Composite scaffold for repair, reconstruction and regeneration of soft tissues

Abstract

To provide a composite scaffold that provides a highly porous and flexible structure substantially maintaining its three-dimensional shape under tension.SOLUTION: The invention provides mechanical reinforcement of the repair or reconstruction, first via scaffold mechanical properties and subsequently through newly regenerated functional tissue as the scaffold is resorbed.SELECTED DRAWING: None

Description

[Technical field]

[0001] FIELD OF THEINVENTION The present disclosure relates to composite scaffolds useful for soft tissue repair and reconstruction, and more specifically, for stabilizing soft tissue injuries or defects while promoting new tissue regeneration. [Background technology]

[0002] 2. Background of the Invention While biological and synthetic scaffolds for use in tissue engineering applications and surgical repair and reconstruction are known, few provide a fully optimized combination of porosity for cellular ingrowth, biological matrix and surface area for cell migration and proliferation, interconnected void volume and dimensions for significant extracellular matrix deposition and tissue remodeling, composite mechanical properties to promote functional tissue maturation while resisting collapse or compression under mechanical loads and distribution of said mechanical loads with local tissues, and a bioresorption timeline to support tissue repair through complete healing while promoting functional tissue regeneration.

[0003] Some scaffolds, such as hernia meshes, have sufficient mechanical properties to complete surgical repairs but lack behavioral properties and are suboptimal for healing and regeneration of soft tissues in the knee, ankle, elbow, and hand, as well as non-musculoskeletal soft tissues. Many of these scaffolds are made of permanent synthetic polymers that can induce acute or chronic deleterious inflammation, pain, or complications. Furthermore, many mesh-like scaffolds are two-dimensional in nature and do not promote functional tissue regeneration because they provide insufficient surface area for cell ingrowth and insufficient void volume for bulk tissue regeneration. Conversely, most biological scaffolds for soft tissue repair and reconstruction are derived from bulk tissue harvested and processed from allogeneic or xenogeneic sources, and often result in slow or incomplete healing due to any combination of bulk structure, tissue source, and processing method. Highly processed biological materials that are remodeled into entirely new structures, such as collagen gels and sponges, can be manufactured with porosity suitable for tissue ingrowth, but lack adequate strength and resistance to collapse for use in ligament and tendon repair.

[0004] Many commercially available scaffolds composed of fibers have adequate mechanical properties but are inadequate for functional tissue regeneration due to structural shortcomings resulting from existing manufacturing processes such as knitting, weaving, braiding, and non-woven methods such as electrospinning, air-spun, melt-blowing, etc., where the fibers either have insufficient space between the filaments and / or fiber bundles (insufficient porosity or void volume or density, e.g., typical electrospun fabrics), or have too little surface area, void volume and dimensions for significant tissue regeneration (e.g., typical planar warp knit fabrics or braids, or fiber bundles), or, even if adequate void volume is created, it is not contiguous to a cellular and biologically relevant extent, or the structure collapses when tension is applied.

[0005] Therefore, there is a need for scaffolds and methods for repairing or regenerating ligament tissue. There is also a need for scaffolds that are composite, ie, that mimic the mechanical properties of natural tendons and ligaments. There is a further need for a scaffold that provides adequate porosity and interconnected void volume for cell infiltration and tissue ingrowth while substantially maintaining its shape under load or tension. There is yet a further need for scaffolds that are bioresorbable over a period of time, supporting healing over weeks or months while promoting regeneration of functional tissue capable of withstanding mechanical loads after resorption of the scaffold. There is also a need for a scaffold that minimizes the composite polymer density of the scaffold and maximizes the surface area to volume ratio, thereby limiting foreign body reaction and improving tissue regeneration.

[0006] There is also a need for a scaffold that is adjustable in length, width, and height to accommodate a variety of procedures. It is also necessary for a bioabsorbable scaffold to regenerate tissue of sufficient strength and thickness after the scaffold material has been completely absorbed. There is also a need for a scaffold that provides a second support matrix spaced from the scaffold that can promote cell proliferation to promote tendon or ligament tissue ingrowth. To improve tissue regeneration and / or surgical processing and implantation, the scaffold will also need to have a design domain of variable dimensions, density, porosity, material composition, fiber type, and surface properties. Summary of the Invention

[0007] SUMMARY OF THE PRESENT APPLICATION Disclosed is a composite scaffold for ligament or tendon repair that provides mechanical reinforcement to the repairing and healing tendon or ligament. In an embodiment, the composite scaffold includes a support structure that defines a void volume. A porous material or hydrogel is disposed within the void volume of the support structure. The support structure reinforces and supports the porous material / hydrogel, enhancing the tensile strength of the scaffold and resisting compression when the scaffold is stretched or subjected to elongation forces. The porous material / hydrogel has a porosity and void volume that allows for appropriate extracellular matrix deposition and new functional tissue regeneration. In an embodiment, the void volume is continuous or essentially continuous along the long axis of the scaffold, which allows cells to migrate fully within the device and form new tissue in an axial orientation of the scaffold while being protected from significant collapse, compression or excessive expansion when the scaffold is subjected to mechanical load or tension. Optionally, all or part of the scaffold may be hydrated with biological fluids such as blood, bone marrow, platelet rich plasma, autologous or allogeneic cells to modulate or manage the immune response and further promote and accelerate healing and tissue regeneration.

[0008] The disclosed composite scaffolds have a large surface area for cell proliferation and migration as well as interconnected voids large enough to allow tissue ingrowth, extracellular matrix deposition, and biomechanical remodeling into functional tissue. Additionally, the scaffolds have the ability to maintain a highly porous structure under tension, e.g., resist collapse during and after implantation during surgery, and maintain the capacity for cell infiltration and new tissue ingrowth throughout the scaffold under physiological loads. These loads are mechanically distributed between the device and local tissues due to the composite mechanical properties of the device, i.e., the device prevents stress shielding of proximal, repair, or native tissues, and the development of neo-tissues within the scaffold itself. Furthermore, these composite mechanical properties facilitate mechanobiological communication of cells within the scaffold to identify and form load-bearing, directional extracellular matrix and connective tissue. The disclosed composite scaffolds can be manufactured using a variety of different weaves and composite manufacturing methods and are not limited to a single manufacturing technique.

[0009] The disclosed composite scaffold provides a highly porous, flexible structure that substantially maintains its three-dimensional shape under tension, providing mechanical reinforcement for repair or reconstruction primarily through the mechanical properties of the scaffold and subsequently through newly regenerated functional tissue as the scaffold is resorbed.

[0010] The disclosed scaffolds may have distinct regions with different mechanical properties to promote fixation or differential tissue regeneration. In embodiments, the composite scaffolds may be impregnated with cells, biological aspirates, or bioactive agents prior to implantation to create a biological "band-aid." In other embodiments, the bioinductive scaffolds are seeded with autologous, allogeneic, or xenogeneic cells for a temporary pre-culture period, allowing the cells to build up a collagen-rich extracellular matrix within the scaffold. The scaffolds are then treated and / or decellularized to provide a fiber-reinforced tissue scaffold that can be subsequently implanted or implanted "as is." The disclosed scaffolds may be compatible with a variety of currently available fixation methods, such as sutures, suture anchors, tacks, staples, etc.

[0011] The disclosed composite scaffold provides a mechanism for spacing tissue fibers apart within the scaffold, providing a place for higher quality tissue ingrowth that is not destroyed by the polymer or the corresponding inflammation. The microporous matrix helps maintain such space and acts as a stabilizer to allow a larger surface for cells to grow, allowing tissue to mature while the primary fibers of the scaffold still retain strength. If the microporous matrix is ​​absorbed at a faster rate than the support structure, there may be a complete loss of mass of the microporous matrix so that tissue can regenerate and remodel within the newly created volume in vivo, while the primary support structure retains strength, allowing cells to initially invade and encapsulate the structure, but also create functional tissue over time. Furthermore, if natural materials are used to create the second matrix, such as collagen, scaffold burning may be reduced, further promoting cell ingrowth into the scaffold despite not being in contact with any of the synthetic fibers that comprise the support structure.

[0012] According to one aspect of the disclosure, a composite scaffold includes a first matrix and an optional second matrix that may be integrally formed with each other to maximize the surface area to volume ratio of the scaffold while still maintaining mechanical and structural integrity. According to an embodiment, the first matrix may implement a three-dimensional woven structure including spaced apart first and second support layers that define an interior space or void between them. A number of spacer elements extend between the first and second support layers to keep the support layers apart. The first and second support layers may have different shapes, fibers, or material compositions. The first and second support layers and the spacer elements may be implemented as a three-dimensional weave including multi-layer knitted or woven surfaces of multifilament or monofilament fibers, or any combination thereof, formed with any combination of synthetic bioabsorbable polymers, natural polymers, and / or additives. The second matrix is ​​disposed within the voids adjacent between the first and second support layers of the first support matrix. The second matrix may implement low density, high surface area materials including sponges, foams, felts, processed fibers or yarns, collagen or tissue derived materials, or any combination thereof. The first and second matrices of the composite scaffold may have the same or different structure, composition, and bioabsorption properties to promote optimal regeneration of functional tissue.

[0013] In one embodiment, a composite scaffold can have a minimum thickness of about 1 mm or greater. The thickness of the scaffold can be uniform along its length or can vary in a repeating or non-repeating manner depending on the particular application for which the scaffold is to be utilized. In other embodiments, the disclosed composite scaffolds can have a length dimension between about 2 mm and 1000 mm depending on the particular application for which the scaffold is to be utilized. The disclosed scaffolds can be manufactured in various incremental lengths or can be manufactured in lengths that can be cut or customized by the physician as needed or for a particular procedure. According to one aspect of the present disclosure, a composite scaffold includes a microporous matrix having a number of interconnected pores that open to an exterior surface of the microporous matrix and collectively define a void space, and a structure supporting the microporous matrix, the composite scaffold having a surface area of ​​about 0.6 m. 2 / gram to 1.2m 2 / gram.

[0014] According to another aspect of the present disclosure, a composite scaffold includes a microporous matrix having a number of interconnected pores that open to an exterior surface of the microporous matrix and collectively define a void having a measurable volume, and a structure supporting the microporous matrix, the void having a volume of about 3.5 cm. 3 / gram to 7cm 3 / gram. According to another aspect of the present disclosure, a composite scaffold includes a microporous matrix having a number of interconnected pores that open to an exterior surface of the microporous matrix and collectively define a void having a measurable volume, the void volume being between about 80% and 90% of the measurable volume of the biomimetic scaffold.

[0015] According to another aspect of the present disclosure, a composite scaffold includes a microporous matrix having a multiplicity of interconnected pores that open to an exterior surface of the microporous matrix and collectively define a void having a measurable volume, the scaffold having a permeability of between about 1400 and 2600 millidarcy. According to another aspect of the present disclosure, a composite scaffold includes a microporous matrix having a multiplicity of interconnected pores that open to an exterior surface of the microporous matrix and collectively define a void having a measurable volume, the multiplicity of interconnected pores having a tortuosity on the order of 5 μm / μm to 45 μm / μm, where the tortuosity defines a ratio of an actual flow path length to a linear distance between a first end and a second end of the microporous matrix.

[0016] According to another aspect of the present disclosure, a composite scaffold includes a microporous matrix having a multiplicity of interconnected pores that open to an exterior surface of the microporous matrix and collectively define a void having a measurable volume, and a structure supporting the microporous matrix, the void surface area relative to the support structure volume being about 7,000 cm. 2 / cm 3 From 14,000cm 2 / cm 3 It is between. According to another aspect of the present disclosure, a composite scaffold includes a support structure defining an interior space and a microporous matrix disposed within the interior space of the support structure, the microporous matrix including a plurality of interconnected pores having a median pore size between about 12 μm and 50 μm.

[0017] According to another aspect of the present disclosure, a composite scaffold includes a support structure defining an interior space and a microporous matrix disposed within the interior space of the support structure, the microporous matrix having a multiplicity of interconnected pores that collectively define voids, at least about 60% of the voids including pores having diameter dimensions of 10 μm or greater. According to another aspect of the present disclosure, a composite scaffold includes a microporous matrix having a multiplicity of interconnected pores that collectively define voids opening to an outer surface of the microporous matrix, and a structure supporting the microporous matrix, the biomimetic scaffold having a measurable dry weight value representative of a weight of the biomimetic scaffold in a substantially dry state and a measurable dry volume value representative of a volume of the biomimetic scaffold in a substantially dry state, wherein the weight value of the biomimetic scaffold increases by between about 200% and 600% due to fluid absorption, causing the dry volume value of the biomimetic scaffold to change by between about 0% and 10%.

[0018] According to another aspect of the disclosure, a composite scaffold includes a microporous matrix having a multiplicity of interconnected pores that collectively define voids opening to an exterior surface of the microporous matrix, and a structure supporting the microporous matrix, wherein the composite scaffold has a measurable dry weight value representative of a weight of the composite scaffold in a substantially dry state and a measurable dry length value representative of a dimensional parameter of the composite scaffold in a substantially dry state, wherein the weight value of the composite scaffold increases by between about 200% and 600% due to fluid absorption such that the dry length value of the composite scaffold changes by less than between about 0% and 3%. According to another aspect of the disclosure, a composite scaffold includes a microporous matrix having a multiplicity of interconnected pores that collectively define voids opening to an exterior surface of the microporous matrix, and a structure supporting the microporous matrix, the composite scaffold having a measurable dry weight value representative of a weight of the composite scaffold in a substantially dry state and a measurable cross-sectional profile value representative of dimensional parameters of the composite scaffold in a substantially dry state, wherein the weight value of the composite scaffold increases by between about 200% and 600% due to fluid absorption, causing the cross-sectional profile value of the composite scaffold to change by between about 0% and 10%.

[0019] According to another aspect of the disclosure, a composite scaffold includes a microporous matrix having a multiplicity of interconnected pores that collectively define voids that open to an exterior surface of the microporous matrix, and a structure supporting the microporous matrix, wherein a minimum dimension of the composite scaffold is a thickness dimension of about 1 mm or greater, and wherein the composite scaffold has a swelling profile in which a measured wet thickness of the composite scaffold changes by no more than 10% as compared to a measured dry thickness of the composite scaffold. According to another aspect of the disclosure, a composite scaffold includes a microporous matrix having a multiplicity of interconnected pores that collectively define voids opening to an exterior surface of the microporous matrix, and a structure supporting the microporous matrix, the composite scaffold having a measurable dry weight value representative of the weight of the composite scaffold in a substantially dry state, wherein the microporous matrix is ​​less than about 6% of the dry weight value of the composite scaffold.

[0020] According to another aspect of the present disclosure, a scaffold includes: a three-dimensional support structure having a length dimension extending between first and second ends of the support structure, where the support structure includes first and second outer layers spaced apart with a space therebetween defining a thickness dimension perpendicular to the length dimension, and a plurality of spacer elements connecting the first and second outer layers to maintain separation therebetween, where the thickness dimension of the support structure changes less than about 35% upon elongation of about 13% in the length dimension. According to another aspect of the present disclosure, a scaffold includes: a three-dimensional support structure having a length dimension extending between first and second ends of the support structure and defining a cross-sectional area perpendicular to the length dimension, where the support structure includes first and second outer layers spaced apart to define an interior space volume therebetween, and a plurality of spacer elements extending through the interior space volume between the first and second layers and attached therebetween to maintain separation of the first and second layers, where the cross-sectional area changes less than about 5% upon elongation of about 13% in the length dimension.

