SAME, METHODS OF IMPLANTING A SYNTHETIC SYMPHYSIS, AND

METHODS FOR TREATING A SUBJECT HAVING A SYMPHYSIS

DYSFUNCTION

RELATED APPLICATION

This application claims priority to U.S. Provisional Patent Application Serial No. 61/092,846, filed August 29, 2008. The contents of this patent application are hereby incorporated by reference in their entirety.

BACKGROUND

Approximately 175,000 anterior cervical spine surgeries are performed each year to correct intervertebral disc dysfunction. Most current technologies use metal-on-metal or metal-on-polymer articulation devices to achieve functionality and restore disc height. These devices require a surgical procedure which is considerably invasive. Thus, a clinical need exists for less invasive devices and techniques that achieve functional standards.

SUMMARY OF THE INVENTION

Aspects of the invention provide nucleus containment devices, methods of fabricating the same, methods of implanting a synthetic symphysis, and methods for treating a subject having a symphysis dysfunction. Embodiments of the invention are particularly applicable to the human spine.

One aspect of the invention provides a nucleus containment device including one or more interfaces defining an internal region adapted to receive a nucleus material.

This aspect can have a variety of embodiments. The one or more interfaces can be textiles. The one or more textiles can be fusible textiles. The one or more fusible textiles can be fused textiles. The one or more textiles can be selected from the group consisting of: polymers, thermoplastic polymers, thermoset polymers, polyesters, polypropylene, and polyethylene. The one or more textiles can include a plurality of adjacent woven textiles. The one or more textiles can include a plurality of non- woven textiles. The one or more textiles can include an internal woven textile, an external woven textile, and one or more woven or non- woven textiles positioned between the internal woven textile and external woven textile. The one or more textiles can include an internal non- woven textile, an external non- woven textile, and one or more woven or non- woven textiles positioned between the internal non- woven textile and external non- woven textile. The one or more interfaces can include a silicone interface. The one or more interfaces can be biocompatible interfaces.

The one or more interfaces can be coupled to define the internal region. The one or more interfaces can be coupled by one or more techniques selected from the group consisting of: mechanical fastening, chemical fastening, and fusing. Mechanical fastening can include one or more techniques selected from the group consisting of: sewing, stapling, and crimping.

Another aspect of the invention provides a method for implanting a synthetic symphysis. The method includes: introducing a nucleus containment device defining an internal region adapted to receive a nucleus material into a space between two bones; and injecting the nucleus material into the internal region; thereby implanting a synthetic symphysis.

This aspect can have a variety of embodiments. The method can include removing an existing symphysis. The method can also include introducing the nucleus containment device via a cannula. The nucleus containment device can be compressed within the cannula. The space can be an intervertebral disc space. The nucleus material can be a natural nucleus material. The nucleus material can be a synthetic nucleus material. The nucleus material can be a recombinant protein hydrogel. The nucleus material can be a polysaccharide hydrogel. The polysaccharide hydrogel can include hyaluronic acid. Another aspect of the invention provides a synthetic symphysis implanted according to the methods herein.

Another aspect of the invention provides a method for fabricating a nucleus containment device defining an internal region adapted to receive a nucleus material. The method includes placing a core having a shape that is substantially complimentary to the desired internal region within one or more fusible textiles; placing the one or more fusible textiles and the core into a mold having a shape that is complimentary to a desired external shape of the nucleus containment device; heating the mold to fuse the one or fusible textiles; and removing the core from the one or more fusible textiles; thereby fabricating a nucleus containment device. This aspect can have a variety of embodiments. The core can be a dissolvable core.

The core can be fabricated from a biocompatible material. The biocompatible material can include one or more salts. The one or more salts can be selected from the group consisting of: calcium sulfate and calcium carbonate. The dissolvable core can be a mixture of about 50% calcium sulfate and about 50% calcium carbonate by mass. The method can include molding the core. The mold can include one or more materials selected from the group consisting of: polytetrafluoroethylene and a metal. The mold can be heated with an oven. The oven can be a convection oven. The convection oven can be heated to a temperature between about 195° C and about 205° C. The mold can be placed in the convection oven for between about 15 minutes and about 20 minutes. The method can include coupling the one or more fusible textiles. The step of coupling can include one or more selected from the group consisting of: mechanical fastening, chemical fastening, and fusing. Mechanical fastening can include one or more techniques selected from the group consisting of: sewing, stapling, and crimping. Another aspect of the invention provides a nucleus containment device prepared according to the methods herein.

Another aspect of the invention provides a method for treating a subject having a symphysis dysfunction. The method includes: removing a dysfunctional symphysis from between two bones; introducing a nucleus containment device defining an internal region adapted to receive a nucleus material into a space between the two bones; and injecting the nucleus material into the internal region; thereby treating a subject having a symphysis dysfunction.

This aspect can have a variety of embodiments. The symphysis dysfunction can include any condition that requires replacement of the dysfunctional symphysis. The symphysis can be an intervertebral symphysis.

FIGURES

For a fuller understanding of the nature and desired objects of the present invention, reference is made to the following detailed description taken in conjunction with the figures wherein: FIG. 1 depicts the anatomy of the vertebral column of a human subject;

FIG. 2 provides a superior view vertebra of a human thoracic vertebra; FIG. 3A depicts the a cross section of a healthy human intervertebral disc and its positioning relatived to a human vertebra;

FIG. 3B provides a superior cross section of a herniated disc; FIG. 4A provides a sagittal cross section of a herniated disc between two vertebrae;

FIG. 4B provides a sagittal cross section of an artificial intervertebral dick between two vertebrae;

FIGS. 5A-5D depict various embodiments of nucleus containment devices; FIGS. 6A and 6B depict lateral and longitudinal cross-sections of a fusible bi- component fiber;

FIG. 7 depicts a method of fabricating a nucleus containment device;

FIG. 8 depicts methods of implanting a synthetic symphysis and treating symphysis dysfunction is provided;

FIG. 9 is a plot of stress vs. strain curves for heat treated and non heat treated textiles;

FIGS. 1OA and 1OB is a photograph of 4x microscopy of non heat treated and heat treated textiles, respectively;

FIG. 11 is a photograph of dissolvable cores and molds for forming dissolvable cores; FIG. 12 is a photograph of a dissolvable core surrounded by textiles and a mold for heat treatment;

FIG. 13 is a photograph of the formation of a plurality of pilot holes in a nucleus containment device by a hand sewing punch;

FIG. 14A depicts a nucleus containment device with excess textiles trimmed; FIG. 14B depicts a nucleus containment device including a plurality of textiles coupled by stitching;

FIG. 14C depicts a nucleus containment device with two concentric rings of machine stitching; and

FIGS. 15A and 15B are fluoroscopic images of nucleus containment devices implanted in a cadaveric cervical spine.

