WO2025096889A1 - Synthetic scaffold and uses thereof - Google Patents

Abstract

A synthetic scaffold for ligament and soft tissue regeneration combines a three-dimensional biodegradable structure with a removable spacer tube that enables the incorporation of autograft, allograft, or xenograft tissue. The design features a hollow core created by the spacer, allowing for easy insertion of tissue grafts while providing structural support through the braided component made from poly-L-lactic acid (PLLA) and/or poly(DL)-lactic acid (PLA). In proof-of-concept testing using a rabbit model, the scaffold demonstrated superior mechanical properties compared to standalone autografts, with peak loads of approximately 500N versus 58N. This innovation addresses limitations in current anterior cruciate ligament (ACL) reconstruction techniques by offering enhanced mechanical support and improved biological healing environment.

Description

SYNTHETIC SCAFFOLD AND USES THEREOF

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63/595,000, filed November 1, 2023, which is incorporated by reference herein in its entirety.

GOVERNMENT SUPPORT

[0002] This invention was made with government support under AR079114 awarded by the National Institutes of Health, and 1332329 awarded by the National Science Foundation. The government has certain rights in the invention.

FIELD OF THE DISCLOSURE

[0003] The invention disclosed herein relates to a synthetic scaffold and uses thereof, and in particular use as augmentation in soft tissue and/or ligament regeneration.

BACKGROUND

[0004] In orthopedic reconstruction, surgeons often replace damaged tissue resulting from trauma, pathological degeneration, or congenital deformity with autogenous grafts.

Reconstructive surgery is based upon the principle of replacing these types of defective tissues with viable, functioning alternatives. The anterior cruciate ligament (ACL) is an essential support structure for the knee joint and is commonly injured in athletes. A fully synthetic graft for ACL reconstruction is yet to gain FDA approval with prior biodegradable grafts issues with graft rupture.

[0005] There is an immediate need for novel synthetic, biodegradable scaffold or device that offers additional structural support.

SUMMARY

[0006] The present disclosure provides, in at least one aspect, synthetic scaffold devices including a sleeve; and a spacer positioned within the sleeve to create a hollow space configured to receive a tissue graft.

[0007] In some embodiments, the spacer comprises at least one of a tube, a rod, a spring, or combinations thereof. In some embodiments, the spacer comprises a biodegradable and biocompatible material selected from the group consisting of poly-L-lactic acid (PLLA), poly(DL)-lactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), and combinations thereof. In some embodiments, the spacer is removable. In some embodiments, the spacer is expandable. In some embodiments, the expandable spacer comprises at least one of: an inflatable component configured to be expanded using a biocompatible fluid; or a mechanical expansion mechanism comprising at least one of a collapsible mesh structure or telescoping segments.

[0008] In some embodiments, the sleeve comprises a component/s (also called as a sleeve component) that is braided, woven, knitted or any combination thereof. In some embodiments, the sleeve comprises a braided component. In some embodiments, the sleeve comprises a woven component. In some embodiments, the sleeve comprises a knitted component. In some embodiments, the sleeve comprises a braided, a woven, and a knitted component. In some embodiments, the sleeve comprises a braided and a woven component. In some embodiments, the sleeve comprises a braided and a knitted component. In some embodiments, the sleeve comprises a woven and a knitted component. In some embodiments, the sleeve comprises biodegradable polymer fibers comprising at least one of poly-L-lactic acid (PLLA), poly(DL)- lactic acid (PLA), or combinations thereof. In some embodiments, the sleeve component terminates in first and second attachment ends and includes a middle region that differs from both of said attachment ends in at least one of size, braiding angle, porosity, or mechanical strength.

[0009] In some embodiments, the device further comprises a tissue graft positioned within the hollow space, wherein the tissue graft comprises at least one of an autograft, an allograft, or a xenograft.

[0010] The present disclosure provides, in at least one aspect, methods of making a synthetic scaffold device, including forming a braided component, positioning a spacer within the sleeve component during formation to create a hollow space, and configuring the hollow space to receive a tissue graft, wherein the spacer comprises either a removable spacer configured to be removed before or during implantation, or a biodegradable spacer configured to degrade after implantation. [0011] In some embodiments, when the spacer is biodegradable, the method further includes selecting the biodegradable spacer to have a degradation rate coordinated with tissue healing timeline.

[0012] In some embodiments, the method further includes removing the spacer when the spacer is removable, inserting a tissue graft into the hollow space, and implanting the synthetic scaffold device and tissue graft in a subject.

[0013] The present disclosure provides, in at least one aspect, synthetic scaffold systems including a sleeve, a spacer positioned within the sleeve, wherein the spacer includes either a removable spacer configured to be removed to create a hollow space for receiving a tissue graft, or a biodegradable spacer configured to degrade in vivo after implantation, and a tissue graft configured to be received within the hollow space.

[0014] In some embodiments, when the spacer is biodegradable, the biodegradable spacer comprises a material selected from the group consisting of poly-L-lactic acid (PLLA), poly(DL)- lactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), and combinations thereof.

[0015] In some embodiments, the tissue graft includes at least one of a heterogeneous autograft, a bone-patella-bone autograft, or an Achilles allograft or other soft tissue graft such as tibialis anterior, hamstring, quad tendon.

[0016] In some embodiments, the sleeve comprises a mixture of high-density and low- density biodegradable polymer fibers configured to modulate degradation rate in vivo.

[0017] The present disclosure provides, in at least one aspect, methods of treating a subject including providing a synthetic scaffold device comprising a braided component, and a spacer positioned within the sleeve, when the spacer is removable, removing the spacer to create a hollow space, when the spacer is biodegradable, maintaining the spacer within the sleeve, inserting a tissue graft into the hollow space, and implanting the synthetic scaffold device and tissue graft to repair, reconstruct, or replace a ligament or tendon in the subject.

[0018] In some embodiments, when the spacer is biodegradable, the method further comprises selecting the biodegradable spacer to have a degradation profile matched to a tissue healing timeline.

[0019] In some embodiments, the method includes incorporating a bioactive material into the synthetic scaffold device prior to implanting. [0020] In some embodiments, when the spacer is removable, the tissue graft and synthetic scaffold device are pre-assembled after spacer removal and stored prior to implanting, and when the spacer is biodegradable, the tissue graft, spacer, and synthetic scaffold device are preassembled and stored prior to implanting.

[0021] These and other aspects of the present invention are described in more detail below.

BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 is a synthetic scaffold and method of manufacture in accordance with the present disclosure.

[0023] Figure 2 is a method of incorporating bioactive materials to a synthetic scaffold in accordance with the present disclosure.

[0024] Figure 3 depicts individual steps of employing a mold to form a synthetic scaffold in accordance with the present disclosure.

[0025] Figure 4 provides a stress strain graph of an autograft and LUCA device on the left, and a stress-strain graph of a Karakow suture and LUCA device (Achilles Tendon Repair) on the right.

[0026] Figure 5 is a stress strain graph comparing the mechanical properties of different number of plies in a synthetic scaffold in accordance with the present disclosure.