[0021] According to another aspect of the present disclosure, a scaffold includes: a three-dimensional support structure having a length dimension extending between first and second ends of the support structure and defining a width dimension perpendicular to the length dimension, where the support structure includes first and second outer layers spaced apart with a space therebetween defining a thickness dimension perpendicular to the length and width dimensions, and a plurality of spacer elements connecting the first and second outer layers to maintain separation therebetween, where the width dimension of the support structure changes less than about 5% upon elongation of about 13% in the length dimension.

[0022] According to another aspect of the present disclosure, a scaffold structure includes: first and second outer layers having a length dimension defined by their respective first and second ends and defining an interior space therebetween, where each of the first and second outer layers includes a plurality of interconnected wales extending substantially parallel to their respective length dimensions; a plurality of spacer elements extending through the interior space substantially perpendicular to their respective length dimensions and attached to each of the first and second outer layers proximate one of the plurality of wales, where the plurality of spacer elements at least partially divide the interior space into a plurality of channels extending along the respective length dimensions of the first and second outer layers.

[0023] According to another aspect of the present disclosure, a composite scaffold having a measurable volume includes a microporous matrix having a multiplicity of interconnected pores that open to an exterior surface of the microporous matrix and collectively define a void space, the composite scaffold having a density on the order of 0.05 g / cc to 0.75 g / cc, where density is defined as the mass per unit volume of the composite scaffold. According to another aspect of the disclosure, a composite scaffold having a measurable volume includes a microporous matrix having a multiplicity of interconnected pores that open to an exterior surface of the microporous matrix and collectively define voids, and a structure supporting the microporous matrix, the composite scaffold having a total surface area to volume ratio on the order of 160,000:1 to 190,000:1, the ratio defining the surface area of ​​the scaffold to the volume of the composite scaffold excluding voids.

[0024] According to another aspect of the present disclosure, a scaffold includes a three-dimensional support structure extending along an axis between a first end and a second end of the support structure, the support structure including first and second layers spaced apart to define an interior space volume therebetween, and a plurality of spacer elements extending through the interior space volume between the first and second layers and attached therebetween to maintain separation of the first and second layers, the spacer elements defining a cross section perpendicular to the axis, the scaffold further including a microporous matrix having a multiplicity of interconnected pores that collectively define a void within the interior space between the first and second ends of the support structure, at least about 60% of the voids include pores having a radial dimension of at least 10 μm or greater, and the void volume is about 3.0 cm. 3 / gram to 9.0cm 3 / gram.

[0025] According to another aspect of the disclosure, a composite scaffold includes a microporous matrix having a number of interconnected pores that open to an outer surface of the microporous matrix and collectively define a void space, and a structure supporting the microporous matrix, the composite scaffold having a substantially rectangular cross-section defined by outer portions, the plurality of interconnected pores opening to one of the outer portions and having a maximum dimension oriented relative to the one outer portion. In one embodiment, the plurality of interconnected pores have a maximum dimension oriented on the order of 45° to 135° relative to the one outer portion. According to another aspect of the present disclosure, a scaffold includes a three-dimensional support structure having a length dimension defined by first and second ends thereof and a thickness dimension perpendicular to the length dimension defined by first and second outer layers separated by a space, and a plurality of spacer elements extending through the space and connecting the first and second outer layers, the surface area to measurable volume of the space being about 500 cm. 2 / cm 3 From 7,000cm 2 / cm 3 That's about it.

[0026] According to another aspect of the present disclosure, a composite scaffold occupying a measurable volume includes a microporous matrix having a number of interconnected pores that collectively define a void having a surface area, and a structure supporting the microporous matrix, the surface area relative to the measurable volume of the void being about 5,000 cm. 2 / cm 3 From 16,000cm 2 / cm 3 It is between. According to another aspect of the present disclosure, a composite scaffold includes a microporous matrix having a multiplicity of interconnected pores that open to an exterior surface of the microporous matrix and collectively define a void space, and a structure supporting the microporous matrix, wherein the surface area of ​​the composite scaffold is about 0.3 m 2 / gram to 15m 2 / gram.

[0027] According to another aspect of the present disclosure, a method for repairing a ligament or tendon injury using a composite scaffold includes: A) providing a composite scaffold; Here, the composite scaffold is i) first and second layers spaced apart to define an interior space therebetween, and a plurality of spacer elements attached to the first and second layers and extending through the interior space; and ii) comprises a microporous matrix having a multitude of interconnected pores disposed within an interior space; and B) pretensioning the composite scaffold along its length dimension; C) Attaching the composite scaffold to an allograft or autograft tendon, or to a damaged or torn ligament or tendon.

[0028] According to another aspect of the present disclosure, a method for repairing a ligament or tendon injury using a composite scaffold includes: A) providing a composite scaffold; Here, the composite scaffold is i) first and second layers spaced apart to define an interior space therebetween, and a plurality of spacer elements attached to the first and second layers and extending through the interior space; and ii) comprises a microporous matrix having a multitude of interconnected pores disposed within an interior space; and B) pretensioning the composite scaffold along its length dimension; C) Attaching the composite scaffold to an allograft or autograft tendon, or to a damaged or torn ligament or tendon.

[0029] According to another aspect of the present disclosure, a method of fabricating a composite scaffold includes: A) constructing a three-dimensional support structure extending along a length dimension between a first end and a second end of the support structure and defining an interior surface within the support structure; B) forming a microporous matrix within the interior surface, wherein the microporous matrix has a multiplicity of interconnected pores in fluid communication with the exterior surface of the support structure; wherein the plurality of interconnected pores are oriented relative to a dimensional characteristic of the support structure. In embodiments, the plurality of interconnected pores are oriented radially inward from an exterior surface of the support structure toward the interior space. In embodiments, the plurality of interconnected pores are oriented relative to a length dimension of the support structure.

[0030] According to another aspect of the present disclosure, a composite scaffold includes a support structure having an exterior profile defining an interior space and extending along a length dimension between first and second ends thereof, and a microporous matrix disposed within the interior space having a plurality of interconnected pores that open to an exterior of the support structure, the plurality of interconnected pores being oriented relative to a dimensional characteristic of the support structure. According to another aspect of the present disclosure, a composite scaffold includes a microporous matrix having a multiplicity of interconnected pores that collectively define voids opening to an exterior surface of the microporous matrix, and a structure supporting the microporous matrix, wherein the composite scaffold has a measurable dry weight value representative of the weight of the composite scaffold in a substantially dry state, and the microporous matrix is ​​less than about 6% of the dry weight value of the composite scaffold.

[0031] In embodiments, the second support matrix, e.g., a sponge, degrades between about 2-12 times faster than the first support matrix based on either mass loss or molecular weight loss. The composite scaffold may have a degradation profile with greater than 50% strength retention for at least about two weeks after implantation and 100% mass loss for about six to twelve months or more after implantation. In an embodiment, the primary and bulk structure of the disclosed scaffold is provided with a higher density or mass of the support matrix compared to the matrix in which it is disposed, which is more porous. More specifically, the first and second support matrices have different densities or mass factors relative to each other. In one embodiment, the first support matrix, e.g., a woven fabric, has a measurable mass or density that is 1 or more times the mass or density of the second support matrix, e.g., a sponge.

[0032] In disclosed embodiments, the pore structure of the microporous matrix is ​​designed to promote cell attachment, proliferation, and ingrowth throughout the dimensions of the scaffold. In embodiments, the surface of the device, the second matrix, or the pore structure can be designed to promote cell migration in a particular direction or structured to promote the formation of aligned tissues such as connective tissue. In other embodiments, the surfaces of the device can differ from each other in physical or chemical properties to reflect use in a particular anatomical location, i.e., one promotes attachment to bone while the other promotes attachment to tendons, or one promotes abdominal wall regeneration while the other prevents adhesion of viscera.

[0033] In embodiments, the composite scaffolds disclosed herein provide a measurably higher surface area to volume ratio compared to existing commercially available devices, facilitating more rapid and greater cell infiltration and tissue ingrowth within the composite scaffold. More specifically, based primarily on the first support matrix, e.g., a woven fabric, the ratio of fiber surface area to device volume, calculated using the denier, polymer density and dimensions of the scaffold, is 10 times or greater.

[0034] In embodiments, the scaffold may have ends that are narrowed, altered to suture-like dimensions, or modified (e.g., sewn or knotted) to attach to traditional sutures used in the procedures described herein. In other embodiments, the first support matrix, e.g., a fabric, may have ends or edges that are heat set, sewn, or impregnated with other materials to promote better manipulation, better integration with existing tissue, and further reduce dimensional distortion of the scaffold under pressure, tension, or shear forces. In other embodiments, monofilament or multifilament sutures of any material may pass lengthwise through the scaffold and exit both ends to be attached or secured to the scaffold.

[0035] In other embodiments, selected sections of the scaffold may be repeated randomly or at a fixed frequency to increase or decrease the density of the scaffold, for example by varying the weave pattern of the first support matrix to increase or decrease the density of the weave. In yet other embodiments, such repeated areas may be selected to alter the surface finish of the scaffold by altering the smoothness or roughness of the outer surface of the scaffold to enhance acceptance of the scaffold when implanted. In one embodiment, the composite scaffold comprises only a single three-dimensional support matrix, which may be the same or different from either the first or second support matrices described herein, and may have any of the properties of the composite scaffolds described herein.

[0036] Also disclosed are methods of treating ligament or tendon injuries where the scaffold is attached to an allograft or autograft tendon and used to replace a damaged ligament or tendon, or where the scaffold is used to augment a damaged or torn ligament or tendon. Methods of use may include preparation of the scaffold with solutions to enhance its performance, pretensioning the scaffold and / or fixation of the femoral epiphysis, and independent tensioning and fixation of the tendon and graft in the tibial tunnel. In use, the composite scaffolds may be utilized in a wide variety of medical procedures, including augmentation of suture repair, repair or reconstruction alone, or reconstruction for fixation purposes using tissue grafts, etc. Augmentation of repair or reconstruction using the composite scaffolds may be applied to the knee, ankle, shoulder, hip, elbow, foot, and hand, as well as non-musculoskeletal soft tissues.

[0037] According to another aspect of the present disclosure, the implant preparation table provides a surface and fixation mechanism that allows for independent tensioning of tissue, e.g., tendons or ligaments, and the composite scaffold prior to or during the implantation procedure. According to another aspect of the present disclosure, a fixation device allows tissue, such as a tendon or ligament, and a composite scaffold to be attached to one another without the need for whip stitching. Such a device may include a clip with legs that pass through the graft and the tendon. [Brief description of the drawings]

[0038] Description of the drawings The various features and advantages of the present invention may be more readily understood by reference to the following detailed description taken in conjunction with the accompanying drawings, in which like reference numerals indicate like structural elements and in which: [Figure 1A] FIG. 1A is a conceptual diagram of a composite scaffold according to the present disclosure. [Figure 1B] FIG. 1B is a photograph of a composite scaffold according to the present disclosure. [Figure 1C]FIG. 1C is a photograph of a composite scaffold according to the present disclosure.

[0039] [Figure 2A] FIG. 2A is a conceptual diagram of a weave pattern that may be used for the outer layer of a composite scaffold according to the present disclosure. [Figure 2B] FIG. 2B is a conceptual diagram of an alternative knitting pattern that can be used for the outer layer of a composite scaffold according to the present disclosure. [Figure 2C] FIG. 2C is a conceptual diagram of a yarn element pattern including the outer layer of FIGS. 2A-B in accordance with the present disclosure. [Figure 2D] FIG. 2D is a perspective conceptual illustration of a fiber pattern for a pair of composite scaffolds useful for ACL and rotor cuff procedures in accordance with the present disclosure.

[0040] [Figure 3A] FIG. 3A is a photograph of a top view of a composite scaffold having at least one outer layer made according to the pattern of FIG. 2A in accordance with the present disclosure. [Figure 3B] FIG. 3B is a photograph of a side view of the composite scaffold of FIG. 3A. [Figure 4A] FIG. 4A is a top view SEM photograph of a composite scaffold having at least one outer layer made according to the pattern of FIG. 2A in accordance with the present disclosure. [Figure 4B] FIG. 4B is a SEM photograph of a side view of the composite scaffold of FIG. 4A. [Figure 4C] FIG. 4C is an SEM photograph of a perspective cross-sectional view of the composite scaffold of FIG. 4A taken along axis 4A-4A of FIG. 4A.

[0041] [Figure 5A] FIG. 5A is a perspective view of a mold useful for making a composite scaffold according to the present disclosure. [Figure 5B-C] 5B-C are plan and side views, respectively, of another mold useful for making a composite scaffold according to the present disclosure. [Figure 5D]FIG. 5D graphically illustrates the relationships between temperature, time, and pressure during a freeze-drying process in accordance with the present disclosure.

[0042] [Figure 6A] 6A-C are SEM photographs of sagittal cross-sectional views of the microporous matrix of the composite scaffold of FIG. 1C taken along line AA in accordance with the present disclosure. [Figure 6B] 6A-C are SEM photographs of sagittal cross-sectional views of the microporous matrix of the composite scaffold of FIG. 1C taken along line AA in accordance with the present disclosure. [Figure 6C] 6A-C are SEM photographs of sagittal cross-sectional views of the microporous matrix of the composite scaffold of FIG. 1C taken along line AA in accordance with the present disclosure. [Figure 6D] FIG. 6D is an SEM photograph of a coronal cross-sectional view of the microporous matrix of the composite scaffold of FIG. 1C taken along line BB in accordance with the present disclosure. [Figure 6E] FIG. 6E is an SEM photograph of a cross-sectional view of the microporous matrix of the composite scaffold of FIG. 1C taken along line BB in accordance with the present disclosure. [Figure 6F] FIG. 6F is an SEM photograph of a sagittal cross-sectional view of the microporous matrix of the composite scaffold of FIG. 1C taken along line AA in accordance with the present disclosure. [Figure 6G] FIG. 6G is an SEM photograph of a coronal cross-sectional view of the microporous matrix of the composite scaffold of FIG. 1C taken along line BB in accordance with the present disclosure. [Figure 6H] FIG. 6H is an SEM photograph of a cross-sectional view of the microporous matrix of the composite scaffold of FIG. 1C taken along line BB in accordance with the present disclosure. [Figure 6I] FIG. 6I is an SEM photograph of a sagittal cross-sectional view of the microporous matrix of the composite scaffold of FIG. 1C taken along line AA in accordance with the present disclosure.

[0043] [Figure 7A]FIG. 7A is an SEM photograph of an exemplary microporous matrix attached to a fibrous support structure of a composite matrix according to the present disclosure. [Figure 7B] FIG. 7B is an SEM photograph of an exemplary microporous matrix attached to a fibrous support structure of a composite matrix according to the present disclosure. [Figure 7C] FIG. 7C is an SEM photograph of the exterior surface of an exemplary microporous matrix of a composite scaffold according to the present disclosure.

[0044] [Figure 8] FIG. 8 graphically illustrates test data defining the relationship of cumulative total pore surface area to pore size in accordance with the present disclosure. [Figure 9] FIG. 9 graphically illustrates the cumulative total pore volume versus pore size for several composite scaffold samples, as well as a woven-only support structure, according to the present disclosure. [Figure 10] FIG. 10 graphically illustrates the relationship of composite scaffolds with respect to mercury pressure for several composite scaffold samples, as well as a woven-only support structure, in accordance with the present disclosure.

[0045] [Figure 11] FIG. 11 graphically illustrates the relationship of pore size distribution to log differential volume in accordance with the present disclosure. [Figure 12] FIG. 12 graphically illustrates the load versus extension relationship for both a tendon alone and a tendon augmented with a composite scaffold according to the present disclosure. [Figure 13A] FIG. 13A is a cross-sectional microscopic view of the composite scaffold of FIG. 1C showing the porous matrix associated with the support matrix in accordance with the present disclosure. [Figure 13B] FIG. 13B is a cross-sectional microscopic view of the composite scaffold of FIG. 1C hydrated with blood, showing how red blood cells completely infiltrate the collagen sponge porous matrix in accordance with the present disclosure.

