Hip-lip scaffold

Abstract

To provide a hip-lip scaffold and a method of annealing a porous foam for use in the hip-lip scaffold.SOLUTION: Provided is a hip-lip scaffold comprising a porous foam, wherein the porous foam comprises a synthetic polymer, and wherein the porous foam has an average pore size of 100 μm to 400 μm.SELECTED DRAWING: Figure 14

Description

[Technical Field]

[0001] (Related Applications) This application claims priority under 35 U.S.C. Section 119(e) to U.S. Provisional Application Serial No. 63 / 029,326, filed May 22, 2020, the entire contents of which are incorporated herein by reference.

[0002] (Field) Generally, it provides a scaffold for the hip labrum (or hip joint labrum). [Background technology]

[0003] (background) Reconstruction of the hip labrum has traditionally been achieved by implanting allografts or xenografts composed of natural tissue. However, such allografts and xenografts can have one or more drawbacks, and their mechanical and biological properties cannot be tailored. Summary of the Invention [Problem to be solved by the invention]

[0004] Therefore, a new hip labrum (or hip joint labrum) scaffold is needed. [Means for solving the problem]

[0005] (Abstract) The present disclosure generally provides a hip labrum (or hip joint labrum) scaffold. The subject matter described in this disclosure relates, in some cases, to interrelated products, alternative solutions to a particular problem, and / or multiple different uses of one or more systems and / or articles.

[0006] In some embodiments, a hip labrum scaffold is provided. The hip labrum scaffold comprises a porous foam. The porous foam comprises a synthetic polymer. The porous foam has an average pore size of 100 microns (μm) to 400 microns (μm).

[0007] In some embodiments, the hip labrum scaffold comprises a porous foam, the porous foam comprising a synthetic polymer, and the porous foam has a suture pull-out strength (or suture pull-out strength or suture pull-out strength) of 3 N / mm or greater.

[0008] In some embodiments, the hip labrum scaffold comprises a porous foam. The porous foam comprises a synthetic polymer. The hip labrum scaffold is configured to degrade (or degenerate) when placed (or positioned or positioned) in a human patient. The hip labrum scaffold is configured to complete degradation in a time (or period) of at least four years and not more than six years after implantation in the human patient.

[0009] In some embodiments, there is provided a method of annealing a porous foam for use in a hip labrum scaffold. The method comprises heating the porous foam to a temperature at least 1° C. above the melting point of the porous foam. The heating increases the average pore size of the porous foam. The porous foam comprises a synthetic polymer.

[0010] In some embodiments, a method for annealing a porous foam comprises heating the porous foam to a temperature at least 1° C. above the melting point of the porous foam. The heating improves one or more mechanical properties of the porous foam while substantially preserving the porosity of the porous foam. The porous foam comprises a synthetic polymer. The one or more mechanical properties are selected from the group consisting of the compressive modulus of the porous foam, the tensile modulus of the porous foam, the tensile strength of the porous foam, and the suture pull-out strength of the porous foam.

[0011] In some embodiments, a method of annealing a porous foam comprises heating the porous foam to a temperature (or process or step) at least 1° C. above the melting point (or melting point) of the porous foam and at most 20° C. above the melting point (or melting point) of the porous foam. The porous foam comprises a synthetic polymer.

[0012] Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the invention when considered in conjunction with the accompanying drawings. In the event that this specification and a document incorporated by reference include conflicting and / or inconsistent disclosure, the specification shall control. In the event that two or more documents incorporated by reference include conflicting and / or inconsistent disclosure with respect to each other, the document having the later effective date shall control.

[0013] Non-limiting embodiments of the present invention will be described in an illustrative manner with reference to the accompanying drawings, which are schematic and not intended to be drawn to scale. In the drawings, identical or nearly identical components (or configurations or elements or components) shown in the drawings are typically each represented by a single numeral. For clarity, not all components (or configurations or elements or components) are shown in every drawing. Furthermore, not all components (or configurations or elements or components) of each embodiment of the present invention are shown unless they are necessary in the drawings for those skilled in the art to understand the invention. The drawings are as follows: [Brief explanation of the drawings]

[0014] [Figure 1] FIG. 1 is a diagram illustrating an example of a porous foam, according to some embodiments. [Figure 2] FIG. 2 illustrates another example of a porous foam, according to some embodiments. [Figure 3A] FIG. 3A is a schematic diagram showing a human crotch (or hips), according to some embodiments. [Figure 3B] FIG. 3B is a schematic diagram illustrating a human crotch (or hips), according to some embodiments. [Figure 4] FIG. 4 is a photomicrograph showing a human hip labrum (or hip joint labrum), according to some embodiments. [Figure 5A] FIG. 5A is a schematic diagram illustrating the shape that a hip labrum scaffold and porous foam may have, according to some embodiments. [Figure 5B] FIG. 5B is a schematic diagram illustrating the shape that the hip labrum scaffold and porous foam may have, according to some embodiments. [Figure 6] FIG. 6 is a photograph showing a hip labrum (or hip joint labrum) scaffold, according to some embodiments. [Figure 7] FIG. 7 is a photograph showing a hip labrum (or hip joint labrum) scaffold, according to some embodiments. [Figure 8] FIG. 8 is a schematic diagram illustrating a hip labrum scaffold including a triangular groove, according to some embodiments. [Figure 9] FIG. 9 is a photograph showing a hip labrum (or hip joint labrum) scaffold, according to some embodiments. [Figure 10] FIG. 10 is a schematic diagram illustrating a hip labrum scaffold including grooves, according to some embodiments. [Figure 11] FIG. 11 is a schematic diagram illustrating a hip labrum scaffold including grooves, according to some embodiments. [Figure 12] FIG. 12 is a photograph showing a hip labrum (or hip joint labrum) scaffold, according to some embodiments. [Figure 13] FIG. 13 is a schematic diagram illustrating a hip labrum scaffold including a rectangular groove, according to some embodiments. [Figure 14] FIG. 14 is a scanning electron micrograph showing a porous foam, according to some embodiments. [Figure 15] FIG. 15 is an X-ray microtomography image showing a porous foam, according to some embodiments. [Figure 16] FIG. 16 is a diagram illustrating a three-dimensional (3D) rendering of a porous foam, according to some embodiments. [Figure 17] FIG. 17 is a scanning electron micrograph showing a porous foam, according to some embodiments. [Figure 18] FIG. 18 is a diagram illustrating the pore features of two porous foams, according to some embodiments. [Figure 19]FIG. 19 is a diagram illustrating the pore features of two porous foams, according to some embodiments. [Figure 20] FIG. 20 illustrates the results of various tests performed on porous foam, according to some embodiments. [Figure 21] FIG. 21 is a diagram illustrating the cohesive modulus (or aggregate modulus) of a cellular foam for various applied compressive strains (or strains), according to some embodiments. [Figure 22] FIG. 22 is a diagram illustrating the permeability (or permeability or permeability) of a porous foam for various applied compressive strains (or strains), according to some embodiments. [Figure 23] FIG. 23 is a diagram illustrating the time constant of a porous foam for various applied compressive strains, according to some embodiments. [Figure 24] FIG. 24 is a scanning electron micrograph showing the porous foam after the application of compressive strain. [Figure 25] FIG. 25 is a scanning electron micrograph showing the porous foam after the application of compressive strain. [Figure 26] FIG. 26 is a scanning electron micrograph (or image) showing the porous foam after the application of compressive strain. DETAILED DESCRIPTION OF THE INVENTION

[0015] (Detailed explanation) Generally, a hip labrum scaffold is provided. In some embodiments, the hip labrum scaffolds described herein have one or more advantageous features. For example, some hip labrum scaffolds may have one or more properties that promote tissue in-growth. Desirably, tissue in-growth may result in the formation of a composite material (e.g., comprising the hip labrum scaffold and ingrowth tissue) that has mechanical and / or biological properties similar to those of a natural, undamaged hip labrum. Such a labrum scaffold, when placed (or positioned) in a patient, can advantageously cause less pain to the patient (e.g., less pain than a labrum scaffold having mechanical and / or biological properties dissimilar to the mechanical and / or biological properties of a natural (or natural), undamaged (or undamaged) labrum) and / or can have improved functionality (e.g., when compared to a labrum scaffold having mechanical and / or biological properties dissimilar to the mechanical and / or biological properties of a natural (or natural), undamaged (or undamaged) labrum).

[0016] Properties that may promote tissue in-growth include the presence of pores (or holes or pores) having one or more properties that promote tissue in-growth, mechanical properties that promote tissue in-growth, and / or chemical compositions that promote tissue in-growth. For example, some hip labrum scaffolds may include pores (or holes or pores) with dimensions (or magnitude or size), shape (or quantity), and / or connectivity (or connectivity) that promote tissue in-growth. As another example, in some embodiments, hip labrum scaffolds designed in accordance with the present disclosure have a relatively high compressive modulus and / or resistance to pore failure (or collapse). Such labral scaffolds can advantageously maintain open pores (where tissue can grow in a facile manner) even when subjected to the pressures typically experienced by the labrum during standing and / or movement. As a third example, some labral scaffolds may be non-toxic to cells and / or have chemistries that allow for cell proliferation.

[0017] Some hip labrum scaffolds described herein, when implanted into a patient as a hip labrum replacement, can advantageously be configured to readily seal the acetabulum against the femoral head. Such sealing may be sufficient to substantially inhibit and / or prevent synovial fluid from leaking out of the sealed cavity enclosed by the hip labrum scaffold, the femoral head, and the acetabulum. This may promote the retention of such synovial fluid in such cavity, which may desirably aid in joint lubrication. Some properties that may promote sealing of the acetabulum against the femoral head include properties that promote tissue in-growth (as tissue in-growth is believed to aid in such sealing) and high flexibility and toughness. It is believed that hip labrum scaffolds with relatively high flexibility and / or toughness may be easily positioned in difficult and / or relatively inaccessible geometries. For example, they may be reversibly and / or irreversibly deformable, thereby allowing them to pass through narrow passages and / or adapt to the shape or geometry in which they are positioned. High flexibility and / or toughness are also believed to help prevent the scaffold from failing when subjected to pressures typically exerted on the hip labrum during standing and / or movement.

[0018] The hip labrum scaffolds described herein can have a variety of suitable morphologies. In some embodiments, the hip labrum scaffold comprises a plurality of pores. As described elsewhere in this disclosure, such pores may facilitate tissue in-growth into the hip labrum scaffold and / or may be configured to facilitate tissue in-growth into the hip labrum scaffold. For example, some hip labrum scaffolds may include pores that facilitate the growth of tissue and / or one or more tissue components (e.g., cells, extracellular membranes).

[0019] In some embodiments, the hip labrum scaffold comprises a porous foam. In other words, a plurality of pores may be disposed (positioned) within the porous foam. The pores may include filled pores, unfilled pores, or both. When filled, the pores may be filled with one or more gases (e.g., air), one or more liquids (e.g., water, biological fluids), one or more gels (e.g., one or more biological gels), and / or one or more solids (excluding the solids surrounding the pores) (e.g., one or more solid biological materials). After implantation into a patient, the pores may be filled with tissue and / or cells. FIG. 1 is a cross-sectional view of one non-limiting embodiment of a porous foam comprising a plurality of pores. In FIG. 1, the porous foam 100 comprises a plurality of pores 200. As shown in FIG. 1, the plurality of pores may include both open pores (e.g., pores 300 shown in FIG. 1) and closed pores (e.g., pores 400 shown in FIG. 1). When a porous foam comprises both open and closed pores, the closed pores may comprise a relatively small or minimal percentage of the total number and / or volume of pores. Additionally, a hip labrum scaffold may include a porous foam comprising exclusively open pores.

[0020] Porous foams may also include pores (or holes or pores) that are interconnected (or bonded or linked or connected or communicating with each other). FIG. 2 shows one non-limiting embodiment of a porous foam having such characteristics. In FIG. 2, porous foam 102 comprises three interconnected (or bonded or linked or connected or communicating with each other) open pores 302, 332, and 362. Such a porous foam also comprises two interconnected (or bonded or linked or connected or communicating with each other) closed pores 402 and 452. The porous foams described in this disclosure may include either, both, or neither of these types of interconnected (or bonded or linked or connected or communicating with each other) pores. In some embodiments, similar to the embodiment shown in FIG. 2, the interconnected (or bonded or linked or connected or in communication with each other) open pores fluidly communicate the porous foam with the external environment (fluid communication through exactly two openings). Alternatively, the porous foam can include open pores (interconnected (or bonded or linked or connected or in communication with each other)) that fluidly communicate the porous foam with the external environment through multiple openings (more than two). For example, in some embodiments, the porous foam includes open pores (interconnected (or bonded or linked or connected or in communication with each other)) that fluidly communicate the porous foam with the external environment through multiple openings (or openings).

[0021] Pores (or holes or pores) that are interconnected (or bonded or linked or connected or in communication with each other) may be pores (or holes or pores) that are in fluid communication with each other via a path that passes exclusively through the interior of the porous foam. In some embodiments, two pores (or holes or pores) that are interconnected (or bonded or linked or connected or in communication with each other) are interconnected such that there is no interfering pore (or hole or pore) disposed (or positioned or positioned) between them. Such pores (or holes or pores) may be considered to be "directly interconnected (or bonded or linked or connected or in communication with each other)" or "in direct fluid communication" with each other. Unless otherwise specified, pores that interconnect or are in fluid communication with each other may be directly interconnected or in fluid communication with each other, or may be indirectly interconnected (i.e. interconnected via one or more pores disposed between them) or in fluid communication with each other.

[0022] The porous foams described herein may have a relatively high porosity and / or may include pores with a relatively high degree of interconnectedness. For example, in some embodiments, a relatively high percentage of the pores may interconnect with one another through a single network. Such pores may also fluidly connect the porous foam to the external environment through a relatively large number of openings. As one example, the porous foam may include a single network through which a significant number of pores interconnect with one another. Such a network may include a relatively large number of openings in the porous foam. It should also be noted that the hip labrum (or hip labrum) scaffold may include porous foam that is an open cell foam and / or porous foam with a majority of the pores open (or porous foam with open pores).

[0023] The pores (or holes or pores) of the porous foam, if present, may have a variety of suitable sizes (or dimensions or dimensions). Without wishing to be bound by any particular theory, it is believed that pores having one or more of the size ranges described below can promote tissue in-growth to a greater extent than pores having other sizes (or dimensions or dimensions). It is believed that cells grow (or proliferate) in a manner that is influenced by the substrate (or base) on which they are immobilized. For this reason, it is believed that a substrate (or base) having one or more properties similar to the extracellular matrix and / or a substrate (or base) with which cells interact in a manner similar to the extracellular matrix can promote better tissue in-growth than a substrate (or base) that is different from the extracellular matrix. In particular, porous foams having an average pore size (or average pore diameter or average pore size) between 100 microns (μm) and 400 microns (μm) are believed to behave (or function) better as an extracellular matrix during tissue in-growth compared to porous foams having other pore sizes. Furthermore, pores smaller than 100 microns (μm) may hinder tissue in-growth because they may be too small for cells to penetrate. Also, pores larger than 400 microns (μm) may allow tissue formation in the porous foam. Such porous foams are believed to have inferior mechanical properties and / or less homogeneity than tissue grown (or propagated) in porous foams with smaller pores.

