Implantable soft tissue repair prosthesis

Abstract

The present disclosure relates to an implantable soft tissue repair prosthesis. Implantable prostheses and related methods are generally described. In some embodiments, the prosthesis may be used for soft tissue reconstruction. The prosthesis may be formed from a three-dimensional load-bearing porous scaffold having interconnected networks of pores, thereby enabling tissue infiltration and allowing native tissue, blood vessels, and cells to colonize on the scaffold. In some embodiments, the scaffold may be formed from a biodegradable material such that it may degrade during the tissue infiltration process, leaving native tissue. In some embodiments, the stent may be formed from a triple periodic minimum surface, such as a helical tetracosahedron, to achieve high compressibility and high porosity. The compressibility of the implant may simulate the mechanical behavior of native tissue and allow the implant to be delivered through a small incision site (e.g., with an implant delivery funnel).

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 459,361, filed on Apr. 14, 2023, under 35 U.S.C.§119(e), the content of which is incorporated herein by reference in its entirety. Technical Field

[0003] The present disclosure relates to implantable prostheses, and more particularly, to prostheses for reconstructing and / or augmenting soft tissue, including the human breast. Background Art

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

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

[0006] The size, shape, and surface texture of breast implants vary. There are a variety of different sizes available, allowing surgeons and patients to choose from a range of protrusions, heights, widths, and overall volumes. In terms of shape, there are round and anatomically shaped implants, and the surface of the implant can be smooth, microtextured, or macrotextured. Generally, round implants have a smooth surface, while anatomically shaped implants have a concave microtextured or macrotextured surface. Summary of the Utility Model

[0007] In some embodiments, an implantable soft tissue repair prosthesis includes a flexible porous scaffold formed by at least one triply periodic minimal surface, wherein the flexible porous scaffold is configured to recover at least 75% of its original volume when compressed by 50% in at least one direction.

[0008] The packing density of the flexible porous scaffold is less than 20%.

[0009] The packing density of the flexible porous scaffold is between 3% and 10%.

[0010] The average pore size of at least a portion of the flexible porous scaffold is between 0.075 mm and 20 mm.

[0011] The average pore size is from 0.5 mm to 10 mm.

[0012] The average pore size is from 1 mm to 5 mm.

[0013] The implantable soft tissue repair prosthesis is configured to form a body that enlarges and / or reconstructs the anatomical shape of the human breast.

[0014] The flexible porous scaffold is a first flexible porous scaffold, wherein the implantable soft tissue repair prosthesis further includes a second flexible porous scaffold, and wherein the packing density of the first flexible porous scaffold is different from the packing density of the second flexible porous scaffold.

[0015] The second flexible porous scaffold is disposed in one or more intermediate layers that at least partially surround a core layer containing the first flexible porous scaffold. The implantable soft tissue repair prosthesis further includes a shell layer containing a third flexible porous scaffold that at least partially surrounds the one or more intermediate layers.

[0016] The packing density of the second flexible porous scaffold and the packing density of the third flexible porous scaffold are both greater than the packing density of the first flexible porous scaffold.

[0017] The third flexible porous scaffold is formed of subunits different from at least one of the second flexible porous scaffold and the first flexible porous scaffold.

[0018] The third flexible porous scaffold is formed in a mosaic pattern.

[0019] The flexible porous scaffold is configured to recover at least 90% of its original volume when compressed 50% in at least one direction.

[0020] The second flexible porous scaffold includes at least one selected from the group consisting of:

[0021] a) a shell,

[0022] b) a base,

[0023] c) a plurality of struts, and / or

[0024] d) one or more openings for inserting a vascular pedicle or other tissue mass.

[0025] The plurality of struts includes at least one curved strut.

[0026] The packing density of the first flexible porous scaffold is between 3% and 10%, and the packing density of the second flexible porous scaffold is between 5% and 10%.

[0027] The flexible porous scaffold is a first flexible porous scaffold, wherein the implantable soft tissue repair prosthesis further comprises a second flexible porous scaffold, and wherein the degradation profile of the first flexible porous scaffold is different from the degradation profile of the second flexible porous scaffold.

[0028] The implantable soft tissue repair prosthesis further comprises a transition portion located between the first flexible porous scaffold and the second flexible porous scaffold.

[0029] The compressive stiffness of the implant in at least one direction is between 10% and 20% of the compressive stiffness of the implant in a second direction.

[0030] The compressive stiffness of the implant in a first direction is greater than the compressive stiffness of the implant in a second direction.

[0031] The density of the implant is between 0.02 g / cm 3 and 0.2 g / cm 3 .

[0032] The flexible porous scaffold is formed of an absorbable polymer.

[0033] The flexible porous scaffold is formed of poly-4-hydroxybutyrate.

[0034] The triply periodic minimal surface is a spiral tetraicosahedron.

[0035] The flexible porous scaffold is at least partially coated with a bioactive agent.

[0036] In some embodiments, a method of implanting an implantable soft tissue prosthesis includes: compressing the implantable prosthesis by at least 50% in at least one direction, the implantable prosthesis including a flexible porous scaffold formed of at least one triply periodic minimal surface; delivering the implantable prosthesis to an implantation site; and restoring at least 90% of the compression in at least one direction.

[0037] It should be understood that the foregoing concepts and additional concepts discussed below can be arranged in any suitable combination, as the present disclosure is not limited in this regard. Further, other advantages and novel features of the present disclosure will become apparent from the following detailed description of various non-limiting embodiments when considered in conjunction with the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] The drawings are not intended to be drawn to scale. In the drawings, each identical or nearly identical component illustrated in various figures may be represented by the same reference numeral. For clarity purposes, not every component is labeled in every drawing. In the drawings:

[0039] Figures 1A to 1C are an isometric view, a side view, and a top view, respectively, of a subunit of a scaffold of an implantable prosthesis according to some embodiments;

[0040] Figures 2A to 2C An isometric view, a side view, and a top view, respectively, of a portion of a stent of an implantable prosthesis according to some embodiments;

[0041] Figure 3 Is a breast implant according to some embodiments;

[0042] Figures 4A to 4B Is a breast implant according to other embodiments;

[0043] Figures 5A to 5C Is a breast implant according to other embodiments, wherein the stent has different spatial frequencies;

[0044] Figures 6A to 6B A top view and a side view, respectively, of a breast implant according to one embodiment;

[0045] Figures 7A to 7B A top view and a side view, respectively, of a breast implant according to another embodiment; and

[0046] Figures 8A to 8B Are still a top view and a side view, respectively, of a breast implant according to another embodiment. Detailed Description

[0047] An increasing number of patients considering breast reconstruction and breast augmentation are reluctant to place permanent breast implants in their breasts. This is especially true for women who have had a mastectomy and are currently considering breast reconstruction. Some of these patients do not want to place a permanent foreign object in their breasts and do not want to risk the complications that may arise due to permanent breast implants. Complications include the following potential problems: capsular contracture, implant rupture or deflation, development of anaplastic large cell lymphoma (ALCL), infection, and displacement of the implant resulting in breast asymmetry. Many of these complications may require surgery to correct, which can be costly and undesirable in addition to the accumulation of scar tissue and delayed healing.

[0048] In addition to the above, conventional breast implants (e.g., silicone-based implants) are typically formed from a homogeneous material whose mechanical properties do not precisely mimic natural soft tissue, which may include vasculature and whose stiffness and compressibility vary due to muscle and fat distribution. In particular, the inventors have recognized that while conventional soft tissue implants are elastic, they generally do not exhibit sufficient natural compressibility to allow the implant to be compressed to a fraction of its original volume and recover to its original volume (or a fraction of its original volume), which is an inherent behavior of natural tissue. This lack of compressibility may also prevent the implant from being compressed during delivery, such that implantation may require a large incision. These incisions may increase the risk of infection, prolong the recovery time, and form large, undesirable scars on the patient.

[0049] In view of the foregoing, the inventors have recognized the benefits associated with implantable prostheses: implantable prostheses balance mechanical properties to support the surrounding anatomical structures with a high tissue infiltration rate, which can promote an appropriate balance of mechanical support and sensation. Accordingly, the inventors have recognized the benefits associated with implantable prostheses: implantable prostheses exhibit sufficient mechanical properties to support the native tissue at the implantation site and have sufficient void space to enable tissue ingrowth. In this way, the prosthesis can provide sufficient mechanical support to the implantation site while still enabling rapid tissue ingrowth. For example, in some embodiments, an implantable prosthesis, which may be referred to as an implant or a prosthesis, can achieve mechanical properties similar to natural tissue by using a load-bearing three-dimensional macroporous flexible scaffold. The flexible scaffold can be formed from one or more types of subunits arranged in a repeating manner. In some embodiments, the macroporous scaffold can include interconnected pores formed between the subunits. These pores can enhance the degradability of the scaffold by increasing the surface area while also increasing the rate of tissue ingrowth. The size and arrangement of the subunits, as well as their material composition, can determine the mechanical properties of the prosthesis. For example, subunits arranged in a more dense manner (e.g., in cases where the spatial frequency or repeat distance between adjacent subunits is smaller) may produce a greater stiffness relative to subunits arranged in a less dense manner. It should be understood that in some embodiments, subunits arranged in a more dense manner may also result in a greater volume of material being used in the prosthesis, which can increase the stiffness of the prosthesis, while a less dense arrangement of subunit scaffolds can produce a prosthesis with a lower stiffness. Thus, the properties of the subunits can be adjusted to optimize the tissue infiltration rate as well as the compressibility of the implant.

[0050] In some embodiments, the three-dimensional macroporous flexible scaffold of the present disclosure can be formed at least in part by subunits formed by undulating walls. The absence of corners and straight lines reduces stress concentration within the implant and allows for greater compressibility. In some embodiments, the undulating walls can have planar symmetric curves that mimic the behavior of natural soft tissue, although other symmetry characteristics are also contemplated. The subunits of the three-dimensional macroporous flexible scaffold can have a minimal surface structure that minimizes its surface area by exhibiting zero mean curvature. The minimal surface structure can specifically be a triply periodic minimal surface (TPMS). These minimal surfaces can result in a high surface area to volume ratio of the implant, which can enhance tissue ingrowth and implant degradation if the implant is formed of a degradable or bioabsorbable material. The high surface area to volume ratio can also increase the porosity of the implant while reducing the weight of the implant, which in turn can reduce the strain at the implant site in the patient. The TPMS of the present disclosure can also achieve tunable isotropic and / or anisotropic properties through the scaffold depending on the arrangement of the scaffold.

[0051] The TPMS subunits can be in the shape of a helicoid dodecahedron, which in some embodiments can be approximated by the following trigonometric relationships with respect to three basic directions:

[0052] sin(x)cos(y)+sin(y)cos(z)+sin(z)cos(x)=0

[0053] Other TPMS structures are also contemplated, such as catenoids, helicoids, ellipsoids, rhomboids, Bonnet family surfaces, Schwarz P surfaces, Schwarz D surfaces, mixtures thereof, and / or other TPMS structures. Such surfaces can reduce stress concentration to improve the overall compressibility of the implant while increasing porosity.