[0046] [Figure 14]FIG. 14 is a photograph of a composite scaffold for MPFL repair or reconstruction in accordance with the present disclosure. [Figure 15] FIG. 15 shows conceptual progression images of a circular woven structure at various stages of manufacture according to the present disclosure. [Figure 16] FIG. 16 conceptually illustrates how the disclosed composites can be utilized for enhanced ACL repair, stabilization, or reconstruction in accordance with the present disclosure. [Figure 17] FIG. 17 graphically illustrates the relationship of pore size distribution to pore percentage as determined according to the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0047] Detailed Description of the Invention Embodiments of the system and method will now be described in detail with reference to the drawings, in which like reference numerals refer to the same or corresponding elements in each of the several drawings. Throughout this description, the phrase "in an embodiment" and variations of this phrase should generally be understood to mean that the particular feature, structure, system, or method described includes at least one iteration of the disclosed technology. Such phrases should not be read or interpreted to mean that the particular feature, structure, system, or method described is either the best or only way in which the embodiment can be practiced. Rather, such phrases should be read to mean one example of how the described technology can be implemented, but not necessarily the only way to do so. Furthermore, directional words such as "top", "bottom", "side", "lower" and "upper", as well as references to particular axes in three-dimensional space, are used merely to help describe the location of elements relative to one another. Directional words are not used to describe absolute directions, i.e., that the "top" part must always be on top, etc.

[0048] 1A-6D, the composite scaffold 10 includes a first three-dimensional support matrix and a second matrix integrally formed with each other to form the composite scaffold 10 that maximizes the surface area to volume ratio and surface area to weight ratio of the scaffold. With reference to FIG. 1A, in an embodiment, the first matrix can be implemented with a support structure 5 including a first outer layer 12 and a second outer layer 14 spaced apart to define an internal void 16 therebetween. A plurality of spacer elements 18 extend between the first outer layer 12 and the second outer layer 14 to maintain separation of the layers. In an embodiment, each of the layers 12, 14, and the spacer elements 18 can be implemented as a three-dimensional woven structure, each having a different shape, fiber, or material composition. For example, any of the outer layers 12, 14, and the spacer elements 18 can be implemented with a woven fabric of multifilament and / or monofilament fibers. Support layers 12 and 14 may be implemented as a substantially planar three-dimensional fabric including a multi-layered knitted surface, and spacer elements 18 may be implemented with interconnecting yarns in a "Z" direction perpendicular to the plane of layers 12 and 14 to provide support to prevent collapse.

[0049] The support structure 5 is intended to provide mechanical support for the growing new tissue and resistance to compression so that the areas intended for new tissue formation are maintained during patient movement and activity. Thus, the support structure 5 provides tensile strength in its long axis and stiffness to resist compression in the "Z direction." In an embodiment, the support structure 5 may be formed from either 30-150 denier multifilament fibers, 30-150 denier monofilament fibers, or 30-150 denier bicomponent yarns, or any combination thereof, such as a combination of multifilament and monofilament fibers, and may optionally be coated with an anti-adhesive material. Unfinished edges of the scaffold 10 may be sealed or secured using methods including, but not limited to, heat setting or sewing. In one embodiment, the support structure 5 is fabricated from 75 denier / 30 filament poly-L-lactic acid (PLLA) with a polymer density of 1.25 g / cc. As described below, the yarn may be braided over a twisted fiber yarn to provide a stiffer yarn for use as a lay-in.

[0050] In an embodiment, one or both of the outer layers 12 and 14 of the support structure 5 may be implemented with a warp knit open pillar stitch 22 using a double yarn, as shown in Figures 2A and 2C, resulting in a woven layer as shown in Figure 3A. As can be seen in Figures 2A and 3A, the outer layer includes a series of wales with double 0° straight lay-in yarns 24 on both sides connected by a single weft lay-in 26 yarn and inserted into a pillar structure, as shown in Figure 2A. The patterns of the first outer layer 12 and the second outer layer 14 may be the same or different. In an embodiment, both outer layers 12 and 14 may have the same number of wales with spacer elements 18 connecting similar corresponding wales in each of the layers 12 and 14. In an embodiment, the outer layers 12 and 14 may have a different number of wales with spacer elements 18 connecting the wales in each of the layers 12 and 14.

[0051] As used herein, a wale is a "row of loops" that run lengthwise within the fabric. Each wale can be monofilament or double-filament for added strength, resulting in increased bulk. Increasing the number of wales, or the number of yarns per wale, increases the ultimate tensile strength of the fabric. By adjusting the number of wales, the width of the fabric can be varied, allowing the same woven design to be used in narrow applications, e.g., 5mm wide ACL augmentation, medium width applications, e.g., 23mm wide rotator cuff applications, and very wide applications, e.g., 200mm wide hernia applications. A method to increase the ultimate tensile strength, resistance to stretching, and initial stiffness can be achieved by adding 0° straight lay-in yarns to the technical side of the fabric. These lay-in yarns are linearly integrated into each wale.

[0052] The machines used to manufacture the scaffold 10 are Karl Mayer double needle bar warp knitting machines. These machines are computer controlled and many parameters can be altered to affect changes in the properties of the fabric. The main variables include the number of wales, the number of yarns per wale, the addition of inlays to the wales, the inlay design, and the number of yarns per inlay. The ability of the fabric to stretch under tensile load can be affected by knitting every two wales together, rather than every three wales, for example.

[0053] 3B and 4B, the spacer elements 18 may be implemented with multiple yarns in a "Z" direction perpendicular to the plane in which the layers 12 and 14 reside, connecting the layers 12 and 14 and providing support to prevent collapse. In an embodiment, each of the outer layers 12 and 14 may have the same number of wales, and the spacer elements 18 may connect corresponding wales in each of the layers 12 and 14. In other embodiments, the spacer elements 18 may cross diagonally between different wales of the layers 12 and 14. The spacer elements 18 may include monofilament, multifilament, or multifilament and / or textured yarns.

[0054] One or both of layers 12 and 14 may be implemented using the weave pattern shown in Figure 2B. Other weave patterns suitable for layers 12 and 14 may include full tricot, lock knit, and queens cord, single atlas, jersey, reverse jersey, Milano interlock, Milano, half Milano, etc. Variations in warp knit surface design may be utilized to adjust the dimensions, density, and mechanical properties of layers 12 and 14, including either the surface design, number of wales, number of yarns per wale, addition of inlays to wales, inlay design, number of yarns per inlay, lengthening or decreasing quality (machine parameters), or lengthening or decreasing gaps (machine parameters).

[0055] An alternative to warp knitting is to use a V-bed knitting machine, such as a whole garment knitting machine, or to produce a woven 3D spacer fabric using a double rapier loom or a flyshot loom. The addition of pull threads between knitted panels distributes tension and holds the panels together without tearing or snagging during the manufacturing process until the pull threads are removed. These pull threads can be removed mechanically or dissolved in the washing process. In an exemplary embodiment, the support structure number 5 having the three-dimensional fabric implemented therein may have the physical parameters as shown in FIG. 1 below. [Table 1]

[0056] A scaffold having the above physical values ​​and defining a gap between first and second outer layers, 12 and 14, respectively, through which a plurality of spacer elements 18 extend, may be constructed having a thickness of approximately 500 cm. 2 / cm 3 From 7,000cm 2 / cm 3 can be calculated to have a measurable void surface area to volume ratio between

[0057] After the scaffold is manufactured, the fabric may be rinsed and cleaned to remove any finishes that may have been used. Rinsing methods can include the use of water, solvents, and water-solvent mixtures. The fabric may be washed in a constrained or unconstrained state. The fabric may also be treated with agents to modify its surface properties, for example to affect its hydrophilicity. A variety of agents can be used for this, including polyethylene glycol. The surface may also be treated with agents such as fibrin to improve cell attachment. If a portion of the scaffold is intended to be placed in contact with a bone region, the surface of the fibers may be coated with calcium phosphate, hydroxyapatite, or bioactive glass or growth factors such as bone morphogenetic proteins, and demineralized bone matrix.

[0058] In embodiments, the composite scaffold 10, or any portion thereof, including layers 12 and 14 or spacer elements 18, may include any combination of synthetic bioabsorbable polymers, natural polymers, and / or additives. Synthetic bioabsorbable polymers suitable for use as part of the composite scaffold may include homopolymers, copolymers, or polymer blends of any of the following: polylactic acid, polyglycolic acid, polycaprolactone, polydioxanone, polyhydroxyalkanoic acid, polyanhydrides, poly(orthoesters), polyphosphazenes, poly(amino acids), polyalkyl cyanoacrylates, poly(propylene fumarate, trimethylene carbonate), poly(glycerol sebacate), poly(glyconate), poly(ethylene glycol), poly(vinyl alcohol), and polyurethanes, or any combination thereof. Natural polymers suitable for use as part of the composite scaffold may include silk, collagen, chitosan, hyaluronic acid, alginate, and amniotic membrane derived matrices.

[0059] Composite scaffold dimensions In embodiments, the composite scaffold 10 may have a thickness, i.e., the vertical height dimension of the scaffold as opposed to its longer length and width dimensions, of between about 0.5 mm and 5 mm, and even more preferably between about 1 mm and 3 mm. Even more preferably, the scaffold may have a minimum thickness of about 1 mm or greater. In embodiments, the thickness of the scaffold 10 may be uniform along its length or may vary in a repeating or non-repeating manner depending on the particular application for which the scaffold is to be utilized.

[0060] In embodiments, the disclosed composite scaffold 10 can have a width dimension between about 2 mm and 1000 mm, depending on the particular application the scaffold is to be utilized. In embodiments, the width of the disclosed scaffolds can be uniform or can vary in a repeating or non-repeating manner, depending on the particular application the scaffold is to be utilized. For example, the scaffold 10 can have ends where the width of the scaffold narrows, dimensionally changes to suture-like dimensions, or is adapted to attach to conventional sutures used in the procedures described herein.

[0061] In embodiments, the disclosed composite scaffolds may have a length dimension between about 2 and 1000 mm, and even more preferably about 10 inches or more, again depending on the particular application for which the scaffold is utilized. In embodiments, the disclosed scaffolds may be manufactured in various incremental lengths, or may be manufactured in lengths that a physician may cut or customize as needed. FIG. 4B is a side view SEM photograph of a composite scaffold 10 having a length dimension and formed from a pair of outer layers 12 and 14 separated by a plurality of spacer elements 18. The photograph in FIG. 4B was taken with a Philips / FEI XL30 ESEM scanning electron microscope (SEM) with a 1 mm scale legend on the image and the distance along the axis of the length dimension between the spacer yarns indicated by reference lines 1-23. Table 1 lists each reference line along with the average distance and the respective distance value in micrometers. As can be seen from Table 1, the average distance along the axis of the length dimension between the spacer yarns is on the order of 200 μm to 300 μm.

[0062] [Table 2]

[0063] FIG. 4C is an SEM photograph of a perspective cross-section of the composite scaffold of FIG. 4A. The photograph in FIG. 4C was taken with an SEM and includes a 1 mm scale legend on the image and reference lines 1-17 indicating the distance along the width axis perpendicular to the length dimension axis between the spacer yarns. Table 2 lists each reference line along with the average distance and their respective distance values ​​in micrometers. As can be seen from Table 2, the average distance along the width axis between the spacer yarns is between about 300 μm and 400 μm (along the axis).

[0064] [Table 3]

[0065] In the disclosed composite scaffold 10, the respective distances between the spacer elements 18, e.g., spacer yarns, create a series of substantially parallel, similarly sized channels that extend through the gap between the outer layers 12 and 14. These channels provide space within the support structure in which the microporous matrix 15 can be formed, as described herein. Importantly, these channels are formed along the axis of the device such that there is a continuous channel between the two ends of the scaffold. Upon replacement with new tissue, the new tissue is robust along the axis of the device and therefore load-bearing, and therefore functional.

[0066] Support Structure Additive A composite scaffold 10 made from any of the aforementioned materials may be combined with additives to enhance various properties of the scaffold, including promoting regenerative cell growth. Such additives suitable for use as part of a composite scaffold may include seeded cells, biological aspirates, and biologics including bioactive agents. Seeded cells suitable for use as part of a composite scaffold may include adipose-derived stem cells, mesenchymal stem cells, and induced pluripotent stem cells, or any combination thereof. Biological aspirates suitable for use as part of a composite scaffold may include whole blood, platelet-rich plasma, and bone marrow aspirate concentrate, or any combination thereof.

[0067] Bioactive agents suitable for use as part of the composite scaffold 10 can include growth factors, extracellular matrix molecules and peptides, therapeutic agents, and osteoinductive or osteoconductive agents, or any combination thereof, and can be added to the support structure 5 either before or after formation of the microporous matrix 15. Growth factors suitable for use as part of the composite scaffold can include transforming growth factor beta superfamily (e.g., transforming growth factor beta, bone morphogenetic protein), insulin-derived growth factor, platelet-derived growth factor, epidermal growth factor, interleukin 1-receptor antagonist, fibroblast growth factor and vascular endothelial growth factor, or any combination thereof.

[0068] Extracellular matrix molecules and peptides suitable for use as part of the composite scaffold may include tenascin-C, hyaluronic acid, glycosaminoglycans (e.g., chondroitin sulfate, dermatan sulfate, and heparan sulfate), fibrin, thrombin, small leucine-rich peptides (e.g., decorin and biglycan), fibronectin, elastin, and arginine-glycine-aspartic acid (RGD) peptides, or any combination thereof.

[0069] Therapeutic agents suitable for use as part of the composite scaffold may include nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., aspirin, ibuprofen, indomethacin, nabumetone, naproxen, and diclofenac), steroidal anti-inflammatory drugs (e.g., cortisone, and hydrocortisone), antibiotics or antimicrobial agents, or any combination thereof. Osteoinductive or osteoconductive agents suitable for use as part of the composite scaffold may include tricalcium phosphate, hydroxyapatite, and bioactive glass, or any combination thereof.

[0070] Microporous Matrix An optional microporous matrix 15 may be formed within the interior voids 16 of the composite scaffold 10. The microporous matrix 15 is supported and held by the support structure 5 and provides a support for cells to colonize and grow upon. The microporous matrix 15 is designed to be absorbable or degradable and rapidly replaced by neo-tissue. A microporous matrix made from the materials described herein would not, by itself, have usable mechanical strength properties, both in terms of tensile strength and resistance to compression.

[0071] In an embodiment, a method of making a composite scaffold is disclosed that includes constructing a three-dimensional support structure extending along a length dimension between a first end and a second end thereof, defining an interior surface within the support structure, and forming a microporous matrix within the interior surface, where the microporous matrix has a number of interconnected pores 60 in fluid communication with an exterior surface of the support structure. The microporous matrix is ​​formed such that the plurality of interconnected pores 60 are oriented relative to a dimensional characteristic of the support structure. For example, those pores closest to the exterior surface of the composite matrix can be oriented to extend substantially perpendicular or radially inward relative to the nearest exterior surface of the support structure. Additionally, others of the plurality of interconnected pores 60 can be oriented toward the length dimension of the support structure in a manner that mimics the orientation of spacer elements 18, e.g., spacer yarns separating exterior layers 12 and 14.

[0072] In embodiments, the microporous matrix 15 may be implemented with high surface area materials such as sponges, foams, or any combination of processed fibers or yarns. Methods of manufacturing the microporous matrix 15 may include freeze-drying, particle leaching, open-cell extrusion, solution casting, solid foaming, and crosslinking. In one embodiment, sponges / foams useful as the microporous matrix may include freeze-dried sponges, open-cell extruded foams, and particle-infused sponges, or any combination thereof.