[0024] In some embodiments, the porous foam comprises pores (or holes or pores) having an average size (or average diameter) of 100 microns (μm) or more, 125 microns (μm) or more, 150 microns (μm) or more, 175 microns (μm) or more, 200 microns (μm) or more, 225 microns (μm) or more, 250 microns (μm) or more, 275 microns (μm) or more, 300 microns (μm) or more, 325 microns (μm) or more, 350 microns (μm) or more, or 375 microns (μm) or more. In some embodiments, the porous foam comprises pores (or holes or pores) having an average size (or average diameter) of 400 microns (μm) or less, 375 microns (μm) or less, 350 microns (μm) or less, 325 microns (μm) or less, 300 microns (μm) or less, 275 microns (μm) or less, 250 microns (μm) or less, 225 microns (μm) or less, 200 microns (μm) or less, 175 microns (μm) or less, 150 microns (μm) or less, or 125 microns (μm) or less. Combinations of the above-mentioned ranges are also possible (e.g., 100 microns (μm) to 400 microns (μm)). Other ranges are also possible. Average pore size (or average pore diameter or average pore diameter) can be measured by scanning electron microscopy.

[0025] In some embodiments, similar to the embodiments shown in FIGS. 1 and 2, the porous foam comprises pores (or holes or pores) having various sizes (or dimensions or dimensions). In other words, the average pore size may be within one or more of the ranges described in the preceding paragraph. However, individual pores (or holes or pores) may have sizes (or dimensions or dimensions) outside of such ranges. It is also possible for the porous foam to have relatively uniform pores (or holes or pores). Similarly, the porous foam may be similar to the porous foam shown in FIGS. 1 and 2 by including pores (or holes or pores) that are relatively spherical and / or have pores (or holes or pores) with relatively circular cross-sections. And / or the porous foam may differ from the porous foam shown in FIGS. 1 and 2 by having pores (or holes or pores) with different shapes (or dimensions). For example, in some embodiments, the porous foam comprises elongated pores (or holes or pores), pores (or holes or pores) with elliptical cross sections, polygonal pores (or holes or pores), and / or pores (or holes or pores) with polygonal cross sections.

[0026] In some embodiments, the porous foam comprises both macropores (e.g., pores (or apertures or pores) having an average size (or average diameter) of 10 microns (μm) or more, e.g., pores (or apertures or pores) having an average size (or average diameter) of 100 microns (μm) or more) and micropores (e.g., pores (or apertures or pores) having an average size (or average diameter) of less than 10 microns (μm)). In such embodiments, the porous foam may have an average pore size (or average pore diameter or average pore diameter) of all pores (or apertures or pores) present in the porous foam, and such average pore size may be within one or more of the above ranges. And / or the average pore size (or average pore diameter or average pore diameter) of all pores (or apertures or pores) observable by scanning electron microscopy may be within one or more of the above ranges. As described further elsewhere in this disclosure, micropores are considered undesirable because they are believed to act as stress concentrations (or stress concentrators).

[0027] Some porous foams advantageously comprise a relatively small amount (or none) of micropores (e.g., pores (or pores or pores) having an average pore size (or average pore diameter or average pore size) of less than 10 microns (μm), 8 microns (μm) or less, 6 microns (μm) or less, 4 microns (μm) or less, 2 microns (μm) or less, or 1 micron (μm) or less). For example, in some embodiments, micropores constitute 15 vol% or less, 12 vol% or less, 10 vol% or less, 7.5 vol% or less, 5 vol% or less, 2 vol% or less, 1 vol% or less, 0.75 vol% or less, 0.5 vol% or less, 0.2 vol% or less, or 0.1 vol% or less of all pores in the porous foam. In some embodiments, the micropores comprise 0% or more, 0.1% or more, 0.2% or more, 0.5% or more, 0.75% or more, 1% or more, 2% or more, 5% or more, 7.5% or more, 10% or more, or 12% or more of the pores of the porous foam by volume. Combinations of the above-mentioned ranges are also possible (e.g., 0% or more to 15% or less). Other ranges are also possible.

[0028] Pores, if present, may comprise a porous foam of various suitable volume fractions. In some embodiments, the porosity of the porous foam (i.e., the volume fraction of the porous foam occupied by pores) is 70% or more, 72.5% or more, 75% or more, 77.5% or more, 80% or more, 82.5% or more, 85% or more, or 87.5% or more. In some embodiments, the porosity of the porous foam is 90% or less, 87.5% or less, 85% or less, 82.5% or less, 80% or less, 77.5% or less, 75% or less, or 72.5% or less. Combinations of the above-mentioned ranges are also possible (e.g., 70% or more to 90% or less). Other ranges are also possible. The porosity of the porous foam can be measured according to ASTM F2450-10.

[0029] The hip labrum scaffolds described herein may have a variety of suitable shapes and sizes. In some embodiments, the hip labrum scaffold is dimensioned to be a suitable substitute for the hip labrum when implanted into a patient. FIG. 3A is a schematic diagram showing a cross section of a human hip (or hip). The hip labrum scaffolds described herein may be configured to be and / or may be positioned in what has been described as the "acetabular labrum" (which is a synonym for the hip labrum). As shown in FIG. 3B, the hip labrum extends around the superior surface of the articular cartilage to form a circular rim.

[0030] There is natural variation in the cross-sectional dimensions and shapes of human hip labrums. Human hip labrums may have a triangular cross-section (e.g., a cross-section like that shown in FIG. 3A , a cross-section resembling an equilateral triangle, a cross-section resembling an isosceles triangle, a cross-section resembling a scalene triangle, a cross-section resembling an acute triangle, a cross-section resembling an obtuse triangle, or a cross-section resembling a right triangle). Human hip labrums may also have cross-sections of other shapes. For example, human hip labrums may have cross-sections that are circular, semicircular, rectangular, irregular, or flat. FIG. 4 shows photomicrographs of human hip labrums with various cross-sections. These labrums are attached to and positioned above the articular cartilage. Each micrograph in FIG. 4 is accompanied by a schematic diagram of the associated hip labrum cross-section.

[0031] In some embodiments, the hip labrum scaffold and / or its components (e.g., porous foam) have a shape that conforms to the shape of a human hip labrum. For example, in some embodiments, the hip labrum scaffold and / or porous foam forms a cylinder or hollow cylinder (or ring) having one or more of the above cross sections. In other words, the hip labrum scaffold and / or porous foam may have a donut-shaped cross section (e.g., a cross section perpendicular to the axis of the cylinder) and a triangular, circular, semicircular, rectangular, irregular, or flattened cross section (e.g., a cross section including the axis of the cylinder). When the hip labrum scaffold and / or porous foam forms a cylinder, the cylinder may be straight (e.g., as exemplarily shown in FIG. 5A) or curved (e.g., as exemplarily shown in FIG. 5B).

[0032] The hip labrum (or hip joint labrum) scaffold and / or porous foam can also have shapes not found in human patients. Such a hip labrum scaffold can be provided to a surgeon, who can then cut the hip labrum scaffold and / or porous foam to a shape that fits the patient's hip labrum. For example, some hip labrum scaffolds and / or porous foams can be shaped like a tube, a ring, a rod, a cigar, etc. In some embodiments, the hip labrum scaffold and / or porous foam has a shape that is suitable for some patients but not for other patients (e.g., a shape with a triangular cross section). Such a hip labrum scaffold and / or porous foam can also be cut by the surgeon to a shape appropriate for a patient with a hip labrum that is shaped differently from the scaffold's shape.

[0033] Further examples of shapes the hip labrum scaffold and / or porous foam may have are shown in FIGS. 6-13. FIGS. 6 and 7 show photographs of the top and bottom of an exemplary hip labrum scaffold. The hip labrum scaffold has the shape of a hollow cylinder or ring, with the cylinder wall including an outer portion parallel to the axis of the cylinder (designated 504 in FIGS. 6 and 7) and a portion extending toward the center of the hip labrum scaffold (designated 604 in FIGS. 6 and 7), which is angled from the top to the base of the hollow cylinder (parallel to the top portion). The space between these portions may be a triangular groove (designated 704 in FIGS. 6 and 7). Such grooves may be in the shape of a right triangle (with the right angle at the base of the cylinder). FIG. 8 is a schematic diagram illustrating such a triangular groove, with the grooves shown as shaded areas. Similar to FIGS. 6-8, in some embodiments, the hip labrum scaffold and / or porous foam comprises a hollow cylinder or ring having one or more sloping sidewalls and / or one or more grooves. The cross-section of the groove (e.g., in a vertical plane) may be generally triangular, other polygonal, and / or generally semicircular in some embodiments. In some embodiments, the hip labrum scaffold and / or porous foam comprises a groove, such groove being positioned on the bottom surface of the hip labrum scaffold and / or porous foam and / or not contacting the lateral sidewall.

[0034] FIG. 9 shows a bottom view of another exemplary hip labrum scaffold. This hip labrum scaffold is similar to that shown in FIGS. 6-7 , except that the angled portion has a lower surface that is higher than the bottom (or base or lower or inferior) surface of the hip labrum scaffold. In other words, the hip labrum scaffold shown in FIG. 9 is in the form of a hollow cylinder (or hollow cylinder or ring), including an inner sidewall that is angled toward the center of the hip labrum scaffold. This hip labrum scaffold further includes a groove. The groove has a polygonal shape and is located (or positioned or positioned) on both the bottom (or base or lower or inferior) surface of the hip labrum scaffold and the inner sidewall of the cylinder. The cylindrical inner sidewall of this hip labrum scaffold is polygonal and includes overhanging portions from the grooves. These features are further shown schematically in Figures 10 and 11.

[0035] FIG. 12 shows a bottom view of a third exemplary hip labrum scaffold. The hip labrum scaffold is in the form of a hollow cylinder (or ring). The cylinder wall is a right triangle with a square (or rectangular) portion removed. In other words, the hip labrum scaffold includes a square (or rectangular) groove that borders the outer sidewall and base of the cylinder. The hip labrum scaffold also includes an inner sidewall that is angled toward the center of the hip labrum scaffold. One corner of the square (or rectangle) is the right angle of the right triangle. FIG. 13 shows a schematic of such a cross section.

[0036] The hip labrum scaffold and porous foam may have any suitable maximum width. As used herein, the maximum width of the hip labrum scaffold or porous foam refers to the longest line that can be drawn across the hip labrum scaffold or porous foam in a direction perpendicular to the thickness direction of the hip labrum scaffold or porous foam. For a hip labrum scaffold or porous foam in the form of a hollow cylinder (or hollow cylinder or ring), the thickness direction of the hip labrum scaffold or porous foam is the axial direction of the cylinder. In some embodiments, the maximum width of the hip labrum scaffold and / or porous foam is 2.5 mm or more, 2.75 mm or more, 3 mm or more, 3.25 mm or more, 3.5 mm or more, 3.75 mm or more, 4 mm or more, 4.25 mm or more, 4.5 mm or more, 4.75 mm or more, 5 mm or more, or 5.25 mm or more. In some embodiments, the maximum width of the hip labrum scaffold and / or porous foam is 5.5 mm or less, 5.25 mm or less, 5 mm or less, 4.75 mm or less, 4.5 mm or less, 4.25 mm or less, 4 mm or less, 3.75 mm or less, 3.5 mm or less, 3.25 mm or less, 3 mm or less, or 2.75 mm or less. Combinations of the above-mentioned ranges are also possible (e.g., 2.5 mm or more to 5.5 mm or less). Other ranges are also possible.

[0037] The hip labrum scaffold and porous foam may have any suitable maximum thickness. As used in this disclosure, the maximum thickness of the hip labrum scaffold or porous foam refers to the longest line that can be drawn generally through the hip labrum scaffold or porous foam in a direction parallel to the direction of the thickness of the hip labrum scaffold or porous foam. In some embodiments, the maximum thickness of the hip labrum scaffold and / or porous foam is 2.5 mm or more, 2.75 mm or more, 3 mm or more, 3.25 mm or more, 3.5 mm or more, 3.75 mm or more, 4 mm or more, 4.25 mm or more, 4.5 mm or more, 4.75 mm or more, 5 mm or more, 5.25 mm or more, 5.5 mm or more, 5.75 mm or more, 6 mm or more, 6.25 mm or more, 6.5 mm or more, 6.75 mm or more, 7 mm or more, 7.25 mm or more, 7.5 mm or more, 7.75 mm or more, 8 mm or more, or 8.25 mm or more. In some embodiments, the maximum thickness of the hip labrum scaffold and / or porous foam is 8.5 mm or less, 8.25 mm or less, 8 mm or less, 7.75 mm or less, 7.5 mm or less, 7.25 mm or less, 7 mm or less, 6.75 mm or less, 6.5 mm or less, 6.25 mm or less, 6 mm or less, 5.75 mm or less, 5.5 mm or less, 5.25 mm or less, 5 mm or less, 4.75 mm or less, 4.5 mm or less, 4.25 mm or less, 4 mm or less, 3.75 mm or less, 3.5 mm or less, 3.25 mm or less, 3 mm or less, or 2.75 mm or less. Combinations of the above-mentioned ranges are also possible (e.g., 2.5 mm or more to 8.5 mm or less). Other ranges are also possible.

[0038] It should be noted that the hip labrum scaffolds described herein may undergo one or more morphological (or form) changes and / or remodeling (or reconstruction or remodeling) after implantation into a patient. For example, as described in further detail below, in some embodiments, the hip labrum scaffold may degrade (or degenerate) over time while inside a patient. As another example, tissue in-growth may affect the morphology (or form) of the hip labrum scaffold over time. Thus, in some embodiments, the hip labrum scaffold may independently have one or more of the above-mentioned ranges of shapes and / or dimensions (or magnitude or size), but at one or more time points before and / or after implantation into a patient.

[0039] As described elsewhere in this disclosure, in some embodiments, the hip labrum scaffold and / or porous foam have an advantageous chemical composition because such a composition allows for tissue in-growth and / or provides the hip labrum scaffold with one or more advantageous mechanical properties. Possible chemistries are further described below.

[0040] Some of the labral scaffolds and / or porous foams described herein may include and / or be formed from synthetic materials (e.g., synthetic polymers). In some embodiments, the labral scaffolds and / or porous foams are formed exclusively from synthetic materials and / or synthetic polymers. In other words, the labral scaffolds and / or porous foams may not include biological materials. Such embodiments may be embodiments in which the labral scaffolds and / or porous foams have not yet been implanted into a patient (i.e., the labral scaffolds and / or porous foams prior to implantation). The labral scaffolds and / or porous foams may also comprise biological materials. For example, after implantation and at least partial tissue in-growth, such material may be disposed (positioned) in at least some of the pores of the labral scaffold and / or porous foam. In some such embodiments, the material forming the matrix in which the pores are disposed does not include a biological material.

