw), not number-average molecular weight (Mn), and is measured by GPC relative to polystyrene.

[0078] As is commonly used in this article to describe coils or springs, “pitch” refers to the distance between the wires of adjacent coils, and is measured from the center of one wire to the center of the adjacent wire.

[0079] "Poly(butylene succinate)" refers to a polymer containing 1,4-butanediol units and succinic acid units. The polymer may contain one or more of the following: branching agents, crosslinking agents, chain extenders, and reactive blending agents. The polymer may be isotopically enriched.

[0080] "Poly(butylene succinate) and copolymers" includes polymers and copolymers prepared using one or more of the following: chain extenders, coupling agents, crosslinking agents, and branching agents.

[0081] As used herein, "poly-4-hydroxybutyrate" refers to a homopolymer containing 4-hydroxybutyrate units. In this context, it can refer to P4HB or TephaFLEX. ® Biomaterials (manufactured by Tepha, Inc., Lexington, MA). The polymers may be isotopically enriched.

[0082] As used in this article, “chest” refers to the area below the skin and above or above the pectoral muscles.

[0083] As used in this article, “skeleton polyhedron” refers to a perimeter frame consisting of the edges and vertices of a polyhedron, and its interior is hollow unless filled.

[0084] As used in this article, "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.

[0085] "Strength retention rate" 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 reabsorbable fiber or strut decreases by half within 3 months of implantation in an animal, the strength retention rate of the fiber or strut at 3 months will be 50%.

[0086] As used in this article, "subglandular" refers to the area below the breast tissue and above the pectoral muscles.

[0087] As used in this article, "below the chest" means at least partially below the pectoral muscles.

[0088] As used in this paper, “surface roughness” (Ra) is the arithmetic mean of the absolute values ​​of the deviations of the profile height from the mean line recorded over the evaluation length.

[0089] As used herein, “bulk density” refers to the ratio of the volume of material in a single cell forming the implant grating to the volume of voids in the implant grating. For example, an implant grating with a bulk density of 20% would contain 20% by volume material and 80% by volume voids. Bulk density is measured before any additives, bioactive agents, cells, and tissues are applied to the grating.

[0090] II. Materials used in the fabrication of implants

[0091] In some implementations, implants can be used to reshape parts of the body, including the breast, nipple, face, and buttocks, as well as to fill gaps, repair hernias, and deliver biological and synthetic materials to aid in tissue regeneration, enlargement, repair, strengthening, and reconstruction. The implant is a soft tissue implant, meaning it can be used for soft tissue regeneration, enlargement, repair, strengthening, and reconstruction. The implant eliminates the need for permanent breast implants during mastectomy, breast fixation, and breast augmentation procedures, as well as the need for permanent implants in other surgical procedures. The implant is biocompatible and, as it degrades, is preferably replaced in vivo by the patient's own tissue. The implant is particularly suitable for filling gaps or enlarging tissue, especially soft tissue. Implants can have a range of properties from rigid, stiff structures to soft structures that temporarily deform under stress. These properties can be designed to resemble soft tissue. Implants manufactured for the breast can be compressed and can return to their shape after compression. Optionally, the implant can be coated with autologous tissue, autologous fat, liposuction, injectable fat, adipocytes, fibroblasts, and stem cells before, during, or after implantation. Implants may also contain one or more openings or channels (including transverse channels) that allow insertion of a vascular pedicle or other tissue block.

[0092] A. Polymers used in the preparation of implants

[0093] In some embodiments, the implant comprises a grid formed by multiple unit cells. The shape or type of the unit cells can vary. The shape of the unit cell can be a skeletal polyhedron with edges and vertices formed by polymer struts or fibers. Alternatively, the unit cell can be a coil or spring formed by 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 by 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 joined unit cells can be the same or different. The grid can contain two or more unit cells, and preferably 50 or more unit cells. The grid can optionally include other features, such as one or more openings or one or more channels (including one or more lateral channels).

[0094] The implant's grating may contain 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 polyethylene terephthalate, polytetrafluoroethylene, polyurethane, poly(ether-urethane), poly(methyl methacrylate), polyetheretherketone, polyolefins, and poly(ethylene oxide). However, the implant's grating preferably contains degradable materials, more preferably thermoplastic or polymer degradable materials, and even more preferably the implant's grating is made entirely of degradable materials.

[0095] In a preferred embodiment, the implant's grating is made of one or more absorbable polymers or copolymers, preferably absorbable thermoplastic polymers and copolymers, and even more preferably absorbable thermoplastic polyesters. The implant's grating can be prepared, for example, from polymers including, but not limited to, glycolic acid, lactic acid, and 1,4-dihydroxyethyl glycolic acid. Polymers of ketones, trimethylene carbonates, 3-hydroxybutyric acid, 4-hydroxybutyrate, and ε-caprolactone, including polyglycolic acid, polylactic acid, and polydimethylethanol. Copolymers of ketones, polycaprolactone, glycolic acid, and lactic acid, such as VICRYL ® Polymer, MAXON ® and MONOCRYL ® Polymers, including poly(lactide-co-caprolactone); poly(orthoester); polyanhydride; poly(phosphazene); polyhydroxyalkanoates; synthetic or bio-based polyesters; polycarbonates; tyrosine polycarbonates; polyamides (including synthetic and natural polyamides, peptides, and poly(amino acids)); polyesteramides; poly(alkylene alkylates); polyethers (e.g., polyethylene glycol PEG and polyethylene oxide PEO); polyvinylpyrrolidone or PVP; polyurethanes; polyether esters; polyacetals; polycyanoacrylates; poly(ethylene oxide) / poly(propylene oxide) copolymers; polyacetals, polyketides; polyphosphates (polyphosphates). Polyphosphates; polyphosphoesters; polyalkylene oxalates; polyalkylene succinates; poly(maleic acid); filaments (including recombinant filaments and filament 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-glycolic acid), or polycaprolactone and their copolymers, including their random copolymers and block copolymers.

[0096] Preferably, the grid of the implant is made of an absorbable polymer or copolymer that will be substantially reabsorbed within a time range of 1 to 24 months after implantation, more preferably 3 to 18 months, and retain some residual strength for at least 2 weeks to 6 months.

[0097] The implant's grid can also be prepared using blends of polymers and copolymers (preferably absorbable polymers). Particularly preferred blends of absorbable polymers are prepared from, but are not limited to, the following absorbable polymers: glycolic acid, lactic acid, 1,4-dihydroxyethyl glycolic acid, and hydroxyethyl glycolic acid. Polymers of ketones, trimethylene carbonates, 3-hydroxybutyric acid, 4-hydroxybutyrate, ε-caprolactone, 1,4-butanediol, 1,3-propanediol, ethylene glycol, glutaric acid, malonic acid, oxalic acid, succinic acid, adipic acid, or copolymers thereof.

[0098] In a particularly preferred embodiment, the implant's grating uses poly-4-hydroxybutyrate (Tepha P4HB). TM Poly-4-hydroxybutyrate (P4HB) is manufactured using polymers (Lexington, MA) or copolymers thereof. Copolymers include P4HB with other hydroxy acids (e.g., 3-hydroxybutyrate) and P4HB with glycolic acid or lactic acid monomers. Poly-4-hydroxybutyrate is a biocompatible and reabsorbable strong, flexible thermoplastic polyester (Williams et al., Poly-4-hydroxybutyrate (P4HB): anew generation of resorbable medical devices for tissue repair and regeneration, Biomed. Tech. 58(5):439-452 (2013)). Upon implantation, P4HB hydrolyzes to its monomers, and the monomers are metabolized into 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, and even more preferably 200 kDa to 450 kDa. Polymers with a weight-average molecular weight of 50 kDa or higher are preferred for processing and mechanical properties.

