Abstract:
Disclosed herein are biomedical implants, and methods of using same, that are derived from bone. Particularly exemplified are implants having a tapered dowel shape that are useful for implantation in the spine, and especially in the cervical region of the spine. The taper of the implants disclosed herein provides an advantage over conventional implants, as it creates the proper support and angulation to maintain the proper curvature of the spine. Optionally, the implants taught herein are associated with osteogenic materials or other biomedical substances.

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     This application claims the benefit under 35 USC § 119(e) of Provisional Application No. 60/186,312 filed Mar. 2, 2000. 
    
    
     BACKGROUND OF THE INVENTION 
     Many advances are being made in the field of orthopedic implants, especially in relation to the treatment of diseases, injuries or defects of the spine. For example U.S. Pat. No. 5,814,084 (&#39;084 patent) discloses a diaphysial cortical dowel designed for vertebral fusions, which represents a marked improvement over the conventional implants to date. The dowel of the &#39;084 patent is made of bone, thus it is remodeled by the patient and does not suffer from many of the drawbacks observed with metals and synthetics, e.g., inflammation, weakening of surrounding tissues, and antigenicity. The subject invention builds on the successes in this field, by providing an implant that is shaped for implantation at certain locations of the spine and aids in maintaining the proper curvature of the spine as well. 
     SUMMARY OF THE INVENTION 
     The subject invention relates to an implant made of bone that comprises an elongated body having a first and second ends, wherein the elongated body tapers down its length from a point on or proximate to the first end to the second end or a point proximate thereto. The term “proximate” as used herein is intended to mean a point or region located on the elongated body of the implant that is closer to the end to which it corresponds than the opposing end. For example, proximate to said first end would mean a point or region closer to the first end than the second end. Specifically exemplified is an implant substantially shaped in the form of a dowel. 
     In a another embodiment, the subject implant has a channel formed therethrough to allow for the disposition therein of osteogenic and other biomedical substances. Optionally, the implant has perforations or holes to facilitate the release and delivery of such substances. 
     In an alternative embodiment, the subject implant comprises a plurality of sections that can be assembled and secured together. As with the other embodiments described herein, the assembled implant can comprise a channel for the disposition of osteogenic and other substances. 
     The subject implant is designed for implantation into the spine during spinal surgeries, especially spinal fusions (arthrodesis). The taper of the subject invention provides an advantage over conventional implants, as it creates the proper support and angulation to maintain the proper curvature of the spine (lordosis). Accordingly, a further embodiment of the subject invention pertains to a method of performing spinal surgery comprising implanting the subject implant into the intervertebral space in a spinal fusion procedure. Further, the novel use of bone as the material for producing the subject implant provides other advantages. Such advantages include the provision of an implant that is remodeled by the body into autogenous bone, and thereby incorporated into the existing bone structure. This leads to a more desirable result with respect to the strength and integrity of the implant. Further, the subject implant does not have the problem of inflammation at the implant site that is often caused by non-remodelable materials, such as metals or plastics. This inflammation can lead to deterioration of the bone surrounding the implant site, which can cause complications and necessitate follow-up surgeries. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows side view ( FIG. 1A ) and an end view ( FIG. 1B ) of a starting bone block that is machined to obtain a tapered implant according to the teachings herein, and which comprises holes to engage a securing device. 
         FIG. 2  shows another embodiment of the subject implant that has a threaded outer surface and comprises a channel that provides a space to dispose biologically active substances.  FIG. 2A  shows a side view of this embodiment and  FIG. 2B  depicts a close-up of the threaded surface. 
         FIG. 3  shows another embodiment of the subject implant that comprises an oval channel and whose threads are slightly modified compared to the threads shown in  FIG. 2 .  FIG. 3A  shows a side view capturing the channel of the implant.  FIG. 3B  represents a close-up of the threads machined on the exterior of the implant.  FIG. 3C  represents an end-view of this embodiment.  FIG. 3D  shows a side-view of this embodiment that is rotated as to show the side walls of the implant adjacent to the channel. 
