WO2007133214A1

WO2007133214A1 - Prosthetic disc nuclear replacement and soft-tissue reconstruction devices

Info

Publication number: WO2007133214A1
Application number: PCT/US2006/018987
Authority: WO
Inventors: Murali Jasty
Original assignee: Massachusetts General Hospital
Priority date: 2006-05-17
Filing date: 2006-05-17
Publication date: 2007-11-22

Abstract

The invention provides medical devices for prosthetic disc nuclear replacement, soft-tissue replacement, reconstruction or augmentation, methods of implanting the devices, methods of treating mammals with disc degenerative disease, and kits for nuclear disc replacement and soft-tissue replacement, reconstruction or augmentation. The invention also provides medical device for intervertebral disc replacement, wound care, cartilage replacement, joint replacement, implantation as a surgical barrier or a gastrointestinal device, a cosmetic and reconstructive operation, ear, chin, cheek, or nose reconstructive operation, or breast or muscle enlargement. Methods of implanting a deflated device into a mammal in a surgical procedure and subsequently inflating the implanted device with a suitable gellant or combination of gellants also are disclosed.

Description

PROSTHETIC DISC NUCLEAR REPLACEMENT AND SOFT-TISSUE RECONSTRUCTION DEVICES

FIELD OF THE INVENTION

The present invention generally relates to medical devices for prosthetic disc nuclear replacement, soft-tissue replacement, reconstruction or augmentation and methods of implanting the medical devices. The invention also relates to methods of treating mammals by implanting the medical devices.

BACKGROUND OF THE INVENTION

The spinal disc is a flexible shock absorbing member interposed between two bony vertebral bodies (see Fig. 1 (I)). It consists of a nucleus (see Fig. 1 (5)), a compliant, somewhat elastic polysaccharide gel (glycosaminoglycan) surrounded by an annulus (see Fig. 1 (3)), which consists of multiple circumferential laminations of flexible but inelastic collagen fibers. The gel acts like the air in a tire, where the swelling keeps the annular ring pressurized, thus stretching the fibers of the annulus and stabilizing the vertebral segment. In case of disc herniation, the annulus ruptures (see Fig. 2 (13)) and the nucleus (see Fig. 2 (5)) is extruded (see Fig. 2 (15)) through the opening and imposes pressure on adjacent nerve roots and causes pain. With advancing disease, the height of the disc is reduced due to loss of the annulus, which leads to the misalignment of posterior facet joints (see Fig. 2 (7)), which in turn leads to degenerative arthritis. Furthermore, compression of the nerves from extruded disc material and the bone spurs also leads to pain. Surgical treatment of the disc degenerative diseases involves the removal of the extruded disc material to relieve the pain. However, the progressive arthritis due to loss of the disc height and mal-alignment of the facet joints continues, which leads to instability and further pain. Spinal fusion is advocated to relieve these symptoms, but the fusion of the spine conies at a cost of impaired function at the fused segment, excessive mobility at the adjacent segments, which leads to further degenerative disorders and pain. Thus, there is a need for disc replacement, which can maintain the disc height, preserve motion, prevent joint degeneration, and reduce the morbidity of the fused spine. However, metallic and plastic disc replacement devices in the prior art have not been popular because of the disadvantages of being very invasive and mechanically unsound in replicating the disc function.

Some of the currently available disc replacement devices contain metallic end- plates and softer polymeric material bearing surfaces between the end-plates. These devices replace the entire disc, including the annulus and the nucleus. The most widely implanted disc to date is the Link SB Charite disc (Waldemar Link GmbH & Co, Hamburg, Germany), which consists of a biconvex ultra high molecular weight polyethylene (UHMWPE) spacer. This core spacer interfaces with two separate end- plates. Although these devices have offered improved outcomes (such as reduced pain, improved walking distance and mobility), device failure, dislocation, and migration still occur in a significant number of cases necessitating further surgery. Mechanical failure and wear of the polymeric material of the device are additional major concerns. Also, it is difficult to implant the Link SB Charite disc with minimally invasive surgical techniques. Implantation of the Link SB Charite disc requires extensive surgery to remove the annulus fibrosis. Thus, extrusion and movement of the prosthesis are also concerns while using the Link SB Charite disc and other similar devices.

Other types of devices, which are generally classified as prosthetic nuclear replacement devices, replace the nuclear material of the disc with prosthetic materials having similar mechanical properties (such as hydrogels). However, unlike the above devices, the annulus fibrosis is not completely removed. Of these, polyvinyl alcohol and polyethylene glycol based hydrogels have been advocated because of their similarities to the nuclear material in load carrying capacity, elastic modulus, and water retaining characteristics.

A variety of hydrogels have been proposed for tissue replacements, including disc replacements. Ku et al. (US Pat. No. 5,981,826) disclose a polyvinyl alcohol hydrogel construct having a wide range of mechanical strengths for use as a human tissue replacement. The process disclosed eliminates the dehydration step of the hydrogel prior to implantation. The construct could be used as a tissue scaffolding or a load bearing surface within the joint. Park et al. (J Biomed Mater Res. 71A(3): 497-507, 2004) describe chemoenzymatic synthesis of sugar-containing biocompatible hydrogels such as crosslinked poly methylgucoside acrylate and polymethylgucoside methacrylate hydrogels synthesized chemoenzymatically. The synthesis were done by lipase-catalyzed esterification of β-methylglucoside with acrylic acid/methacrylic acid/vinyl acrylate/vinyl methacrylate in a solvent as well as in a solvent-free process for the formation of sugar- containing monomers. The polymerization process was a free-radical polymerization with or without a crosslinker (such as ethylene glycol dimethacrylate). Thus, it was possible to make various hydrogels using chemical processes, employing free-radical polymerization, and by crosslinking.