[0099] In another preferred embodiment, the grid 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 grid 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 of other diols, other diacids, or combinations thereof. For example, the polymer can be a poly(butylene succinate) copolymer further comprising one or more of the following: 1,3-propanediol, 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 glycol succinate), and poly(butylene succinate-co-propylene glycol succinate). The poly(butylene succinate) polymer or copolymer may further comprise one or more of the following: chain extenders, coupling agents, crosslinking agents, and branching agents. For example, poly(butylene succinate) or its copolymers may be branched or crosslinked by adding one or more of the following agents: malic acid, trimethylolpropane, trimesic acid, citric acid, glycerol propoxylate, and tartaric acid. A particularly preferred agent for branching or crosslinking poly(butylene succinate) polymers or copolymers thereof is a hydroxycarboxylic acid unit. Preferably, the hydroxycarboxylic acid unit has two carboxyl groups and one hydroxyl group, two hydroxyl groups and one carboxyl group, three carboxyl groups and one hydroxyl group, or two hydroxyl groups and two carboxyl groups. In a preferred embodiment, the grid 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-butanediol-malic acid copolyester, or poly(1,4-butanediol-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-butanediol, and malic acid. In another preferred embodiment, malic acid can be used as a branching or crosslinking agent for preparing copolymers of poly(butylene succinate) and adipate, which may be referred to as poly[(butylene succinate)-co-adipate] crosslinked with malic acid. As used herein, "poly(butylene succinate) and copolymers" includes polymers and copolymers prepared using one or more of the following: chain extenders, coupling agents, crosslinking agents, and branching agents.In a particularly preferred embodiment, poly(butylene succinate) and its copolymers contain at least 70 wt%, more preferably 80 wt%, even more preferably 90 wt% of succinic acid and 1,4-butanediol units. Based on gel permeation chromatography (GPC) relative to polystyrene standards, the weight-average molecular weight (Mw) of polymers containing diacids and diols, including poly(butylene succinate) and its copolymers and other polymers containing diacids and diols described herein, is preferably from 10,000 to 400,000, more preferably from 50,000 to 300,000, and even more preferably from 100,000 to 200,000. In a particularly preferred embodiment, the weight-average molecular weight of the polymers and copolymers is from 50,000 to 300,000, more preferably from 75,000 to 300,000. In a preferred embodiment, the poly(butylene succinate) or its copolymer used to manufacture the grille has one or more, or all, of the following properties: 1.23 g / cm³. 3 to 1.26 g / cm³ 3 of 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 / 2.16 kgf of 2 g / 10 min to 10 g / 10 min, and a tensile strength of 30 to 60 MPa.

[0100] In another embodiment, the polymers and copolymers (including P4HB and its copolymers and PBS and its copolymers) described herein for preparing the grille for implants include polymers and copolymers in which the isotopes of hydrogen, carbon, and / or oxygen are known to be enriched. Hydrogen has three naturally occurring isotopes, including 1 ¹H (protium), 2 ²H (deuterium), and 3 ³H (tritium), where the most common is the 1 ¹H isotope. The isotope content of the polymer or copolymer can be enriched such that, for example, the polymer or copolymer contains a higher proportion of a particular one or more isotopes than the natural proportion. The carbon and oxygen content of the polymer or copolymer can also be enriched to contain a higher proportion of carbon and oxygen isotopes, including but not limited to 13 ¹³C, 14 ¹⁴C, 17 ¹⁸O, or 18O. Other isotopes of carbon, hydrogen, and oxygen are known to those skilled in the art. The preferred hydrogen isotope enriched in P4HB or its copolymers or PBS or their copolymers is deuterium, i.e., deuterated P4HB or its copolymers or deuterated PBS or their copolymers. The deuteration percentage can 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 higher.

[0101] In a preferred embodiment, the polymers and copolymers used to prepare the grid (including P4HB and its copolymers, and PBS and its copolymers) have a low moisture content. This is preferred to ensure the production of implants with high tensile strength, extended strength retention, and good shelf life. In a preferred embodiment, the moisture content of the polymers and copolymers used to prepare the implant is 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%).

[0102] The compositions used to prepare implants desirably have low endotoxin content. In some preferred embodiments, the endotoxin content is low enough that the implant produced from the polymer composition has an endotoxin content of less than 20 endotoxin units / device, as determined by a horseshoe crab lysate (LAL) assay. In one embodiment, the polymer composition used to prepare the grid of the implant has an endotoxin content of <2.5 EU / g polymer or copolymer. For example, the endotoxin content of P4HB polymer or copolymer or PBS polymer or copolymer is <2.5 EU / g polymer or copolymer.

[0103] B. Additives

[0104] Certain additives can be incorporated into the implant, preferably into the polymer composition used to manufacture the grid. In one embodiment, these additives are incorporated into the polymer or copolymer described herein during a compounding process to produce granules that can be subsequently processed to produce the grid. For example, the granules can be injection molded, extruded, or printed to form the grid or grid unit cells. In another embodiment, the granules can be milled to produce a powder suitable for further processing, for example, by 3D printing. Alternatively, powder suitable for further processing, for example, by 3D printing, can be formed directly by blending the additives with the polymer or copolymer. If desired, the powder for processing can be sieved to select an optimal particle size range. In another embodiment, a solution-based method can be used to incorporate the additives into the polymer composition used to prepare the grid of the implant.

[0105] In a preferred embodiment, the additive is biocompatible, and even more preferably, the additive is biocompatible and reabsorbable.

[0106] In one embodiment, the additive may be a nucleating agent and / or a plasticizer. These additives may be added to the polymer composition used to prepare the grating for the implant in an amount sufficient to produce the desired results. Typically, these additives may be added in amounts from 1% to 20% by weight. Nucleating agents may be incorporated to increase the crystallization rate of the polymer, copolymer, or blend. Such agents can be used, for example, to facilitate the manufacture of the grating and improve its mechanical properties. 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.

[0107] Plasticizers that can be incorporated into polymer compositions used to prepare implant grids include, but are not limited to, dibutyl maleate, methyl laurate, dibutyl fumarate, di(2-ethylhexyl)(dioctyl)maleate, paraffin wax, dodecyl alcohol, olive oil, soybean oil, polytetramethylene glycol, methyl oleate, n-propyl oleate, tetrahydrofurfuryl oleate, epoxidized linseed oil, 2-ethylhexyl epoxy tall oil, triacetin, methyl linoleate, dibutyl fumarate, methyl acetyl ricinoleate, acetyl tri(n-butyl) citrate, acetyl triethyl citrate, tri(n-butyl) citrate, triethyl citrate, and bis(2-hydroxyethyl) dimer. Dimethyl ricinoleate, butyl ricinoleate, glyceryl tris(acetyl ricinoleate), methyl ricinoleate, n-butyl acetyl ricinoleate, propylene glycol ricinoleate, diethyl succinate, diisobutyl adipate, dimethyl azelaate, di(n-hexyl) azelaate, tributyl phosphate, and mixtures thereof. A particularly preferred plasticizer is citrate.

[0108] C. Bioactive agents, cells and tissues

[0109] Implants may load, fill, coat, or otherwise incorporate bioactive agents. Bioactive agents may be included in implants for a variety of reasons. For example, bioactive agents may be included to improve tissue inward growth into the implant, to improve tissue maturation, to provide delivery of the active agent, to improve the wettability of the implant, to prevent infection, and to improve cell adhesion. Bioactive agents may also be incorporated into the grid structure of the implant.

[0110] Implants may contain active agents designed to stimulate inward cell growth, including growth factors, cell adhesion factors (including cell adhesion peptides), cell differentiation factors, cell recruitment factors, cell receptors, cell binding factors, and cell signaling molecules, such as cytokines and molecules that promote cell migration, cell division, cell proliferation, and extracellular matrix deposition. Such active agents include fibroblast growth factor (FGF), transforming growth factor (TGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), granulocyte-macrophage colony-stimulating factor (GMCSF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), hepatocyte growth factor (HGF), interleukin-1-β (IL-1β), interleukin-8 (IL-8), and nerve growth factor (NGF), and combinations thereof. As used herein, the term "cell adhesion peptide" refers to a compound having at least two amino acids per molecule that can bind to cells via cell surface molecules. Cell adhesion peptides include any extracellular matrix protein known to play a role in cell adhesion, including fibronectin, porphyrin, laminin, elastin, fibrinogen, type I, type II, and type V collagen, as well as synthetic peptides with similar cell adhesion properties. Cell adhesion peptides also include peptides derived from any of the aforementioned proteins, including fragments or sequences containing a binding domain.

[0111] The implant may incorporate a wetting agent designed to improve the wettability of the grid structure surface, allowing fluids to readily adhere to the implant surface and promoting cell attachment and / or modifying 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 thereof, such as PLURONICS. ® Other suitable wetting agents include surfactants or emulsifiers.

[0112] Implants may contain gels, hydrogels, or mixtures of live hydrogels to further improve wetting properties and promote cell growth throughout the implant's grid structure. Hydrogel mixtures consist of live cells encapsulated in biocompatible hydrogels such as gelatin, methacrylated gelatin (GelMa), silk gel, and hyaluronic acid (HA) gel.

[0113] Other bioactive agents that can be incorporated into implants include antimicrobial agents, particularly antibiotics, disinfectants, oncology agents, anti-scarring agents, anti-inflammatory agents, anesthetics, small molecule drugs, anti-adhesion agents, cell proliferation inhibitors, anti-angiogenic and pro-angiogenic factors, immunomodulators, and coagulants. Bioactive agents can be proteins such as collagen, as well as antibodies, peptides, polysaccharides such as chitosan, alginate, hyaluronic acid and its derivatives, nucleic acid molecules, low molecular weight compounds such as steroids, inorganic materials such as hydroxyapatite and ceramics, or complex mixtures such as platelet-rich plasma. Suitable antimicrobial agents include bacitracin, biguanides, triclosan, gentamicin, minocycline, rifampin, vancomycin, cephalosporins, copper, zinc, silver, and gold. Nucleic acid molecules can include DNA, RNA, siRNA, miRNA, antisense, or aptamers.