[0041] Various suitable types of synthetic polymers may be employed in the hip labrum scaffolds and porous foams described herein. In some embodiments, two or more synthetic polymers may be employed in the same hip labrum scaffold and / or porous foam. In such cases, it should be understood that each synthetic polymer may independently possess some, all, or none of the characteristics described herein. It is also possible, of course, that the hip labrum scaffold and / or porous foam may be formed from a single synthetic polymer. When one or more synthetic polymers are employed in the hip labrum scaffold or synthetic polymer, such polymer(s) may include thermoset polymer(s) and / or thermoplastic polymer(s). Similarly, amorphous (e.g., elastomeric), crystalline, and / or semicrystalline synthetic polymers may be employed in the hip labrum scaffold and / or porous foam. Various types of homopolymers and copolymers may also be suitable. For example, in some embodiments, the hip labrum scaffold and / or porous foam comprises a block copolymer. For such polymers, each block may independently be amorphous (e.g., elastomeric), crystalline, and / or semicrystalline.

[0042] In some embodiments, the hip labrum scaffold and / or porous foam comprises a synthetic polymer, such as polyurethane. The polyurethane may comprise a hard block and a soft block. The hard block may be crystalline, semicrystalline, glassy, ​​and / or resistant to deformation. The soft block may be a rubber block and / or an elastomeric block. In some embodiments, the polyurethane comprises a hard block that is phase-separated from the soft block. Such hard blocks may act as physical and / or chemical crosslinkers, which reduce and / or prevent deformation of the soft block beyond a certain distance. Some polyurethanes may include polymer chains, each of which includes multiple hard blocks and multiple soft blocks, and the hard and soft blocks may be joined together by urethane linkages.

[0043] In some embodiments, species comprising alcohol groups (e.g., diols or polyols) react with species comprising isocyanate groups to form urethane linkages. Diols and polyols are sometimes referred to as "prepolymers." The reaction between such species and species comprising isocyanate groups may be referred to as "end-capping." For some diols and polyols, the alcohol groups may be located exclusively at the ends of the molecule (i.e., such molecules have the structure: R-(OH) n(where n is 2 or greater). Alternatively, they may be located exclusively at locations other than the ends of the molecule. Alternatively, they may be located at both the ends and locations other than the ends of the molecule. Similarly, a diol or polyol may contain an alcohol group at each end. Alternatively, some ends of a diol or polyol may contain an alcohol group. Alternatively, a diol or polyol may not contain an alcohol group at its end. Non-limiting examples of suitable diols and polyols include small molecular weight diols and polyols, oligomeric diols and polyols, and macrodiols and macropolyols. Macrodiols and macropolyols may include a polymer located between at least two alcohol groups. For diols or polyols, polymers, oligomers, or small molecules located between multiple alcohol groups of the diol or polyol may be incorporated into the polyurethane being formed (or produced) as soft blocks.

[0044] Further examples of suitable diols and polyols (the diols and polyols may be low molecular weight, oligomeric, or polymeric) include aliphatic diols and polyols (e.g., diols and polyols comprising aliphatic repeat units (or repeat units) between the alcohol groups (e.g., linear aliphatic repeat units and / or branched aliphatic repeat units); cycloaliphatic diols and polyols (e.g., diols and polyols comprising cycloaliphatic repeat units between the alcohol groups); diols and polyols comprising the reaction product of polyester and / or ester-containing monomers; diols and polyols comprising the reaction product of polyether and / or ether-containing monomers (e.g., diols and polyols comprising polycaprolactone); diols and polyols comprising the reaction product of polycarbonate and / or carbonate-containing monomers (e.g., 1,6 hexanediol Examples of suitable ester-containing monomers include ε-caprolactone, lactide, glycolide, and δ-valerolactone. One non-limiting example of a suitable ether-containing monomer is 1,4-dioxane-2-one. Non-limiting examples of suitable carbonate-containing monomers include 1,5-dioxepan-2-one, oxepane-2,7-dione, trimethylene carbonate, tetramethylene carbonate, 1,3-dioxepan-2-one, and 1,3,8,10-tetraoxacyclotetradecane.

[0045] In some instances, the diol or polyol comprises a copolymer. After reacting a species comprising an isocyanate group with the diol or polyol, the copolymer may be incorporated into the polyurethane as a soft block. The copolymer may comprise one or more repeat units described in the preceding paragraph. An example of a suitable copolymer is a copolycarbonate (e.g., a copolycarbonate comprising the reaction product of one or more carbonate monomers described in the preceding paragraph, but comprising repeat units that do not contain carbonate groups).

[0046] The diol or polyol may also contain moieties having a structure other than that of the repeating units in the oligomer or polymer therein. For example, in some embodiments, a diol or polyol is formed by reacting a diol or polyol with a monomer whose polymerization is initiated by the diol or polyol. In such cases, species located between the alcohol groups may be incorporated into the soft block between the diol- or polyol-initiated polymer or oligomer. Non-limiting examples of such suitable diols include C1-C 10 Alkyl diols (for example, 1,4-butanediol) are included.

[0047] Similarly to the diols and polyols described above, species comprising one or more isocyanate groups (e.g., diisocyanates) may also be reacted, resulting in the reaction product being incorporated into a polyurethane. For such species, the isocyanate groups may be located exclusively at the ends of the molecule (i.e., the molecule may have the structure: R-(NCO) n(where n is 2 or greater). Alternatively, they may be located exclusively at locations other than the ends of the molecule. Alternatively, they may be located both at the ends of the molecule and at locations other than the ends of the molecule. Similarly, each of the related species (or chemical species or species) may contain an isocyanate group. Alternatively, some of the related species (or chemical species or species) may contain an isocyanate group. Alternatively, none of the related species (or chemical species or species) may contain an isocyanate group at their ends. Non-limiting examples of suitable species (or chemical species or species) comprising one or more isocyanates include species (or chemical species or species) containing polymers, oligomers, or small molecules located between multiple isocyanate groups. Furthermore, similar to the diols and polyols described above, species (or chemical species or species) located between multiple isocyanate groups may be incorporated into the resulting polyurethane. Such species may form the hard blocks.

[0048] In some embodiments, the one or more isocyanate-containing species is a C-C 14 Aliphatic groups (e.g., linear C2-C 14 Aliphatic groups, branched C2-C 14 aliphatic groups) and / or cycloaliphatic groups (e.g., between multiple isocyanate groups). In some embodiments, 14 The aliphatic group is C2-C 14 Alkylene groups (e.g., linear C2-C 14 Alkylene group, branched C2-C 14 The cycloaliphatic group may be a cycloalkylene group. 14 For either the aliphatic and / or alkylene groups, such groups may be C3-C 12and / or C3-C6 groups. Non-limiting examples of suitable diisocyanates include 4,4'-dicyclohexanemethane, 1,4-transcyclohexane-diisocyanate, isophorone diisocyanate, 1,6-hexane diisocyanate, and 1,4-butane diisocyanate.

[0049] Some of the hard blocks may also contain the reaction product of a chain extender. A chain extender can react with the isocyanate group(s) in the reaction product to form a longer polymer. This process may also be referred to as "chain extension." This process may be performed after reacting a species containing isocyanate groups with a diol and / or polyol. In the first initial reaction, the relative amounts of diol, polyol, and species containing isocyanate groups may be selected so that the majority of the reaction product contains isocyanate end groups. Such isocyanate end groups may be further reacted with chain extenders to form longer polymers comprising longer hard blocks.

[0050] In some embodiments, the chain extender has the structure: n(e.g., this structure has a central R group and one or more Y functional groups that are reactive toward isocyanate groups). When n=2, the chain extender has the structure: YRY. For any value of n, each Y may independently be OH (i.e., an alcohol functional group), NH (i.e., a primary amine functional group), or NHR′ (i.e., a secondary amine functional group). In some embodiments, all Y are OH (i.e., the chain extender is itself a diol or polyol). It is also possible for all Y to be NH and / or NHR′ (i.e., the chain extender may be a diamine or polyamine). Y groups that are OH may react with isocyanate groups to form urethane linkages. Y groups that are NH or NHR′ may react with isocyanate groups to form (or generate) urea linkages.

[0051] Chain extender structure: RY n In some embodiments, R is a C2-C 14 In some embodiments, R' is an aliphatic group (e.g., a straight-chain aliphatic group, a branched-chain aliphatic group, a straight-chain alkylene group, a branched-chain alkylene group) and / or a cyclic aliphatic group (e.g., a cycloalkylene group). In some embodiments, R' is a C-C 12 Aliphatic groups (e.g., linear C1-C 12 Aliphatic groups, branched C1-C 12 aliphatic groups). Any of the above types of C2-C 14 For any of the aliphatic and / or alkylene groups, the groups are C3-C 12 and / or C3-C6 groups.

[0052] Each Y is NH2 and R is C1-C 12Non-limiting examples of aliphatic chain extenders include ethylenediamines (e.g., 1,2-ethylenediamine), propylenediamines, butylenediamines (e.g., 1,4-butanediamine), and hexamethylenediamines (e.g., 1,6-hexamethylenediamine). 14 Non-limiting examples of cycloalkylene groups include 1,4-isophoronediamine and 1,4-cyclohexanediamine.

[0053] Specific, non-limiting examples of chain extenders where each Y is OH and R is an alkylene group include ethylene glycol, diethylene glycol, dipropylene glycol, 1,4-butanediol, 1,6-hexanediol, 1,8-octanediol, neopentyl glycol, 1,12-dodecanediol, cyclohexanedimethanol, and 1,4-cyclohexanediol.

[0054] Further examples of chain extenders in which each Y is OH include diol block chain extenders (or diol block chain extenders). The diol block chain extender may include the reaction product of a diisocyanate and a diol. In some embodiments, the diol block may be prepared by reacting a diisocyanate with at least two equivalents of a diol. Unreacted excess diol may then be removed (e.g., by evaporation or extraction). Non-limiting examples of suitable diol block chain extenders include the reaction product of 1,4-butanediisocyanate (BDI) with 1,4-butanediol (BDO), the reaction product of BDI with 1,6-hexanediol (HDO), and the reaction product of 1,6-hexanediisocyanate (HDI) with HDO. Such diol blocks can have the following structures, respectively: BDO-BDI-BDO, HDO-BDI-HDO, and HDO-HDI-HDO. The diol block chain extender can also contain a total of 5, 7, or more blocks. For example, the diol block chain extender can be (BDO / HDO)-(BDI / HDI-BDO / HDO).n where n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments, the diol block chain extender is formed by a catalyst-free method.

[0055] The internal blocks (e.g., hard blocks, soft blocks, blocks comprising polyester (e.g., polycaprolactone), blocks comprising polycarbonate and / or copolycarbonate) of a block copolymer (e.g., polyurethane) may have various suitable molecular weights. In some embodiments, the polymer comprises blocks having a number average molecular weight of 0.6 kg / mol or greater, 0.7 kg / mol or greater, 0.8 kg / mol or greater, 0.9 kg / mol or greater, 1 kg / mol or greater, 1.1 kg / mol or greater, 1.2 kg / mol or greater, 1.3 kg / mol or greater, 1.4 kg / mol or greater, 1.5 kg / mol or greater, 1.6 kg / mol or greater, 1.7 kg / mol or greater, 1.8 kg / mol or greater, 1.9 kg / mol or greater, 2 kg / mol or greater, 2.1 kg / mol or greater, 2.2 kg / mol or greater, 2.3 kg / mol or greater, 2.4 kg / mol or greater, 2.5 kg / mol or greater, 2.6 kg / mol or greater, 2.7 kg / mol or greater, 2.8 kg / mol or greater, or 2.9 kg / mol or greater. In some embodiments, the polymer comprises blocks having a number average molecular weight of 3 kg / mol or less, 2.9 kg / mol or less, 2.8 kg / mol or less, 2.7 kg / mol or less, 2.6 kg / mol or less, 2.5 kg / mol or less, 2.4 kg / mol or less, 2.3 kg / mol or less, 2.2 kg / mol or less, 2.1 kg / mol or less, 2 kg / mol or less, 1.9 kg / mol or less, 1.8 kg / mol or less, 1.7 kg / mol or less, 1.6 kg / mol or less, 1.5 kg / mol or less, 1.4 kg / mol or less, 1.3 kg / mol or less, 1.2 kg / mol or less, 1.1 kg / mol or less, 1 kg / mol or less, 0.9 kg / mol or less, 0.8 kg / mol or less, or 0.7 kg / mol or less. Combinations of the above-mentioned ranges are also possible (e.g., from 0.6 kg / mol to 3 kg / mol, or from 1 kg / mol to 2 kg / mol). Other ranges are also possible.

[0056] It should be understood that when a block copolymer comprises one or more blocks, each block may independently have a number average molecular weight within one or more of the ranges set forth above. Similarly, when a polymer comprises multiple blocks of a single type (e.g., multiple soft blocks, multiple hard blocks, multiple blocks comprising polyesters (e.g., polycaprolactone), multiple blocks comprising polycarbonates and / or copolycarbonates), the weight average molecular weight averaged over all of the blocks of a single type may independently be within one or more of the ranges set forth above for each type of block.

[0057] In block copolymers, the number average molecular weight of the blocks can be determined by gel permeation chromatography.

[0058] The synthetic polymers present in the hip labrum scaffold and / or porous foam as a whole may have a variety of suitable number average molecular weights. In some embodiments, the hip labrum scaffold and / or porous foam comprises a synthetic polymer having a number average molecular weight of 100 kg / mol or greater, 105 kg / mol or greater, 110 kg / mol or greater, 115 kg / mol or greater, 120 kg / mol or greater, 125 kg / mol or greater, 130 kg / mol or greater, 135 kg / mol or greater, 140 kg / mol or greater, 145 kg / mol or greater, 150 kg / mol or greater, 165 kg / mol or greater, 170 kg / mol or greater, 175 kg / mol or greater, 180 kg / mol or greater, 185 kg / mol or greater, 190 kg / mol or greater, 195 kg / mol or greater, 200 kg / mol or greater, 205 kg / mol or greater, 210 kg / mol or greater, 215 kg / mol or greater, 220 kg / mol or greater, 225 kg / mol or greater, 230 kg / mol or greater, or 235 kg / mol or greater. In some embodiments, the hip labrum scaffold and / or porous foam has a mechanical strength of 240 kg / mol or less, 235 kg / mol or less, 230 kg / mol or less, 225 kg / mol or less, 220 kg / mol or less, 215 kg / mol or less, 210 kg / mol or less, 205 kg / mol or less, 200 kg / mol or less, 195 kg / mol or less, 190 kg / mol or less, 185 kg / mol or less, 180 kg / mol or less, 175 kg / mol or less, 180 kg / mol or less, 18 ... The polymers may comprise synthetic polymers having a number average molecular weight of 170 kg / mol or less, 165 kg / mol or less, 160 kg / mol or less, 155 kg / mol or less, 150 kg / mol or less, 145 kg / mol or less, 140 kg / mol or less, 135 kg / mol or less, 130 kg / mol or less, 125 kg / mol or less, 120 kg / mol or less, 115 kg / mol or less, 110 kg / mol or less, or 105 kg / mol or less. Combinations of the above-referenced ranges are also possible (e.g., from 100 kg / mol to 240 kg / mol, or from 100 kg / mol to 150 kg / mol). Other ranges are also possible.