[0054] Depending on the shape, the stent of the implantable prosthesis is compressible in both its radial and axial directions. Additionally, in some embodiments, the implant may be isotropic or anisotropic in one or more mechanical properties. For example, in some embodiments, the implant may exhibit one or more mechanical properties in a first direction that may be within 10% to 20% of the mechanical properties in a second direction. Additionally or alternatively, in some embodiments, the implant may exhibit one or more mechanical properties in a first direction that may be only 2%, 5%, 10%, 20%, 30%, or 40% of the mechanical properties in a second direction. For example, in some embodiments, the compressive stiffness of the implant in the radial direction may be approximately 2%, 5%, 10%, 20%, 30%, or 40% of the compressive stiffness of the implant in the axial direction. Combinations of the foregoing are also contemplated. For example, in some embodiments, the radial compressive stiffness may be between about 2% and about 40% of the axial compressive stiffness or equal to about 2% and about 40% of the axial compressive stiffness, between about 5% and about 30% of the axial compressive stiffness or equal to about 5% and about 30% of the axial compressive stiffness, between about 10% and about 20% of the axial compressive stiffness or equal to about 10% and about 20% of the axial compressive stiffness, or between about 5% and about 20% of the axial compressive stiffness or equal to about 5% and about 20% of the axial compressive stiffness. Additionally, it will be understood that different mechanical properties may have different isotropy characteristics such that a first mechanical property may be isotropic (e.g., the first property in a first direction is within 10% or 20% of the first property in a second direction, or within 10% to 20% of the first property in a second direction), while a second mechanical property may be anisotropic (e.g., the second property in a first direction is 2%, 5%, 10%, 20%, 30%, 40% of the second property in a second direction, or between 2% and 40% of the second property in a second direction). Additionally, the implant may be non-dilatant (e.g., exhibit a positive Poisson's ratio) to better mimic natural tissue, but it should be understood that dilatant implants (e.g., exhibit a negative Poisson's ratio) are also contemplated.

[0055] In some embodiments, the macroporous implant may include more than one type of subunit. For example, a portion of the scaffold of the implant may include a spiral icosahedron, while another portion of the scaffold may include another minimal surface structure. It should be understood that alternative subunits may be used in combination with the TPMS subunits described above, including but not limited to closed cavities, partially closed cavities, repeating unit cells or reticulated unit cells, foam cells, Kelvin foam cells or other open or closed cell foam structures, cross-shaped structures, struts, nodules, channels (whether open, closed or partially closed), waveguides, triangular structures, tetrahedrons or other pyramid shapes, cubes, octahedrons, octagonal prisms, icosahedrons, rhombic triacontahedrons or other polyhedral shapes or modules (including Kelvin minimal surface decahedrons, prisms or other polyhedral shapes), pentagons, hexagons, octagons and other polygonal structures or prisms, polygonal meshes or other three-dimensional structures, honeycomb structures, tessellation structures such as Voronoi structures or other structures (which may include a pattern of shapes formed without overlap or gaps between the shapes), and / or other suitable structures. The three-dimensional implant may include a combination of the aforementioned three-dimensional subunit structures in an interconnected network.

[0056] In some embodiments, the flexible scaffold of the implantable prosthesis may have a structure that provides a large surface area and voids, which is suitable for allowing the scaffold to be colonized by cells and infiltrated by tissue, blood vessels, or a combination thereof after implantation. Thus, the implantable prosthesis of the present disclosure is characterized by a packing density, which is defined as the ratio of the volume occupied by the implant material in the scaffold to the total volume of the implant, expressed as a percentage. The packing density can be designed to balance tissue infiltration, which can be maximized by reducing the packing density, and have sufficient compressive strength to support the surrounding tissue at the implantation site.

[0057] The inventors have also recognized that the weight of conventional permanent implants can range between 150 cc and 1200 cc, more commonly between 300 cc and 800 cc, that conventional permanent implants are generally heavier than natural breast tissue of equivalent size, and can thus impose excessive strain on a patient's anatomy, such as the chest wall. Such strain can cause patient discomfort and pain and, in some cases, can result in an undesirable drooping or sagging of the implant. In view of the foregoing, the inventors have recognized the benefits associated with lightweight soft tissue implants, which can reduce the risk of patient discomfort and improve aesthetic outcomes. As previously described, the implants of the present disclosure can exhibit a porosity characterized by a packing density. In some embodiments, at the time of implantation, the weight of the implants of the present disclosure can be about 80% to 97% of the weight of a conventional silicone implant. In some embodiments, the packing density can also determine the total weight of the implant at the time of implantation. It should be understood that the porous scaffolds of the present disclosure can generally be lighter than conventional silicone implants, which can reduce the load on nearby tissues. In some embodiments, the weight of the implant can be less than 10 grams, although other weights can also be contemplated as the weight of the implant can depend on a variety of parameters, including the desired application, material composition, geometry, and packing density, among others.

[0058] It should be understood that, compared to conventional permanent implants, the total weight of the implant can change over time due to material degradation. The gradual change in implant weight can allow for cell infiltration, maturation, and aggregation (e.g., tissue formation). After a longer period of time following implantation, the weight of the mound can be comparable to that of natural breast tissue and, in some embodiments, can be less than the weight of a permanent (e.g., silicone-formed) implant of equivalent size.

[0059] In some embodiments, the filling density of an implantable prosthesis according to any of the embodiments disclosed herein can be less than or equal to about 60% to induce tissue infiltration while still exhibiting desired mechanical properties. In some embodiments, the implantable prosthesis of the present disclosure can have a filling density greater than or equal to about 1%, 2%, 4%, 5%, 6%, 8%, 9%, 10%, 12%, 15%, 20%, 30%, 40%, 50%, combinations thereof, and / or any other suitable filling density. The implantable prosthesis can also have a filling density less than or equal to about 60%, 50%, 40%, 30%, 20%, 15%, 12%, 10%, 9%, 8%, 6%, 5%, 4%, 2%, 1%, combinations thereof, and / or any other suitable filling density. Combinations of the foregoing are contemplated, including but not limited to filling densities between about 1% and 60%, between about 3% and 15%, and between about 3% and 10%. In some embodiments, the filling density can be between about 4% and 8%. It should be understood that the filling density of the implant can depend on the geometry of the subunits employed, the overall size of the implant, the manufacturing method, the implant site requirements, and / or any other suitable parameters. Thus, the implant of the present disclosure can have any suitable filling density.

[0060] In some embodiments, the size of the pores of the implant scaffold can be large enough to allow a needle to be inserted into the pores of the scaffold for delivering bioactive agents, cells, adipocytes, and / or other suitable compositions by injection. In some embodiments, the architecture of the scaffold is designed to allow needles sized 12 to 21 to be inserted into the scaffold to allow the delivery or loading of cells, tissues, collagen, bioactive agents, and additives, including adipocytes, using a syringe without significantly damaging the scaffold and / or the delivery materials delivered into the scaffold. In some embodiments, the scaffold can allow the insertion of needles with an outer diameter between 0.5 mm and 3 mm or equal to 0.5 mm and 3 mm. Of course, depending on the specific needs of the patient, the scaffold can be designed to accommodate larger and smaller gauge needles, as the present disclosure is not limited thereto.

[0061] The characteristics of the scaffold of the implantable prosthesis can also lie in the weight per unit volume, which is determined by the density of the constituent materials of the subunits, the size of the prosthesis, the filling density, and the number / size of the subunits, as well as many other parameters. In some embodiments, the weight per unit volume of the scaffold can be between about 0.01 g / cm 3 and 0.2 g / cm 3 , between about 0.02 g / cm 3 and 0.2 g / cm 3 , between about 0.03 g / cm 3 and 0.05 g / cm 3between, about 0.01 g / cm 3 and 0.5 g / cm 3 therebetween, combinations thereof, and / or any other suitable unit volume weight. Of course, unit volume weights less than and greater than those described above can be envisioned, as the present disclosure is not limited thereto.

[0062] A high surface area can increase the available volume for tissue infiltration throughout the scaffold. A high surface area can also increase the volume of therapeutic compounds that can be delivered with the implant (e.g., coated on the implant, as will be described in detail below). Thus, in some embodiments, the scaffolds disclosed herein may also be characterized by a suitably high surface area. In some embodiments, the surface area of the scaffold of the implant can be greater than or equal to about 500 cm 2 , 1000 cm 2 , 5000 cm 2 , 1 m 2 , 2 m 2 and / or any other suitable surface area. The surface area of the scaffold can also be less than or equal to about 2 m 2 , 1 m 2 , 5000 cm 2 and / or any other suitable surface area to ensure that there is sufficient material to support the surrounding tissue. Combinations of the foregoing are envisioned, including, for example, areas between 500 cm 2 and 2 m 2 or equal to 500 cm 2 and 2 m 2 although other suitable areas can also be used.

[0063] In some embodiments, the implant can be compressible, and thus it can be delivered to the implant site through a delivery device, such as a Keller funnel. In some embodiments, the implant can be delivered into the breast through a funnel having a neck diameter (i.e., the narrowest part of the funnel) of about 2.5 cm to 7.5 cm, and more preferably 3.75 cm to 6.25 cm. In some embodiments, the implant can be delivered through a funnel having a neck diameter of 2.5 cm to 7.5 cm and recover to a percentage of the original volume of the implant after being delivered through the neck of the funnel to the implant site. In some embodiments, the implant can have anisotropic compression stiffness to facilitate delivery of the implant through the delivery device and / or incision. For example, as described above, the compression stiffness of the implant in the radial direction is less than the compression stiffness in the axial direction, such that the base of the implant can be compressed when passing through the neck diameter and / or incision. However, it will be understood that isotropic embodiments can also be suitable for delivery through a funnel.

[0064] In view of the above, the implant can thus have a compressive modulus to enable it to be delivered through an incision smaller than the original size of the implant to the implantation site, thereby reducing the amount of scarring at the implantation site to achieve faster recovery and better aesthetics. The compressive modulus can also allow the implant to be compressed when a compressive force is applied and to recover from the compression when the compressive force is removed. The implant can be designed to feel soft to the touch, similar to a natural breast. In some embodiments, the implant can allow the surgeon to restore or increase breast mass while maintaining or restoring the tactile sensation of the breast.

[0065] In some embodiments, the implant can have a compressive modulus between about 0.1 kPa to 10 MPa, 0.3 kPa to 1 MPa, and / or 3 kPa to 200 kPa, although other compressive modulus ranges greater than or less than those ranges can also be contemplated depending on the needs of the tissue at the implantation site.

[0066] In some embodiments, the compressibility of the implant can be characterized by a compression elasticity calculated as the work done during compression recovery divided by the work done during compression multiplied by 100. The compression elasticity of the implants described herein can be between 1% and 80%, although other ranges such as greater than or equal to about 50%, 60%, 70%, 80%, 90%, etc. can also be contemplated.