[0114] The implant may also comprise allogeneic and xenograft materials, including acellular dermal matrix materials and small intestinal submucosal (SIS) materials. In one embodiment, the implant may comprise a vascular pedicle or other tissue block. The vascular pedicle or other tissue block is preferably autologous tissue.

[0115] In another implementation, the implant may be incorporated into a system for the controlled release of therapeutic or prophylactic agents.

[0116] In one embodiment, the implant is coated with allogeneic grafts or xenografts and cells before, during, or after implantation, or any combination thereof. In a particularly preferred embodiment, the implant is coated with autologous tissue and cells from the patient before, during, or after implantation, or any combination thereof. The autologous tissue and cells are preferably one or more of the following: autologous fat, liposuction, adipose tissue, injectable fat, adipose tissue, adipocytes, fibroblasts, and stem cells, including human adipose tissue-derived stem cells (also known as preadipocytes or adipose tissue-derived progenitor cells) and fibroblast-like stem cells. In a preferred embodiment, the implant may be coated with autologous tissue and cells as described herein, and may further include a vascular pedicle or other tissue block. As will be apparent herein, the lattice structure of the implant is designed not only to produce the shape of the implant (e.g., a breast implant), but also to produce a large surface area that can retain autologous tissue and cells to promote inward tissue growth.

[0117] III. Methods for preparing implants from skeletal polyhedral cells, coiled cells, reticular cells, and foam cells

[0118] There are many methods that can be used to manufacture implants.

[0119] A. Implant shape

[0120] In one implementation, the implants are designed such that they are three-dimensional during manufacturing.

[0121] Their shape allows surgeons to increase tissue volume, fill gaps, reconstruct lost or missing tissue or structures, outline tissue, enlarge 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 the breast, nipple, face, and buttocks. In one implementation, implants allow for alteration or sculpting of soft tissue structures without the use of permanent implants.

[0122] Within the scope described herein, it should be understood that a variety of implant shapes and sizes exist, and the invention is not limited in terms of the three-dimensional shape and size of implants except as set forth in the appended claims. Implants can be assembled or printed to have any size and shape suitable for use as implants. For example, implants having the following three-dimensional shapes can be readily fabricated, such as spheres, hemispheres, cylinders, cones, domes, cuboids, tetrahedrons, triangular or quadrangular prisms, dodecahedrons, tori, and ellipsoids, and custom shapes can optionally be produced with the aid of computer-aided design. For example, cylindrical implants for nipple reconstruction or dome-shaped implants for breast reconstruction can be produced. The size of the implant can be sized to increase tissue volume, replace previous tissue volume, change tissue volume distribution, change tissue appearance, or replace existing tissue volume with a smaller volume.

[0123] In a preferred embodiment, the implant is shaped to alter the soft tissue volume of the breast without the use of a permanent breast implant, such as a silicone breast implant. In some embodiments, the implant can be prepared in a shape and size intended to increase breast size, replace breast tissue volume and shape after a mastectomy, and produce a specific appearance of the breast. For example, the implant can be prepared such that, when implanted in the breast, it produces a breast with a specific ratio of upper pole volume (UPV) to lower pole volume (LPV). In some embodiments, the implant is a breast implant with a volume size such that implantation produces 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 with a specific upper and lower pole tissue volume ratio, the size and shape of the implant can be selected to provide a highly desired lower pole, upper pole shape, and degree of breast protrusion from the chest wall. In some embodiments, the implant is a breast implant designed such 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) defines the distance the breast protrudes from the chest wall. It will thus be apparent that the implant of the present invention can be used to produce a very attractive reconstructed breast by having the following specific shapes: (i) defining the ratio of UPV to LPV; (ii) defining the curvature of the upper and lower poles; (iii) defining the extent of the breast protruding from the chest wall; and (iv) defining the angle of the nipple on the breast.

[0124] Another shape of the implant is described in U.S. Patent Application No. 16 / 262,018, filed on January 30, 2019, entitled “FULL CONTOUR BREAST IMPLANT”.

[0125] Implants designed for use in the breast can be fabricated to a size large enough to allow for use in mastectomy and breast reconstruction. These implants are wide enough to span the width of the breast. In one implementation, four sizes and shapes of implants are used in breast surgery: small, medium, large, and extra-large. These four sizes of implants are shown in Table 1, where IMF-UP is the longitudinal distance between the lowest point of the implant in the breast (located at the point closest to the inframammary fold (IMF) after implantation) and the highest point in the breast (located at the point closest to the intersection between the breast and the chest wall at the upper pole after implantation), MD-LT is the width of the implant measured from the inside to the outside, CHST-NAC is the maximum projection distance of the implant when implanted into the chest wall, and LP radius is the radius of curvature of the implant at the lower pole. As can be clearly seen from Table 1, implants used in breast surgery can 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 size of the implant, which imparts an upper pole shape in the region, can vary. In this region, the implant shape is preferably slightly concave or straight.

[0126] Table 1

[0127] Size of breast implants

[0128]

[0129] In some implementations, the implant can be fabricated with a porous outer shell. For example, Figure 9A and 9B This demonstrates how breast implants can be constructed with skeletal polyhedral cells and porous shells. Figure 9A A cross-section of implant 480 is shown, in which unit cell 482 is visible within the porous outer shell 490 of the implant, and Figure 9B The top of the porous outer membrane 490 covering the implant is shown. The implant has a large surface area that can be coated with, for example, autologous fat, cells, collagen, or bioactive agents.

[0130] B. Unit

[0131] Implants comprising grates of different shapes can be produced using the same or different types of unit cells. Unit cells can be assembled to form a grates, or 3D printed to form a grates. A grates can comprise two or more unit cells, but more preferably five, ten, fifteen, twenty, twenty, twenty-five, thirty, thirty-five, forty ... The size of the unit cell allows for the formation of a low-volume-density grid that can be colonized by cells and invaded by tissues, blood vessels, or combinations thereof. The unit cell size also allows the grid of the implant to be coated with allogeneic or xenograft tissues and cells, preferably autologous tissues and cells, including but not limited to autologous fat, liposuction, fat grafts, injectable fat, adipocytes, fibroblasts, and stem cells. In a preferred embodiment, the unit cell size allows the interior of the grid formed by the unit cell to be coated with fat, liposuction, injectable fat, adipocytes, fibroblasts, and stem cells. The unit cell size is also designed to allow the grid to be coated with collagen and / or hyaluronic acid or derivatives thereof. Cells and other compositions, such as collagen and hyaluronic acid, can be coated onto the grid before, after, or both before and after implantation. Preferably, the unit cell size is large enough to allow needles to be inserted into the grid structure for injection delivery of bioactive agents, cells, fat, and other compositions. In some embodiments, the grid consists of unit cells that allow needles of gauges 12 to 21 to be inserted into the grid. This characteristic allows the use of syringes to load the grid with cells, tissues, collagen, bioactive agents, and additives, including fat, without damaging the grid. Preferably, the grid allows the insertion of needles with an outer diameter of 0.5 to 3 mm.

[0132] The size and shape of the unit cells can be selected to provide different types of grids with varying bulk densities. The properties of the 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 prepare them. 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 prepare them. Selecting specific unit cell sizes and materials can produce grids from unit cells with properties ranging from rigid, hard, or stiff to elastic, soft, or compressible. In some embodiments, the mechanical properties of the grid can be changed without altering 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 elastic modulus or compressive strength, are known, the required strut thickness or diameter 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 such that the implant grid prepared from the unit cells has properties similar to those of the soft tissue in which the implant is placed. 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 restore its original shape when the compressive force is released.

[0133] i. Skeletal polyhedral unit cell

[0134] In some embodiments, the unit cell is a skeletal polyhedron with edges and vertices formed by polymer struts or fibers. The edges and vertices or struts / fibers of the skeletal unit cell can have different dimensions, thicknesses, lengths, and angles, and can be rigid, stiff, flexible, elastic, or spring-like, and can be made of oriented or non-oriented polymers. In one embodiment, the grid can be prepared from skeletal unit cells having one or more of the following shapes: tetrahedron, cuboid, pentahedron, hexahedron, heptahedron, octahedron, icosahedron, decahedron, dodecahedron, tetradecahedron, and their prisms, antiprisms, and truncated polyhedra. Examples of unit cells in the shape of prisms, antiprisms, and truncated polyhedra are hexagonal prisms, octagonal antiprisms, and truncated dodecahedrons. In one embodiment, the skeletal unit cell is formed from an elongated polyhedron. In a preferred embodiment, the skeletal unit cell has 4, 6, 8, 12, or 20 faces. In a particularly preferred embodiment, the skeletal unit cell is a dodecahedron, and even more preferably a rhombic dodecahedron. Therefore, for example, a unit cell with a rhombic dodecahedral shape can be formed as a grid for an implant, which is then implanted in, for example, the breast, nipple, face, or buttocks. Alternatively, the grid can be formed from a unit cell with an octagonal shape. In other embodiments, the grid can be made from two or more different skeletal unit cells, such as a combination of dodecahedral and octagonal shapes.