[0059] When the hip labrum implant and / or porous foam comprises two or more synthetic polymers, each synthetic polymer may independently have a number average molecular weight in one or more of the ranges described in the preceding paragraph, and / or all synthetic polymers in the hip labrum implant and / or porous foam together may have a number average molecular weight in one or more of the ranges described in the preceding paragraph.

[0060] The number average molecular weight of the synthetic polymer can be determined by gel permeation chromatography.

[0061] The synthetic polymers present in the hip labrum scaffold and / or porous foam as a whole may have a wide range of polydispersities (or polydispersities or polydispersities). In some embodiments, the polydispersity (or polydispersities or polydispersities) of the hip labrum scaffold and / or porous foam is 3 or less, 2.75 or less, 2.5 or less, 2.25 or less, 2 or less, 1.75 or less, 1.5 or less, or 1.25 or less. In some embodiments, the polydispersity (or polydispersities or polydispersities) of the hip labrum scaffold and / or porous foam is 1 or more, 1.25 or more, 1.5 or more, 1.75 or more, 2 or more, 2.25 or more, 2.5 or more, or 2.75 or more. Combinations of the above-referenced ranges are also possible (e.g., 1 or more to 3 or less). Other ranges are also possible.

[0062] When the hip labrum implant and / or porous foam comprises two or more synthetic polymers, the synthetic polymers may each independently have a polydispersity (or polydispersity or polydispersity) in one or more of the ranges described in the preceding paragraph, and / or all of the synthetic polymers in the hip labrum implant and / or porous foam together may have a polydispersity (or polydispersity or polydispersity) in one or more of the ranges described in the preceding paragraph.

[0063] The polydispersity (or polydispersity or polydispersity) of synthetic polymers can be determined by gel permeation chromatography.

[0064] In some embodiments, the synthetic polymer present in the hip labrum scaffold and / or porous foam contains relatively low levels of impurities. For example, in some embodiments, such synthetic polymers comprise a relatively small amount of catalyst. Such catalysts may be present during the synthesis of the synthetic polymer (e.g., the catalyst may catalyze the polymerization of monomers to form the synthetic polymer), but are then largely or completely removed after completion of the synthesis. Non-limiting examples of such catalysts include alkyl tin carboxylates, alkyl tin oxides, alkyl tin mercaptides, triethylenediamine, dimethylcyclohexylamine, dimethylethanolamine, bis-(2-dimethylaminoethyl) ether, and dibutyl tin dilaurate. Synthetic polymers can also be synthesized in a catalyst-free manner.

[0065] In some embodiments, the mixture reacting to form (or produce) the hip labrum scaffold, porous foam, and / or synthetic polymer comprises no more than 0.001 wt%, no more than 0.0001 wt%, and / or 0 wt% of any particular catalyst, and all types of catalysts together can comprise no more than 0.001 wt%, no more than 0.0001 wt%, and / or 0 wt% of the mixture reacting to form (or produce) the hip labrum scaffold, porous foam, and / or synthetic polymer.

[0066] It should be noted that the mixture reacting to form (or produce) the hip labrum scaffold, porous foam, and / or synthetic polymer may include any particular catalyst (e.g., in addition to other catalysts) in an amount of one or more of the preceding paragraphs. The mixture reacting to form (or produce) the hip labrum scaffold, porous foam, and / or synthetic polymer may also include the total amount of all catalysts in one or more of the ranges in the preceding paragraphs.

[0067] Various techniques can be employed to form (or produce) synthetic polymers suitable for use in the hip labrum scaffolds and porous foams described herein. For example, some synthetic polymers may be produced (or prepared) by step-growth techniques. Some synthetic polymers may be produced (or prepared) by chain-growth techniques. Non-limiting examples of suitable chain-growth techniques include free radical polymerization, cationic polymerization, and anionic polymerization. One specific method suitable for producing (or preparing) polyurethanes for use in the hip labrum scaffolds and porous foams described herein is described in further detail below.

[0068] In some embodiments, synthesizing a polyurethane (or a method or process) includes forming a macrodiol (e.g., a macrodiol having one or more chemical compositions described elsewhere in this disclosure). The macrodiol may be formed by reacting a diol with a monomer. In some embodiments, an alcohol group present in the diol initiates ring-opening polymerization of the monomer. The monomer then polymerizes at both ends as the chain grows to form the macrodiol. The macrodiol may include repeat units formed by the polymerized monomer. Such repeat units are described elsewhere in this disclosure. The reaction to form the macrodiol may be carried out in the presence of a solvent or in bulk. Non-limiting examples of suitable solvents include dimethyl sulfoxide, dimethylformamide, chloroform, 1,4-dioxane, N-methylpyrrolidone, and m-cresol.

[0069] The ring-opening polymerization may be carried out until a majority (or proportion or percentage (%)) of the monomers initially present in the reaction mixture are incorporated into the macrodiol. While not wishing to be bound by theory, it is believed that this reduces the amount of unreacted monomers present in the final product. Because unreacted monomers present in the final product are often erroneously included in the calculated amount of macrodiol, and the stoichiometry of the various reagents in subsequent reactions is often selected based on the calculated amount of macrodiol, reducing the amount of unreacted monomers in the final product may advantageously facilitate better control in polyurethane synthesis. In some embodiments, the reaction is carried out until 99.5 mol % or more, or 99.8 mol % or more of the initial monomer content of the reaction mixture is incorporated into the macrodiol to form the macrodiol. The content of the initial monomers incorporated into the macrodiol can be determined by nuclear magnetic resonance (NMR).

[0070] During the formation (or production) of the macrodiol, the temperature of the reaction mixture may generally be selected as desired. In some embodiments, the temperature is 140°C or higher, 145°C or higher, 150°C or higher, 155°C or higher, 160°C or higher, or 165°C or higher. In some embodiments, the temperature is 170°C or lower, 165°C or lower, 160°C or lower, 155°C or lower, 150°C or lower, or 145°C or lower. Combinations of the above-mentioned ranges are also possible (e.g., 140°C or higher and 170°C or lower). Other ranges are also possible.

[0071] After forming (or generating) the macrodiol, the macrodiol may be reacted with a diisocyanate to form (or generate) a macrodiisocyanate. In other words, the macrodiol may be reacted with two equivalents of diisocyanate to generate (or generate) a longer chain capped with an isocyanate group. In the reaction product, the structure initially disposed between the two diol groups of the macrodiol may be connected at both ends by a urethane bond (to the structure initially disposed between the isocyanate groups of the diisocyanate). An excess of diisocyanate relative to the macrodiol may be provided in the reaction mixture. The ratio of diisocyanate to macrodiol (or diisocyanate / macrodiol) may be 2 (e.g., stoichiometrically, the macrodiol reacts with the diisocyanate to form the macrodiisocyanate) or may be greater. While not wishing to be bound by any particular theory, it is believed that the greater the ratio of diisocyanate to macrodiol (or diisocyanate / macrodiol), the more than one macrodiol may react with a single diisocyanate to produce a longer chain macrodiisocyanate (e.g., a structure of (isocyanate)-(urethane bond)-[(a species (or chemical species or species) initially disposed between the alcohol functional groups of the macrodiol)-(urethane bond)-(a species (or chemical species or species) initially disposed between the isocyanate functional groups of the diisocyanate)-(a species (or chemical species or species) initially disposed between the alcohol functional groups of the macrodiol)). n It is believed that this inhibits the formation (or generation) of species (or chemical species or species) that form macrodiisocyanates having -(urethane bond)-(isocyanate) (wherein n is 1 or greater).

[0072] In some embodiments, the ratio of diisocyanate to macrodiol (or diisocyanate / macrodiol) is 2 or more, 2.5 or more, 3 or more, 3.5 or more, 4 or more, 4.5 or more, 5 or more, 5.5 or more, 6 or more, 6.5 or more, 7 or more, 7.5 or more, 8 or more, or 8.5 or more. In some embodiments, the ratio of diisocyanate to macrodiol (or diisocyanate / macrodiol) is 9 or less, 8.5 or less, 8 or less, 7.5 or less, 7 or less, 6.5 or less, 6 or less, 5.5 or less, 5 or less, 4.5 or less, 4 or less, 3.5 or less, 3 or less, or 2.5 or less. Combinations of the above-mentioned ranges are also possible (e.g., 2 or more to 9 or less). Other ranges are also possible.

[0073] During the formation (or generation) of the macrodiisocyanate, the temperature of the reaction mixture may generally be selected as desired. In some embodiments, the temperature is 50°C or higher, 55°C or higher, 60°C or higher, 65°C or higher, 70°C or higher, 75°C or higher, 80°C or higher, 85°C or higher, 90°C or higher, 95°C or higher, 100°C or higher, 105°C or higher, 110°C or higher, or 115°C or higher. In some embodiments, the temperature is 120°C or lower, 115°C or lower, 110°C or lower, 105°C or lower, 100°C or lower, 95°C or lower, 90°C or lower, 85°C or lower, 80°C or lower, 75°C or lower, 70°C or lower, 65°C or lower, 60°C or lower, or 55°C or lower. Combinations of the above-mentioned ranges are also possible (e.g., 50°C or higher to 120°C or lower). Other ranges are also possible.

[0074] Additionally, the reaction time for carrying out the reaction to form (or generate) the macrodiisocyanate may generally be selected as desired. In some embodiments, the reaction time is 3.5 hours or more, 4 hours or more, 4.5 hours or more, 5 hours or more, 5.5 hours or more, 6 hours or more, 6.5 hours or more, 7 hours or more, or 7.5 hours or more. In some embodiments, the reaction time is 8 hours or less, 7.5 hours or less, 7 hours or less, 6.5 hours or less, 6 hours or less, 5.5 hours or less, 5 hours or less, 4.5 hours or less, or 4 hours or less. Combinations of the above-mentioned ranges are also possible (e.g., 3.5 hours or more to 8 hours or less). Other ranges are also possible.

[0075] In some embodiments, the reaction mixture is maintained at a temperature within one or more of the above ranges throughout the entire reaction time. The reaction time may also include one or more periods during which the reaction mixture is maintained at a temperature within one or more of the above ranges and at a temperature outside one or more of the above ranges. Alternatively, the reaction mixture may be maintained at a temperature outside the above ranges throughout the entire reaction time.

[0076] The reaction to form (or generate) the macrodiisocyanate may be carried out in the presence of a solvent or in bulk. Non-limiting examples of suitable solvents include dimethyl sulfoxide, dimethylformamide, chloroform, 1,4-dioxane, N-methylpyrrolidone, and m-cresol.

[0077] After formation of the macrodiisocyanate, unreacted diisocyanate may be removed from the reaction mixture by applying reduced pressure (e.g., a pressure of 0.01 mbar or less, a pressure of 0.003 mbar or less) and / or elevated temperature (e.g., a temperature between 50°C and 90°C). In some embodiments, reduced pressure and / or elevated temperature are applied until at least 95 mol% of the initial diisocyanate is incorporated into or removed from the macrodiisocyanate, until at least 98 mol% of the initial diisocyanate is incorporated into or removed from the macrodiisocyanate, until at least 99 mol% of the initial diisocyanate is incorporated into or removed from the macrodiisocyanate, and / or until at least 99.5 mol% of the initial diisocyanate is incorporated into or removed from the macrodiisocyanate. The amount of diisocyanate removed may be determined by nuclear magnetic resonance (NMR).

[0078] After the macrodiisocyanate is formed, it may be reacted with a chain extender. This reaction may be carried out in the presence of a solvent or in bulk. Non-limiting examples of suitable solvents include dimethyl sulfoxide, dimethylformamide, chloroform, 1,4-dioxane, N-methylpyrrolidone, and m-cresol. In the reaction mixture, the molar ratio of chain extender to macrodiisocyanate (or chain extender / macrodiisocyanate) may be 1 or greater, 1.01 or greater, 1.02 or greater, 1.03 or greater, 1.04 or greater, 1.05 or greater, 1.06 or greater, 1.07 or greater, or 1.08 or greater. In the reaction mixture, the molar ratio of chain extender to macrodiisocyanate (or chain extender / macrodiisocyanate) can be 1.09 or less, 1.08 or less, 1.07 or less, 1.06 or less, 1.05 or less, 1.04 or less, 1.03 or less, 1.02 or less, or 1.01 or less. Combinations of the above-referenced ranges are also possible (e.g., 1 or more to 1.09 or less). Other ranges are also possible.

[0079] The reaction of the macrodiisocyanate with the chain extender can be carried out at a variety of suitable temperatures, in some embodiments, the temperature is 50°C or higher, 55°C or higher, 60°C or higher, 65°C or higher, 70°C or higher, 75°C or higher, 80°C or higher, 85°C or higher, 90°C or higher, 95°C or higher, 100°C or higher, 105°C or higher, 110°C or higher, 115°C or higher, 120°C or higher, 125°C or higher, 130°C or higher, 135°C or higher, 140°C or higher, or 145°C or higher. In some embodiments, the temperature is 150° C. or less, 145° C. or less, 140° C. or less, 135° C. or less, 130° C. or less, 125° C. or less, 120° C. or less, 115° C. or less, 110° C. or less, 105° C. or less, 100° C. or less, 95° C. or less, 90° C. or less, 85° C. or less, 80° C. or less, 75° C. or less, 70° C. or less, 65° C. or less, 60° C. or less, or 55° C. or less. Combinations of the above-mentioned ranges are also possible (e.g., 50° C. or more and 150° C. or less). Other reactions are also possible.

[0080] Various techniques can be employed to form porous foams from synthetic polymers (e.g., polyurethanes). In some embodiments, the method includes forming a porous scaffold by first forming a mixture, wherein the synthetic polymer is phase-separated from one or more additional components. The method then includes removing the additional component(s) from the mixture. The locations where the component(s) were located before removal from the mixture may become pores in the synthetic polymer after removal of the component(s). In one specific example, the mixture comprises a crystalline synthetic polymer, one or more solvents, and a particulate material that is insoluble in the solvent(s). The synthetic polymer may be miscible with the solvent(s) at higher temperatures and immiscible with the solvent(s) at lower temperatures. Thus, cooling the mixture may microphase separate the synthetic polymer from the solvent(s). If the temperature at which the synthetic polymer and solvent(s) microphase separate exceeds the melting point of the synthetic polymer and the melting point of the solvent(s), cooling the mixture can induce liquid-liquid microphase separation between the solvent(s) and the synthetic polymer prior to crystallization of the synthetic polymer or solvent(s). Further cooling can then fix the microphase-separated structure in place by crystallization of the synthetic polymer and / or solvent(s). After crystallization, the mixture may be washed with a fluid that is a solvent for the particulate material and solvent(s) but a non-solvent for the synthetic polymer, removing the particulate material and solvent(s) from the mixture and leaving behind pores.

