Abstract:
A composition for spinal disc repair comprising a plurality of uniformly shaped demineralized cancellous bone pieces ranging in size from about 2.0 mm to about 4.0 mm loaded into a porous mesh container with the cancellous bone pieces being treated so that they are not osteoinductive and are packed in the porous mesh container under compression forces.

Description:
RELATED APPLICATIONS 
       [0001]    This application claims priority from Provisional Application No. 60/832,956 filed Jul. 25, 2006. 
     
     FIELD OF THE INVENTION 
       [0002]    The present invention generally relates to tissue forms used for augmentation, restoration or replacement of intervertebral discs. 
         [0003]    A healthy intervertebral disc facilitates motion between pairs of vertebrae while absorbing and distributing compression forces and torque forces. The disc is composed of two parts; namely a tough outer ring (the annulus fibrosis) which holds and stabilizes a soft central core material (the nucleus pulposus) that bears the majority of the load forces. 
         [0004]    The tissue form of the present invention is dense cancellous tissue be derived from proximal and distal femur, proximal and distal tibia, talus, calcaneus, proximal humerus, patella, or ilium that is first fully demineralized, cleaned, treated such that the bone is non-osteoinductive, and then processed into small uniform geometries that may be either cuboidal, disc-shaped (“mini-discs”), or spherical. The relative sizes of these shapes are on the order of 1.0 mm to 4.0 mm in either length or diameter. The tissue forms, following demineralization, are compressible such that individual units can be packed tightly together in a confined space and when packed together behave mechanically as one coherent unit while providing suitable load-bearing properties in the disc nucleus. When confined in the disc space under normal loading conditions, this plurality of shaped units functions as an elastic body, which is deformable, yet resilient under dynamic loading and has intrinsic shape-memory properties. 
       BACKGROUND OF THE INVENTION 
       [0005]    Minimally invasive surgery that is aimed to treat degenerative disc disease and preserve motion in the spine is currently under investigation. Since the onset of the degenerative cascade in the disc is typically associated with dehydration and volume loss in the nucleus pulposus, a potential early intervention step may involve adding mechanically suitable material to the nucleus pulposus at the first observable signs of discomfort and loss of disc height. This procedure would restore nuclear volume and pressure against the inner wall of the annulus fibrosus. In certain embodiments, a degree of decompression or “lift” between the adjacent vertebrae may be possible with this technique. In effect, the result would be the “re-inflation” of the annulus fibrosus, the annular “tire”. Desirable outcomes of the procedure would be motion preservation, pain relief, and maintenance or restoration of disc height. Long-term re-modeling of the biological allograft-based implant into fibrous tissue or disc-like tissue would also provide favorable clinical outcomes. 
         [0006]    At present, there are no nucleus pulposus replacement devices or augmentation technologies available for clinical usage in the United States. The Prosthetic Disc Nucleus (PDN), which is manufactured by Raymedica, was the first implant designed for nucleus replacement with the intention of attempting to restore natural mechanics in the spine. This implant is an acrylic-based hydrogel encased in a polyethylene jacket. While this technology has been implanted in over 3000 patients in Europe, significant issues regarding implant migration and implant hardening have been encountered. Other drawbacks in the design of this implant include the requirement of a substantial annulotomy and total nucleotomy as well as the inability of the implant to fill the entire nuclear cavity. In addition, the limited ability of the implant to swell inside the disc nucleus leads to high extrusion rates and inadequate load transfer of compressive forces in the disc nucleus to tensile forces on the annulus fibrosus. 
         [0007]    Generally speaking artificial disc replacements falls into two general categories, total disc replacement and nuclear displacement. Total disc replacement devices have a number of problems; namely that they are large and non-compressible, require the removal of a large portion of the annulus and require a highly invasive surgical approach in order to be implanted. If these disc replacement devices do not remain firmly attached to the vertebral bodies, these implants can extrude or migrate from their intended position, cause significant complications and are very difficult to revise. The second category of disc replacement is nuclear replacement which is a form of partial disc replacement. Various types of methods and devices have been used to attempt to accomplish successful disc replacement. 