DETAILED DESCRIPTION

The instant invention is most clearly understood with reference to the following definitions:

The term "biocompatible" shall be understood to refer to any material that is nontoxic and, optionally, does not provoke an immunological rejection. Biocompatible materials can be naturally occurring or synthetic and permit diffusion of liquids, gases, and/or ions.

The term "braided" shall be understood to refer to any textile formed by interlacing warp and weft fibers at an angle other than substantially perpendicular to each other.

The term "health care provider" shall be understood to mean any person providing medical care to a patient. Such persons include, but are not limited to, medical doctors, physician's assistants, nurse practitioners (e.g., an Advanced Registered Nurse Practitioner (ARNP)), nurses, residents, interns, medical students, or the like. Although various licensure requirements may apply to one or more of the occupations listed above in various jurisdictions, the term health care provider is unencumbered for the purposes of this patent application.

The term "knitted" shall be understood to refer to any textile formed by interloping fibers into vertical columns and horizontal rows of loops. The term "non- woven" shall be understood to refer to any textile formed with fibers positioned at random orientations to each other. Fibers in non-woven textiles can be formed by chemically, thermally, and/or mechanically bonding. Examples of non- woven fabrics include felts, batting, and the like.

The term "nucleus containment device" shall be understood to include any device capable of substantially containing a nucleus material.

The term "subject" shall be understood to include any mammal including, but not limited to, humans, primates, swine, cows, sheep, and rats.

The term "symphysis dysfunction" shall be understood to include any disease, disorder, degeneration, pathology, and the like requiring the replacement of the symphysis. The term "synthetic symphysis" shall be understood to be include any man-made device capable of substantially replicating the operation of a fibrocartilaginous joint.

The term "textile" shall be understood to refer to a material having a network of fibers. The fibers can be natural or synthetic. Exemplary categories of textiles include braided, knit, non- woven, and woven textiles. The term "woven" shall be understood to refer to any textile formed by interlacing warp and weft fibers at substantially perpendicular angle to each other.

DESCRIPTION OF THE INVENTION

Aspects of the invention provide nucleus containment devices, methods of fabricating the same, methods of implanting a synthetic symphysis, and methods for treating a subject having a symphysis dysfunction. Embodiments of the invention are particularly applicable to the human spine. Spine Anatomy

Referring now to FIG. 1, the human vertebral column 100, or spine, is a combination of bone, ligaments, intervertebral discs, and muscles that are interconnected to form a complex and flexible structure lining the neck and back. The spine 100 is responsible for several important functions: supporting the weight of the head and torso (not depicted) and allowing their movement, protecting the spinal cord (not depicted) and permitting spinal nerves (not depicted) to exit the spinal cord, and providing a viable site for muscle attachment. The spine 100 is segmented into nine fused and twenty-four flexible vertebrae. The nine fused vertebrae located at the base of the spine are called the sacrum 102 and coccyx 104. The sacrum 102 is made up of five fused vertebras to make one single bone. The pelvis (not depicted), or hip bone, is attached to the sacrum 102. The coccyx 104, which is also known as the tailbone, is made up of four fused vertebras. It is located below the sacrum 102 and has a much smaller body.

The flexible vertebrae are classified as cervical, thoracic, or lumbar. The seven cervical vertebrae 106 make up the neck and are labeled C1-C7 from top to bottom. There are two distinct vertebrae found in the cervical region called the atlas (Cl) and the axis (C2). These two vertebrae are responsible for the attachment and movement of the head (not depicted) upon the spine 100. The C3-C7 vertebras are more closely related to the rest of the spine 100 in function and appearance. There are twelve thoracic vertebrae 108, designated T1-T12 from top to bottom, where the ribs (not depicted) are attached to the vertebral bodies. The five lumbar vertebrae 110, designated L1-L5 from top to bottom, connect the thoracic vertebrae 108 and the sacrum 102. The lumbar vertebrae 110, which are the largest vertebras, support the lower back.

Referring now to FIG. 2, each vertebra 200 has three main parts: a body 202, an arch 204, and several processes 206, 208. The body 202 is the load bearing part of the vertebra 200. The vertebral arch 204 is responsible for enclosing and protecting the spinal column which runs the length of the spine 100 and through the vertebral foramen 206 of each vertebra 200. The various processes 208, 210 protrude out from the vertebral body 202 and are necessary for muscle attachment to the spine 100, which provides a mechanical means of moving the spine 100.

Referring now to FIG. 3A, there are twenty-three intervertebral discs (IVDs) 300 in the spine 100 — one intervertebral disc 300 between each vertebra 200. These discs 300 allow for the forward, backward, and lateral motions of the spine 100 while also absorbing and distributing the loads throughout the spinal column 100. Although, the motion of each individual vertebra 200 and intervertebral disc 300 is limited, the combined effects of each segment allows the spine 100 to have a large range of motion in several directions. The total range of motion observed in the cervical region 106 is 80°-90° of flexion (forward head movement), 70° of extension (backward head movement), 20°-45° of lateral bending (left and right head movement), and 90° of rotation (twisting). The maximum range of motions for any single level in the cervical region (C3-C7) are +10° for flexion or extension, +11° lateral bending, and +7° rotation. The intervertebral disc 300 is a cartilaginous joint called a symphysis. A symphysis is a pad or disc of fibrocartilage that connects two bones, such as two vertebras 200. The intervertebral disc 300 includes two basic parts: the annulus fibrosis 302 and the nucleus pulposus 304, as shown in FIG. 3A. The annulus 302 is highly oriented fibrocartilage which surrounds and contains the gel-like nucleus pulposus 304. Spinal cord 306 (surrounded with dura mater 308) is also depicted.

The fibrocartilage in the IVD 300 is one of three types of cartilage found in the human body. Hyaline and elastic cartilages are the other two types. Each type of cartilage differs by the amounts of matrix and ratio of collagenous to elastic fibers. Fibrocartilage is classified by having a small amount of matrix and high fibrous collagen contents. Fibrocartilage is associated with dense connective tissues in the body like the IVD and has the highest tensile strength of the three types of cartilage.

