US20020173851A1 - Intervertebral disc treatment devices and methods - Google Patents
Intervertebral disc treatment devices and methods Download PDFInfo
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- US20020173851A1 US20020173851A1 US10/165,347 US16534702A US2002173851A1 US 20020173851 A1 US20020173851 A1 US 20020173851A1 US 16534702 A US16534702 A US 16534702A US 2002173851 A1 US2002173851 A1 US 2002173851A1
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Definitions
- the present invention relates generally to devices and methods for restoring function to the spine. Specifically, the invention relates to devices and methods for treating a damaged intervertebral disc while retaining the annulus fibrosis of the disc and, advantageously, stimulating tissue formation to restore function to the original disc structure.
- Intervertebral discs located between the endplates of adjacent vertebrae, stabilize the spine, distribute forces between vertebrae, and cushion vertebral bodies.
- An intervertebral disc includes the annulus fibrosus, a structure that surrounds and confines an inner component, the nucleus pulposus.
- the annulus fibrosis is composed of a ring of collagen fibers and fibrocartilage embedded in a generally amorphous base substance.
- the nucleus pulposus is comprised of a mucoid material containing mainly glycoproteins and some collagen. In a healthy, undamaged spine, the annulus fibrosus prevents the nucleus pulposus from protruding outside the disc space and also resists torsional and bending forces applied to the disc.
- Intervertebral discs may be displaced or damaged due to disease or aging. Disruption of the annulus fibrosus can allow the nucleus pulposus to protrude into the vertebral canal or intervertebral foramen, a condition known as a herniated or slipped disc. A rupture in the annulus fibrosis can allow the escape of nucleus pulposus components. The extruded nucleus pulposus may press on a spinal nerve, which may result in nerve damage, pain, numbness, muscle weakness and paralysis. Furthermore, as a disc dehydrates and hardens due to age or disease, the disc space height will be reduced, leading to instability of the spine, decreased mobility and pain. Moreover, excessive movement of the spinal segments caused by the disc space height reduction could weaken the annulus fibrosus and, in certain cases, tear it.
- the present invention relates to methods and devices for repairing an intervertebral disc which include promoting synthesis of tissue components, such as nucleus pulposus and/or annulus fibrosus components, of the disc.
- the present invention provides a device which can be used to promote the synthesis of disc components in vivo to treat intervertebral discs.
- a device for treating an intervertebral disc of a vertebrate while retaining an intact annulus fibrosis the device including a compressible fibrous body configurable to a compressed state for passage through an opening in the annulus fibrosis and into a disc cavity defined by the annulus fibrosis.
- the body is also configurable to an expanded state to reside within the disc cavity and have a dimension greater than the opening so as to resist expulsion from the opening.
- the body incorporates an effective amount of an active agent, such as a tissue growth factor, or cells (e.g. stem, nucleus pulposus, annulus fibrosis, or fibroblast cells), such cells optionally genetically modified to express effective amounts of a tissue growth factor, to stimulate tissue growth in the disc structure.
- an active agent such as a tissue growth factor, or cells (e.g. stem, nucleus pulposus, annulus fibrosis, or fibroblast cells), such cells optionally genetically modified to express effective amounts of a tissue growth factor, to stimulate tissue growth in the disc structure.
- an intervertebral disc treatment device including a fibrous body sized for passage through an opening in the annulus fibrosis and into a disc cavity defined by the annulus fibrosis.
- the body is formed of fibers having coated thereon a solid carrier matrix incorporating a substance for promoting tissue growth.
- the body of the device may be partially or completely bioresorbable.
- the body may be sized and configured to provide temporary or permanent prosthetic function, by being dimensioned to participate in the distribution of compressive loads between adjacent vertebral bodies.
- the body may be adapted to physically maintain a space in the disc as new tissue is generated, and provide a substrate for tissue ingrowth which locks the implant in place and reinforces regenerated tissues to help maintain disc space height.