         [0008]    U.S. Pat. No. 6,652,593 issued Nov. 25, 2003 is directed toward an osteoinductive implant comprising demineralized cancellous bone, which comprises a non-particulate bone. A unitary bone block is compressed into a smaller configuration such as a pellet and then hardened via drying. Upon re-hydration, the pellet will expand and assume its original shape inside a cavity. The implant is capable of being compressed and hardened into a first shape and then capable of expanding into a second shape larger than the first shape when re-softened and permitted to expand. The &#39;593 implant is designed to be supplied either in geometries that fill correspondingly sized voids or in compressed initial geometries that are used to expand and fill any given shape smaller than or equal to their expanded size. 
         [0009]    United States Patent Publication 2006/0030948 filed Sep. 21, 2005 is directed toward an osteogenic implant having a predetermined shaped formed of an aggregate of different sized elongate (possessing a high median length to median thickness ratio) bone particles. 
         [0010]    United States Patent Publication No. 2004/0054414 filed on Sep. 18, 2002 is directed toward a method of augmenting an intervertebral disc nucleus by the surgical addition of a particulate collagen-based material. The collagen-based material, having a mean particle size ranging from 0.05 mm to 5 mm, may be injected in either a wet or dry state and may be supplemented with growth factors, proteoglycans, and cells. The &#39;414 publication notes the use of demineralized bone matrix particles with sizes ranging from between 0.05 mm and 3 mm and the use of elongated cylindrical plugs. The plugs are described to be dehydrated and compressed in the radial direction and are inserted into delivery cannula for delivery into the disc space. The cylindrical plugs are delivered via extrusion through a cannula, and expand upon exiting the cannula by re-hydrating in the disc space. Examples 6 and 7 refer to the design and implementation of cylindrical plugs, which can be fabricated from solid, porous, or fibrous collagen. 
         [0011]    Additional continuing United States Published Patent Applications Nos. 2005/0197707 filed Apr. 25, 2005 and 2005/0119754 filed Jan. 6, 2005 are based on the &#39;414 publication. The &#39;707 publication is directed toward the use of small particles of particulate fascia lata, particulate disc annulus material, annulus fibrosis, demineralized bone matrix and collagen which are added to the nucleus of an intervertebral disc. The &#39;754 publication covers a method of augmenting an intervertebral disc nucleus by adding a plurality of collagen-rich tissue particles having a mean particle size between 0.25 and 1.0 mm to the disc plus a biologically active substance that promotes healing, repair or regeneration of the disc. This biologically active substance is further defined to be stem cells, hyaluronic acid, or growth factors while the collagen material is stated to be potentially allograft tissue. Radio contrast material may be added to enhance imaging of the injected material. 
         [0012]    Another United States Patent Publication No. 2005/0055094 filed Nov. 5, 2003 discloses a system for replacing a disc nucleus involving an injection tube, a volume of fibrous tissue material to fill a nuclear cavity, and an insertion device for dispensing the tissue promoting material into the disc. Suitable fibrous tissue promoting material is listed as fascia, natural and/or man made polymeric fiber, fibrous tissue inducers such as talc, pharmaceuticals and/or minerals and fibrous tissue morphogenic protein. 
         [0013]    U.S. Pat. No. 5,571,189 issued Nov. 5, 1996 describes an expandable bag filled with biological tissue for spinal fusion but does not show motion preservation in the spine. 
         [0014]    The present inventive disc nucleus implant is a combination of multiple units of demineralized cancellous tissue treated to be non-osteoinductive that are designed to be small uniform geometric shapes which have the ability to pack together and act mechanically as a single unit under the compression of packing and not to comprise a non-particulate portion of a bone. The inventive tissue forms are compressed upon delivery into a cavity, but only to fit into the delivery device and not into a defined shape. In addition, the inventive tissue forms do not regain their original dimensions following the completion of the implantation procedure. In fact, the appropriate mechanical properties are only achieved if the mass of units is under compression and behaving as a coherent load-bearing material. The plurality of units that constitute the inventive implant, when taken together in an uncompressed state, have a geometry that is substantially larger than the cavity into which they are placed. Thus, the inventive implant takes on a smaller size in the confined space into which it is placed. Finally, the inventive allograft tissue form is treated to be non-osteoinductive, which achieves the desired outcome of motion preservation in the spine versus spinal fusion. 