Bao et al. (US Pat. No. 5,800,549) disclose a method and apparatus for inserting an elastic spinal implant made of polyvinyl hydrogel. This device has a tapered canola and a force generating and transmitting elements. This device is useful in inserting solid or semisolid implants, which are formed outside the body and prior to inserting into the disc space. The process requires drilling of the annulus to make an opening into the annulus to insert the device. The process does not include in situ formation of solid implants or in situ shape formation of the implant. Although the prosthetic nuclear replacement devices leave portions of the annulus intact, and can be inserted through minimally invasive techniques, they do require removal of a part of the annulus. The opening in the annulus allows the devices to extrude from the disc space into the exterior and requires revision surgery. Another hydrogel based prosthetic disc nucleus implant is reported to replicate the normal function of the disc (Bjorn Branth, Third Middle East Spine Group, Beirut, Lebanon, in September, 1998). This implant's hydrogel core exhibited swelling pressures, essentially the same as the replaced nucleus, and changed in response to diurnal force bearing. Encasing the hydrogel is a flexible inelastic jacket of woven high molecular weight polyethylene, which allows fluid exchange while protecting the hydrogel. Complications related to this device included extrusion of the implant in one out of three patients. The device extruded into the epidural space through the annular opening in two patients. Thus, extrusion of the disc implant is known as a major problem for these types of devices. Hubbell (US Pat. No. 6,129,761) describes the use of an injectable hydrogel composition to reconstruct muscle and cartilage tissues, and to repair defects such as reflux and incontinence. Hubbell also disclosed a method for making and implanting a cell-hydrogel suspension into an animal whereas the biocompatible polymer is crosslinked to form a hydrogel matrix. The application of such hydrogen composition is limited to tissue augmentation or use as a replacement material. Ruberti et al. (US Publication Nos. 20040171740 and 20040092653) also describe injectable hydrogels and methods for in situ solidification of poly vinyl alcohol hydrogels. However, use of such materials and methods in disc replacement is not feasible, because injected materials will not be able to form a desired nuclear disc shape. Lozier (US Pat. No. 6,733,533) discloses a spinal disc prosthesis, to replace a natural human spinal disc. The prosthesis contains a flexible braided fiber annulus and a pair of woven metallic end-plates with micro-fixation means for initial fixation to adjacent bone. In this device both the annulus and the nucleus are replaced. The annulus is replaced by a flexible ring of a predetermined size and shape. Fluid inside the hollow interior of the annulus inflates to the size and shape of the spinal disc annulus. Inside the annulus contained another flexible shell containing a hollow interior, which is the prosthetic spinal nucleus. A second fluid is added to the hollow interior to inflate the nucleus. Apparently, the device contains two chambers. The disadvantage of this device is that two chambers are required to replace the annulus and the nucleus. Moreover, an artificial annulus cannot replace a biologically active natural annulus containing living tissue with instant blood supply, which instantly can repair and remodel the disc. Therefore, in order to treat a disc degenerative disorder, it is essential to replace only the nuclear material, which does not require instant blood supply and allows the natural annulus to re-grow and repair the disorder. Soft-tissue reconstruction or augmentation, such as expansion of ear, nose, lip, and other body parts, has been practiced by primitive cultures for aesthetic or religious purposes. Tissue expanders are now used widely in medicine in many applications, such as the expansion of scalp to treat male pattern baldness, nose, ear, and eyelid reconstruction, facial resurfacing, breast augmentation, raising musculocutaneous flaps, bladder reconstructions and cosmetic surgeries. The tissue expanders are usually silastic balloons which are filled with saline over a period of time ranging from minutes to days. The problems with tissue expansion and augmentation devices include leakage of fluid, difficulties in obtaining and maintaining the shape of the implanted devices, biocompatibility and foreign body reactions of the materials, and scar from the surgery used to implant the devices. Pooling of injected saline, disproportionate expansion of tissue, and gravitational descent of the implant also are listed with major disadvantages.

Another known approach for small volume of tissue augmentation involves injection of collagen gels directly into the tissue, however, foreign body reaction to the collagens and difficulties in maintaining the shape of the injected materials are of major concerns. Moreover, leakage of silicone from breast implants and the tissue reactions to the silicone, which lead to considerable morbidity, is another major problem associated with the tissue augmentation devices known in the art.

Craniofacial Reconstruction: Auricular, nasal and eyelid reconstructions use tissue expansion to expand the skin in the areas. Once adequate skin become available, the cartilage framework is placed into the expanded area and reconstruction is performed.

This involves staged surgical procedures, first to expand the skin and then to reconstruct the desired organ by filling the expanded spaces with biological or non-biological materials. Problems associated with leakage of the expansion device and inability to rigidly maintain the shape of the device occur with these techniques. Pooling of injected saline, disproportionate expansion of tissue, and gravitational descent of the implant also can occur with these procedures.

Soft-tissue fillers, most commonly injectable collagen or fat, can help fill in these lines and creases, temporarily restoring a smoother, more youthful-looking appearance. When injected beneath the skin, these fillers plump up creased and sunken areas of the face. They also can add fullness to the lips and cheeks. Injectable fillers may be used alone or in conjunction with a resurfacing procedure, such as a laser treatment, or a recontouring procedure, such as a facelift. Hylaform, a hylauronic acid derivative is indicated for injection into the mid-to-deep dermis for correction of moderate to severe facial wrinkles and folds (such as nasolabial folds). The drawbacks of these procedures include the biologic components of these materials, such as collagen, which is immunogenic and can give rise to inflammatory tissue reaction. Furthermore, the maintenance of the shape of the implanted materials is not possible, because these materials are liquid and easily deform. U.S. Patent No. 5,219,360 discloses a mammary prosthesis containing a liquid gel of crosslinked hylauronic acid inside a medical grade elastomer. While the hylauronic acid is more biocompatible than silicone and is similar to saline, it also is a liquid-gel like substance, and has the inherent problems associated with leaking, wrinkling, folding and sagging. U.S. Patent No. 5,632,774 discloses an implantable breast prosthesis which prevents bleeding by using a new filler material made out of discrete biocompatible crosslinked hydrogel bodies or units in various possible shapes. The hydrogel units are cross-liked polymeric beads or balls, mechanically stable, non-soluble and have a network of hydrophilic pores capable of trapping, retaining all the injected water and expanding with water absorption. However, the fillers in such prosthesis has the disadvantage of not being liquid and therefore, are not injectable. Furthermore, it is difficult to control the shape of the resulting prosthesis, which is dependent upon the absorption of water after the prosthesis is inserted for expansion.

Therefore, there is a need in the field to eliminate the problems associated with the leakage of mammary prosthesis, weather the filler material is biocompatible or immunogenic. Because, replacement of a leaking implant needs invasive surgical procedure.

SUMMARY OF THE INVENTION The present invention provides medical devices for prosthetic disc nuclear replacement, soft-tissue reconstruction devices, methods of implanting the devices, and methods of treating mammals with disc degenerative diseases. More specifically, the invention provides compositions and methods for implanting a deflated or empty or a partially filled pouch or device into a mammal by a minimally invasive surgical procedure. Subsequently, the implanted device is inflated by injecting a suitable gellant or a combination of gellants, and to allow the device to solidify and form a medical device of desired size and shape.