- the body may be non-prosthetic, while delivering a substance for promoting tissue growth in the disc structure.
- the device can be dimensioned, or can be formed of a material having compressive properties, such that it does not participate in the distribution of loads between the adjacent vertebral bodies. Nonetheless, such a non-prosthetic body may deliver the tissue growth substance so as to enhance the function or integrity of the disc structure.
- Another feature of the invention provides an intervertebral disc repair apparatus that has a disc treatment device as described above in combination with a delivery apparatus.
- the delivery apparatus is adapted to retain and selectively release the treatment device into the disc cavity, and may for example include a member having a proximal end, a distal end and a lumen extending longitudinally therethrough.
- the disc repair device is disposed within the lumen of the apparatus.
- the delivery apparatus is adapted to translate the disc repair device distally through the lumen, through an opening in the annulus fibrosis, and into the disc cavity.
- Yet other features of the invention include methods for treating an intervertebral disc, which involve introducing a disc treatment device as described above into the disc cavity of a damaged disc.
- methods for treating a disc having an annulus fibrosis having an opening therein which methods include providing a body configured for passage through the opening and for blocking effluence from the opening once positioned within the disc cavity. The body is passed through the opening and into the disc cavity, so as to block effluence from the opening.
- a tissue growth composition is also provided within the disc cavity, either as a component of the body or separately.
- FIG. 1 is a perspective view of a disc treatment device of the present invention.
- FIG. 2 is an enlarged, cross-sectional view of the device of FIG. 1 taken along a vertical plane through line 2 - 2 and viewed in the direction of the arrows.
- FIG. 3 is a perspective view of a further disc treatment device of the present invention having an annular ring shape.
- FIG. 4 is a perspective view of a further disc treatment device of the present invention.
- FIG. 5 is a side cross-sectional view illustrating the disc repair device shown in FIG. 1 positioned within an intervertebral disc.
- FIG. 6 is a superior view of the disc treatment device of FIG. 1 positioned in the disc cavity of an intervertebral disc.
- FIG. 7 is a superior view of the disc treatment device of FIG. 3 positioned in the disc cavity of an intervertebral disc.
- FIG. 8 is a superior view of the disc treatment device of FIG. 4 positioned in the disc cavity of an intervertebral disc.
- FIG. 9 is a superior view illustrating two disc treatment devices positioned in the disc cavity of an intervertebral disc, and wherein an opening in the annulus fibrosis is sealed with a sealant composition.
- FIG. 10 is a superior view illustrating first and second disc treatment devices positioned within the disc cavity of an intervertebral disc, wherein one functions to seal a rupture in the annulus fibrosis.
- FIG. 11 is a side cross-sectional view of a disc treatment apparatus, showing the disc treatment device of FIG. 3 in a compressed conformation in the lumen of a delivery apparatus.
- FIG. 12 is a side cross-sectional view of a disc treatment apparatus, showing the disc treatment device of FIG. 4 in a compressed conformation in the lumen of a delivery apparatus.
- FIGS. 13 and 14 are superior views illustrating the use of the disc treatment apparatus of FIG. 11 to release the disc treatment device of FIG. 3 into a disc cavity.
- FIG. 15 is a perspective view of another disc treatment device of the invention.
- FIGS. 16 - 18 illustrate elongate implants of the invention and apparatuses and methods for their introduction into the disc cavity.
- FIGS. 19 - 21 illustrate elongate implants of the invention and additional apparatuses and methods for their introduction into the disc cavity.
- the present invention provides intervertebral disc treatment devices, apparatuses and methods.
- Preferred devices include a fibrous body configurable to smaller (compressed) and larger (relaxed) dimensional states. In the small configuration the body is adapted for passage through an opening in the annulus fibrosis and into a disc cavity defined by the annulus fibrosis. In the larger configuration the body is dimensioned sufficiently to resist expulsion from the annulus opening when positioned within the disc cavity. The body incorporates an effective amount of a substance which promotes tissue formation in the disc structure.