Like the meniscus in the knee, the IVD 300 is predominantly comprised of extracellular matrix (ECM) and has very few cells. The IVD 300 also lacks a direct blood supply. Blood vessels reach the outer annulus but do not penetrate inward within the IVD 300. Therefore, the disc 300 receives all nutrients and hydration through diffusion from the outside of the disc 300. Nutrients and hydration are very important as the disc 300 ages.

The ECM of the IVD 300 is a composite of mainly of water, proteoglycans, collagens, and other proteins. During compression of the IVD 300, it is possible to induce flow of water through the extracellular matrix. However, there is a high resistance to the flow of water due to the presence of proteoglycans. This resistance is termed "hydrostatic pressure" and is responsible for the resilient quality of the IVD 300 and its ability to absorb loads and cushion joints.

Proteoglycans are macromolecules with a protein core and polysaccharide branches. 80-90% of the proteoglycans in cartilage are aggrecans. Aggrecans are long extended proteins chains with highly branched polysaccharides, primarily chondroitin sulfate and keratin sulfate, which have the ability to trap large amounts of water. Collagen fibers in the ECM trap proteoglycans helping to maintain disc hydration and the load absorption properties it provides. Collagen fibers in cartilage also provide the tensile strength of the IVD. All known types of collagen share a similar triple helix structure. Type II and type I collagen are the most prevalent collagen types in the IVD 300.

The nucleus pulposus 304 has a high water content that is responsible for the cushioning effect of the disc 300 and a rebound in disc height after loading. The nucleus 304 is composed of 20% collagen with the rest being water and proteoglycans. Of the available collagen in the nucleus 304, 80% is type II collagen. Type I collagen is not present in the nucleus 304. As the amount of type II collagen increases so does the amount of proteoglycans present in the disc 300. As the disc 300 is loaded, the low fiber content allows the nucleus 304 to experience greater deformations and therefore volume changes. During compression, the inner annulus 302 and the nucleus 304 are deformed and forced outward in the radial direction. These deformations generate hydrostatic pressure in the disc 300, thereby dissipating energy throughout the disc 300.

The outer annulus includes mostly type I collagen and its primary function is to contain the inner annulus and nucleus 304 by resisting the tensile loads in generated in the disc 300. The main collagenous fibers in the annulus 302 change from type I collagen in the outer rings to type II in the inner annulus. The total ratio of the annulus 302 is about 40% type I collagen and 60% type II collagen. The collagen fibers in the annulus 302 are oriented into laminates or sheets surrounding the nucleus 304. The outer annulus, with more densely packed fiber structure resists this expansion and tensile loading. If there is an injury or loss of functionality in either the nucleus 304 or annulus 302, the mechanical behavior of the disc 300 can greatly be affected.

Spinal anatomy and physiology is further described in a variety of publications including: U.S. Patent Application Publication Nos. 2007/0016302; 2007/0173821; 2007/0173822; 2007/0213822; and 2007/0270950. Spinal anatomy and physiology is also described in treatises including: J. A.

Buckwalter et al., "Orthopaedic Basic Science: Biology & Biomechanics of Musculoskeletal System" 548-66 (2000); Henry Gray, "Gray's Anatomy" 2-23 (15th ed. 1901); E.C.B. HaIl- Craggs, "Anatomy as a Basis for Clinical Medicine" (1990); "Musculoskeletal Medicine" (J. Berstein, J. Berstein ed., 1st ed. 2003); R.R. Seeley et al., "Essentials of Anatomy & Physiology" 125-26, 137 (1999); H. Sherk, "Functional Anatomy of Joints, Ligaments, & Discs" in "The Cervical Spine" (C. Clark ed. 1998); G.A. Thibodeau et al., "Anatomy & Physiology" 202-03, 231-54, 257 (2003); "Clinical Biomechanics of the Spine" (A. White & M. Panjabi eds. 1990); W.F. Windle, "The Spinal Cord & its Reaction to Traumatic Injury: Anatomy, Physiology, Pharmacology, Therapeutics" 384 (1980); H. Yamada, "Strength of Biological Materials" (1970).

Journal articles discussing spinal anatomy and physiology include: M. A. Adams & PJ. Roughley, "What is intervertebral disc degeneration, and what causes it?," 31(18) Spine 2151-61 (2006); H. S. Ahn & DJ. DiAngelo, "Biomechanical testing simulation of a cadaver spine specimen: development & evaluation study," 32(11) Spine E330-36 (2007); P. A. Anderson & J.P. Rouleau, "Intervertebral disc arthroplasty," 29(23) Spine 2779-86 (2004); M.M. Durbhakula & G. Ghiselli, "Cervical total disc replacement, part I: rationale, biomechanics, and implant types," 36(3) Orthop. Clin. North. Am. 349-54 (2005); M.F. Eijkelkamp et al., "Requirements for an artificial intervertebral disc," 24(5) Int. J. Artif. Organs 311-21 (2001); H.D. Link et al., "Choosing a cervical disc replacement," 4(6 Supp.) J. Spine 294S-302S (2004); J. S. Schwab et al., "Motion compensation associated with single- level cervical fusion: where does the lost motion go?," 21(21) Spine 2439-48 (2006); M.E. Smith et al., "A biomechanical study of a cervical spine stabilization device: Roy-Camille plate," 22(1) Spine 38-43 (1997); E.E. Swartz et al, "Cervical spine functional anatomy and the biomechanics of injury due to compressive loading," 40(3) J. Athl. Train. 155-61 (2005); and AJ. Walsh & J.C. Lotz, "Biological response of the intervertebral disc to dynamic loading," 37(3) J. Biomech. 329-37 (2004). Disc Dysfunction