The invention also provides medical devices for intervertebral disc replacement, soft-tissue reconstruction, wound care, cartilage replacement, joint replacement, implantation as a surgical barrier or a gastrointestinal device, a cosmetic and reconstructive operation, including the expansion of soft tissues, replacement for the spinal disc, augmentation of breast or muscle enlargement, chin, cheek, ear and nose, as an implant in reinforcing the sphincter muscles of the esophagus, bladder, and wherever tissue reinforcement or augmentation is needed.

According to one aspect, the invention provides medical devices for prosthetic disc nuclear replacement comprising: a) a flexible empty or partially filled pouch, wherein the pouch is implanted into a selected site in a mammal; and b) at least one type of gellant, wherein the gellant is injected into the pouch in situ, and wherein the gellant solidifies within the pouch.

According to another aspect, the invention provides methods of replacing prosthetic disc nucleus in mammal, wherein the method comprises: a) implanting a flexible empty or partially filled pouch into a selected site of the mammal; and b) injecting at least one type of gellant into the pouch, wherein the gellant solidifies within the pouch, thereby replacing the disc nucleus.

According to another aspect, the invention provides methods of treating mammals by partially or completely replacing a prosthetic disc nucleus, wherein the method comprises: a) implanting a flexible empty or partially filled pouch into a selected site of the mammal; and b) injecting at least one type of gellant into the pouch, wherein the gellant solidifies within the pouch, thereby partially or completely replacing the disc nucleus.

According to another aspect, the invention provides kits for providing medical devices for prosthetic disc nuclear replacement to a region of interest comprising: a) a container containing flexible empty or partially filled pouches; b) a container containing at least one type of gellant; and c) delivery device, wherein the delivery device is used to inject the gellant into the pouch to form a medical device in situ.

According to another aspect, the invention provides medical devices for soft- tissue replacement, reconstruction, or augmentation comprising: a) a flexible empty or partially filled pouch, wherein the pouch is implanted into a selected site in a mammal; and b) at least one type of gellant, wherein the gellant is injected into the pouch in situ, and wherein the gellant solidifies within the pouch.

According to another aspect, the invention provides methods of implanting medical devices for replacing, reconstructing, or augmenting a soft-tissue in a mammal, wherein the method comprises: a) implanting a flexible empty or partially filled pouch into a selected site of the mammal; and b) injecting at least one type of gellant into the pouch, wherein the gellant solidifies within the pouch, thereby implanting the medical device.

According to another aspect, the invention provides methods of treating mammals by partially or completely replacing, reconstructing, or augmenting a soft-tissue, wherein the method comprises: a) implanting a flexible empty or partially filled pouch into a selected site of the mammal; and b) injecting at least one type of gellant into the pouch, wherein the gellant solidifies within the pouch, thereby partially or completely replacing, reconstructing, or augmenting the soft-tissue. According to another aspect, the invention provides kits for providing medical devices for soft-tissue replacement, reconstruction, or augmentation to a region of interest comprising: a) a container containing flexible empty or partially filled pouches; b) a container containing at least one type of gellant; and c) delivery device, wherein the delivery device is used to inject the gellant into the pouch to form a medical device in situ.

Another aspect of the invention provides methods of implanting a medical device for prosthetic disc nuclear replacement into a selected site of a mammal, wherein the method comprises: a) implanting a flexible empty or a hollow or a partially filled pouch into the selected site; and b) injecting at least one type of gellant into the pouch, wherein the gellant solidifies within the pouch and forms a solidified medical device of a desired shape.

Another aspect of the invention provides methods of treating a mammal comprising implanting a medical device for prosthetic disc nuclear replacement into a selected site of the mammal, wherein the method comprises: a) implanting a flexible empty, hollow or a partially filled pouch into the selected site; and b) injecting at least one type of gellant into the pouch, wherein the gellant solidifies within the pouch and forms a solidified medical device of a desired shape. Yet, another aspect of the invention provides kits for providing a medical device for prosthetic disc nuclear replacement to a region of interest comprising: a) a container containing flexible empty or partially filled pouches, wherein the pouches are for implantable into a selected site in a mammal; b) a container containing at least one type of gellant; and c) delivery device, wherein the delivery device is used to inject the gellant into the implanted pouch to solidify within the pouch and to form a medical device in situ.

In another aspect, the invention provides medical devices for soft-tissue reconstruction and/or augmentation comprising: a) a flexible empty or a partially filled pouch, wherein the pouch is implanted into a selected site in a mammal; and b) at least one type of gellant, wherein the gellant is injected into the pouch in situ, and wherein the gellant solidifies within the pouch and provides a medical device of a desired shape.

In another aspect, the invention provides methods of implanting a medical device for soft-tissue reconstruction and/or augmentation into a selected site of a mammal, wherein the method comprises: a) implanting a flexible empty or a partially filled pouch into the selected site; and b) injecting at least one type of gellant into the pouch, wherein the gellant solidifies within the pouch and forms a solidified medical device of a desired shape.

Still in another aspect, the invention provides methods of treating a mammal comprising implanting a medical device for soft-tissue reconstruction and/or augmentation into a selected site of the mammal, wherein the method comprises: a) implanting a flexible empty or a partially filled pouch into the selected site; and b) injecting at least one type of gellant into the pouch, wherein the gellant solidifies within the pouch and forms a solidified medical device of a desired shape. Yet in another aspect, the invention provides kits for providing a medical device for soft-tissue reconstruction and/or augmentation to a region of interest comprising: a) a container containing flexible empty or partially filled pouches; b) a container containing at least one type of gellant; and c) delivery device, wherein the delivery device is used to inject the gellant into an implanted pouch to solidify within the pouch and to form a medical device in situ.

According to one aspect of the invention, the medical device is implanted into a mammal in a surgical procedure for intervertebral disc replacement, wound care, cartilage replacement, joint replacement, implantation as a surgical barrier or a gastrointestinal device, a cosmetic and reconstructive operation, or breast or muscle enlargement. According to another aspect of the invention, the medical device is implanted into a mammal to fill-in a cavity in a cartilage defect, in a joint such as hip, knee, or a nuclear cavity, the nuclear space within the intervertebral disc, and act as an articular or load- bearing surface.

According to another aspect of the invention, the injected gellant forms the desired final shape of a spinal nucleus when solidified.

According to another aspect of the invention, the flexible pouch contains a porous surface and allows in-growth or re-growth of annulus. According to another aspect of the invention, the pouch further comprising porous metallic end-plates on the top and/or bottom of the pouch surfaces. In another aspect, the end-plates comprise titanium, tantalum, cobalt chrome alloys, or stainless steel.