- inventive apparatuses are provided which include such fibrous bodies in combination with a delivery apparatus adapted to retain and selectively release the bodies into the disc cavities, and inventive methods are also provided can be performed using the devices and apparatuses of the invention.
- a preferred intervertebral disc treatment device 11 that includes an outer surface 12 , and opposing ends 13 .
- Device 11 is elongate in shape, having a generally cylindrical configuration with a circular cross-section.
- Device 11 has a length L and a cross-sectional dimension adapted for insertion into the disc cavity of a damaged disk.
- length L will be about equal to or less than a horizontal cross-sectional dimension of the disc cavity of a human disc (e.g. the anterior-posterior width and/or the lateral width of the disc cavity), typically in the range of about 1.5 cm to about 3.5 cm.
- device 11 will be of a size and composition so as to avoid the exertion of substantial lateral pressure upon the annulus fibrosis by the device, which may cause or facilitate the development of a rupture in the annulus fibrosis.
- Device 11 will have or be compressible radially to have a greatest cross-sectional dimension which renders device 11 suited for insertion into an opening in a disc annulus, such greatest cross-sectional dimension typically being in the range of about 0.3 cm to about 2.0 cm.
- Device 11 may, for instance, have a body comprised of a woven or nonwoven fibrous material, including but not limited to a fibrous mesh.
- the body of device 11 is also preferably swellable in the presence of aqueous fluids, for example swelling upon absorbing aqueous fluids into pores created between fibers in a fibrous body, and/or upon hydration of the fibers themselves.
- device 11 may be formed as a roll of a sheet material, for instance a fibrous mesh, to provide a multi-layered device.
- the device may be constructed to prevent, or alternatively to allow, for unrolling or unfolding of the layers after insertion into the disc cavity.
- layers may be permanently affixed to one another such as by bonding, crosslinking or stitching, to prevent unfolding.
- layers may be free of permanent affixation to one another (e.g.
- Such unfolding may, for example, participate in configuring the device to resist expulsion from an annulus fibrosis opening, and/or to occupy a modified volume within the disc cavity for supporting tissue ingrowth.
- the device may assume a variety of other configurations including spherical, rectangular, conical, ring, and other shapes. It is preferred that the device be shaped so that it can facilitate blocking an opening in the annulus fibrosus of a damaged intervertebral disc when positioned in the disc cavity.
- the device may have a first end having a cross-sectional dimension smaller than another cross-sectional dimension along the device, for example having an increasing cross-sectional dimension along the device length such as occurs in a generally conical device.
- such a disc repair device 21 having a generally conical shape with a larger end 22 and an outer surface 23 that tapers towards a smaller opposing end 24 .
- the device may be collapsible in upon itself to have a smaller overall cross-sectional dimension in a direction in which it is to be inserted, for example in the case of an annular ring.
- Shown in FIG. 4 is such a disc treatment device 31 , having the shape of an annular ring.
- Device 31 preferably has an outer diameter, when expanded, approximating the horizontal width of the disc cavity, and can be collapsed upon itself to adopt a smaller overall cross-sectional dimension for insertion through an opening in the annulus fibrosis.
- FIG. 5 shown is a side cross-sectional view of a intervertebral disc having positioned therein disc treatment device 11 of FIG. 1.
- an intervertebral disc 41 includes the annulus fibrosus 42 formed from multiple layers of type II collagenous tissue, bounding an internal disc cavity 43 .
- Disc treatment device 11 is sized and configured to be contained within the disc cavity and in the illustrated embodiment has a vertical dimension to contact the upper and lower surfaces of the disc cavity formed by end plates of adjacent vertebrae.
- device 11 has a horizontal dimension substantially spanning the horizontal width of the disc cavity 43 .
- Device 11 also abuts the inner surface of the annulus fibrosus 42 so as to facilitate blockage of effluence from disc cavity 43 via opening 44 in annulus fibrosus 42 .