[0067] In some embodiments, the implant can be configured to recover at least 50% of its original volume after a compressive force is applied and then removed. This behavior can facilitate delivery through an incision smaller than the size of the implant and can also provide a more natural feel to the implant. For example, after being compressed by 50%, the implants of the present disclosure can recover at least about 75% of their original volume. In some embodiments, after a compressive force sufficient to compress the implant by 50% is applied and then removed, the implant can recover at least greater than or equal to about 50%, 70%, 75%, 80%, 90%, 95%, 98%, and / or any other suitable percentage of its original volume. In some embodiments, after a 50% relative compressive displacement occurs in one or more directions, the implant can preferably recover at least about 90% and more preferably 95% of its original volume. Depending on the embodiment, this recovery of the material after compression can be isotropic, although embodiments can be contemplated in which the recovery of the material is anisotropic (e.g., radial compressibility and recovery is greater than or less than axial compressibility and recovery).

[0068] In some embodiments, the implant may be characterized by a compressive modulus. The implant may have a compressive modulus that matches that of natural tissue to achieve a more natural feel. In some embodiments, the implant may have a compressive modulus between about 0.01 kPa to 290 MPa, 0.1 kPa to 10 MPa, 0.1 kPa to 1 MPa, 0.1 kPa to 100 kPa, 2 kPa to 100 kPa, 0.1 kPa to 1 MPa, and combinations thereof and / or any other suitable compressive modulus for the application. For example, in the case where the implant is used in breast reconstruction surgery, the compressive modulus may be between about 0.1 kPa to 1 MPa or between 2 kPa to 100 kPa. Embodiments are envisioned where the implant compressive modulus is greater than or less than those described above.

[0069] It should be understood that since the implant degrades and is replaced by natural tissue, the compressive modulus (and / or any other mechanical property) of the implant may change over time. Thus, the above compressive modulus ranges may refer to the implant prior to or at the time of implantation. In some embodiments, the compressive modulus of the implant may gradually decrease and approach the properties of natural breast tissue, which may exhibit a modulus between about 2 kPa to 70 kPa, for example. The implant may approach the properties of natural breast tissue within any suitable time period after implantation, including but not limited to a time period of about 1 month to 5 years, about 3 months to 3 years, about 6 months to 2 years, and / or combinations thereof.

[0070] In some embodiments, the implantable prosthesis may have one or more regions. In some embodiments, the one or more regions may differ in terms of degradation rate and strength loss distribution by any suitable means, any suitable means including but not limited to regional variations in packing density, composition polymer molecular weight, fiber size, structural design, combinations thereof, and / or any other suitable means. For example, in some embodiments, the prosthesis may include a first radial region formed by a first subunit arrangement and a second radial region formed by a second subunit arrangement having a greater packing density than the first region. Other exemplary embodiments will be described in detail below. In other embodiments, the implantable prosthesis may have one or more gradients that range between one or more subunit arrangements (e.g., size, distribution, packing density, etc.). For example, the implant may include a transition region between two regions to allow for a gradual change in properties. Thus, there may be a smooth (e.g., linear or non-linear, etc.) transition between properties that may depend on the subunit arrangement, such as compressive stiffness. Embodiments are envisioned that include one or more different regions and one or more gradient regions. Thus, the various scaffold and implant properties described herein may refer to the entire scaffold or may refer to a portion of the scaffold.

[0071] In addition to the above, in embodiments in various regions including different characteristics, the characteristics of the implant may lie in the average characteristics of the entire implant. For example, the average filling density can be calculated by multiplying the filling density of each region by the volume occupied by that region, summing the products for each region, and dividing by the number of regions. In some embodiments, the implant may have an average filling density greater than or equal to about 1%, 2%, 4%, 5%, 6%, 8%, 9%, 10%, 12%, 15%, 20%, 30%, 40%, 50%, combinations thereof, and / or any other suitable average filling density. The implantable prosthesis may also have an average filling density less than or equal to about 60%, 50%, 40%, 30%, 20%, 15%, 12%, 10%, 9%, 8%, 6%, 5%, 4%, 2%, 1%, combinations thereof, and / or any other suitable average filling density. Combinations of the foregoing are envisioned, including but not limited to average filling densities between about 1% and 60%, between about 3% and 15%, and between about 3% and 10%. In some embodiments, the average filling density may be between 4% and 8% or equal to 4% and 8%. It should be understood that the average filling density of the implant may depend on the number of regions employed, the geometry of the subunits employed in each region, the overall size of the implant, the manufacturing method, the implant site requirements, and / or any other appropriate parameters. Thus, the implants of the present disclosure may have any suitable average filling density.

[0072] As previously mentioned, in some embodiments, the implants of the present disclosure may be formed with anisotropic characteristics to better mimic the characteristics of natural tissue, which is typically non - homogeneous and includes multiple materials arranged in precise ways. Thus, the implant may have non - uniform characteristics in one or more directions of the implant and may thus be anisotropic in one or more ways (e.g., through mechanical or geometric characteristics or a combination thereof). For example, the implant may have a first compressive modulus in the radial direction and a second different compressive modulus in the axial direction. In some embodiments, the characteristics may vary in a gradient manner in one or more directions of the implant. As previously mentioned, the scaffold may include one or more transition regions to effect a gradual change in characteristics between two regions in the implant. Thus, it should be understood that the characteristics described herein may refer to the whole or a part or multiple parts of the implant.

[0073] In some embodiments, changes in mechanical properties, such as compressive stiffness, may be due to changes in geometric properties. For example, smaller subunits with a smaller spatial frequency relative to other adjacent parts of the implant can result in a greater packing density, which can subsequently result in a greater compressive stiffness relative to a scaffold with larger subunits. Thus, the mechanical properties of the scaffold may be directly affected by the geometric properties of the scaffold. In some embodiments, changes in mechanical properties may be due to changes in the constituent material properties of the subunits. For example, the implant may include two subunit regions having substantially the same geometric structure but made of different materials (and / or coated with different materials) to create differences in mechanical properties. As will be described in more detail below, in some embodiments, the implant may include a support structure for providing local mechanical support to the implant.

[0074] In some embodiments, the implantable prosthesis of the present disclosure may preferably have a generally dome-shaped shape to mimic the natural shape of the breast. In other embodiments, the implantable prosthesis may have a generally spherical or ellipsoidal shape to mimic the anatomical cavity left by a tissue removal surgery (e.g., a lumpectomy) and / or any other natural or surgically created cavity. However, it should be understood that the implantable prosthesis of the present disclosure may have any suitable three-dimensional shape, including but not limited to spherical, dome-shaped, ellipsoidal, hemispherical, cylindrical, conical, domed, cuboid, tetrahedral, triangular or square prism, dodecahedral, toroidal, combinations thereof, and / or customized geometries. Partial versions of the foregoing geometries are contemplated, such as a semi-dome shape. Combinations of the foregoing geometries are also contemplated, including, for example, a teardrop shape, a partial teardrop shape having a rounded shape at a first end portion and a tapered shape at a second end portion, or other suitable shapes. It should be understood that the foregoing geometries, including their partial versions and combinations, may be selected and / or configured to mimic, augment, and / or otherwise achieve a desired anatomical shape, such as the desired shape of a natural breast or a part of a natural breast. It should be understood that the term "ellipsoidal" as used herein refers to an ellipsoidal three-dimensional shape (which may have different average diameters in two or more directions), a spheroidal shape, and a spherical shape (which may have substantially similar average diameters in all directions). In some embodiments, the implantable prosthesis may be formed by an assembly of one or more scaffolds. For example, a spherical implant for use in a lumpectomy procedure may be formed by fusing or otherwise joining two hemispherical implants.

[0075] In some cases, the implantable prostheses disclosed herein can have an asymmetric shape. For example, the implantable prosthesis can have different shapes in the anterior bottom region and the anterior top region of the implant. The size of the implant can be sized to increase breast tissue volume, replace a previous breast tissue volume, change the volume distribution of breast tissue, change the appearance of breast tissue, or replace an existing breast tissue volume with a smaller volume. The implantable prosthesis can be sized or shaped to provide a low, medium, or high profile shape to the breast, wherein the implant profile determines the protrusion of the breast. The implantable prosthesis with a high profile shape can be used to increase the height of the breast sidewall and provide the patient with greater upper pole fullness or cleavage. A smaller increase in the height of the breast sidewall can be obtained using an implantable prosthesis with a low or medium profile shape. The implantable prosthesis can be designed for use in the breast and be large enough to allow the implantable prosthesis to be used for breast fixation and breast reconstruction. Patient-specific customized implant sizes are also envisioned. In some embodiments, the implantable prosthesis can have a volume between 100 cc and 1200 cc (cubic centimeters) and / or a volume between 120 cc and 850 cc, but other volumes larger and smaller than those mentioned above are also possible.

[0076] The implantable prosthesis of the present disclosure can be formed of a biocompatible material that can promote rapid ingrowth of tissue or muscle into and around the prosthesis. In some embodiments, the implant can be formed of an absorbable material that can be replaced by the patient's natural tissue in the body as the implant degrades.

[0077] In some embodiments, the prosthesis can be formed of an absorbable material (e.g., a polymer or copolymer) that can be substantially resorbed within a time range of 1 month to 24 months or 3 months to 18 months after implantation and retain some residual strength for at least 2 weeks to 6 months.

[0078] In some embodiments, the implant or scaffold can include an absorbable polymer that includes or is prepared from one or more monomers selected from the group consisting of glycolide, lactide, glycolic acid, lactic acid, 1,4-dioxanone, trimethylene carbonate, 3-hydroxybutyric acid, 3-hydroxybutyrate, 4-hydroxybutyric acid, 4-hydroxybutyrate, ε-caprolactone, 1,4-butanediol, 1,3-propanediol, ethylene glycol, glutaric acid, malic acid, malonic acid, oxalic acid, succinic acid, and adipic acid.

[0079] In some embodiments, the implant may be formed of poly-4-hydroxybutyrate (P4HB) and its copolymers, or poly(butylene succinate) (PBS) and its copolymers. In embodiments, the P4HB and PBS polymers and their copolymers may not be crosslinked. In embodiments, the PBS polymers and copolymers may further include 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 embodiments.

[0080] In some embodiments, the polymers used to prepare the implant may have a weight average molecular weight of 50 kDa to 1,000 kDa, 90 kDa to 600 kDa, and / or from 200 kDa to 450 kDa relative to polystyrene determined by GPC, but polymers of other weight average molecular weights are contemplated.