According to another aspect of the invention, the pouch surface is porous to allow tissue in-growth or non-porous to provide a fluid barrier.

According to another aspect of the invention, the flexible pouch has a prescribed shape, hi another aspect, the flexible pouch contains a hollow interior.

According to another aspect of the invention, the injected gellant forms the desired final shape when solidified. According to another aspect of the invention, the gellant comprises polymer, polymer blends, copolymers, or combinations thereof. In another aspect, the gellant comprises polyvinyl alcohol (PVA), polyethylene glycol (PEG), poly ethylene oxide (PEO), polyvinyl pyrrolidone (PVP), poly-N-isopropyl acrylamide (PNIAAm)₅ polymethyl methacrylate, polyethyl methacrylate, polybutyl methacrylate, hydroxyethyl methacrylate, polyacrylonitrile (PAN) (for example, Kevlar™), polysulfone, polyamide, polylactic acid, silicone, polyfumarate, polyetheretherketone, polybutyl methacrylate and polyurethane, polyolefins, polyhydrocarbons, polyamines, biologic polymers such as fibrin, hylauronic acid, chitin, albumin, collagen, chondroitin sulfate, or combinations thereof. However, any polymers of hydrocarbons and biologic materials can be suitable depending on the mechanical needs of the tissue.

According to another aspect of the invention, the gellant further comprising materials selected from the group consisting carbon fiber, metal fiber, collagen fiber, proteoglycan, growth factor and antibiotic.

According to another aspect of the invention, the pouch surface comprises polytetrafluoroethylene (PTFE) (for example, Gortex™), vinyl polymers, polyethylene such as UHMWPE, polyacrylonitrile (PAN) (for example, Kevlar™), polysulfone, silastic, polyester (for example, polyethylene tetraphthalate such as Dacron™), polyamide, nylon, valour, polyurethane, polyolefins, polyhydrocarbons, or combinations thereof. According to another aspect, the pouch surface comprises polymer, polymer blends, copolymers, or combinations thereof. Yet, according to another aspect, the pouch surface comprises polyvinyl alcohol (PVA), polyvinyl chloride (PVC), hydroxyethyl methacrylate, polyethylene glycol (PEG), poly ethylene oxide (PEO), polyvinyl pyrrolidone (PVP), poly-N-isopropyl acrylamide (PNIAAm), polymethyl methacrylate, polyethyl methacrylate, polysulfone, polyamide, polylactic acid, silicone, silastic, polyfumarate, polyetheretherketone, polybutyl methacrylate and polyurethane, polyamines, fibrin, hylauronic acid, chitin, albumin, collagen, chondroitin sulfate, or combinations thereof as well as other hydrocarbons.

Unless otherwise defined, all technical and scientific terms used herein in their various grammatical forms have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described below. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not limiting.

Further features, objects, and advantages of the present invention are apparent in the claims and the detailed description that follows. It should be understood, however, that the detailed description and the specific examples, while indicating preferred aspects of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 depicts a schematic diagram of two vertebral segments (1) and an enclosed disc. The disc is in between the vertebral bodies (1) and is composed of an exterior annulus fibrosis (3) and an interior nucleus pulposis (5).

Figure 2 shows a diagrammatic representation of the pathology involved in degenerative disc diseases. The annulus develops a tear or a rupture (13) leading to the extravasation of the nuclear material to out side of the disc space (15), which in turn leads to slippage of the facet joints (7). Figure 3 illustrates an implanted flexible pouch or sac (2), in a nuclear space. The pouch contains an empty or a hollow or a partially filled interior and is in a deflated state.

Figure 4 depicts an inflated implanted pouch (4) as a result of injected suitable gellant (such as polymeric materials) or a combination of gellants.

Figure 5 Illustrates a deflated pouch (2) introduced into the nuclear space and a subsequent state when the device is inflated with a liquid or semisolid gellant.

Figure 6 shows porous metal end-plates (6) placed on top and bottom of a deflated and subsequently inflated device. Figure 7 depicts a schematic diagram of repeated injections of gellants into an implanted pouch (4) to provide the implant a gradient of stiffness or other desired physico-chemical or mechanical properties, or to repair a fractured implant (8).

DETAILED DESCRIPTION OF THE INVENTION

The present invention generally relates to medical devices for prosthetic disc nuclear replacement, soft-tissue replacement, reconstruction, augmentation, methods of implanting the devices, and methods of treating and preventing the progression of nuclear disc degenerative disease. Degenerative disease of the disc is one of the most frequently treated spinal disc degenerative conditions.

The invention also relates to medical devices for intervertebral disc replacement, soft-tissue reconstruction, wound care, cartilage replacement, joint replacement, implantation as a surgical barrier or a gastrointestinal device, a cosmetic and reconstructive operation, including the expansion of soft-tissues, replacement for the spinal disc, augmentation of breast or muscle enlargement, chin, cheek, ear and nose, as an implant in reinforcing the sphincter muscles of the esophagus, bladder, and wherever tissue reconstruction, reinforcement, or augmentation is needed.

Embodiments of this disclosure provides medical devices comprising a flexible pouch of a preformed shape which upon injection of a gellant or hardening hydrogel forms rigid or semi-rigid medical device. The medical devices serve the purposes of a tissue expansion, tissue reconstruction, tissue augmentation, and/or tissue replacement. According to one embodiment, a flexible porous or non-porous solid polymeric pouch of a preformed shape is placed into a body for a tissue to be reconstructed, replaced, augmented or expanded through minimally invasive techniques. The implanted pouch is injected, preferably in situ, with suitable biomaterial hardening gellants or hydrogels, which expand the pouch into a desirable shape. Hardening of the gels preserves the shape of the pouch and thus the shape of the tissue being reconstructed or replaced. The device can be used in a variety of reconstructive procedures, including the expansion of soft tissues, replacement of spinal disc, augmentation of breast, chin, cheek, ear, and nose, as an implant in reinforcing the sphincter muscles of the esophagus, bladder, and wherever tissue reconstruction, reinforcement or augmentation is needed.

One embodiment of this disclosure provides tissue expansion, reconstruction, and augmentation devices, which are shaped after insertion into a body and filled in situ with polymerized and/or crosslinked hydrogels. Implanted hydrogels are solidified in situ and retain the shape of the implanted medical device. The solidified filler material maintains specific shape of the tissue that is reconstructed or replaced, and the shape of the implanted pouch is maintained within the body.