- Opening 44 in annulus fibrosis 42 often occurs posterolaterally, where the annulus fibrosis is no longer supported by the posterior longitudinal ligament.
- device 11 or other disc treatment devices of the invention can be inserted via a posterolateral approach, although other approaches may be used which correspond to the location of the rupture in the disc to be treated, or which involve insertion of the device through a conservative, alternate opening created in a spaced location from the rupture.
- FIGS. 6, 7, and 8 shown are superior views of disc treatment devices 11 , 21 , and 31 , respectively, positioned within the disc cavity of a ruptured disc.
- the disc treatment devices of the invention may be formed from a wide variety of natural and/or synthetic materials, preferably natural and/or synthetic polymers.
- Natural polymers include, for example, collagen, elastin, and cellulose and may be obtained from natural sources by methods known to the skilled artisan, synthesized by methods known to those skilled in the art, or may be obtained commercially.
- Synthetic polymers which may be used in the present invention include, for example, polyamides, polyesters (e.g., Dacron), polyethylene, polyacrylonitrile, polyurethanes, polypropylenes or mixtures thereof. Combinations of natural and synthetic materials may also form an appropriate fibrous body for use in the present invention.
- the preferred devices of the invention advantageously incorporate a tissue growth factor.
- the device includes a liquid or solid carrier containing the tissue growth factor.
- a solid or liquid carrier containing the growth factor may be used to coat the exterior of the device, and/or may be incorporated within interstitial spaces (e.g. pores) occurring internally of the device.
- a solid carrier matrix containing the growth factor may be used to coat individual fibers from which the body of the disc treatment device is formed.
- the growth factor is generally suited to promote the formation of tissues, especially of the type(s) naturally occurring as internal or external components of the disc.
- the growth factor may promote the growth or viability of tissue or cell types occurring in the nucleus pulposus such as nucleus pulposus cells and chondrocytes, as well as space filling cells such as fibroblasts and connective tissue cells such as ligament and tendon cells.
- the growth factor may promote the growth or viability of tissue types occurring in the annulus fibrosus, as well as space filling cells such as fibroblasts and connective tissue cells such as ligament and tendon cells.
- Such growth factors include Transforming Growth Factor-beta (TGF-B) and members of the TGF-B superfamily, Fibroblast Growth Factor (FGF) and members of the FGF family, Platelet Derived Growth Factor (PDGF) and members of the PDGF family, members of the hedgehog family of proteins, interleukins, Insulin-like Growth Factor (IGF) and members of the IGF family, colony-stimulating factor (CSF) and members of the CSF family, Growth Differentiation Factors (GDFs), Cartilage Derived Growth Factors (CDGFs), Cartilage Derived Morphogenic Proteins (CDMPs), Bone Morphogenetic Proteins (BMPs), and mixtures thereof. BMPs are preferred.
- TGF-B Transforming Growth Factor-beta
- FGF Fibroblast Growth Factor
- PDGF Platelet Derived Growth Factor
- GDFs Growth Differentiation Factors
- CDGFs Cartilage Derived Growth Factors
- BMPs A wide variety of BMPs have been identified and may be used in the present invention.
- Human BMPs especially recombinant human BMPs, are preferred, including for instance BMPs 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 and 18.
- a variety of such BMPs have proven effective for forming soft connective tissues such as cartilage (e.g. BMP-2 and BMP-4) or ligament and tendon (e.g. BMP-12 and BMP-13), and these and other similarly functional proteins are used with preference in the instant invention.
- BMPs are available from Genetics Institute, Inc., Cambridge, Mass. and may also be prepared by one skilled in the art as described in U.S. Pat. No.
- BMPs are contemplated whether obtained as above or isolated from bone. Methods for isolating BMP from bone are described in U.S. Pat. No. 4,294,753 to Urist and in Urist et al., PNAS 371, 1984. Most preferably, the BMP or other growth factor will be non-osteoinductive or at the least insufficiently osteoinductive to cause a bony fusion of the vertebrae above and below the disc under treatment.