[0081] Also, procedures similar to those described in the preceding paragraphs can be used, except that in such procedures, a pore-forming agent (or hole-forming agent or pore-forming agent) can be employed in place of the particulate material rather than the particulate material. Non-limiting examples of particulate materials and pore-forming agents include small organic molecules (e.g., sugar(s) (e.g., saccharose and / or glucose)) and salt(s). The salt(s) can be alkali and / or alkaline salts and / or chloride salts. Non-limiting examples of suitable salts include NaCl, KCl, CaCl, and MgCl.

[0082] When provided as particles, the particle size (or particle diameter or particle size) of the pore former (or hole former or pore forming agent) may generally be selected as desired. In some embodiments, the average diameter of the particulate material is 30 microns (μm) or more, 50 microns (μm) or more, 75 microns (μm) or more, 100 microns (μm) or more, 150 microns (μm) or more, 200 microns (μm) or more, 250 microns (μm) or more, 300 microns (μm) or more, 350 microns (μm) or more, 400 microns (μm) or more, 500 microns (μm) or more, 600 microns (μm) or more, 700 microns (μm) or more, 800 microns (μm) or more, 1 mm or more, or 1.25 mm or more. In some embodiments, the particulate material has an average diameter of 1.5 mm or less, 1.25 mm or less, 1 mm or less, 800 microns (μm) or less, 700 microns (μm) or less, 600 microns (μm) or less, 500 microns (μm) or less, 400 microns (μm) or less, 350 microns (μm) or less, 300 microns (μm) or less, 250 microns (μm) or less, 200 microns (μm) or less, 150 microns (μm) or less, 100 microns (μm) or less, 75 microns (μm) or less, or 50 microns (μm) or less. Combinations of the above-mentioned ranges are also possible (e.g., 30 microns (μm) to 1.5 mm). Other ranges are also possible. The average particle diameter can be determined by microscopy.

[0083] The pore former may be present in the mixture described herein at a variety of suitable concentrations, in some embodiments, the pore former is present in the mixture at a concentration of 100 wt% / vol (or weight % / volume or weight % / volume or weight % / volume) or greater, 125 wt% / vol or greater, 150 wt% / vol or greater, 175 wt% / vol or greater, 200 wt% / vol or greater, 225 wt% / vol or greater, 250 wt% / vol or greater, 275 wt% / vol or greater, 300 wt% / vol or greater, 325 wt% / vol or greater, 350 wt% / vol or greater, or 375 wt% / vol or greater. In some embodiments, the pore former is present in the mixture at a concentration of 400 wt% / vol (or weight % / volume or weight % / volume or weight % / volume) or less, 375 wt% / vol or less, 350 wt% / vol or less, 325 wt% / vol or less, 300 wt% / vol or less, 275 wt% / vol or less, 250 wt% / vol or less, 225 wt% / vol or less, 200 wt% / vol or less, 175 wt% / vol or less, 150 wt% / vol or less, or 125 wt% / vol or less. Combinations of the above-mentioned ranges are also possible (e.g., 100 wt% / vol or more to 400 wt% / vol). Other ranges are also possible.

[0084] In some embodiments, the mixture to which the pore former (e.g., particulate material) is added is heated after such addition. Such mixture may be heated to a temperature of 50° C. or more, 60° C. or more, 70° C. or more, 80° C. or more, 90° C. or more, 100° C. or more, 110° C. or more, 120° C. or more, or 130° C. or more. The mixture may be heated to a temperature of 140° C. or less, 130° C. or less, 120° C. or less, 110° C. or less, 100° C. or less, 90° C. or less, 80° C. or less, 70° C. or less, 60° C. or less, or 50° C. or less. Combinations of the above-mentioned ranges are also possible (e.g., 50° C. or more to 140° C. or less). Other ranges are also possible.

[0085] Non-limiting examples of suitable solvents include dimethyl sulfoxide, dimethylformamide, cresol, 1,4-dioxane, and chloroform. Such solvents may be particularly suitable when the synthetic polymer is a polyurethane.

[0086] In some embodiments, a procedure similar to that described above is carried out, where the mixture further comprises one or more liquids that are non-solvents for the synthetic polymer at all temperatures to which the mixture is exposed. The non-solvent(s) may be added with the solvent and / or may be added to the mixture comprising the synthetic polymer and solvent. In some embodiments, an optional non-solvent is added to such a mixture, and then an optional pore-forming agent (e.g., a particulate material) is added to the mixture comprising the synthetic polymer, solvent(s), and non-solvent(s). If added to the mixture comprising the synthetic polymer and solvent, the resulting mixture may then be stirred together. Stirring may proceed for a period of 10 minutes or more, 12.5 minutes or more, 15 minutes or more, 17.5 minutes or more, 20 minutes or more, 22.5 minutes or more, 25 minutes or more, or 27.5 minutes or more. Stirring may proceed for a period of time (or duration) of 30 minutes or less, 27.5 minutes or less, 25 minutes or less, 22.5 minutes or less, 20 minutes or less, 17.5 minutes or less, 15 minutes or less, or 12.5 minutes or less. Combinations of the above-mentioned ranges are also possible (e.g., 10 minutes or more to 30 minutes or less). Other ranges are also possible.

[0087] In some embodiments, the mixture includes a polar non-solvent and / or a non-polar non-solvent and / or is miscible with the solvent(s). Non-limiting examples of suitable polar non-solvents include C1-C6 alkyl alcohol(s) (e.g., ethanol) and water. Non-limiting examples of suitable non-polar non-solvents include diethyl ether, pentane, and hexane. When the non-solvent(s) includes water and the synthetic polymer includes polyurethane, it may be desirable to add the water quickly and not stir the mixture for too long. It is believed that the polyurethane may contain unreacted NCO groups. It is believed that water may function as a chain extender for the NCO groups. It is also believed that any unreacted NCO groups may react with water to form amine groups. It is also believed that the amine groups may react with NCO groups.

[0088] In some embodiments, a mixture of C1-C6 alkyl alcohol and water is employed as the non-solvent. The C1-C6 alkyl alcohol may comprise 5 vol% (or volume %, volume %, or volume %) or more, 10 vol% or more, 15 vol% or more, 20 vol% or more, or 25 vol% or more of the alcohol-water mixture. The C1-C6 alkyl alcohol may comprise 30 vol% or less, 25 vol% or less, 20 vol% or less, 15 vol% or less, or 10 vol% or less of the alcohol-water mixture. Combinations of the above-mentioned ranges are also possible (e.g., 5 vol% or more to 30 vol% or less). Other ranges are also possible.

[0089] The non-solvent(s), when present, may comprise 2 vol% or more, 3 vol% or more, 5 vol% or more, 7.5 vol% or more, 10 vol% or more, 12.5 vol% or more, 15 vol% or more, 17.5 vol% or more, 20 vol% or more, 22.5 vol% or more, 25 vol% or more, or 27.5 vol% or more of the total volume (or capacity or volume) of the solvent(s) and non-solvent(s) combined. In some embodiments, the non-solvent(s) comprise 30 vol% or less, 27.5 vol% or less, 25 vol% or less, 22.5 vol% or less, 20 vol% or less, 17.5 vol% or less, 15 vol% or less, 12.5 vol% or less, 10 vol% or less, 7.5 vol% or less, 5 vol% or less, or 3 vol% or less of the total volume (or capacity or volume) of the solvent(s) and non-solvent(s). Combinations of the above-mentioned ranges are also possible (eg, greater than or equal to 2 vol % and less than or equal to 30 vol %), and other ranges are also possible.

[0090] In some embodiments, a porous foam is produced (or prepared) according to the above procedure. The relative amounts of solvent and synthetic polymer are selected to increase the likelihood of forming pores with the desired morphology (or form). For example, a mixture may contain relative amounts of solvent and synthetic polymer such that, when formed, the pores comprise a desired volume fraction of the mixture. This may be achieved by matching such a volume fraction of solvent in the phase-separated mixture to a porous foam with the desired porosity (or porousness or porosity).

[0091] In some embodiments, the amount of synthetic polymer is selected to provide at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, or 85% of the equilibrium concentration of the synthetic polymer in the synthetic polymer-rich phase of the phase-separated mixture at the melting point (or melting point) of the synthetic polymer or solvent. In some embodiments, the amount of synthetic polymer is selected to provide at most 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, or 45% of the equilibrium concentration of the synthetic polymer in the synthetic polymer-rich phase of the phase-separated mixture at the melting point (or melting point) of the synthetic polymer or solvent. Combinations of the above-mentioned ranges are also possible (e.g., 40% to 90%). Other ranges are also possible. For polyurethanes in polar solvents, in particular, one or more of the above ranges may correspond to the amount of polyurethane in the mixture, the amount being between 20 wt% / vol and 50 wt% / vol and / or between 30 wt% / vol and 45 wt% / vol.

[0092] Without wishing to be bound by any particular theory, it is believed that in phase-separated mixtures, the volume fraction of each phase can be determined by the lever principle. For mixtures consisting of a synthetic polymer and a solvent, the volume fraction of the solvent-rich phase can be determined using the lever principle as follows: [(volume fraction of synthetic polymer in the mixture) - (volume fraction of synthetic polymer in the solvent-rich phase)] / [(volume fraction of synthetic polymer in the synthetic polymer-rich phase) - (volume fraction of synthetic polymer in the solvent-rich phase)] If the volume fraction of the synthetic polymer in the solvent-rich phase is near zero (0), the above expression (or equation) simplifies to: (Volume fraction of synthetic polymer in the blend) / (Volume fraction of synthetic polymer in the synthetic polymer-rich phase)

[0093] After forming the mixture of synthetic polymer, solvent(s), particulates and / or pore formers, and / or non-solvent(s), the mixture may be agitated. Agitation may be performed at a variety of suitable temperatures. In some embodiments, the mixture is agitated at a temperature of 60°C or higher, 65°C or higher, 70°C or higher, 75°C or higher, 80°C or higher, or 85°C or higher. In some embodiments, the mixture is agitated at a temperature of 90°C or lower, 85°C or lower, 80°C or lower, 75°C or lower, 70°C or lower, or 65°C or lower. Combinations of the above-mentioned ranges are also possible (e.g., 60°C or higher and 90°C or lower). Other ranges are also possible.

[0094] The amount of time for which stirring is performed may generally be selected as desired. In some embodiments, the stirring time is 1 hour or more, 1.5 hours or more, 2 hours or more, 2.5 hours or more, 3 hours or more, 3.5 hours or more, 4 hours or more, 4.5 hours or more, 5 hours or more, or 5.5 hours or more. In some embodiments, the stirring time is 8 hours or less, 7.5 hours or less, 6 hours or less, 5.5 hours or less, 5 hours or less, 4.5 hours or less, 4 hours or less, 3.5 hours or less, 3 hours or less, 2.5 hours or less, 2 hours or less, or 1.5 hours or less. Combinations of the above-mentioned ranges are also possible (e.g., 1 hour or more to 6 hours or less). Other ranges are also possible.

[0095] In some embodiments, the mixture is held (or maintained) at one or more of the above-mentioned temperature ranges throughout the entire stirring period. The stirring period may also include one or more periods (or times) during which the mixture is held (or maintained) at one or more of the above-mentioned temperature ranges and periods (or times) during which the mixture is held (or maintained) at one or more temperatures outside of the above-mentioned ranges. Alternatively, the mixture may be held (or maintained) at a temperature outside of the above-mentioned ranges throughout the entire stirring period.

[0096] During the stirring, the molecular weight of the synthetic polymer may increase.

[0097] As explained above, in some embodiments, following formation of a mixture comprising a synthetic polymer, one or more solvents, one or more pore formers, and / or one or more non-solvents, the resulting mixture may be placed in a mold (or form or form) and then cooled. The mixture may be cooled to 30° C. or less, 20° C. or less, 10° C. or less, 0° C. or less, −10° C. or less, −20° C. or less, −30° C. or less, −40° C. or less, −50° C. or less, −60° C. or less, −70° C. or less, −80° C. or less, or −90° C. The mixture may be cooled to ≧−100° C., ≧−90° C., ≧−80° C., ≧−70° C., ≧−60° C., ≧−50° C., ≧−40° C., ≧−30° C., ≧−20° C., ≧−10° C., ≧0° C., ≧10° C., ≧20° C., ≧20° C. Combinations of the above-mentioned ranges are also possible (eg, greater than or equal to -100°C and less than or equal to 30°C), and other ranges are also possible.

[0098] Non-limiting examples of suitable fluids for washing the phase-separated and crystallized mixture include organic solvents, aqueous solvents, and mixtures thereof. Non-limiting examples of organic solvents include dimethyl sulfoxide, N-methylpyrrolidone, dimethylformamide, dimethylacetamide, dioxane, and ethanol. Such fluids may be suitable when the synthetic polymer is polyurethane and / or when the solvent, non-solvent, and / or particulate material are those described elsewhere in this disclosure. With particular reference to polyurethane, it may be desirable to employ the following order of fluids for washing the phase-separated and crystallized mixture: 80wt%:20wt% water:ethanol mixture, 95wt%:5wt% ethanol:water mixture, then diethyl ether, hexane or pentane

[0099] In some embodiments, after the porous foam is washed, it is subjected to a further annealing process (or step). The annealing process (or step) may include heating the porous foam (e.g., heating at atmospheric pressure) to a temperature above the melting point (or melting point) of the materials forming the porous foam (e.g., synthetic polymers and / or polymers therein). Without wishing to be bound by theory, it is believed that annealing the porous foam may strengthen the porous foam (e.g., annealing the porous foam may increase the compressive modulus, tensile modulus, tensile strength, and / or suture pull-out strength of the porous foam). It is believed that the size, shape, and / or interconnectivity of the pores (or holes or pores) may be advantageously developed (or developed or expanded). This may occur without a substantial decrease in the porosity of the porous foam (e.g., the porosity of the porous foam may be substantially maintained while the size, shape, and / or interconnectivity of the pores (or holes or pores) are changed). It is believed that annealing the porous foam may also cause smaller pores (e.g., pores having a diameter of 1 micron (μm) or less) therein to be combined (or coalesced). These smaller pores are believed to act unnecessarily as stress concentrators, and the coalescence of these pores is believed to improve the mechanical properties of the porous foam.Also, larger pores formed by bonding (or coalescence) promote more tissue in-growth compared to smaller pores that have not undergone bonding (or coalescence), and more bonding (or coalescence) may also improve (or enhance) tissue in-growth into the porous foam.