[0081] In some embodiments, the prosthesis may be formed of a degradable material, including but not limited to thermoplastic or polymeric degradable materials. Combinations of the foregoing are contemplated. In some embodiments, the prosthesis may be formed of one or more absorbable polymers or copolymers, absorbable thermoplastic polymers and copolymers, and / or absorbable thermoplastic polyesters. The prosthesis may be formed of polymers including but not limited to: polymers formed of glycolic acid, lactic acid, 1,4-dioxanone, trimethylene carbonate, 3-hydroxybutyric acid, 4-hydroxybutyrate, ε-caprolactone, including polyglycolic acid, polylactic acid, poly-dioxanone, polycaprolactone, copolymers of glycolic acid and lactic acid, such as polymers, and Polymers, and include poly(lactide-co-caprolactone); poly(orthoester); polyanhydride; poly(phosphazene); polyhydroxyalkanoate; polyesters prepared synthetically or biologically; polycarbonate; tyrosine polycarbonate; polyamides (including synthetic polyamides and natural polyamides, polypeptides and poly(amino acids)); polyesteramides; poly(alkylene alkylates); polyethers (such as polyethylene glycol PEG and poly(ethylene oxide) PEO); polyvinylpyrrolidone or PVP; polyurethanes; polyether esters; polyacetals; polycyanoacrylates; poly(ethylene oxide) / poly(propylene oxide) copolymers; polyacetals, polyketals; polyphosphates; (phosphorus-containing) polymers; polyphosphoesters; polyalkylene oxalates; polyalkylene succinates; poly(maleic acid); silk (including recombinant silk and silk derivatives and analogs); chitin; chitosan; modified chitosan; biocompatible polysaccharides; hydrophilic or water-soluble polymers, such as polyethylene glycol (PEG) or polyvinylpyrrolidone (PVP), and other blocks of biocompatible or biodegradable polymers, such as poly(lactide), poly(lactide-co-glycolide) or polycaprolactone and their copolymers, including their random copolymers and block copolymers.

[0082] In some embodiments, an implantable prosthesis can be loaded, filled, and / or coated with a suitable therapeutic composition, including by blending the material composition of the prosthesis with the therapeutic composition and / or filler. In some embodiments, the filler can include nanoparticles (e.g., silver nanoparticles) and / or nanotubes (e.g., single-walled carbon nanotubes) for antimicrobial properties. Any suitable filler material known in the art for enhancing the antimicrobial properties of the implant can be employed, as the present disclosure is not limited thereto. This can include coatings, absorbent materials retained in the porous scaffold of the prosthesis, absorbent materials, compounds functionally bound to the material of the implantable prosthesis, and / or any other suitable means of associating the therapeutic composition with the implantable prosthesis. Suitable types of therapeutic compositions can include, but are not limited to, cells, stem cells, differentiated cells, adipocytes, muscle cells, platelets, pedicles, vascular pedicles, tissue chunks, extracellular adipose matrix proteins, gels, hydrogels, hyaluronic acid, collagen, bioactive agents, drugs, antibiotics, and other suitable therapeutic compositions that may be desired to be delivered to the implant site. The cells and tissues that can be delivered and / or coated or injected into the prosthesis can be autologous. The prosthesis can be used for autologous fat transfer. The cells added, coated, or injected onto the prosthesis can include islet cells, hepatocytes, and stem cells genetically altered to contain genes for treating the patient's disease. The prosthesis can include bioactive agents for stimulating cell ingrowth, including growth factors, cell adhesion factors, cell differentiation factors, cell recruitment factors, cell receptors, cell binding factors, cell signaling molecules such as cytokines, and molecules for promoting cell migration, cell division, cell proliferation, and extracellular matrix deposition. The prosthesis can also be partially or fully coated and / or contain agents for preventing tissue adhesion or agents for preventing cell proliferation, particularly for delaying cell invasion into the prosthesis.

[0083] In some embodiments, an implantable prosthesis can be partially or fully loaded, filled, coated, or otherwise combined with a bioactive agent. The bioactive agent can be included in the prosthesis for a variety of reasons. For example, a bioactive agent can be included to improve tissue ingrowth into the implant, improve tissue maturation, provide delivery of the active agent, improve the wettability of the implant, prevent infection, and improve cell attachment. The bioactive agent can also be incorporated into the material composition of the substrate of the subunit, including by blending the material composition and the bioactive agent.

[0084] The prosthesis may include an active agent designed to stimulate cell ingrowth, the active agent including growth factors, cell adhesion factors including cell adhesion polypeptides, cell differentiation factors, cell recruitment factors, cell receptors, cell binding factors, cell signaling molecules such as cytokines, and molecules for promoting 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-B (IL-1B), interleukin-8 (IL-8), and nerve growth factor (NGF) and combinations thereof. As used herein, the term "cell adhesion polypeptide" refers to a compound having at least two amino acids per molecule that is capable of binding to a cell via a cell surface molecule. Cell adhesion polypeptides include any protein in the extracellular matrix known to function in cell adhesion, the proteins including fibronectin, vitronectin, laminin, elastin, fibrinogen, type I collagen, type II collagen, and type V collagen, and synthetic peptides having similar cell adhesion properties. Cell adhesion polypeptides also include peptides derived from any of the foregoing proteins, including fragments or sequences containing binding domains.

[0085] In some embodiments, the implantable prosthesis may be loaded, filled, coated, or otherwise combined with a wetting agent designed to improve the wettability of various surfaces of the prosthesis to allow fluids to readily adsorb onto the prosthesis surface and to promote cell attachment and / or modify the water contact angle of the prosthesis surface. Examples of wetting agents include polymers of ethylene oxide and propylene oxide such as polyethylene oxide, polypropylene oxide, or copolymers of ethylene oxide and propylene oxide such as Other suitable wetting agents may include surfactants or emulsifiers.

[0086] In some embodiments, the implantable prosthesis may be loaded, filled, coated, or otherwise combined with a gel, hydrogel, or active hydrogel mixture to further improve wetting properties and to promote cell growth throughout the prosthesis. The hydrogel mixture may consist of live cells encapsulated in a biocompatible hydrogel such as gelatin, methacrylated gelatin (GelMa), silk hydrogel, and hyaluronic acid (HA) gel.

[0087] Other bioactive agents that can be incorporated into the prosthesis can include antimicrobial agents, particularly antibiotics, disinfectants, tumor agents, anti-scarring agents, anti-inflammatory agents, anesthetics, small molecule drugs, anti-adhesion agents, cell proliferation inhibitors, anti-angiogenic factors and angiogenic factors, immunomodulators, and coagulants. The bioactive agent can be a protein such as collagen and antibodies, peptides, polysaccharides such as chitosan, alginate, hyaluronic acid and its derivatives, nucleic acid molecules, small 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, biguanide, triclosan, gentamicin, minocycline, rifampicin, vancomycin, cephalosporin, copper, zinc, silver, and gold. Nucleic acid molecules can include DNA, RNA, siRNA, miRNA, antisense molecules, or aptamers.

[0088] In some embodiments, the implantable prosthesis can be loaded, filled, coated, or otherwise combined with allograft materials and xenograft materials, including acellular dermal matrix materials and small intestinal submucosa (SIS). In an embodiment, the prosthesis can contain a vascular pedicle or other tissue mass. In some embodiments, the prosthesis can incorporate a system for the controlled release of therapeutic or prophylactic agents.

[0089] In some embodiments, the implantable prosthesis can be loaded, filled, coated, or otherwise combined with allograft or xenograft tissues and cells before implantation, during implantation, after implantation, or any combination thereof. In some embodiments, the prosthesis can be coated with autologous tissues and cells from the patient before implantation, during implantation, after implantation, or any combination thereof. Autologous tissues and cells can include one or more of the following: autologous fat, lipoaspirate, adipose tissue, injectable fat, fatty tissue, adipocytes, fibroblasts, and stem cells, where the stem cells include human adipose tissue-derived stem cells, also known as preadipocytes or adipose tissue-derived progenitor cells, and fibroblast-like stem cells. In one embodiment, the prosthesis can be coated with autologous tissues and cells as described herein and can further include a vascular pedicle or other tissue mass. As will be apparent herein, the prosthesis is designed to create not only the shape of the implant, such as a breast implant, but also a large surface area that can retain autologous tissues and cells to promote tissue ingrowth.

[0090] In some embodiments, the polymeric and copolymeric compositions of the prosthesis can have a low moisture content to ensure that the prosthesis can be produced with an extended strength retention and good shelf life. In some embodiments, the polymers and copolymers used to prepare the prosthesis have a moisture content of less than 1,000 ppm (0.1 wt%), less than 500 ppm (0.05 wt%), less than 300 ppm (0.03 wt%), less than 100 ppm (0.01 wt%), and / or less than 50 ppm (0.005 wt%).

[0091] It should be understood that the prosthesis should have an appropriately low endotoxin content before implantation. The compositions used to prepare the prosthesis can have a low endotoxin content. In some embodiments, the endotoxin content can be low enough such that the prosthesis produced from the polymeric composition has an endotoxin content of less than 20 endotoxin units per prosthesis as determined by the Limulus Amebocyte Lysate (LAL) assay. For example, the endotoxin content of the polymeric composition used to prepare the prosthesis can be <2.5 EU / g of polymer or copolymer. In another example, the endotoxin content of a P4HB polymer or copolymer or a PBS polymer or copolymer is <2.5 EU / g of polymer or copolymer.

[0092] In some embodiments, the prosthesis of the present disclosure can include one or more markers for external detection of the prosthesis location. For example, the prosthesis can include radiopaque markers (e.g., metal tags, radiopaque materials incorporated into the printed walls of implants formed by additive manufacturing processes, or other suitable types of markers) that can be visible and distinct on nearby anatomical structures during x-ray imaging. The markers can be formed from any suitable medical material that can be used for medical imaging. Medical imaging can be performed using, for example, radiographic imaging modalities (e.g., x-ray imaging), magnetic resonance imaging (MRI), ultrasound, fluoroscopy, or computed tomography. The markers can thus be formed from any non-absorbable biocompatible material, which can be defined as a material that does not cause any adverse reactions to the patient's health and does not decompose over the patient's lifetime. Non-absorbable biocompatible materials can include, but are not limited to, metal-containing materials, polymeric materials, ceramic materials, or composite materials comprising metals, polymers, or combinations of metals and polymers. Suitable metals can include, but are not limited to, gold, iridium, nickel, rhodium, silver, tantalum, titanium, stainless steel and its alloys, combinations thereof, and / or other metals. Suitable polymers include, but are not limited to, polyvinyl alcohol, polyurethane, polyolefin, polyester, polypropylene, polyimide, polyetherimide, fluoropolymer, thermoplastic liquid polymer (LCP) such as, for example, that of Celanese Corporation polyethylene ether ketone such as, for example, PEEK of Vitrex Corporation TM, polyamides, polycarbonates such as, for example, those from Bayer Polymers , polysulfones, polyethersulfones, polyphenylsulfones such as, for example, those from Rowland Technologies , nylons, nylon copolymers, combinations thereof, and / or other polymers. In some embodiments, the marker may include a shape memory material, including but not limited to nitinol, titanium, or any shape memory polymer.

[0093] Certain additives can be incorporated into the implant, preferably into the polymer composition used to manufacture the scaffold. In one embodiment, these additives are combined with the polymers or copolymers described herein during the compounding process to produce pellets, which can then be processed to produce the scaffold. For example, the pellets can be injection molded, extruded, or more preferably printed using an additive manufacturing process to form the scaffold or the cells of the scaffold. In another embodiment, the pellets can be ground to produce a powder suitable for further processing, such as further processing using an additive manufacturing process. Alternatively, a powder suitable for further processing, such as further processing using an additive manufacturing process, can be formed directly by blending the additive and the polymer or copolymer. If desired, the powder for processing can be sieved to select the optimal particle size range. In another embodiment, the additive can be incorporated into the polymer composition of the scaffold used to prepare the implant using a solution-based method.