- BMP-12 and/or BMP-13 will be employed in an effective amount to stimulate growth of ligament and/or tendon connective tissue within the disc cavity, for instance as may be evidenced by increased synthesis of proteoglycans and collagens.
- Recombinant human BMP-13 is most preferred in this regard.
- a wide variety of materials may be utilized as solid carriers. Examples include natural polymers such as collagen, gelatin, elastin, cellulose, and the like.
- the carrier is collagen.
- types of collagen may be used, including type I (found primarily in skin, tendon and bone), type II (found in cartilage), type III (found primarily in skin), fibrillar and non-fibrillar collagen.
- the collagen may be isolated from skin, bone, tendon, or cartilage by methods known to the skilled artisan and may be purified by methods known in the art. Alternately, the collagen may be purchased commercially. Moreover, atelopeptidic or telopeptidic collagen may be used.
- the tissue growth factor may be applied to the device as described above or may be introduced into the disc space or cavity separately (e.g. by injection), or by recombinant DNA methods.
- a nucleic acid sequence such as a deoxyribonucleic acid sequence, encoding the particular growth factor, or an active fragment thereof, may be introduced into an appropriate vector.
- the vector may be a wide variety of vectors typically used in gene transfer protocols, including, for example, retroviral vectors or adenovirus vectors.
- the vector construct may be synthesized by methods known to the skilled artisan.
- the nucleic acid sequence may be under the control of, and operably linked to, a promoter or other regulatory sequence known in the art.
- the promoter is preferably one which may be activated in the target cell by regulatory elements present in the target cell.
- the disc repair device advantageously includes a therapeutically effective amount of the tissue growth factor. What constitutes an effective amount will vary depending on factors known to the skilled artisan, such as the specific growth factor used and the extent and type of the damage to the intervertebral disc. However, the disc repair device will typically contain about 2 mg to about 20 mg of the growth factor. When BMP-9 is used, for example, amounts applied may include about 8 mg to about 12 mg.
- an intervertebral disc treatment apparatus that includes a disc repair device as described above in combination with a delivery apparatus.
- apparatus 61 is shown that includes the generally conical disc repair device 21 of FIG. 3, in compressed configuration within the apparatus.
- the disc treatment apparatus 61 includes tubular or barrel member 62 having proximal end, a distal end, and a lumen 63 extending longitudinally therethrough.
- Member 62 may be similar to the barrel of a syringe as known in the art.
- Lumen 63 is configured for housing the disc repair device.
- Member 62 may be constructed of a wide variety of materials, including polytetrafluoroethylene (Teflon), polyethylene, polyurethane, nylon, glass, or combinations thereof.
- Disc repair delivery apparatus 61 further includes a translation member 64 at the proximal end of tubular member 62 or forcing the disc repair device 21 distally through lumen 63 , through an opening in the annulus fibrosus of a damaged disc, and into the disc cavity of the disc.
- Translation member 64 may be an elongated member sized to at least partially fit within lumen 63 of member 62 and which is capable of pushing the disc repair device distally along lumen 63 .
- member 64 may be a plunger including a handle 67 , an elongate rod 66 , and an internal member 65 substantially spanning the lumen 63 of tubular member 62 , as seen in FIG. 8.
- translation member 64 may be replaced by other means for translating device 21 along lumen 63 .
- fluid (e.g. liquid) driven mechanisms may be used.
- the disc repair device such as disc repair device 21 , is preferably placed in a collapsed or compressed conformation as shown in FIG. 11, advantageously by manual force, prior to or upon positioning the device 21 in lumen 63 shown in FIG. 12 is a similar disc treatment apparatus 71 except including therein device 31 of FIG. 4 in compressed configuration, instead of device 21 of FIG. 3.
- a method of treating an intervertebral disc includes providing a disc treatment device as described above, such as a fibrous body sized for introduction into an opening of an annulus fibrosus of a damaged intervertebral disc, and inserting the fibrous body into and through the opening, and blocking effluence from the opening.