[0135] In some embodiments, the implant is formed of a skeletal polyhedron, wherein the diameter or width of the edges and vertices of the unit cells forming the skeletal 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 skeletal 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 breaking elongation of the edges and vertices of the unit cells forming the skeletal 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 skeletal 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, breaking elongation, and elastic modulus of the edges and vertices of the unit cells may be the same throughout the skeletal polyhedron or unit cells, or these values ​​may be different throughout the skeletal polyhedron or unit cells. The polymer struts forming the edges and apex 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.

[0136] In some embodiments, the elastic modulus of the implant formed by the skeletal polyhedron 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 polymer struts or fibers forming the unit cells of the skeletal polyhedron have one or more of the following properties: (i) a diameter of 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 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 of 22% to 1,000%, more preferably from 100% to 700%; and (iv) an elastic modulus of 0.05 to 10 GPa, more preferably from 0.1 to 3 GPa, even more preferably from 0.2 to 0.8 GPa.

[0137] In some embodiments, the implant is a breast implant formed of a skeletal polyhedron, 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 polymer struts or fibers forming the unit cells of the skeletal polyhedron have one or more of the following properties: (i) a diameter of 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 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 of 22% to 1,000%, more preferably from 100% to 700%; and (iv) an elastic modulus of 0.05 to 10 GPa, more preferably from 0.1 to 3 GPa, even more preferably from 0.2 to 0.8 GPa.

[0138] Reference Figure 1 The breast implant 10 is shown as comprising a grid made of interconnected rhombic dodecahedral unit cells. The implant 10 has a low bulk density that provides a large surface area and void volume.

[0139] Figures 2A to 2D Showing the generation Figure 1 Different views of the skeletal rhombic dodecahedral unit cell 20 of the grid implant 10 shown. The skeletal rhombic dodecahedral 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.

[0140] Figure 3 This illustrates the fabrication of a grid containing desired properties using single cells with specific dimensions and polymer materials. Figure 3 In the example shown, a breast implant 30 comprising a grating is illustrated, where it is evident that the grating can be compressed by relatively light pressure from a finger 32 sufficient to compress the grating structure. When the finger is removed, the grating returns to its original position. Figure 1 The original shape is shown. Implants containing compressible grids are particularly suitable for the breast because the compressibility of the grids can be designed to mimic the properties of breast tissue. Therefore, when massaging the breast, the patient will not feel the hard implant in the breast.

[0141] Refer again Figures 2A to 2D The length (L) of the struts or fibers in the skeletal 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 needles with an outer diameter (OD) of 0.5 to 3 mm to be inserted into a grid made of the unit cell.

[0142] The height (H) of the unit cell can 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.

[0143] The width (W) of the struts or the diameter of the fibers in the skeletal polyhedral 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, as well as the strut or fiber length, required to produce a grid with a specific elastic modulus or other mechanical properties can be calculated for a given material.

[0144] In a particularly preferred embodiment, the skeletal unit cell is compressible, and even more preferably, capable of returning to its original size after compression. A particularly preferred embodiment is a compressible breast implant comprising a skeletal unit cell capable of returning to its original size after compression. Implants of different shapes can also be produced using the same or different units, wherein the unit cell is a skeletal unit cell.

[0145] ii. A unit cell with a coil or spring

[0146] In other embodiments, the unit cells used to form the grid of the implant are coils, springs, or helices formed of polymer. An example of a unit cell having coils and springs is... Figure 4 As shown in the figure. In this example, the unit cell is a coiled cylindrical unit cell 40 consisting of three spiral struts or lines 42, 44, 46 supporting the top ring 48 and the 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 angled at 120 degrees to each other at a constant spacing of 0.75 cm. In one embodiment, the outer diameter of the unit cell, serving 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 units can be angled at 10 to 180 degrees to each other, and the spacing between the helical struts can be 0.5 to 5 cm. The number of helical struts in the unit cell is preferably 1 to 20, but more preferably 2 to 5.

[0147] The required dimensional specifications of unit cells containing 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 return to their original dimensions after being compressed. Implants with different shapes can also be produced using the same or different unit cells, wherein the unit cells are coils and / or springs.

[0148] In some embodiments, the implant is formed from a unit cell containing 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 breaking load of the coil or spring in the unit cell forming the skeletal 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 breaking elongation of the coil or spring in the unit cell forming the skeletal polyhedron is 22% to 1,000%, more preferably 100% to 700%. In some embodiments, the elastic modulus of the coil or spring in the unit cell forming the skeletal 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, breaking elongation, and elastic modulus of the coil or spring in the unit cell may be the same throughout the skeletal polyhedron or unit cell, or these values ​​may be different throughout the skeletal polyhedron or unit cell. The coil or spring of the unit cell preferably has one or more of the following characteristics: (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.

[0149] In some embodiments, the elastic modulus of the implant formed by the grid of coils or springs 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 coils or springs forming the grid have one or more of the following characteristics: (i) a diameter of 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 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 of 22% to 1,000%, more preferably from 100% to 700%; and (iv) an elastic modulus of 0.05 to 10 GPa, more preferably from 0.1 to 3 GPa, even more preferably from 0.2 to 0.8 GPa.

[0150] In some embodiments, the implant is a breast implant formed of a grid of coils or springs, and the elastic modulus of the breast 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 coils or springs forming the grid have one or more of the following characteristics: (i) a diameter of 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 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 of 22% to 1,000%, more preferably from 100% to 700%; and (iv) an elastic modulus of 0.05 to 10 GPa, more preferably from 0.1 to 3 GPa, even more preferably from 0.2 to 0.8 GPa.

[0151] In a preferred embodiment, the unit cell made of coils and / or springs also includes fasteners that can be used to assemble the unit cell into a grid. Figure 5 The image shows an example of a unit cell 60 made of coils and springs, also containing fasteners. In this example, the top ring 62 and bottom ring 64 of the unit cell contain fasteners. The fasteners can be any suitable mechanism that allows the unit cells to engage together. Figure 5 In the example shown, the unit cell includes a male connector 66 and a female connector 68 that can be joined together to assemble the unit cell into a grid. Figure 5 In the unit cell, both convex and concave fasteners are visible in the upper and lower rings, which are separated by a 90-degree angle. Although in Figure 5 While not visible in the diagram, the illustrated unit cell contains two male connectors and two female connectors in each of its top and bottom rings, with the male and female connectors alternating and positioned at 90-degree intervals. The number of fasteners used to connect the unit cell on the upper and lower rings can be more or less than four, but preferably each ring contains two male connectors and two female connectors alternating at 90-degree intervals. If desired, the fasteners can also be positioned on the helical struts of the unit cell.

[0152] iii. Reticulate unit

[0153] In yet another embodiment, the unit cell is formed of a web and fibers. The unit cell may have a top plate formed of a web and a bottom plate formed of a web. The top plate and bottom plate are joined together by fibers to form a web-like unit cell. Preferably, the top plate and bottom plate are joined by interlacing fibers, more preferably by interlacing the top plate and bottom plate with monofilament fibers.

[0154] Figure 12 This is a diagram showing a top plate 110 and a bottom plate 120 of a mesh unit cell 100, and a support 130 connecting the top and bottom plates. The top and bottom plates are formed of mesh. Fiber inserts 140 from the mesh are shown on the top and bottom plates, and interlacing loops 142 of the mesh are also shown. Figure 12 The supports shown are preferably formed of fibers, more preferably of monofilament fibers. The mesh unit cell has a low bulk density, providing a large surface area and void volume. The top and bottom plates, as well as the supports, can have different dimensions, angles, and lengths, and can be rigid, stiff, flexible, elastic, or spring-like, and can be made of oriented or non-oriented polymers. The mesh unit cell can be formed into any suitable shape. In one embodiment, the mesh unit cell has a polyhedral shape, including elongated polyhedral shapes. In a preferred embodiment, the mesh unit cell has six faces. In a particularly preferred embodiment, the mesh unit cell is a cuboid. The interior of the mesh unit cell can be hollow, or it can contain additional fibers. For example, the mesh unit cell can contain additional fibers that join the top and bottom plates. The mesh unit cell can also contain additional fibers located between the top and bottom plates to increase the surface area of ​​the unit cell. The latter may result in an increased binding capacity of the unit cell, such as an increased ability to bind fats.

[0155] In a preferred embodiment, the reticular cells are compressible; in an even more preferred embodiment, the reticular cells are compressible and recover after being compressed. Implants having a grid formed by compressible reticular cells are particularly suitable for the breast because the grid thus formed is compressible and can be designed to mimic the properties of breast tissue.

[0156] The length of the struts or fibers of the mesh 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 needles with an outer diameter of 0.5 to 3 mm to be inserted into the grid made of the unit cell.

[0157] The diameter of the fibers used to prepare the reticular unit cells is preferably 20 μm to 2 mm, more preferably 50 μm to 1 mm, and even more preferably 80 μm to 500 μm or 100 μm to 250 μm.