[0094] In some embodiments, the additives mentioned above can be nucleating agents and / or plasticizers. These additives can be added to the polymeric composition for preparing the scaffold of the implant in an amount sufficient to produce the desired results. Generally, these additives can be added in an amount between 1 wt% and 20 wt% relative to the total weight of the material. Nucleating agents can 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 scaffold and to improve the mechanical properties of the scaffold. 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.

[0095] Plasticizers that can be incorporated into the polymer composition for preparing the scaffold of the implant include, but are not limited to, dibutyl maleate, methyl laurate, dibutyl fumarate, bis(2-ethylhexyl)(dioctyl) maleate, paraffin wax, dodecanol, olive oil, soybean oil, polytetramethylene glycol, methyl oleate, n-propyl oleate, tetrahydrofurfuryl oleate, epoxidized linseed oil, 2-ethylhexyl epoxy tallate, glyceryl triacetate, methyl linoleate, dibutyl fumarate, methyl acetyl ricinoleate, acetyl tri(n-butyl) citrate, acetyl triethyl citrate, tri(n-butyl) citrate, triethyl citrate, bis(2-hydroxyethyl) dimer, butyl ricinoleate, glyceryl tri(acetyl ricinoleate), methyl ricinoleate, n-butyl acetyl ricinoleate, propylene glycol ricinoleate, diethyl succinate, diisobutyl adipate, dimethyl azelate, di(n-hexyl) azelate, tributyl phosphate, and mixtures thereof. Particularly preferred plasticizers are citrate esters.

[0096] In some embodiments, due to the complex geometry of the subunits, the implantable prosthesis can be formed using additive manufacturing techniques. For example, additive manufacturing techniques can be used to construct a flexible scaffold of the implant, which allows for precise control of the shape of the scaffold of the implant. Suitable methods for forming the subunit scaffold include fused filament fabrication, fused granulate deposition, melt extrusion deposition, selective laser melting (e.g., molten powder bed), printing slurries and solutions using a coagulation bath, printing using an adhesive solution and powder particles, stereolithography printing, melt extrusion deposition (MED), and / or other suitable additive manufacturing processes. In some embodiments, the scaffold of the implant can preferably be prepared by melt extrusion deposition (MED), but any suitable additive manufacturing process can be used. Although specific manufacturing techniques are listed above, it should be understood that any manufacturing system or method can be employed to form any part (e.g., scaffold) of the implant described herein, as the present disclosure is not limited thereto.

[0097] In some embodiments, the three-dimensional implant of the present disclosure may include a scaffold as previously described and one or more support structures for locally modifying the characteristics of the implant. The support structures may also be used to facilitate processes such as delivery or implantation. The implant may include support structures such as buttresses, rods, columns, fibers, paddles, protrusions, pins, recesses, rings, channels, tubes, shells, panels, beams (including I-beams, U-beams, W-beams, and columnar beams), combinations thereof, and / or any other suitable structures for helping to modify the local characteristics of the implant. For example, the implant may include columns that extend partially or fully along one or more directions (e.g., radially, axially) relative to the implant and may have linear, non-linear, curved, combinations thereof, and / or any other suitable structures. In some embodiments, the implant may include one or more growth chambers for cells and tissues. In some embodiments, the implant may include one or more openings for allowing a vascular pedicle or other tissue mass to be inserted into the implant or for the implant to clamp onto a vascular pedicle or other tissue mass and one or more openings or passages for allowing a vascular pedicle or other tissue mass to be inserted within the implant, including one or more lateral passages.

[0098] In some embodiments, the implant may include an outer shell or coating that may be disposed on at least a portion of the outer surface of the scaffold (or optionally, completely surround it). The shell may be used to deliver an initial dose of a bioactive agent (or any other material) and / or may provide a mechanical or structural function to the implant. In some embodiments, the thickness of the shell or coating may be in the range of from about 0.01 mm to 5 mm, from 0.5 mm to 2 mm, from 0.1 mm to 1 mm, and / or any other suitable thickness range. In some embodiments, the shell may be formed by a concentric stack of wires at the periphery of the scaffold. In other embodiments, the thickness of the shell is formed by more than one layer of wires. In still other embodiments, the shell may be formed from a foam having interconnected pores. In an embodiment, the shell is an open-cell foam and / or an open-cell foam comprising poly-4-hydroxybutyrate or a copolymer thereof or poly(butylene succinate) or a copolymer thereof. In some embodiments, the shell may be heat-treated to minimize the roughness of the outer surface of the shell.

[0099] In some embodiments, the housing or coating can be needle-penetrable such that a surgeon can suture or otherwise secure the implant at the implantation site. Alternatively or in combination therewith, the implant can include retainers, such as barbs or staples, located on one or more outer surfaces of the implant such that the implant can be anchored in the body without the use of sutures. The implant can include retainers located in the peripheral boundary of the implant or in the scaffold structure of the implant. In an embodiment, the retainers can be located on the implant to allow the implant to be anchored to the chest wall.

[0100] In some embodiments, the implant can include one or more suture protrusions such that the implant can be anchored in the body using sutures or staples. The number of protrusions can depend on the size of the implant (e.g., a larger implant may require more protrusions). The protrusions attached to the implant can have sufficient strength retention in the body to resist mechanical loads and allow sufficient tissue ingrowth into the implant to prevent subsequent movement of the implant after implantation. In some embodiments, the suture pull-out strength of the protrusions attached to the implant can be greater than 10 N and / or greater than 20 N. It should be understood that the implant can be directly secured in the body without the use of suture protrusions or a housing as the present disclosure is not limited thereto.

[0101] In some embodiments, a method of implanting an implant in a patient's breast can at least include the following steps: (i) creating at least one incision to gain access to the patient's breast tissue, (ii) separating the skin and subcutaneous fascia from the mammary mound of the breast, (iii) positioning the implant on the mammary mound of the breast, (iv) securing the implant to the tissue surrounding the mammary mound of the breast, and (v) closing the incision in the breast. In some embodiments, the method further includes one or more of the following steps: a) preparing a sample of lipoaspirate and coating or filling the implant with the sample before implanting the implant, (b) preparing a sample of lipoaspirate and coating or filling the implant with the sample after implanting the implant, preferably by injecting the sample into the implant, (c) inserting a vascular pedicle into the implant before or after implanting the implant, and (d) suturing or stapling the implant in place. The implant can be implanted in a subglandular position, a subpectoral position, or a prepectoral position. In an embodiment, the implant can be sutured to the tissue surrounding the mammary mound (e.g., the fascia around the pectoralis muscle under the mammary mound).

[0102] As previously mentioned, in some embodiments, a soft tissue implantable prosthesis can be used for soft tissue regeneration, augmentation, repair, enhancement, replacement, and / or reconstruction. For example, the implant can be used to reshape the breast, fill voids in the breast, lift the breast, and augment the breast. The implant can reduce the need for permanent breast implants during mastectomy, mastopexy, lumpectomy, and breast augmentation procedures. The implant can be biocompatible and, in some cases, absorbable, such that the implant can be replaced by the patient's tissue in the body as the implant degrades. The implant can have a compressive modulus that allows the implant to temporarily deform under a compressive force, recover its shape from the compression when the force is removed, and have a feel similar to breast tissue. In some embodiments, the implant can be coated or filled with materials to induce tissue ingrowth and / or reduce the risk of infection. For example, the implant can be coated or filled with autologous tissue, autologous fat, lipoaspirate, injectable fat, adipocytes, fibroblasts, and stem cells before, during, or after implantation.

[0103] In view of the foregoing, the disclosed implantable prosthesis can be used for many different applications and can provide many different benefits. This can include, for example, soft tissue reconstruction and / or augmentation. This can include reconstruction of surgically excised or resected tissue (e.g., in a lumpectomy procedure), as well as natural soft tissue volume loss. The prosthesis can have mechanical and geometric properties similar to natural tissue to mimic the natural feel of the tissue. In some embodiments, the prosthesis can also serve as a scaffold for tissue ingrowth, where tissue can grow into the prosthesis. Tissue ingrowth into the void spaces of the prosthesis can also have the additional benefits of improved cosmetic results, resistance to migration and dislocation, and reduced risk of capsular contracture. The prosthesis can also serve as an indicator for biopsy and / or tissue resection sites. The prosthesis can be visible using one or more medical imaging systems to enable external detection of the site for treatment and imaging applications. The prosthesis can have the benefits of reducing the clinical target volume in radiotherapy and improving the cosmetic results after lumpectomy. However, it is also possible for the systems and methods disclosed herein to provide different benefits.

[0104] The implantable prosthesis of the present disclosure can be used in any suitable application. In some embodiments, the prosthesis can be implanted into soft tissue after a biopsy (and / or any other procedure) during the treatment of cancers such as breast cancer, abdominal cancer, liver cancer, muscle cancer, kidney cancer, lung cancer, and prostate cancer. In some embodiments, the prosthesis can be used in soft tissue reconstruction applications such that the prosthesis can be used as a breast implant, breast lift device, breast augmentation device, nipple implant, facial reconstruction device, buttock implant, zygomatic augmentation device, cosmetic repair device, soft tissue regeneration device, hernia implant, hernia plug, wound healing device, tissue engineering scaffold, scaffold for a vascular pedicle or other tissue mass, guided tissue repair / regeneration device, expansion or filling device, void filler, device for treating vesicoureteral reflux, cell seeding device, drug delivery device, combinations thereof, and / or any other suitable application. In an embodiment, the implant has a shape and size suitable for use in breast surgeries including breast augmentation, breast reconstruction, and mastopexy.

[0105] As used herein generally, "absorbable" means that the material degrades in the body and the degradation products are eliminated or excreted from the body. The terms "absorbable", "resorbable", "degradable", and "erodible" - with or without the prefix "bio" - may be used interchangeably herein to describe materials that break down and are gradually absorbed, excreted, or eliminated by the body, regardless of whether the degradation is primarily due to hydrolysis or mediated by metabolic processes.

[0106] As used herein generally, "bioactive agent" refers to a therapeutic, prophylactic, or diagnostic agent, an agent that promotes host tissue healing and regeneration, and also a therapeutic agent that prevents, inhibits, or eliminates infection. "Agent" includes such an agent alone and is also intended to include combinations of agents.

[0107] As used herein generally, "biocompatible" means that the biological response to the material or device is suitable for the intended in vivo application of the device. Any metabolites of these materials should also be biocompatible.

[0108] As used herein generally, "blend" means a physical combination of different polymers, as opposed to a copolymer formed from two or more different monomers.