- a disc repair delivery apparatus 61 or 71 as described above may be used.
- lumen 63 of tubular member 62 is aligned with the opening in the annulus fibrosus of an intervertebral disc so that the disc repair device may be pushed distally along lumen 63 , through the opening in the annulus and into the disc cavity.
- the disc repair device will then adopt an expanded conformation as seen in FIG. 14.
- FIG. 15 shown is an alternative disc treatment device 70 , having a generally bulbous end 71 and a generally cylindrical end 72 .
- Bulbous end 71 has a greatest cross-sectional diameter greater than that of cylindrical end 72 .
- device 70 can be compressed and loaded into a cylindrical delivery apparatus, and delivered through a hole in the annulus and into the disc cavity, preferably first introducing bulbous end 71 . Device 70 can then expand within the disc cavity.
- FIGS. 16 - 18 illustrated is one mode of introducing an elongate implant body through an opening 75 in an annulus 76 (e.g. in the location of a rupture opening), and into the disc cavity 77 .
- An elongate, cylindrical implant 78 is provided (e.g. a Dacron mesh cylinder) having an internal suture 79 or other similar structure running therethrough and tied off or otherwise connected at an end 80 of implant 78 .
- the other end of suture 79 is tied to a curved needle 81 .
- implant 78 can be loaded within a rigid tube 82 , with needle 81 and an exposed length of suture 79 extending therefrom.
- Needle 81 can be passed through opening 75 in annulus 76 and into the disc cavity 77 , and then back through the annulus 76 at a spaced location from opening 75 , for example at an opposite, posterolateral position which can be surgically accessed separately. Suture 79 can then be pulled to in turn pull implant 78 into the disc cavity 77 . Suture 79 can then be closely cut or broken so as to partially retract into the annulus.
- FIG. 19 illustrates another apparatus and method for delivering an implant 85 , such as a cylindrical Dacron mesh implant, into a disc cavity.
- Implant 85 is loaded within a rigid cannula tube 86 , which in turn is passed through the opening in the annulus.
- implant 85 can be loaded in a dry or wet state, preferably a dry, compressed state.
- Implant 85 is then advanced through the tube 86 using push or plunger rod 87 , and into the disc cavity.
- a dry implant 85 will hydrate, and preferably swell, in situ in the disc cavity.
- the internal surface of the tube 86 and the exterior surface of the rod 87 can be provided with respective cooperating members, such as threads, to assist in controllably advancing implant 85 through the tube 86 .
- the inner surface of tube 86 may bear threads, while the external surface of rod 87 bears corresponding threads. In this fashion, rotation of rod 87 in relation to tube 86 will advance rod 87 through tube 86 , thereby pushing implant 85 through tube 86 .
- the implant 85 and/or the internal surface of tube 86 may be coated with a suitable, biocompatible lubricant to reduce the friction between the implant 85 and the tube 86 during the advancement operation.
- a rigid cannula tube 90 defines an opening such as a slot 91 in a sidewall thereof.
- a plurality of openings may also be provided.
- a friction member 92 is mounted over tube 90 and includes an engaging portion 93 extending into slot 91 so as to provide frictional contact with an implant 94 inside tube 90 .
- implant 94 can be advanced through tube 90 by corresponding advancement of the friction member 92 while its engaging portion 93 frictionally engages implant 94 through slot 91 .
- the frictional engagement of the implant 94 can optionally be facilitated by the presence of teeth 95 (e.g.
- engaging portion 93 with implant 94 may be releasable, for example by constructing a deflectable friction member 92 which in a relaxed state disengages engaging portion 93 from the implant, but in a compressed state (e.g. by manually squeezing) engages engaging portion 93 with the implant 94 , or vice versa.
- a tissue growth factor may be provided on the body of or within the device, separately within the disc space of the intervertebral disc, or both. When included separately in the disc space, the tissue growth factor may be provided within the disc space either before or after the disc repair device is positioned. Injection of an aqueous fluid containing the tissue growth factor into the disc repair device may also facilitate expansion of a hydratable, swellable disc repair device immediately after implantation.