[0027] Figure 6 provides a visual illustration of the braiding procedure (Right) and the final product including a braid and a spacer such as tubing (Left).

[0028] Figure 7 provides a visual illustration of a synthetic scaffold with an expandable spacer in accordance with the present disclosure.

[0029] Figure 8 depicts the different elements of a LUCA graft in accordance with the present disclosure.

[0030] Figure 9 depicts isolation of rabbit’s autograft for fabrication of a synthetic scaffold in accordance with the present disclosure.

[0031] Figure 10 depicts the process of integrating the autograft into the braid involved the use of a suture needle. One end of the autograft was affixed to the suture yarn, and subsequently, the graft was threaded through the tubing. Following this, the tubing was extracted, leaving the autograft positioned at the center of the braid, resulting in the final LUCA graft. [0032] Figure 11 depicts the surgical reconstruction of the rabbit’ s ACL using cadaveric tissue. The LUCA graft was implanted subsequent to the creation of bone tunnels.

[0033] Figure 12 depicts a LUCA graft inside of knee after reconstruction surgery on rabbit’s cadaver.

[0034] Figure 13 is a stress-strain graph of the LUCA scaffold.

[0035] Before any embodiments are explained in detail, it is to be understood that the present disclosure is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the accompanying drawings. The present disclosure is capable of other embodiments and of being practiced or of being carried out in various ways.

DETAILED DESCRIPTION

[0036] Before the disclosed processes and materials are described, it is to be understood that the aspects described herein are not limited to specific embodiments, or examples, and as such can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and, unless specifically defined herein, is not intended to be limiting.

[0037] U.S. Pat. No. 8,945,218 discloses a degradable, polymeric fiber-based, three- dimensional braided ligament or tendon scaffold for use as graft materials in ligament and tendon repair, reconstruction and replacement, however, soft tissues like autograft, allograft, and xenograft cannot be used with this braided scaffold as it lacks additional support for the implanted soft tissue. This important drawback is overcome by the novel design of the disclosed scaffold herein.

[0038] Figure 1 provides a representative embodiment of the disclosed scaffold and method. In an aspect, disclosed is a synthetic scaffold (or device) including a synthetic, biodegradable sleeve including a braided component, and a spacer such as a tube. The “spacer” as used herein means a device or a piece used to create or maintain a desired amount of space (for example, space within a braided component to hold a ligament and/or soft tissue such as autograft, allograft, and xenograft). In an aspect, disclosed is a synthetic scaffold/device including a degradable, polymeric, fiber-based, three-dimensional braid and a spacer. In an aspect, disclosed is synthetic scaffold/device including a degradable, polymeric, fiber-based, three-dimensional braid; a spacer; and a soft tissue such as autograft, allograft, and xenograft.

[0039] Any suitable spacer can be used, some nonlimiting examples of the spacer are a tube, a rod, a spring, or a combination thereof. In an embodiment, the spacer is biocompatible. In an embodiment, the spacer is removable. In an embodiment, the spacer is a tube. Any suitable tube can be used. In an embodiment, the tube is made from biocompatible materials. In an embodiment, the spacer is a rod. In an embodiment, the spacer is expandable. The expandable spacer may comprise an inflatable component that can be expanded using air, saline, or other biocompatible fluids to achieve different diameters. In another embodiment, the expandable spacer may include a mechanical expansion mechanism, such as a collapsible mesh structure or telescoping segments, that can be adjusted to various diameters through mechanical actuation. This expandability feature allows surgeons to customize the internal diameter of the scaffold to accommodate different sizes of autografts, allografts, or xenografts during the surgical procedure. The expandable spacer can be designed to maintain its expanded configuration temporarily during graft placement and then be deflated or collapsed for removal, leaving the graft securely positioned within the braided structure.

[0040] In an aspect, disclosed is synthetic scaffold/device including a degradable, polymeric, fiber-based, three-dimensional braid (a sleeve) and a soft tissue such as autograft, allograft, and xenograft. In an aspect, disclosed is a synthetic scaffold/device that offer additional structural support. In an aspect, disclosed is a synthetic scaffold/device that offers a favorable biologic environment for healing and soft tissue and/or ligament regeneration. Any suitable soft tissue and/or ligament can be used. Some nonlimiting examples of the soft tissue and ligaments include a heterogeneous or other type of autograft/allograft - such as a bone-patella-bone autograft that includes bony ends and a tendon in between, or an achilles allograft that includes a bone plug on one end and tendon on the other end or a hamstring or quad tendon allograft/autograft. The device can incorporate and conform to these diverse uses of grafts.

[0041] In an embodiment, the scaffold is for a soft tissue and/or ligament regeneration in a subject. In an embodiment, the scaffold is for a soft tissue regeneration such as muscle or tendon in a subject. In an embodiment, the scaffold is for ligament regeneration in a subject. In an embodiment, the scaffold is for nerve, vascular, fascial and/or connective tissue regeneration. In an embodiment, the sleeve/braid includes biodegradable polymer fibers. In an embodiment, the fiber includes at least one lactic acid polymer. In one embodiment, the spacer such as a tube within the braided component may possess sufficient biocompatibility to avoid interfering with autografts, allografts, or xenografts, thereby preventing toxicity. In another aspect, the spacer’s flexibility enables it to be gathered by a collector post-braiding, facilitating continuous production. In an embodiment, the spacer’s (such as a tubing) inner diameter is large enough to allow the insertion of autograft, allograft, and xenograft.

[0042] In some embodiments, the scaffold may incorporate bioactivc materials to enhance tissue regeneration and integration. As shown in Figures 2 and 3, incorporating bioactive materials may involve several discrete steps. First, a mold is created to form the desired spacer configuration. The mold is then filled with a selected bioactive solution or hydrogel, such as collagen or gelatin. The graft is carefully positioned within the mold containing the bioactive material. For hydrogel-based bioactive materials, the combined device and hydrogel can be removed from the mold and used directly in surgical procedures. For other bioactive solutions, the graft and bioactive material combination undergoes a drying process. Once the drying process is complete, the final product - consisting of the graft integrated with the bioactive materials - is removed from the mold and is ready for use. This process ensures uniform distribution and incorporation of the bioactive materials throughout the scaffold structure.

[0043] When incorporating bioactive materials, the processing method varies depending on the type of bioactive material used. For hydrogel-based materials, the device-hydrogel combination can be utilized immediately after removal from the mold, maintaining the hydrogel’s natural properties. For other bioactive solutions, various drying methods may be employed, including: lyophilization (preserves the structural integrity of the bioactive materials while creating a porous structure), air drying (allows for gradual dehydration under controlled conditions), or oven drying (provides accelerated drying under precise temperature control). The choice of drying method is determined by the specific properties of the bioactive material and the desired final characteristics of the scaffold.

[0044] In an embodiment, the braid includes at least one biodegradable polymer. In an embodiment, the biodegradable polymer includes poly-L-lactic acid (PLLA) and poly(DL)-lactic acid (PLA). In an embodiment, the scaffold/device allows for an incorporation of a host tissue autograft, allograft, or xenograft. In an embodiment, the braid is prepared by a three dimensional braiding technique. In an embodiment, the braid includes biodegradable polymer fibers, wherein the braid terminates in three-dimensional, braided first and second attachment ends and the braid includes a three-dimensional, braided middle region that differs from both of said attachment ends in size, braiding angle, porosity, and mechanical strength to facilitate a differential cellular response in said middle region as compared with said first and second attachment ends.

[0045] In an embodiment, the sleeve/braid has a substantially circular cross-section. In an embodiment, the sleeve/braid has a substantially rectangular cross- section. In an embodiment, the biodegradable polymer fibers include poly-L-lactic acid (PLLA), poly(DL)-lactic acid (PLA), or a combination thereof. In an embodiment, the biodegradable polymer fibers include poly-L- lactic acid (PLLA). In an embodiment, the biodegradable polymer fibers include poly(DL)-lactic acid (PLA). In an embodiment, the biodegradable polymer fibers include poly-L-lactic acid (PLLA) and poly(DL)-lactic acid (PLA). In an embodiment, the sleeve/braid is formed from a plurality of bundles comprising about 5 to about 120 fibers per bundle. In an embodiment, the sleeve/braid is formed from a plurality of bundles comprising about 10 to about 60 fibers per bundle. In an embodiment, the braid is formed using a three dimensional braiding technique that utilizes a row and column braider. In an embodiment, the scaffold is adapted to repair, reconstruct, or replace an anterior cruciate ligament (ACL). In an embodiment, the said braid terminates in three-dimensional, braided first and second attachment ends and said braid includes a three-dimensional, braided middle region that differs from both of said attachment ends in size, braiding angle, porosity, and mechanical strength.

[0046] In an aspect, disclosed is a method including implanting a scaffold disclosed herein in a subject or a patient in need thereof. In an embodiment, the method includes implanting the scaffold to repair, reconstruct, or replace an anterior cruciate ligament of the subject. In an embodiment, the braid is formed using a three dimensional braiding technique that utilizes a rectangular and/or circular braider. In an embodiment, the method includes implanting the scaffold to repair, reconstruct or replace other soft tissues such as muscle, tendon, including but not limited to the rotator cuff or a combination thereof. In an embodiment, the braid has a substantially circular cross-section. In an embodiment, the braid has a substantially rectangular cross-section. In an embodiment, the braid includes braided bundles of multi-filament, biodegradable polymer fibers.

[0047] In certain embodiments, the disclosed scaffold can augment traditional ACL reconstruction by providing early mechanical strength, support, and other biologic healing properties to facilitate healing, regeneration, and/or ligamentization to the tendon autograft, in addition to allograft, and xenograft. In certain embodiments, the device can be used for muscle, tendon, ligament, bone, nerve, vessel, and/or cutaneous regeneration. In an embodiment, a tom rotator cuff tendon or other tendon or ligament can be repaired with the device described herein where the device can attach to, wrap around, or otherwise combine with the tendon or ligament at the site of repair to facilitate both increased mechanical strength and other biologic healing properties to facilitate healing and/or regeneration. In certain embodiments, the scaffold can decrease morbidity intra-operatively, and post-operatively prevent the need for revision surgery. Figure 4 illustrates how an augmented graft of the present disclosure compares in mechanical strength to conventional autograph techniques.

[0048] In an aspect, the device may significantly decrease post-operative morbidity. In an aspect, the synthetic scaffold/device offers a favorable biologic environment for healing and soft tissue and/or ligament regeneration. Post-operative rehabilitation and time to return to activity can be significantly decreased if the patient has the device implanted, which can allow early structural support to the knee joint while the autograft, allograft, or xenograft matures. The terms Autograft, allograft, and xenograft as used herein have the same meaning as commonly understood by one of ordinary skill in the art. For example, autograft tissue is harvested from the patient/ subject and allograft tissue is taken from a donor or a human cadaver used to reconstruct or replace the anterior cruciate ligament, while xenograft tissue is from animal tissue.

[0049] The present disclosure provides a new geometric design and method of fabrication to allow for the protection and incorporation of autograft, allograft, and xenograft. In instances, a standalone synthetic graft is used for ACL reconstruction/replacement without any spacer or other tissue resulting suboptimal outcomes and long recovery times. The present disclosure provides a significant improvement to this technology.

[0050] The present disclosure has an improved design that will allow for incorporation of autografts, allografts, and xenografts. In an embodiment, the disclosed design can also be used for soft tissue repair such as but not limited to ACL repair. The scaffold/device described herein can be wrapped around, fixed to, or otherwise incorporated with host tissue that is to be repaired in situ/in vivo with known surgical techniques. In an embodiment, the device provides additional structural support and/or biologic properties to facilitate healing of a repaired ligament, ACL or other soft tissue. [0051] In an embodiment, the disclosed scaffold/device includes poly-L-lactic acid (PLLA) and/or poly(DL)-lactic acid (PLA) braided component that has a unique structure to allow for the incorporation of host tissue autograft, allograft, or xenograft. The scaffold/device includes a braided component that serves as a structural support, with a spacer such as a tube placed at the center of the braid. The unique structure includes a hollow space created by the spacer such as a tube that allows placement of a soft tissue like autograft, allograft, or xenograft. To construct the example scaffold, a braiding machine loaded with 24 yarn bobbins was employed. The spacer such as a tube was positioned within the yarns at the center during the braiding process. As shown in Figure 5, by changing the number of plies in the yarns, the mechanical properties can be controlled. A higher number of plies results in higher mechanical strength, but the degradation time also increases.

[0052] In an embodiment, the scaffold may be further enhanced through the incorporation of bioactive materials. The process begins with the creation of a customized mold designed to accommodate both the spacer and the intended bioactive materials. The mold’s dimensions and configuration are optimized to ensure uniform distribution of the bioactive materials throughout the scaffold structure. Various bioactive solutions or hydrogels may be utilized, including but not limited to collagen and gelatin, each selected based on their specific regenerative properties and compatibility with the intended tissue type.

[0053] Figure 6 provides an example fabrication process and resulting possible embodiment of the scaffold, including the braided component or structure and the spacer such as tube. The spacer such as tube enables surgeons to easily insert autografts, allografts, xenografts, or a combination thereof. In an embodiment, the spacer is designed to be expandable through either fluid inflation or mechanical means, as shown in Figure 7. The expandable design allows the spacer to be adjusted to various diameters, accommodating different graft sizes and ensuring optimal fit within the braided structure. When using fluid expansion, the spacer can be inflated with sterile saline or air through a valve system, achieving precise diameter control. Mechanical expansion may utilize telescoping segments or expandable mesh designs that can be locked at desired diameters. This adjustability feature provides surgeons with greater flexibility during graft placement and ensures proper tissue positioning. Once the graft material is inserted, the spacer such as tube can be subsequently removed, either by deflation in the case of inflatable designs or by collapsing mechanical expansion mechanisms. The spacer such as tube helps to create a hollow space inside the braided component that enables easy insertion of autografts, allografts, xenografts, or a combination thereof. The spacer such as tube can be made of any suitable material, for example, any suitable non-toxic polymer including but not limited to PVC, and PTFE. In an embodiment, the spacer such as tube is biocompatible.

[0054] Figure 8 illustrates an embodiment with the elements of the scaffold, in a combination of soft tissue of (for example, autograft, allograft, or xenograft) integrated with a braided structure. The scaffold may be called as LUCA ligament or graft with a new design wherein the spacer such as tube (not shown in Figure 8) helps to create a hollow space (hollow core) within the scaffold allows for the easy insertion of a tendon autografts, allografts, and/or xenografts.

[0055] In an embodiment, the spacer is removed to create a hollow core or space followed by placement of the autograft, allograft, or xenograft, and the scaffold is implanted in a subject. In an embodiment, the autograft, allograft, or xenograft is placed while spacer is still present in the braided structure, and the spacer is removed before implanting the scaffold in a subject. In an embodiment, the spacer is not removed from the scaffold and is implanted with the autograft, allograft, or xenograft, and the scaffold in a subject. In an embodiment, the spacer includes a biodegradable and biocompatible material. Some examples of the biodegradable and biocompatible material include but are not limited to PLLA, PLA, PGA, PLGA, or a combination thereof.

[0056] In embodiments incorporating bioactive materials, the timing and sequence of spacer removal may be coordinated with the bioactive material application process. When using hydrogels, the bioactive material may be applied either before or after spacer removal, depending on the specific surgical requirements and desired therapeutic outcomes. For lyophilized or dried bioactive materials, the application process is typically completed prior to spacer removal to ensure optimal integration with the scaffold structure.

[0057] In an aspect, disclosed is a method for using a synthetic scaffold/device for soft tissue and/or ligament regeneration in a subject. In an embodiment, the method is for soft tissue regeneration in a subject. In an embodiment, the method is for ligament regeneration in a subject. In an embodiment, the method includes providing a scaffold disclosed herein; providing an autograft, allograft, or xenograft; and implanting the scaffold and the autograft, allograft, or xenograft in a subject. In an embodiment, a spacer from the scaffold is removed before implanting the scaffold and the autograft, allograft, or xenograft in the subject. In an embodiment, a spacer from the scaffold is not removed before implanting the scaffold and the autograft, allograft, or xenograft in the subject. In an embodiment, the spacer is biodegradable. In an embodiment, the spacer is non-biodegradable. In an embodiment, the subject is human.

[0058] In an embodiment, an electrospinning technique can be used to fabricate microfiber nonwoven matrices. In an embodiment, the sleeve/braid was formed using a 3-D textile braiding technique. In an embodiment, the 3-D textile braiding technique used is a 4-step process which uses a track and column method to create the fiber matrix. However, as will be understood by those of skill in the art upon reading this disclosure, other suitable techniques for preparing 3-D braided scaffolds can also be used, such as knitting or weaving fibers.

[0059] In an embodiment, a rabbit’ s autograft was employed. In an embodiment, the poly-L- lactic acid (PLLA) and/or poly(DL)-lactic acid (PLA) braided scaffold can be utilized for the insertion of both allograft and xenograft. In an embodiment, biodegradable polymers of different density can be used to include both high-density and low-density fibers as a hybrid construct. In an embodiment, the braid can vary with a mixture of high and low density fibers which can modulate the degradation rate in vivo and allow optimization of graft maturity through loadsharing balance.

[0060] The incorporation of bioactive materials may further enhance the scaffold’s biological properties and tissue integration capabilities. The selection of specific bioactive materials can be customized based on the target tissue type and its regenerative requirements, the desired rate of bioactive material release and degradation, compatibility with the chosen polymer density combinations, and/or the intended therapeutic effect (e.g., enhanced cell adhesion, growth factor delivery, anti-inflammatory properties)

[0061] Those skilled in the art understand that the degradation rate and mechanical properties of the braid can be modulated. The degradation rate is the rate of destruction of the polymeric braid in the body because of hydrolysis or other degradative process. In an embodiment, while PLLA fibers arc utilized, other kinds of suitable polymeric and/or biodegradable fibers can be used for making the braid. It should be noted that any suitable biodegradable and/or nonbiodegradable polymers can be utilized, as recognized by experts in this field when reviewing this disclosure.

[0062] When bioactive materials are incorporated into the scaffold, their degradation characteristics must be considered in conjunction with the polymer degradation rate. The combined degradation profiles of the polymeric scaffold and bioactive materials can be tailored to optimize tissue regeneration by; matching the release rate of bioactive compounds with the tissue healing timeline; ensuring appropriate mechanical support throughout the regeneration process; and/or maintaining an optimal microenvironment for tissue formation and maturation. [0063] The favored biodegradable polymers are those that break down through hydrolysis. Any suitable biodegradable polymer that may degrade by other means than hydrolysis can also be used. Examples of polymeric fibers suitable for the current invention encompass, but arc not restricted to, fibers composed of poly(hydroxy)esters, such as polylactic acid, polyglycolic acid, and their co-polymers. The preferred biodegradable polymers are lactic acid-based polymers, including poly(L-lactic acid) (PLLA), poly(DL-lactic acid) (PLA), and poly(DL-lactic-co- glycolic acid) (PLGA). The ideal co-monomer ratios for poly(DL-lactic-co-glycolic acid) range from 100:0 to 50:50. Specifically, the most preferred co-monomer ratios fall between 85:15 (PLGA 85:15) and 50:50 (PLGA 50:50). Additionally, blends of PLLA with PLGA, particularly PLGA 85:15 and PLGA 50:50, can also be employed for these scaffolds. Other biodegradable polymers suitable for the scaffolds in this invention encompass, but are not confined to, polyorthoesters, polyanhydrides, polyphosphazenes, polycaprolactones, polyhydroxybutyrates, degradable polyurethanes, polyanhydrideco-imides, polypropylene fumarates, and polydiaxonane.

[0064] In an embodiment, a xenograft or allograft could be loaded into the scaffold and stored before intra-operative use. The combined scaffold with allograft or xenograft could be sterilized and stored, and used off the shelf/out of cold storage directly as a graft for ACL reconstruction or other soft tissue procedure.

Example: An autograft in a rabbit cadaver.

[0065] As depicted in Figures 9 and 10, an embodiment of the disclosed scaffold was incorporated with a segment of the rabbit’ s own tendon as an autograft into the PLLA braid. Subsequently, this scaffold, also referred to as the LUCA graft, was utilized for an ACL reconstruction procedure in the rabbit cadaver, as shown in Figures 11 and 12. After successful ACL reconstruction in this rabbit model, The LUCA graft added significant stability to the knee. Lachmann test revealed firm endpoint and minimal tibial translation under stress. [0066] As shown in Table 1 and Figure 13, the mechanical tests revealed that the LUCA graft exhibits significantly improved mechanical properties compared to the standalone autograft (mechanical strength of about 58N). Therefore, the LUCA graft is a great structural support for autograft (or xenograft and allograft) during ligament healing.

Table 1. Mechanical properties of autograft and the LUCA graft.

[0067] The 3-D braided scaffolds disclosed herein may be particularly useful as replacement constructs for the above-described exemplary ligaments and tendons, as well as any other ligaments or tendons which have been damaged, as these scaffolds arc degradable, porous, biocompatible, exhibit sufficient strength and promote formation of ligament and tendon tissue. The fiber based design of the scaffold emulates the natural ligament or tendon and the braided structure offers mechanical strength as well as needed porosity for cell attachment and ingrowth. [0068] While the present disclosure has been described with reference to an exemplary embodiment, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but that the invention will include all embodiments falling within the scope of the appended claims. Any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.

Definitions

[0069] The following terms are used to describe the invention of the present disclosure. In instances where a term is not specifically defined herein, that term is given an art-recognized meaning by those of ordinary skill applying that term in context to its use in describing the present disclosure. [0070] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the ait. For example, any nomenclatures used in connection with, and techniques of, cell and tissue culture, molecular biology, immunology, microbiology, genetics, and protein and nucleic acid chemistry and hybridization described herein are well known and commonly used in the ail. In case of conflict, the present disclosure, including definitions, will control. Exemplary methods and materials are described below, although methods and materials similar or equivalent to those described herein can be used in practice or testing of the embodiments and aspects described herein.

[0071] Compounds and materials are described using standard nomenclature. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this invention belongs. The following terms are used to describe the invention of the present disclosure. In instances where a term is not specifically defined herein, that term is given an art-recognized meaning by those of ordinary skill applying that term in context to its use in describing the present disclosure.

[0072] The use of the terms “a” and “an” and “the” and similar referents (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. By way of example, “an element” means one element or more than one element.

[0073] As used herein, the term “substantially” means to a great or significant extent, but not completely.

[0074] It should also be understood that, in certain methods described herein that include more than one step or act, the order of the steps or acts of the method is not necessarily limited to the order in which the steps or acts of the method are recited unless the context indicates otherwise. Furthermore, the terms first, second, etc., as used herein are not meant to denote any particular ordering, but simply for convenience to denote a plurality of, for example, layers.

[0075] The terms “comprising”, “having”, “including”, and “containing” arc to be construed as open-ended terms (i.e., meaning “including, but not limited to”) unless otherwise noted.

[0076] The terms “about” or “approximately,” as used herein, is inclusive of the stated value and means within an acceptable range of deviation for the particular value as determined by one of ordinary skill in the art, considering the measurement in question and the error associated with measurement of the particular quantity (i.e., the limitations of the measurement system). For example, “about” can mean within one or more standard deviations, or within ± 10% or 5% of the stated value. Recitation of ranges of values are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All ranges disclosed herein include both end points as discrete values as well as all integers and fractions specified within the range. For example, a range of 0.1-2.0 includes 0.1, 0.2, 0.3, 0.4 . . . 2.0. All methods described herein can be performed in a suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”), is intended merely to better illustrate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any nonclaimed element as essential to the practice of the invention as used herein.

[0077] The phrase “and/or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with “and/or” should be construed in the same fashion, i.e., “one or more” of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the “and/or” clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, a reference to “A and/or B”, when used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.

[0078] As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and/or” as defined above. For example, when separating items in a list, “or” or “and/or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of” or “exactly one of,” or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e., “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.”

[0079] As used herein in the specification and in the claims, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified. Thus, as a nonlimiting example, “at least one of A and B” (or, equivalently, “at least one of A or B,” or, equivalently “at least one of A and/or B”) can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc.

[0080] The phrase “one or more,” as used herein, means at least one, and thus includes individual components as well as mixtures/combinations of the listed components in any combination.

[0081] Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients and/or reaction conditions are to be understood as being modified in all instances by the term “about,” meaning within 10% of the indicated number (e.g., “about 10%” means 9%- 11% and “about 2%” means 1.8%-2.2%).

[0082] All percentages and ratios are calculated by weight unless otherwise indicated. All percentages are calculated based on the total composition unless otherwise indicated. Generally, unless otherwise expressly stated herein, “weight” or “amount” as used herein with respect to the percent amount of an ingredient refers to the amount of the raw material comprising the ingredient, wherein the raw material may be described herein to comprise less than and up to 100% activity of the ingredient. Therefore, weight percent of an active in a composition is represented as the amount of raw material containing the active that is used and may or may not reflect the final percentage of the active, wherein the final percentage of the active is dependent on the weight percent of active in the raw material.

[0083] All ranges and amounts given herein are intended to include subranges and amounts using any disclosed point as an end point. Thus, a range of “1% to 10%, such as 2% to 8%, such as 3% to 5%,” is intended to encompass ranges of “1% to 8%,” “1% to 5%,” “2% to 10%, ” and so on. All numbers, amounts, ranges, etc., are intended to be modified by the term “about,” whether or not so expressly stated. Similarly, a range given of “about 1% to 10%” is intended to have the term “about” modifying both the 1% and the 10% endpoints. Further, it is understood that when an amount of a component is given, it is intended to signify the amount of the active material unless otherwise specifically stated.

[0084] As used herein, the term “administering” means the actual physical introduction of a composition into or onto (as appropriate) a subject, a host, or cell. Any and all methods of introducing the composition into the subject, host or cell are contemplated according to the invention; the method is not dependent on any particular means of introduction and is not to be so construed. Means of introduction are well-known to those skilled in the art, and also are exemplified herein. “Providing” means giving, administering, selling, distributing, transferring (for profit or not), manufacturing, compounding, or dispensing.

[0085] As used herein, “optional” or “optionally” means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not.

[0086] The term “subject” or “patient” is used herein to refer to an animal, such as a mammal, including a primate (such as a human, a non-human primate, e.g., a monkey, and a chimpanzee), a non-primate (such as a cow, a pig, a camel, a llama, a horse, a goat, a rabbit, a sheep, a hamster, a guinea pig, a cat, a dog, a rat, a mouse, and a whale), a bird (e.g., a duck or a goose), and a shark. In an embodiment, the subject or patient is a human subject or a human patient, such as a human being treated or assessed for a disease, disorder or condition, a human at risk for a disease, disorder or condition, a human having a disease, disorder or condition, and/or human being treated for a disease, disorder or condition as described herein. In one embodiment, the subject is about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 years of age. In another embodiment, the subject is about 5-10, 10-15, 15- 20, 20-25, 25-30, 30-35, 35-40, 40-45, 45-50, 50-55, 55-60, 60-65, 65-70, 70-75, 75-80, 80-85, 85-90, 90-95, 95-100 years of age. Values and ranges intermediate to the above recited ranges are also intended to be part of this invention. In addition, ranges of values using a combination of any of the above-recited values as upper and/or lower limits are intended to be included. As used herein, a subject is “in need of treatment” if such subject would benefit biologically, medically, or in quality of life from such treatment. A subject in need of treatment does not necessarily present symptoms, particular in the case of preventative or prophylaxis treatments.

[0087] All methods described herein can be performed in a suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”), is intended merely to better illustrate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention as used herein. Unless defined otherwise, technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art of this disclosure.

[0088] Furthermore, the disclosure encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, and descriptive terms from one or more of the listed claims are introduced into another claim. For example, any claim that is dependent on another claim can be modified to include one or more limitations found in any other claim that is dependent on the same base claim. Where elements are presented as lists, e.g., in Markush group format, each subgroup of the elements is also disclosed, and any element(s) can be removed from the group.

[0089] All compounds are understood to include all possible isotopes of atoms occurring in the compounds. Isotopes include those atoms having the same atomic number but different mass numbers and encompass heavy isotopes and radioactive isotopes. By way of general example, and without limitation, isotopes of hydrogen include tritium and deuterium, and isotopes of carbon include ⁿC, ¹³C, and ¹⁴C. Accordingly, the compounds disclosed herein may include heavy or radioactive isotopes in the structure of the compounds or as substituents attached thereto. Examples of useful heavy or radioactive isotopes include ¹⁸F, ¹⁵N, ¹⁸O, ⁷⁶Br, ¹²⁵I and ¹³¹I.

[0090] A significant change is any detectable change that is statistically significant in a standard parametric test of statistical significance such as Student’s t-test, where p < 0.05.

[0091] All statements herein reciting principles, aspects, and embodiments of the disclosure, as well as specific examples thereof, are intended to encompass both structural and functional equivalents thereof. Additionally, it is intended that such equivalents include both currently known equivalents as well as equivalents developed in the future, i.e., any elements developed that perform the same function, regardless of structure.

[0092] Various other components may be included and called upon for providing for aspects of the teachings herein. For example, additional materials, combinations of materials and/or omission of materials may be used to provide for added embodiments that are within the scope of the teachings herein. Adequacy of any particular element for practice of the teachings herein is to be judged from the perspective of a designer, manufacturer, seller, user, system operator or other similarly interested party, and such limitations are to be perceived according to the standards of the interested party.

[0093] In the disclosure hereof any element expressed as a means for performing a specified function is intended to encompass any way of performing that function including, for example, a) a combination of circuit elements and associated hardware which perform that function or b) software in any form, including, therefore, firmware, microcode or the like as set forth herein, combined with appropriate circuitry for executing that software to perform the function.

Applicants thus regard any means which can provide those functionalities as equivalent to those shown herein. No functional language used in claims appended herein is to be construed as invoking 35 U.S.C. § 112( ) interpretations as “means-plus-function” language unless specifically expressed as such by use of the words “means for” or “steps for” within the respective claim. [0094] When introducing elements of the present invention or the embodiment(s) thereof, the articles “a,” “an,” and “the” are intended to mean that there are one or more of the elements.

Similarly, the adjective “another,” when used to introduce an element, is intended to mean one or more elements. The terms “including” and “having” are intended to be inclusive such that there may be additional elements other than the listed elements. The term “exemplary” is not intended to be construed as a superlative example but merely one of many possible examples.

[0095] While the invention has been described with reference to an exemplary embodiment, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but that the invention will include all embodiments falling within the scope of the appended claims. Any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.

Other Embodiments

[0096] Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation many equivalents to the specific embodiments described herein. The scope of the present embodiments described herein is not intended to be limited to the above Description, but rather is as set forth in the appended claims.

[0097] For reasons of completeness, various aspects of the disclosure are set out in the following numbered clauses:

[0098] Clause 1. A synthetic scaffold device/system comprising: a sleeve comprising a component that is braided, woven, knitted or any combination thereof; and a spacer positioned within the component to create a hollow space configured to receive a tissue graft.

[0099] Clause 2. A synthetic scaffold device/system comprising: a sleeve comprising a component that is braided, woven, knitted or any combination thereof; a spacer positioned within the sleeve, wherein the spacer comprises either: a removable spacer configured to be removed to create a hollow space for receiving a tissue graft; or a biodegradable spacer configured to degrade in vivo after implantation; and a tissue graft configured to be received within the hollow space.

[0100] Clause 3. The synthetic scaffold device of any one of clauses 1 or 2, wherein the spacer comprises at least one of a tube, a rod, a spring, or combinations thereof.

[0101] Clause 4. The synthetic scaffold of clause 1, further comprising a hydrogel positioned within the hollow space.

[0102] Clause 5. The synthetic scaffold of clause 4, wherein the hydrogel is augmented.

[0103] Clause 6. The synthetic scaffold of any one of clauses 4 or 5, wherein the hydrogel comprises fibrin gel, hyaluronic acid, or any combination thereof.

[0104] Clause 7. The synthetic scaffold device of any one of clauses 1-6, wherein the spacer comprises a biodegradable and biocompatible material comprising poly-L-lactic acid (PLLA), poly(DL)-lactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), and combinations thereof.

[0105] Clause 8. The synthetic scaffold device of any one of clauses 1-7, wherein the spacer is removable.

[0106] Clause 9. The synthetic scaffold device of any one of clauses 1-8, wherein the spacer is expandable.

[0107] Clause 10. The synthetic scaffold device of clause 9, wherein the expandable spacer comprises at least one of: an inflatable component configured to be expanded using a biocompatible fluid; or a mechanical expansion mechanism comprising at least one of a collapsible mesh structure or telescoping segments.

[0108] Clause 11. The synthetic scaffold device of any one of clauses 1-10, wherein the component comprises biodegradable polymer fibers comprising at least one of poly-L-lactic acid (PLLA), poly(DL)-lactic acid (PLA), or combinations thereof.

[0109] Clause 12. The synthetic scaffold device of any one of clauses 1-11, wherein the component terminates in first and second attachment ends and includes a middle region that differs from both of said attachment ends in at least one of size, braiding angle, porosity, or mechanical strength.

[0110] Clause 13. The synthetic scaffold device of clause 1, further comprising a tissue graft positioned within the hollow space, wherein the tissue graft comprises at least one of an autograft, an allograft, or a xenograft.

[0111] Clause 14. The synthetic scaffold device/system of clause 2, wherein when the spacer is biodegradable, the biodegradable spacer comprises a material comprising poly-L-lactic acid (PLLA), poly(DL)-lactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), or combinations thereof.

[0112] Clause 15. The synthetic scaffold device/system of clause 2, wherein the tissue graft comprises at least one of a heterogeneous autograft, a bonc-patclla-bonc autograft, an Achilles allograft, or other tendon allograft or autograft such as quad tendon, or hamstring tendon.

[0113] Clause 16. A composite tissue scaffold comprising: a load-bearing scaffold structure formed from biodegradable polymers (braided, woven, knitted or any combination thereof); a temporary spacing element disposed within the load-bearing scaffold structure; and wherein the temporary spacing element maintains a tissue insertion channel during storage and transportation.

[0114] Clause 17. The scaffolds of any one of clauses 2, 6, or 16, wherein: when the scaffold comprises a sleeve, the sleeve comprises a mixture of high-density and low-density biodegradable polymer fibers configured to modulate degradation rate in vivo; and when the scaffold comprises a load-bearing scaffold structure, the load-bearing scaffold structure comprises a mixture of high-density and low-density biodegradable polymer fibers configured to modulate degradation rate in vivo.

[0115] Clause 18. The synthetic scaffold of clause 6, wherein the sleeve comprises a component/s that is braided, woven, knitted or any combination thereof.

[0116] Clause 19. The synthetic scaffold of clause 6, wherein the sleeve comprises a braided component.

[0117] Clause 20. The synthetic scaffold of clause 6, wherein the sleeve comprises a woven component.

[0118] Clause 21. The synthetic scaffold of clause 6, wherein the sleeve comprises a knitted component.

[0119] Clause 22. The synthetic scaffold of clause 6, wherein the sleeve comprises braided, woven, and knitted components.

[0120] Clause 23. The synthetic scaffold of clause 6, wherein the sleeve comprises at least one sleeve layer.

[0121] Clause 24. The synthetic scaffold of clause 6, wherein the sleeve comprises plurality of sleeve layers.

[0122] Clause 25. The synthetic scaffold of clause 24, wherein the sleeve comprises plurality of component layers wherein the component layer comprises a braided component, a woven component, a knitted component, or any combination thereof.

[0123] Clause 26. The scaffolds of any one of clauses 6, 16, or 18-25, wherein the biodegradable fibers comprise a first set of fibers having a first degradation rate and a second set of fibers having a second degradation rate different from the first degradation rate.

[0124] Clause 27. The scaffolds of any one of clauses 1, 2, 6, or 16, comprising a hydrogel positioned within the hollow space. [0125] Clause 28. The synthetic scaffold of clause 6, wherein the sleeve comprises zones of different braid patterns along its length.

[0126] Clause 29. The synthetic scaffold of clause 6, wherein the spacer comprises a nonstick surface treatment to facilitate removal.

[0127] Clause 30. The synthetic scaffold of clause 6, wherein the biodegradable fibers comprise a first set of fibers having a first degradation rate and a second set of fibers having a second degradation rate different from the first degradation rate.

[0128] Clause 31. The synthetic scaffold of clause 6, further comprising anti-adhesion properties at an interface between the spacer and the sleeve.

[0129] Clause 32. The synthetic scaffold of clause 6, wherein the sleeve comprises regions of different porosity configured to promote differential tissue ingrowth.

[0130] Clause 33. The synthetic scaffold of clause 6, wherein the spacer comprises visual markers indicating orientation for implantation.

[0131] Clause 34. The composite tissue scaffold of clause 16, wherein the temporary spacing element is configured to be removed and replaced with biological tissue without damaging the load-bearing scaffold structure.

[0132] Clause 35. A method of making a synthetic scaffold device/system, comprising: [0133] forming a sleeve comprising a component that is braided, woven, knitted or any combination thereof; positioning a spacer within the sleeve during formation to create a hollow space; and configuring the hollow space to receive a tissue graft; wherein the spacer comprises either a removable spacer configured to be removed before or during implantation, or a biodegradable spacer configured to degrade after implantation.

[0134] Clause 36. The method of clause 35, wherein when the spacer is biodegradable, the method further comprises selecting the biodegradable spacer to have a degradation rate coordinated with tissue healing timeline.

[0135] Clause 37. The method of clause 35, further comprising: removing the spacer when the spacer is removable; inserting a tissue graft into the hollow space; and implanting the synthetic scaffold device and tissue graft in a subject.

[0136] Clause 38. A method of ligament reconstruction comprising: providing a scaffold (braided, woven, knitted or any combination thereof) having a removable spacer disposed therein; preparing a tissue graft for implantation; removing the spacer from the scaffold to create an insertion pathway; inserting the tissue graft through the insertion pathway; and securing the scaffold containing the tissue graft to bone.

[0137] Clause 39. A method of manufacturing a tissue scaffold comprising: braiding, wowing, and/or knitting biodegradable fibers around a removable mandrel to form a sleeve; treating the sleeve and mandrel with a bioactive solution; drying the bioactive solution to form a coating; and maintaining the mandrel within the sleeve until time of use.

[0138] Clause 40. A method of preparing a tissue scaffold comprising: forming a polymer sleeve (braided, woven, knitted or any combination thereof) around a removable core; incorporating bioactive agents into the braided polymer sleeve; packaging the polymer sleeve with the removable core; and maintaining sterility of an inner lumen defined by the removable core.

[0139] Clause 41. The method of any one of clauses 35, 38, 39, or 40, further comprising incorporating a bioactive material into the synthetic scaffold device prior to implanting.

[0140] Clause 42. The method of clause 38, further comprising applying a bioactive material to at least one of the scaffolds or the tissue graft prior to securing the scaffold.

[0141] Clause 43. The method of clause 38, wherein securing comprises anchoring the scaffold within bone tunnels.

[0142] Clause 44. The method of clause 38, wherein preparing the tissue graft comprises sizing the tissue graft to match an inner diameter of the insertion pathway.

[0143] Clause 45. The method of clause 38, further comprising modifying the tissue graft with growth factors prior to insertion into the scaffold.

[0144] Clause 46. A system for soft tissue repair comprising: a biomaterial scaffold (braided, woven, knitted or any combination thereof) having a longitudinal axis; a removable core member extending along the longitudinal axis; and a bioactive material disposed between the biomaterial scaffold and the removable core member.

[0145] Clause 47. The system of clause 46, wherein the bioactivc material comprises a lyophilized hydrogel configured to rehydrate upon implantation.

[0146] Clause 48. The system of clause 46, wherein the removable core member comprises a polymer selected to non-permanently adhere to the biomaterial scaffold. [0147] Those of ordinary skill in the art will appreciate that various changes and modifications to this description may be made without departing from the spirit or scope of the present invention, as defined in the following claims.

Claims

What is claimed is:

1. A synthetic scaffold device/system comprising: a sleeve comprising a component that is braided, woven, knitted or any combination thereof; and a spacer positioned within the component to create a hollow space configured to receive a tissue graft.

2. A synthetic scaffold device/system comprising: a sleeve comprising a component that is braided, woven, knitted or any combination thereof; a spacer positioned within the sleeve, wherein the spacer comprises either: a removable spacer configured to be removed to create a hollow space for receiving a tissue graft; or a biodegradable spacer configured to degrade in vivo after implantation; and a tissue graft configured to be received within the hollow space.

3. The synthetic scaffold device of any one of claims 1 or 2, wherein the spacer comprises at least one of a tube, a rod, a spring, or combinations thereof.

4. The synthetic scaffold of claim 1, further comprising a hydrogel positioned within the hollow space.

5. The synthetic scaffold of claim 4, wherein the hydrogel is augmented.

6. The synthetic scaffold of any one of claims 4 or 5, wherein the hydrogel comprises fibrin gel, hyaluronic acid, or any combination thereof.

7. The synthetic scaffold device of any one of claims 1-6, wherein the spacer comprises a biodegradable and biocompatible material comprising poly-L-lactic acid (PLLA), poly(DL)- lactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), and combinations thereof.

8. The synthetic scaffold device of any one of claims 1-7, wherein the spacer is removable.

9. The synthetic scaffold device of any one of claims 1-8, wherein the spacer is expandable.

10. The synthetic scaffold device of claim 9, wherein the expandable spacer comprises at least one of: an inflatable component configured to be expanded using a biocompatiblc fluid; or a mechanical expansion mechanism comprising at least one of a collapsible mesh structure or telescoping segments.

11. The synthetic scaffold device of any one of claims 1-10, wherein the component comprises biodegradable polymer fibers comprising at least one of poly-L-lactic acid (PLLA), poly(DL)-lactic acid (PLA), or combinations thereof.

12. The synthetic scaffold device of any one of claims 1-11, wherein the component terminates in first and second attachment ends and includes a middle region that differs from both of said attachment ends in at least one of size, braiding angle, porosity, or mechanical strength.

13. The synthetic scaffold device of claim 1, further comprising a tissue graft positioned within the hollow space, wherein the tissue graft comprises at least one of an autograft, an allograft, or a xenograft.

14. The synthetic scaffold device/system of claim 2, wherein when the spacer is biodegradable, the biodegradable spacer comprises a material comprising poly-L-lactic acid (PLLA), poly(DL)-lactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), or combinations thereof.

15. The synthetic scaffold device/system of claim 2, wherein the tissue graft comprises at least one of a heterogeneous autograft, a bone -patella-bone autograft, an Achilles allograft, or other tendon allograft or autograft such as quad tendon, or hamstring tendon.

16. A composite tissue scaffold comprising: a load-bearing scaffold structure formed from biodegradable polymers (braided, woven, knitted or any combination thereof); a temporary spacing element disposed within the load-bearing scaffold structure; and wherein the temporary spacing element maintains a tissue insertion channel during storage and transportation.

17. The scaffolds of any one of claims 2, 6, or 16, wherein: when the scaffold comprises a sleeve, the sleeve comprises a mixture of high-density and low-density biodegradable polymer fibers configured to modulate degradation rate in vivo; and when the scaffold comprises a load-bearing scaffold structure, the load-bearing scaffold structure comprises a mixture of high-density and low-density biodegradable polymer fibers configured to modulate degradation rate in vivo.

18. The synthetic scaffold of claim 6, wherein the sleeve comprises a component/s that is braided, woven, knitted or any combination thereof.

19. The synthetic scaffold of claim 6, wherein the sleeve comprises a braided component.

20. The synthetic scaffold of claim 6, wherein the sleeve comprises a woven component.

21. The synthetic scaffold of claim 6, wherein the sleeve comprises a knitted component.

22. The synthetic scaffold of claim 6, wherein the sleeve comprises braided, woven, and knitted components.

23. The synthetic scaffold of claim 6, wherein the sleeve comprises at least one sleeve layer.

24. The synthetic scaffold of claim 6, wherein the sleeve comprises plurality of sleeve layers.

25. The synthetic scaffold of claim 24, wherein the sleeve comprises plurality of component layers wherein the component layer comprises a braided component, a woven component, a knitted component, or any combination thereof.

26. The scaffolds of any one of claims 6, 16, or 18-25, wherein the biodegradable fibers comprise a first set of fibers having a first degradation rate and a second set of fibers having a second degradation rate different from the first degradation rate.

27. The scaffolds of any one of claims 1, 2, 6, or 16, comprising a hydrogel positioned within the hollow space.

28. The synthetic scaffold of claim 6, wherein the sleeve comprises zones of different braid patterns along its length.

29. The synthetic scaffold of claim 6, wherein the spacer comprises a non-stick surface treatment to facilitate removal.

30. The synthetic scaffold of claim 6, wherein the biodegradable fibers comprise a first set of fibers having a first degradation rate and a second set of fibers having a second degradation rate different from the first degradation rate.

31. The synthetic scaffold of claim 6, further comprising anti-adhesion properties at an interface between the spacer and the sleeve.

32. The synthetic scaffold of claim 6, wherein the sleeve comprises regions of different porosity configured to promote differential tissue ingrowth.

33. The synthetic scaffold of claim 6, wherein the spacer comprises visual markers indicating orientation for implantation.

34. The composite tissue scaffold of claim 16, wherein the temporary spacing element is configured to be removed and replaced with biological tissue without damaging the loadbearing scaffold structure.

35. A method of making a synthetic scaffold device/system, comprising: forming a sleeve comprising a component that is braided, woven, knitted or any combination thereof; positioning a spacer within the sleeve during formation to create a hollow space; and configuring the hollow space to receive a tissue graft; wherein the spacer comprises either a removable spacer configured to be removed before or during implantation, or a biodegradable spacer configured to degrade after implantation.

36. The method of claim 35, wherein when the spacer is biodegradable, the method further comprises selecting the biodegradable spacer to have a degradation rate coordinated with tissue healing timeline.

37. The method of claim 35, further comprising: removing the spacer when the spacer is removable; inserting a tissue graft into the hollow space; and implanting the synthetic scaffold device and tissue graft in a subject.

38. A method of ligament reconstruction comprising: providing a scaffold (braided, woven, knitted or any combination thereof) having a removable spacer disposed therein; preparing a tissue graft for implantation; removing the spacer from the scaffold to create an insertion pathway; inserting the tissue graft through the insertion pathway; and securing the scaffold containing the tissue graft to bone.

39. A method of manufacturing a tissue scaffold comprising: braiding, wowing, and/or knitting biodegradable fibers around a removable mandrel to form a sleeve; treating the sleeve and mandrel with a bioactive solution; drying the bioactive solution to form a coating; and maintaining the mandrel within the sleeve until time of use.

40. A method of preparing a tissue scaffold comprising: forming a polymer sleeve (braided, woven, knitted or any combination thereof) around a removable core; incorporating bioactive agents into the braided polymer sleeve; packaging the polymer sleeve with the removable core; and maintaining sterility of an inner lumen defined by the removable core.

41. The method of any one of claims 35, 38, 39, or 40, further comprising incorporating a bioactive material into the synthetic scaffold device prior to implanting.

42. The method of claim 38, further comprising applying a bioactive material to at least one of the scaffolds or the tissue graft prior to securing the scaffold.

43. The method of claim 38, wherein securing comprises anchoring the scaffold within bone tunnels.

44. The method of claim 38, wherein preparing the tissue graft comprises sizing the tissue graft to match an inner diameter of the insertion pathway.

45. The method of claim 38, further comprising modifying the tissue graft with growth factors prior to insertion into the scaffold.

46. A system for soft tissue repair comprising: a biomaterial scaffold (braided, woven, knitted or any combination thereof) having a longitudinal axis; a removable core member extending along the longitudinal axis; and a bioactive material disposed between the biomaterial scaffold and the removable core member.

47. The system of claim 46, wherein the bioactive material comprises a lyophilized hydrogel configured to rehydrate upon implantation.

48. The system of claim 46, wherein the removable core member comprises a polymer selected to non-permanently adhere to the biomaterial scaffold.