Aging naturally changes the biomechanical behavior of the intervertebral disc 300 because the disc 300 changes in composition, shape, volume and micro structure in response to loading over time. This change in composition can affect the disc 300 by decreasing motion and causing further spinal disorders. Two very common disorders are degenerative disc disease and herniated nucleus (also known as a "slipped disc"). Degenerative Disc Disease The nucleus 304 is highly susceptible to degeneration as it ages. The high concentration of proteoglycans loses their propensity to bind water. The protein chains in aggrecan become fragmented. The nucleus 304 also increases its collagen content and becomes more fibrotic. The reduced water content of the nucleus 304 and disc 300 in general cause hydrostatic pressure to be reduced. These changes lessen the effectiveness of the disc 300 to behave as a shock absorber. Essentially, a loss in water content leads to a reduced disc height and function. This nucleus degeneration is due in large part because there is a limited blood supply to the nucleus 304. Poor diffusion restricts transport of nutrients, such as oxygen, into the disc 300. Therefore, the cells in the nucleus 304 must undergo anaerobic metabolism. A build up of lactic acid occurs in the nucleus 304 because poor diffusion also restricts the transport of the waste out of the disc 300. In this situation, the pH becomes acidic and negatively affects the proteins compromising the disc's ability to recover from any type of injury. Herniated Disc

The annulus 302 is also affected during aging. However, the outer annulus is usually the slowest to age and least affected part of the disc 300. During disc degeneration, the annulus 302 slowly becomes a stiffer, but weaker fibrocartilage. At the same time, the nucleus 304 begins to lose its ability to retain water. This fluid pressure is essential for shielding the solid matrix from large stresses in the annulus 302. Without the fluid, the disc 300 becomes a compressed mass of fibrous material between the vertebrae 200. This mass can bulge outward and press against the spinal cord 308.

When the annulus 302 assumes loading, the same fibrocartilage orientation in the annulus 302 that was effective in tension is not as effective in dealing with compressive loads. The non-uniform loading creates stress concentrations, which in turn create fissures in the annulus 302. The fissures then lead to a herniated disc 300b depicted in FIG. 3B as the nucleus 304 protrudes through the annulus 302. Direct contact of the nucleus 304 with the dura mater 308 and/or spinal nerves 310 can cause a large amount of pain and in some cases cause a loss of function in the arms and/or legs of the subject.

In one method for treating a herniated disc 300b in contact with the spinal nerves 310 or spinal cord 308, the herniated material is removed in a procedure referred to as "discectomy." As a result, the disc 300b is further weakened and additional bulging can occur. One treatment approach solve this dilemma is to restore the disc height between the vertebras 200. This

Total Disc Replacement

Referring to FIGS. 4A and 4B, one discectomy technique is a total disc replacement (TDR) in which a dysfunctional disc 402 (a herniated disc in FIG. 4A) is replaced with an artificial intervertebral disc (AID) 404. In some TDR procedures, the AID 404 includes nucleus containment device 406 encapsulating a nucleus 408 as further described herein. Nucleus Containment Device

Referring now to FIGS. 5A and 5B, a top view and a cross section, respectively, of a nucleus containment device 500a including one or more textiles 502a, 502b are provided. The textiles 502 are arranged to define an internal region 504 adapted to receive a nucleus material.

Nucleus containment device 500a can be fabricated from a variety of interfaces 502.

In some embodiments, the one or more interfaces 502 are textiles, e.g. biocompatible textiles. In some embodiments, the one or more interfaces 502 include natural interfaces such as cotton, silk, wool, and the like. In other embodiments, the one or more interfaces 502 include synthetic textiles including polymers, thermoplastic polymers, thermoset polymers, polyesters (also known as polyethylene terephthalate or PET), polypropylene, polyethylene, and the like. In some embodiments, the one or more interfaces 502 are fusible textiles in order to reduce the pore size of the one or more interfaces 502 while retaining the strength of the textiles. For example, fusible textiles can be fabricated from a variety of bi-component fibers as illustrated in FIGS. 6 A and 6B. A fusible bi-component fiber 600 can include a high melting temperature core 602 surrounded by a lower melting temperature sheath 604. When a textile containing fusible fibers 600 is heated to a temperature between the melting temperature of the sheath 604 and the melting temperature of the core 602, the sheath 604 will melt and fuse with adjacent fibers while the core 602 remains intact to provide structural support. This process is generally referred to herein as "heat treatment."

As discussed in the Working Examples herein, the use of fusible textiles advantageously improves retention of a nucleus material injected into the nucleus containment device 500.

In another embodiment, the one or more interfaces 502 include a membrane such as a silicone membrane. In one example, interface 502 can include a self-sealing material sandwiched between two layers of silicone. After piercing with a non-coring needle during injection of the nucleus material, the interface 502 will seal. In some embodiments, a number of pores can be formed in the one or more interfaces to allow a controlled amount of fluid to enter and exit the nucleus containment device 500

Referring again to FIG. 5A, the one or more interfaces 502 can be coupled together to define the internal region 502. The interfaces 502 can be coupled using a variety of techniques including mechanical fastening, chemical fastening, fusing, and the like.

Examples of mechanical fastening techniques include sewing, stapling, crimping, riveting, and the like. (Interfaces 502a, 502b in nucleus containment device 500 are coupled by thread 506.) Chemical fastening techniques include the use of adhesives, epoxies, bonding agents, and the like. Fusing includes using an energy source such as a heat source, a laser, an ultrasound device, and the like to raise the temperature in a local region of the interfaces 502 to cause the interfaces to wholly or partially melt and thereby bond upon cooling.

Nucleus containment device 500 can be fabricated in variety of shapes and sizes to reflect varying shapes of intervertebral discs 300 within the spine 100 generally and in particular subjects. For example, a "small" nucleus containment device 500 can have a height h of about 7 mm, a width w of about 14 mm, and a depth d of about 11 mm. In another example, a "medium" nucleus containment device 500 can have a height h of about 8 mm, a width w of about 17 mm, and a depth d of about 13 mm. In still another example, a "large" nucleus containment device 500 can have a height h of about 9 mm, a width w of about 20 mm, and a depth d of about 15 mm. Various nucleus containment devices can be fabricated for specific subjects. Alternatively, a variety of nucleus containment devices 500 can be sold as a kit to allow for custom fitting in the operating room.

Referring now to FIG. 5C, the one or more interfaces 502 can be a composite of a plurality of woven, knit, braided, and/or non-woven layer. For example, interfaces 502 in FIG. 5C include non-woven layer 508b sandwiched between an internal woven layer 508a and an external woven layer 508c. A variety of other composite interfaces 502 can be fabricated to facilitate desired flow rates across interfaces 502. For example, interfaces 502 can include the following layers (recited from the internal layer to the external layer, wherein 'W denotes a woven textile layer and 'N' denotes a non-woven textile layer): W, N, W-W, N-N, W-W-W, W-N-W, W-W-N, N-W-W, W-N-N, N-W-N, N-N-W, N-N-N, W-W-W-W- W, W-N-W-N-W, N-W-N-W-N, N-N-N-N-N, and the like.