[0073] A suitable material for implementing the micropores 15 is collagen, including bovine collagen type 1. Other materials that can be used for the porous matrix 15 instead of or in addition to collagen include hydrogels based on polyethylene glycol (PEG), polycaprolactone (PCL), or poly(glycolide-co-caprolactone) (PGCL), or combinations thereof. The collagen solution can be infiltrated into the support structure 5 using a mold that holds the scaffold. A second scaffold material can also coat the outer surface of the support structure 5 in an encapsulating manner. The mold along with the fabric and collagen solution is placed in a shelf freeze-dryer, also known as a lyophilizer, which uses temperature-controlled shelves to freeze the contents of the mold to very low temperatures, for example, down to -55°C, forming a crystalline structure in the collagen solution and forming a matrix of interconnected pores in the collagen structure that occupies the interior voids 16 of the support structure 5. A vacuum is drawn in the freeze-drying chamber and the temperature of the shelves is gradually increased to provide energy to the frozen solvent and trigger the process of sublimation. The sublimated solvent is collected in a separate condenser and is completely removed from the combustion. After a period of heating and vacuum, a highly porous, low density collagen matrix forms within the fabric.

[0074] The porosity of the collagen within the microporous matrix 15 can be affected in many ways during this process. The bulk porosity can be increased or decreased by decreasing or increasing the weight percentage of the collagen solution, respectively. The pore size can be adjusted by varying the freezing rate within the mold. Increasing the freezing rate results in a smaller average diameter, while decreasing the freezing rate results in a larger average diameter.

[0075] The total surface area of ​​the pores is related to the pore size, e.g., many small pores have a larger surface area than a few large pores, so as the freezing rate increases, the average pore size decreases, and therefore the total surface area increases, whereas as the freezing rate decreases, the average size increases, and therefore the total surface area of ​​the microporous matrix decreases. Figure 5D is a graph showing the relationship between temperature, pressure, and time during the freezing process.

[0076] Varying the mold material, including Delrin, aluminum, stainless steel, or other materials, can result in different microporous matrix structures due to different heat transfer and altered crystallization of the collagen solution upon freezing. For example, a mold made of Delrin, a thermoplastic used in precision component manufacturing, will transfer heat more slowly, resulting in larger pore sizes in the collagen solution. Conversely, a mold made of aluminum will transfer heat very quickly, resulting in a microporous matrix with relatively small pore sizes. A stainless steel mold will transfer heat more slowly than aluminum, resulting in larger pores than those produced in an aluminum mold, but smaller than those produced in a Delrin mold.

[0077] Additionally, adjusting the thickness of the mold between the bottom of the mold and the bottom of the holes can have a similar effect of increasing or decreasing the heat transfer rate, resulting in different microporous matrix structures. In an embodiment, the molds shown in Figures 5A and 5B are fabricated from stainless steel and have the hole dimensions set forth in Table 2 below, where the row of dimensions 5x260 mm refers to mold 50 shown in Figure 5A and the row of dimensions 23x30 mm refers to mold 57 shown in Figure 5B. Mold 50 defines a plurality of rectangular holes 52 and has clamps 54 with fixable pins 55 at its ends. Mold 57 includes an array of rectangular holes 59 and throw holes 53.

[0078] [Table 4]

[0079] The mold shown in FIG. 5A utilizes Delrin end clips that can be secured to the mold body and used to clamp the woven scaffold during the freezing process. In an exemplary embodiment, the holes 52 of the mold 50 have a substantially rectangular cross-sectional shape. Other cross-sectional shapes may be utilized to maximize contact between the surface areas of the support structures 5 during the process of forming the microporous matrix therein. Specifically, scaffolds having either a D-shape, a U-shape, an O-shape, or a C-shape may be utilized during freezing to maximize the surface area of ​​the scaffold shape and further promote orientation of the pores of the microporous matrix during the freezing process. Specifically, for support structures 5 having a cylindrical or tubular shape, a cylindrical mold may be utilized during the freezing process, whether oriented horizontally or vertically.

[0080] Pore ​​access to the scaffold dimensions can be achieved through contact with the mold surface, and as shown in the cross-sectional SEM images of Figures 6D-E and 6G-H, it can be seen that the pores in the microporous matrix 15 are formed close to the mold surface, perpendicular to the contact plane with the mold. In embodiments, Applicants have discovered that the pores can be oriented between 45° and 135° proximal to the interface with the mold. In embodiments, using a mold similar to that shown in FIG. 5A, a significant number of the pores are oriented perpendicular to the interface with the interior of the mold, toward the center of the support structure 5. Such an orientation promotes more rapid ingrowth of cells into the composite scaffold 10.

[0081] An alternative mold design utilizes similar holes as above, but adds a tightly shaped, airtight top. As with injection molding, suction, or pressure, or other means may be used to fill the mold with collagen solution from one end and release trapped gas at the other end to allow further passage of collagen fibers during the injection process. Further alternative mold designs use holes that place the fabric on its sides so that the plane of the fabric is perpendicular to the bottom of the mold. Further alternative mold designs may use holes with a "U" shaped cross-sectional profile or other shapes, which creates a satisfactory scaffold with a shape that is more suitable for a particular type of implantation. There are a variety of manufacturing methods that can be used to create a microporous matrix within the voids of the woven support structure, including salt leaching, gas extrusion, and other methods that use either high pressure or suction and gas.

[0082] The absorption and mechanical properties of the microporous matrix can be further modified by crosslinking. Generally, materials used for crosslinking have potential cytotoxicity, so it is highly beneficial to be able to use lower concentrations. It is an advantage of the disclosed procedure that the use of the support structure 5 allows the microporous matrix 15 to utilize lower concentrations of crosslinking. The 3D fabric filled with the dry highly porous, low density collagen microporous matrix is ​​removed from the mold cavity and placed in a sealed chamber on a permeable shelf such as a wire rack. The formaldehyde and ethanol solution is poured into a tray, this tray is placed under the rack of scaffolds, and the chamber door is sealed. The tray completely encompasses the basic dimensions of the chamber (LxW) and uses the vapor from the solution to crosslink the collagen in the 3D fabric. After a set time, the tray is removed and the product is transferred to an aeration chamber where clean dry air, or alternatively another gas such as nitrogen, is pumped in and out of the chamber, which effectively stops the crosslinking process. It is possible to increase the crosslinking of the collagen by increasing the time in the chamber, increasing the concentration of formaldehyde in the ethanol solution, or reducing aeration. Similarly, cross-linking can be reduced by decreasing the time in the chamber and by lowering the concentration of formaldehyde in the ethanol solution.

[0083] Alternatively, chemical crosslinking agents may be added to the collagen solution. These agents include, but are not limited to, aldehydes in various concentrations, such as glutaraldehyde, genipin, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), EDC / N-hydroxysuccinimide (EDC / NHS), etc. A further alternative mode of crosslinking may come in the form of photochemically activated crosslinking, which may involve the use of UV or visible light to trigger the crosslinking process, with or without a crosslinking initiator.

[0084] Composite scaffold mechanical properties The mechanical properties of the composite scaffold 10 disclosed herein result in a composite scaffold optimized for use in a wide range of medical procedures including suture repair, repair or reconstruction alone, or augmentation such as reconstruction for fixation purposes using tissue grafts. Composite scaffolds 10 made according to the description herein and Examples 1, 2 and 3 were tensile tested using a Mark-10 tensile tester at a crosshead speed of 20 mm / min and the results are listed in Table 3.

[0085] [Table 5]

[0086] An advantage of the composite scaffold 10, and specifically the support structure 5, as disclosed herein, is its ability to resist compression during tension. In an embodiment, as can be seen from the values ​​in Table 3 above, the width, height, and cross-sectional area of ​​the three-dimensional fabric that comprises the support structure 5 resists compression from substantial forces. In particular, a cross-sectional area of ​​about 9.92 mm 2 For a support structure 5 having a thickness (height) of about 2.17 mm and a width of about 4.57 mm, stretching the support structure 5 along its length axis with a force of 35 N causes an extension of the length dimension of the support structure 5 by about 13%. In embodiments, the thickness dimension of the support structure changes by less than about 31% when stretched by about 13% in the length dimension. In embodiments, the cross-sectional area changes by less than about 35% when stretched by about 13% in the length dimension. In embodiments, the width dimension of the support structure changes by less than about 5% upon stretching of about 13% in the length dimension.

[0087] In embodiments, the length of the support structure 5 implemented with the three-dimensional woven scaffold disclosed herein may have an ultimate load at a percentage of elongation in the length dimension between about 30% and 125%. In embodiments, the scaffold may have a yield at a percentage of elongation in the length dimension between about 5% and 15%. In embodiments, the scaffold may have a tensile strength between about 0.073 grams-force / denier and 1.102 grams-force / denier. In embodiments, the scaffold may have a stiffness on the order of 2.5 N / mm to 25 N / mm, stiffness defining the degree to which the scaffold resists deformation in response to an applied force. In embodiments, the scaffold may have a strain at break on the order of 20% to 70%. In embodiments, the scaffold can have a tensile strength at break on the order of 0.3 grams-force / denier to 2 grams-force / denier.

[0088] In an exemplary embodiment, the support structure 5 as disclosed herein implemented with a three-dimensional woven scaffold having a width of 5 mm and a length of 40 mm and a thickness of about 1 mm may have an ultimate displacement on the order of 5 mm to 50 mm, the ultimate displacement defining the change in displacement with the amount of load applied to the biomimetic scaffold above which the biomimetic scaffold fails. Such testing is performed with a gauge length of 40 mm and according to standards set by the American Society for Testing and Materials (ASTM). In an exemplary embodiment, the scaffold may have a yield displacement on the order of 1 mm to 8 mm, the yield displacement defining the change in displacement at which the biomimetic scaffold begins to deform. In an exemplary embodiment, the scaffold may have a yield force on the order of 20 N to 70 N, the yield force defining the force at which the biomimetic scaffold begins to deform. In an exemplary embodiment, the scaffold may have a stiffness on the order of 2.5 N / mm to 25 N / mm, where stiffness defines the extent to which the biomimetic scaffold resists deformation in response to an applied force. In an exemplary embodiment, the scaffold may have an ultimate strain on the order of 20% to 70%, where ultimate strain defines the deformation of the biomimetic scaffold due to stress. In an exemplary embodiment, the scaffold may have an ultimate load on the order of 100 N to 200 N, where ultimate load is defined as the amount of load applied to the biomimetic scaffold above which the scaffold fails. In an exemplary embodiment, the scaffold may have an ultimate strength on the order of 2.5 MPa to 20 MPa, where ultimate strength is defined as the ability of the biomimetic scaffold to withstand a load that tends to stretch the biomimetic scaffold. In an exemplary embodiment, the scaffold may have an ultimate stress on the order of 2.5 MPa to 20 MPa, where ultimate stress is defined as the maximum stress the structure can withstand above which the structure fails. In an exemplary embodiment, the scaffold may have an elastic modulus on the order of 2.5 MPa to 70 MPa, where elastic modulus defines the amount of stiffness of the biomimetic scaffold, including voids.In an exemplary embodiment, the scaffold may have an elastic modulus on the order of 150 MPa to 600 MPa, where the elastic modulus defines a measure of stiffness of the biomimetic scaffold without voids, where the elastic modulus is calculated using the cross-sectional area of ​​only the material comprising the composite scaffold.

[0089] According to embodiments, the composite scaffolds disclosed herein provide greater support for larger amounts of regenerating tissue due to differential degradation rates of the scaffold's elements. More specifically, the first and second support matrices 5 and 15 of the scaffold 10 have different degradation rates. In one embodiment, the second support matrix 15, e.g., a sponge, degrades 2-12 times faster than the first support structure 5 based on mass loss or molecular weight loss. For example, a sponge including a second support matrix may have mass loss by 3-6 months after implantation, while a woven fabric including a first support matrix may have mass loss at 12 months after implantation. This difference in degradation rates allows significant tissue ingrowth, facilitated by the internal porosity of the scaffold 10, to remain supported by the woven fabric for a longer period of time. As shown, the parameters of material degradation may be measured via mass loss or molecular weight loss. In one embodiment, the composite scaffold may have a mass loss degradation profile of 50% or greater strength retention for at least about 4 weeks after implantation and 100% mass loss between about 6 and 12 months after implantation.

[0090] According to embodiments, the composite scaffolds disclosed herein may have features that enhance their usefulness and better performance when implanted. In embodiments, the scaffold 10 may have ends that are narrowed, altered to suture-like dimensions, or modified (e.g., sewn or knotted) to attach to conventional sutures used in the procedures described herein. In embodiments, the support structure 5, e.g., the fabric, may have ends or edges that are heat set, sewn, or impregnated with other materials to facilitate better manipulation, better integration with existing tissue, and further reduce dimensional distortion of the scaffold 10 under pressure, tension, or shear forces. In embodiments, selected sections of the scaffold 10 may be repeated at random or constant rates to increase or decrease the density of the scaffold, e.g., by changing the weave pattern of the first support structure 5 to increase or decrease the density of the weave. In embodiments, such repeating regions may be selected to modify the surface finish of the scaffold by altering parameters of lyophilization, smoothness or roughness of the outer surface of the scaffold to enhance acceptance of the scaffold when implanted.

[0091] 2D, the spacer elements 18 may be disposed in only a portion of the interior space 16 of the scaffold 10, e.g., the hollow lumen. In other embodiments, the spacer elements 18 may have either a regular or irregular repeating arrangement pattern within the interior space 16 between layers 12 and 14 of the scaffold 10. In other embodiments, the spacer elements 18 themselves may be implemented with a fabric, such as a felt, or a tissue or tissue-derived material, or as otherwise described herein.

[0092] According to embodiments, the composite scaffold can also be seeded with cells for a temporary pre-culture period to allow the cells to fabricate a collagen-rich extracellular matrix on the sponge and woven elements. The scaffold can then be optionally decellularized to leave a matrix template with native extracellular matrix proteins on the woven structure, after which the scaffold can be implanted to repair tendons or ligaments in vivo.

[0093] Scaffold pore characteristics Many samples of composite scaffolds manufactured by the processes described in Examples 1 and 2 and herein have been tested to determine various behavioral characteristics, as described below. The microporous matrix in each sample composite scaffold has numerous interconnected pores that open to the microporous matrix and to the outer surface of the composite scaffold. Various properties of the pores in the microporous matrix, and therefore in the composite scaffold, can be measured by mercury intrusion porosimetry (MIP), or gas adsorption methods. Mercury is a non-wetting liquid and does not actively fill the porous structure. However, by applying pressure using MIP, mercury can be forced into the pores of the microporous matrix, and higher pressures allow the mercury to enter the smaller pores. By precisely monitoring the volume of mercury while applying incremental pressure in increments, the pore size (diameter) and pore volume can be precisely measured. Pore size and volume measurements can be used to determine many properties of the microporous matrix and composite scaffolds in general.