[0100] The temperature to which the porous foam is heated during the annealing process (or step) may be higher than the melting point (or melting point) of the porous foam by at least 1° C., 2° C., 3° ​​C., 4° C., 5° C., 7.5° C., 10° C., 12.5° C., 15° C., or 17.5° C. or higher. In some embodiments, the temperature to which the porous foam is heated during the annealing process (or step) is higher than the melting point (or melting point) of the porous foam by at most 20° C., 17.5° C., 15° C., 12.5° C., 10° C., 7.5° C., 5° C., 4° C., 3° ​​C., 2° C., or 1° C. or lower. Combinations of the above-mentioned ranges are also possible (e.g., 1° C. or higher and 20° C. or lower). Other ranges are also possible. The melting point (or melting point) of the porous foam may be determined by differential scanning calorimetry.

[0101] The time (or duration) for the annealing step (or step) may generally be selected as desired. In some embodiments, the annealing step (or step) is performed for a duration (or time) of 1 minute or more, 2 minutes or more, 3 minutes or more, 4 minutes or more, 5 minutes or more, 7.5 minutes or more, 10 minutes or more, 12.5 minutes or more, 15 minutes or more, or 17.5 minutes or more. In some embodiments, the annealing step (or step) is performed for a duration (or time) of 20 minutes or less, 17.5 minutes or less, 15 minutes or less, 12.5 minutes or less, 10 minutes or less, 7.5 minutes or less, 5 minutes or less, 4 minutes or less, 3 minutes or less, or 2 minutes or less. Combinations of the above-mentioned ranges are also possible (e.g., 1 minute or more to 20 minutes or less). Other ranges are also possible.

[0102] In some embodiments, the porous foam is held (or maintained) at a temperature within one or more of the above ranges throughout the entire annealing time. The annealing time can also include one or more periods (or times) during which the porous foam is held (or maintained) at a temperature within one or more of the above ranges and periods (or times) during which the porous foam is held (or maintained) at a temperature outside one or more of the above ranges. Alternatively, the porous foam can be held (or maintained) at a temperature outside the above ranges throughout the annealing time.

[0103] As described elsewhere in this disclosure, in some embodiments, the hip labrum scaffold and / or porous foam possess one or more advantageous mechanical properties, examples of which are described in more detail below.

[0104] In some embodiments, the compressive modulus of the hip labrum (or hip joint labrum) scaffold and / or porous foam is 100 kPa or greater, 200 kPa or greater, 300 kPa or greater, 400 kPa or greater, 500 kPa or greater, 600 kPa or greater, 700 kPa or greater, 800 kPa or greater, 900 kPa or greater, 1000 kPa or greater, 1100 kPa or greater, 1200 kPa or greater, 1300 kPa or greater, or 1400 kPa or greater. In some embodiments, the compressive modulus of the hip labrum scaffold and / or porous foam is 1500 kPa or less, 1400 kPa or less, 1300 kPa or less, 1200 kPa or less, 1100 kPa or less, 1000 kPa or less, 900 kPa or less, 800 kPa or less, 700 kPa or less, 600 kPa or less, 500 kPa or less, 400 kPa or less, 300 kPa or less, or 200 kPa or less. Combinations of the above-mentioned ranges are also possible (e.g., 100 kPa or more to 1500 kPa or less). Other ranges are also possible. The compressive modulus of the hip labrum scaffold or porous foam may be determined according to ISO 3386 / 1-1986(E).

[0105] In some embodiments, the tensile strength (or tensile strength) of the hip labrum scaffold and / or porous foam is 600 kPa or more, 625 kPa or more, 650 kPa or more, 675 kPa or more, 700 kPa or more, 725 kPa or more, 750 kPa or more, or 775 kPa or more. In some embodiments, the tensile strength of the hip labrum scaffold and / or porous foam is 800 kPa or less, 775 kPa or less, 750 kPa or less, 725 kPa or less, 700 kPa or less, 675 kPa or less, 650 kPa or less, or 625 kPa or less. Combinations of the above-mentioned ranges are also possible (e.g., 600 kPa or more to 800 kPa or less). Other ranges are also possible. The tensile strength of the hip labrum scaffold or porous foam may be determined according to ISO 527-1.

[0106] In some embodiments, the tensile modulus of the hip labrum scaffold and / or porous foam is 500 kPa or more, 525 kPa or more, 550 kPa or more, 575 kPa or more, 600 kPa or more, 625 kPa or more, 650 kPa or more, 675 kPa or more, 700 kPa or more, 725 kPa or more, 750 kPa or more, or 775 kPa or more. In some embodiments, the tensile modulus of the hip labrum scaffold and / or porous foam is 800 kPa or less, 775 kPa or less, 750 kPa or less, 725 kPa or less, 700 kPa or less, 675 kPa or less, 650 kPa or less, 625 kPa or less, 600 kPa or less, 575 kPa or less, 550 kPa or less, or 525 kPa or less. Combinations of the above-mentioned ranges are also possible (e.g., 500 kPa or greater and 800 kPa or less).The tensile modulus of the hip labrum scaffold or porous foam may be determined according to ISO 527-1.

[0107] In some embodiments, the flexibility (or pliability or flexibility) of the hip labrum scaffold and / or porous foam is 100% or more, 125% or more, 150% or more, 175% or more, 200% or more, 225% or more, 250% or more, 275% or more, 300% or more, 325% or more, 350% or more, 375% or more, 400% or more, 410% or more, 420% or more, 430% or more, 440% or more, 450% or more, 460% or more, 470% or more, 480% or more, or 490% or more. In some embodiments, the flexibility of the hip labrum scaffold and / or porous foam is 500% or less, 490% or less, 480% or less, 470% or less, 460% or less, 450% or less, 440% or less, 430% or less, 420% or less, 410% or less, 400% or less, 375% or less, 350% or less, 325% or less, 300% or less, 275% or less, 250% or less, 225% or less, 200% or less, 175% or less, 150% or less, or 125% or less. Combinations of the above-mentioned ranges are also possible (e.g., 100% or more and 500% or more, or 400% or more and 500% or more). Other ranges are also possible. The flexibility of a hip labrum scaffold or porous foam may be determined in accordance with ISO 178:2001. The percentages above refer to the ratio of the elongation at break to the distance of the suture from the edge of the sample being tested (or elongation at break / distance), multiplied by 100 (%). In some embodiments, the flexibility values ​​referred to above refer to samples (samples in which the distance of the suture from the edge of the sample being tested is 3 mm).

[0108] In some embodiments, the suture pull-out strength (or suture pull-out strength or suture pull-out strength) of the hip labrum scaffold and / or porous foam is 2 N / mm or greater, 2.25 N / mm or greater, 2.5 N / mm or greater, 2.75 N / mm or greater, 3 N / mm or greater, 3.25 N / mm or greater, 3.5 N / mm or greater, 3.75 N / mm or greater, 4 N / mm or greater, 4.25 N / mm or greater, 4.5 N / mm or greater, or 4.75 N / mm or greater. In some embodiments, the suture pull-out strength of the hip labrum scaffold and / or porous foam is 5 N / mm or less, 4.75 N / mm or less, 4.5 N / mm or less, 4.25 N / mm or less, 4 N / mm or less, 3.75 N / mm or less, 3.5 N / mm or less, 3.25 N / mm or less, 3 N / mm or less, 2.75 N / mm or less, 2.5 N / mm or less, or 2.25 N / mm or less. Combinations of the above-mentioned ranges are also possible (e.g., 2 N / mm or more to 5 N / mm or less). Other ranges are also possible.

[0109] The suture pull-out strength (or suture thread pull-out strength or suture pull-out strength) of a hip labrum scaffold or porous foam may be determined by the following steps (1) to (5). (1) Cutting the hip labrum scaffold or porous foam to form a sample having a thickness of 12 mm; (2) Using a needle, place two 2-0 MERSILENE (braided polyester) sutures 3 mm from the edge of the sample; (2) Clamping the pointed edge of the sample into one of the clamps of an Instron Tensile Tester (or tensile tester) (4) Clamping (or clamping) both ends of the suture into the other clamp of an Instron Tensile Tester (or tensile tester) (or process or step); (5) moving the clamps apart at a rate of 10 mm / min (or process or step); The ratio of the force applied when the hip labrum scaffold or porous foam fractured to the thickness of the sample (or specimen) (or force / thickness) is the suture pull-out strength (or suture pull-out strength or suture pull-out strength).

[0110] In some embodiments, the hip labrum scaffold can be configured and / or capable of retaining a significant number of pores and / or a significant number of open pores and / or a significant porosity, even when subjected to a significant compressive strain. The porosity retention of the hip labrum scaffold after being subjected to a compressive strain may be determined by the following (1) to (11): (1) Rehydrating a 10 mm diameter, 2-3 mm thick hip labrum scaffold overnight in a water bath; (2) placing the rehydrated hip labrum scaffold into a confining chamber (a chamber having a diameter of 10 mm and a thickness greater than the thickness of the hip labrum scaffold); (3) filling the remainder of the containment chamber with water; (4) inserting a 10 mm diameter indenter into the confinement chamber at a rate of 50 microns (μm) / second until a compressive strain of 60% is applied; (5) removing the indenter (or indenter); (6) Regenerating (or restoring) the hip labrum scaffold for 5 minutes (or a process or step); (6) compressing the labral scaffold with a porous brass filter (10 mm diameter) at a rate of 150 microns (μm) / second until a compressive strain of 60% is applied; (7) applying a constant compressive load to the hip labrum scaffold using a porous brass filter, the porous brass filter having a magnitude equal to the load applied when a 60% compressive strain was first achieved, for a period of 3 hours; (8) Releasing the compressive load (or stress or load) (or process or step), (9) Removing excess water from the hip labrum scaffold (or process or step); (10) using a clamp (or process or step) to compress the hip labrum scaffold to the thickness resulting from step (7); and (11) Using an SEM, photograph (or photograph or image or image) the fixed (or clamped) hip labrum scaffold.

[0111] In some embodiments, the hip labrum scaffold, when subjected to a compressive strain of at least 60%, retains at least 50%, at least 60%, at least 70%, or at least 80% of the open pores it had prior to the application of the compressive strain.

[0112] In some embodiments, the hip labrum scaffolds described herein are configured to be implanted into a patient (e.g., a human patient). Similarly, some embodiments relate to methods of implanting the hip labrum scaffolds described herein into a patient (e.g., a human patient, a non-human mammalian patient (e.g., a dog or a horse)). The hip labrum scaffolds may be configured to be implanted by a variety of suitable techniques (e.g., arthroscopic techniques, open surgical techniques, and mini-open surgical techniques). For example, the hip labrum scaffold may be delivered to its target location through a cannula. Alternatively, it may be inserted directly into its target location through an incision. A method for implanting a labral scaffold may be performed after removing a portion (or part or section) of a torn human labrum (or damaged human labrum) from a patient. Alternatively, a location where the labral scaffold can be inserted may be prepared for such insertion, and then the labral scaffold may be implanted. For example, a bone anchor may be placed on the rim of the patient's acetabulum. After implantation, the labral scaffold may be sutured to the rim of the patient's acetabulum.

[0113] After removal of the torn or damaged labrum and / or after performing any other preparatory process, a labrum scaffold may be implanted into the patient's hip at the location where the portion of the labrum was located before removal. For example, the labrum scaffold may be implanted into the acetabular labrum location shown in FIGS. 3 and 4 . In some embodiments, the labrum scaffold is implanted adjacent to the patient's pelvis and / or adjacent to the patient's acetabulum. And / or the labrum scaffold is configured to be implanted. Once positioned, the labrum scaffold may be secured, for example, using suture anchors and / or sutures. After the labral scaffold has been implanted, it may be sutured to any bone anchors present and / or any portion of the remaining acetabular labrum (e.g., the healthy portion that did not need to be removed).

[0114] After implantation into a patient (e.g., a human patient), the hip labrum scaffold described herein may be configured to degrade (or degenerate). Degradation may be facilitated by the chemical environment in which the hip labrum scaffold is placed (e.g., water, salts, and / or other chemicals present in the patient's location in which the hip labrum scaffold is placed) and / or by one or more biological processes (e.g., cells). In some embodiments, the degradation of the hip labrum scaffold may involve a chemical reaction in which one or more species (e.g., synthetic polymers) present in the hip labrum scaffold break down into two or more smaller, lower molecular weight reaction products. Without wishing to be bound by theory, it is believed that the bonds broken by the degradation process may be those that are more susceptible to degradation if they are exposed to a higher level of the surrounding environment. This is because portions of the synthetic polymer that come into higher levels of contact with biological materials present in the patient may degrade more rapidly than portions of the synthetic polymer that come into lower levels of such contact. Also, the presence of crystals may inhibit contact between the bonds positioned within the crystals and the surrounding environmental materials, so the crystalline portions of the labrum scaffold (e.g., polyurethane hard blocks) may degrade more slowly than the amorphous portions of the labrum scaffold (e.g., polyurethane soft blocks and / or elastomeric blocks).

[0115] Additionally, and without wishing to be bound by any particular theory, it is believed that urethane and ester linkages present in synthetic polymers may be particularly susceptible to degradation (e.g., hydrolytic degradation). For this reason, it is believed that hip labral scaffolds described herein comprising such linkages may be prone to degradation. Such degradation occurs through the breakdown of such linkages, generating (or forming) degradation products (e.g., lower molecular weight degradation products compared to materials that have degraded prior to degradation). It is also believed that ester linkages degrade more rapidly in human patients than urethane linkages. Thus, polyurethanes comprising both types of linkages may degrade first from the ester linkages, followed by the ether linkages. In some embodiments, the degradation products are non-toxic. For example, the degradation products may cause minimal to no immune response, sensitization, irritation, cytotoxicity, and / or genotoxicity when present in a human patient at concentrations that may occur during degradation of the hip labrum scaffold.

[0116] Some hip labrum scaffolds are configured to degrade, and in so doing, may be configured to degrade relatively slowly. For example, in some embodiments, the hip labrum scaffold is configured to degrade in a patient (e.g., a human patient) over a period (or time) of 4 years or more, 4.25 years or more, 4.5 years or more, 4.75 years or more, 5 years or more, 5.25 years or more, 5.5 years or more, or 5.75 years or more. In some embodiments, the hip labrum scaffold is configured to degrade in a patient over a period (or time) of 6 years or less, 5.75 years or less, 5.5 years or less, 5.25 years or less, 5 years or less, 4.75 years or less, 4.5 years or less, or 4.25 years or less. Combinations of the above-mentioned ranges are also possible (e.g., 4 years or more to 6 years or less). Other ranges are also possible.

[0117] Degradation of the hip labrum scaffold may be determined by assessing the molecular weight and chemical composition of the hip labrum scaffold. Complete degradation may be determined, such that complete degradation has occurred, provided that the number average molecular weight of any remaining component of the hip labrum scaffold is 5% or less of its initial molecular weight.