[0158] In some embodiments, the implant is formed of fibrous reticular cells, and the breaking load of the fibers is 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 of fibrous reticular cells, and the breaking elongation of the fibers is 22% to 1,000%, more preferably 100% to 700%. In some embodiments, the implant is formed of fibrous reticular cells, and the elastic modulus of the fibers is 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 reticular cells preferably have one or more of the following characteristics: (i) a breaking load of 0.1 to 200 N; (ii) a breaking elongation of 22% to 1,000%; and (iii) an elastic modulus of 0.05 to 10 GPa.

[0159] In some embodiments, the implant formed from fibrous reticular cells 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 fibers of the reticular cells have one or more of the following characteristics: (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) a breaking elongation of 22% to 1,000%, more preferably 100% to 700%; and (iv) an elastic modulus of 0.05 to 10 GPa, more preferably 0.1 to 3 GPa, even more preferably 0.2 to 0.8 GPa.

[0160] In some embodiments, the implant is a breast implant formed of reticular 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 reticular cells have one or more of the following characteristics: (i) a diameter of 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 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 of 22% to 1,000%, more preferably from 100% to 700%; and (iv) an elastic modulus of 0.05 to 10 GPa, more preferably from 0.1 to 3 GPa, even more preferably from 0.2 to 0.8 GPa.

[0161] iv. Foam unit

[0162] In another embodiment, the unit cell is formed of foam, preferably compressible foam. The foam unit cell preferably contains interconnected pores. The pores can be of uniform size (i.e., each pore has an equal size) or of different sizes. The foam unit cell has a low bulk density, providing 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 elongated polyhedral shapes. In a preferred embodiment, the foam unit cell has six faces. In a particularly preferred embodiment, the foam unit cell is a cuboid.

[0163] In one implementation, the foam unit cell also includes male anchors and female anchors. The anchors allow multiple units to join together to form a grid of implants.

[0164] Reference Figure 16C A cross-sectional view showing the pores 330 in the foam 340 of a compressible foam unit cell 300 having a convex anchor 310 and a concave anchor 320. The foam 340 is preferably formed of a polymer, more preferably an absorbable polymer.

[0165] Figure 16A , 16B Figures 16C and 16C illustrate a method for forming foam units according to an embodiment of the invention. Specifically, Figure 16A A mold cavity 336 filled with leaching pore-forming agent beads 340 is shown. Optionally, the mold cavity may be characterized by a concave anchor portion 344 and a convex anchor portion 346, which are further described herein.

[0166] Reference Figure 16B This process involves coating beads 340 with a polymer solution 350 in a volatile solvent. The solvent is then evaporated, leaving behind pore-forming beads trapped within the polymer. For example... Figure 16C As shown, by leaching pore-forming agent beads trapped in the polymer, an array of pores 330 is left in foam 354, thereby forming an open foam unit cell 300. Optionally, as described herein, convex anchors 310 and concave anchors 320 are created to assemble the foam unit cells together.

[0167] Implants with a grid formed from compressible foam units are particularly suitable for the breast because the grid formed in this way is compressible and can be designed to mimic the properties of breast tissue.

[0168] C. Construction of the implant

[0169] Various methods can be used to manufacture implants. The implant comprises a grid formed by two or more single cells, but more preferably by multiple single cells or a large number of single cells. The single cells are repeated within the volume of the grid. In some embodiments, the grid of the implant is capable of providing one or more of the following: (i) structural support, (ii) a scaffold for tissue inward growth, (iii) a scaffold for delivering cells, tissues, collagen, hyaluronic acid, and bioactive agents (including fat, liposuction, adipocytes, fibroblasts, and stem cells), (iv) a structure that can provide mechanical spacing, (v) a structure that allows grafts to be incorporated into the grid structure, such as a vascular pedicle, and (vi) the ability to coat cells, tissues, collagen, hyaluronic acid, and bioactive agents onto the inside of the grid using a needle injection. The structure of the agent (including fat, fat aspirate, adipocytes, fibroblasts and stem cells), (vii) has properties similar to or the same as soft tissue (meaning within ±50% of the property value), (viii) has an elastic modulus within ±50% of the elastic modulus value of breast tissue, more preferably within ±25%, (viii) has a structure with high strength relative to its bulk density, (ix) has a compression design or spring design (meaning the grid can deform under force and return to its original shape when the force is removed), and (x) has an anisotropic mechanical property.

[0170] In one embodiment, the implant is formed by fabricating a grid of unit cells, wherein the unit cells are coils and springs. In another embodiment, the implant is formed by fabricating a grid of unit cells, wherein the unit cells are skeletal polyhedra having edges and vertices formed by struts or fibers and having a hollow or porous interior. Preferably, the skeletal polyhedral unit cells meet adjacent skeletal polyhedral unit cells at their corners to form a grid. In yet another embodiment, the implant is formed by fabricating a grid of mesh unit cells, wherein the mesh unit cells contain a mesh on two opposite faces of the unit cell, and the mesh is joined by struts or fibers. In yet another embodiment, the implant is formed by fabricating a grid of foam unit cells.

[0171] In a preferred embodiment, the implant's grid is formed of unit cells, wherein the unit cells are formed of polymer. The unit cells can be polymer coils and springs, skeletal polyhedra where the edges and vertices of the skeletal polyhedra are formed of polymer struts or fibers, or the unit cells can be polymer meshes connected by polymer fibers, or the unit cells can be polymer foams.

[0172] In a preferred embodiment, the implant is formed from a grid of single cells, wherein the single cells have a low volumetric density providing an open network through the grid, and such that when a single cell is placed at the center of the grid, it is surrounded by other single cells. For example, if all the single cells of the grid have a dodecahedral shape with 12 faces, each face of the dodecahedron will connect to 12 adjacent single cells. Connecting single cells in this way creates a grid network in which a continuous path through the grid exists, promoting and allowing tissue to grow inward 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 single cells forming the grid will depend in part on the desired grid volume and the unit volume of the single cell. For example, a grid with a volume of 1 cm 3 The volume of the same unit cell was 500 cm³. 3 The grid will contain up to 500 individual cells.

[0173] The grating of the implant can be defined by its bulk density. In a preferred embodiment, the bulk density of the implant grating, i.e., the ratio of the volume of material used to manufacture the grating to the volume of voids in the grating, is 1% to 50%. In a more preferred embodiment, the bulk density of the grating is 1% to 25%, and in an even more preferred embodiment, the bulk density of the grating is 1% to 17%. For clarity only, a grating with a bulk density of 25% has 25% material and 75% void space by volume. The bulk density of the grating refers to the bulk density before the addition of cells or other substances. gratings with low bulk density (e.g., less than 50%) are preferred because they provide large void spaces that can be occupied by, for example, cells, tissues, collagen, and bioactive agents (including fat, liposuction, 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, tissues, collagen, and bioactive agents, including fat, liposuction, adipocytes, fibroblasts, and stem cells.

[0174] The struts, fibers, coils, and springs of a unit cell can be manufactured by any suitable method. A preferred method for manufacturing unit cells is 3D printing. 3D printing is a computer-controlled program that uses additive manufacturing methods to create three-dimensional objects from 3D CAD (Computer-Aided Design) models. Objects can be manufactured by depositing, bonding, or solidifying materials (typically plastics or metals). 3D printing can be used to manufacture unit cells and also to manufacture lattice structures. The latter method is particularly preferred when the lattice of an implant comprises unit cells that are skeletal polyhedra, but it can also be used to manufacture unit cells containing coils or springs. Suitable 3D printing techniques include selective laser melting (SLM), melt extrusion deposition (MED), fused pellet deposition (FPD), filament fabrication, printing with slurries and solutions using a coagulation bath, and printing with binder solutions 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 the following: 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 unit cells and / or lattice of the implant are formed by 3D printing one or more of the following: poly-4-hydroxybutyrate and copolymers, and poly(butylene succinate) or copolymers, optionally wherein these polymers and copolymers have been cross-linked.

[0175] A particularly preferred method for 3D printing unit cells is selective laser melting (SLM). Figure 6 This is an example of a coiled cylindrical unit cell 400 fabricated by SLM. The coiled unit cell has three helical struts supporting a top and bottom ring, with a total height of 7.5 mm, and the helical struts are angled at 120 degrees to each other at a constant spacing of 0.75 cm. The outer and inner diameters of the top and bottom rings are 10 mm and 8 mm, respectively, and the rings have a 2 mm circular cross-section. The 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 solvent.

[0176] 3D printing can also be used to form, for example Figure 5 The example shown is a coiled cylindrical unit cell with built-in fasteners. After printing, the coiled cylindrical unit cell containing fasteners 66, 68 (as shown in the example) can be connected by the male and female connectors on the top and bottom rings of the unit cell. Figure 5 As shown, they are assembled together to form as Figure 7The illustrated implant has a grating structure 410. In a preferred embodiment, coiled cylindrical units including fasteners are assembled into a grating, wherein the grating is compressible and returns to its original shape after being compressed. In an even more preferred embodiment, coiled cylindrical units including fasteners are assembled into a grating of a breast implant, wherein the grating is compressible and optionally returns to its original shape after being compressed.