         [0015]    The noted prior art publications cite examples of various allograft tissues for usage such as demineralized bone matrix, disc annulus, fascia, ligaments, tendons, skin, or other connective tissues. The inventive tissue implant would not be provided in a dehydrated state and will be compressed axially inside the delivery tube rather than radially. 
         [0016]    Advantages of the present inventive approach in comparison to other techniques include its ability to be entirely performed in a minimally invasive manner, total nucleotomy is not required and the implant size is adjustable by the volume of material that is added into the pouch. If desired an expandable pouch that is intended to hold the shaped units can be inserted into the disc nucleus through a small diameter hole and it will be enlarged with implant material to a size considerably larger than the insertion hole allowing the implant dimensions to conform to the existing cavity of the disc nucleus, with the porous pouch preventing the escape of material from the nuclear space while allowing the free transfer of fluid across its surface along with potential tissue ingrowth. 
       SUMMARY OF THE INVENTION 
       [0017]    The implantable allograft tissue form represents uniform demineralized cancellous tissue units treated to be non-osteoinductive placed under compression which will allow them to pack closely in the confined space inside an annulus. Following implantation, when the units are tightly pressed together, the collective volume of implanted material can play a similar biomechanical role inside the disc as native nucleus pulposus. The implant represents a motion preserving alternative in the treatment of degenerative disc disease. 
         [0018]    The steps of the surgical technique described here represent a minimally invasive method for replacing or augmenting a spinal disc nucleus and includes the complete or partial removal of nucleus material, sizing of the resulting cavity, inserting an expandable, porous pouch into the nucleus through either an existing annular tear or through an annulotomy, filling the pouch with compressed small fully demineralized, non-osteoinductive cancellous bone tissue forms, and closing the pouch. 
         [0019]    Another object of the invention is the usage of a biologic nuclear implant material which can experience tissue ingrowth and reorganization once implanted within the disc space. Alternatively, the biological and structural nature of the demineralized cancellous bone allows it to be a potential scaffold that can be potentially supplemented with cells and/or growth factors, which may induce matrix remodeling and the subsequent regeneration of nucleus-like tissue inside the disc following implantation. 
         [0020]    These and other objects, advantages, and novel features of the present invention will become apparent when considered with the teachings contained in the detailed disclosure which along with the accompanying drawings constitute a part of this specification and illustrate embodiments of the invention which together with the description serve to explain the principles of the invention. 