         FIG. 4  shows a further embodiment of the subject implant that comprises a wedge-like end to aid in manipulating the implant.  FIG. 4A  shows a side view which depicts the channel and wedge-like end.  FIG. 4B  shows a perspective view of this embodiment.  FIG. 4C  shows an end-view of the wedge-like end.  FIG. 4D  shows a side view that is rotated as to show the side walls of the implant adjacent to the channel. 
         FIG. 5  shows a further embodiment of the subject implant that tapers from one end to the other but has a region in the middle of the implant that is more narrow than either end. 
         FIG. 6  shows a further embodiment of the subject implant that comprises a slot formed on the wider of the two ends.  FIG. 6A  is a perspective view of this embodiment.  FIG. 6B  is a side view of this embodiment.  FIG. 6C  is an end-view of the wider end of this embodiment. 
         FIG. 7  shows an end-view ( FIGS. 7B–C ) and side view ( FIG. 7A ) of several drives for securing the subject implant into place. 
         FIG. 8  shows side views ( FIGS. 8A–B ) and end view ( FIG. 8C ) of a further embodiment of the subject implant. 
         FIG. 9  shows a further embodiment of the subject implant that comprises pinch cut out for engaging a securing device.  FIG. 9A  is a side view of an embodiment that has a channel and smooth exterior.  FIG. 9B  is an end view of the embodiment shown in  FIG. 9A .  FIG. 9C  is a side view of the embodiment of  FIG. 9A  which has a threaded exterior surface. 
         FIG. 10  shows a perspective view of another embodiment of the subject invention that comprises a number of separate pieces ( FIG. 10A ) that are assembled into a single unit ( FIG. 10B ). 
         FIG. 11  shows a perspective view ( FIG. 11A ), an end-view ( FIG. 11B ), a cross-sectional view ( FIG. 11C ), and a side view ( FIG. 11D ) of another embodiment of the subject implant that is perforated to facilitate delivery of biologically active substances. 
         FIG. 12  shows a perspective view ( FIG. 12A ), an end-view ( FIG. 12B ), a cross-sectional view ( FIG. 12C ), and a side-view ( FIG. 12D ) of an embodiment of the subject implant which is a variation of the embodiment shown in  FIG. 11 . 
         FIG. 13  depicts an example of a bone that is an appropriate source for deriving an implant having a wedge-like end. 
         FIG. 14  represents a schematic for procuring a bone block from the bone depicted in  FIG. 13 , which can then be machined to form an implant according to the teachings of the subject invention. 
     
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Turning now to the drawings,  FIGS. 1A–B  show an example of a bone block  100  that is then tapered according to the teachings of the subject invention. The dashed lines A depict the tapering of the bone block, which can be accomplished by conventional machining methods, e.g., with a lathe and in particular, a CNC lathe. Holes  105  are drilled into the bone block via a drill to engage a securing device for positioning of the implant of the subject invention into the spine. Preferably, 4 holes are drilled in a square configuration suitable for engaging a specially adapted securing device having four prongs for insertion into holes  105 . Typically, the subject implant is secured by rotation. See  FIG. 1B . Machining attachment hole  110  is formed in the bone block  100  which provides a means for the block to be positioned in a machine such as a mill or lathe to hold the block steady during machining, to ensure proper alignment, and to permit rotation of the workpiece during machining. 