[0118] For convenience, certain terms used in the specification, examples, and appended claims are listed below. Specific functional group and chemical term definitions are explained in more detail below. For purposes of the present invention, chemical elements are identified according to the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th Ed. (inside cover), and specific functional groups are generally defined as described therein. Furthermore, general rules of organic chemistry, as well as specific functional moieties and reactivities, are described in Organic Chemistry, Thomas Sorrell, University Science Books, Sausalito: 1999.

[0119] The term "aliphatic" as used herein includes both saturated and unsaturated, non-aromatic, straight-chain (i.e., unbranched) and branched-chain, acyclic and cyclic (i.e., carbocyclic) hydrocarbon(s), which may be optionally substituted with one or more functional groups. As will be understood by one of ordinary skill in the art, "aliphatic" is intended in this disclosure to include, but is not limited to, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, and cycloalkynyl moieties. Thus, as used in this disclosure, the term "alkyl" includes straight-chain, branched-chain and cyclic alkyl groups. Similar variations (or conversions) apply to other generic terms such as, for example, "alkenyl," "alkynyl," etc. Furthermore, as used in this disclosure, the terms "alkyl," "alkenyl," "alkynyl," and the like encompass both saturated and unsaturated groups. In certain embodiments, as used in this disclosure, "aliphatic" is used to refer to an aliphatic group (cyclic, acyclic, substituted, unsubstituted, branched or unbranched) having 1 to 20 carbon atoms. Substituents for aliphatic groups include, but are not limited to, any of the substituents described herein, which result in the formation of a stable moiety (e.g., aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, acyl, oxo, imino, thioxo, cyano, isocyano, amino, azido, nitro, hydroxyl, thiol, halo, aliphatic amino, heteroaliphatic amino, alkylamino, heteroalkylamino, arylamino, heteroarylamino, alkylaryl, arylalkyl, aliphaticoxy, heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy, heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, acyloxy, etc., each of which may or may not be further substituted).

[0120] The term "alkyl" refers to the group (or radical) of a saturated aliphatic group. Alkyl includes straight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl (aliphatic) groups, alkyl-substituted cycloalkyl groups, and cycloalkyl-substituted alkyl groups. Alkyl groups can be optionally substituted (as described more fully below). Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, 2-ethylhexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like. A "heteroalkyl" group is an alkyl group in which at least one atom is a heteroatom (e.g., oxygen, sulfur, nitrogen, phosphorus, etc.) and the remaining atoms are carbon atoms. Examples of heteroalkyl groups include, but are not limited to, alkoxy, poly(ethylene glycol)-, alkyl-substituted amino, tetrahydrofuranyl, piperidinyl, morpholinyl, and the like.

[0121] The terms "alkenyl" and "alkynyl" refer to unsaturated aliphatic groups analogous (or analogous) to the alkyl groups described above, but which contain at least one double or triple bond, respectively. "Heteroalkenyl" and "heteroalkynyl" refer to alkenyl and alkynyl groups described in this disclosure in which one or more atoms is a heteroatom (or heteroatom) (e.g., oxygen, nitrogen, sulfur, etc.).

[0122] The term "aryl" refers to an aromatic carbocyclic group having a single ring (e.g., phenyl), multiple rings (e.g., biphenyl), or multiple condensed rings, at least one of which is aromatic (e.g., 1,2,3,4-tetrahydronaphthyl, naphthyl, anthryl, or phenanthryl), all of which may be optionally substituted. A "heteroaryl" group is an aryl group in which at least one ring atom in the aromatic ring is a heteroatom (or heteroatom), and the remaining ring atoms are carbon atoms. Examples of heteroaryl groups include furanyl, thienyl, pyridyl, pyrrolyl, N-lower alkyl-pyrrolyl, pyridyl-N-oxide, pyrimidyl, pyrazinyl, imidazolyl, indolyl, and the like, all of which may be optionally substituted.

[0123] The terms "amine" and "amino" refer to both unsubstituted and substituted amines, for example, amines of the general formula: N(R')(R'')(R'') wherein R', R'', and R''' each independently represent a group allowed by valency rules. The term "a" refers to a site that can be represented by the following formula:

[0124] The terms "acyl," "carboxyl," or "carbonyl" are art-recognized and can include, for example, a moiety that can be represented by the general formula:

[0125] [ka]

[0126] wherein W is H, OH, O-alkyl, O-alkenyl, or a salt thereof. Where W is O-alkyl, the above formula represents an "ester". Where W is OH, the above formula represents a "carboxylic acid." In general, where the oxygen atom of the above formula is replaced by a sulfur atom, the above formula represents a "thiolcarbonyl" group. Where W is S-silyl, the above formula represents a "thiolester." Where W is SH, the above formula represents a "thiolcarboxylic acid." On the other hand, when W is alkyl, the above formula represents a "ketone" group. Where W is hydrogen (H), the above formula represents an "aldehyde" group.

[0127] As used herein, the terms "heteroaromatic" or "heteroaryl" refer to a monocyclic or polycyclic heteroaromatic ring (or group (or radical) thereof) that contains carbon atom ring members and one or more heteroatom ring members (e.g., oxygen, sulfur, or nitrogen). Typically, heteroaromatic rings have from 5 to about 14 ring members, at least one of which is a heteroatom selected from oxygen, sulfur, and nitrogen. In another embodiment, the heteroaromatic ring is a 5- or 6-membered ring and may contain from 1 to about 4 heteroatoms (or heteroatoms). In another embodiment, the heteroaromatic ring system may have 7 to 14 ring members and contain 1 to about 7 heteroatoms. Representative heteroaryls include pyridyl, furyl, thienyl, pyrrolyl, oxazolyl, imidazolyl, indolizinyl, thiazolyl, isoxazolyl, pyrazolyl, isothiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, triazolyl, pyridinyl, thiadiazolyl, pyrazinyl, quinolyl, isoquinolyl, indazolyl, benzoxazolyl, benzofuryl, benzothiazolyl, indolizinyl, imidazopyridinyl, isothiazolyl, tetrazolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, benzoxadiazolyl, carbazolyl, indolyl, tetrahydroindolyl, azaindolyl, imidazopyridyl, quinazolinyl, purinyl, pyrrolo[2,3]pyrimidyl, pyrazolo[3,4]pyrimidyl, benzo(b)thienyl, and the like. Such heteroaryl groups may be optionally substituted with one or more substituents.

[0128] The term "substituted" (or "substituted") is intended to include all permissible substituents of organic compounds, where "permissible" is within the context of the chemical rules of valency known to those skilled in the art. In some cases, "substituted" may generally mean that a hydrogen atom is replaced with a substituent group as described in this disclosure. However, "substituted" as used in this disclosure does not encompass the replacement and / or modification of an important functional group (or key functional group) that identifies the molecule (e.g., the "substituted" functional group becomes a different functional group through substitution, etc.). For example, a "substituted phenyl," by this definition, must still contain a phenyl moiety and cannot be modified by substitution. For example, it cannot be modified to become a heteroaryl group (e.g., pyridine). In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic substituents of organic compounds. For example, illustrative substituents include those described herein. For suitable organic compounds, the permissible substituents can be one or more and the same or different. For purposes of this invention, heteroatoms (or heteroatoms), such as nitrogen, may have hydrogen substituents and / or any permissible substituents of organic compounds described herein, provided that the valence of the heteroatom is satisfied. This invention is not intended to be limited in any manner or manner by the permissible substituents of organic compounds.

[0129] Examples of substituents include, but are not limited to, alkyl, aryl, aralkyl, cyclic alkyl, heterocycloalkyl, hydroxy, alkoxy, aryloxy, perhaloalkoxy, aralkoxy, heteroaryl, heteroaryloxy, heteroarylalkyl, heteroaralkoxy, azido, amino, halogen, alkylthio, oxo, acyl, acylalkyl, carboxyester, carboxyl, carboxamido, nitro, acyloxy, aminoalkyl, alkylaminoaryl, alkylaryl, alkylaminoalkyl, alkoxyaryl, arylamino, aralkylamino, alkylsulfonyl, carboxamidoalkylaryl, carboxamidoaryl, hydroxyalkyl, haloalkyl, alkylaminoalkylcarboxy, aminocarboxamidoalkyl, alkoxyalkyl, perhaloalkyl, arylalkyloxyalkyl, and the like.

[0130] When ranges of values ​​are listed, it is intended that each value and subrange (or subrange) be included within the range. For example, "C1-C6 alkyl" is intended to include C1, C2, C3, C4, C5, C6, C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, C2-C6, C2-C5, C2-C4, C2-C3, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5 and C5-C6 alkyl. [Example]

[0131] Example 1 This example describes the preparation of porous foams comprising synthetic polymers and methods for measuring some of the physical properties of the porous foams, which, when fabricated to have the appropriate shape, may be suitable for use in hip labrum scaffolds.

[0132] First, a sample was prepared as described in U.S. Patent No. 7,943,678. Briefly, this process comprises the following steps (1) to (9): (1) A process (or step) for synthesizing poly(ε-caprolactone) (PCL) prepolymer, in which ε-caprolactone is subjected to ring-opening addition polymerization (catalyst-free) using 1,4-butanediol (BDO) as an initiator; (2) end-capping the resulting PCL prepolymer with butane diisocyanate (BDI); (3) chain extending BDI end-capped PCL with BDO, thereby forming a polyurethane; (4) a step of dissolving the produced (or formed) polyurethane in dimethyl sulfoxide; (5) adding a small amount of water to the solution, thereby reducing the solvent quality; (6) adding NaCl particles to the solution, thereby forming a slurry; (7) A process (or step) of pouring (or placing) the slurry into a mold (or form or mold frame); (8) A process (or step) of freezing the mold (or form or form) and the slurry, thereby inducing liquid-liquid phase separation; and (9) A step of washing away NaCl with water and ethanol. The formed porous foam was then subjected to annealing at 108°C for 7 minutes. This annealing treatment improved the strength and toughness of the porous foam, while causing only a minimal decrease in the porosity of the porous foam and causing the porous foam to shrink slightly.

[0133] Figure 14 shows a scanning electron micrograph of the final porous foam. Figure 15 shows an X-ray microtomography image of the final porous foam. Figure 16 shows a three-dimensional (3D) rendering of the final porous foam. Figure 17 shows an electron micrograph of another equivalent porous foam that had not undergone the annealing process. Table 1 shows some of the structural and mechanical characteristics of the final porous foam and another equivalent porous foam that had not undergone the annealing process.

[0134] [Table 1]

[0135] Figures 18-19 show the pore features of the final porous foam and compare them with porous foams produced by different methods. Figure 20 shows the results of tensile tests performed on the final porous polymer foam to evaluate its tear strength, as well as the results of the same tensile tests performed on other equivalent porous foams that had not undergone the annealing process and on a porous foam formed from collagen.

[0136] Example 2 This example describes the measurement of some of the mechanical properties of porous foams comprising synthetic polymers. Such porous foams, when manufactured to have the appropriate shape, may be suitable for use in hip labrum scaffolds.

[0137] The porous foams were produced (or made) using the same procedures as described in Example 1. Various properties, as described below, were evaluated by employing the same methods described above for evaluating open pore retention upon application of compressive strain, followed by further analysis of data collected during the process and / or further testing. However, for some of the measured mechanical properties, compressive strain values ​​other than 60% were applied and are indicated as such.

[0138] Figure 21 shows the aggregate modulus versus various applied compressive strains. Figure 22 shows the permeability versus various applied compressive strains. Figure 23 shows the time constant versus various applied compressive strains. These mechanical properties were determined by conventionally fitting a mechanical model to the displacement of the indenter over time at each applied strain.

[0139] 24-26 show scanning electron micrographs (or images) of the porous foam after various compressive strains are applied. In these images, it can be seen that for all three values ​​of applied compressive strain, a significant number of pores remain open in the porous foam even after the application of compressive strain.

[0140] While several embodiments of the present invention have been described and illustrated in this disclosure, those skilled in the art will readily envision various other means and / or structures for performing the functions described herein and / or obtaining the results and / or one or more benefits described herein. Each such variation and / or modification is deemed to be within the scope of the present invention. Moreover, generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described in this disclosure are meant to be exemplary, and the actual parameters, dimensions, materials, and / or configurations will depend on the specific application(s) and / or use of the techniques of the present invention. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Accordingly, it should be understood that the above-described embodiments are offered by way of example only. It is also understood that, within the scope of the appended claims and their equivalents, the invention may be practiced otherwise than as specifically described and claimed. The present invention is directed to each individual feature, system, article, material, kit, and / or method described in this disclosure. Furthermore, where such features, systems, articles, materials, kits, and / or methods are not mutually inconsistent, any combination of two or more such features, systems, articles, materials, kits, and / or methods is within the scope of the present invention.

[0141] All definitions (as defined and used in this disclosure) should be understood to be controlling over dictionary definitions, definitions set forth in documents incorporated by reference, and / or ordinary meanings of the defined terms.

[0142] The indefinite articles "a" and "an," as used in the specification and claims of this disclosure, unless expressly indicated to the contrary, should be understood to mean "at least one."

[0143] The phrase "and / or" as used in the specification and claims of this disclosure should be understood to mean "either or both" of the elements so connected. That is, it should be understood to mean elements conjunctively present in some cases and non-conjunctively present in other cases. Multiple elements listed with "and / or" should be interpreted in the same manner, i.e., "one or more" of the elements so connected. Other elements, whether related or unrelated to those specifically identified by the "and / or" clause, may optionally also be present. Thus, as a non-limiting example, a reference to "A and / or B," when used in combination with open-ended language such as "comprising," can mean, in one embodiment, only A (optionally including elements other than B); in another embodiment, only B (optionally including elements other than A); in yet another embodiment, both A and B (optionally including other elements), etc.

[0144] As used in the specification and claims of this disclosure, "or" should be understood to have the same meaning as "and / or" as defined above. For example, when separating items in a list, "or" or "and / or" should be interpreted as being inclusive, i.e., including at least one of the elements or elements of the list, but also including one or more elements, and, if necessary, including additional items not in the list. Only in terms clearly indicating the contrary (e.g., "only one of" or "exactly one of"), or when used in the claims, "consisting of" means including exactly one element (or configuration or element) of a number or list of elements (or configurations or elements). Generally, the term "or," as used in this disclosure, shall only be construed as including exclusive alternatives (i.e., "either or the other, but not both") when preceded by exclusive terms (e.g., "either," "one of," "only one of," or "exactly one of"). "Consisting essentially of," when used in the claims, shall have its ordinary meaning as used in the field of patent law.