[0177] 3D printing can also be used to directly form the lattice structure of implants without assembling the lattice from individual cells. Figure 8 It is achieved by 3D printing multiple coiled cylindrical unit cells 440 (similar to...) Figure 4 The image shows a lattice structure 430 of the implant formed from individual cells, wherein the cells are connected to each other during the printing of the lattice. In a preferred embodiment, the lattice thus formed is compressible and returns to 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 returns to its original shape after being compressed.

[0178] In other preferred embodiments, the lattice with skeletal polyhedral unit cells can be directly formed by 3D printing. An example of a 3D-printed implant lattice 10 made from skeletal polyhedral unit cells is shown in... Figure 1 As shown in the figure. In a preferred embodiment, such as 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 a 3D-printed skeletal polyhedron lattice, 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 skeletal polyhedral unit cells, wherein the shape of the unit cell is: tetrahedron, cuboid, pentahedron, hexahedron, heptahedron, octahedron, icosahedron, decahedron, dodecahedron, tetradecahedron, and their prisms, inverse prisms, and truncated polyhedra. In a preferred embodiment, these skeletal unit cells have 4, 6, 8, 12, or 20 faces. In another embodiment, these skeletal unit cells are formed from elongated polyhedra. In a particularly preferred embodiment, the skeletal unit cells of the 3D-printed implant (including breast, nipple, facial, or buttock implants) are dodecahedrons, even more preferably rhombic dodecahedrons. In other implementations, the lattice can be 3D printed from two or more different types of skeletal unit cells. For example, the lattice can be printed from a combination of dodecahedral and octagonal shapes.

[0179] In other embodiments, the grid unit cells can be prepared by injection molding. For example, they can be prepared by injection molding respectively in... Figure 4 and Figure 5 The cells 40 and 60 are shown in the figure, and the cells are assembled to form a grid. Figure 4 The injection-molded unit cells 40 of the type shown can be used, for example, to fuse the unit cells together using heat, pressure and / or solvents to form a grid. Figure 5 The injection-molded unit 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 unit cells are formed as a compressible grid that optionally returns to its original shape after compression. In a particularly preferred embodiment, the injection-molded unit cells are formed as a grid for compressible breast, nipple, facial, and buttock implants. Preferably, these grids return to their shape after compression.

[0180] Reticulated units can be prepared by fabricating two nets and connecting them with supports or fibers to form a unit cell. In a preferred embodiment, the reticulated unit cell is prepared using a double needle bed knitter. (See reference...) Figures 12 to 15 The top plate 110 of the mesh unit cell 100 can be knitted on the front bed of a double-needle bed knitting machine, and the bottom plate 120 of the mesh unit 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 and back beds to form the mesh unit cell. Preferably, the mesh in the mesh unit cell is warp knit and can be prepared using a double-needle bed knitting machine. In a particularly preferred embodiment, the mesh unit cell comprises a warp knit mesh interwoven with monofilament fibers to form the mesh unit cell on opposite sides of the cell. In a particularly preferred embodiment, the mesh unit cell comprises a warp knit mesh interwoven with monofilament fibers and is compressible.

[0181] In a preferred embodiment, the reticular unit cell is prepared from fibers (preferably monofilament fibers) with 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 reticular units using these polymer compositions can be used as breast implants.

[0182] Any suitable method can be used to assemble the reticular cells into an implant. For example, the reticular cells can be fused to form a grid of implants, for example, by applying heat, pressure, and / or solvents. More preferably, fibers can be used to connect the reticular cells together. In one embodiment, fibers can be used to suture the reticular cells together.

[0183] In one embodiment, the unit cells are made of foam and the foam unit cells can be assembled into an implant. For example, the foam unit cells can be fused to form a grid of implants, for example, by applying heat, pressure, and / or solvent. More preferably, a grid of implants containing foam unit cells can be formed by connecting convex and concave anchors together.

[0184] D. Physical properties of the implant's lattice

[0185] In one embodiment, the mechanical properties of the grating are designed to approximate those of tissue. In one embodiment, the elastic modulus of the implant grating is from 0.01 kPa to 290 MPa, more preferably from 0.1 kPa to 10 MPa, and even more preferably from 0.1 kPa to 1 MPa or from 0.1 kPa to 100 kPa. In a particularly preferred embodiment, the implant is a breast implant, and the elastic modulus of the breast implant grating is from 0.01 kPa to 1 MPa, more preferably from 0.01 kPa to 100 kPa. In another embodiment, the implant is a breast implant, and the elastic modulus of the breast implant grating is ±50% of the elastic modulus of breast tissue. In other embodiments, the elastic modulus of the implant grating is ±50%, more preferably ±25%, of the elastic modulus of glandular tissue, adipose tissue, skin, pectoral fascia, or breast tissue. For reference, the elastic moduli of glandular tissue, adipose tissue, skin, pectoral fascia, and breast tissue have been 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 grid of the breast implant comprising skeletal polyhedral cells, spiral or coiled cells, or mesh cells is 0.167 kPa ± 50% to 66 kPa ± 50%.

[0186] Figure 10A An example of a breast implant 500 with a spring design is shown, which provides the implant with a compressive modulus similar to that of breast tissue. The implant 500 includes segments 502 that define gaps 504 between adjacent segments. Figure 10B The image shows a cross-section of a breast implant. In this example, the implant's grid is made of stacked rhomboid unit cells 510. The implant has a large surface area that can be coated with, for example, autologous fat, cells, collagen, or bioactive agents.

[0187] Figure 11The image shows an alternative embodiment of a breast implant 530 designed to have an elastic modulus similar to that of breast tissue.

[0188] 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 different second elastic modulus in a second direction. The grating of the breast implant can have different properties in the vertical direction of the breast compared to its properties in the lateral-to-medial 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 that first direction.

[0189] To allow tissue to grow inward into the lattice of the implant, the lattice should have a sufficient strength retention rate to allow cells and blood vessels to invade and proliferate within the implant. In some embodiments, the strength retention rate of the implant lattice is 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 lattice of the implant is designed to support mechanical forces acting on the implant and allow these forces to transition smoothly from the lattice to the regenerating host tissue. In particular, the lattice of a breast implant is designed to support mechanical forces acting on the breast implant and allow these forces to transition smoothly from the lattice to the new host tissue.

[0190] E. Other characteristics of the implant

[0191] Implants or their gratings can be trimmed or cut using scissors, blades, other sharp cutting tools, or hot knives to provide the desired implant or grating shape. Laser cutting technology can also be used to cut implants or gratings into the desired shape. This can be particularly advantageous in shaping fiber-based, mesh-based, and strut-based implants because the technology is versatile and, importantly, it can provide shaped implants and gratings without sharp edges.

[0192] In some embodiments, the implant may also include pillars to reinforce the implant or facilitate implantation. Pillars can, for example, help reshape the implant after implantation. Preferably, the pillars are incorporated into a grid structure to reinforce or facilitate implantation. The pillars can be incorporated into the implant by any suitable method, including fusion, molding, weaving, knitting, or printing. In a preferred embodiment, the pillars are incorporated by fusing absorbable polymer fibers or struts into the grid of the implant. In some embodiments, the diameter or width of the pillars can be 0.1 to 5 mm, more preferably 0.5 to 3 mm. The absorbable polymer fibers or struts can be oriented or unoriented, but are preferably unoriented, and more preferably unoriented poly(4-hydroxybutyrate) fibers or struts. In another embodiment, flexible pillars can be printed directly onto the grid of the implant, or incorporated into the grid during the printing of the grid.

[0193] Implants may include retainers, such as barbs or staples, that allow the implant to be anchored in the body without the use of sutures. The retainer is preferably included in the outer periphery of the implant or in the lattice structure of the implant. When the implant is a breast implant, the retainer is preferably located on the implant to allow anchorage to the chest wall.

[0194] The implant may include suture pieces, allowing it to be anchored in the body using, for example, sutures and / or U-shaped staples. The number of pieces can vary. In one embodiment, the number of pieces will depend on the load applied to the implant. A larger number of pieces may be required when the implant is heavier or larger. In some embodiments, the implant contains 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more pieces, but preferably 4 to 12. When the implant is a breast implant, it preferably contains 4 or more pieces, preferably 4 to 12 pieces, to anchor the breast implant to the chest wall. The size of the pieces is preferably from 0.5 cm × 0.5 cm to 5 cm × 4 cm, preferably 2 cm × 2.5 cm. The patch attached to the implant must have sufficient strength retention in vivo to resist mechanical loads and allow sufficient inward tissue growth into the implant to prevent subsequent displacement of the implant after implantation. In a preferred embodiment, the suture pull-out strength of the patch attached to the implant is greater than 10 N, more preferably greater than 20 N.