According to another embodiment, if necessary, surgery can be performed endoscropically, with minimally invasive surgical techniques, to inject additional filler materials or gellants to finalize the size and/or shape of an implanted medical device. The filler materials can be any material which can form solid gels after polyemerizing and/or crosslinking, such as fibrin gels, keratin gels, hylauronic acid gels, and the like. Hydrogels used for tissue augmentation are biocompatible, harden with tunable material properties, such as compressive stiffness and viscoelastic behavior, can be made soft and compressible, and elicit little foreign body reaction.

The solidified pouches or the medical devices can be flexible, depending on the mechanical properties of the solidified gellant or combination of gellants. Gellants, for example, upon injection into a pouch or an implanted pouch, provide the pouch or the medical device a desirable shape, size, and mechanical strength. Referring to the term "solidified" or the phrase "gellants solidifies", indicates that the gellants undergo solidification process inside the pouch or the medical device and provide and maintain the pouch or the medical device a desirable shape, size, and mechanical strength, however, the solidified pouch or the medical device still can be flexible. An implanted gellant-filled solidified pouch maintains a shape memory and can revert back to its original shape or shape that is approximate to the original shape once a deforming force is eliminated.

According to one aspect, the invention provides a flexible pouch or a device or a sac, made of polymeric fabric, for implanting into a body cavity, for example, intervetebral nuclear disc. Subsequently, a suitable gellant or polymeric materials or a combination of gellants are injected to inflate the pouch to a desired final shape and allow the gellant(s) to solidify within the pouch to become solid or semisolid materials.

According to another aspect of the invention, the surface of the pouch or device is porous and allows annulus to re-grow into the surface and seal the nuclear space from the exterior. The pouch/device is inserted through minimally invasive surgical techniques. According to another aspect, the pouch/device is augmented or covered with porous metallic end-plates on top and bottom surfaces to allow bone in-growth. The pouch/device allows repeated injections of either the same gellant or polymeric materials as originally used or materials of different mechanical properties so that the height and mechanical characteristics of the device is maintained over a period of time. Referring to Figure 1, which generally depicts a schematic diagram of two vertebral segments (1) and an enclosed disc. The disc is in between the vertebral bodies (1) and is composed of an exterior annulus fibrosis (3) and an interior nucleus pulposis (5). The annulus is a tough fibrous ligamentous structures that surrounds the nucleus (5), which is a gel like structure. The annulus (3) completely encircles and confines the nucleus (5) and is attached to the top and bottom vertebral bodies (1). The pedicles, lamina, transverse processes, spinous processes, and the facet joints (7) are the bony structures posteriorly and are attached to the vertebral bodies (1). These form a bony ring through which the spinal cord and nerve roots (9) pass from top to bottom of the spine. The two facet joints (7) and the spinal disc are the joints between the two spinal segments (11) and together with the ligaments provide stability to the spine. Referring to Figure 2, which shows a general diagrammatic representation of the pathology involved in degenerative disc diseases. A tear in the annulus is shown as (13). The annulus develops a tear or a rupture (13) leading to the extravasation of the nuclear material, such as extruded disc, to out side of the disc space (15). This leads to loss of load carrying capacity of the disc, which in turn leads to loss of height of the disc space. This in turn leads to slippage of the facet joints (7) which in later stages leads to arthritis of the facet joints as well as the development of bone spurs and nerve root irritation.

Rupture of the spinal disc is related in part to the loss of the water carrying capacity of the nuclear material confined within the annulus. Because the nucleus, which is primarily composed of glycosaminoglycans and chondroitin sulfate, is able to trap considerable amount of water within its molecular structure through hydrogen bonds. Thus, it acts as an incompressible gel within the confines of the annulus, which tends to hold the vertebral bodies apart. With aging, chemical changes in the nuclear material decreases its water carrying capacity and thus its load carrying capacity. This leads to rupture within the annular fibrosis, which surrounds the nucleus. The rupture of the annular fibers allows the nuclear material to escape, leading to the collapse of the disc height which further reduces its load carrying capacity. The rupture leads to a progression of degenerative disc disease into adjacent joints and causes pain, because, the extruded nuclear material irritates adjacent nerve roots.

In order to treat and prevent the progression of the degenerative disc disease following two measures should be taken into consideration:

(1) the disc height should be maintained using a suitable material, which is capable of carrying heavy loads and providing shock absorption (preferably by hydrostatic pressure, loads of as much as 1000 Newtons can be produced on the disc space in activities such as bending, which requires a compressive strength of the disc of at least 4MN/square meter); and

(2) provide a confined space for the nuclear material so that under load the material will not extrude out of the disc space. According to one aspect of the invention, the above measures are taken by replacing the nuclear gel with a load carrying material, which is capable of carrying heavy loads under hydrostatic pressure, as described above, and allows regeneration of the annulus fibrosis by scar tissues, and maintains the height of the disc space. The procedure is completed with minimally invasive surgical techniques and can be done repeatedly in necessary.

According to one aspect, the invention provides medical devices to replace the nuclear material with a solid or semisolid polymer, which is contained within a pouch and allows the expansion of the pouch to close the opening in the annulus and seal. When filled with gellant(s), the pouch, according to the invention, can be of any shape or mixtures thereof, for example, a cylindrical shape, a spherical shape, a ellipsoidal shape, a trapezoidal shape, a rhomboid shape and/or irregular shapes, or the shape of a body cavity or a nuclear space. Since the instant device expands within the confines of the annulus, the potential of the nucleus to extrude though the annulus opening is substantially low. In one aspect, a deflated pouch or a medical device is inserted into a nuclear space with a minimally invasive technique, since it occupies a very little space in its collapsed, deflated, or non expanded state.

According to embodiments of this disclosure, prior to implanting a deflated pouch or a medical device, the degenerated or partially degenerated nucleus or the nuclear material is removed by minimally invasive surgical techniques known in the art (for example, percutaneous nucleaplasty, thermal or electrosurgical coblation, coblation assisted microdiscectomy, micro-endoscopic-discectomy and chemonuclolysis are disclosed in Marin FZ. CAM versus nucleoplasty. Acta Neurochir Suppl. 2005, 92:111- 114; Bach et ah, Minimally invasive spine surgery for low back pain. Dis Mon. 2005, 51(l):34-57; Alexandre et ah, Percutaneous nucleoplasty for discoradicular conflict. Acta Neurochir Suppl. 2005, 92:83-86; and Kuh et ah, Surgical treatments for lumbar disc disease in adolescent patients; chemonucleolysis / microsurgical discectomy/ PLIF with cages. YonseiMedJ. 2005, 46(1):125-132). According to one aspect, the shape of a filled or inflated or partially inflated pouch depends upon the shape of the pouch itself and/or the in situ surrounding or the body cavity or the nuclear space in which the pouch is implanted.