- the disc repair device may be adapted and dimensional such that when in its expanded or swollen conformation, the device is of a sufficiently large dimension to contact the overlying and underlying endplates, preferably under compression, so as to secure the device in place in the disc cavity and desirably dissipate compressive loads from the spine.
- All or a portion of the nucleus pulposus of a damaged intervertebral disc may be removed prior to inserting the device. Moreover, the method may also be followed for preventing escape of the nucleus pulposus from a damaged intervertebral disc, as the disc repair devices of the present invention may act as a plug.
- a single disc repair device can have its longitudinal axis positioned perpendicular to longitudinal axis of the vertebral column, or two or more devices can be positioned in this manner (e.g. two devices used in a bilateral configuration).
- Disc treatment devices may be inserted through pre-existing (e.g. rupture) opening in the annulus fibrosus or they may be inserted through a cut or incised opening.
- the one or more devices provided to the disc cavity will substantially fill the existing void in the cavity, and may also have a sufficient vertical dimension to contact the upper and lower surfaces within the cavity, for instance so as to be effective to absorb compressive loads of the spine.
- Delivery apparatuses in accordance with the invention may also be adapted for non- or minimally-invasive delivery of the intervertebral disc treatment device.
- an apparatus can include a cannulated device of sufficient length to extend to the disc cavity from an exterior operating position, and the disc treatment device can be advanced (e.g. in compressed or collapsed form) through and out the distal end of the cannula and into the disc cavity.
- the disc treatment device can be advanced (e.g. in compressed or collapsed form) through and out the distal end of the cannula and into the disc cavity.
- a procedure may immediately follow a known discectomy protocol, including for instance microdiscectomies, endoscopic discectomies, and laparoscopic discectomies.
- the delivery of the disc treatment device may be conducted under endoscopic or other similar visualization techniques.
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Priority Applications (3)
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US11/877,235 US8349012B2 (en) | 1999-12-06 | 2007-10-23 | Intervertebral disc treatment devices and methods |
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US10/165,347 US20020173851A1 (en) | 1999-12-06 | 2002-06-06 | Intervertebral disc treatment devices and methods |
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PCT/US2000/042610 Continuation WO2001045577A2 (en) | 1999-12-06 | 2000-12-06 | Intervertebral disc treatment devices and methods |
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US11/877,235 Expired - Lifetime US8349012B2 (en) | 1999-12-06 | 2007-10-23 | Intervertebral disc treatment devices and methods |
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US11/877,235 Expired - Lifetime US8349012B2 (en) | 1999-12-06 | 2007-10-23 | Intervertebral disc treatment devices and methods |
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EP (1) | EP1244388B1 (de) |
JP (1) | JP4672947B2 (de) |
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Also Published As
Publication number | Publication date |
---|---|
ES2278648T3 (es) | 2007-08-16 |
EP1244388B1 (de) | 2007-01-17 |
CA2392721C (en) | 2009-01-20 |
AU4309901A (en) | 2001-07-03 |
DE60033055D1 (de) | 2007-03-08 |
US20060004456A1 (en) | 2006-01-05 |
CA2392721A1 (en) | 2001-06-28 |
EP1244388A2 (de) | 2002-10-02 |
US8349012B2 (en) | 2013-01-08 |
JP4672947B2 (ja) | 2011-04-20 |
WO2001045577A9 (en) | 2002-12-05 |
CY1106498T1 (el) | 2012-01-25 |
WO2001045577A3 (en) | 2002-07-11 |
AU774481B2 (en) | 2004-07-01 |
US20080114458A1 (en) | 2008-05-15 |
WO2001045577A2 (en) | 2001-06-28 |
JP2003518021A (ja) | 2003-06-03 |
DK1244388T3 (da) | 2007-05-14 |
US7318840B2 (en) | 2008-01-15 |
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