     
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0021]      FIG. 1  shows an enlarged perspective view of a plurality of cancellous cube shaped units of the present invention in a schematic container; 
           [0022]      FIG. 2  shows an enlarged perspective view of a plurality of cancellous disc shaped units of the present invention in a schematic container; 
           [0023]      FIG. 3  shows an enlarged perspective view of a plurality of cancellous cubes, discs and sphere shaped units of the present invention in a schematic container; 
           [0024]      FIG. 4  shows a perspective view of a filled porous mesh pouch with demineralized cancellous tissue units placed in the disc nucleus following the creation of a lateral portal through the disc annulus; 
           [0025]      FIG. 5  is a chart showing the angular motion in flexion and extension of human cadaveric motion segments (a) for an intact disc, (b) the disc following nucleotomony, (c) the disc directly following implantation of the present invention and (d) the implanted disc after allowing 30 minutes for additional hydration; 
           [0026]      FIG. 6  is a chart showing the deviation of the motion segment flexibility in flexion-extension from the intact disc; 
           [0027]      FIG. 7  is a chart showing the angular motion in left and right lateral bending of human cadaveric motion segments (a) for the intact disc, (b) the disc following nucleotomy, (c) the disc directly following implantation of the present invention, and (d) the implanted disc after allowing 30 minutes for additional hydration; and 
           [0028]      FIG. 8  is a chart showing the deviation of the motion segment flexibility in lateral bending from the intact disc. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0029]    The preferred embodiment and best mode of the invention is seen in  FIGS. 1 to 4 . The present invention is directed toward an implant that formed of a plurality of small, substantially demineralized cancellous bone shapes  10  that can be loaded and packed into a cannula or hollow rod and then inserted by packing the small shaped bone units into a disc nucleus in a non-dehydrated state. This packed material is to be utilized to augment, restore, or replace a disc nucleus. In a preferred embodiment, the tissue forms described within are to be delivered into an expandable porous mesh pouch  16  that has been pre-placed in the disc nucleus  20  through a small lateral opening  22  in the disc annulus such that the allograft material will be contained and not extrude out of the nucleus through an annular defect. The deformable nature of wet, demineralized cancellous bone will allow the tissue forms to pack tightly together in a confined space during delivery under sufficient pressure. A suitable amount of tissue is inserted so that the nuclear cavity is tightly filled and the resulting conglomerate implant acts as a single coherent mass under mechanical loading. This invention is implemented for patients with degenerative disc disease, particularly those in earlier stages of degeneration who still possess a competent annulus fibrosus. 
         [0030]    Cancellous bone may be derived from proximal or distal femur, proximal or distal tibia, proximal humerus, talus, calceneus, patella, or ilium. Cancellous tissue is first processed into sheets or blocks, which preferably range in thickness of about 2 m to 3 mm, although sheets of about 1.0 mm to about 4.0 mm can be used. Blood and lipids are flushed from the tissue using high pressure water. The cancellous tissue is then substantially demineralized in dilute acid until the bone contains less than 0.1% wt/wt residual calcium. Demineralization of the cancellous bone creates a material that is spongy and pliable in nature, yet still possesses elastic properties and shape memory following deformation. 
         [0031]    Following decalcification, the cancellous tissue is cleaned and treated via chemical or thermal treatment or by high energy irradiation so that the cancellous tissue is non-osteoinductive. 
         [0032]    In a preferred embodiment, the cancellous tissue is treated with hydrogen peroxide for at least 1 hour in order to further clean the tissue and to achieve a non-osteoinductive material. The tissue is then soaked in ethanol as an additional cleaning step. After these steps, the tissue is soaked in phosphate buffered saline (PBS) in order to restore the pH of the tissue within the range of 6.6 to 7.4. After these treatment steps, small units of cancellous tissue are fabricated from the cancellous sheets or blocks. The cancellous tissue form units have a defined shape that may be cuboidal, spherical, or discoid in nature and are loaded into filler tubes prior to implantation. The cancellous shapes may have a single dimension ranging from 1.0 mm to 4 mm and preferably are between 2 mm to 3 mm. 
         [0033]    In the most preferred embodiment, the fully demineralized cancellous sheets are then cut into cube shaped tissue forms  12  with a side dimension of 2 mm to 3 mm using a chip press cutting device. The cancellous cubes are then lyophilized to less than 6% residual moisture. Following the dehydration step, a specific amount of dry cancellous cubes is weighted out ranging between 0.4 to 1.2 g. This amount of dry cancellous tissue is hydrated in excess water or saline and then loaded into a small diameter tube (2 mm to 4 mm in inner diameter) that is to be used to fill the disc nucleus during the surgical procedure. 
         [0034]    In  FIG. 2 , disc shaped tissue forms  13  are formed using a mechanical press that acts as a multiple hole-punch. A preferred disc size is 2-3 mm in diameter and 2-3 mm in height. In another unit form spheres  14  are formed using a cutting device. A preferred sphere size is about 2-3 mm in diameter.  FIG. 3  shows multiple unit configurations of cuboidal, spherical or discoid in shape used together. All of the shaped units are lyophilized to less than 6% residual moisture weighed in a dehydrated state, and then hydrated in excess water or saline before loading into an insertion tube or container. 