In one embodiment, the dimension or size of the pouch can of any size depending on the size of a body cavity. For example, the size of a pouch for a nuclear replacement or soft-tissue reconstruction can be at least about one cubic millimeters and less than about five cubic centimeters. More specifically, the dimension of a nuclear disc replacement or soft-tissue reconstruction pouch can be about 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0 cubic millimeters, 1.0, 2.0, 3.0, 4.0 or 5.0 cubic centimeters, or a dimension thereabout or therebetween. The dimension of the size of a pouch depends on location of the pouch in a body or a body cavity. For other medical devices, for example, nose, ear, or breast, the pouch dimension can be of any desired size. For example, for a breast implant, the pouch size can be at least about five cubic centimeters. In another embodiment, the pouch can be of any shape or mixtures thereof, for example, spherical, elliptical, cylindrical, ellipsoidal, rhomboidal, trapezoidal, and/or irregular shapes, or the shape of a bodily cavity or a nuclear space. For the disc replacement, for example, the preferred shape is cylindrical and for breast implant, the preferred shape is ellipsoidal. In another embodiment, the shape of a filled or inflated or partially inflated pouch depends upon the shape of the pouch itself and/or the in situ surrounding or the body cavity in which the pouch is implanted.

In another embodiment, the consistency of a pouch is comparable to the consistency of a fabric, a cloth, or a membrane. Pouch surface materials can be prepared under suitable conditions to obtain a desirable consistency.

Bladders filled with air or saline to replace a discs are known in the art. However, bladders containing gases, liquids, or liquid gels do not retain their shape and are readily deformable. Therefore, such bladders are currently not being used in replacing the disc. The bladders must be permanently impermeable to avoid leakage, which is difficult to achieve in vivo for a longer period of time when filled with gases or liquids. However, a leak-proof permanent bladder also would not solve the problem if the permanent bladder do not support the re-growth of the annulus. Thus, a disc capable of load sharing between the nuclear and annular material, which mimics the natural disc and is desirable. The re- grown annulus can get blood supply and is a living tissue, which can repair itself biologically, as long as the load is not excessive. Another aspect of the invention provides disc devices to replicate the load carrying mechanical properties of the nucleus by suitable materials (polymers such as in situ setting hydrogels, or in situ setting methacrylates, or in situ setting polylactic acids or in situ setting biologic polymers. According to one aspect, the present invention provides a confined space within a disc space and within the remaining of an annulus whereby liquid gelling/polymerizing solutions can be mixed and made to solidify or polymerize into a desired shape, for example, spherical, elliptical, cylindrical, ellipsoidal, rhomboidal, trapezoidal, and/or irregular shapes or the shape of a body cavity. The gellants or polymers can be hydrogels, acrylic polymers such as polymethylmethacrylate or polyethylmethacrylate, or any other polymers such as polylactic acid, polyolefins, polyhydrocarbons, or combination thereof. Reinforcing materials also can be added to these gellants or polymers, for example, carbon or metal fibers, biological materials such as collagen fibers and chondroitin sulfates, as well as therapeutic compounds such as antibiotics and growth factors. According to another aspect, the invention provides means for tissue in-growth and long term biologic anchorage of the prosthesis to the surrounding tissue. It is known in the art that prosthesis with porous surfaces can allow in-growth of adjacent tissue if appropriate pore size and configuration of the surface and initial stability of the prosthesis are obtained. The prosthetic nuclear replacement disc of the invention allows the annulus to re-grow and seal the rupture, which originally caused the disc nucleus to extrude. A suitable porous surface of the pouch made of materials such as vinyl polymers, polyethylene such as UHMWPE, or nylon can allow the annulus to re-grow into the pouch surface and can provide long term anchorage and seal. This also can place the nuclear replacement material under hydrostatic loading, thereby improving the load carrying function of the nuclear replacement material. The porous surface of the pouch is made of a variety of materials, for example, polytetrafluoroethylene (PTFE) (for example, Gortex™), polyolefins, polyhydrocarbons, vinyl polymers, polyethylene such as UHMWPE,, polyacrylonitrile (PAN) (for example, Kevlar™), polysulfone, silastic, polyester (for example, polyethylene tetraphthalate such as Dacron™), polyamide, nylon, valour, polyurethane, or combinations thereof.

The fixation of the device to the vertebral end-plates can be improved by augmenting the device with porous coated metal end-plates. Metal end-plates can be made of materials such as titanium, tantalum, cobalt chrome alloys, or stainless steel.

Polyvinyl alcohol (PVA) and polyethylene glycol (PEG) based hydrogels are good substitutes for nuclear material since they possess analogous mechanical properties, such as compressive strength and viscoelastic behavior. They are analogous to the nuclear material, which itself is a hydrogel, since they hold large amounts of water and can handle cyclical loading without loss of elasticity. Of particular benefit, in minimally invasive surgery, polyvinyl alcohols and polyethylene glycols can be made to undergo gelation in situ by forming physical or chemical crosslinks. Pharmaceutical agents such as antibiotics and/or chemotherapeutic agents, and biologic agents such as tissue growth factors, transforming growth factors, platelet derived growth factors, fibroblast growth factors, angiogenic factors and the like can be incorporated readily into the gels, which provides additional benefits for enhancing tissue growth and delivery of antibiotics. The pouches are preferably made in a sealed position, however, also can be made by heat sealing a pouch surface or the sheet materials along the seams. Sealing of a pouch is not necessary following the injection of the gellant(s), because the solidified gel is not likely to leak out after the pouch.