Referring now to FIG. 5D, some embodiments of the nucleus containment devices herein consist of a single interface 502e folded upon itself to define internal region 504. Such an arrangement can be advantageous due to the reduction in the seams and the attendant reduction in coupling materials and labor as well as reduction of potential failure points.

One or more stitching techniques can be used at the seams between interfaces 502. For example, a bound seam can be formed by coupling an additional interface over the exterior of the seam. Bound seams are described in publications such as U.S. Patent No. 4,753,182. In another example, a superimposed seam can be formed by folding one or more of the interfaces 502 upon itself and/or another interface 502. In some embodiments, an overlock, overedge, serge, or merrow stitch is used. Methods of Fabricating a Nucleus Containment Device

Referring now to FIG. 7, a method 700 of fabricating a nucleus containment device 500 is provided. In step S702, a core is placed within one or more interfaces 502. The core preferably has a shape that is substantially complimentary to the desired internal region for the nucleus containment device 500. In some embodiments, the core is a dissolvable core. For example, the core can be fabricated from a biocompatible material such a biocompatible salt. Suitable salts include any salt or salt mixture that will not degrade at the heat treatment temperature for the interface (e.g., about 205° C) and that has a high saturation point in a solvent. Exemplary salts include calcium phosphates, sodium chloride, and the like. In one embodiment, the dissolvable core consists of a mixture of about 50% calcium sulfate (CaSO ₄ ) and about 50% calcium carbonate (CaCO ₃ ) by mass. The core can be formed with a variety of techniques including the use of molds (e.g., molds formed dental impression material).

In some embodiments, the interface(s) 502 are coupled (S704) before the interfaces 502 are placed in the mold. The interface(s) can be coupled according to the methods described herein. Alternatively, coupling step S704 can occur during a variety of intervals during process 700 as depicted in FIG. 7. In step S706, the one or more interfaces 502 and the core are placed into a mold having a shape that is complimentary to a desired external shape of the nucleus containment device 500. The mold is preferably capable of withstanding a temperature sufficient to fuse the fibers in certain embodiments of the invention. Suitable mold materials include polytetrafluoroethylene (PTFE) and metals. In step S708, the mold is heated. In some embodiments, the mold is placed in an oven

(e.g., a traditional oven, a convection oven, a microwave oven, and the like). In a particular embodiment, the mold is heated in convection oven set to about 205° C for between about 15 minutes and about 20 minutes. In other embodiments, a heating element is integrated within or is placed adjacent to the mold. In step S710, the mold is cooled (e.g. to room temperature). Cooling can be controlled by placing the mold in a cool environment, flowing a cooled fluid over and/or through the mold, and the like.

In step S712, the one or more interfaces 502 and core are removed from the mold. Removal may be enhanced by the use of a mold fabricated from a non-stick material such as PTFE or a mold coated with a release agent.

In step S714, the core is removed from the one or more interfaces 502. In some embodiments, the core is removed in a single piece via an opening in the interface(s) 502. In other embodiments, the interface(s) are coupled to completely enclose the internal region 504 and therefore the core. In such embodiments, the core can be dissolved in an acidic solution. For example, the molded interfaces 502 enclosing the core can be placed in a stirred solution of 3 M hydrochloric acid for approximately one to four hours to dissolve the core while maintaining the structural viability of the interfaces 502. In step S716, the molded nucleus containment device 500 is rinsed to remove any toxic residues. For example, the nucleus containment device 500 can be rinsed in de-ionized water until the pH is neutralized.

Methods for Implanting a Synthetic Symphysis and Treating Symphysis Dysfunction Referring now to FIG. 8, methods 800 of implanting a synthetic symphysis and treating symphysis dysfunction is provided.

Optionally, an existing symphysis is removed in step S802. The existing symphysis can be removed using existing surgical techniques such as a discectomy. Discectomies and other surgical procedures useful in the methods herein are described in publications such as "The Cervical Spine: An Atlas of Surgical Procedures" (Henry H. Sherk et al., eds. 1994).

In step S 804, a nucleus containment device is inserted between two bones. The nucleus containment device can be an embodiment of the nucleus containment devices described herein.

In some embodiments, the nucleus containment device 500 is introduced via a cannula to minimize the invasiveness method 800. The nucleus containment device 500 can be placed within the cannula (e.g., by packing, rolling, folding, and the like) for insertion into the joint. The nucleus containment device 500 can then be pushed out of the cannula into the joint. Depending on the shape memory properties of the interfaces 502, the nucleus containment device 500 can, in some embodiments, expand to desired shape with little or no manipulation. In other embodiments, the nucleus containment device 500 can be manipulated with existing surgical tools to achieve the desired shape and orientation.

In step S806, a nucleus material is injected into the internal region 504 of nucleus containment device 500. A variety of nucleus materials can be injected into the nucleus containment device 500 to reflect the desired characteristics of the joint. In some embodiments, the injected nucleus material is a natural nucleus material.

Such a material can be harvested from one or more discs (including, but not limited the subject's recently removed disc). In still another embodiment, the nucleus material can be a naturally occurring material such as various gutta percha compounds discussed in U.S. Patent No. 6,206,921. In other embodiments, the injected nucleus material is a synthetic nucleus material. A variety of synthetic nucleus materials including polymers, hydrogels, and ceramics are discussed in publications such as U.S. Patent No. 3,200,102; 3,926,930; 4,107,121; 4,331,783; 4,337,327; 4,369,294; 4,370,451; 4,379,874; 4,420,589; 4,653,358; 4,943,618; 5,047,055; 5,192,326; 5,252,692; 5,537,028; 5,562,736; 5,674,925; 5,674,295; 5,688,855; 5,817,303; 5,824,093; 6,022,376; 6,033,654; 6,132,465; 6,232,406; 6,264,695; 6,423,333; 6,451,922; 6,533,817; 6,602,291; 6,617,390; 6,726,721; 7,204,897; and 7,556,50; U.S. Patent Application Publication No. 2002/0193531; 2007/0270950; 2005/0171611; and 2007/0299201; and J. Vernengo et al., "Evaluation of Novel Injectable Hydrogels for Nucleus Pulposus," J. Biomed. Mat. Res. Part B: Applied Biomaterials 64-69 (2007).