[0094] surface area An important property of the disclosed composite scaffolds is the ratio of scaffold surface area per unit weight of the scaffold. The disclosed composite scaffolds have a large surface area where cell migration and subsequent neotissue development can occur due to the large number of interconnected pores in the microporous matrix supported by a 3D woven support structure. The interconnected pores and total external surface area of ​​the composite scaffold can be more accurately measured using MIP than simply geometric dimensions and image quantification. The surface area can be calculated from the known diameter of the pores measured via MIP by assuming the pores are spheres using the following formula:

number

[0095] Thus, the surface area parameter represents the amount of surface area of ​​the composite scaffold per unit weight of the composite scaffold area and is expressed in square meters per gram (m 2 8 is a graph 80 of test data showing the relationship of cumulative total pore surface area to pore size, measured in micrometers, for several composite scaffold samples as well as a sample including only a 3D woven support structure 5. In the samples of FIG. 8, the 3D woven support structure 5 included PLLA fibers, whether alone or filled with a microporous matrix 15. All samples were manufactured according to the methods described herein and Examples 1 and 2. In an embodiment, the disclosed composite scaffold has a surface area of ​​about 0.3 m 2 / gram to 1.5m 2 The disclosed composite scaffolds can have a surface area per unit of weight ranging between about 0.6 m / gram. 2 / gram to 1.2m 2 The disclosed composite scaffolds can have a surface area per unit of weight ranging between about 0.71 m / gram. 2 / gram to 1.0m 2 The surface area per unit of weight may be between 1 / gram.

[0096] The total external surface area of ​​the interconnected pores and composite scaffold can also be more accurately measured using gas adsorption techniques, such as with krypton gas, rather than simply quantification of geometric dimensions and images. The table below shows two samples with a width of 5 mm and a length of 40 mm. The surface area of ​​the composite scaffold is approximately 0.3 m2 when measured by krypton gas adsorption for pores with diameters less than 1 μm. 2 / gram to 15m 2 / gram. [Table 6]

[0097] Total Pore Volume Another important property of composite scaffolds is the large volume of voids, due in part to the number, diameter, orientation, and interconnectivity of the pores that collectively define the void space within the microporous matrix. Such a large total pore volume promotes more rapid blood absorption, cell migration, and subsequent development of new tissue. The total volume of pores that collectively form the void space within the microporous matrix may be measured directly using MIP by monitoring the change in mercury volume during the MIP process. Thus, the pore volume parameter of a composite scaffold is the total cumulative void volume per unit weight of the composite scaffold, e.g., cm 3 9 represents the cumulative total pore volume, measurable in cubic centimeters per gram, versus pore diameter, measured in micrometers, for several composite scaffold samples as well as a woven-only support structure. In the samples of FIG. 9, the woven support structure includes PLLA fibers, whether alone or filled with a microporous matrix. All samples were manufactured by the methods described herein. In an embodiment, the disclosed composite scaffold has a pore diameter of about 3.0 m. 3 / g to 9.0m 3 The disclosed composite scaffolds can have a total pore volume ranging between about 3.5 m / gram. 3 / g to 7.0m 3The disclosed composite scaffolds can have volumes ranging between about 4.0 m / gram. 3 / gram to 5.0m 3 The total pore volume may range between 1 / gram and 1 / gram.

[0098] porous Another important property of the composite scaffold is porosity, which is a measurement of the void volume within the microporous matrix as a percentage of the measurable volume of the composite scaffold itself. Such calculations can be performed using measurements made during MIP. By monitoring the mercury volume during the MIP process, the mass of each sample is known, as is the volume occupied by the sample. At the lowest applied pressure during MIP, there should be no mercury loaded into the scaffold, so the volumetric density of the composite scaffold can be calculated. As the pressure applied during MIP increases, the composite scaffold should be nearly completely loaded with mercury. Thus, the skeletal density of the scaffold can be calculated as follows: Porosity = 100*1-(density at low pressure / density at high pressure)

[0099] In this way, the measurable volume of the composite scaffold is calculated by the relative density, not by geometry. FIG. 10 is a graph 100 of the relationship of composite scaffold density in grams per cubic centimeter with respect to mercury pressure measured in pounds per square inch (absolute), i.e., in a vacuum, measured in micrometers, for several composite scaffold samples as well as a woven-only support structure. In the samples of FIG. 10, the woven support structure includes PLLA fibers, whether alone or filled with a microporous matrix. All samples were manufactured by the methods described herein. In embodiments, the disclosed composite scaffolds can have a porosity ranging between about 75% and 98%. In embodiments, the disclosed composite scaffolds can have a porosity ranging between about 80% and 90%. In embodiments, the disclosed composite scaffolds can have a porosity ranging between about 80% and 85%.

[0100] Transmittance Another important property of the composite scaffold is the permeability of the microporous matrix, which promotes more rapid absorption of fluids, especially blood, both during and after implantation to accelerate the process of cell migration and subsequent neotissue development. The microporous structure within the woven support structure, e.g., collagen, promotes a more uniform and well-defined pore structure compared to the collagen sponge alone, which has a permeability of approximately 200% of that of the collagen sponge itself. This is due, at least in part, to a more uniform and well-defined structure of interconnected pores. Reproducible permeability values ​​can be calculated from mercury intrusion porosimetry (MIP) data using the Katz-Thompson equation shown below:

number

[0101] A description of how to calculate permeability using the Katz-Thompson formula above is provided in a publication by Goa and Hu entitled estimating permeability using median poor - throat radius obtained from Mercury intrusion precocity in J.Geophysics.Eng.(2013). In this manner, reproducible permeability values ​​can be calculated from data collected during MIP. In embodiments, the disclosed composite scaffolds can have a permeability ranging between about 1200 and 3000 millidarcy. In embodiments, the disclosed composite scaffolds can have a porosity ranging between about 1400 and 2600 millidarcy. In embodiments, the disclosed composite scaffolds can have a porosity ranging between about 1600 and 2000 millidarcy.

[0102] Total surface area / scaffold volume Another important property of a composite scaffold is the ratio of total surface area / scaffold volume. The surface area for a given sample can be determined from the MIP. The scaffold density can be calculated as explained above with reference to the porosity parameter. The surface area is expressed in units of square meters (m 2 The volume of the scaffold is reported in grams per gram (g) and can be converted to meters cubed by multiplying by the sample mass. The scaffold volume is equal to the sample mass divided by the scaffold density. In embodiments, the disclosed composite scaffolds have a volume of about 5,000 cm 2 / cm 3 From 16,000cm 2 / cm 3 In embodiments, the disclosed composite scaffolds can have a void surface area to scaffold volume of between about 7,000 cm 2 / cm 3 From 14,000cm 2 / cm 3 In embodiments, the disclosed composite scaffolds can have a void surface area to scaffold volume of between about 9,000 cm 2 / cm 3From 12,000cm 2 / cm 3 The scaffold may have a void surface area relative to the scaffold volume between.

[0103] Pore ​​diameter Another important characteristic of the composite scaffold is the median pore size, measured in micrometers, of the interconnected pores within the voids of the microporous matrix 15. The pores of the microporous matrix must be large enough to allow cell infiltration, but not so large as to retard cell proliferation and neotissue formation prior to resorption of the microporous matrix after implantation. According to the present disclosure, the number of pores of a given diameter is effectively measured by observing the invaded volume at a given pressure during MIP. From this, the median pore size and pore size distribution are both reported. FIG. 12 is a graph 120 that graphically illustrates the relationship of the distribution of pore diameters, measured in micrometers, to the logarithmic differential volume, measured in cubic centimeters per gram. In an embodiment, the microporous matrix may have a plurality of interconnected pores with a median pore size between about 10 μm and 70 μm. In embodiments, the microporous matrix may have a plurality of interconnected pores with a median pore size of between about 12 μm and 50 μm, In embodiments, the microporous matrix may have a plurality of interconnected pores with a median pore size of between about 20 μm and 35 μm.

[0104] Another important characteristic of the composite scaffold is the distribution of pore sizes within the voids of the microporous matrix of the composite scaffold, measured in micrometers. The cumulative pore volume can be determined from the MIP. The fractional contribution of pores over a certain diameter to the voids can be calculated as the cumulative voids at a given pore diameter divided by the total voids. The distribution of pore sizes within the voids of the microporous matrix is ​​also shown in FIG. 12. As can be seen from FIG. 12, the majority of the collective voids within the microporous matrix include pores with diameter parameters greater than 10 μm. In an embodiment, the microporous matrix has a large number of interconnected pores that collectively define the voids, with at least about 99% of the voids including pores with diameter dimensions of 10 μm or greater. In an embodiment, the microporous matrix has a large number of interconnected pores that collectively define the voids, with at least about 95% of the voids including pores with diameter dimensions of 10 μm or greater. In embodiments, the microporous matrix has a multiplicity of interconnected pores that collectively define voids, with at least about 80% of the voids comprising pores having diameter dimensions of 10 μm or greater.

[0105] Swelling and Absorption According to embodiments, the composite scaffolds disclosed herein provide a relatively high absorptive capacity, e.g., the ability to absorb aqueous media or hygroscopicity, facilitating faster and greater absorption of biological fluids and / or cells within the scaffold. Specifically, the absorptive capacity of the composite scaffold can be measured from the following formula: % Absorption = (Sample Wet Weight - Sample Dry Weight) / Sample Dry Weight * 100

[0106] In embodiments, the disclosed composite scaffold has a measurable dry weight value representative of the weight of the scaffold in a substantially dry state and a measurable dry volume value representative of the volume of the scaffold in a substantially dry state, where the weight value of the scaffold increases by between about 200% and 600% due to fluid absorption, resulting in a change in the dry volume value of the scaffold of between about 0% and 10%. The percent volume change of the composite scaffold can be determined from the following formula: % Volume Change = (Sample Wet Volume - Sample Dry Volume) / Sample Dry Volume * 100

[0107] According to embodiments, the composite scaffolds disclosed herein provide a reduced swelling profile that resists dimensional change due to, for example, increased fluid uptake. Specifically, the percent swelling change of a composite scaffold can be measured from the following formula: % Swelling = (wet mass of sample - dry mass of sample) / (wet mass of sample)*100

[0108] In embodiments, the disclosed composite scaffolds have a measurable dry weight value representative of the weight of the composite scaffold in a substantially dry state and a measurable dry length value representative of a dimensional parameter of the composite scaffold in a substantially dry state, where the weight value of the composite scaffold increases by between about 200% and 600% due to fluid absorption such that the dry length value of the composite scaffold changes by less than between about 0% and 3%. The percent length change of the composite scaffold is measurable from the following formula: % Length Change = (Sample Wet Length - Sample Dry Length) / Sample Dry Length * 100

[0109] In embodiments, a disclosed composite scaffold has a measurable dry weight value representative of the weight of the composite scaffold in a substantially dry state and a measurable cross-sectional profile value representative of a dimensional parameter of the composite scaffold in a substantially dry state, where the weight value of the composite scaffold increases by between about 200% and 600% due to fluid absorption, causing the cross-sectional profile value of the composite scaffold to change by between about 0% and 10%. The percent cross-sectional profile change of the composite scaffold can be measured from the following formula: % Cross-Section Profile Change = ((Sample Wet Width * Sample Wet Height) - (Sample Dry Width * Sample Dry Height)) / (Sample Dry Width * Sample Dry Height) * 100

[0110] Other relevant equations are as follows: % Density Wet = ((Sample Wet Weight / Sample Wet Volume) / (Sample Dry Weight / Sample Dry Volume)*100 % thickness change = (wet sample height - dry sample height) / dry sample height * 100 % weight wet = sample wet weight / sample dry weight * 100 % of sample volume filling = (sample wet mass - sample dry mass) / (sample dry volume)

[0111] The composite scaffold devices are weighed throughout the manufacturing process to obtain both the mass of the fabric alone, the mass after coating with PEG400, and the mass after addition of collagen solution and subsequent lyophilization. The mass of the collagen microporous matrix of each device can be calculated as follows: mass コラーゲン =mass スキャフォールド -mass 織物+PEG400

[0112] The % dry weight of collagen compared to the entire composite scaffold device can then be calculated as follows:

number

[0113] Scaffold Density Categories Another important characteristic of a composite scaffold is the density of the scaffold. According to embodiments, the composite scaffolds disclosed herein having a higher density or mass of the support matrix compared to the more porous matrix disposed therein provide the primary and bulk structure of the disclosed scaffold. More specifically, the first and second support matrices 5 and 15 of the scaffold 10 have different densities or mass components relative to each other. In one embodiment, the first support structure 5, e.g., a woven fabric, has a measurable mass or density that is greater than or equal to 1 times the mass or density of the second support matrix 15, e.g., a sponge, more preferably between 2-5 times the mass or density of the second support matrix 15. In embodiments, the disclosed composite scaffolds have a density of less than 0.5 g / cm 3 Less than about 0.05 g / cm 3 from 0.3 g / cm 3 The maximum scaffold density may be between 0.01 and 0.05.

[0114] Manufacturing method The method of manufacturing a composite scaffold according to the present disclosure is as follows: A 5 mm wide, 3 mm high, 260 mm long composite scaffold for ACL repair or augmentation made from a 3-dimensional PLLA fabric filled with a highly porous collagen matrix is ​​manufactured as follows: A three-dimensional (3D) fabric containing a support structure is manufactured using a double pillar pattern shown in FIG. 2A by the warp knitting technique described. The resulting structure has upper and lower layers of 6 wales each. The corresponding wales of the upper and lower layers are interconnected by a series of knitted spaced apart yarns that extend through the gaps, for example in the Z direction perpendicular to the XY plane of the outer layers 12 and 14, interconnecting the layers 12 and 14. The 3D fabric is received as a continuous long fabric of 5 mm wide and 3 mm high and is ultrasonically washed, for example, in a solution of DI and IPA to remove particles and spin finish of the yarns. Many washes are performed with solutions exchanged between washes. The temperature of the washing solution can be room temperature or up to 40°C. The 3D fabric is then air dried and cut to length.

[0115] An alternative method of preparing the 3D fabric prior to coating with the hydrophilic solution involves wrapping a continuous length of fabric around a frame or suture rack, also known as a tenter frame, with moderate tension and no overlap. The wrapped frame is then submerged in a solution of distilled water and isopropyl alcohol and washed and agitated in an ultrasonic or shaker bath. Multiple washes can be performed with solutions changed between washes. The temperature of the wash solution can be room temperature or up to 40°C. The 3D fabric is then air-dried on a rack under tension. The fabric is then cut to length on a rack under tension to a uniform length. By utilizing a suture rack, washing under tension, and drying under tension, the fabric is heat set, reducing wrinkles, keeping the top and bottom fabric faces against each other, and tightening the knitted structure, resulting in less stretch in the final fabric under load.

[0116] The rinsed and cut to length 3D fabric is then submerged in a solution of polyethylene glycol (PEG) and ethanol to increase hydrophilicity. The concentration of PEG in the ethanol is specifically controlled such that the weight percent of PEG on the 3D fabric is controlled as a result. The 3D fabric is then air-dried. An alternative method of preparing the 3D fabric prior to coating with the hydrophilic solution includes submerging the 3D fabric in a solution of PEG and ethanol after rinsing and before cutting to length. Further alternative methods include submerging the 3D fabric in a solution of PEG and ethanol after rinsing and before cutting as it is wound onto the frame, utilizing many combinations of each alternative in the steps above to achieve the same results.

[0117] A 0.6 wt% collagen solution is then made using low molar acetic acid, mixed with powdered type 1 bovine collagen, and vacuum treated to remove trapped air bubbles. Another low molar acid, such as hydrochloric acid, may be used to make the collagen solution. Additionally, trapped air bubbles may be removed by an alternative process, for example, by spinning the solution in a centrifuge. Different weight percent collagen solutions can be used. Increasing the weight percent of collagen will increase the amount of collagen in the matrix. Decreasing the weight percent of collagen will decrease the amount of collagen in the matrix. Such modifications will affect the final collagen matrix density, structural properties, and porosity when utilizing the freeze-drying process described herein.