     In  FIGS. 2A–B , there is shown another embodiment  200  of the subject implant. As shown in  FIG. 1 , embodiment  200  comprises holes  205  for engaging a securing and driving device. Further, this embodiment comprises a channel  220  that preferably transverses completely through the implant. Channel  220  provides a space into which an osteogenic material can be disposed to aid in the healing and bone formation process. Also, the inventors have discovered that provision of the channel  220  aids in release of bone morphogenetic proteins (BMP) naturally present in the bone used for producing the subject implant and better contact of adjacent vertebrae with the osteogenic material within said dowel. In addition, in embodiments of this invention, channels, pores or the like may be formed, preferably connecting the exterior of the implant with the channel, to better induce seepage of growth factors from the osteogenic material in the channel or in the bone into the surrounding tissue. Embodiment  200  also comprises a machining attachment hole  210 . Various dimensions of the implant are noted in  FIGS. 2A–B , represented by the letters B–G. The skilled artisan will readily appreciate that these dimensions can be adapted to suit various sized patients, including infants, children, and adults. The following values are to be viewed as preferred values. Length B can range from about 5 to about 25 mm, and preferably from about 10 to about 15 mm. The root diameter C can range from about 3 to about 15 mm, and preferably from about 4 to about 11 mm. The taper angle D can range from about 1 to about 8 degrees, and preferably from about 3 to about 5 degrees. E can range from about 0.3 mm to about 1 mm, and preferably from about 0.4 mm to about 0.6 mm. The radius F of the thread profile can range from about 0.3 mm to about 1.3 mm, and preferably from about 0.5 mm to about 0.9 mm. The pitch G of the thread profile can range from about 0.08 to about 2 mm, and preferably from about 1 mm to about 1.8 mm. 
     In  FIGS. 3A–D , there is shown a further embodiment  300  of the subject implant that is similar to embodiment  200  except that the channel  320  is oval in shape and the thread profile is slightly modified. The oval shape of the channel  320  is achieved by drilling a circular hole through the implant, and then drawing an appropriately dimensioned broach through the circular hole. Preferably, the broach has disposed thereon cutting teeth which change in shape as the diameter of the broach increases from a circular to an oval circumference. Embodiment  300  also comprises a machining attachment hole  310 . Those dimensions noted in  FIGS. 3A–D  have similar values to that described above for embodiment  200  unless otherwise indicated. Dimension H comprises the length of the channel  320  which can range from about 4 to about 8 mm. It represents the angular relation of the holes  305  from the center axis of the implant. As shown, holes  305  are preferably placed 45 degrees above and below the x-axis.  FIG. 3B  shows the thread profile comprising a ridge J, which can range from about 0.05 mm to about 0.15 mm. Further, embodiment  300  comprises a machining attachment hole  310 . 
       FIGS. 4A–D , show a further embodiment  400  of the subject implant which comprises oblique sides  415  thereby forming a “roof-top” or wedge-like shape on end  410  of the implant to engage a securing device, wherein the securing device is shaped to conform to end  410 . Embodiment  400  comprises a channel  420 . Further, the dimensions noted in  FIGS. 4A–D  have the same values as above, unless otherwise indicated. Embodiment  400  comprises a substantially planar or flat end  425  having a dimension L toward which oblique sides  415  slope and connect. Dimension L preferably ranges from 0.5 to about 5 mm. A securing device hole  430  is formed into the wedge end which is designed to engage to a securing device to thereby further stabilize the implant on the securing and driver device during implantation. Dimensions M and N preferably range from about 0.5 mm to about 7 mm. More preferably, dimension N is equal to or larger than dimension M. Wedge angle P preferably ranges from about 45 to about 90 degrees, and preferably is set to a standard style angle to match a reciprocal angle on a driver tool. 
     It is appreciated in the art that human donor tissue is extremely limited in supply. Thus, it is always advantageous to develop methods of maximizing the use of donor tissue. With this goal in mind, it was discovered that the use of the natural architecture of certain bones in the body are suitable for providing a wedged end as described above for embodiment  400 . For example, the tibia comprises an anterior ridge along a substantial portion of its length. It was found that excising block sections along such a ridge can provide oblique sides, thereby avoiding having to machine and discard precious bone material to produce such oblique sides, while preserving donor bone stock for other applications. Where donor bone is less scarce, as in the use of xenograft bone stock, (including but not limited to bovine, ovine, equine, canine or the like) or if allograft bone is in abundant supply, use of the wedge shaped driving structure is less critical. Where used, however, the wedge-shaped driving structure fits conveniently into a complementary driver device for rotation of the implant. 