         [0035]    A sufficient amount of cancellous bone is added to the expandable mesh pouch container  16  such that the volume of the nucleus is restored when the implant is packed so that it conforms to the shape of the nuclear cavity. Due to the design of the implant, the amount of filling material loaded into the bag may thus be customized for the specific size of the target nuclear cavity of the patient. In certain embodiments, the pouch may be filled with cancellous bone until it expands to a volume greater than that of the existing nuclear cavity, thereby providing a degree of decompression or “lift” between the two adjacent vertebrae. After the pouch is tightly packed with the shaped demineralized cancellous bone shaped units, the implant is designed to possess mechanical properties that withstand the compressive loads in the spine and facilitate load transfer from the nucleus to the annulus. Once filling is complete, pouches will be closed or sealed to prevent the escape of any cancellous tissue. 
         [0036]    As shown in  FIGS. 5 and 6 , disc-shaped fully demineralized allograft cancellous bone units (3 mm diameter×3 mm height were loaded into an expandable polyester mesh in situ at a packing density ranging from between 1.50 to 1.60 g/cc based on the hydrated mass of the tissue and the measured cavity size of the denucleated disc. The figures represent the acute restoration of stability to the spinal motion segment following nucleotomy and the implantation of the inventive implant device. Testing was performed on each cadaveric motion segment (either L 2 -L 3  or L 4 -L 5 ) at four different stages: the intact disc, the disc following nucleotomy, the denucleated disc directly following the implantation of the inventive device and the implanted disc after allowing for 30 minutes of hydration in saline.  FIG. 5  depicts the angular motion in flexion and extension of human cadaveric motion segments over a constant range of bending moments.  FIG. 6  represents the deviation of the motion segment flexibility in flexion-extension from the intact disc.  FIG. 7  represents the angular motion in left and right lateral bending of human cadaveric motion segments over a constant range of bending moments: (a) for the intact disc, (b) the disc following nucleotomy, (c) the disc directly following implantation of the present invention, and (d) the implanted disc after allowing 30 minutes for additional hydration. The data shows the biomechanical instability introduced to the discs following the nucleotomy and demonstrates the recovery of normal range of motion following the implantation of the inventive implant device.  FIG. 8  is a chart showing the deviation of the motion segment flexibility in lateral bending from the intact disc. Error bars on all figures indicated the standard deviation from the mean. 
         [0037]    Additional embodiments of this invention may include the supplementation of the cancellous bone with synthetic material that is of similar physical dimensions as the implanted cancellous tissue forms. Such synthetics may include polymeric hydrogels, biodegradable polymers, rubbers, or other materials that are elastic in nature and capable of being packed together in a similar fashion to the cancellous tissue. 
         [0038]    Other additional embodiments of this invention may include the addition of cells and/or biological agents to the cancellous bone either prior to implantation or post-implantation. Transplanted cells may include those derived from bone marrow, other pluripotent stem cells, chondrocytes, and nucleus pulposus cells. Bioactive molecules may include viral particles, plasmids, hormones, extracellular matrix proteins, platelet rich plasma, or growth factors such as those in the TGF-β, FGF, VEGF, IGF, and BMP families. Another embodiment of the invention may include the addition of a radio-opaque marker to the cancellous tissue in order to make the implant visible during surgery. The radio-opaque marker may be derived from beryllium copper, brass, bronze, carbon steel, clad metals, copper, kovar, molybdenum, nickel, niobium, stainless steel, tantalum, titanium, zirconium, or other radio-opaque material. Other suitable materials may include barium, platinum, platinum iridium, gold and iodine-containing compounds. 