For example, the polymer materials can include polyurethane, polyolefin, silicone, silicone polyurethane copolymers, polymethylmethacrylate, epoxy, cyanoacrylate, hydrogels, resorbable polymers, and the like. Further, the polyolefin materials can include polypropylene, polyethylene, halogenated polyolefin, flouropolyolefin, and the like. The hydrogels can include polyacrylamide (PAAM), poly-N-isopropylacrylamine

(PNIPAM), polyvinyl methylether (PVM), polyvinyl alcohol (PVA), polyethyl hydroxyethyl cellulose, poly (2-ethyl) oxazoline, polyethyleneoxide (PEO), polyvinyl ether, polyethylglycol (PEG), polyacrylacid (PAA), polyacrylonitrile (PAN), polyvinylacrylate (PVA), polyvinylpyrrolidone (PVP), and the like. Hydrogels are further described in publications such as I-III "Hydrogels in medicine & pharmacy" (Nikoload A. Peppas, ed. 1987) and "Hydrogels for medical & related applications" (Joseph D. Andrade, ed. 1976).

The resorbable polymers can include polylactide (PLA), polyglycolide (PGA), polylactide-co-glycolide (PLG), Poly-e-caprolactone, polydiaoxanone, polyanhydride, trimethylene carbonate, poly-β-hydroxybutyrate (PHB), poly-g-ethyl glutamate, poly-DTH- iminocarbonate, poly-bisphenol-A-iminocarbonate), polyorthoester (POE), polyglycolic lactic acid (PGLA), and the like.

The ceramics can include calcium phosphate, hydroxyapatite, calcium sulfate, bioactive glass, and the like.

The injected nucleus material can also include one or more additives. For example, the additives can include water, solvents, radiocontrast media, drugs, cellular matters, biological factors, or a combination thereof. In a particular embodiment, the drugs can include antibiotics, analgesics, anti-inflammatory drugs, anti-TNF-alpha, steroids, or a combination thereof. Further, the cellular matters can include bone marrow derived stem cells, lipo derived stem cells, or a combination thereof. Also, the biological factor can include bone morphogenetic protein (BMP), cartilage-derived morphogenetic protein (CDMP), platelet derived growth factor (PDGF), insulin-like growth factor (IGF), LIM mineralization protein, fibroblast growth factor (FGF), osteoblast growth factor, and the like. A variety of other suitable additives are described in U.S. Patent Application Publication No. 2007/0213822. Commercially available injectable nucleus materials are available under the DASCOR® trademark from Disc Dynamics, Inc. of Eden Prairie, Minnesota and under the NUCORE® trademark from Spine Wave, Inc. of Shelton, Connecticut. Working Example 1 : Textile Performance In order to verify the beneficial effects of heat treating a textile, several tests were conducted on a polyester textile prepared from 81 denier bi-component monofilament fibers by Biomedical Structures, LLC of Warwick, Rhode Island. Several pieces of the textile were placed between two metal plates and heat treated in an oven at 205 ⁰ C for 15-20 minutes. Tensile Testing of Fusible Woven Textiles The tensile test is one of the most basic experiments for determining mechanical properties. Results are typically recorded as a load or force divided by a displacement or elongation. Many samples tested can vary greatly in size and shape and are therefore hard to compare to other materials. By normalizing the load vs. elongation diagram to stress vs. strain diagram, materials can be compared to other materials for engineering comparisons and selections. Below in Table 1, the maximum loads normalized for width and average areas under the curve or toughness values for each type of textile are reported. Results are given as the average and the standard deviation for each of the textile samples tested.

TABLE 1 Tensile data showing maximum loading and total energy of the various fabric samples

Fabric Type Max Load at Failure Ultimate Ultimate Tensile Modulus of

(N) Strain (%) Stress (MPa) Toughness (MJ/m ³ )

Warp (Untreated) 665.2 + 18.4 35 + 2 498 + 19 7270 + 417

Warp (Treated) 646.1 + 24.7 62 + 4 512 + 14 14279 + 1321

Weft (Untreated) 594.8 + 8.1 127 + 9 509 + 7 20921 + 2341

Weft (Treated) 670.8 + 28.2 229 + 18 573 + 24 50034 + 6318 Statistical analysis using 2-factor ANOVA with Tukey' s HSD multiple comparison test performed on the data shows significant differences at 95% confidence (p = 0.05) between all textile samples with respect to maximum load at failure. Only the heat treated weft textile type was significantly different from the other three textile types in the ultimate tensile test analysis at (p<0.05). With regards to modulus of toughness, heat treated weft fabric was significantly different from the three other test groups at p < 0.05. The non heat treated warp textile was also significantly different to the other three textile types at p < 0.05. FIG. 9 depicts the stress vs. strain curves of the textiles tested.

Statistically, each textile is significantly different. However, due to the difference in gauge lengths during testing, it would be erroneous to make a direct comparison between warp and weft directions. Even though it is difficult to draw conclusions about the differences between warp and weft directions, conclusions about the effects of the heat treatment on the textile can be drawn from the data. It is important to note that in both directions, warp and weft, the heat treatment enhances the textile's capacity for work (also known as "toughness").

Tensile strengths for the native annulus tissue have been reported to be between a range of 0.3-15 MPa. "Clinical Biomechanics of the Spine" (A. White & M. Panjabi eds. 1990); H. Yamada, "Strength of Biological Materials" (1970). The tensile stresses of the fabrics tested were found to be higher than the reported tensile stresses of the annulus from the literature with the fabrics having an ultimate tensile strength close to 500 MPa. A higher ultimate strength is favorable as an AID where the fabric containment device could withstand the forces exerted through the disc during loading. Another important result observed from the tensile testing is that the total work of the fabric is increased after the heat treatment and the elastic modulus is reduced in both the warp and weft directions. Both of these conditions are due to the polymer chains being relaxed after the temperature was raised above the glass transition temperature of the polymer. It then takes additional energy to straighten the polymer chains before the chains are loaded directly. In an application such as an artificial disc replacement where cyclic loads are experienced, it is beneficial to have a material with increased toughness and a lower stiffness. These device qualities enhance durability, as well as increased range of motion compared to more rigid devices, such as graft and plate seen in fusion, which may accelerate adjacent disc degeneration. There is also a concern that stiffer metal AIDs may cause osteoporotic endplates of the spine to collapse after implantation, which a less stiff medical textiles nucleus containment device could avoid. Flex Abrasion Measurements of Fusible Woven Textiles Three samples of both heat treated and non heat treated textiles were tested using a flex abrasion test. The flex abrasion test applies a severe form of abrasion to fabrics. "Wellington Sears Handbook of Industrial Textiles" 40-52, 87-157, 329-55 (S. Adanur, ed. 1995). The metal abrader has right angled corners that harshly apply abrasion on the textile surface. Based on this data, a trend on the polyester textile performance in abrasion testing after a heat treatment compared to pre heat treatment conditions was determined.