     In an alternative embodiment, as shown in  FIGS. 13 and 14 , a method of procuring the subject implant comprises obtaining a long bone, such as the tibia  1300 , and cutting off the ends  1310  and  1320  from the elongated central portion (dashed lines AA).  FIG. 14  shows an end-view of the resulting central portion section produced after excision of the end portions  1310  and  1320 . At this point, sections (dashed lines BB) along the ridge  1340  of the tibia are excised which comprise a wedge end as a result of the natural architecture of the bone. Those skilled in the art will understand that this method can be applied to other bones in the body having a desired architecture. 
     In  FIG. 5 , there is shown a further embodiment  500  of the subject implant that tapers from one end to the other but has a region in the middle of the implant  505  that is more narrow than either end. Embodiment  500  also preferably comprises oblique sides  515  and a securing device hole  530 . 
     In  FIGS. 6A–C , there is shown another embodiment  600  of the subject implant having a slot  635  formed on the wider of the two ends of the implant. The slot  635  is designed to engage a securing and driving device, such as, for example, a flat-head screwdriver. As in other embodiments, embodiment  600  comprises a channel  620  and a securing device hole  630 . Dimensions B, D, H, and O shown in  FIGS. 6A–C , have similar values as described above. 
     In  FIGS. 7A–D , there are shown further embodiments of the subject implant that comprises a peg  705  contiguous with and extending from end  750 , the wider of the two ends of the implant. The peg acts as driver to turn and secure the implant when engaged to a securing device. The peg device may be round for being driven by a collet, or may be square or otherwise shaped for secure torquing by a reciprocal driving means.  FIG. 7B  shows an end-view of the narrower end  755 .  FIGS. 7C  and D show various alternatives for the shape of the peg, e.g., square and hexagonal. The skilled artisan will appreciate other appropriate shapes can be used, e.g. octagonal, triagonal, etc. In addition, it will be appreciated that the drive means may be recessed into the implant and driven by an appropriately shaped driver. 
     In  FIGS. 8A–C , there is shown another embodiment  800  of the subject implant that comprises both a wedge-like end  810  and a raised vertex  805  to further aid in engaging a securing device. Embodiment  800  comprises a securing device hole  830  as well.  FIG. 8C  shows an end-view of embodiment  800  showing the raised vertex  805 , securing device hole  830 , and the oblique sides  815 . The value of D is the same as that described above. Preferably, as shown in  FIG. 8A , the implant comprises a channel  820 . 
       FIGS. 9A–C  show a further embodiment  900  of the subject invention that comprises two or more pinch cut outs  905  from the edge of the wider of the two ends  950  of the implant. The pinch cut outs  905  act to engage a securing device for securing the implant in the patient.  FIG. 9A  shows a version of the embodiment  900  that does not have threads disposed on its surface.  FIG. 9B  shows an end-view of the wider end  950 , which depicts two pinch cut outs  905  positioned on opposing sides of the implant.  FIG. 9C  shows a threaded embodiment.  FIG. 9D  shows an embodiment that comprises a channel  920  and a narrower stepped portion  930  at its wider end  950 . 
     Those skilled in the art will appreciate that the subject implant does not necessarily comprise threads. However, threads are preferred in most cases, as they aid in securing the implant in the patient. Rotation of the subject implant results in the threads digging into the adjacent bones thereby forming a tight contact. 
     In  FIGS. 10A–B , there is shown another embodiment  1000  of the subject implant that is comprised of two or more sections that are assembled into a single unit. Embodiment  1000  comprises a first section  1004  and a second section  1005  that are placed contiguous to each other and then secured together by pins  1010 . The pins  1010  may be formed from any appropriate material, including but not limited to cortical bone, titanium, stainless steel, hydroxyapatite, bioactive glass, polylactic acid and like polymers. The second section has a slot  1015  formed thereon for engaging a securing device, as well as a securing device hole  1030  for further stabilization on the securing device during implantation.  FIG. 10B  shows the embodiment  1000  as assembled. In addition to the slot  1015  and the securing device hole  1030 ,  FIG. 10B  illustrates the formation of a channel  1020  when the implant is assembled. Those skilled in the art equipped with the teachings herein will appreciate that the second section  1005  comprising the slot  1015  could be configured to have formed thereon any of the other driver means described herein, e.g., wedge, raised ridge, peg, pinch, 4-pin, etc. 