[0118] A stainless steel mold 57, shown in FIG. 5B, is used to guide the filling of the collagen solution into the 3D fabric, which will then be freeze-dried to create the collagen sponge matrix construct. The mold cavity is filled with a small amount of collagen solution. A cut length of the 3D fabric is then placed into the mold with the 3D fabric facing parallel to the bottom of the cavity, and clamps are used at each end to secure the 3D fabric and prevent movement. These clamps have the added benefit of creating flat areas at each end free of porous collagen matrix that are used for product processing and suture attachment in the next step, freeze-drying.

[0119] Additional collagen solution is then filled into the cavity containing the fabric, completely submerging the fabric in the collagen solution. The mold containing the fabric and collagen solution is then vacuumed to remove any remaining air inside the 3D fabric and completely fill the fabric with the solution. The mold containing the fabric and collagen solution is placed in a shelf freeze dryer, which reduces the temperature to -55°C over a period of approximately 2 hours. The fabric, now filled with a dry highly porous, low-density collagen matrix, is removed from the cavity of the mold and placed in a sealed chamber on a wire rack. A solution of formaldehyde and ethanol is poured into a tray, which is placed under the rack of products and the door of the chamber is sealed. Vapors from the solution crosslink the collagen in the fabric. After approximately 2 hours, the tray is removed and the product is moved to an aeration chamber where clean, dry air is pumped in and out of the chamber, which effectively stops the crosslinking process. After a period of warming and vacuum, a highly porous, low-density collagen matrix is ​​formed within the 3D fabric.

[0120] A composite scaffold with a width of 23 mm, height of 3 mm, and length of 30 mm for rotator cuff repair or augmentation made from a three-dimensional PLLA fabric filled with a highly porous collagen matrix is ​​fabricated as follows: A composite scaffold with a width of 5 mm, height of 3 mm, and length of 260 mm for ACL repair or augmentation made from a three-dimensional PLLA fabric filled with a highly porous collagen matrix is ​​fabricated as described below: A three-dimensional (3D) fabric containing the support structure is fabricated using a double pillar pattern shown in FIG. 2A by the warp knitting technique described. The resulting structure has upper and lower layers of 25 wales each. Corresponding wales of the upper and lower layers are interconnected by a series of knitted spaced yarns that extend through the gaps in the Z direction to interconnect the layers.

[0121] The 3D fabric is received as a continuous length of fabric 5 mm wide and 3 mm tall and is ultrasonically rinsed, e.g., washed, in solutions of DI and IPA to remove particles and yarn spin finish. Many washes are performed with solutions exchanged between washes. The temperature of the wash solution can be room temperature or up to 40°C. The 3D fabric is then air-dried and cut to length. The rinsed and cut to length 3D fabric is then submerged in a solution of PEG and ethanol to increase hydrophilicity. The concentration of PEG in ethanol is specifically controlled such that the weight percentage of PEG on the 3D fabric is controlled as a result. The 3D fabric is then air-dried. Next, a 0.6 wt% collagen solution is made using low molar acetic acid, mixed with powdered type 1 bovine collagen, and vacuum treated to remove any trapped air bubbles.

[0122] A stainless steel mold, shown in Figure 5B, is used to guide the filling of the collagen solution into the 3D fabric, which will then be freeze-dried in the next step, creating the collagen sponge matrix construct. The mold cavity is filled with a small amount of collagen solution. A cut length of the 3D fabric is then placed into the mold, with the 3D fabric facing parallel to the bottom of the cavity, and clamps are used at each end to secure the 3D fabric and prevent movement. These clamps have the added benefit of creating flat areas at each end free of porous collagen matrix that are used for product processing and suture attachment in the next step, freeze-drying.

[0123] Additional collagen solution is then filled into the cavity containing the fabric, completely submerging the fabric in the collagen solution. The mold containing the fabric and collagen solution is then vacuumed to remove any remaining air inside the 3D fabric and completely fill the fabric with the solution. The mold containing the fabric and collagen solution is placed in a shelf freeze dryer, where the temperature is reduced to -55°C over a period of 2 hours. A vacuum is drawn in the freeze drying chamber and the shelf temperature is gradually increased to provide energy to the frozen solvent, triggering the process of sublimation. The sublimated solvent is collected in a separate condenser and completely removed from the inflammation. After a period of warming and vacuum, a highly porous, low-density collagen matrix is ​​formed within the 3D fabric.

[0124] The design of the mold can allow the entire scaffold to be encapsulated in collagen gel, which can have the advantage of protecting the body from the woven scaffold elements with a more biocompatible collagen gel.

[0125] Medical Treatment The composite scaffolds described herein may be utilized in a wide variety of medical procedures, including augmentation such as suture repair, sole repair or reconstruction, or reconstruction for fixation purposes using tissue grafts. The augmentation of repair or reconstruction using composite scaffolds may be applied to the knee, ankle, shoulder, elbow, and hand, and non-musculoskeletal soft tissues. The knee may include any of the following injuries: ACL (anterior cruciate ligament), PCL (posterior cruciate ligament), LCL (lateral collateral ligament), MCL (medial collateral ligament), MPFL (medial patellofemoral ligament), ALL (anterolateral ligament), and posterolateral corner injury (lateral collateral ligament, popliteofibular ligament). The ankle may include any of the following injuries: ATFL (anterior talofibular ligament) and CFL (calcaneofibular ligament). The shoulder, elbow, and hand may include any of the rotor cuff (supraspinatus, infraspinatus, subscapularis, and teres minor tendons), acromioclavicular ligament, UCL (medial collateral ligament), and flexor tendons. Non-musculoskeletal soft tissues may include any of the chest, abdominal wall, and pelvic floor. The composite scaffolds described herein may be utilized for fixation of permanent and resorbable materials, including sutures, suture anchors, tacks, and staples.

[0126] The physical dimensions and biomechanical properties of the composite scaffolds disclosed herein are optimized for use in a wide variety of medical procedures, including augmentation of suture repair, sole repair or reconstruction, or reconstruction for fixation purposes using tissue grafts. Augmentation of repair or reconstruction using composite scaffolds may be applied to knees, ankles, shoulders, elbows, and hands, as well as non-musculoskeletal soft tissues. Such physical properties differ to some extent from those of commercially available products such as hernia meshes and orthopedic suture tapes, making them more suitable for the procedures described above. For example, orthopedic suture tapes exist and are measurable as three-dimensional entities, but from any point of view relevant to surgery, they are effectively two-dimensional with little value in regenerating the volume of tissue required to enhance or mimic the properties of tendons or ligaments. For surgical meshes and patches constructed of bioabsorbable materials that have a wide range of applications and can be considered scaffolds, the resulting tissue surface that forms after the material is fully absorbed can be very thin and weak, due to a lack of sufficient void volume of thickness and / or appropriate pore size for cell ingrowth within the scaffold. Therefore, there is a clear need to create tissue scaffolds that are thick enough to regenerate a thicker and stronger tissue surface after polymer degradation.

[0127] In an exemplary embodiment, FIG. 12 and Table 4 below show that for several samples, tendons augmented with the disclosed composite scaffolds are consistently stronger and can handle greater forces for similar extension than tendons alone. [Table 7]

[0128] Another alternative to the disclosed composite scaffold is to utilize a tubular spacer, whether warp or weft knitted, that can be used as a "sheath" for an autograft, allograft, or repaired tendon or ligament. One way to create this is to use a flat spacer fabric and attach opposing edges by sewing, heat welding, or other means to create a tube, as shown in FIG. 14. Alternatively, a customized circular knit can be used to weave a tubular spacer fabric with no interlocking seams. Another alternative method to create a tubular spacer is to weave the structure in the manner of a 3D circular woven preform, the method and structure shown in FIG. 15.

[0129] An alternative method to manufacture textile elements as structures holding a porous matrix is ​​to 3D print the structure out of an elastic or inelastic material and then fill it with the porous matrix. Alternatively, both the structure and matrix can be 3D printed from one or many materials as separate but combined entities, or as a single entity that provides both strength, porosity, and resistance to compression.

[0130] In embodiments, the scaffold comprises a composite structure with a woven outer skin to provide strength and a 3D printed inner support structure to provide resistance to compression. Such scaffolds can be either rectangular or tubular in shape. Braiding can be used as a cost-effective method to manufacture tubular structures. Braiding over a 3D printed inner support structure insert provides the continuous space required for tissue ingrowth. The outer braided structure can be provided with longitudinally braided polymer fibers to further tune the tensile properties of the scaffold.

[0131] Working Example Example 1 - Fabrication of a woven scaffold A 75 denier / 30 filament poly-L-lactic acid (PLLA) yarn was produced for use in the manufacture of scaffold fabrics. A warp beam was produced for use on a Karl Mayer double needle bar machine to produce the fabrics. A 5 mm wide fabric with 6 Wales across its width and a 23 mm wide fabric with 27 Wales across its width were produced, i.e. using a 22 gauge needle bed. The two surface layers were separated in the Z direction by spacer yarns to create a 2 mm thick fabric. The fabrics were rinsed in a mixture of deionized water and isopropyl alcohol in an ultrasonic bath and dried.

[0132] Example 2 – Fabrication of an ACL Augmentation / Repair Device A 0.6% collagen solution (by weight) was made using low molar acetic acid and powdered type 1 bovine collagen. The solution was mixed and vacuumed to remove any trapped air bubbles. A stainless steel mold as shown in FIG. 5A was filled with a small amount of collagen solution into the hole. A woven scaffold from Example 1, with a sample 26 cm long and 5 mm wide, was placed into the mold with the woven surface parallel to the bottom of the hole, and clamps were used at each end to secure the fabric and prevent movement. Additional collagen solution was filled into the hole containing the fabric, completely submerging the fabric in the collagen solution. The mold with the fabric and collagen solution was vacuumed to remove any remaining air inside the fabric and completely fill the fabric with the solution.

[0133] The molds were then placed into a SP Scientific AdVantage Plus freeze dryer and the samples were freeze-dried; the freeze-drying process took place inside the freeze dryer from room temperature to -55°C for 2 hours. The fabric, filled with the dried highly porous, low-density collagen matrix, was removed from the mold holes and placed in a sealed chamber on a wire rack. A solution of formaldehyde and ethanol was poured into a tray, the tray was placed under the rack of products, and the chamber door was sealed. Vapors from the solution cross-link the collagen within the fabric. After 2 hours, the tray was removed and the product was moved to an aeration chamber where clean, dry air was pumped in and out of the chamber, which effectively stopped the cross-linking process. The final device was suitable for use in ACL augmentation or repair.

[0134] Example 3 - Fabrication of a Rotator Cuff Augmentation / Repair Device Following the methodology of Example 2, but instead using the mold of Figure 5B, a 50 mm x 23 mm piece of fabric from Example 1 was impregnated using a mold adapted to accommodate a 23 mm wide fabric. The final device was suitable for use in rotator cuff augmentation or repair.

[0135] Example 4 – Preparation of matrix material A 0.6% collagen solution (by weight) was made using low molar acetic acid and powdered type 1 bovine collagen. The solution was mixed and vacuumed to remove trapped air bubbles. The solution was then freeze-dried as in Examples 2 and 3.

[0136] Example 5 – Demonstration of Tendon Augmentation Porcine flexor digitorum profundus muscles were obtained from a local slaughterhouse. The composite scaffold device of Example 1 was doubled over the tissue and whipstitched at one end with a #2 suture. A tensile tester was used to mimic an implant preparation table. The whipstitched end was secured to the upper grip jaw of the tensile tester. Pretension was applied by loading both ends of the composite scaffold with an appropriate force and securing the lower grip jaw. The construct was cycled through a 3.75 mm extension and return to zero. Performance data is shown in Table 3 below and demonstrates the ability of the composite scaffold pretension to control the reinforcement provided by the scaffold.

[0137] [Table 8]

[0138] The size of the composite scaffolds described herein may vary depending on the intended application, however, it is contemplated that the scaffolds may have lengths up to 1000 mm and widths from 3 mm to 1000 mm to accommodate different soft tissue sizes and applications. Additionally, the width may taper towards the suture width at the ends of the scaffold.

[0139] The present disclosure will be more fully understood through the following description, which should be read in conjunction with the drawings. In this description, like numbers refer to like elements in various embodiments of the present disclosure. Those skilled in the art will readily appreciate that the methods, apparatus, and systems described herein are merely exemplary and modifications may be made without departing from the spirit and scope of the present disclosure. The terms "comprise", "include", and / or, each plural, are open-ended and include the recited parts and may also include additional parts not recited. The term "and / or" is open-ended and includes one or more of the recited parts and combinations of the recited parts.

[0140] At various places in the specification, values ​​are disclosed in groups or in ranges, and it is specifically intended that the description include each and every subcombination of the members of such groups and ranges, and any combination of the various endpoints of such groups or ranges. For example, integers in the range of 0 to 40 are specifically intended to individually disclose 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, and 40, and integers in the range of 1 to 20 are specifically intended to individually disclose 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20. Real numbers include values ​​to at least three decimal places and are intended to be inclusive as well. The foregoing description has been presented for purposes of illustration. It is not exhaustive or limited to the precise forms or embodiments disclosed. Modifications and adaptations will be apparent to those skilled in the art from consideration of the specification and practice of the disclosed embodiments.

[0141] As used herein, "a" and "an" mean "one or more." Similarly, use of the term "plurality" does not necessarily mean "plurality" unless such is clear in a given context. Words such as "and" or "or" mean "and / or" unless specifically stated otherwise. Moreover, since numerous modifications and variations will readily occur from studying this disclosure, it is not desired to limit the disclosure to the exact construction and operation as illustrated and described, and therefore, all suitable modifications and equivalents within the scope of the disclosure may be reclassified.

[0142] Although several embodiments of the present disclosure are shown in the figures, it is not intended that the disclosure be limited thereto, as the disclosure is as broad as the art will permit, and the specification is intended to be read in the same manner. Any combination of the above-mentioned embodiments is also contemplated and within the scope of the appended claims. Furthermore, while exemplary embodiments are described herein, the scope of any and all embodiments includes equivalent elements, modifications, omissions, combinations (e.g., of aspects across various embodiments), adaptations, and / or alterations that would be understood by a person skilled in the art based on this disclosure. The limitations of the claims should be interpreted broadly based on the language used in the claims, and not limited to the examples described in this application. The examples should be construed as non-exclusive. Furthermore, the steps of the disclosed methods may be modified in any manner, including rearranging steps, and / or inserting or deleting steps. Accordingly, it is intended that the specification and examples be considered as exemplary only, with a true scope and spirit being indicated by the following claims and the full scope of their equivalents.

[0143] Although several embodiments of the present disclosure have been shown in the drawings, it is not intended to limit the disclosure thereto, as the disclosure is as broad as the art will permit, and the specification is intended to be read in the same manner. Any combination of the above-described embodiments is contemplated and is within the scope of the appended claims. Thus, the above description should not be construed as limiting, but merely as exemplifications of specific embodiments. Those skilled in the art will envision other modifications within the scope and spirit of the claims appended hereto.

Claims

1. 1. A composite scaffold comprising: a microporous matrix having a multiplicity of interconnected pores opening to an exterior surface of the microporous matrix and collectively defining a void space; and a structure supporting the microporous matrix; The composite scaffold has a surface area of ​​about 0.3 m ２ / gram to 15.0m ２ / grams, The scaffold.

2. The composite scaffold has a surface area of ​​about 0.6 m ２ / gram to 1.2m ２ 13. The composite scaffold of claim 1, wherein the composite scaffold has a viscosity of between 1000:1 and 1000:

1.

3. The composite scaffold has a surface area of ​​about 0.7 m ２ / gram to 1.0m ２ 13. The composite scaffold of claim 1, wherein the composite scaffold has a viscosity of between 1000:1 and 1000:

1.