         [0039]    This invention also utilizes a method of treating a degenerative spinal disc by replacing or augmenting the disc nucleus with allograft tissue through a minimally invasive approach. In a preferred embodiment, the allograft tissue form comprises small uniformly shaped fully demineralized, non-osteoinductive cancellous bone units. The target disc will be accessed and nuclear material will be removed via microdiscectomy or minimally invasive nucleotomy. Following this step, the resulting nuclear cavity is sized and an expandable, porous pouch is inserted into the disc nucleus via an existing annular tear or a small annulotomy. The pouches are initially empty and in a collapsed state such that it can be passed through a small diameter portal in the disc annulus (˜3 mm-4 mm). This mesh bag may be made from synthetic materials such as polyester or biological material such as allograft bone, dermis, or fascia, hyaluronic acid, collagen, or other structural protein. In a preferred embodiment, a woven fabric mesh is utilized as the implantable pouch, with a pore size that is sufficiently small such that allograft material units do not extrude through the mesh openings. This containment device may also be sewn such that it expands into a disc nucleus-like shape upon addition of implant material and may have a radiographic marker in order to track its location following implantation. The porous nature of the pouch may allow the transfer of fluid from the surrounding disc tissue to the implant material and vice-versa. The porosity and mesh size of the pouch may also be critical for obtaining an appropriate biological response to the allograft material contained within it. By allowing cellular infiltration and fluid exchange, it may be possible for tissue remodeling or fibrous tissue formation to occur inside the implanted mesh pouch within the disc. 
         [0040]    After the porous pouch has been inserted and positioned inside the disc, a plurality of small, demineralized non-osteoinductive cancellous bone units are passed into the bag through a hollow rod until the bag is appropriately filled. In a preferred embodiment, the hollow rod has an internal diameter between 3 mm to 4 mm, and is utilized in combination with cancellous units that are cube shaped with 2 mm to 3 mm sides or disc-shaped with a diameter of 2 mm to 3 mm and a height of 2 mm to 3 mm or spherical with a diameter of 2 mm to 3 mm. The cancellous tissue forms may have a defined shape that may be spherical, discoid, or cuboidal in nature and may be loaded into filler tubes prior to implantation. The cancellous tissue forms may also have a single dimension of no more than 5 mm and no less than 1.0 mm and will be designed to pack tightly under pressure. It is recognized the size of the individual units will be considerably smaller than the diameter of the filler bag once it has been expanded. 
         [0041]    In operation, a small nucleotomy is created in the disc annulus by first making an incision in the disc and then expanding the same using dilators of increasing size. The nucleus is then mechanically removed while avoiding damage to the inner annulus or the cartilaginous end plates. Following the nucleotomy, an inflatable balloon is inserted in the disc nucleus and the nucleus is filled with radio contrast fluid to a specific pressure between 30 to 60 psi such that the nuclear cavity is visible under fluoroscopy. This step allows visualization of the cavity created by the nucleotomy and also provides a measurement of the cavity volume, which will be used to select the mesh size and determine the amount of fill material needed for the implant. After sizing, the porous mesh is inserted through the portal in the disc annulus. In order to ensure that the mesh is not restricted from deploying properly, an inflatable balloon is placed into the empty mesh in situ and the balloon is again filled with radio contrast material. Subsequently, the balloon is removed from the mesh and demineralized non-osteoinductive cancellous tissue in the form of cubes, discs or spheres is added to the mesh by extruding the filler implant material that has been pre-loaded in small diameter tubes. Based on the empty cavity volume of the disc nucleus, the mesh will be filled to a packing density of 0.3 to 0.9 g/cc where the weight of the tissue is based upon its dry weight. After the filling step, the mesh is released from its holder tube and its opening is tied off to prevent migration of the cancellous tissue from the disc space. In another embodiment of the invention, a degenerated or diseased intervertebral disc is treated with the above noted steps where after the step of removing a portion of or the entire disc nucleus via mechanical disruption, at least one region of the vertebral end plates is removed or disrupted. 
         [0042]    The principles, preferred embodiments and modes of operation of the present invention have been described in the foregoing specification. However, the invention should not be construed as limited to the particular embodiments which have been described above. Instead, the embodiments described here should be regarded as illustrative rather than restrictive. Variations and changes may be made by others without departing from the scope of the present inventions defined by the following claims: