WO2010127390A1

WO2010127390A1 - Orthopaedic device for the treatment of spinal disc degeneration disease

Info

Publication number: WO2010127390A1
Application number: PCT/AU2010/000510
Authority: WO
Inventors: Graham Jenkin; Tony Goldschlager; George Thouas; Jingyun Ll
Original assignee: Monash University
Priority date: 2009-05-04
Filing date: 2010-05-03
Publication date: 2010-11-11

Abstract

An orthopaedic device is provided for the treatment of spinal disc degeneration disease (DDD). The device comprises a vertebral body spacer capable of being placed between a first vertebral body and a second vertebral body of a human or vertebrate animal subject such that said vertebral body spacer forms or occupies an intervertebral space between the vertebral bodies, and wherein the vertebral body spacer comprises a body housing at least one tooth therein, where the, or each, tooth is adapted to be driven from this housed position to a position where the tooth extends beyond the body to permit engagement with adjacent vertebral end plate(s) to thereby render the device resistant to migration. The device may be provided with a therapeutically effective amount of cells capable of differentiating into disc cartilage-type cells and/or intervertebral disc (FVD)-like tissue.

Description

ORTHOPAEDIC DEVICE FOR THE TREATMENT OF SPINAL DISC DEGENERATION DISEASE

FIELD OF THE INVENTION The invention is directed to the field of medicine and, more particularly, to orthopaedic devices for use in the treatment of spinal disc degeneration disease.

INCORPORATION BY REFERENCE

This patent application claims priority from: - Australian Provisional Patent Application No 2009901967 titled "Medical Device" filed 4 May 2009. The entire content of this application is hereby incorporated by reference.

This patent also makes reference to: - International Patent Specification No WO 2010/012025 titled "Amnion epithelial cells for treatment of degenerative disc disease". The entire content of this application is also hereby incorporated by reference.

BACKGROUND OF THE INVENTION The main role of intervertebral discs (IVDs) is to provide the vertebral column with the necessary biomechanical properties for movement and compressive strength. Alteration of the biomechanical properties of IVDs is suspected to be the leading cause of disc degeneration disease (DDD) and of debilitating back pain. A diverse range of factors including mechanical, biochemical, nutritional and genetic factors such as, for example, abnormal mechanical loading, genetic predisposition, reduced cellular activity and combinations of these, are known to impact upon the biomechanical degeneration of

ΓVDS¹.

The gradual degeneration of IVDs is known to commence as early as the second decade of life, with the majority of IVD damage occurring in the 30 years thereafter. The most severe cases of DDD tend to be observed in older patients. As the demography of many Western nations is tending towards increasingly ageing populations, the incidence of DDDs is rapidly rising. However, young people are also affected by cartilage disorders and most commonly present with trauma related injuries, such as injuries sustained from sporting activities¹. Cartilage focal lesions are common in this demographic and, in some instances, this articular surface damage can lead to progressive joint degeneration².

The rVD is composed of three tissue types, the annulus fibrosis (AF), the nucleus pulposis (NP) and vertebral end plates. The AF consists of a series of loosely connected concentric layers of collagen tissue that surround the NP and distribute pressure evenly across the disc. The NP is a remnant from the notochord and is formed from a network of collagen fibrils that are loosely embedded in a gelatinous matrix of proteoglycan aggrecans and chondrocytes of a specific cartilage cell phenotype. The proteoglycan aggrecans comprise long chains of hyaluronan, which comprise side chains of chondroitin sulfate and keratan sulfate. The NP exhibits a high affinity for water due to the highly negatively-charged sulphated hyaluronan¹. Under compressive loads, the NP functions to distribute hydraulic pressure within each disc. Most commonly, DDD is associated with a loss of function in the NP.

The treatment of pain associated with DDDs usually involves conservative treatments, such as physical therapy and medication. Surgical intervention, usually by discectomy, is reserved for those patients who fail conservative treatment. It provides relief from pain originating from the compression of neural structures by removing disc tissue; however, such surgeries do not treat the underlying biological problem. Discectomy may also involve artificial disc replacement, which is used clinically in selected cases but is expensive and non-biological. Alternatively, biological disc allograft transplants from human organ donors has been trialled, however this is not a practical or feasible option within current clinical practice. Further, surgical fusion of the upper and lower vertebral bodies (ie vertebrae) has commonly been performed in combination with discectomy to immobilise the affected vertebrae. Indeed, anterior cervical discectomy and fusion is the most common surgical approach for treatment of cervical radiculopathy anαVor myelopathy. Fusion is performed either by using autologous iliac crest bone grafting with a vertebral bone plate (which is fixed to, for example, two ("one level") or three ("two level") adjacent vertebral bodies to stabilise the spine, and maintain the discectomy-created intervertebral space, into which the grafted bone is placed, such that the bone graft resists migration) or by using a synthetic vertebral body spacer or interbody "cage" (eg LT-CAGE®; Medtronic Australasia Pty Ltd, North Ryde, NSW, Australia) provided with a bone graft substitute material (ie a synthetic biocompatible material which provides a scaffold or composition to encourage new bone growth such as, for example, INFUSE® Bone Graft (Medtronic Australasia Pty Ltd) and ChronOS™ comprising pure beta-tricalcium phosphate (Synthes Inc, West Chester, PA, United States of America)), which is fitted into the discectomy-created intervertebral space. The former provides a superior rate of fusion between the vertebrae, however, it can lead to significant donor site morbidity and, intrinsically, results in another location for post-operative pain. On the other hand, the use of a vertebral body spacer with a bone graft substitute material offers the advantage of avoiding donor site morbidity (thereby providing a shorter surgical duration), but there is a risk of migration of the vertebral body spacer while bone growth and fusion is being achieved. Such migration can be caused by the relative movement between adjacent vertebrae when, for example, the patient bends their body and/or neck.

Several approaches have been made to prevent or provide resistance to the migration of vertebral body spacers when fitted to an invertebral space. For example, various orthopaedic pins, screws, wires, braces and plates have been used to aid in maintaining the vertebral body spacer in a fixed position. An example of a plate that has been used for this purpose is the Atlantis™ plate (Medtronic Australasia Pty Ltd) which may be secured to the adjacent vertebrae to essentially "clamp" the vertebral body spacer within the intervertebral body space, while International Patent Specification No WO 2008/154326 describes an example of a vertebral body spacer provided with a retention piece adapted to receive two screws to enable the spacer to be fixed to the adjacent vertebrae. This spacer also exemplifies a further approach to provide resistance to migration; that is, to provide the upper and lower surfaces of the spacer with corrugations or ridges to engage with the vertebral end plates. Another cage, known as the Fidji™ cervical cage (Anadolu Medikal Sanayi ve Ticaret Ltd Sti, Istanbul, Turkey) similarly utilises corrugations to prevent migration, but also employs sharp fins located centrally on the upper and lower surfaces which, when the vertebral body spacer is fitted into the invertebral space, strongly engage with the adjacent end plates and vertebrae to resist movement. However, while such cages have achieved considerable success, they can be difficult for the surgeon to correctly fit or, otherwise, may further complicate the surgical procedure. Further, once fitted, such cages may be difficult to withdraw and/or relocate if necessary. The present invention is therefore directed at providing an alternative vertebral body spacer that may provide one or more advantages over the prior art.

SUMMARY OF THE INVENTION

In a first aspect, the present invention provides an orthopaedic device comprising a vertebral body spacer capable of being placed between a first vertebral body and a second vertebral body of a human or vertebrate animal subject such that said vertebral body spacer forms or occupies an intervertebral space between said first and second vertebral bodies, and wherein said vertebral body spacer comprises a body housing at least one tooth therein, where the, or each, tooth is adapted to be driven from this housed position to a position where the tooth extends beyond the body.

In a second aspect, the present invention provides an orthopaedic device for the delivery of cells capable of differentiating into disc cartilage-type cells and/or IVD-like tissue to an intervertebral space in a human or vertebrate animal subject, said device comprising a vertebral body spacer capable of being placed between a first vertebral body and a second vertebral body of said subject such that said vertebral body spacer forms or occupies an intervertebral space between said first and second vertebral bodies, wherein the vertebral body spacer comprises a body housing at least one tooth therein, where the, or each, tooth is adapted to be driven from this housed position to a position where the tooth extends beyond the body, and wherein said vertebral body spacer is provided with a therapeutically effective amount of cells in combination with a pharmaceutically-acceptable carrier.

Preferably, the vertebral body spacer comprises a pair of oppositely directed teeth.

In one embodiment of the device of the present invention, the vertebral body spacer comprises an actuator adapted to assist the driving of the, or each, tooth from the housed position to the extended position. In a further embodiment, the body of the vertebral body spacer rotatably supports a shaft to which the, or each, tooth is secured, so that rotation of the shaft causes the, or each, tooth to be both driven to and from the housed position within the body.