4. The volume of the gap is about 3.0 cm ３ / gram to 9.0 cm ３ 13. The composite scaffold of claim 1, wherein the composite scaffold has a viscosity of between 1000:1 and 1000:

1.

5. 1. A composite scaffold comprising: a microporous matrix having a multiplicity of interconnected pores that open to an exterior surface of the microporous matrix and collectively define a void having a measurable volume; and a structure supporting the microporous matrix; The volume of the gap is about 3.0 cm ３ / gram to 9.0 cm ３ / grams, The scaffold.

6. The volume of the gap is about 3.5 cm ３ / gram to 7.0 cm ３ 6. The composite scaffold of claim 5, wherein the composite scaffold has a viscosity of between 1000:1 and 1000:

1.

7. The volume of the gap is about 4.0 cm ３ / gram to 5.0 cm ３ 6. The composite scaffold of claim 5, wherein the composite scaffold has a viscosity of between 1000:1 and 1000:

1.

8. The composite scaffold has a surface area of ​​about 0.3 m ２ / gram to 1.5m ２ 6. The composite scaffold of claim 5, wherein the composite scaffold has a viscosity of between 1000:1 and 1000:

1.

9. 1. A composite scaffold comprising: a microporous matrix having a multiplicity of interconnected pores that collectively define a void having a volume and that open to an exterior surface of the microporous matrix; and a structure supporting the microporous matrix; the void volume being between about 75% and 98% of the measurable volume of the composite scaffold; The scaffold.

10. 10. The composite scaffold of claim 9, wherein the void volume is between about 80% and 90% of a measurable volume of the composite scaffold.

11. 10. The composite scaffold of claim 9, wherein the void volume is between about 80% and 85% of a measurable volume of the composite scaffold.

12. Approximately 0.3m ２ / gram to 1.5m ２ 10. The composite scaffold of claim 9 having a surface area of ​​between 1000 and 1500 g / g.

13. A composite scaffold having a volume and a surface area, a microporous matrix having a multiplicity of interconnected pores that collectively define voids that open to an exterior surface of the microporous matrix; and a structure supporting the microporous matrix; the composite scaffold has a permeability of between about 1200 millidarcy and 3000 millidarcy; The scaffold.

14. 14. The composite scaffold of claim 13, having a permeability of between about 1400 millidarcy and 2600 millidarcy.

15. 14. The composite scaffold of claim 13, having a permeability of between about 1500 millidarcy and 2200 millidarcy.

16. The volume of the gap is about 3.0 cm ３ / gram to 9.0 cm ３ 14. The composite scaffold of claim 13, wherein the composite scaffold has a viscosity of between 1000:1 and 1000:

1.

17. The composite scaffold has a surface area of ​​about 0.3 m ２ / gram to 1.5m ２ 14. The composite scaffold of claim 13, wherein the composite scaffold has a viscosity of between 1000:1 and 1000:

1.

18. 1. A composite scaffold comprising: a microporous matrix having a multiplicity of interconnected pores that collectively define voids that open to an exterior surface of the microporous matrix and have a void volume; and a structure supporting the microporous matrix; the multiplicity of interconnected pores has a tortuosity on the order of 1 μm / μm to 50 μm / μm, where the tortuosity defines a ratio of an actual channel length to a linear distance between a first end and a second end of the microporous matrix; The scaffold.

19. 20. The composite scaffold of claim 18, wherein the multiple interconnected pores have a tortuosity on the order of 5 μm / μm to 30 μm / μm.

20. 20. The composite scaffold of claim 18, wherein the multiple interconnected pores have a tortuosity on the order of 6 μm / μm to 20 μm / μm.

21. A composite scaffold occupying a measurable volume, comprising: a microporous matrix having a multiplicity of interconnected pores that collectively define a void space having a surface area; and a structure supporting the microporous matrix; The surface area for the measurable volume of the void is approximately 5,000 cm ２ / cm ３ From 16,000 cm ２ / cm ３ Between The scaffold.

22. The surface area to measurable volume of the void is about 7,000 cm ２ / cm ３ From 14,000 cm ２ / cm ３ 22. The composite scaffold of claim 21 , wherein the composite scaffold is between

23. The surface area to measurable volume of the void is about 9,000 cm ２ / cm ３ From 12,000 cm ２ / cm ３ 22. The composite scaffold of claim 21 , wherein the composite scaffold is between

24. 1. A composite scaffold comprising: A support structure defining an interior space; and a microporous matrix disposed within the interior space of the support structure; The microporous matrix comprises a plurality of interconnected pores having a median pore size of between about 10 μm and 100 μm. The scaffold.

25. 25. The composite scaffold of claim 24, wherein the microporous matrix comprises a plurality of interconnected pores having a median pore size of between about 12 μm and 70 μm.

26. 25. The composite scaffold of claim 24, wherein the microporous matrix comprises a plurality of interconnected pores having a median pore size of between about 20 μm and 40 μm.

27. 1. A composite scaffold comprising: A support structure defining an interior space; and a microporous matrix disposed within the interior space of the support structure; the microporous matrix having a multiplicity of interconnected pores that collectively define a void space; At least about 60% of the voids include pores having a diameter dimension of 10 μm or more; The scaffold.

28. 30. The composite scaffold of claim 27, wherein at least about 70% of the voids comprise pores having a diameter dimension of 10 μm or greater.

29. 30. The composite scaffold of claim 27, wherein at least about 80% of the voids comprise pores having a diameter dimension of 10 μm or greater.

30. 30. The composite scaffold of any one of claims 1-29, having an elongation at tensile break of between about 20% and 125%.

31. 30. The composite scaffold of any one of claims 1-29, having an elongation at yield of between about 5% and 50%.

32. 30. The composite scaffold of any one of claims 1 to 29, having a stiffness on the order of 2.5 N / mm to 25 N / mm.

33. 30. The composite scaffold of any one of claims 1 to 29, having an ultimate strain of about 0.2 to 0.

7.

34. 30. The composite scaffold of any one of claims 1 to 29, having an ultimate strength of about 2.5 MPa to about 30 MPa.

35. 30. The composite scaffold of any one of claims 1 to 29, having an ultimate stress on the order of 2.5 MPa to 30 MPa.

36. 30. The composite scaffold of any one of claims 1 to 29, having an elastic modulus of about 2.5 MPa to about 70 MPa, where the elastic modulus is defined as the stress divided by the strain in a cross-sectional area of ​​the composite scaffold including the voids.

37. 30. The composite scaffold according to any one of claims 1 to 29, having an elastic modulus of about 150 MPa to 600 MPa, the elastic modulus being defined as the stress divided by the strain of the bulk material constituting the composite scaffold excluding the voids.

38. 30. The composite scaffold of any one of claims 1-29, having an ultimate load displacement on the order of 5mm to 50mm.

39. 30. The composite scaffold of any one of claims 1-29, having a yield displacement on the order of 1 mm to 8 mm.

40. 30. The composite scaffold of any one of claims 1 to 29, having a yield strength of about 20N to 70N.

41. 30. The composite scaffold of any one of claims 1 to 29, which may have a stiffness on the order of 2.5 N / mm to 25 N / mm.

42. 30. The composite scaffold of any one of claims 1 to 29, having an ultimate strain on the order of 20% to 70%.

43. 30. The composite scaffold of any one of claims 1 to 29, having an ultimate load of about 100N to 200N.

44. 9. The composite scaffold of any one of claims 1-3 and 8, wherein a surface area of ​​the composite scaffold is measured using mercury intrusion porosimetry.

45. 45. The composite scaffold of claim 44, wherein a surface area of ​​the composite scaffold comprises a surface area of ​​pores approximately 1 μm or greater in diameter.

46. The volume of the gap is about 3.0 cm ３ / gram to 9.0 cm ３ 20. The composite scaffold of claim 18, wherein the composite scaffold has a viscosity of between 1000:1 and 1000:

1.

47. The composite scaffold has a surface area of ​​about 0.3 m ２ / gram to 1.5m ２ 20. The composite scaffold of claim 18, wherein the composite scaffold has a viscosity of between 1000:1 and 1000:

1.

48. The volume of the gap is about 3.0 cm ３ / gram to 9.0 cm ３ 30. The composite scaffold of claim 27, wherein the composite scaffold is between 100 / gram.

49. The composite scaffold has a surface area of ​​about 0.3 m ２ / gram to 1.5m ２ 30. The composite scaffold of claim 27, wherein the composite scaffold is between 100 / gram.

50. The composite scaffold has a surface area of ​​about 0.3 m ２ / gram to 1.5m ２ 30. The composite scaffold of claim 27, wherein the composite scaffold is between 100 / gram.

51. A composite scaffold occupying a measurable volume, comprising: a microporous matrix having a multiplicity of interconnected pores that collectively define a void space having a surface area; and a structure supporting the microporous matrix; The surface area to measurable volume of the void is about 5,000 cm ２ / cm ３ From 16,000 cm ２ / cm ３ Between The scaffold.

52. The surface area to measurable volume of the void is about 7,000 cm ２ / cm ３ From 14,000 cm ２ / cm ３ 52. The composite scaffold of claim 51 , wherein:

53. The surface area to measurable volume of the void is about 9,000 cm ２ / cm ３ From 12,000 cm ２ / cm ３ 52. The composite scaffold of claim 51 , wherein:

54. 1. A composite scaffold comprising: a microporous matrix having a multiplicity of interconnected pores opening to an exterior surface of the microporous matrix and collectively defining a void space; and a structure supporting the microporous matrix; The composite scaffold has a surface area of ​​about 0.3 m ２ / gram to 15m ２ / grams, The scaffold.

55. 55. The composite scaffold of claim 54, wherein a surface area of ​​the composite scaffold is measured using a gas adsorption method.

56. 56. The composite scaffold of claim 55, wherein a surface area of ​​the composite scaffold is measured using krypton gas adsorption.

57. 55. The composite scaffold of claim 54, wherein a surface area of ​​the composite scaffold comprises a surface area of ​​pores approximately 1 μm or less in diameter.

58. 1. A composite scaffold comprising: a microporous matrix having a multiplicity of interconnected pores that collectively define voids that open to an exterior surface of the microporous matrix; and a structure supporting the microporous matrix; the composite scaffold having a measurable dry weight value representative of a weight of the composite scaffold in a substantially dry state and a measurable dry volume value representative of a volume of the composite scaffold in a substantially dry state; the weight value of the composite scaffold increases by between about 200% and 600% due to fluid absorption, thereby changing the dry volume value of the composite scaffold by between about 0% and 10%. The scaffold.

59. 60. The composite scaffold of claim 58, wherein the dry weight value of the composite scaffold increases by between about 300% and 600% due to fluid absorption, causing the dry volume value of the composite scaffold to change by between about 2% and 7%.

60. 60. The composite scaffold of claim 58, wherein the dry weight value of the composite scaffold increases by between about 300% and 600% due to fluid absorption, causing the dry volume value of the composite scaffold to change by between about 4% and 6%.

61. 60. The composite scaffold of claim 58, wherein the dry weight value of the composite scaffold increases by between about 300% and 600% due to fluid absorption, causing a dry length value of the composite scaffold to change by between about 0% and 3%.

62. 60. The composite scaffold of claim 58, wherein the dry weight value of the composite scaffold increases by between about 300% and 600% due to fluid absorption, causing a dry length value of the composite scaffold to change by between about 0% and 2%.

63. 1. A composite scaffold comprising: a microporous matrix having a multiplicity of interconnected pores that collectively define voids that open to an exterior surface of the microporous matrix; and a structure supporting the microporous matrix; the composite scaffold having a measurable dry weight value representative of a weight of the composite scaffold in a substantially dry state and a measurable dry length value representative of a dimensional parameter of the composite scaffold in a substantially dry state; the weight value of the composite scaffold increases by between about 200% and 600% due to fluid absorption, causing the dry length value of the composite scaffold to change by less than between about 0% and 3%. The scaffold.

64. 64. The composite scaffold of claim 63, wherein the dry weight value of the composite scaffold increases by between about 300% and 600% due to fluid absorption, causing the dry length value of the composite scaffold to change by between about 0% and 2%.

65. 64. The composite scaffold of claim 63, wherein the dry weight value of the composite scaffold increases by between about 500% and 600% due to fluid absorption, causing the dry length value of the composite scaffold to change by less than about 1%.

66. 64. The composite scaffold of claim 63, wherein the dry weight value of the composite scaffold increases by between about 300% and 600% due to fluid absorption, causing the dry volume value of the composite scaffold to change by between about 2% and 7%.

67. 64. The composite scaffold of claim 63, wherein the dry weight value of the composite scaffold increases by between about 300% and 600% due to fluid absorption, causing the dry volume value of the composite scaffold to change by between about 4% and 6%.

68. 1. A composite scaffold comprising: a microporous matrix having a multiplicity of interconnected pores that collectively define voids that open to an exterior surface of the microporous matrix; and a structure supporting the microporous matrix; the composite scaffold having a measurable dry weight value representative of a weight of the composite scaffold in a substantially dry state and a measurable cross-sectional profile value representative of dimensional parameters of the composite scaffold in a substantially dry state; the weight value of the composite scaffold increases by between about 300% and 600% due to fluid absorption, causing the cross-sectional profile value of the composite scaffold to change by between about 0% and 3%. The scaffold.

69. 70. The composite scaffold of claim 68, wherein the dry weight value of the composite scaffold increases by between about 300% and 600% due to fluid absorption, causing the cross-sectional profile value of the composite scaffold to change by between about 0% and 2%.

70. 70. The composite scaffold of claim 68, wherein the dry weight value of the composite scaffold increases by between about 500% and 600% due to fluid absorption, causing the cross-sectional profile value of the composite scaffold to change by less than about 1%.

71. 70. The composite scaffold of claim 68, wherein the dry weight value of the composite scaffold increases between about 300% and 600% due to fluid absorption, resulting in an increase in the cross-sectional profile value of the composite scaffold of between about 0% and 2%.

72. 70. The composite scaffold of claim 68, wherein the dry weight value of the composite scaffold increases by between about 500% and 600% due to fluid absorption, causing the cross-sectional profile value of the composite scaffold to increase by less than about 1%.

73. 1. A composite scaffold comprising: a microporous matrix having a multiplicity of interconnected pores that collectively define voids that open to an exterior surface of the microporous matrix; and a structure supporting the microporous matrix; The minimum dimension of the composite scaffold is a thickness dimension of about 1 mm or greater; and the composite scaffold has a swelling profile in which the measured wet thickness of the composite scaffold changes by no more than 10% as compared to the measured dry thickness of the composite scaffold; The scaffold.

74. 1. A composite scaffold comprising: a microporous matrix having a multiplicity of interconnected pores that collectively define voids that open to an exterior surface of the microporous matrix; and a structure supporting the microporous matrix; the composite scaffold having a measurable dry weight value representative of the weight of the composite scaffold in a substantially dry state; the microporous matrix is ​​less than about 6% of the dry weight of the composite scaffold; The scaffold.

75. A scaffold, a three-dimensional support structure having a length dimension defined by first and second ends thereof and a thickness dimension perpendicular to said length dimension defined by first and second outer layers separated by a space; and a plurality of spacer elements extending through the space and connecting the first outer layer and the second outer layer; the thickness dimension of the support structure changes by less than about 10% upon elongation of about 5% in the length dimension; The scaffold.

76. A scaffold, a three-dimensional support structure having a length dimension defined by first and second ends thereof and a cross-sectional area perpendicular to said length dimension defined at least in part by first and second outer layers bounded by a space; and a plurality of spacer elements extending through the space and connecting the first outer layer and the second outer layer; the cross-sectional area changes by less than about 35% upon elongation of about 13% in the linear dimension; The scaffold.