[0109] As used herein, "compression modulus" is measured using a mechanical test stand (QTest TM / 1L, MTS, USA) at 20 mm / min -1Measured at the crosshead speed of. The sample was preloaded (10% of the initial compressive load) to apply the load and compressed until 1 mm (20%) of the original height of the sample. The clinically relevant cyclic load was repeated 10 times, and the compressive modulus was calculated based on the secondary cyclic load, which is an artifact due to the absorption of relaxation and the alignment or seating of the sample. The compressive modulus can also be measured using ASTM standard ASTM D1621-16 or ASTM D695-15.

[0110] As used herein, "compressive resilience" is calculated as the work done during compression recovery divided by the work done during compression multiplied by 100.

[0111] As commonly used herein, "copolymer of poly-4-hydroxybutyrate" means any polymer containing 4-hydroxybutyrate with one or more different hydroxy acid units. The copolymer can be isotope-enriched.

[0112] As commonly used herein, "copolymer of poly(butylene succinate)" means any polymer containing 1,4-butanediol and diacid units and one or more different diol or diacid units. The copolymer can contain one or more of the following: branching agents, crosslinking agents, chain extenders, and reactive blending agents. The copolymer can be isotope-enriched.

[0113] As commonly used herein, "endotoxin content" refers to the amount of endotoxin present in the implant or sample and is determined by the Limulus Amebocyte Lysate (LAL) assay.

[0114] As used herein, "packing density" is the ratio of the volume occupied by the 3D printing material in the implant scaffold to the total volume of the 3D printed scaffold, expressed as a percentage.

[0115] As commonly used herein, "poly(butylene succinate)" means a polymer containing 1,4-butanediol units and succinic acid units. The polymer can contain one or more of the following: branching agents, crosslinking agents, chain extenders, and reactive blending agents. The polymer can be isotope-enriched.

[0116] "Poly(butylene succinate) and copolymers" include polymers and copolymers prepared with one or more of the following: chain extenders, coupling agents, crosslinking agents, and branching agents.

[0117] As commonly used herein, "poly-4-hydroxybutyrate" means a homopolymer containing 4-hydroxybutyrate units. Poly-4-hydroxybutyrate can refer to P4HB or a biomaterial (manufactured by Tepha, Inc. of Lexington, Massachusetts). The polymer can be isotope-enriched.

[0118] As used herein, "soft tissue" means body tissue that is not hardened or calcified. Soft tissue does not include hard tissues such as bone and enamel.

[0119] "Strength retention rate" refers to the amount of time that a material retains a particular mechanical property after being implanted into a human or animal body. For example, if the tensile strength of a resorbable fiber or strut decreases by half after 3 months when implanted into an animal body, the strength retention rate of the fiber or strut at 3 months will be 50%.

[0120] As used herein, "surface roughness" (Ra) is the arithmetic mean of the absolute values of the profile height deviations from the midline recorded within the evaluation length.

[0121] Turning to the drawings, specific non-limiting embodiments are described in further detail. It should be understood that the various systems, components, features, and methods described in relation to these embodiments can be used alone and / or in any desired combination, as the present disclosure is not limited to the specific embodiments described herein.

[0122] Figure 1A An exemplary subunit 20 of an implant stent according to some embodiments is shown. Subunit 20 may include a TPMS or spiral icosahedron surface 22 that forms large pores 25 extending through the resulting stent to provide a series of interconnected pores extending through the implant. As Figure 1A shown in the isometric view of, the spiral icosahedron surface 22 can increase the surface area of subunit 20 while reducing local stress, such that the subunit and the stent formed by the subunit can be highly compressible and can recover the compressibility, as previously described.

[0123] Figures 1B to 2C Shown are Figure 1A various views of subunit 20 having a spiral icosahedron surface 22 from Figure 1BAs shown. It should be understood that for the exemplary subunit 20, the lengths in all three basic directions can be approximately equal. However, subunits with non-cubic lengths are envisioned. In some embodiments, as discussed above, the larger the length L1 of the subunit, the larger the size of the pores 25, such that the density and thus the weight of the implant can be reduced, while the strength or recoverability of the scaffold can be decreased. The length L1 of the subunit can thus be selected to provide a desired balance between these two parameters based on the application and various other parameters of the implant (e.g., stiffness of the constituent material). Thus, the length L1 of the subunit can be any suitable value, including but not limited to greater than or equal to about 2 mm, 5 mm, 1 cm, 2 cm, 3 cm, and / or any other suitable length. The length L1 can also be less than or equal to 3 cm, 2 cm, 1 cm, 5 mm, 2 mm, and / or any other suitable length. Combinations of the foregoing ranges are envisioned, including a subunit length L1 between 2 mm and 3 cm, as well as ranges larger and smaller than the foregoing ranges. For ease of viewing, the repeating subunits are shown as being generally cubic, and it should be understood that the repeating subunits can be any polyhedral shape or curved three-dimensional shape. Where applicable, the length L1 can be associated with the sidewall length or average diameter of the repeating subunit.

[0124] As Figure 1B shown, the pores 25 of the subunit 20 can have an average diameter D1. It should be understood that in some embodiments, the average pore diameter D1 can be proportional to the length L1 of the subunit in some way. For example, if the wall thickness, shown as thickness T1 in Figure 1C is approximately the same, a subunit with a length of 1 cm can have an average pore diameter of approximately 2.5 mm, and a subunit with a length of 2 cm can have an average pore diameter of approximately 5 mm. In other embodiments, if other geometric parameters (e.g., wall thickness) are also adjusted, the average pore diameter may not be proportional to the length of the subunit. Thus, the spiral icosahedron subunits of the present disclosure can have any suitable average pore diameter, or other suitable type of maximum lateral dimension, depending on the desired pore geometry for the application (e.g., tissue infiltration and / or degradation rate, compressibility, implant site mechanics), independent of the subunit size.

[0125] Exemplary and non-limiting average pore diameters D1 or other lateral dimensions of the sub-units can be greater than or equal to about 0.05 mm, 0.075 mm, 0.1 mm, 0.5 mm, 1 mm, 2 mm, 5 mm, 1 cm or other suitable dimensions. The average pore diameter or other lateral dimension can also be less than or equal to about 2 cm, 1 cm, 5 mm, 2 mm, 1 mm, 0.5 mm, 0.1 mm, 0.075 mm, 0.05 mm and / or any other suitable dimension. Combinations of the foregoing ranges are envisioned, including average pore diameters or other lateral dimensions between about 0.075 mm and 2 cm, between 0.5 mm and 1 cm, between 1 cm and 5 mm, between 0.5 mm and 2 cm, as well as ranges larger and smaller than the foregoing ranges.

[0126] As Figure 1C shown, the wall thickness T1 of the sub-unit 20 can be determined at least in part based on various parameters, including the desired compressibility and strength of the implant, the degradation rate (if applicable, based on the material composition), and the manufacturing method. For example, if the scaffold is formed using MED technology, the minimum wall thickness can be determined by the minimum possible deposited wire diameter. In some embodiments, the wire diameter can correspond to the nozzle diameter of the system. However, the wire diameter can be greater than or less than the nozzle diameter, depending on the scan speed. In some embodiments, the wall thickness T1 can correspond to a single wire diameter. In other embodiments, more than one wire can be used to form a thicker wall thickness.

[0127] Exemplary and non-limiting wall thicknesses T1 of the sub-units can be greater than or equal to about 0.01 mm, 0.05 mm, 0.1 mm, 0.15 mm, 0.2 mm, 0.25 mm, 0.3 mm, 0.4 mm, 0.5 mm, 1 cm, and / or less than or equal to about 1 cm, 0.5 mm, 0.4 mm, 0.3 mm, 0.25 mm, 0.2 mm, 0.15 mm, 0.1 mm, 0.05 mm, 0.01 mm and / or any other suitable thickness. Combinations of the foregoing are envisioned, including wall thicknesses between 0.01 mm and 1 cm, as well as ranges larger and smaller than the foregoing ranges.

[0128] Figures 2A to 2C Shown are various views of one embodiment of a partial scaffold 50 formed by eight sub-units 20, which views are similar to Figures 1A to 1C those shown. The scaffold can have interconnected macropores 25 formed between the helical icosahedral surfaces of the sub-units. It should be understood that although eight sub-units are shown in the partial exemplary scaffold of Figures 2A to 2C , any suitable number of sub-units 20, greater than eight sub-units and less than eight sub-units, can be employed depending on the application of the implant.

[0129] Figures 1A to 2C The helical tetrakaidecahedron TPMS of the subunits shown in Figures 1A to 2C can exhibit approximately isotropic behavior in more than one direction, such that their mechanical properties in more than one direction can be approximately equal. This behavior can more precisely mimic natural tissue, while also enabling the implant to be delivered through a small incision site without a significant risk of injury or discomfort to the patient.

[0130] Figure 3 An exemplary breast implant 100 is shown in Figure 3 , and the implant can be formed from Figures 1A to 2C the TPMS scaffold shown in Figures 1A to 2C . The implant can be sized and shaped to fit the anatomical site. For example, the implant can be a dome shape as shown in Figure 3 . It should be understood that although the dome top is shown as being symmetric, asymmetric shapes that more precisely mimic natural tissue are envisioned, as described in more detail above. Figure 3 In the depicted embodiment, the implant 100 can have an average base diameter D2, and the average base diameter D can be wide enough to span the width of the reconstructed or augmented breast. The average base diameter D2 can be specific to the patient and can thus be any suitable size, including but not limited to greater than or equal to about 6 cm, 8 cm, 10 cm, 12 cm, 15 cm, 18 cm, 20 cm, 22 cm and / or less than or equal to about 22 cm, 20 cm, 18 cm, 15 cm, 12 cm, 10 cm, 8 cm, 6 cm and / or any other suitable average diameter. Combinations of the foregoing ranges are envisioned, including average base diameters between about 6 cm and 22 cm, between 8 cm and 18 cm, and / or ranges larger and smaller than the foregoing ranges.

[0131] It should be understood that in other applications (e.g., lumpectomy), the average diameter of the implant can be smaller to correspond to the size of the resection site. Thus, the implants of the present disclosure are not limited by their shape and / or size.

[0132] The implant 100 can also have an average projection height H1, as shown in . Similar to the base diameter D2, the projection height H1 can be customized for the patient and can thus be any suitable size, including but not limited to between about 2 cm and 15 cm, between 3 cm and 10 cm, between 4 cm and 7 cm and combinations thereof and / or any other suitable size.

[0133] Figure 3

[0134] Figures 4A to 4BShows different views of an embodiment of a breast implant scaffold formed by spiral icosahedral subunits. The implant 100 is designed to have an average base diameter of 11 cm and a protrusion height of 5 cm. The spiral icosahedral subunits have interconnected macropores 25 formed by the spiral icosahedral surface 22, such that the scaffold can have open porosity. As Figures 4A to 4B shown, when the scaffold shape is different from the subunit shape (e.g., a dome scaffold versus a cubic subunit), partial subunits can be employed. Thus, the implants of the present disclosure can include partial subunits to form a desired scaffold size.