[0195] F. Implant coating and filling

[0196] In some embodiments, the implant is manufactured with a coating and / or some or all of the grating serving 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, allogeneic grafts, 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, aspirated fat, or injectable fat is coated onto the implant and inserted into the void spaces of the implant. In another preferred embodiment, a vascular pedicle can be inserted into the void spaces of the implant. In yet another preferred embodiment, the implant may be coated with or partially or completely filled with one or more bioactive agents. Particularly preferred bioactive agents that can be coated onto or used to partially or completely fill the implant include collagen and hyaluronic acid. In other embodiments, the implant may be coated with one or more antibiotics.

[0197] Any suitable method can be used to coat the implant and fill its voids 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 or partially or completely filled with cells, tissues, bioactive agents, and 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 for injecting cells, tissues, fat, fat aspirate, bioactive agents, collagen, hyaluronic acid, and other additives is 0.5 mm to 5 mm.

[0198] IV. Methods for implanting implants

[0199] In some embodiments, the implant is inserted into the body. Preferably, the implant is inserted into a site of reconstruction, remodeling, repair, and / or regeneration. In a preferred embodiment, connective tissue and / or the vascular system will invade the lattice of the implant after implantation. In a particularly preferred embodiment, the implant comprises absorbable material, and connective tissue and / or the vascular system will also invade spaces where the absorbable material has degraded. The cells of the lattice may be colonized before or more preferably after implantation, and the pores of the lattice may be invaded by tissue, blood vessels, or a combination thereof.

[0200] The implant may be coated or filled with transplanted cells, stem cells, fibroblasts, adipocytes, and / or tissues 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 grating of the implant. The implant may also be coated or filled with platelets, extracellular lipid matrix proteins, gels, hydrogels, and bioactive agents before implantation. In one embodiment, the implant may be coated with antibiotics before implantation, for example, by immersing the implant in an antibiotic solution.

[0201] Implants can be used to deliver autologous cells and tissues to specific locations in a patient, such as the breast, nipple, face, and buttocks. Preferred autologous tissues include one or more of the following: autologous fat, liposuction, injectable fat, adipocytes, fibroblasts, and stem cells.

[0202] The implant can be used to fill and deliver fat into a patient. In a particularly preferred embodiment, autologous fat 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. Autologous fat tissue is preferably prepared by liposuction at a donor site on the patient's body. After centrifugation, the lipid phase containing fat cells is separated from the blood components and is incorporated into the implant before implantation or injected or otherwise inserted into the implant after implantation. In one embodiment, the implant is injected with or filled with 1% to 50% of the total volume of the grid, more preferably 1% to 20% of the total volume of the grid.

[0203] In another embodiment, before adding the aspirated fat to the implant, the aspirated fat tissue taken from the patient can be mixed with a biological or synthetic scaffold matrix (e.g., very small fibers or particles). In this embodiment, the added matrix is ​​used to hold or bind fat microspheres and disperse and retain them within the lattice of the implant. In some embodiments, the use of the added matrix may help prevent fat accumulation that can lead to necrosis and / or help enhance angiogenesis in the implant.

[0204] In another implementation, a vascular pedicle or other tissue block is harvested from the patient and inserted into the implant. The pedicle or other tissue block can be inserted into the implant before implantation, and then the implant with the pedicle or other tissue block can be implanted into the patient, or the pedicle or other tissue block can be inserted into the implant after the implant has been implanted into the patient.

[0205] In a preferred embodiment, the implant is placed in the patient's breast. In another embodiment, the implant is placed and secured in both breasts. In some embodiments, the implant is placed in the patient during breast fixation and augmentation procedures, including corrective procedures. In a particularly preferred embodiment, the implant is placed in patients who have undergone: (i) mastectomy, (ii) breast lift with a need for enlargement, (iii) breast reduction with a need for support, lift, or reshaping of the reduced breast, or (iv) have previously undergone silicone or saline breast implant surgery and wish to remove the silicone or saline implant and subsequently undergo breast reconstruction that will provide a fuller or larger breast. Implants can also be placed in patients who have undergone breast surgery to enlarge the projection of the breast away from the chest, and optionally, additional fat graft volume can be added to the implant after placement to further increase the projection. Additional fat graft volume can be added to the implant immediately after placement, but can also be added at subsequent examinations. For example, additional fat graft volume can be added to the implant at one or more times, days, weeks, or months after placement. The procedures described in this article can also be performed by removing breast tissue, excising and redistributing breast tissue.

[0206] In one embodiment, a method of implanting an implant into the breast includes 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 tumulus; (iii) positioning the implant on the tumulus of the breast; (iv) securing the implant to the tissue surrounding the tumulus of the breast; and (v) closing the incision in the breast. Preferably, the method further includes one or more of the following steps: (a) preparing a liposuction sample and coating or filling the implant with the sample before implantation; (b) preparing a liposuction sample and, preferably, coating or filling the implant with the sample after implantation by injecting the sample into the implant; (c) inserting a vascular pedicle into the implant before or after implantation; and (d) suturing or stapling the implant in place. In a preferred embodiment, the implant is implanted in a subglandular, subthoracic, or anterior chest location. In some embodiments, the implant is sutured to the tissue surrounding the tumulus, and even more preferably to the fascia surrounding the pectoral muscles beneath the tumulus. In another embodiment, the implant comprises a sheet, and the sheet is sutured to the tissue surrounding the mons lumps.

[0207] Implants can also be coated or filled with cells and tissues other than fat grafts before or after implantation, as well as with cytokines, platelets, and extracellular lipid 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 genetically modified stem cells containing genes used to treat a patient's disease.

[0208] In some embodiments, the implant is placed inside the body. Preferably, the implant is placed in a site of reconstruction, remodeling, repair, and / or regeneration. In a preferred embodiment, connective tissue and / or the vascular system will invade the lattice of the implant after implantation.

[0209] In one embodiment, the implant has the property of allowing it to be delivered via a small incision in a minimally invasive manner. The implant may, for example, be designed so that it can be rolled up or folded to allow delivery via a small incision. This minimally invasive approach can reduce patient morbidity, scarring, and the chance of infection. In an even more preferred embodiment, the implant has a three-dimensional shape and shape memory properties that allow it to recover its original three-dimensional shape unassistedly after delivery via the incision and into an appropriately sized anatomical tissue plane. For example, the implant can be temporarily deformed by rolling it into a small-diameter cylindrical shape, delivered using an inserter, and then allowed to recover its original three-dimensional shape unassistedly in vivo.

[0210] Example

[0211] The invention will be further understood by referring to the following non-limiting embodiments.

[0212] Example 1: Implant with a porous grid of interconnected skeletal polyhedral unit cells formed by SLS printing

[0213] As described in this article, the preparation... Figure 1The implant shown. P4HB granules (Tepha, Inc., Mw 480 kDa) were cryogenically milled and then continuously sieved to produce P4HB powder with a particle size of 40 to 60 micrometers. The P4HB powder was made from P4HB granules with an average size of 2 mm × 2 mm × 3 mm, cooled to -70°C and injected in a cryogenic mill with a high-speed cross-collision path. The resulting powder was sieved using a 60-micrometer shaker followed by a 40-micrometer shaker to remove particles larger than 60 micrometers and smaller than 40 micrometers. The sieved P4HB powder (40 to 60 micrometer particles) was then dried, rinsed with nitrogen, and packaged in foil. The moisture content of the P4HB powder was less than 650 ppm. The P4HB powder was loaded into the powder bed of a 3D selective laser sintering (SLS) printer. The powder layer thickness was set to 100 micrometers, the laser power to 0.3 watts, and the laser beam speed to 20 cm / s. Under these conditions, the energy used per unit area was 1 J / cm². 2 The 3D printer loads an STL file to print. Figure 1 The implant shown has an open porous scaffold structure.

[0214] The resulting structure has a dome or crown shape with a base diameter of 12 cm and a protrusion of 5.5 cm (height from base to apex). The implant forms 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 in the scaffold unit is 1.5 mm, and the distance between nodes or intersections (i.e., the length (L) of the struts in the unit) is 10 mm. The implant has an elastic modulus of 16 kPa, shape memory, and is as follows: Figure 3 As shown, it can be compressed by gently pressing with your fingers.

[0215] The following content corresponds to the original claims in the parent application and is incorporated herein as part of the specification:

[0216] 1. A breast implant comprising a porous grid, wherein the grid further comprises connected unit cells, and wherein the unit cells are selected from the following structural types: (i) a skeletal polyhedron, wherein the edges and vertices of the skeletal polyhedron are formed of polymer struts or fibers, (ii) a coil or spring, wherein the coil or spring is formed of polymer struts or fibers, (iii) a top plate and a bottom plate connected by fibers, wherein the top plate and the bottom plate are formed of a knitted mesh, or (iv) foam.

[0217] 2. The implant of claim 1, wherein the unit cell is compressible.