In Table 2, the abrasion tests results are reported in average number of cycles until failure along with standard deviation between the three samples. TABLE 2 Number of cycles until failure for non-heatset vs. heatset fabrics in flex abrasion testing

Textile Non Heat Treatment Heat Treatment

12500 28230

Number of Cycles 11320 9700 11440 12250

Average (# of Cycles) 11753 16727 Std Dev (# of Cycles) 649 10043

Due to a high standard deviation of the heat treated textiles, the two textiles samples were not statistically different at p < 0.05. Therefore, the data and number of samples could not define any differences. However, a trend, based on the average number of cycles to failure, shows the heat treated fabrics are able to withstand greater numbers of cycles than the non heat treated fabric.

One possible conclusion from the trend is that the heat treated textile fails at higher a number of cycles due to the increased toughness caused by the heat treatment. This result was also seen in the tensile testing evaluation. This trend reinforces the point that, with an increased toughness due to heat treatments, the textiles are capable of performing more work before failure compared to the non heat treated textiles. Pore Size Before and After Heat Treatment The pore size of the polyester fabric was calculated from examination of the images analyzed using the BIOQUANT® OSTEO™ II software (available from BioQuant, Inc. of Ann Arbor, Michigan) and comparing pore sizes before and after heat treatment.

Observations from FIG. 1OA show that there are larger pores present and evenly spaced through the non heat treated textile. These larger pores look like bright rectangles throughout the textile weave. In the heat treated image, FIG. 1OB, the larger pores are still evident, although many of the larger, evenly spaced pores have significantly decreased in size and some have even closed completely. These larger pores are obvious openings in the fabric weave and should be included into any calculation of pore size because these larger pores will contribute to the bulk fluid flow in and out of the nucleus containment device 500 after implantation. The larger pore sizes are also important to allow the relatively viscous nucleus material to completely permeate the nucleus containment device 500 and allow for fluid flow and nutrient transfer within the device 500.

Smaller pores have also been observed in the fabric between the individual fibers, which could allow some fluid and smaller molecules to diffuse through the nucleus containment device 500. Although the smaller light areas in FIGS. 1OA and 1OB look like pores between fibers, many of these areas are actually light passing through individual fibers giving the illusion of pores. A few of these smaller areas are actual pores, but the imaging software is not robust enough to distinguish between actual pores and light passing through individual fibers. It was confirmed with a second microscope that there are pores sparsely located between the individual fibers that could contribute to diffusion of fluids to rehydrate the nucleus material. However these smaller areas have not been quantified. Most of the fluid transfer will be accomplished through the large pores and even though the imaging software does report measurements of the smaller pore sizes from the images captured, only the large pore areas will by used for average area calculations due to the above-mentioned complications.

In Table 3 below, pore size is reported as an average area of the large pores along with the standard deviations. The pore size is measured in μm ² . Statistical analysis determined an extremely significant difference between heat treated and non heat treated samples (p = 8.3 x 10 ^~20 ). TABLE 3

Pore size averages of fusible woven fabric before and after heat treatment

Large Pores Only

Non-heatset Heatset

Average (μm ^z ) 4545.80 761.95 Std Dev (μm ² ) 2891.86 954.22

Average pore size decreased approximately 80-85% during the heat treatment. A decreased pore size can be very beneficial to the nucleus material before and after polymerization for different reasons. Before polymerization, smaller pores allow just enough fluid transfer for the nucleus material to disperse throughout the nucleus containment device 500 and polymerize within the device 500. After polymerization, the nucleus material remains trapped inside the device 500 because the polymerized nucleus material is not able to physically pass through the relatively smaller pores. This containment was observed in the experiments discussed herein. Working Example 2: Fabrication of Nucleus Containment Devices

Referring now to FIG. 11 , a plurality of dissolvable cores 1102 were molded within dental impression material to substantially approximate the desired internal region 504 of nucleus containment device 500. The dissolvable cores were formed from a mixture of about 50% calcium sulfate and about 50% calcium carbonate by mass. Molds 904 were formed with POLYJEL® NF polyether dental impression material available from Dentsply International, Inc. of York, Pennsylvania.

Referring now to FIG. 12, a dissolvable core 902 was placed between two pieces of woven polyester textile 1202. The polyester textile 1202 is approximately 1.5 inches wide and was prepared from 81 denier bi-component monofilament fibers by Biomedical

Structures, LLC of Warwick, Rhode Island. The textiles 1202 and core 1102 were placed in a PTFE mold 1204. Mold 1204 includes a top piece 1206a and a bottom piece 1206b. Each piece 1206 defines a profile 1208 of the exterior of the nucleus containment device 500. Mold pieces 1206 were held together through the use of bolts 1210. Assembled mold 1204 was placed in a Lindberg/Blue M 1420S A-I mechanical convection oven heated to 205° C for between 15 and 20 minutes. The mold 1204 was then removed from the convection oven and cooled to room temperature. The textiles 1202 and the core 1102 were then removed from the mold 1204.

Referring now to FIG. 13, a hand sewing punch 1302 was used to create a plurality of approximately 0.75 mm diameter pilot holes in textiles 1202 for sewing.

