Compressible soft tissue prostheses and related methods

Abstract

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-references to related applications

[0002] This application claims the benefit of U.S. Provisional Application 63 / 459,361, filed April 14, 2023, pursuant to 35 U.SC §119(e), the contents of which are incorporated herein by reference in their entirety. Technical Field

[0003] This disclosure relates to implantable prostheses, and more specifically, to prostheses for reconstructing and / or enlarging soft tissue, including human breasts. Background Technology

[0004] Breast reconstruction after mastectomy has become an integral and important part of breast cancer treatment, offering patients both aesthetic and psychosocial benefits. In the United States, nearly 65% ​​of breast reconstruction surgeries currently use tissue expanders to create a pocket for a permanent breast implant in the first step of the procedure. In some patients, a pocket for the breast implant can be formed without the use of tissue expanders. 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 mastectomy to increase breast size. In mastectomy, breast lift is combined with breast augmentation. Most commonly, breast implants are placed in a pocket beneath the breast tissue, but in some cases, they are implanted below the chest wall.

[0006] Breast implants vary in size, shape, and surface texture. A variety of sizes are available, allowing surgeons and patients to choose from a range of protrusions, heights, widths, and overall volumes. In terms of shape, implants exist in both round and anatomical shapes, and their surfaces can be smooth, microtextured, or macrotextured. Generally, round implants have a smooth surface, while anatomically shaped implants have a recessed microtextured or macrotextured surface. Summary of the Invention

[0007] In some embodiments, the implantable soft tissue repair prosthesis includes a flexible porous scaffold formed of at least one triple periodic minimum 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] 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 comprising a flexible porous scaffold formed of at least one triple periodic minimum surface; delivering the implantable prosthesis to the implantation site; and restoring at least 90% of the compression in at least one direction.

[0009] It should be understood that the foregoing concepts and the additional concepts discussed below can be arranged in any suitable combination, as this disclosure is not limited in this respect. Furthermore, other advantages and novel features of this disclosure will become apparent when considered in conjunction with the accompanying drawings, based on the following detailed description of various non-limiting embodiments. Attached Figure Description

[0010] The accompanying 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 numerals. For clarity, not every component is labeled in every drawing. In the drawings:

[0011] Figures 1A to 1C These are, respectively, isometric views, side views, and top views of subunits of an implantable prosthesis stent according to some embodiments;

[0012] Figures 2A to 2C These are, respectively, isometric views, side views, and top views of a portion of a stent for an implantable prosthesis according to some embodiments;

[0013] Figure 3 These are breast implants according to some implementation methods;

[0014] Figures 4A to 4B It is a breast implant according to other embodiments;

[0015] Figures 5A to 5C It is a breast implant according to other embodiments, wherein the stent has a different spatial frequency;

[0016] Figures 6A to 6B These are a top view and a side view of a breast implant according to one embodiment;

[0017] Figures 7A to 7B These are, respectively, a top view and a side view of a breast implant according to another embodiment; and

[0018] Figures 8A to 8B These are, respectively, a top view and a side view of a breast implant according to another embodiment. Detailed Implementation

[0019] A growing number of patients considering breast reconstruction and breast augmentation are reluctant to have permanent breast implants placed in their breasts. This is particularly true for women who have already undergone mastectomy and are currently considering breast reconstruction. Some of these patients do not want permanent foreign objects in their breasts and do not want to risk the potential complications associated with permanent breast implants. Complications include the following potential problems: capsular contracture, implant rupture or shrinkage, development of anaplastic large cell lymphoma (ALCL), infection, and implant displacement leading to breast asymmetry. Many of these complications may require surgical correction, which can be costly and undesirable, in addition to the accumulation of scar tissue and delayed healing.

[0020] In addition to the above, conventional breast implants (e.g., silicone-based implants) are typically formed from homogeneous materials whose mechanical properties do not accurately mimic natural soft tissue, which may include a vascular system and whose stiffness and compressibility vary due to the distribution of muscle and fat. In particular, the inventors have recognized that while conventional soft tissue implants are elastic, they typically do not exhibit sufficient natural compressibility to allow the implant to be compressed to a portion of its original volume and return to its original volume (or a portion thereof), a behavior inherent to natural tissue. This lack of compressibility may also prevent the implant from being compressed during delivery, potentially requiring large incisions for implantation. These incisions may increase the risk of infection, prolong recovery time, and result in large, undesirable scars on the patient.

[0021] In light of the above, the inventors have recognized the benefits associated with implantable prostheses: implantable prostheses balance mechanical properties to support surrounding anatomical structures with high tissue infiltration rates, which can promote an appropriate balance between mechanical support and sensation. Therefore, the inventors have recognized the benefits associated with implantable prostheses: implantable prostheses exhibit sufficient mechanical properties to support the natural tissue at the implantation site and have sufficient porosity to allow tissue to grow inward. In this way, the prosthesis can provide sufficient mechanical support to the implantation site while still allowing rapid tissue growth inward. For example, in some embodiments, implantable prostheses, which may be referred to as implants or prostheses, can achieve mechanical properties similar to natural tissue by using a 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 may include interconnected pores formed between the subunits. These pores can enhance the biodegradability of the scaffold by increasing the surface area, while also increasing the rate of tissue growth inward. The size and arrangement of the subunits, as well as their material composition, can determine the mechanical properties of the prosthesis. For example, denser subunits (e.g., with smaller spatial frequencies or repetition distances between adjacent subunits) may produce greater stiffness compared to less densely arranged subunits. It should be understood that in some embodiments, denser subunit arrangements can also allow for the use of a larger volume of material in the prosthesis, which can increase the prosthesis's stiffness, while a less densely arranged subunit scaffold can produce a less stiff prosthesis. Therefore, the characteristics of the subunits can be tuned to optimize tissue infiltration and the compressibility of the implant.

[0022] In some embodiments, the load-bearing three-dimensional macroporous flexible scaffold of this disclosure can be formed at least partially by subunits formed of corrugated walls. The absence of corners and straight lines reduces stress concentration within the implant and allows for greater compressibility. In some embodiments, the corrugated walls can have planar symmetric curves mimicking the behavior of natural soft tissue, but other symmetry characteristics are also considered. The subunits of the three-dimensional macroporous flexible scaffold can have a minimal surface structure, minimizing their surface area by exhibiting zero mean curvature. Specifically, the minimal surface structure can be a triple periodic minimal surface (TPMS). These minimal surfaces can result in a high surface area to volume ratio of the implant, which can enhance tissue inward growth and implant degradation if the implant is formed of a degradable or bioabsorbable material. A high surface area to volume ratio can also increase the porosity of the implant while reducing its weight, which in turn reduces strain at the implantation site in the patient. The TPMS of this disclosure can also achieve adjustable isotropic and / or anisotropic properties through the scaffold arrangement.

[0023] The TPMS sub-unit can be in the shape of a helical icosahedron, and in some implementations, it can be approximated by the following trigonometric relationship about the three basic directions:

[0024]

[0025] Other TPMS structures have also been envisioned, such as catenary surfaces, helical surfaces, elliptical surfaces, rhomboid surfaces, Bonnet family surfaces, Schwarz P surfaces, Schwarz D surfaces, hybrids thereof, and / or other TPMS structures. Such surfaces can reduce stress concentration to improve the overall compressibility of the implant while increasing porosity.

[0026] Depending on its shape, the implantable prosthesis's stent is compressible in both its radial and axial directions. Furthermore, 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, which may be between 10% and 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 the first direction, which may be only 2%, 5%, 10%, 20%, 30%, or 40% of the mechanical properties in the 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 or equal to about 2% and about 40% of the axial compressive stiffness, or between or equal to about 5% and about 30% of the axial compressive stiffness, or between or equal to about 10% and about 20% of the axial compressive stiffness, or between or equal to about 5% and about 20% of the axial compressive stiffness. Furthermore, it will be understood that different mechanical properties may have different isotropic characteristics, such that the first mechanical property may be isotropic (e.g., the first property in the first direction is within 10% or 20% of the first property in the second direction, or within 10% to 20%), while the second mechanical property may be anisotropic (e.g., the second property in the first direction is 2%, 5%, 10%, 20%, 30%, 40% of the second property in the second direction, or between 2% and 40%). In addition, implants can be non-stretchable (e.g., exhibiting a positive Poisson's ratio) to better mimic natural tissue, but it should be understood that stretchable implants (e.g., exhibiting a negative Poisson's ratio) can also be envisioned.

[0027] In some implementations, large-pore implants may include more than one type of subunit. For example, a portion of the implant's scaffold may include a helical icosahedron, while another portion of the scaffold may include another minimal surface structure. It should be understood that alternative subunits may be used in conjunction with the TPMS subunits described above, including but not limited to closed cavities, partially closed cavities, repeating unit units or mesh unit units, foam units, Kelvin foam units or other open or closed unit foam structures, cruciform structures, struts, nodular portions, channels (whether open, closed or partially closed), waveguides, triangular structures, tetrahedral or other pyramidal shapes, cubes, octahedrons, octagonal prisms, icosahedrons, rhombic icosahedrons 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, mosaic structures such as Voronoi structures or other structures (which may include shape patterns formed without overlap or gaps between shapes), and / or other suitable structures. Three-dimensional implants may include combinations of the aforementioned three-dimensional sub-unit structures in an interconnected mesh.