[0145] As used in this disclosure, in the specification and claims, the phrase "at least one," when referring to one or more elements of a list, should be understood to mean at least one element selected from any one or more elements included in the list, but not necessarily including at least one of each and every element specifically listed in the list, nor excluding any combination of elements in the list. This definition also allows for the possibility that other elements (or configurations or elements) may be present, as appropriate, in addition to the elements (or configurations or elements) specifically identified in the enumerated elements (or configurations or elements) referred to by the phrase "at least one," and such elements (or configurations or elements) may be either related or unrelated to the specifically identified elements (or configurations or elements). Thus, as a non-limiting example, "at least one of A and B" (or, equivalently, "at least one of A or B," or, equivalently, "at least one of A and / or B") may have the following meanings, etc. In one embodiment, it may refer to at least one (including one or more, as appropriate) A (provided that B is absent (and may include elements (or configurations or components) other than B as appropriate). In another embodiment, it may refer to at least one (including one or more, as appropriate) B (provided that A is absent (and may, as appropriate, include elements (or configurations or components) other than A)). In yet another embodiment, it can refer to at least one (including, where appropriate, one or more) A and at least one (including, where appropriate, one or more) B (which may, where appropriate, include other elements (or configurations or elements)), etc.

[0146] It should also be understood that, unless expressly stated to the contrary, in any method claimed in this disclosure, when the method includes one or more steps or operations (or actions or acts), the order of the steps (or steps) or operations (or actions or acts) included in the method is not necessarily limited to the order in which the steps (or steps) or operations (or actions or acts) included in the method are described.

[0147] In the claims, as well as in the foregoing specification, all transitional words (or transitional phrases) (e.g., "comprising," "including," "carrying," "having," "containing," "involving," "holding," "composed of," etc.) are to be understood to be open-ended, i.e., to mean "including, but not limited to." Only the transitional phrases "consisting of" and "consisting essentially of" are closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03.

Claims

1. 1. A hip labrum scaffold comprising a porous foam, the porous foam comprises a synthetic polymer; The porous foam has an average pore size of 100 μm or more and 400 μm or less. Hip labrum scaffold.

2. 1. A hip labrum scaffold comprising a porous foam, the porous foam comprises a synthetic polymer; The porous foam has a suture pull-out strength of 3 N / mm or more. Hip labrum scaffold.

3. 1. A hip labrum scaffold comprising a porous foam, the porous foam comprises a synthetic polymer; the hip labrum scaffold is configured to degrade upon placement in a human patient; The decomposition is completed within a period of not less than four years and not more than six years after implantation into the human patient. Hip labrum scaffold.

4. 1. A method of annealing a porous foam for use in a hip labrum scaffold, the method comprising: heating the porous foam to a temperature at least 1° C. above the melting point of the porous foam; Including, the heating increases the average pore size of the porous foam; The porous foam comprises a synthetic polymer. method.

5. 1. A method of annealing a porous foam for use in a hip labrum scaffold, comprising: heating the porous foam to a temperature at least 1° C. above the melting point of the porous foam; Including, said heating improving one or more mechanical properties of said porous foam while substantially preserving the porosity of said porous foam; the porous foam comprises a synthetic polymer; the one or more mechanical properties are selected from the group consisting of a compressive modulus of the porous foam, a tensile modulus of the porous foam, a tensile strength of the porous foam, and a suture pull-out strength of the porous foam; method.

6. 1. A method of annealing a porous foam for use in a hip labrum scaffold, the method comprising: heating the porous foam to a temperature at least 1°C above the melting point of the porous foam and at most 20°C above the melting point of the porous foam; Including, The porous foam comprises a synthetic polymer. method.

7. The hip labrum scaffold or method of any one of claims 1 to 6, wherein the polymer is polyurethane.

8. 8. The hip labrum scaffold or method of any one of claims 1 to 7, wherein the polyurethane comprises aliphatic repeating units.

9. 9. The hip labrum scaffold or method of any one of claims 1 to 8, wherein the aliphatic repeating units are linear.

10. 10. The hip labrum scaffold or method of any one of claims 1 to 9, wherein the aliphatic repeating units are branched.

11. 11. The hip labrum scaffold or method of any one of claims 1 to 10, wherein the polyurethane comprises cycloaliphatic repeating units.

12. The hip labrum scaffold or method of any one of claims 1 to 11, wherein the polymer comprises polycaprolactone blocks.

13. 13. The hip labrum scaffold or method of any one of claims 1 to 12, wherein the polycaprolactone block has a molecular weight of 1 kDa or more and 2 kDa or less.

14. The hip labrum scaffold or method of any one of claims 1 to 13, wherein the polymer comprises the reaction product of a macrodiol.

15. 15. The hip labrum scaffold or method of any one of claims 1 to 14, wherein the macrodiol comprises a reaction product of ε-caprolactone, lactide, glycolide, δ-valerolactone, 1,4-dioxan-2-one, 1,5-dioxepan-2-one, oxepane-2,7-dione, polycarbonate and / or copolycarbonate.

16. 16. The hip labrum scaffold or method of any one of claims 1 to 15, wherein the copolycarbonate comprises the reaction product of trimethylene carbonate, tetramethylene carbonate, 1,3-dioxepan-2-one, and / or 1,3,8,10-tetraoxacyclotetradecane.

17. 17. The hip labrum scaffold or method of any one of claims 1 to 16, wherein the macrodiol comprises 1,6-hexanediol polycarbonate.

18. Macrodiol is C １ -C １０ 18. The hip labrum scaffold or method of any one of claims 1 to 17, comprising a reaction product of an alkyl diol.

19. Said C １ -C １０ 19. The hip labrum scaffold or method of any one of claims 1 to 18, wherein the alkyl diol is 1,4-butanediol.

20. The hip labrum scaffold or method of any one of claims 1 to 19, wherein the polymer comprises a reaction product of a diisocyanate.

21. The diisocyanate is C ２ -C １４ 21. The scaffold or method of any one of claims 1 to 20, comprising alkylene and / or cycloalkylene groups of the formula:

22. Said C ２ -C １４ The scaffold or method of any one of claims 1 to 21, wherein the alkylene group is linear.

23. Said C ２ -C １４ The hip labrum scaffold or method of any one of claims 1 to 22, wherein the alkylene group is branched.

24. 24. The hip labrum scaffold or method of any one of claims 1 to 23, wherein the diisocyanate is 4,4'-dicyclohexanemethane, 1'-transcyclohexane-diisocyanate, isophorone diisocyanate, 1,6-hexane diisocyanate and / or 1,4-butane diisocyanate.

25. The hip labrum scaffold or method of any one of claims 1 to 24, wherein the polymer comprises the reaction product of a chain extender.

26. 26. The hip labrum scaffold or method of any one of claims 1 to 25, wherein the chain extender has the structure YRY.

27. Each Y is independently OH, NH ２ 27. The hip labrum scaffold or method of any one of claims 1 to 26, wherein the scaffold is NHR' or NHR'.

28. 28. The hip labrum scaffold or method of any one of claims 1 to 27, wherein both Y's are OH.

29. Both Y's are NH ２ 29. The hip labrum scaffold or method of any one of claims 1 to 28, wherein:

30. R is C ２ -C １４ 30. The scaffold or method of any one of claims 1 to 29, wherein the alkylene and / or cycloalkylene groups are:

31. R' is C １ -C １２ 31. The hip labrum scaffold or method of any one of claims 1 to 30, wherein the aliphatic group is

32. 32. The hip labrum scaffold or method of any one of claims 1 to 31, wherein the aliphatic group is linear.

33. 33. The hip labrum scaffold or method of any one of claims 1 to 32, wherein the aliphatic group is branched.

34. 34. The hip labrum scaffold or method of any one of claims 1 to 33, wherein the chain extender is ethylenediamine, propylenediamine, butanediamine and / or hexamethylenediamine.

35. 35. The hip labrum scaffold or method of any one of claims 1 to 34, wherein the chain extender is 1,2-ethylenediamine and / or 1,6-hexamethylenediamine.

36. 36. The hip labrum scaffold or method of any one of claims 1 to 35, wherein the chain extender is a cycloaliphatic diamine.

37. 37. The hip labrum scaffold or method of any one of claims 1 to 36, wherein the cycloaliphatic diamine is 1,4-isophoronediamine and / or 1,4-cyclohexanediamine.

38. 38. The hip labrum scaffold or method of any one of claims 1 to 37, wherein the chain extender is 1,4-butanediamine.

39. 39. The hip labrum scaffold or method of any one of claims 1 to 38, wherein the chain extender is an aliphatic diol.

40. 40. The hip labrum scaffold or method of any one of claims 1-39, wherein the aliphatic diol is ethylene glycol, diethylene glycol, dipropylene glycol, 1,4-butanediol, 1,6-hexanediol, 1,8-octanediol, neopentyl glycol, 1,12-dodecanediol, cyclohexanedimethanol, and / or 1,4-cyclohexanediol.

41. 41. The hip labrum scaffold or method of any one of claims 1 to 40, wherein the polymer has a number average molecular weight of 100 kg / mol or greater and 150 kg / mol or less.

42. 42. The hip labrum scaffold or method of any one of claims 1 to 41, wherein the catalyst comprises 0.001% by weight or less of the polymer.

43. The hip labrum scaffold or method of any one of claims 1 to 42, wherein the polymer is semi-crystalline.

44. The hip labrum scaffold or method of any one of claims 1 to 43, wherein the polymer comprises an elastomeric block.

45. 45. The hip labrum scaffold or method of any one of claims 1 to 44, wherein the porosity of the porous foam is greater than or equal to 70% and less than or equal to 90%.

46. 46. ​​The hip labrum scaffold or method of any one of claims 1 to 45, wherein the porous foam comprises interconnected pores.

47. 47. The hip labrum scaffold or method of any one of claims 1 to 46, wherein prior to implantation of said hip labrum scaffold into a patient, said hip labrum scaffold is free of biological material.

48. 48. A hip labrum scaffold or method according to any preceding claim, wherein the compressive modulus of the porous foam is greater than or equal to 300 kPa.

49. 49. The hip labrum scaffold or method of any one of claims 1 to 48, wherein the tensile strength of the porous foam is equal to or greater than 600 kPa and equal to or less than 800 kPa.

50. 50. The hip labrum scaffold or method of any one of claims 1 to 49, wherein the tensile modulus of the porous foam is equal to or greater than 500 kPa and equal to or less than 800 kPa.

51. 51. A hip labrum scaffold or method according to any one of claims 1 to 50, wherein the flexibility of the porous foam is greater than or equal to 100% and less than or equal to 500%.

52. 52. The hip labrum scaffold or method of any one of claims 1 to 51, wherein the porous foam has a suture pull-out strength of 2 N / mm or more and 5 N / mm or less.

53. 53. The hip labrum scaffold or method of any one of claims 1-52, wherein said hip labrum scaffold, when subjected to a compressive strain of 60% or greater, retains at least 80% of the open pores it had prior to applying said compressive strain.

54. 54. The hip labrum scaffold or method of any one of claims 1 to 53, wherein the hip labrum scaffold has a triangular cross section.

55. 55. The hip labrum scaffold or method of any one of claims 1 to 54, wherein said hip labrum scaffold has a round cross section.

56. 56. The hip labrum scaffold or method of any one of claims 1 to 55, wherein the hip labrum scaffold has a semi-circular cross section.

57. 57. The hip labrum scaffold or method of any one of claims 1 to 56, wherein the hip labrum scaffold has a square cross section.

58. 58. The hip labrum scaffold or method of any one of claims 1 to 57, wherein said hip labrum scaffold has a cross section in the form of a groove.

59. 59. The hip labrum scaffold or method of any one of claims 1-58, wherein the groove is located near a bottom of the hip labrum scaffold.

60. 60. The hip labrum scaffold or method of any one of claims 1 to 59, wherein the groove is triangular.

61. 61. The hip labrum scaffold or method of any one of claims 1 to 60, wherein the groove is square.

62. 62. The hip labrum scaffold or method of any one of claims 1-61, wherein the hip labrum scaffold is tubular.

63. 63. The hip labrum scaffold or method of any one of claims 1-62, wherein the hip labrum scaffold has a donut-shaped cross-section.

64. 64. The hip labrum scaffold or method of any one of claims 1-63, wherein the width of said hip labrum scaffold is equal to or greater than 2.5 mm and equal to or less than 5.5 mm.

65. 65. The hip labrum scaffold or method of any one of claims 1-64, wherein the thickness of the hip labrum scaffold is equal to or greater than 2.5 mm and equal to or less than 8.5 mm.

66. 66. The hip labrum scaffold or method of any one of claims 1-65, wherein the hip labrum scaffold is configured to form a seal between a patient's acetabulum and a head of the patient's femur.

67. 67. The hip labrum scaffold or method of any one of claims 1-66, wherein said hip labrum scaffold is configured to be implanted into a patient via an arthroscopic technique.

68. 68. The hip labrum scaffold or method of any one of claims 1 to 67, wherein said hip labrum scaffold is configured to be implanted into a patient via an open surgical technique.

69. 69. The hip labrum scaffold or method of any one of claims 1-68, wherein said hip labrum scaffold is configured to be implanted into a patient using a mini-open surgical technique.

70. 70. The hip labrum scaffold or method of any one of claims 1-69, wherein said hip labrum scaffold is positioned adjacent the patient's pelvis.

71. 71. The hip labrum scaffold or method of any one of claims 1 to 70, wherein the hip labrum scaffold is positioned adjacent the patient's acetabulum.

72. 72. The method of any one of claims 1-71, further comprising implanting the hip labrum scaffold of any one of claims 1-71 into a patient.

73. 73. The hip labrum scaffold or method of any one of claims 1-72, wherein when said hip labrum scaffold is placed in a patient, said hip labrum scaffold is configured to completely degrade over a period of not less than four years and not more than six years.

74. 74. The hip labrum scaffold or method of any one of claims 1 to 73, wherein the degradation products are non-toxic.

75. The method comprises: preparing a solution of a synthetic polymer in a solvent, said synthetic polymer comprising from 20 wt% / vol to 50 wt% / vol of said solution; adding to the solution a non-solvent for the synthetic polymer; adding a pore former to the solution; pouring the solution into a mold; and Washing the mold with a fluid, wherein the synthetic polymer is immiscible and the solvent, non-solvent, and pore former are miscible.

75. The method of any one of claims 1 to 74, comprising forming the porous foam by

76. 76. The method of any one of claims 1 to 75, wherein the temperature is higher than the melting point of the porous foam by no more than 10 degrees.

77. The method of any one of claims 1 to 76, wherein heating is carried out for at least 1 minute and not more than 20 minutes.

78. 78. The method of any one of claims 1 to 77, wherein the synthetic polymer comprises between 30 and 45 wt% / vol of the solution.

79. 79. The method of any one of claims 1 to 78, wherein the solvent comprises dimethyl sulfoxide, dimethyl formamide, chloroform, 1,4-dioxane, N-methylpyrrolidone, m-cresol and / or dimethylacetamide.

80. 80. The method of any one of claims 1 to 79, wherein the non-solvent comprises water.

81. 81. The method of any one of claims 1 to 80, wherein the non-solvent comprises from 5 vol% to 30 vol% of the combined volume of the solvent and the non-solvent.

82. 82. The method of any one of claims 1 to 81, wherein the non-solvent comprises from 5 vol% to 10 vol% of the combined volume of the solvent and the non-solvent.

83. 83. The method of any one of claims 1 to 82, wherein the pore former is a sugar.

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