       FIG. 11A  shows a perspective view of further embodiment  1100  of the subject implant, having a tapered body resulting in a smaller diameter for the front end  1110 , and a larger diameter for the back end  1120 . The back end  1120  comprises a hex drive  1130  formed therein for insertion and rotation of the implant. Implant  1100  defines a channel  1140  for use of packing biologically active substances. Holes  1150 , which radiate from the channel  1140  to the cortical surface  1160 , allow the biologically active substances to penetrate through the entire implant  1100 .  FIG. 11B  is an end plan view of implant  1100  showing the back end  1120  along with the hex drive  1130 .  FIG. 11C  depicts a transverse section of implant  1100  along the AA axis shown in  FIG. 11B . The hex drive  1130  is shown running from the front end  1110  to the back end  1120 .  FIG. 11D  shows a side view of implant  1100 , holes  1150 , and screw threads  1170  which are inscribed from the front end  1110  to the back end  1120 . The screw threads  1170  ease insertion and help to hold the implant in place. 
       FIGS. 12A–12D  show an alternate embodiment of the cervical tapered dowel depicted in  FIGS. 11A–11D .  FIG. 12A  shows a perspective view of implant  1200 , having a tapered body resulting in a smaller diameter for the front end  1210  and a larger diameter for the back end  1220 . The back end  1220  contains an instrument hole  1230  along with a score mark  1240  for use with an insertion device to provide torque to the implant. Implant  1200  contains a channel  1250  for packing biologically active substances along with holes  1260  that radiate from the channel  1250  to the cortical surface  1270 .  FIG. 12B  is an end plan view of implant  1200  showing back end  1220  along with the instrument hole  1230  and the score mark  1240 .  FIG. 12C  depicts a transverse section of implant  1200  along the AA axis shown in  FIG. 12B . The instrument hole  1230  is shown extending partially through the implant into the channel  1250 .  FIG. 12D  shows a side view of implant  1200 . The screw threads  1280  ease insertion and help the implant retain its position once implanted. 
     It will further be appreciated from the present disclosure that the implant may be contacted with cells prior to implantation. For example, bone implants according to this invention may be cultured with stem cells, fibroblasts, muscle cells, neuronal cells or the like or simply contacted therewith or be infused therewith prior to implantation. Preferably, the cells that are contacted with the implant are stem cells, such as those known in the art or which become known hereafter. For example, human mesenchymal or other stem cells, such as those disclosed in any of U.S. Pat. Nos. 5,486,359; 5,811,094; 5,197,985; 5,591,625; 5,733,542; 5,736,396; 5,908,784; 5,942,255; 5,906,934; 5,827,735; 5,962,325; 5,902,741; 4,721,096; 4,963,489; (all of which are hereby incorporated by reference), may be contacted with, infused into or cultured on the implants of the present invention. The plurality of holes in the implant of this invention thus permit for interpenetration of such cells into the interior of the implant prior to implantation, and from the interior of the implant, to assist in remodeling, subsequent to implantation. 
     Alternatively, perforations or holes can be formed in the subject implants, which can control and improve the release and delivery of biologically active substances loaded in the channel, or otherwise infused, embedded or coated on or in the implants. Naturally, the rate of release will be dependent on the size and number of holes provided. As discussed above, the channel of the subject dowels can be packed with various biologically active substances, including, but not limited to, growth factors, antibiotics, nucleic acids, proteins, peptides, antineoplastics, and anti-inflammatory compounds, and the like. Furthermore, the plurality of holes taught herein can facilitate the migration and growth of cells and tissues into the implant. It will be appreciated that any appropriate carrier may be used in association with these biologically active substances, including, but not limited to, gelatin, collagen, mixtures thereof, synthetic compositions, biologically resorbable pastes and the like. Furthermore, the composition may comprise a bone paste composition comprising cortical bone chips, cancellous bone chips, demineralized bone matrix powder (DBM), bioactive glass or other ceramics, growth factors, nucleic acids, proteins, peptides, carbohydrates, lipids and the like. Preferably, the substance packed in the canal is an osteogenic substance and/or comprises tissue regenerating growth factors. See, for example, WO98/40113, herein incorporated by reference. Optionally, or in addition to packing the canal, the subject implants can be infused, soaked and/or coated with various biologically active substances. 