[0028] In some embodiments, the flexible scaffold of the implantable prosthesis may have a structure providing a large surface area and voids, suitable for allowing the scaffold to be colonized by cells and infiltrated by tissue, blood vessels, or a combination thereof after implantation. Therefore, the implantable prosthesis of this disclosure is characterized by a fill density, defined as the ratio, expressed as a percentage, of the volume occupied by the implant material in the scaffold to the total volume of the implant. The fill density can be designed to balance tissue infiltration, which can be maximized by reducing the fill density, and to have sufficient compressive strength to support the tissue surrounding the implantation site.

[0029] The inventors also recognize that conventional permanent implants can weigh between 150 cc and 1200 cc, more commonly between 300 cc and 800 cc. Conventional permanent implants are typically heavier than equivalent-sized natural breast tissue and may therefore exert excessive strain on the patient's anatomy, such as the chest wall. This strain can cause patient discomfort and pain, and in some cases, may lead to undesirable sagging or drooping of the implant. In light 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 results. As previously described, the implants of this disclosure can exhibit porosity characterized by filler density. In some embodiments, the weight of the implants of this disclosure at implantation can be approximately 80% to 97% of the weight of conventional silicone implants. In some embodiments, filler density can also determine the total weight of the implant at implantation. It should be understood that the porous scaffolds of this disclosure can generally be lighter than conventional silicone implants, which can reduce the load on surrounding tissues. In some implementations, the implant may weigh less than 10 grams, although other weights are also conceivable, as the weight of the implant can depend on a variety of parameters, including the desired application, material composition, geometry, and filler density.

[0030] It should be understood that the total weight of an implant may vary over time due to material degradation, compared to conventional permanent implants. This gradual change in implant weight allows for cell infiltration, maturation, and aggregation (e.g., tissue formation). Long after implantation, the weight of a mulch can be comparable to that of natural breast tissue, and in some implementations, it can be less than the weight of a permanent implant of equivalent size (e.g., formed from silicone).

[0031] In some embodiments, the filler density of an implantable prosthesis according to any of the embodiments disclosed herein may be less than or equal to about 60% to induce tissue infiltration while still exhibiting the desired mechanical properties. In some embodiments, the implantable prosthesis of this disclosure may have a filler density greater than or equal to about 1%, 2%, 4%, 5%, 6%, 8%, 9%, 10%, 12%, 15%, 20%, 30%, 40%, 50%, or combinations thereof and / or any other suitable filler density. The implantable prosthesis may also have a filler density less than or equal to about 60%, 50%, 40%, 30%, 20%, 15%, 12%, 10%, 9%, 8%, 6%, 5%, 4%, 2%, 1%, or combinations thereof and / or any other suitable filler density. Combinations of the foregoing are contemplated, including but not limited to filler densities between about 1% and 60%, between about 3% and 15%, and between about 3% and 10%. In some embodiments, the filler density may be between about 4% and 8%. It should be understood that the filler density of an implant can depend on the geometry of the subunit used, the overall size of the implant, the manufacturing method, the implantation site requirements, and / or any other suitable parameters. Therefore, the implants of this disclosure can have any suitable filler density.

[0032] In some embodiments, the aperture of the implant scaffold may be large enough to allow needle insertion into the aperture of the scaffold for delivery of bioactive agents, cells, adipocytes, and / or other suitable compositions by injection. In some embodiments, the scaffold architecture is designed to allow insertion of needles with gauges 12 to 21 into the scaffold to allow 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 material delivered into the scaffold. In some embodiments, the scaffold may allow 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 may be designed to accommodate larger and smaller gauge needles, as this disclosure is not limited thereto.

[0033] The implantable stent can also be characterized by its weight per unit volume, which is determined by the density of the constituent materials of the subunits, the size of the prosthesis, the filler density, the number / size of the subunits, and many other parameters. In some embodiments, the stent's weight per unit volume can be approximately 0.01 g / cm³. 3 With 0.2 g / cm 3 Between, approximately 0.02 g / cm³ 3 With 0.2 g / cm 3 Between, approximately 0.03 g / cm 3 With 0.05 g / cm 3Between, approximately 0.01 g / cm 3 With 0.5 g / cm 3 Between, or in combination thereof, and / or for any other suitable unit volume weight. Of course, unit volume weights less than and greater than those described above can be envisioned, as this disclosure is not limited thereto.

[0034] A high surface area increases the available volume of tissue infiltration throughout the scaffold. A high surface area also increases the volume of therapeutic compounds that can be delivered with the implant (e.g., coated onto the implant, as will be described in detail below). Therefore, 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 may be greater than or equal to approximately 500 cm². 2 1000cm 2 5000 cm 2 1 m 2 2 m 2 And / or any other suitable surface area. The surface area of ​​the support may also be less than or equal to approximately 2 m². 2 1 m 2 5000 cm 2 And / or any other suitable surface area to ensure sufficient material is available to support the surrounding tissue. Combinations of the foregoing are envisioned, including, for example, within 500 cm². 2 With 2 m 2 The area between them is equal to or equal to 500 cm² 2 and 2 m 2 The area, although other suitable areas can also be used.

[0035] In some embodiments, the implant may be compressible, thus allowing it to be delivered to the implantation site via a delivery device, such as a Keller funnel. In some embodiments, the implant may be delivered into the breast via a funnel with a neck diameter (i.e., the narrowest part of the funnel) of approximately 2.5 cm to 7.5 cm, and more preferably 3.75 cm to 6.25 cm. In some embodiments, the implant may be delivered via a funnel with a neck diameter of 2.5 cm to 7.5 cm and recover a percentage of its original volume after being delivered to the implantation site through the neck of the funnel. In some embodiments, the implant may have anisotropic compressive stiffness to facilitate delivery via a delivery device and / or incision. For example, as described above, the compressive stiffness of the implant in the radial direction is less than its compressive stiffness in the axial direction, such that the base of the implant can be compressed as it passes through the neck diameter and / or incision. However, it will be understood that isotropic embodiments may also be suitable for delivery via a funnel.

[0036] In light of the above, implants can therefore possess a compressive modulus, allowing them to be delivered to the implantation site through an incision smaller than the implant's original size, thereby reducing scarring at the implantation site for faster recovery and better aesthetics. The compressive modulus also allows the implant to be compressed when compressive forces are applied and to recover from compression when the compressive forces are removed. Implants can be designed to make the breast feel soft, similar to a natural breast. In some implementations, implants can allow surgeons to restore or increase breast mass while maintaining or restoring tactile sensation.

[0037] In some implementations, the implant may have a compressive modulus between approximately 0.1 kPa and 10 MPa, 0.3 kPa and 1 MPa and / or 3 kPa and 200 kPa, but other compressive modulus ranges greater than or less than those ranges may also be conceived depending on the needs of the implantation site tissue.

[0038] In some implementations, the compressibility of the implant can be characterized by compressive elasticity, which is calculated as the work done during compression recovery divided by the work done during compression multiplied by 100. The compressive elasticity of the implant described herein can be between 1% and 80%, although other ranges are also conceivable, such as greater than or equal to approximately 50%, 60%, 70%, 80%, 90%, etc.

[0039] In some embodiments, the implant may be configured to recover at least 50% of its original volume after a compressive force is applied and subsequently removed. This behavior allows for easy delivery through incisions smaller than the size of the implant and also provides a more natural feel to the implant. For example, after 50% compression, the implant of this disclosure may recover at least about 75% of its original volume. In some embodiments, after applying and subsequently removing the compressive force required to compress the implant by 50%, the implant may recover at least greater than or equal to about 50%, 70%, 75%, 80%, 90%, 95%, 98%, and / or any other suitable proportion of its original volume. In some embodiments, after a 50% relative compressive displacement occurs in one or more directions, the implant may preferably recover at least about 90%, and more preferably 95%, of its original volume. According to embodiments, this recovery of the material after compression may be isotropic, although embodiments in which the recovery of the material is anisotropic (e.g., radial compressibility and recovery greater than or less than axial compressibility and recovery) are contemplated.

[0040] In some embodiments, the implant may be characterized by its compressive modulus. The implant may have a compressive modulus that matches that of natural tissue for a more natural feel. In some embodiments, the implant may have a compressive modulus between approximately 0.01 kPa and 290 MPa, 0.1 kPa and 10 MPa, 0.1 kPa and 1 MPa, 0.1 kPa and 100 kPa, 2 kPa and 100 kPa, 0.1 kPa and 1 MPa, and combinations thereof, and / or any other suitable compressive modulus for the application. For example, in the case of the implant used in breast reconstruction surgery, the compressive modulus may be between approximately 0.1 kPa and 1 MPa or between 2 kPa and 100 kPa. Embodiments with implant compressive moduli greater than or less than those described above are contemplated.

[0041] It should be understood that the compressive modulus (and / or any other mechanical properties) of the implant can vary over time as the implant degrades and is replaced by natural tissue. Therefore, the aforementioned range of compressive modulus can be referenced to the implant before or at the time of implantation. In some embodiments, the compressive modulus of the implant can gradually decrease and approximate the properties of natural breast tissue, which may exhibit, for example, a modulus between approximately 2 kPa and 70 kPa. The implant can approximate the properties of natural breast tissue for any suitable period after implantation, including but not limited to approximately 1 month to 5 years, approximately 3 months to 3 years, approximately 6 months to 2 years, and / or combinations thereof.

[0042] In some embodiments, the implantable prosthesis may have one or more regions. In some embodiments, the one or more regions may differ in any suitable manner in terms of degradation rate and strength loss distribution, including but not limited to variations in the following aspects: filler density, molecular weight of constituent polymers, fiber size, structural design, combination thereof, and / or any other suitable manner. For example, in some embodiments, the prosthesis may include a radial region formed by a first subunit arrangement and a second radial region formed by a second subunit arrangement having a greater filler 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 ranging between one or more subunit arrangements (e.g., size, distribution, filler density, etc.). For example, the implant may include a transition region between two regions to allow for a gradual change in properties. Thus, a smooth (e.g., linear or nonlinear, etc.) transition may exist between properties that may depend on the subunit arrangement, such as compressive stiffness. Embodiments including one or more distinct regions and one or more gradient regions are contemplated. Therefore, the various scaffold and implant properties described herein may refer to the entire scaffold or a portion thereof.

[0043] In addition to the above, in embodiments where different regions include 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 of 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 approximately 1%, 2%, 4%, 5%, 6%, 8%, 9%, 10%, 12%, 15%, 20%, 30%, 40%, 50%, or any other suitable average filling density. Implantable prostheses may also have an average filling density less than or equal to approximately 60%, 50%, 40%, 30%, 20%, 15%, 12%, 10%, 9%, 8%, 6%, 5%, 4%, 2%, 1%, or any other suitable average filling density. The aforementioned combinations are contemplated, including but not limited to average filling densities between approximately 1% and 60%, between approximately 3% and 15%, and between approximately 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 fill density of the implant can depend on the number of regions used, the geometry of the subunits used in each region, the overall size of the implant, the manufacturing method, the implantation site requirements, and / or any other suitable parameters. Therefore, the implants of this disclosure can have any suitable average fill density.

[0044] As previously described, in some embodiments, the implants of this disclosure can be formed with anisotropic properties to better mimic the properties of natural tissue, which is typically non-homogeneous and comprises a variety of materials arranged in a precise manner. Therefore, the implant can have non-uniform properties in one or more directions and can thus be anisotropic in one or more ways (e.g., by mechanical or geometric properties or combinations thereof). For example, the implant can have a first compressive modulus in the radial direction and a second different compressive modulus in the axial direction. In some embodiments, the properties can vary in a gradient manner in one or more directions of the implant. As previously described, the stent can include one or more transition regions to achieve a gradual change in properties between two regions in the implant. Therefore, it should be understood that the properties described herein can refer to the entire implant or a portion or more of the implant.

[0045] In some embodiments, variations in mechanical properties, such as compressive stiffness, may be due to variations in geometry. For example, a smaller subunit with a lower spatial frequency relative to other adjacent portions of the implant can produce a larger filler density, which can subsequently result in greater compressive stiffness relative to a stent with a larger subunit. Therefore, the mechanical properties of the stent may be directly influenced by the stent's geometry. In some embodiments, variations in mechanical properties may be due to variations in the properties of the constituent materials of the subunits. For example, the implant may include two subunit regions having substantially the same geometry but made of (and / or coated with) different materials to produce differences in mechanical properties. As will be described in more detail below, in some embodiments, the implant may include a support structure for providing localized mechanical support to the implant.

[0046] In some embodiments, the implantable prosthesis of this 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 anatomical cavities left by tissue removal surgery (e.g., mass excision) and / or any other natural or surgically formed cavity. However, it should be understood that the implantable prosthesis of this disclosure may have any suitable three-dimensional shape, including but not limited to spheres, domes, ellipsoids, hemispheres, cylinders, cones, domes, cuboids, tetrahedrons, triangular or square prisms, dodecahedrons, tori, combinations thereof, and / or custom geometries. Partial versions of the aforementioned geometries are contemplated, such as a semi-domed shape. Combinations of the aforementioned geometries are also contemplated, including, for example, a teardrop shape, a partially 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 aforementioned geometries, including partial versions and combinations thereof, can be selected and / or constructed to simulate, enlarge, and / or otherwise achieve a desired anatomical shape, such as the desired shape of a natural breast or a portion 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 quasi-spherical shape, and a spherical shape (which may have substantially similar average diameters in all directions). In some embodiments, the implantable prosthesis can be formed from an assembly consisting of one or more scaffolds. For example, a spherical implant for use in a mass resection procedure can be formed by fusing or otherwise combining two hemispherical implants.

[0047] In some cases, the implantable prostheses disclosed herein may have asymmetrical shapes. For example, implantable prostheses may have different shapes in the anterior base region and the anterior top region of the implant. The size of the implant may be designed to increase breast tissue volume, replace previous breast tissue volume, alter the volume distribution of breast tissue, change the appearance of breast tissue, or replace existing breast tissue volume with a smaller volume. Implantable prostheses may be sized or shaped to provide a low, medium, or high profile to the breast, wherein the implant profile determines the prominence of the breast. High-profile implantable prostheses may be used to increase the height of the breast lateral walls and provide patients with greater upper pole fullness or cleavage. Smaller increases in breast lateral wall height can be achieved using implantable prostheses with low or medium profiles. Implantable prostheses may be designed for use in the breast and are large enough to allow for use in mastectomy and breast reconstruction. Patient-specific custom implant sizes are also envisioned. In some implementations, the implantable prosthesis may have a volume between 100 cc and 1200 cc (cubic centimeters) and / or between 120 cc and 850 cc, but other volumes larger and smaller than those mentioned above are also possible.

[0048] The implantable prosthesis disclosed herein can be formed of a biocompatible material that promotes rapid inward growth 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 in the body by the patient's natural tissue as the implant degrades.

[0049] In some implementations, the prosthesis may be formed of an absorbable material (e.g., a polymer or copolymer) that can be substantially reabsorbed within a timeframe of 1 to 24 months or 3 to 18 months after implantation, and retain some residual strength for at least 2 weeks to 6 months.

[0050] In some embodiments, the implant or stent may include an absorbable polymer comprising or 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.

[0051] In some embodiments, the implant may be formed from poly-4-hydroxybutyrate (P4HB) and its copolymers, or poly(butylene succinate) (PBS) and its copolymers. In some embodiments, the P4HB and PBS polymers and their copolymers may not be cross-linked. In some embodiments, the PBS polymers and copolymers may also include one or more of the following: branching agents, cross-linking agents, chain extenders, and reactive blending agents. The PBS and P4HB polymers and copolymers may be isotopically enriched in some embodiments.

[0052] In some embodiments, the polymer 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 the polystyrene determined by GPC, but polymers with other weight average molecular weights are contemplated.

[0053] In some embodiments, the prosthesis may be formed of a biodegradable material, including but not limited to thermoplastic or polymeric biodegradable 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 from glycolic acid, lactic acid, 1,4-dioxane, trimethylene carbonate, 3-hydroxybutyric acid, 4-hydroxybutyrate, and ε-caprolactone, including polyglycolic acid, polylactic acid, polydioxane, polycaprolactone, copolymers of glycolic acid and lactic acid, such as VICRYL. ® Polymer, MAXON ® and MONOCRYL ®Polymers, including poly(lactide-co-caprolactone); poly(orthoester); polyanhydride; poly(phosphazene); polyhydroxyalkanoates; polyesters prepared synthetically or biologically; polycarbonates; tyrosine polycarbonates; polyamides (including synthetic and natural polyamides, peptides and poly(amino acids)); polyesteramides; poly(alkylene alkylates); polyethers (such as polyethylene glycol PEG and polyethylene oxide PEO); polyvinylpyrrolidone or PVP; polyurethanes; polyether esters; polyacetals; polycyanoacrylates; poly(ethylene oxide) / poly(propylene oxide) copolymers; polyacetals, polyketides; polyphosphates (polyphosphates). osphate); (phosphorus-containing) polymers; polyphosphoesters; polyalkylene oxalates; polyalkylene succinates; poly(maleic acid); filaments (including recombinant filaments and filament derivatives and analogs); chitin; chitosan; modified chitosan; biocompatible polysaccharides; hydrophilic or water-soluble polymers, such as polyethylene glycol (PEG) or polyvinylpyrrolidone (PVP), and blocks of other biocompatible or biodegradable polymers, such as poly(lactide), poly(lactide-co-glycolic acid), or polycaprolactone and their copolymers, including their random copolymers and block copolymers.

[0054] In some embodiments, the implantable prosthesis may 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 may 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 may be used, as this disclosure is not limited thereto. This may include coatings, absorbent materials retained in a porous scaffold of the prosthesis, absorbent materials, compounds of materials functionally bound to the implantable prosthesis, and / or any other suitable manner of associating the therapeutic composition with the implantable prosthesis. Suitable types of therapeutic compositions may include, but are not limited to, cells, stem cells, differentiated cells, adipocytes, muscle cells, platelets, pedicles, vascular pedicles, tissue blocks, extracellular fatty 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 implantation site. The cells and tissues that can be delivered and / or coated or injected into the prosthesis may be autologous. The prosthesis may be used for autologous fat transfer. Cells added, coated, or injected onto the prosthesis may include pancreatic islet cells, hepatocytes, and stem cells genetically modified to contain genes used to treat a patient's disease. The prosthesis may include bioactive agents to stimulate inward cell growth, 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 to promote cell migration, cell division, cell proliferation, and extracellular matrix deposition. The prosthesis may also be partially or completely coated and / or contain agents to prevent tissue adhesion or to prevent cell proliferation, particularly delaying cell invasion into the prosthesis.

[0055] In some embodiments, the implantable prosthesis may be partially or completely loaded, filled, coated, or otherwise incorporated with a bioactive agent. The bioactive agent may be included in the prosthesis for a variety of reasons. For example, it may be included to improve tissue inward growth into the implant, improve tissue maturation, provide delivery of the active agent, improve the wettability of the implant, prevent infection, and improve cell adhesion. The bioactive agent may also be incorporated into the material composition of the subunit's substrate, including by blending the material composition with the bioactive agent.

[0056] The prosthesis may contain active agents designed to stimulate inward cell growth. These active agents include growth factors, cell adhesion factors including cell adhesion peptides, cell differentiation factors, cell recruitment factors, cell receptors, cell binding factors, cell signaling molecules such as cytokines, and molecules that promote cell migration, cell division, cell proliferation, and extracellular matrix deposition. 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-1β (IL-1β), interleukin-8 (IL-8), and nerve growth factor (NGF), and combinations thereof. As used herein, the term "cell adhesion peptide" refers to a compound having at least two amino acids per molecule that can bind to cells via cell surface molecules. Cell adhesion peptides include any protein in the extracellular matrix known to play a role in cell adhesion, including fibronectin, porphyrin, laminin, elastin, fibrinogen, type I collagen, type II collagen, and type V collagen, as well as synthetic peptides with similar cell adhesion properties. Cell adhesion peptides also include peptides derived from any of the aforementioned proteins, including fragments or sequences containing a binding domain.

[0057] In some embodiments, the implantable prosthesis may be loaded, filled, coated, or otherwise incorporated with a wetting agent designed to improve the wettability of various surfaces of the prosthesis to allow fluids to readily adhere to 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 PLURONICS®. Other suitable wetting agents may include surfactants or emulsifiers.

[0058] In some embodiments, the implantable prosthesis may be loaded, filled, coated, or otherwise incorporated with a gel, hydrogel, or mixture of active hydrogels to further improve wetting properties and promote cell growth throughout the prosthesis. The hydrogel mixture may consist of living cells encapsulated in biocompatible hydrogels such as gelatin, methacrylated gelatin (GelMa), silk gel, and hyaluronic acid (HA) gel.

[0059] Other bioactive agents that can be incorporated into prostheses can include antimicrobial agents, particularly antibiotics, disinfectants, oncology agents, anti-scarring agents, anti-inflammatory agents, anesthetics, small molecule drugs, anti-adhesion agents, cell proliferation inhibitors, anti-angiogenic and pro-angiogenic factors, immunomodulators, and coagulants. Bioactive agents can be proteins such as collagen and antibodies, peptides, polysaccharides such as chitosan, alginate, hyaluronic acid and its derivatives, nucleic acid molecules, low molecular weight compounds such as steroids, inorganic materials such as hydroxyapatite and ceramics, or complex mixtures such as platelet-rich plasma. Suitable antimicrobial agents include bacitracin, biguanide, triclosan, gentamicin, minocycline, rifampin, vancomycin, cephalosporins, copper, zinc, silver, and gold. Nucleic acid molecules can include DNA, RNA, siRNA, miRNA, antisense molecules, or aptamers.

[0060] In some embodiments, the implantable prosthesis may be loaded, filled, coated, or otherwise incorporated with allogeneic and xenograft materials, including acellular dermal matrix materials and small intestinal submucosal (SIS) materials. In embodiments, the prosthesis may include a vascular pedicle or other tissue block. In some embodiments, the prosthesis may be incorporated into a system for the controlled release of therapeutic or prophylactic agents.

[0061] In some embodiments, the implantable prosthesis may be loaded, filled, coated, or otherwise incorporated with allogeneic or xenograft tissues and cells before, during, or after implantation, or any combination thereof. In some embodiments, the prosthesis may be coated with autologous tissues and cells from the patient before, during, or after implantation, or any combination thereof. Autologous tissues and cells may include one or more of the following: autologous fat, liposuction, adipose tissue, injectable fat, adipose tissue, adipose cells, fibroblasts, and stem cells, including human adipose tissue-derived stem cells, also known as precursor adipose cells or adipose tissue-derived precursor cells, and fibroblast-like stem cells. In one embodiment, the prosthesis may be coated with autologous tissues and cells as described herein and may further include a vascular pedicle or other tissue blocks. As will be apparent herein, the prosthesis is designed not only to produce the shape of an implant, such as a breast implant, but also to produce a large surface area that can retain autologous tissues and cells to promote inward tissue growth.

[0062] In some embodiments, the polymer and copolymer composition of the prosthesis may have a low moisture content to ensure that the prosthesis can be manufactured with extended strength retention and a good shelf life. In some embodiments, the polymer and copolymer 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%).

[0063] It should be understood that the prosthesis should have an appropriately low endotoxin content before implantation. The composition used to prepare the prosthesis can have a low endotoxin content. In some embodiments, the endotoxin content can be low enough that the prosthesis produced from the polymer composition has an endotoxin content of less than 20 endotoxin units per prosthesis, as determined by horseshoe crab lysate (LAL) assay. For example, the endotoxin content of the polymer composition used to prepare the prosthesis can be <2.5 EU / g polymer or copolymer. In another example, the endotoxin content of the P4HB polymer or copolymer or the PBS polymer or copolymer is <2.5 EU / g polymer or copolymer.

[0064] In some embodiments, the prosthesis of this disclosure may include one or more markers for external detection of the prosthesis position. For example, the prosthesis may include radiopaque markers (e.g., metallic tags, radiopaque material incorporated into the printed wall of an implant formed by an additive manufacturing process, or other suitable types of markers) that are visible and conspicuous on nearby anatomical structures during x-ray imaging. The markers may be formed from any suitable medical material suitable for medical imaging. Medical imaging may be performed using, for example, radiographic imaging modalities (e.g., x-ray imaging), magnetic resonance imaging (MRI), ultrasound, fluoroscopy, or computed tomography. The markers may therefore be formed from any non-absorbable biocompatible material, which may refer to a material that will not cause any adverse effects on the patient's health and will not degrade during the patient's lifetime. Non-absorbable biocompatible materials may include, but are not limited to, metallic materials, polymeric materials, ceramic materials, or composite materials comprising metals, polymers, or combinations of metals and polymers. Suitable metals may 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, polyolefins, polyesters, polypropylene, polyimide, polyetherimide, fluoropolymers, thermoplastic liquid polymers (LCPs) such as Vectra® from Celanese, polyvinyl ether ketone such as PEEK™ from Vitrex, polyamides, polycarbonates such as Makrolon® from Bayer Polymers, polysulfone, polyethersulfone, polyphenylsulfone such as Radel® from Rowland Technologies, nylon, nylon copolymers, combinations thereof, and / or other polymers. In some embodiments, the marking may include shape memory materials, including but not limited to nitinol, titanium, or any shape memory polymer.

[0065] Certain additives can be incorporated into implants, preferably into polymer compositions used to manufacture scaffolds. In one embodiment, these additives are combined with the polymers or copolymers described herein during a compounding process to produce granules, which can then be processed to produce scaffolds. For example, the granules can be injection molded, extruded, or more preferably printed using additive manufacturing processes to form scaffolds or scaffold cells. In another embodiment, the granules can be ground to produce powders suitable for further processing, such as using additive manufacturing processes. Alternatively, powders suitable for further processing, such as using additive manufacturing processes, can be formed directly by blending the additives with the polymer or copolymer. If desired, the powders for processing can be sieved to select an optimal particle size range. In another embodiment, the additives can be incorporated into polymer compositions used to prepare scaffolds for implants using a solution-based method.

[0066] In some embodiments, the additives mentioned above may be nucleating agents and / or plasticizers. These additives may be added in sufficient quantities to the polymeric composition used to prepare the implant scaffold to produce the desired results. Typically, these additives may be added in amounts between 1 wt% and 20 wt% relative to the total weight of the material. Nucleating agents may be combined to increase the crystallization rate of the polymer, copolymer, or blend. Such agents may be used, for example, to facilitate the manufacture of the scaffold and improve its mechanical properties. Preferred nucleating agents include, but are not limited to, salts of organic acids such as calcium citrate, polymers or oligomers of PHA polymers and copolymers, high-melting-point polymers such as PGA, talc, micronized mica, calcium carbonate, ammonium chloride, and aromatic amino acids such as tyrosine and phenylalanine.

[0067] Plasticizers that can be incorporated into polymer compositions used to prepare implant scaffolds include, but are not limited to, dibutyl maleate, methyl laurate, dibutyl fumarate, di(2-ethylhexyl)(dioctyl)maleate, paraffin wax, dodecyl alcohol, olive oil, soybean oil, polytetramethylene glycol, methyl oleate, n-propyl oleate, tetrahydrofurfuryl oleate, epoxidized linseed oil, 2-ethylhexyl epoxy tall oleate, glyceryl triacetate, methyl linoleate, and dibutyl fumarate. Methylacetyl 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-butylacetyl ricinoleate, propylene glycol ricinoleate, diethyl succinate, diisobutyl adipate, dimethyl azelaate, di(n-hexyl) azelaate, tributyl phosphate, and mixtures thereof. A particularly preferred plasticizer is citrate.

[0068] 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 flexible scaffolds for implants, allowing for precise control over the shape of the scaffold. Suitable methods for forming subunit scaffolds include fused filament fabrication, fused pellet deposition, melt extrusion deposition, selective laser melting (e.g., fused powder bed), printing pastes and solutions using a coagulation bath, printing using binder solutions and powder particles, stereolithography, 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 used to form any part (e.g., scaffold) of the implant described herein, as this disclosure is not limited thereto.

[0069] In some embodiments, the three-dimensional implant of this disclosure may include a scaffold as previously described and one or more support structures for locally modifying the properties 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 to help modify the local properties of the implant. For example, the implant may include columns that extend partially or entirely along one or more directions relative to the implant (e.g., radial, axial) and may have linear, non-linear, curved, combinations thereof, and / or any other suitable structure. 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 block to be inserted into the implant or for causing the implant to clamp a vascular pedicle or other tissue block, and for allowing a vascular pedicle or other tissue block to be inserted into one or more openings or pathways in the implant, including one or more lateral pathways.

[0070] 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 stent (or optionally, completely surrounding it). The shell may be used to deliver an initial dose of the bioactive agent (or any other material) and / or to provide mechanical or structural functionality to the implant. In some embodiments, the thickness of the shell or coating may be in the range of approximately 0.01 mm to 5 mm, 0.5 mm to 2 mm, 0.1 mm to 1 mm, and / or any other suitable thickness. In some embodiments, the shell may be formed from concentric stacks of filaments at the periphery of the stent. In other embodiments, the shell thickness is formed from more than one layer of filaments. In still other embodiments, the shell may be formed from a foam having interconnected pores. In embodiments, the shell is an open-cell foam and / or includes open-cell foam comprising poly-4-hydroxybutyrate or copolymers thereof or poly(butylene succinate) or copolymers thereof. In some embodiments, the shell may be heat-treated to minimize the roughness of the outer surface of the shell.

[0071] In some embodiments, the shell or coating may be needle-permeable, allowing a surgeon to suture or otherwise secure the implant to the implantation site. Alternatively or in combination, the implant may include retainers, such as barbs or pins, located on one or more outer surfaces of the implant, allowing the implant to be anchored in the body without the use of sutures. The implant may include retainers located at the peripheral boundary of the implant or within the scaffold structure of the implant. In embodiments, retainers may be located on the implant to allow the implant to be anchored to the chest wall.

[0072] In some embodiments, the implant may include one or more suture protrusions, allowing the implant to be anchored in the body using sutures or staples. The number of protrusions may depend on the implant size (e.g., larger implants may require more protrusions). The protrusions attached to the implant may have sufficient strength retention in the body to resist mechanical loads and allow sufficient inward tissue growth 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 may be greater than 10 N and / or greater than 20 N. It should be understood that the implant may be directly secured in the body without the use of suture protrusions or a shell, as this disclosure is not limited thereto.

[0073] In some embodiments, a method of implanting an implant into a patient's breast may include at least the following steps: (i) making at least one incision to obtain access to the patient's breast tissue; (ii) separating the skin and subcutaneous fascia from the mammary ridges of the breast; (iii) positioning the implant on the mammary ridges of the breast; (iv) securing the implant to the tissue surrounding the mammary ridges 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 liposuction and coating or filling the implant with the sample before implantation; (b) preparing a sample of liposuction and coating or filling the implant with the sample after implantation, preferably by injecting the sample into the implant; (c) inserting a vascular pedicle into the implant before or after implantation; and (d) suturing or stapled the implant into place. The implant may be implanted in a subglandular, subpectoral, or anterior pectoral location. In one implementation, the implant can be sutured to the tissue surrounding the mound of the breast (e.g., the fascia around the pectoral muscle beneath the mound of the breast).

[0074] As previously mentioned, in some embodiments, soft tissue implantable prostheses can be used for soft tissue regeneration, enlargement, repair, enhancement, replacement, and / or reconstruction. For example, implants can be used to reshape the breast, fill gaps in the breast, lift the breast, and enlarge the breast. Implants can reduce the need for permanent breast implants during mastectomy, breast fixation, lump removal, and breast augmentation surgery. Implants can be biocompatible and, in some cases, absorbable, allowing them to be replaced by the patient's tissue within the body as the implant degrades. Implants can have a compressive modulus that allows the implant to temporarily deform under compressive forces, recover its shape from compression when the force is removed, and have a feel similar to breast tissue. In some embodiments, implants can be coated or filled with materials to induce inward tissue growth and / or reduce the risk of infection. For example, implants can be coated or filled with autologous tissue, autologous fat, liposuction, injectable fat, adipocytes, fibroblasts, and stem cells before, during, or after implantation.

[0075] In view of the foregoing, the disclosed implantable prostheses can be used in many different applications and can provide many different benefits. This can include, for example, soft tissue reconstruction and / or enlargement. This can include reconstruction of surgically removed or excised tissue (e.g., in a mass excision 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 infiltration, where tissue can grow into the prosthesis. Inward tissue growth into the prosthesis's pore space 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 of biopsy and / or tissue excision sites. The prosthesis can be visible using one or more medical imaging systems to enable external detection of the site used for therapeutic and imaging applications. The prosthesis can have the benefits of reducing the volume of clinical targets in radiotherapy and improving cosmetic results after mass excision. However, examples of different benefits provided by the systems and methods disclosed herein are also possible.

[0076] The implantable prostheses disclosed herein can be used in any suitable application. In some embodiments, the prostheses can be implanted into soft tissue after a biopsy (and / or any other procedure) during treatment for cancers such as breast cancer, abdominal cancer, liver cancer, muscle cancer, kidney cancer, lung cancer, and prostate cancer. In some embodiments, the prostheses can be used in soft tissue reconstruction applications, such that the prostheses can be used as breast implants, breast lift devices, breast enlargement devices, nipple implants, facial reconstruction devices, buttock implants, cheekbone enlargement devices, cosmetic repair devices, soft tissue regeneration devices, hernia implants, hernia plugs, wound healing devices, tissue engineering scaffolds, scaffolds for vascular pedicles or other tissue blocks, guided tissue repair / regeneration devices, expansion or filling devices, void fillers, devices for treating vesicoureteral reflux, cell seeding devices, drug delivery devices, combinations thereof, and / or any other suitable application. In embodiments, the implants have shapes and sizes suitable for use in breast surgery procedures including breast enlargement, breast reconstruction, and mastectomy.

[0077] As is commonly used in this article, “absorbable” means that a material degrades in the body and that the degradation products are eliminated or excreted from the body. The terms “absorbable,” “reabsorbable,” “degradable,” and “erosive”—with or without the prefix “bio”—are used interchangeably in this article to describe materials that are broken down and gradually absorbed, excreted, or eliminated by the body, whether the degradation is primarily due to hydrolysis or mediated by metabolic processes.

[0078] As is commonly used in this article, "bioactive agent" refers to therapeutic agents, preventative or diagnostic agents, agents that promote the healing and regeneration of host tissues, and therapeutic agents that prevent, inhibit, or eliminate infection. "Agent" includes such agents alone, and is also intended to include multiple agents.

[0079] As is commonly used in this article, "biocompatibility" means that the biological response of a material or device is suitable for its intended in vivo application. Any metabolites of these materials should also be biocompatible.

[0080] As is commonly used in this article, “blend” refers to a physical combination of different polymers, as opposed to a copolymer formed from two or more different monomers.

[0081] As used in this article, "compression modulus" is measured using a mechanical testing machine (QTest™ / 1L, MTS, USA) at 20 mm / min. −1 The measurements were taken at crosshead speeds. Samples were preloaded (10% of the initial compressive load) to incorporate the load and compressed until 1 mm (20%) of the sample's original height. Clinically relevant cyclic loading was repeated 10 times, and the compressive modulus was calculated based on the second cyclic load, which is an artificial product of relaxation absorption and sample alignment or seating. The compressive modulus can also be measured using ASTM standards ASTM D1621-16 or ASTM D695-15.

[0082] As used in this article, “compression resilience” is calculated as the work done during compression recovery divided by the work done during compression multiplied by 100.

[0083] As is commonly used herein, “polymer of poly-4-hydroxybutyrate” means any polymer containing 4-hydroxybutyrate having one or more different hydroxy acid units. The copolymer may be isotopically enriched.

[0084] As is commonly used herein, "polymer of poly(butylene succinate)" means any polymer comprising 1,4-butanediol and diacid units, as well as one or more different diol or diacid units. The copolymer may contain one or more of the following: branching agents, crosslinking agents, chain extenders, and reactive blending agents. The copolymer may be isotopically enriched.

[0085] As is commonly used in this article, “endotoxin content” refers to the amount of endotoxin present in the implant or sample, and is determined by horseshoe crab amoeboid lysate (LAL) analysis.

[0086] As used in this article, “fill density” is the ratio of the volume of 3D printed material in the implant scaffold to the total volume of the 3D printed scaffold, expressed as a percentage.

[0087] As is commonly used herein, "poly(butylene succinate)" refers to a polymer containing 1,4-butanediol and succinic acid units. The polymer may contain one or more of the following: branching agents, crosslinking agents, chain extenders, and reactive blending agents. The polymer may be isotopically enriched.

[0088] "Poly(butylene succinate) and copolymers" includes polymers and copolymers prepared using one or more of the following: chain extenders, coupling agents, crosslinking agents, and branching agents.

[0089] As is commonly used in this document, "poly-4-hydroxybutyrate" refers to a homopolymer containing 4-hydroxybutyrate units. Poly-4-hydroxybutyrate may also refer to P4HB or TephaFLEX® biomaterials (manufactured by Tepha, Inc., Lexington, Massachusetts). The polymer may be isotopically enriched.

[0090] As used in this article, "soft tissue" refers to body tissue that is not hardened or calcified. Soft tissue does not include hard tissues such as bone and tooth enamel.

[0091] "Strength retention rate" refers to the amount of time a material retains specific mechanical properties after being implanted into a human or animal. For example, if the tensile strength of a reabsorbable fiber or strut decreases by half after 3 months when implanted into an animal, the strength retention rate of the fiber or strut after 3 months will be 50%.

[0092] As used in this paper, “surface roughness” (Ra) is the arithmetic mean of the absolute values ​​of the profile height deviation from the centerline recorded over the evaluation length.

[0093] Turning to the accompanying drawings, specific non-limiting embodiments are described in further detail. It should be understood that the various systems, components, features, and methods described with respect to these embodiments can be used individually and / or in any desired combination, as this disclosure is not limited to the specific embodiments described herein.

[0094] Figure 1A An exemplary subunit 20 of an implant scaffold according to some embodiments is shown. Subunit 20 may include a TPMS or helical icosahedral surface 22, which forms large apertures 25 extending through the resulting scaffold to provide a series of interconnected apertures extending through the implant. Figure 1A As shown in the isometric view, the helical icosahedral surface 22 can increase the surface area of ​​the sub-unit 20 while reducing local stress, so that the sub-unit and the support formed by the sub-unit can be highly compressible and can restore the compressibility, as previously described.

[0095] Figures 1B to 2C Showing from Figure 1A Various views of the sub-unit 20 having a helical icosahedral surface 22. The sub-unit 20 may have a length L1 associated with a single repeating sub-unit of the support, such as Figure 1B As shown in the illustration. It should be understood that for this exemplary subunit 20, the length can be approximately equal in all three fundamental directions. However, subunits with non-cubic lengths are contemplated. In some embodiments, as discussed above, the larger the subunit length L1, the larger the aperture 25 size, such that the density and therefore weight of the implant can be reduced, while the strength or recoverability of the stent can be decreased. The subunit length L1 can therefore be selected to provide a desired balance between these two parameters depending on the application and various other parameters of the implant (e.g., the stiffness of the constitutive material). Thus, the subunit length L1 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, including subunit lengths L1 between 2 mm and 3 cm, as well as ranges larger than the foregoing ranges and ranges smaller than the foregoing ranges, are contemplated. For ease of observation, the repeating sub-unit is shown as a roughly cubic shape, and it should be understood that the repeating sub-unit can be any polyhedral shape or a curved three-dimensional shape. Where applicable, the length L1 can be associated with the sidewall length or average diameter of the repeating sub-unit.

[0096] like Figure 1B As shown, the aperture 25 of sub-unit 20 may have an average diameter D1. It should be understood that in some embodiments, the average aperture D1 may be proportional to the length L1 of the sub-unit in some way. For example, if the sub-unit's... Figure 1C If the wall thickness is approximately the same as that shown in the diagram (where thickness T1 is constant), then 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. Therefore, the helical icosahedral subunits of this disclosure can have any suitable average pore diameter, or other suitable type of maximum lateral dimension, depending on the geometry of the pore desired for the application (e.g., tissue infiltration and / or degradation rate, compressibility, implantation site mechanics), and independent of the subunit size.

[0097] The exemplary and non-limiting average aperture D1 or other lateral dimension of the sub-unit may be greater than or equal to approximately 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 aperture or other lateral dimension may also be less than or equal to approximately 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 dimensions. Combinations of the foregoing ranges are contemplated, including average apertures or other lateral dimensions between approximately 0.075 mm and 2 cm, between 0.5 mm and 1 cm, between 1 cm and 5 mm, and between 0.5 mm and 2 cm, as well as ranges larger than the foregoing ranges and ranges smaller than the foregoing ranges.

[0098] like Figure 1C As shown, the wall thickness T1 of subunit 20 can be determined at least in part based on various parameters, including the desired compressibility and strength of the implant, the degradation rate (based on material composition, if applicable), and the manufacturing method. For example, if a scaffold is formed using MED technology, the minimum wall thickness can be determined by the minimum possible deposited filament diameter. In some embodiments, the filament diameter can correspond to the nozzle diameter of the system. However, the filament diameter can be larger or smaller than the nozzle diameter, depending on the scan rate. In some embodiments, the wall thickness T1 can correspond to the diameter of a single filament. In other embodiments, more than one filament can be used to form a thicker wall thickness.

[0099] The exemplary and non-limiting wall thickness T1 of the subunit may be greater than or equal to approximately 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 approximately 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 contemplated, including wall thicknesses between 0.01 mm and 1 cm, as well as ranges larger and smaller than the foregoing ranges.

[0100] Figures 2A to 2C Various views of one embodiment of the partial support 50 formed by eight sub-units 20 are shown, these views being similar to Figures 1A to 1C The views shown. The support may have large interconnected holes 25 formed between the helical icosahedral surfaces of the sub-units. It should be understood that, although in Figures 2A to 2CThe exemplary scaffold shown in the example has 8 sub-units, but depending on the application of the implant, any suitable number of sub-units 20, more than 8 sub-units, or less than 8 sub-units may be used.

[0101] Figures 1A to 2C The helical icosahedral TPMS of the subunits shown can exhibit approximately isotropic behavior in more than one direction, allowing their mechanical properties to be approximately equal in more than one direction. This behavior can more accurately mimic natural tissue while also enabling implant delivery through small incision sites without a significant risk of injury or discomfort to the patient.

[0102] Figure 3 An exemplary breast implant 100 according to some embodiments is shown. The implant may be made of... Figures 1A to 2C The TPMS scaffold shown is formed. The implant can be sized and shaped to fit the anatomical site. For example, the implant can be as follows: Figure 3 The dome shape shown is illustrated. It should be understood that although the dome is shown as symmetrical, a more accurate simulation of the asymmetrical shape of natural tissue is envisioned, as described in more detail above.

[0103] In the depicted embodiment, the implant 100 may have an average base diameter D2, which may be wide enough to span the width of the reconstructed or enlarged breast. The average base diameter D2 may be patient-specific and therefore may be any suitable size, including but not limited to greater than or equal to approximately 6 cm, 8 cm, 10 cm, 12 cm, 15 cm, 18 cm, 20 cm, 22 cm and / or less than or equal to approximately 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 contemplated, including average base diameters between approximately 6 cm and 22 cm, between 8 cm and 18 cm, and / or ranges larger than and smaller than the foregoing ranges.

[0104] It should be understood that in other applications (e.g., tumor resection), the average diameter of the implant can be smaller to correspond to the size of the resection site. Therefore, the implants disclosed herein are not limited in their shape and / or size.

[0105] Implant 100 can also have an average protrusion height H1, such as Figure 3As shown in the diagram. Similar to the base diameter D2, the protrusion height H1 can be customized for the patient and can therefore be any suitable size, including but not limited to between approximately 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.

[0106] Figures 4A to 4B A different view of one embodiment of a breast implant scaffold formed from helical icosahedral subunits is shown. The implant 100 is designed with an average base diameter of 11 cm and a protrusion height of 5 cm. The helical icosahedral subunits have interconnected large apertures 25 formed by the helical icosahedral surfaces 22, allowing the scaffold to have open pores. Figures 4A to 4B As shown, when the scaffold shape differs from the subunit shape (e.g., a dome scaffold compared to a cubic subunit), partial subunits can be used. Therefore, implants of this disclosure may include partial subunits to form a desired scaffold size.

[0107] Figures 5A to 5C It shows the use of and Figures 4A to 4B The design shown is similar to that of three flexible breast implants with helical icosahedral subunits. Specifically, the depicted implants are formed with helical icosahedral subunits having different spatial frequencies, wherein... Figure 5A The implant forms a minimum spatial frequency (i.e., the largest subunit size), and Figure 5C The implant forms a maximum spatial frequency (i.e., the smallest subcell size). Without being bound by theory, the spatial frequency of the subcell can be proportional to the fill density, such that a larger spatial frequency (i.e., a smaller subcell size) can be associated with a larger fill density. For example, Figure 5A Implant 200 with a 3% filler density is shown. Figure 5B An implant 300 with a 5% filler density is shown, and Figure 5C An implant 400 with an 8% fill density is shown. As shown in the figure, the size of the helical icosahedral subunit can be proportional to the fill density, such that with higher fill density subunit sizes (e.g., ...), Figure 5C Compared to lower fill density, lower fill density can produce larger sub-cells (e.g., Figure 5A ).

[0108] Formed by P4HB Figures 5A to 5CThe implants are formed using melt extrusion. In some exemplary embodiments, granules of poly-4-hydroxybutyrate (P4HB) (Tepha, Lexington, MA, MW 450kDa) can be loaded into the hopper of a MED-based 3D printer, which includes a horizontal extruder feeding into a vertical extruder equipped with a vertical plunger and a movable platform. An exemplary process for using melt extrusion to spray a series of droplets as needed in the preparation of implants is described in patent publication No. 2019 / 0375149, filed June 11, 2019, entitled “METHODS FOR 3DPRINTING OF POLY-4 HYDROXYBUTYRATE AND COPOLYMERS”, which is incorporated herein by reference in its entirety.

[0109] P4HB pellets 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 by purging with air through a silica bed. The temperature distribution 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 nozzle orifice diameter of the vertical extruder can be 0.15 mm, and for filling, the droplet printing frequency can be 240 drops / second. Additional exemplary settings for the 3D printer are shown in Table 1.

[0110]

[0111] Table 1: Exemplary parameters for MED printing of compressible P4HB breast implants

[0112] Table 2 below summarizes the composition of P4HB material and Figures 5A to 5C Various measured properties of three 3D-printed compressible breast implants formed by helical icosahedral subunits.

[0113]

[0114] Table 2: Characteristics of implants with porous helical icosahedral design

[0115] Figures 5A to 5CThree implants underwent cyclic compression testing for mechanical evaluation. Table 3 shows the average maximum compressive load at 50% strain, stiffness at 20%–40% and 40%–50% strain, and dimensional height recovery after cyclic loading. The results show that the implants recovered more than 97% of their dimensional height (the protrusion from the base to the apex of the implant) after cyclic compression.

[0116]

[0117] Table 3: Cyclic compression in the axial direction of implants with porous helical icosahedral design

[0118] Figures 5A to 5B The breast implant also passed through the Keller funnel and maintained its shape and volume, demonstrating that the breast implant could be delivered to the implantation site through a small inlet without significant damage or deformation.

[0119] Figures 5A to 5C An implant formed entirely of a helical icosahedral scaffold with generally uniform characteristics is depicted. However, implants with different scaffold regions are envisioned.

[0120] Figures 6A to 6B A breast implant 500 according to some embodiments is depicted. The breast implant may include a first TPMS scaffold 505 and a second scaffold 515 arranged radially diverging from the center of the implant 500. The second scaffold may include a TPMS scaffold having subunits different from the first scaffold. For example, the second scaffold 515 may be formed from subunits with feature dimensions larger than those of the first scaffold 505, which can facilitate radial compression of the implant. For example, the spatial frequency of the first scaffold may be lower than that of the second scaffold, allowing the second scaffold to be more compact and therefore 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 It can represent a top view of the implant, as well as a scaled cross-sectional view of the implant taken along the axial direction. Figure 6B This can be represented by a side view of the implant, as well as a cross-sectional view of the implant taken along the radial direction. It should be understood that more than one scaffold type can be used in any suitable arrangement to facilitate the desired mechanical and tissue infiltration profile.

[0121] It should also be understood that although stents 505 and 515 are shown as different, implementations with smooth gradient transitions between stent regions are also envisioned.

[0122] In some implementations... Figures 6A to 6B The second support 515 can represent a support structure, such as a strut, that extends on the surface of the support 505 to provide localized mechanical support. In some embodiments, the support structure formed by the second support 515 can be used for delivering biological agents. It should be understood that... Figures 6A to 6B The arrangement of the areas shown is merely exemplary, and other arrangements of the second bracket and / or support structure are contemplated.

[0123] Figures 7A to 7B A breast implant 600 according to another embodiment is depicted. The breast implant 600 may be formed of a plurality of layers 612, 614, 616, 618 of a scaffold, said layers being 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 each other to provide desired mechanical behavior. (As along...) Figure 7A The 7B-7B cut of the implanted thread Figure 7B As shown in the cross-sectional view, these layers can extend through the body of the implant 600. In some embodiments, layer 618 can serve as the base of the implant. (As opposed to...) Figures 6A to 6B As described, the various layers can be different or can be arranged as a gradient through the implant. It should also be understood that... Figures 7A to 7B The four layers shown are merely exemplary, and other arrangements of the support layers are contemplated.

[0124] Figures 8A to 8B A breast implant 700 is depicted having a plurality of concentric supports 712, 714, 716, 718 disposed on and at least partially surrounding a lower layer, wherein layer 718 is the bottommost layer of the implant. Figure 8B It shows along Figure 8A A cross-sectional view of the implant taken by line 8B-8B. In some embodiments, the outermost layer 712 may serve as a shell or coating, as previously described, but shellless implants are also contemplated. It should also be understood that... Figures 8A to 8B The four layers shown are merely exemplary, and other arrangements of the support layers are contemplated.

[0125] Figures 6A to 8BEach layer or region shown may represent a difference in subunit type, including different materials, spatial frequencies, filler densities, subunit types, and / or other differences that provide different properties for different parts of the implant. These regional differences in properties may also be affected by geometric differences in layers or regions, such as differences in thickness for each region or layer. As previously described, these region-by-region variations in subunit properties and regional geometry can provide differences in stiffness, tissue infiltration characteristics, volume of the therapeutic composition, surface roughness, and / or any other desired properties in each region. Furthermore, these variations may affect the overall properties of the implant. Therefore, it should be understood that layers or regions (e.g., scaffold regions or support structures, such as…) can be employed… Figures 6A to 8B Any combination of the scaffold area or support structure in the implant to achieve the desired mechanical behavior, tissue infiltration behavior, degradation behavior, or physical properties for a specific area or for the entire implant.

[0126] For example, as described above, in some embodiments, it may be desirable for the implant to have low compressive stiffness in the radial direction (e.g., to allow the base to be compressed as it passes through the funnel or incision) and high 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 to the touch. 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 shorter distances between adjacent edges of the stent and / or by using different sub-unit geometries with alternative geometries. This can advantageously improve the operation of the system during implantation, among other possible benefits. Additionally or alternatively, in some embodiments, it may be desirable for the implant (e.g., by providing low filler density, large pore size, etc.) to facilitate tissue infiltration. The inventors have recognized and realized that by providing regions or layers of the implant with specific characteristics, such a combination of desired properties for the implant can be achieved, which collectively produce the desired properties throughout the implant.

[0127] exist Figures 8A to 8BIn exemplary embodiments, the characteristics of the individual layers 712 to 718 can be selected to achieve these and / or other desired characteristics in the implant 700. For example, the core layer 718 may be formed with a relatively low filler density and / or a relatively large pore size. In some embodiments, the core layer may include a TPMS or helical icosahedral scaffold having a filler density that may optionally be between approximately 4% and 6%. This can be advantageous for relatively low compressive stiffness in the radial direction compared to a higher filler density or a smaller pore size. Additionally or alternatively, such a low-density core can facilitate tissue infiltration, as discussed above.

[0128] Furthermore, in some embodiments, the first intermediate layer 716 and the second intermediate layer 714 may have a higher fill density than the core layer 718 and / or a smaller pore size than the pore size in the core layer 718, such as... Figure 8B As shown, each of the first intermediate layer 716 and the second intermediate layer 714 may be concentric with and / or at least partially surround the core layer 718. This can contribute to higher compressive stiffness in the axial direction while allowing radial compressive stiffness to remain within a desired range. In some embodiments, the filler density can be increased from the first intermediate layer 716 to the second intermediate layer 714, wherein 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 may comprise a TPMS or helical icosahedral scaffold with a filler density of approximately 8%, and the second intermediate layer 714 may comprise a TPMS or helical icosahedral scaffold with a filler density of approximately 12%. Such increases may occur discretely or using a gradient of scaffold properties, as described above. The thicknesses of the intermediate layers 716, 714 may also be selected to achieve the desired stiffness. For example, in some embodiments, the first intermediate layer 716 may have a thickness of approximately 5 mm to 10 mm, while the second intermediate layer may have a thickness of approximately 1 mm to 3 mm.

[0129] Although the illustrated embodiments include two intermediate layers, it will be understood that in some embodiments only a single intermediate layer may be present. For example, some embodiments may include a single intermediate layer having a fill density of approximately 8% to 12% or any other suitable fill density, and a thickness of approximately 2 mm to 10 mm, 5 mm to 8 mm or any other suitable thickness, to achieve the desired properties in that layer or in the implant. Alternatively, more than two intermediate layers may be present, or a continuous gradient of fill density may exist from the core layer to the shell layer, making it impossible to distinguish between different intermediate layers.

[0130] Furthermore, in some implementations, such as Figure 8B As shown, the outer layer 712 may be concentric with one or more intermediate layers 714, 716 and / or core layer 718 and / or may at least partially surround one or more intermediate layers 714, 716 and / or core layer 718, and the outer layer 712 may have a greater fill density compared to the intermediate layers and / or core layer. The outer layer 712 may be formed to provide desired properties for the outer surface of the implant, such as smoothness, therapeutic compound load, and / or other suitable parameters, for example, by utilizing a higher fill density and / or different sub-unit types. In some embodiments, the following sub-unit types may provide a smoother feel or other desired properties compared to TPMS or helical icosahedral sub-unit types: the sub-unit type has a polygonal or honeycomb geometry, such as a hexagonal or octagonal geometry, or has a mosaic pattern, such as a Voronoi pattern or other pattern. Thus, in some embodiments, the outer layer may be formed with a Voronoi sub-unit type and may have a fill density of approximately 20% to 24% or optionally approximately 22%. Furthermore, in some embodiments, the outer layer may have a relatively small thickness, sufficient to achieve the desired surface feel without substantially affecting the desired stiffness in one or more directions. For example, the outer layer 712 may have a thickness of approximately 0.1 mm to 1.0 mm or approximately 0.5 mm.

[0131] It should be understood that although the above embodiments illustrate examples of varying filler density, subunit type, and layer thickness in different regions to achieve desired characteristics of the implant, the variations in each region are not limited to filler density, subunit type, and layer thickness. As mentioned above, other characteristics that can be varied by region include material type, material properties, spatial frequency, pore size, etc. Furthermore, although embodiments with a greater filler density in the outer region compared to the inner region have been described above, it will be understood that embodiments with a lower filler density in the inner region compared to one or more intermediate / outer regions are also contemplated, as are embodiments with substantially uniform filler density in different regions (e.g., where the regions may be defined by differences in pore size, spatial frequency, subunit type, or other characteristics).

[0132] Example: Rabbit model test

[0133] The implants from the three groups were experimentally tested by implanting them into rabbits. All three groups were generally dome-shaped and included a first TPMS scaffold with varying filler density across the groups and a second TPMS scaffold with a filler density of 11% across all groups. The second scaffold was arranged from the center of the implant along four radially diverging lines, which, when viewed axially, formed a plus sign at right angles. The filler density of the first scaffold in the first, second, and third groups was approximately 4.5%, 6.7%, and 9.0%, respectively. All implants were 3D printed using P4HB. Implants from each group were removed after 4, 12, and 26 weeks of implantation. After removal, the implants were evaluated for: 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 removal of infiltrated tissue).