[0218] 3. The implant of claim 1, wherein the length of the strut or fiber is 3 mm to 3 cm or 3 mm to 8 mm.

[0219] 4. The implant of claim 1, wherein each type of unit cell in the lattice is identical.

[0220] 5. The implant of claim 1, wherein the thickness or diameter of the strut or fiber is 50 μm to 5 mm.

[0221] 6. The implant of claim 1, wherein the porous grid comprises a plurality of holes, and the diameter of the holes in the grid is at least 0.5 mm.

[0222] 7. The implant of claim 1, wherein the elastic modulus of the grid is from 0.01 kPa to 1 MPa, such that the implant is compressible and can recover its shape after being compressed.

[0223] 8. The implant of claim 1, wherein the strut, fiber, coil or spring has one or more of the following properties: (i) a breaking load of 0.1 to 200 N, 1 to 100 N, or 2 to 50 N; (ii) an elongation at break of 22% to 1,000% or 100% to 700%; and (iii) an elastic modulus of 0.05 to 10 GPa, 0.1 to 3 GPa, or 0.2 to 0.8 GPa.

[0224] 9. The implant of claim 1, wherein the grid is reabsorbable.

[0225] 10. The implant of claim 1, wherein the polymer strut or fiber is made of a polymer or copolymer comprising one or more of the following monomers: 4-hydroxybutyric acid, 3-hydroxybutyric acid, glycolic acid, lactic acid, 1,4-dihydroxybutyric acid, hydroxybutyric acid, hydroxyethyl ... Alkyl ketone, trimethylene carbonate, ε-caprolactone, succinic acid, adipic acid, 1,4-butanediol and ethylene glycol, or containing poly-4-hydroxybutyrate or copolymers thereof, or poly(butylene succinate) or copolymers thereof, optionally wherein said polymer or copolymer has been crosslinked.

[0226] 11. The implant of claim 1, further comprising (i) one or more of the following: autologous fat, liposuction, injectable fat, adipocytes, fibroblasts, stem cells, gels, hydrogels, hyaluronic acid, collagen, antimicrobial agents, antibiotics, bioactive agents, and diagnostic devices; (ii) one or more anchors, fasteners, or pieces, said one or more anchors, fasteners, or pieces optionally securing said implant; or (iii) one or more openings for insertion into a vascular pedicle or other tissue block.

[0227] 12. The implant of claim 1, wherein the implant is manufactured by a process selected from: (i) forming the struts or fibers of the unit cell by injection molding of a polymer composition and assembling the unit cell to form the grid of the implant; (ii) forming the grid of the implant by 3D printing the struts or fibers of the unit cell; (iii) forming the unit cell of the grid by warp knitting of fibers and assembling the unit cell to form the grid of the implant; (iv) forming the unit cell by foaming and assembling the unit cell to form the grid of the implant; and (v) forming the grid of the implant by melt extrusion deposition printing.

[0228] 13. The implant of claim 1, wherein the porous grid has a dome shape.

[0229] 14. A method of manufacturing a breast implant, comprising forming a grid by one of the following: (i) forming a plurality of said unit cells by injection molding a polymer composition to form pillars or fibers of a unit cell, and assembling said unit cells to form a grid; (ii) forming a plurality of unit cells by warp knitting of fibers, and assembling said unit cells to form a grid; (iii) directly forming said grid from a polymer composition by 3D printing polymer pillars or fibers of said grid; (iv) forming a plurality of unit cells by foaming, and assembling said foam unit cells to form a grid; and (v) forming said grid by melt extrusion deposition printing.

[0230] 15. The method of claim 14, wherein the polymer composition is selected from polymers or copolymers comprising one or more of the following monomers: 4-hydroxybutyric acid, 3-hydroxybutyric acid, glycolic acid, lactic acid, 1,4-dihydroxybutyric acid, hydroxybutyric acid, hydroxyethyl ... Alkyl ketone, trimethylene carbonate, ε-caprolactone, succinic acid, adipic acid, 1,4-butanediol and ethylene glycol, or containing poly-4-hydroxybutyrate or copolymers thereof, or poly(butylene succinate) or copolymers thereof, optionally wherein said polymer composition has been crosslinked.

[0231] 16. The method of claim 14, wherein the support or fiber has one or more of the following properties: (i) a thickness or diameter of 50 μm to 5 mm, 150 μm to 2 mm, or 200 μm to 1.5 mm; (ii) a breaking load of 0.1 to 200 N, 1 to 100 N, or 2 to 50 N; (iii) an elongation at break of 22% to 1,000%, or 100% to 700%; and (iv) an elastic modulus of 0.05 to 10 GPa, 0.1 to 3 GPa, or 0.2 to 0.8 GPa.

[0232] 17. The method of claim 14, wherein the implant is formed in the process of incorporating one or more of the following into the grid: autologous fat, fat aspirate, injectable fat, adipocytes, fibroblasts, stem cells, gel, hydrogel, hyaluronic acid, collagen, antimicrobial agent, antibiotic, bioactive agent, and diagnostic device.

[0233] 18. The method of item 14, wherein the grid is formed by injection molding, warp knitting, 3D printing or foaming and has an elastic modulus of 0.01 kPa to 1 MPa.

[0234] 19. A method of implanting an implant according to claim 1 into a breast, comprising: (i) making at least one incision to access a patient’s breast tissue; (ii) separating the skin and subcutaneous fascia of the breast from the mammary bud; (iii) positioning the implant in the anterior chest, subglandular, or subchest region; (iv) securing the implant to nearby tissue; and (v) closing the incision in the breast.

[0235] 20. The method of claim 19, further comprising coating or injecting one or more of the following into the implant at one or more times before or after the implantation in the patient: autologous fat, liposuction, injectable fat, adipocytes, fibroblasts, stem cells, gels, hydrogels, hyaluronic acid, collagen, antimicrobial agents, antibiotics, and bioactive agents.

[0236] 21. The method of item 19, wherein the implant is fixed to the pectoral fascia.

Claims

1. A breast implant comprising a porous grid, wherein the grid further comprises connected unit cells, and wherein the unit cells comprise coils, springs, or helices, and the coils, springs, or helices are formed of polymer struts or fibers.

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

3. The implant of claim 1, wherein the length of the strut or fiber is 3 mm to 3 cm or 3 mm to 8 mm.

4. The implant of claim 1, wherein the thickness or diameter of the strut or fiber is 50 μm to 5 mm.

5. The implant of claim 1, wherein the porous grid comprises a plurality of holes, and the diameter of the holes in the grid is at least 0.5 mm.

6. The implant of claim 1, wherein the elastic modulus of the grid is from 0.01 kPa to 1 MPa, such that the implant is compressible and can recover its shape after being compressed.

7. The implant of claim 1, wherein the coil, spring or helix has one or more of the following characteristics: (i) a breaking load of 0.1 to 200 N, 1 to 100 N, or 2 to 50 N; (ii) an elongation at break of 22% to 1,000% or 100% to 700%; and (iii) an elastic modulus of 0.05 to 10 GPa, 0.1 to 3 GPa, or 0.2 to 0.8 GPa.

8. The implant of claim 1, wherein the grating is reabsorbable.

9. The implant of claim 1, wherein the polymer strut or fiber is made of a polymer or copolymer comprising one or more of the following monomers: 4-hydroxybutyric acid, 3-hydroxybutyric acid, glycolic acid, lactic acid, 1,4-dihydroxybutyric acid, hydroxybutyric acid, hydroxyethyl ... Alkyl ketone, trimethylene carbonate, ε-caprolactone, succinic acid, adipic acid, 1,4-butanediol and ethylene glycol, or containing poly-4-hydroxybutyrate or copolymers thereof, or poly(butylene succinate) or copolymers thereof, optionally wherein said polymer or copolymer has been crosslinked.

10. The implant of claim 1, further comprising (i) one or more of the following: autologous fat, fat aspirate, injectable fat, adipocytes, fibroblasts, stem cells, gel, hydrogel, hyaluronic acid, collagen, antimicrobial agent, antibiotic, bioactive agent, and diagnostic device; (ii) one or more anchors, fasteners, or pieces, said one or more anchors, fasteners, or pieces optionally securing said implant; or (iii) one or more openings for insertion into a vascular pedicle or other tissue block.

11. The implant of claim 1, wherein the porous grid has a dome shape.

12. The breast implant of claim 1, further comprising a plurality of fasteners connecting the unit cells together.

13. The breast implant of claim 1, wherein at least one of the coils, springs, or helices comprises an upper ring, a lower ring, and a helical support.

14. The breast implant of claim 13, further comprising a fastener attached to the upper ring, wherein the fastener is configured to attach the at least one coil, spring, or helix to another coil, spring, or helix.

15. The breast implant of claim 13, further comprising a second fastener attached to the lower ring.

16. The breast implant of claim 13, further comprising a fastener attached to the helical strut, wherein the fastener is configured to attach the at least one coil, spring, or helix to another coil, spring, or helix.

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