The porous pouch surface can vary in pore sizes to allow fibrous tissue in-growth. The pore sizes can range from a few angstroms (A) to a few millimeters (mm), because the pouch surface porosity controls ingress and egress of fluid and other materials into and out of the pouch, as well as controls the tissue in-growth of the fibrous tissue. Generally, a pouch surface contains pores of different sizes, for example, pore sizes from 1 to 400 microns are desirable for fibrous tissue in-growth. The term "gellant" refers to a gelling or solidifying agent. The gellants can be salts, alcohols, polyols, amino acids, sugars, proteins, polysaccharides, aqueous solutions thereof, or mixtures thereof. For example, gellant used in loading or inflating a pouch or a medical device can be hydrogels, polymer, polymer blends, or copolymers of polyvinyl alcohol (PVA), polyethylene glycol (PEG), poly ethylene oxide (PEO), polyvinyl pyrrolidone (PVP), poly-N-isopropyl acrylamide (PNIAAm), polyfumarate, polyetheretherketone, polybutyl methacrylate and polyurethane, polyolefins, polyhydrocarbons, polyamines, fibrin, hylauronic acid, chitin, albumin, collagen, or chondroitin sulfate, dextran sulfate, dermatin sulfate, and the like. According to one embodiment, this disclosure provides gellants comprising polymer, polymer blends, copolymers, polyolefins, polyhydrocarbons, or combinations thereof. For example, polyvinyl alcohol (PVA), polyethylene glycol (PEG), poly ethylene oxide (PEO), polyvinyl pyrrolidone (PVP), poly-N-isopropyl acrylamide (PNIAAm), polymethyl methacrylate, polyethyl methacrylate, polysulfone, polyamide, polylactic acid, silicone, polyfumarate, polyetheretherketone, polybutyl methacrylate and polyurethane, polyamines, fibrin, hylauronic acid, chitin, albumin, collagen, chondroitin sulfate, or combinations thereof. In another embodiment, the gellants include carbon fibers, metal fibers, collagen fibers, proteoglycans, growth factors, and antibiotics.

Yet in another embodiment, this disclosure provides materials, for example, polytetrafluoroethylene (PTFE) (for example, Gortex™), vinyl polymers, polyethylene such as UHMWPE, polyolefins, polyhydrocarbons, polyacrylonitrile (PAN) (for example,

Kevlar™), polysulfone, silastic, polyester (for example, polyethylene tetraphthalate such as Dacron™), polyamide, nylon, valour, and polyurethane, which can be used to make pouch surface, fabric, film, or sheet-like materials. In addition, the above listed gellants also can be used to make pouch surface, fabric, film, or sheet-like materials.

The molecular weight of the polyethylene can range from a few thousand to 5 millions depending on the tensile strength required for a specific application. For example, for pouch materials, low density linear polyethylene, nylon, or polytetrafluoroethylene (PTFE) (for example, Gortex™) is preferred. The term "gelation" refers to a process of gel formation or solidification of a matrix or a nuclear material inside a pouch containing at least one gellant. The term "gelation" also refers to the formation of permanent physical cross-links due to the crystallization of the polymer solution, for example, the PVA solution and/or at least one of the gellants.

According to one embodiment of this disclosure, the gels can be cross linked chemically or physically to obtain different mechanical properties. For example, cross-linking can be accomplished by using agents such as sulfur, salts of alkali metals such as sodium chloride and potassium chloride (cross links fibrin, polyvinyl alcohol based hydrogels), benzolyl peroxide (polymerizes methacrylate based materials), and the like.

The invention is further described by the following schematic drawings and examples, which do not limit the invention in any manner.

Figure 3 illustrates an implanted flexible empty or a hollow pouch or a sac (2) in a nuclear space and the pouch is in a deflated state. The pouch is inserted to the nuclear space which was previously occupied by the nucleus (see (5) in Figure 2). The pouch (2) is injected, using a delivery device (12), with a suitable gellant (such as polymeric materials) or a combination of gellants to form a desired final shape of a spinal nucleus.

Figure 4 depicts an inflated implanted pouch (4) as a result of injected suitable gellant (such as polymeric materials) or a combination of gellants and the pouch formed the shape of the spinal nucleus.

Figure 5 illustrates a deflated pouch (2) introduced into the nuclear space, preferably with minimally invasive surgical techniques. The figure shows a deflated device and tear in the annulus. The figure also illustrates the state when the device is inflated with a liquid or semisolid gellant (for example,, a polymer or a combination of polymers) to form a final shape. The inflated device (4) is polymer cured and the hole in the annulus is sealed by the device. The inflated pouch also seals the hole in the nucleus. The gellant is solidified within the pouch and maintains the desired final shape of the spinal nucleus (4). The pouch (2) can be made of materials described in embodiments of this disclosure, for example, polytetrafluoroethylene (PTFE) (for example, Gortex™), which allows the annulus (see (3) in Figure 4) to grow in the pouch and seal the defect in the annulus. Figure 6 shows porous metal end-plates (6) placed on top and bottom of a deflated device. The figure 6 on the right shows that the deflated device is filled with cured polymer. The figure also shows inflated device containing the porous metal end-plates (6) on top and bottom of the device, which allows bone in-growth of the vertebral bone into the device (pouch). The bone ingrowth further enhances the stability of the device by osseous in-growth from the vertebral bone.

Figure 7 depicts an example repeated injection of gellants into an implanted medical device. The figure depicts a schematic diagram of repeated injections of gellants or polymerizing materials (using new filling polymer) of the same type or different types, injected sequentially into the implanted pouch (4), to provide the medical device a gradient of stiffness (for example, harder polymer for the outer wall and or softer polymer cured for the inner section of the device) or other desired physico-chemical or mechanical properties. The repeated injections (using new filling polymer) also can be used, if the nuclear replacement materials fails in time due to conditions such as fractures or cracks (for example, old polymer with fractures are generally seen) in the solidified gellant/polymer in the pouch (8), to structurally reinforce the gellant or the polymer.

It is to be understood that the description, specific examples and data, while indicating exemplary embodiments, are given by way of illustration and are not intended to limit the present invention. Various changes and modifications within the present invention will become apparent to the skilled artisan from the discussion, disclosure and data contained herein, and thus are considered part of the invention.

Claims

CLAIMS:

1. A medical device for prosthetic disc nuclear replacement comprising: a) a flexible empty or partially filled pouch, wherein the pouch is implanted into a selected site in a mammal; and b) at least one type of gellant, wherein the gellant is injected into the pouch in situ, and wherein the gellant solidifies within the pouch.

2. A method of replacing a prosthetic disc nucleus in a mammal, wherein the method comprises: a) implanting a flexible empty or partially filled pouch into a selected site of the mammal; and b) injecting at least one type of gellant into the pouch, wherein the gellant solidifies within the pouch, thereby replacing the disc nucleus.

3. A method of treating a mammal by partially or completely replacing a prosthetic disc nucleus, wherein the method comprises: a) implanting a flexible empty or partially filled pouch into a selected site of the mammal; and b) injecting at least one type of gellant into the pouch, wherein the gellant solidifies within the pouch, thereby partially or completely replacing the disc nucleus.