[0134] All three groups exhibited similar material degradation. Scanning electron microscopy (SEM) evaluation revealed 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.

[0135] Although all groups exhibited good tissue infiltration behavior, the 4.5% group showed the highest infiltration rate, while the 9.0% group showed the lowest. At the 4-week time point, loose fibrovascular tissue had formed in all groups. At the 12-week time point, soft, 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.

[0136] As described above, compressive stiffness was tested with and without infiltrated tissue still present on the implant (i.e., in an "as is" state) and with infiltrated tissue removed via an enzymatic process (i.e., in a "digested" state). Compressive stiffness was also assessed for all three groups prior to implantation, with pre-implantation stiffness of approximately 235 kPa in 4.5% of the group, approximately 354 kPa in 6.7% of the group, and approximately 449 kPa in 9.0% of the group.

[0137] All three groups exhibited high compressive stiffness after implantation and tissue infiltration. In the 4.5% group, stiffness in the as-is condition increased by approximately 83% at the 4-week time point, then decreased at the 12-week and 26-week time points. At 26 weeks, the as-is stiffness was approximately 53% higher than the pre-implanted stiffness. In the 6.7% group, stiffness in the as-is condition increased by approximately 66% at the 4-week time point. At 12 weeks, stiffness had increased to approximately 207% higher than the pre-implanted stiffness. At 26 weeks, the as-is stiffness in the 6.7% group had decreased relative to the 12-week stiffness, but still exceeded the pre-implanted stiffness by approximately 86%. In the 9.0% group, stiffness in the as-is condition increased by approximately 55% at 4 weeks and was approximately 161% higher than the pre-implanted stiffness at 12 weeks. At 26 weeks, the as-is stiffness in the 9.0% group was approximately 152% higher than the pre-implanted stiffness. In all groups, the stiffness under digestion conditions decreased over time, consistent with the material degradation results, indicating that the material is degrading and / or absorbing.

[0138] The embodiments described herein can be implemented as methods, examples of which have been provided. The actions performed as part of the method can be ordered in any suitable manner. Therefore, embodiments in which actions are performed in an order different from the illustrated order can be constructed, and embodiments may include performing several actions simultaneously, even if these actions are shown as sequential actions in the illustrative embodiments.

[0139] Although this teaching has been described in conjunction with various embodiments and examples, it is not intended to limit this teaching to these embodiments or examples. Rather, as those skilled in the art will understand, this teaching includes various alternatives, modifications, and equivalents. Therefore, the foregoing description and figures are by way of example only.

[0140] Although several embodiments of the invention have been described and illustrated herein, those skilled in the art will readily conceive of various other means and / or structures for performing the functions and / or obtaining one or more of the results and / or advantages described herein, and each of such variations and / or modifications is considered to be within the scope of the invention. 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 actual parameters, dimensions, materials, and / or configurations will depend on one or more specific applications for which the teachings of the invention are applied. Those skilled in the art will recognize or be able to determine many equivalents of the specific embodiments of the invention described herein using only conventional experimentation. Therefore, it should be understood that the foregoing embodiments are presented by way of example only, and that the invention can be practiced in ways other than the specific descriptions and claims within the scope of the appended claims and their equivalents. The invention relates to each individual feature, system, article of manufacture, material, kit, and / or method described herein. Furthermore, any combination of two or more such features, systems, articles, materials, kits, and / or methods is also included within the scope of this invention if such features, systems, articles, materials, kits, and / or methods are not inconsistent with each other.

Claims

1. An implantable soft tissue repair prosthesis, comprising: A flexible porous scaffold formed from at least one triple periodic minimum 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 prosthesis according to claim 1, wherein, The filling density of the flexible porous scaffold is less than approximately 20%.

3. The prosthesis according to claim 1 or claim 2, wherein, The filling density of the flexible porous scaffold is between approximately 3% and 10%.

4. The prosthesis according to any one of the preceding claims, wherein, The average pore diameter of at least a portion of the flexible porous support is between approximately 0.075 mm and 20 mm.

5. The prosthesis according to claim 4, wherein, The average aperture is approximately 0.5 mm to 10 mm.

6. The prosthesis according to claim 4, wherein, The average aperture is approximately 1 mm to 5 mm.

7. The prosthesis according to any one of the preceding claims, wherein, The prosthesis is constructed to enlarge and / or reconstruct the anatomical shape of the human breast.

8. The prosthesis according to any one of the preceding claims, wherein, The flexible porous stent is a first flexible porous stent, wherein the prosthesis further includes a second flexible porous stent, and wherein the filling density of the first flexible porous stent is different from the filling density of the second flexible porous stent.

9. The prosthesis according to claim 8, wherein, The second flexible porous stent is disposed in one or more intermediate layers, the one or more intermediate layers at least partially surrounding the core layer containing the first flexible porous stent, and the prosthesis also includes a shell layer containing a third flexible porous stent, the shell layer at least partially surrounding the one or more intermediate layers.

10. The prosthesis according to claim 9, wherein, The filling density of the second flexible porous support and the filling density of the third flexible porous support are both greater than the filling density of the first flexible porous support.

11. The prosthesis according to claim 9 or claim 10, wherein, The third flexible porous support is formed from a subunit that is different from at least one of the second flexible porous support and the first flexible porous support.

12. The prosthesis according to any one of claims 9 to 11, wherein, The third flexible porous support is formed in an inlay pattern.

13. The prosthesis according to any one of the preceding claims, wherein, The flexible porous support is configured to recover at least 90% of its original volume when compressed by 50% in at least one direction.

14. The prosthesis according to claim 8, wherein, The second flexible porous scaffold includes at least one selected from the group consisting of: a) Shell, b) Base, c) Multiple pillars, and / or d) One or more openings for inserting a vascular pedicle or other tissue block.

15. The prosthesis according to claim 14, wherein, The second flexible porous support includes the plurality of pillars, wherein the plurality of pillars includes at least one curved pillar.

16. The prosthesis according to any one of claims 8 to 15, wherein, The first flexible porous scaffold has a filling density between approximately 3% and 10%, and the second flexible porous scaffold has a filling density between 5% and 10%.

17. The prosthesis according to any one of the preceding claims, wherein, The flexible porous stent is a first flexible porous stent, wherein the prosthesis further includes a second flexible porous stent, and wherein the degradation spectrum of the first flexible porous stent is different from that of the second flexible porous stent.

18. The prosthesis according to any one of claims 8 to 17, further comprising a transition portion located between the first flexible porous stent and the second flexible porous stent.

19. The prosthesis according to any one of the preceding claims, wherein, 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 prosthesis according to any one of the preceding claims, wherein, 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 prosthesis according to any one of the preceding claims, wherein, The density of the implant is between 0.02 g / cm³. 3 With 0.2 g / cm 3 between.

22. The prosthesis according to any one of the preceding claims, wherein, The flexible porous scaffold is formed from an absorbable polymer.

23. The prosthesis according to claim 22, wherein, The absorbable polymer comprises 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.

24. The prosthesis according to any one of the preceding claims, wherein, The flexible porous scaffold is formed of poly-4-hydroxybutyrate.

25. The prosthesis according to any one of the preceding claims, wherein, The triple periodic minimum surface is a helical icosahedron.

26. The prosthesis according to any one of the preceding claims, wherein, The flexible porous scaffold is at least partially coated with a bioactive agent.

27. A method for manufacturing an implantable soft tissue repair prosthesis according to any one of claims 1 to 26, the method comprising: The prosthesis is formed using an additive manufacturing process.

28. A method for implanting an implantable soft tissue prosthesis, the method comprising: The implantable prosthesis is compressed by at least 50% in at least one direction, the implantable prosthesis comprising a flexible porous scaffold formed by at least one triple periodic minimum surface; The implantable prosthesis is delivered to the implantation site; as well as At least 90% of the compression is restored in at least one of the at least two directions.

29. The method of claim 28, further comprising: (i) Make at least one incision to obtain access to the patient’s breast tissue, (ii) separate the skin and subcutaneous fascia from the mammary mound of the breast, (iii) position the implant under the gland, under the pectoral muscle or under the fascia, (iv) secure the implant to nearby tissue, and (v) close the incision in the breast.

30. The method of any one of claims 28 or 29, further comprising passing the implant through an implant delivery funnel disposed at the implantation site.

31. The method according to any one of claims 28 to 30, further comprising forming the prosthesis using an additive manufacturing process, the additive manufacturing process including at least one of: melt extrusion deposition, fused filament fabrication, fused pellet deposition, melt extrusion deposition, selective laser melting, printing pastes and solutions using a coagulation bath, and printing using an adhesive solution and polymer particles.

32. The method according to any one of claims 28 to 31, wherein, The filling density of the flexible porous scaffold is less than approximately 20%.

33. The method according to any one of claims 28 to 32, wherein, The flexible porous scaffold is formed from an absorbable polymer.

34. The method according to any one of claims 28 to 33, wherein, The flexible porous scaffold is formed of poly-4-hydroxybutyrate.

35. The method according to any one of claims 28 to 34, wherein, The triple periodic minimum surface is a helical icosahedron.

36. The method according to any one of claims 28 to 35, wherein, The flexible porous scaffold is at least partially coated with a bioactive agent and / or includes a bioactive agent.

Images