[0135] Figures 5A to 5C Shows the use of Figures 4A to 4B three flexible breast implants having spiral icosahedral subunits manufactured using a design similar to the design shown. Specifically, the depicted implants are formed with spiral icosahedral subunits having different spatial frequencies, where Figure 5A the implant of Figure 5C is formed with the lowest spatial frequency (i.e., the largest subunit size), and Figure 5A the implant of Figure 5B is formed with the highest spatial frequency (i.e., the smallest subunit size). Without wishing to be bound by theory, the spatial frequency of the subunits can be proportional to the packing density, such that a higher spatial frequency (i.e., a smaller subunit size) can be associated with a higher packing density. For example, Figure 5C shows an implant 200 having a 3% packing density, Figure 5C and Figure 5A shows an implant 300 having a 5% packing density, and

[0136] formed by P4HB Figures 5A to 5CThe implant is formed using MED. In some exemplary embodiments, pellets of poly-4-hydroxybutyrate (P4HB) (Tepha Inc., Lexington, Massachusetts, MW 450 kDa) can be loaded into the hopper of an MED-based 3D printer that includes a horizontal extruder feeding a vertical extruder equipped with a vertical plunger and a movable platform. An exemplary process for using melt extrusion to eject a series of droplets as needed in the preparation of an implant is described in Patent Publication No. 2019 / 0375149, filed on June 11, 2019, and titled "METHODS FOR 3D PRINTING OF POLY-4-HYDROXYBUTYRATE AND COPOLYMERS", which is incorporated herein by reference in its entirety.

[0137] The pellets of P4HB can have an average diameter of 3.5 mm, a moisture content of less than 100 ppm, and can be kept dry in the hopper using a purge of air dried by a silica bed. The temperature profile of the horizontal extruder can be set to 12 °C to 14 °C in the build chamber, 100 °C in the first transition zone, 135 °C in the second transition zone, and 185 °C in the extrusion zone. The residence time of the polymer in the MED horizontal extruder can be 22 min / cm 3 . The back pressure can be set to 50 bar (5 MPa). The diameter of the nozzle orifice of the vertical extruder can be 0.15 mm, and for filling, the droplet printing frequency can be 240 drops per second.

[0138] Additional exemplary settings for the 3D printer are shown in Table 1.

[0139] Printhead Temperature (°C) 185 Cartridge Zone 2 (°C) 135 Cartridge Zone 1 (°C) 110 Build Chamber Temperature (°C) 12 to 14 Screw Speed (m / min) 4 Back Pressure (MPa) 5 Retraction Stroke (mm) 6 Deco Speed (mm / s) 2 Deco Stroke (mm) 4 Discharge nr (%) 55 Packing Density Vol (%) 3 to 8 Droplet Rate 1 to 1.3

[0140] Table 1: Exemplary parameters for MED printing of a compressible P4HB breast implant

[0141] The following Table 2 outlines the various measured properties of three 3D-printed compressible breast implants formed from P4HB material and Figures 5A to 5C the spiral icosahedral subunits.

[0142]

[0143]

[0144] Table 2: Properties of implants with a porous spiral icosahedral design

[0145] Figures 5A to 5CThree implants underwent cyclic compression testing for mechanical evaluation of the implants. The average maximum compression load at 50% strain, the stiffness at 20% to 40% and 40% to 50% strain, and the dimensional height recovery after cyclic loading are shown in Table 3. The results show that the implants recovered to greater than 97% of their dimensional height (the protrusion from the base to the apex of the implant) after cyclic compression.

[0146]

[0147]

[0148] Table 3: Cyclic Compression in the Axial Direction of Implants with a Porous Spiral Icosahedron Design

[0149] Figures 5A to 5B The breast implant also passed through the Keller funnel and maintained the shape and volume of the breast implant, indicating that the breast implant can be delivered to the implant site through a small incision without significant damage or deformation.

[0150] Figures 5A to 5C Depicts an implant formed entirely of a spiral icosahedron scaffold that has substantially uniform properties over the implant. However, implants with different scaffold regions are envisioned.

[0151] Figures 6A to 6B Depicts a breast implant 500 according to some embodiments. The breast implant may include a first TPMS scaffold 505 and a second scaffold 515 arranged along lines radially diverging from the center of the implant 500. The second scaffold may include a TPMS scaffold with subunits different from the first scaffold. For example, the second scaffold 515 may be formed of subunits with a feature size larger than the feature size of the first scaffold 505, which may facilitate radial compression of the implant. For example, the spatial frequency of the first scaffold may be less than the spatial frequency of the second scaffold, such that the second scaffold may be denser and thus more rigid. In some embodiments, the second scaffold may be disposed on the outer surface of the first scaffold, while in other embodiments, the second scaffold may extend through the body of the first scaffold. For example, Figure 6A May represent a top view of the implant, and a scaled cross-sectional view of the implant taken along the axial direction. Figure 6B May represent a side view of the implant, and a cross-sectional view of the implant taken along the radial direction. It should be understood that more than one scaffold type may be employed in any suitable arrangement to facilitate the desired mechanical and tissue ingrowth profile.

[0152] It should also be understood that although the scaffolds 505, 515 are shown as being different, embodiments with a smooth gradient transition between the scaffold regions are also envisioned.

[0153] In some embodiments, Figures 6A to 6B the second support 515 may represent a support structure, such as a strut, that extends on the surface of the support 505 to provide local mechanical support. In some embodiments, the support structure formed by the second support 515 may be used to deliver a biological agent. It should be understood that Figures 6A to 6B the arrangement of the regions shown in

[0154] Figures 7A to 7B is merely exemplary, and other arrangements of the second support and / or the support structure are envisioned. Figure 7A depicts a breast implant 600 according to other embodiments. The breast implant 600 may be formed by a plurality of layers 612, 614, 616, 618 of a support, which are disposed on top of each other in a stacked configuration relative to the axial direction of the implant. Each of these layers may be different from one another to provide a desired mechanical behavior. As shown in a cross-sectional view taken along Figure 7B the line 7B-7B of the implant in Figures 6A to 6B these layers may extend through the body of the implant 600. In some embodiments, the layer 618 may serve as the base of the implant. As described with respect to Figures 7A to 7B the various layers may be different or may be arranged as a gradient through the implant. It should also be understood that

[0155] Figures 8A to 8B the four layers shown in Figure 8B are merely exemplary, and other arrangements of the support layers are envisioned. Figure 8A depicts a breast implant 700 having a plurality of concentric supports 712, 714, 716, 718 that are disposed on a lower layer and at least partially surround the lower layer, where the layer 718 is the bottommost layer of the implant. Figures 8A to 8B shows a cross-sectional view of the implant taken along the line 8B-8B of

[0156] Figures 6A to 8BEach layer or region shown in [the figure] can represent differences in subunit type, including different materials, spatial frequencies, packing densities, subunit types, and / or other differences that provide different properties for different parts of the implant. These regional differences in properties can also be affected by geometric differences in the layer or region, such as differences in thickness used for each region or layer. As previously described, these region-by-region variations in subunit properties and regional geometries can provide differences in stiffness, tissue infiltration properties, volume for therapeutic compositions, surface roughness, and / or any other desired property in the various regions. Additionally, these variations may generally affect the properties of the entire implant. Thus, it should be understood that any combination of layers or regions (e.g., scaffold regions or support structures, such as Figures 6A to 8B the scaffold region or support structure in [the figure]) can be used to achieve the desired mechanical behavior, tissue infiltration behavior, degradation behavior, or physical properties for a particular region or for the entire implant.

[0157] For example, as described above, in some embodiments, it may be desirable for the implant to have a lower compressive stiffness in the radial direction (e.g., to allow the base to be compressed when passing through a funnel or incision) and a greater compressive stiffness in the axial direction (e.g., to maintain the desired shape over time and / or to mimic the feel of natural tissue). Additionally or alternatively, in some embodiments, it may be desirable for the outer portion of the implant to feel smooth. In some embodiments, the presence of sharp edges and / or overall surface roughness of the outer surface of the implant can be reduced, for example, by providing a shorter distance between adjacent edges of the scaffold and / or using different subunit geometries with alternative geometries. This can beneficially improve the operation of the system during implantation and other possible benefits. Additionally or alternatively, in some embodiments, it may be desirable for the implant (e.g., by providing a low packing density, large pore size, etc.) to facilitate tissue infiltration. The inventors have recognized and realized that such a combination of desired properties for the implant can be achieved by providing regions or layers of the implant with specific properties that generally result in the desired properties throughout the implant.

[0158] In Figures 8A to 8BIn an exemplary embodiment, the properties of each of the layers 712 to 718 can be selected to achieve these properties and / or other desired properties in the implant 700. For example, the core layer 718 can be formed to have a relatively low packing density and / or a relatively large pore size. In some embodiments, the core layer can include a TPMS or a spiral icosahedron scaffold having a packing density that can optionally be between approximately 4% and 6%. This can be beneficial for a relatively low compressive stiffness in the radial direction compared to a higher packing density or a smaller pore size. Additionally or alternatively, such a low-density core can be beneficial for tissue infiltration, as discussed above.

[0159] Furthermore, in some embodiments, the first intermediate layer 716 and the second intermediate layer 714 can have a packing density higher than that in the core layer 718 and / or a pore size smaller than that in the core layer 718, as Figure 8B shown, each of the first intermediate layer 716 and the second intermediate layer 714 can be concentric with the core layer 718 and / or can at least partially surround the core layer 718. This can contribute to a higher compressive stiffness in the axial direction while allowing the radial compressive stiffness to remain within a desired range. In some embodiments, the packing density can increase from the first intermediate layer 716 to the second intermediate layer 714, where the first intermediate layer 716 is disposed between the core layer 718 and the second intermediate layer 714. In one possible embodiment, the first intermediate layer 716 can include a TPMS or a spiral icosahedron scaffold with a packing density of approximately 8%, and the second intermediate layer 714 can include a TPMS or a spiral icosahedron scaffold with a packing density of approximately 12%. Such an increase can occur discretely or using a gradient of scaffold properties, as described above. The thicknesses of the intermediate layers 716, 714 can also be selected to achieve the desired stiffness. For example, in some embodiments, the first intermediate layer 716 can have a thickness of approximately 5 mm to 10 mm, while the second intermediate layer can have a thickness of approximately 1 mm to 3 mm.

[0160] Although the illustrated embodiment includes two intermediate layers, it should be understood that in some embodiments there can be only a single intermediate layer. For example, some embodiments can include a single intermediate layer having a packing density of approximately between 8% and 12% or any other suitable packing density, and a thickness of approximately 2 mm to 10 mm, 5 mm to 8 mm or any other suitable thickness to achieve desired properties in the layer or in the implant. Alternatively, there can be more than two intermediate layers, or there can be a continuous gradient of packing density from the core layer to the shell layer such that the different intermediate layers may not be distinguishable.