4. A kit for providing a medical device for prosthetic disc nuclear replacement to a region of interest comprising: a) a container containing flexible empty or partially filled pouches; b) a container containing at least one type of gellant; and c) delivery device, wherein the delivery device is used to inject the gellant into the pouch to form a medical device in situ.

5. A medical device for soft-tissue replacement, reconstruction, or augmentation comprising: a) a flexible empty or partially filled pouch, wherein the pouch is implanted into a selected site in a mammal; and b) at least one type of gellant, wherein the gellant is injected into the pouch in situ, and wherein the gellant solidifies within the pouch.

6. A method of implanting a medical device for replacing, reconstructing, or augmenting a soft-tissue in a mammal, wherein the method comprises: a) implanting a flexible empty or partially filled pouch into a selected site of the mammal; and b) injecting at least one type of gellant into the pouch, wherein the gellant solidifies within the pouch, thereby implanting the medical device.

7. A method of treating a mammal by partially or completely replacing, reconstructing, or augmenting a soft-tissue, wherein the method comprises: a) implanting a flexible empty or partially filled pouch into a selected site of the mammal; and b) injecting at least one type of gellant into the pouch, wherein the gellant solidifies within the pouch, thereby partially or completely replacing, reconstructing, or augmenting the soft-tissue.

8. A kit for providing a medical device for soft-tissue replacement, reconstruction, or augmentation to a region of interest comprising: a) a container containing flexible empty or partially filled pouches; b) a container containing at least one type of gellant; and c) delivery device, wherein the delivery device is used to inject the gellant into the pouch to form a medical device in situ.

9. The medical device, method, or kit according to any of the above claims, wherein the medical device is implanted into a mammal in a surgical procedure for intervertebral disc replacement, wound care, cartilage replacement, joint replacement, implantation as a surgical barrier or a gastrointestinal device, a cosmetic or reconstructive operation, ear, chin, cheek, or nose reconstructive operation, or breast or muscle enlargement.

10. The medical device, method, or kit according to any of the above claims, wherein the medical device is implanted into a mammal to fill-in a cavity in a cartilage defect, in a joint including hip, knee, or a nuclear cavity, the nuclear space within the intervertebral disc, and act as an articular or load-bearing surface.

11. The medical device, method, or kit according to any of the above claims, wherein the injected gellant forms the desired final shape of a spinal nucleus when solidified.

12. The medical device, method, or kit according to any of the above claims, wherein the flexible pouch contains a porous surface and allows in-growth or re-growth of annulus.

13. The medical device, method, or kit according to any of the above claims, wherein the pouch further comprising porous metallic end-plates on top and/or bottom of the pouch surfaces.

14. The medical device, method, or kit according to any of the above claims, wherein the end-plates comprise titanium, tantalum, cobalt chrome alloys, or stainless steel.

15. The medical device, method, or kit according to any of the above claims, wherein the pouch surface is porous or non-porous.

16. The medical device, method, or kit according to any of the above claims, wherein the flexible pouch has a prescribed shape.

17. The medical device, method, or kit according to any of the above claims, wherein the flexible pouch contains a hollow interior.

18. The medical device, method, or kit according to any of the above claims, wherein the injected gellant forms the desired final shape when solidified.

19. The medical device, method, or kit according to any of the above claims, wherein the gellant comprises polymer, polymer blends, copolymers, or combinations thereof.

20. The medical device, method, or kit according to any of the above claims, wherein the gellant comprises polyvinyl alcohol (PVA), polyethylene glycol (PEG), poly ethylene oxide (PEO), polyvinyl pyrrolidone (PVP), poly-N-isopropyl acrylamide (PNIAAm), polymethyl methacrylate, polyethyl methacrylate, polybutyl methacrylate, hydroxyethyl methacrylate, polyacrylonitrile (PAN), Kevlar™, polysulfone, polyamide, polylactic acid, silicone, polyfumarate, polyetheretherketone, polybutyl methacrylate and polyurethane, polyolefins, polyhydrocarbons, polyamines, fibrin, hylauronic acid, chitin, albumin, collagen, chondroitin sulfate, or combinations thereof or any combinations of hydrocarbons.

21. The medical device, method, or kit according to any of the above claims, wherein the gellant further comprising materials selected from the group consisting carbon fiber, metal fiber, collagen fiber, proteoglycan, growth factor and antibiotic.

22. The medical device, method, or kit according to any of the above claims, wherein the pouch surface comprises polytetrafluoroethylene (PTFE), Gortex™, vinyl polymers, polyethylene, UHMWPE, polyacrylonitrile (PAN), Kevlar™, polysulfone, silastic, polyester, polyethylene tetraphthalate, Dacron™, polyamide, nylon, valour, polyurethane, polyolefins, polyhydrocarbons, or combinations thereof.

23. The medical device, method, or kit according to any of the above claims, wherein the pouch surface comprises polymer, polymer blends, copolymers, polyolefins, polyhydrocarbons, or combinations thereof.

24. The medical device, method, or kit according to any of the above claims, wherein the pouch surface comprises polyvinyl alcohol (PVA), polyethylene glycol

(PEG), poly ethylene oxide (PEO), polyvinyl pyrrolidone (PVP), polyvinyl chloride (PVC), hydroxyethyl methacrylate, poly-N-isopropyl acrylamide (PNIAAm), polymethyl methacrylate, polyethyl methacrylate, polyacrylonitrile (PAN), Kevlar™, polysulfone, polyolefins, polyhydrocarbons, polyamide, polylactic acid, silicone, polyfumarate, polyetheretherketone, polybutyl methacrylate and polyurethane, polyamines, polyhydrocarbons, fibrin, hylauronic acid, chitin, albumin, collagen, chondroitin sulfate, or combinations thereof.

25. The medical device, method, or kit according to any of the above claims, wherein the pouch for a nuclear replacement is at least about one cubic millimeters to less than about five cubic centimeters in dimension.

26. The medical device, method, or kit according to any of the above claims, wherein the pouch for a nuclear replacement is about 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, or 9.0 cubic millimeters in dimension.

27. The medical device, method, or kit according to any of the above claims, wherein the pouch for a nuclear replacement is about 1.0, 2.0, 3.0, 4.0 or 5.0 cubic centimeters in dimension.

28. The medical device, method, or kit according to any of the above claims, wherein the pouch is spherical, elliptical, cylindrical, ellipsoidal, rhomboidal, trapezoidal, or irregular in shape.

29. The medical device, method, or kit according to any of the above claims, wherein the pouch is cylindrical in shape.