77. A scaffold, a three-dimensional support structure having a length dimension defined by first and second ends thereof and a width dimension perpendicular to said length dimension defined at least in part by first and second outer layers; the first and second outer layers being separated by a space and further defining a thickness dimension perpendicular to the length and width dimensions; and a plurality of spacer elements extending through the space and connecting the first outer layer and the second outer layer; said width dimension changes by less than about 5% upon elongation of about 13% in said length dimension; The scaffold.

78. 1. A scaffold structure comprising: first and second outer layers having a length dimension defined by their respective first and second ends and defining an interior space therebetween; wherein each of the first and second outer layers includes a plurality of interconnected wales extending substantially parallel to a respective length dimension; a plurality of spacer elements extending through the interior space substantially perpendicular to the respective length dimensions and attached to each of the first and second outer layers adjacent one of the plurality of wales, wherein the plurality of spacer elements at least partially divide the interior space into a plurality of channels extending along the respective length dimensions of the first and second outer layers; The structure comprising:

79. 80. The scaffold structure of claim 78, wherein each of first and second outer layers has a corresponding number of wales, and wherein the plurality of spacer elements are attached to corresponding wales of each of the first and second outer layers.

80. 80. The scaffold structure of claim 78, wherein the plurality of spacer elements comprises spacer yarns.

81. 80. The scaffold structure of claim 78, wherein a distance between spacer elements along a wale of the first or second outer layer is between about 100 μm and 2500 μm.

82. 80. The scaffold structure of claim 78, wherein a distance between wales of the first or second outer layer is between about 200 μm and 5000 μm.

83. 80. The scaffold structure of claim 78, wherein the plurality of spacer elements have a length extending between the first and second outer layers of between about 100 μm and 5000 μm.

84. 80. The scaffold structure of claim 78, wherein the wale of one of the first and second outer layers comprises pillar stitches and axial lay-in yarns.

85. 85. The scaffold structure of any one of claims 75-84, wherein the scaffold has an elongation at tensile break of between about 20% to 125%.

86. 85. The scaffold structure of any one of claims 75-84, wherein the scaffold has an elongation at yield point of between about 5% to 50%.

87. 85. The scaffold structure of any one of claims 75-84, wherein the scaffold has a stiffness on the order of 2.5 N / mm to 25 N / mm.

88. 85. The scaffold structure of any one of claims 75-84, wherein the scaffold has an ultimate strain on the order of 20% to 70%.

89. The scaffold structure of any one of claims 75-84, wherein the scaffold has an ultimate stress on the order of 2.5 MPa to 30 MPa.

90. The scaffold structure of any one of claims 75-84, wherein the scaffold has a yield stress of about 2.5 MPa to 30 MPa.

91. 85. The scaffold structure of any one of claims 75 to 84, wherein the scaffold has an elastic modulus of about 2.5 MPa to about 70 MPa, where the elastic modulus is defined as the stress divided by the strain of a cross-sectional area of ​​the scaffold including the voids.

92. The scaffold structure according to any one of claims 75 to 84, wherein the scaffold has an elastic modulus of about 150 MPa to 600 MPa, the elastic modulus being defined as stress divided by strain of a bulk material constituting the scaffold excluding the voids.

93. 85. The scaffold structure of any one of claims 75-84, wherein the scaffold can have a stiffness on the order of 2.5 N / mm to 250 N / mm.

94. 85. The scaffold structure of any one of claims 75-84, wherein the scaffold has an ultimate strain on the order of 20% to 70%.

95. 85. The scaffold structure of any one of claims 75-84, wherein the scaffold has a tensile strength on the order of 0.07 grams-force / denier to 1.10 grams-force / denier.

96. 85. The scaffold of any one of claims 75-84, having a tensile strength at break of about 0.3 grams-force / denier to 2 grams-force / denier.

97. 85. The scaffold of any one of claims 75-84, wherein at least a portion of the scaffold is coated with a hydrophilic solution.

98. 98. The scaffold of claim 97, wherein the hydrophilic solution comprises polyethylene glycol (PEG).

99. 98. The scaffold of claim 97, comprising monofilament, multifilament, or textured yarns, or any combination thereof, knitted into a three dimensional structure.

100. 85. The scaffold of any one of claims 75-84, comprising any combination of bioabsorbable polymers, natural polymers, and / or additives.

101. 101. The scaffold of claim 100, comprising any of a homopolymer, copolymer, or polymer blend of any of the following: polylactic acid, polyglycolic acid, polycaprolactone, polydioxanone, polyhydroxyalkanoic acid, polyanhydrides, poly(orthoesters), polyphosphazenes, poly(amino acids), polyalkylcyanoacrylates, poly(propylene fumarate, trimethylene carbonate, poly(glycerol sebacate), poly(glyconate), poly(ethylene glycol), poly(vinyl alcohol), and polyurethane, or any combination thereof.

102. 85. The scaffold structure of any one of claims 75 to 84, wherein the composite scaffold is 3 mm ２ From 3000mm ２ wherein the cross-sectional area defines an area of ​​a two-dimensional shape of the scaffold at a point perpendicular to a length of the scaffold, and wherein the cross-sectional area changes by less than about 10% at a 5% elongation.

103. A scaffold, a three-dimensional support structure having a length dimension defined by first and second ends thereof and a thickness dimension perpendicular to said length dimension defined by first and second outer layers separated by a space; and a plurality of spacer elements extending through the space and connecting the first outer layer and the second outer layer; The surface area of ​​the void relative to the measurable volume is 500 cm ２ / cm ３ From 7,000 cm ２ / cm ３ To an extent, The scaffold.

104. 1. A composite scaffold comprising: a microporous matrix having a multiplicity of interconnected pores that collectively define voids that open to an exterior surface of the microporous matrix; and a structure supporting the microporous matrix; The composite scaffold has a density of about 0.05 g / cc to about 0.75 g / cc, the density being defined as the mass per unit volume of the composite scaffold; The scaffold.

105. 105. The composite scaffold of claim 104, having a density on the order of 0.10 g / cc to 0.50 g / cc.

106. 105. The composite scaffold of claim 104, having a density on the order of 0.15 g / cc to 0.25 g / cc.

107. 1. A composite scaffold comprising: a three-dimensional support structure having a length dimension defined by first and second ends thereof, the three-dimensional support structure being defined by first and second outer layers bounded by an interior space; a plurality of spacer elements extending through the space and connecting the first outer layer and the second outer layer; a microporous matrix disposed in the interior space and having a number of interconnected pores that collectively define a void between the first end and the second end of the support structure. The scaffold.

108. 108. The composite scaffold of claim 107, wherein at least about 60% of the voids comprise pores having a radial dimension of at least 10 μm or greater.

109. The volume of the gap is about 3.0 cm ３ / gram to 9.0 cm ３ 108. The composite scaffold of claim 107, wherein the composite scaffold is between 1 / gram.

110. 3mm ２ From 250 mm ２ 110. The composite scaffold of any one of claims 104-109, wherein the cross-sectional area changes by less than about 17% at a strain rate of 13%.

111. The composite scaffold has a surface area of ​​about 0.3 m ２ / gram to 1.5m ２ 108. The composite scaffold of claim 107, wherein the composite scaffold is between 1 / gram.

112. 1. A composite scaffold comprising: a microporous matrix having a multiplicity of interconnected pores opening to an exterior surface of the microporous matrix and collectively defining a void space; and a structure supporting the microporous matrix; the composite scaffold has a substantially rectangular cross-section defined by an outer portion; a plurality of said interconnected pores adjacent one of the outer portions have a largest dimension oriented toward the one outer portion; The scaffold.

113. 113. The composite scaffold of claim 112, wherein the plurality of interconnected pores have a maximum dimension oriented at about 45° to 135° to one outer side.

114. 113. The composite scaffold of claim 112, wherein the plurality of interconnected pores have a maximum dimension oriented on the order of 60 degrees to 120 degrees relative to one outer side.

115. 113. The composite scaffold of claim 112, wherein the plurality of interconnected pores have a maximum dimension oriented at about 75° to 105° to an outer side.

116. 113. The composite scaffold of any one of claims 104-112, having an ultimate strain of between about 0.2 and 1.

25.

117. 1. A composite scaffold comprising: a microporous matrix having a multiplicity of interconnected pores opening to an exterior surface of the microporous matrix and collectively defining a void space; and a structure supporting the microporous matrix; The volume of the gap is about 3.0 cm ３ / gram to 9.0 cm ３ / grams, The scaffold.

118. The volume of the gap is about 3.5 cm ３ / gram to 7.0 cm ３ 118. The composite scaffold of claim 117, wherein the composite scaffold is between 1 / gram.

119. The volume of the gap is about 4.0 cm ３ / gram to 5.0 cm ３ 118. The composite scaffold of claim 117, wherein the composite scaffold is between 1 / gram.

120. 113. The composite scaffold of any one of claims 104-112, having an ultimate stress on the order of 2.5 MPa to 30 MPa.

121. 113. The composite scaffold of any one of claims 104-112, having a yield stress on the order of 2.5 MPa to 30 MPa.

122. 113. The composite scaffold of any one of claims 104-112, wherein the composite scaffold has an elastic modulus on the order of 2.5 MPa to 70 MPa, where the elastic modulus is calculated using a cross-sectional area of ​​material including the composite scaffold and the voids.

123. 113. The composite scaffold of any one of claims 104-112, wherein the composite scaffold has an elastic modulus on the order of 150 MPa to 600 MPa, where the elastic modulus is calculated using a cross-sectional area of ​​only material comprising the composite scaffold.

124. 120. The composite scaffold of any one of claims 104-119, wherein the structure supporting the microporous matrix comprises a three-dimensional woven structure.

125. 120. The composite scaffold of any one of claims 104-119, wherein the microporous matrix comprises either a sponge, a foam, or textured fibers or yarns, or any combination thereof.

126. 126. The composite scaffold of claim 125, wherein the microporous matrix comprises a lyophilized sponge, an open cell extruded foam, a particle infused sponge, or any combination thereof.

127. 126. The composite scaffold of claim 125, wherein the microporous matrix comprises any of a sponge, a foam, or textured fibers or yarns disposed within the scaffold by any of knitting, weaving, freeze drying, particle infusion, open cell extrusion, solution casting, solid foaming, and crosslinking, or any combination thereof.

128. 120. The composite scaffold of any one of claims 104-119, wherein the microporous matrix comprises one of collagen and a hydrogel.

129. 120. The composite scaffold of any one of claims 104-119, comprising monofilaments, multifilaments, or textured yarns, or any combination thereof, knitted into a three dimensional structure.

130. 120. The composite scaffold of any one of claims 104-119, comprising any combination of synthetic bioabsorbable polymers, natural polymers, and / or additives.

131. 131. The composite scaffold of claim 130 comprising any of a homopolymer, copolymer, or polymer blend of any of the following: polylactic acid, polyglycolic acid, polycaprolactone, polydioxanone, polyhydroxyalkanoic acid, polyanhydrides, poly(orthoesters), polyphosphazenes, poly(amino acids), polyalkylcyanoacrylates, poly(propylene fumarate, trimethylene carbonate, poly(glycerol sebacate), poly(glyconate), poly(ethylene glycol), poly(vinyl alcohol) and polyurethane, or any combination thereof.

132. A composite scaffold occupying a measurable volume, comprising: a microporous matrix having a multiplicity of interconnected pores that collectively define a void space having a surface area; and a structure supporting the microporous matrix; The surface area to measurable volume of the void is about 5,000 cm ２ / cm ３ From 16,000 cm ２ / cm ３ Between The scaffold.

133. The surface area to measurable volume of the void is about 7,000 cm ２ / cm ３ From 14,000 cm ２ / cm ３ 133. The composite scaffold of claim 132, wherein:

134. The surface area to measurable volume of the void is about 9,000 cm ２ / cm ３ From 12,000 cm ２ / cm ３ 133. The composite scaffold of claim 132, wherein:

135. 1. A method for repairing a ligament or tendon injury using a composite scaffold, comprising: A) providing a composite scaffold, said composite scaffold comprising: i) first and second layers spaced apart to define an interior space therebetween, and a plurality of spacer elements extending through the interior space and attached to the first and second layers; and ii) a microporous matrix having a multiplicity of interconnected pores disposed within said interior space; Contains, and B) pretensioning the composite scaffold along its length dimension; C) Attaching the composite scaffold to an allograft or autograft tendon, or to a damaged or torn ligament or tendon. The method comprising:

136. 1. A method of fabricating a composite scaffold, comprising: A) constructing a three-dimensional support structure extending along a length dimension between a first end and a second end thereof and defining an interior surface within said support structure; B) forming a microporous matrix within said interior surface, said microporous matrix having a multiplicity of interconnected pores in fluid communication with an exterior surface of said support structure; Including, the plurality of interconnected pores being oriented relative to a dimensional characteristic of the support structure; The method.

137. 137. The method of claim 136, wherein the plurality of interconnected pores are oriented radially inward from an outer surface of the support structure toward the interior space.

138. 137. The method of claim 136, wherein the plurality of interconnected pores are oriented toward a length dimension of the support structure.

139. The support structure has an outer profile, and B) B1) placing the support structure in a mold filled with a solution having a cross-sectional profile that at least partially mimics an exterior profile of the support structure; and B2) modifying the temperature of the mold to induce crystallization of the solution within the interior space of the support structure.

137. The method of claim 136, comprising:

140. C) at least partially covering the support structure with a hydrophilic material.

137. The method of claim 136, further comprising:

141. A) A1) assembling a scaffold including first and second layers spaced apart to define an interior space therebetween, but attached together by a plurality of spacer elements extending through said interior space.

137. The method of claim 136, comprising:

142. The method of claim 140, wherein at least partially covering the three-dimensional support structure with a hydrophilic material occurs prior to disposing a microporous matrix within the internal space.

143. 141. The method of claim 140, wherein the hydrophilic material comprises at least in part polyethylene glycol (PEG).

144. The method of claim 2 , wherein the microporous matrix comprises one of collagen and a hydrogel.

145. 137. The method of claim 136, wherein the support structure comprises a scaffold comprising any combination of synthetic bioabsorbable polymers, natural polymers, and / or additives.

146. 146. The method of claim 145, wherein the scaffold comprises monofilaments, multifilaments, or multifilaments and textured yarns, or any combination thereof, knitted into a three dimensional structure.

147. 137. The method of claim 136, wherein the microporous matrix comprises either a sponge, a foam, or textured fibers or yarns, or any combination thereof.

148. 137. The method of claim 136, wherein the microporous matrix comprises a freeze-dried sponge, an open-cell extruded foam, a particle-infused sponge, or any combination thereof.

149. 137. The biomimetic scaffold of claim 136, wherein B) comprises forming a microporous matrix by any of freeze-drying, particle leaching, open-cell extrusion, solution casting, solid foaming, and cross-linking.

150. 1. A composite scaffold comprising: a support structure defining an interior space and having an exterior profile extending along a length dimension between a first end and a second end thereof; a microporous matrix disposed within the interior space having a multiplicity of interconnected pores that open to an exterior of the support structure; a plurality of interconnected pores oriented relative to a dimensional characteristic of the support structure; The scaffold.

151. 151. The composite scaffold of claim 150, wherein the plurality of interconnected pores are oriented radially inward from an exterior surface of the support structure toward the interior space.

152. 151. The composite scaffold of claim 150, wherein the plurality of interconnected pores are oriented toward a length dimension of the support structure.

153. 151. The composite scaffold of claim 150, wherein the support structure has a substantially rectangular shaped cross-sectional exterior profile.

154. 151. The composite scaffold of claim 150, wherein the support structure has a cross-sectional exterior profile that is substantially circular in shape.

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