     EXAMPLE 
     Procedure for Procuring an Implant Having a Wedged End from a Human Tibia 
     Equipment 
     Sherline Mill with 3″ vice attached to cross table 
     Modified Sherline machining lathe with tail stock and tooling bit 
     Modified Sherline lathe with threading attachment 
     Core Cutters, 12 mm and 14 mm 
     3 mm drill bit 
     #0 starter drill 
     Dial calipers 
     Fine toothbrush 
     Scraping tool 
     Procedure 
     An appropriate size cutter was loaded in the chuck of the Sherline mill. The tibia segment was clamped in the vice on the mill table with the anterior of the segment facing up and aligned properly and tightened, and the cutter was aligned to the segment. The motor assembly was adjusted to about 200 RPM, and the cutter was lowered down to the bone and cut through the segment. The cutter was retracted to its original position and the cut dowel was removed from the cutter. The foregoing was repeated until all of the dowels were cut. 
     To form the wedge end of the dowel, a cut dowel as described above was placed with the anterior end facing the tooling bit in the chuck of the machining lathe and tightened. The lathe motor was turned on and the end of the dowel was machined to form 3.5 mm oblique side on the end. Using the center drill in the tail-stock, a starter hole was drilled in the end of the dowel. This operation was repeated until all of the dowels were machined with the oblique side and had the starter hole drilled therein. 
     The ends of machined dowels opposite the oblique sides were flattened and cancellous bone was removed. To accomplish this, each dowel was individually placed into the chuck with the posterior end of the dowel facing the tooling bit and tightened. The end of the dowel was machined until all the cancellous bone was removed and the dowel was flat. The dowel was then removed from the chuck and measured to determine if the length was at a desired length and to determine whether more bone needed to be removed. Using the center drill in the tail stock, a starter hole in the flattened end of the dowel was drilled. This procedure was repeated for all of the machined dowels. Next, the 3 mm drill bit was secured in the chuck in the tail-stock and tightened. A dowel with the 3.5 mm flat was placed in the chuck facing the drill bit and tightened. The tail-stock was advanced forward until the tip of the drill bit was about 1 mm from the end of the dowel and the tail-stock was tightened to the lathe bed. The motor was activated and the drill bit was advanced into the dowel to form a hole 6 mm in depth. This procedure was repeated for all of the dowels. 
     The dowels having the oblique sides, flattened end and holes drilled on both ends were then subjected to the threading lathe. The dowel was placed in the threading lathe and tightened. The air motor was activated with the milling cutter attached and advanced into the dowel until lightly touching the dowel. The threading handle was turned to move the cutter assembly to the right until it cleared the dowel. The cutter was advanced forward to remove the desired amount of bone to achieve the desired dowel diameter. The foregoing procedure was repeated for all of the dowels. Using a burring tool or a scraper, any burrs present were removed from the dowel. A fine tooth brush was used to brush the threads on the dowel to remove any fine burrs. 
     The teachings of all of the references cited throughout this specification are incorporated herein by this reference to the extent that they are not inconsistent with the teachings herein. Thus, for example, a device made from metal is known for application to the cervical spine (see U.S. Pat. No. 5,782,919; U.S. Pat. No. 5,669,909, herein incorporated by reference for this purpose). The present invention provides an improvement to such devices in that the bone material of the present implant is remodelable, such that autogenous bone replaces implant bone over time to induce a permanent fusion, while metallic implants frequently require removal or cause stress shielding, ultimately causing the implant to fail. It should be understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and the scope of the appended claims.