As depicted in FIG. 14A, the textiles 1202 were then stitched with a heavyweight nylon upholstery stitching thread 1402a from Coats & Clark of Greenville, South Carolina to further couple textiles 1202. Excess textiles 1402 were trimmed from to produce nucleus containment device 500. The nucleus containment device 500 (still containing the dissolvable core) was placed in a stirred solution of 3 M hydrochloric acid for approximately 3-4 hours to dissolve the core. The nucleus containment device 500 was then rinsed in de-ionized water until its pH was neutralized. Finally, the nucleus containment device 500 was inspected for any material faults. Working Example 3: Compression Testing of Nucleus Containment Device

To test compression, one medium sized prototype of each of nine nucleus containment device 500 variations was injected with NUCORE® nucleus material and allowed to cure for 30 minutes in sterile phosphate buffered solution (PBS) at 37° C in a water bath. Volumes of injections were logged. The prototypes were placed on an MTS-810 servohydraulic load frame (available from MTS Systems Corp. or Eden Prairie, Minnesota) for compression testing using a standard Spine Wave compression testing protocol. The test consisted of evaluating the loads experienced in a filled device 500 compressed between a stationary flat platform and a traversing load cell equipped with a flat plate. The test was performed at constant displacement rate of 1 mm/sec. MTS FlexTest SE software (available from MTS Systems Corp. of Eden Prairie, Minnesota) was used to digitally collect load and displacement data at 50 Hz.

Table 4 provides compression test data for several embodiments of nucleus containment devices 500. TABLE 8

Compression test data of 9 nucleus containment prototype variations listing fill volumes, maximum loading, and cause of failure of each variation.

Prototype Fill volume Max Load Failure Cause

Variation (CC) (N)

1 Layer 0.6-0.7 202.8 Delamination and nucleus expulsion at seam

(W)

1 Layer 0.7 241.9 Nucleus expulsion through injection site

(N)

2 Layer 0.8 507.9 Delamination and nucleus expulsion at seam

(N-N)

3 Layer 0.7 130.8 Delamination and nucleus expulsion at seam

(W-W-W)

3 Layer 0.8-0.9 159.0 Delamination and nucleus expulsion at seam

(W-N-W)

3 Layer 0.8 317.5 Delamination and nucleus expulsion at seam

(N-W-N)

5 Layer 0.7 132.4 Delamination and nucleus expulsion at seam

(W-W-W-W-W)

5 Layer 0.8 328.7 Delamination and nucleus expulsion at seam

(W-N-W-N-W)

5 Layer 0.8 372.4 Delamination and nucleus expulsion at seam

(N-W-N-W-N)

Although testing revealed that the stitched seam is weakest link in the tested embodiments of the nucleus containment device 500, the prototypes did handle compressive loads observed during daily living in the cervical spine. As previously discussed, typical compressive loading of the cervical spine ranges from 70-150 N. The 3-layer W-W-W prototype failed at 130 N, which is the lowest load recorded during testing. The 2-layer N-N device did not fail until loads of over 500 N. This is almost five times the normal daily loads. Based on the fact that woven fabric has stronger tensile properties than non- woven fabrics, if a device was made with a higher woven to non- woven fabric ratio and the seam was reinforced, the nucleus containment prototype could be capable of handling compressive loads well within an appropriate factor of safety for an AID. Clinical literature suggests failure of cervical vertebral bodies occur with in the range 950-4450 N tested at different loading rates. Therefore, current prototypes have shown the capability to contain a nucleus material and handle 25-50% of the necessary compressive loading. Further testing of nucleus containment devices with machine- stitched seams demonstrated increased robustness and decreased delamination and expulsion of nucleus expulsion. An machine stitched nucleus containment device before trimming of excess textiles is depicted in FIG. 14C. The nucleus containment device includes two concentric rings of stitching 1402b, 1402c. Additionally, a ring of stitching 1402d surrounds a target filling point. Working Example 4: Implantation and Functional Characterization

To verify the efficacy of the invention, several nucleus containment devices 500 were implanted in a cadaveric cervical spine. A discectomy was performed on the C3-C7 discs with out disturbing the end plates. A nucleus containment devices 500 was inserted into each disc space and injected with NUCORE® nucleus material mixed with radiopaque additives in accordance with manufacturer Spine Wave's protocols for fluoroscopic imaging. Injection volumes were logged.

Table 4 shows the prototype size and variation chosen for implantation into cervical spine of a cadaver after a discectomy. Table 4 also describes the disc level the prototype was implanted at and the volume of NUCORE® nucleus material injected into each nucleus containment device 500. Comments describing observations taken during prototype fitting and filling are included.

TABLE 4 Cadaveric fitting and filling of nucleus containment prototypes

Prototype Fit Level Injection Observations/Comments Placement Volume

Small 3 Layer C3-C4 0.4 cc Implanted easily, prototype void is not pre (W-N-W) compressed, good fill and containment Med 2 layer C4-C5 0.5 cc Too much fabric, prototype is compacted, (N-N) adequate fill and containment Med 1 Layer C5-C6 0.3-0.4 cc Adequate fill and containment, injection (W) possibly too posterior Small 5 Layer C6-C7 0.6 cc Good containment, too much fabric fills disc (N-W-N-W-N) space, not a good opportunity for NuCore® functional support

Images (e.g., FIGS. 15A and 15B) were recorded with an OEC® 9000 Digital C-Arm Fluoroscope available from The General Electric Company of Schenectady, New York. Fluoroscopic images are useful to visualize the filled device 500 in the disc space. Even though polyester is not visible during fluoroscopic imaging, the containment can be inferred by observing the shape and depth of the radiopaque nucleus material. FIG. 15A shows a fluoroscopic image taken from a lateral view of a cadaveric cervical spine with nucleus containment prototypes implanted at C4-C5, C5-C6, and C6-C7. FIG. 15B shows another fluoroscopic image captured from an anterior view of nucleus containment prototype implanted at levels C3-C4, C4-C5, C5-C6, and C6-C7.

As illustrated in FIGS. 15A and 15B, the nucleus containment devices 500 contained the nucleus material and did not allow ingress into the vertebral foramen, where the spinal cord is located.

EQUIVALENTS

The functions of several elements may, in alternative embodiments, be carried out by fewer elements, or a single element. Similarly, in some embodiments, any functional element may perform fewer, or different, operations than those described with respect to the illustrated embodiment. Also, functional elements shown as distinct for purposes of illustration may be incorporated within other functional elements, separated in different hardware, or distributed in a particular implementation.

While certain embodiments according to the invention have been described, the invention is not limited to just the described embodiments. Various changes and/or modifications can be made to any of the described embodiments without departing from the spirit or scope of the invention. Also, various combinations of elements, steps, features, and/or aspects of the described embodiments are possible and contemplated even if such combinations are not expressly identified herein.

INCORPORATION BY REFERENCE

The entire contents of all patents, published patent applications, and other references cited herein are hereby expressly incorporated herein in their entireties by reference.