[0161] Furthermore, in some embodiments, as Figure 8BAs shown, outer layer 712 can be concentric with one or more intermediate layers 714, 716 and / or core layer 718 and / or can at least partially surround one or more intermediate layers 714, 716 and / or core layer 718, and the outer layer 712 can have a greater packing density compared to the intermediate and / or core layers. The outer layer 712 can be formed, for example, by using a higher packing density and / or different subunit types to provide desired properties for the outer surface of the implant, such as smoothness, therapeutic compound loading, and / or other suitable parameters. In some embodiments, compared to a TPMS or spiral icosahedron subunit type, the following subunit types can provide a smoother feel or other desired properties: the subunit type has a polygonal or honeycomb geometry, such as a hexagonal or octagonal geometry, or has a tessellated pattern, such as a Voronoi pattern or other pattern. Thus, in some embodiments, the outer layer can be formed to have a Voronoi subunit type and can have a packing density of about 20% to 24% or optionally about 22%. Additionally, in some embodiments, the outer layer can have a relatively small thickness that is sufficient to achieve the desired surface feel while substantially not affecting the desired stiffness in one or more directions. For example, the outer layer 712 can have a thickness of about 0.1 mm to 1.0 mm or about 0.5 mm.

[0162] It should be understood that although the above embodiments illustrate examples where the packing density, subunit type, and layer thickness vary in different regions to achieve the desired properties of the implant, the variations in each region are not limited to the packing density, subunit type, and layer thickness. As described above, other properties that can be varied by region include material type, material properties, spatial frequency, pore size, etc. Additionally, although embodiments have been described above where the outer region has a greater packing density compared to the inner region, it should be understood that embodiments where the inner region has a lower packing density compared to one or more intermediate / outer regions are also contemplated, as are embodiments where the packing density in different regions is substantially uniform (e.g., where the regions can be defined by differences in pore size, spatial frequency, subunit type, or other properties).

[0163] Example: Rabbit Model Test

[0164] The above three groups of implants were experimentally tested by implanting them into rabbits. All three groups were generally dome-shaped and included a first TPMS scaffold with a varying packing density among the groups and a second TPMS scaffold with a packing density of 11% in all groups. The second scaffold was arranged along four radially diverging lines from the center of the implant, which, when viewed from the axial direction, were arranged at right angles to form a plus shape. The packing densities of the first scaffold in the first, second, and third groups were approximately 4.5%, approximately 6.7%, and approximately 9.0%, respectively. All implants were 3D printed using P4HB. Implants from each group were removed after 4 weeks, 12 weeks, and 26 weeks of implantation. After removal, the implants were evaluated for the following aspects: material degradation (using scanning electron microscopy (SEM) and by assessing changes in molecular weight); dimensional stability (by measuring height and base diameter); tissue infiltration (using histological evaluation and computed tomography (CT) scans); and compressive stiffness (both before and after removing the infiltrated tissue).

[0165] All three groups exhibited similar material degradation. Scanning electron microscopy (SEM) evaluation showed significant surface erosion and pitting in all three groups, and all three groups retained approximately 84% of their molecular weight after 4 weeks, approximately 56% to 57% after 12 weeks, and approximately 27% after 26 weeks.

[0166] Although all groups exhibited good tissue infiltration behavior, the 4.5% group had the highest tissue infiltration rate, while the 9.0% group had the lowest tissue infiltration rate. At the 4-week time point, loose fibrovascular tissue had formed in all groups. At the 12-week time point, soft and mature fibrovascular tissue had developed in all groups, with adipose tissue developing throughout the 4.5% group and at the periphery of the 9.0% group.

[0167] As described above, compressive stiffness was tested with the infiltrated tissue still present on the implant (i.e., in the "as received" state) and after removing the infiltrated tissue by an enzymatic process (i.e., in the "digested" state). All three groups were also evaluated for compressive stiffness before implantation, with the pre-implantation stiffness of the 4.5% group being approximately 235 kPa, the 6.7% group being approximately 354 kPa, and the 9.0% group being approximately 449 kPa.

[0168] All three groups exhibited high compressive stiffness after implantation and tissue infiltration. The stiffness of the 4.5% group in the as-received state increased by approximately 83% at the 4-week time point and then decreased at the 12-week and 26-week time points. At 26 weeks, the stiffness in the as-received state was approximately 53% higher than the pre-implantation stiffness. The stiffness of the 6.7% group in the as-received state increased by approximately 66% at the 4-week time point. At 12 weeks, the stiffness had increased to approximately 207% higher than the pre-implantation stiffness. At 26 weeks, the as-received stiffness of the 6.7% group had decreased relative to the stiffness at 12 weeks but was still approximately 86% higher than the pre-implantation stiffness. The stiffness of the 9.0% group in the as-received state had increased by approximately 55% at 4 weeks and was approximately 161% higher than the pre-implantation stiffness at 12 weeks. At 26 weeks, the as-received stiffness of the 9.0% group was approximately 152% higher than the pre-implantation stiffness. In all groups, the stiffness in the digested state decreased over time, consistent with the material degradation results, indicating that the material was degrading and / or being absorbed.

[0169] The embodiments described herein can be implemented as a method, and examples of the method have been provided. The actions performed as part of the method can be ordered in any suitable way. Accordingly, embodiments can be constructed in which the actions are performed in an order different from the illustrated order, and the embodiments can include performing some actions simultaneously, even if those actions are shown as sequential actions in the illustrative embodiments.

[0170] Although the present teachings have been described in connection with various embodiments and examples, the present teachings are not intended to be limited to these embodiments or examples. On the contrary, as will be understood by those skilled in the art, the present teachings include various alternatives, modifications, and equivalents. Accordingly, the foregoing description and drawings are merely illustrative.

[0171] Although several embodiments of the present inventive concept have been described and illustrated herein, those of ordinary skill in the art will readily conceive of various other devices and / or structures for performing the functions and / or obtaining the results and / or one or more of the advantages described herein, and each such variation and / or modification is considered to be within the scope of the present inventive concept. More generally, those skilled in the art will readily understand that all parameters, dimensions, materials, and configurations described herein are intended to be exemplary, and the actual parameters, dimensions, materials, and / or configurations will depend upon one or more specific applications for which the teachings of the present inventive concept are used. Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation many equivalents to the specific embodiments of the present inventive concept described herein. Accordingly, it is to be understood that the foregoing embodiments are presented by way of example only, and that within the scope of the appended claims and their equivalents, the present inventive concept may be practiced otherwise than as specifically described and claimed. The present inventive concept pertains to each and every separate feature, system, article, material, kit, and / or method described herein. Additionally, any combination of two or more such features, systems, articles, materials, kits, and / or methods, if not mutually inconsistent, is also included within the scope of the present inventive concept.

Claims

1. An implantable soft tissue repair prosthesis, characterized in that: The implantable soft tissue repair prosthesis comprises: A flexible porous scaffold formed from at least one triply periodic minimal surface, wherein the flexible porous scaffold is configured to recover at least 75% of its original volume when compressed by 50% in at least one direction.

2. The implantable soft tissue repair prosthesis according to claim 1, characterized in that: The packing density of the flexible porous scaffold is less than 20%.

3. The implantable soft tissue repair prosthesis according to claim 1, characterized in that: The packing density of the flexible porous scaffold is between 3% and 10%.

4. The implantable soft tissue repair prosthesis according to claim 1, characterized in that: The average pore size of at least a portion of the flexible porous support is between 0.075 mm and 20 mm.

5. The implantable soft tissue repair prosthesis according to claim 4, characterized in that: The average pore diameter is 0.5 mm to 10 mm.

6. The implantable soft tissue repair prosthesis according to claim 4, characterized in that: The average pore diameter is 1 mm to 5 mm.

7. The implantable soft tissue repair prosthesis according to claim 1, characterized in that: The implantable soft tissue repair prosthesis forms a body configured to augment and / or reconstruct the anatomical shape of a human breast.

8. The implantable soft tissue repair prosthesis according to claim 1, characterized in that: The flexible porous scaffold is a first flexible porous scaffold, wherein the implantable soft tissue repair prosthesis further comprises a second flexible porous scaffold, and wherein a packing density of the first flexible porous scaffold is different from a packing density of the second flexible porous scaffold.

9. The implantable soft tissue repair prosthesis according to claim 8, characterized in that: The second flexible porous support is arranged in one or more intermediate layers, and the one or more intermediate layers at least partially surround the core layer containing the first flexible porous support. The implantable soft tissue repair prosthesis also includes a shell layer containing a third flexible porous support, and the shell layer at least partially surrounds the one or more intermediate layers.

10. The implantable soft tissue repair prosthesis according to claim 9, characterized in that: The packing density of the second flexible porous support and the packing density of the third flexible porous support are both greater than the packing density of the first flexible porous support.

11. The implantable soft tissue repair prosthesis according to claim 10, characterized in that: The third flexible porous support is formed of different subunits than at least one of the second flexible porous support and the first flexible porous support.

12. The implantable soft tissue repair prosthesis according to claim 11, characterized in that: The third flexible porous support is formed in a mosaic pattern.

13. The implantable soft tissue repair prosthesis according to claim 1, characterized in that: The flexible porous scaffold is configured to recover at least 90% of the original volume of the flexible porous scaffold when compressed 50% in the at least one direction.

14. The implantable soft tissue repair prosthesis according to claim 8, characterized in that: The second flexible porous support comprises at least one selected from the following group: a) Shell, b) the base, c) Multiple pillars, and / or d) One or more openings for insertion of a vascular pedicle or other tissue mass.

15. The implantable soft tissue repair prosthesis according to claim 14, characterized in that: The plurality of struts includes at least one curvilinear strut.

16. The implantable soft tissue repair prosthesis according to claim 8, characterized in that: The packing density of the first flexible porous support is between 3% and 10%, and the packing density of the second flexible porous support is between 5% and 10%.

17. The implantable soft tissue repair prosthesis according to claim 1, characterized in that: The flexible porous scaffold is a first flexible porous scaffold, wherein the implantable soft tissue repair prosthesis further comprises a second flexible porous scaffold, and wherein the degradation spectrum of the first flexible porous scaffold is different from the degradation spectrum of the second flexible porous scaffold.

18. The implantable soft tissue repair prosthesis according to claim 8, characterized in that: Also included is a transition portion between the first flexible porous support and the second flexible porous support.

19. The implantable soft tissue repair prosthesis according to claim 1, characterized in that: The compressive stiffness of the implant in at least one direction is between 10% and 20% of the compressive stiffness of the implant in a second direction.

20. The implantable soft tissue repair prosthesis according to claim 1, characterized in that: The compressive stiffness of the implant in the first direction is greater than the compressive stiffness of the implant in the second direction.

21. The implantable soft tissue repair prosthesis according to claim 1, characterized in that: The density of the implant is between 0.02g / cm 3 With 0.2g / cm 3 between.

22. The implantable soft tissue repair prosthesis according to claim 1, characterized in that: The flexible porous scaffold is formed of an absorbable polymer.

23. The implantable soft tissue repair prosthesis according to claim 1, characterized in that: The flexible porous scaffold is formed from poly-4-hydroxybutyrate.

24. The implantable soft tissue repair prosthesis according to claim 1, characterized in that: The triply periodic minimum surface is a helical icosahedron.

25. The implantable soft tissue repair prosthesis according to claim 1, characterized in that: The flexible porous scaffold is at least partially coated with a bioactive agent.

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