Preferably, the device of the present invention comprises an actuator adapted to assist the driving of the, or each, tooth from the housed position to the extended position, wherein the actuator is attached to an end of a shaft to which the, or each, tooth is secured, said shaft being rotatably supported by the body of the vertebral body spacer. Preferably, said actuator is removably attached to the end of the shaft, however, in an alternative form, the actuator is integral with the shaft.

In one particular embodiment of the present invention, the body of the vertebral body spacer may define an internal cavity and rotatably supports a shaft so that the shaft extends through the cavity, at least a pair of oppositely directed teeth extending from the shaft, and wherein the shaft is rotatable between a first position (ie housed position) in which the teeth are housed within the body, and a second position (ie extended position) in which the teeth extend beyond the body.

When the device is fitted into an intervertebral space, the, or each, tooth is driven from the housed position to a position where the, or each, tooth extends beyond the body. In this position, the, or each, tooth can engage the adjacent vertebral end ρlate(s) and/or vertebral body(ies) such that the device will be resistant to migration. By securing the, or each, tooth to a shaft rotatably supported by the vertebral body spacer, the device permits the surgeon to readily disengage the, or each, tooth should he/she consider that the vertebral body spacer is not properly positioned.

BWEF DESCRIPTION OF THE FIGURES The invention is hereinafter described by way of the following, non-limiting exemplary embodiment, example and accompanying figures, wherein:

Figure 1 provides an isometric view of a device according to the present invention comprising a vertebral body spacer and an actuator therefor;

Figure 2 provides a plan view of the vertebral body spacer and actuator illustrated in Figure 1;

Figure 3 is a side view of the vertebral body spacer and actuator illustrated in Figures 1 and 2;

Figure 4 is an isometric view of an underside of an upper part of a body of the vertebral body spacer illustrated in Figures 1 through 3;

Figure 5 provides a side view of the body upper part illustrated in Figure 4; Figure 6 is an isometric view of an upper side of a lower part of a body of the vertebral body spacer illustrated in Figures 1 through 3;

Figure 7 is an isometric view of a shaft from the vertebral body spacer illustrated in Figures 1 through 3;

Figure 8 provides an end view of the shaft illustrated in Figure 7; and

Figure 9 is an isometric view of the actuator illustrated in Figures 1 through 3.

In the following description, like reference characters designate like or corresponding parts throughout the several views of the figures.

DETAILED DESCRIPTION OF THE INVENTION Referring now to Figures 1 through 9, where an exemplary embodiment of a device according to the present invention is illustrated. The device comprises a vertebral body spacer 1 comprising a body 2 of generally parallelepiped shape, said body 2 comprising a pair of rectangular end walls 4a and 4b, a pair of approximately rectangular side walls 6, and substantially square but fenestrated top 8 and bottom walls 10. The end 4 and side walls 6 are wider than they are high.

The six walls of the body, these being end walls 4a, 4b, sidewalls 6, top and bottom walls 8 and 10, define a cavity 12, the cavity 12 being accessible via a pair of windows 14 in each of the top 8 and bottom 10 walls. These windows 14 are separated by medial portions 16 of these walls 8, 10 which extend across the body between the end walls 4 thereof. The body 2 then has the general form of what is referred to by persons skilled in the art as a "cage".

It is necessary to qualify the use of the terms "generally parallelepiped" and "approximately rectangular" above. This is because the body 2 of the vertebral body spacer 1 tapers slightly between the end walls 4 thereof, so that one end wall 4a (see Figure 3) is marginally higher than the other end wall 4b. The reason for this will be discussed in greater detail below.

The vertebral body spacer 1 further comprises a shaft 20 (as best illustrated in Figure 7) that carries two pairs 22, 24 of oppositely directed teeth 26, the two pairs 22, 24 being spaced apart along the shaft 20. The shaft 20 passes through apertures providing shaft 20 with plain bearing supports in the end walls 4 of the body 2, so that the shaft 20 is rotatably supported thereby. The teeth 26 are elongate and tapered to an outermost point. Each of the teeth 26 in an oppositely directed pair 22, 24 extends from an opposite side of the shaft 20, and each tooth in such a pair is offset to an opposing side of the centre line CL of the shaft 20 (see Figure 7).

The shaft 20 is supported so as to pass through, at or near the centre of the body 2 of the vertebral body spacer 1 , so that it is between the medial portions 16 of the top 8 and bottom 10 walls. These medial portions 16 are each equipped with a further plain bearing support portion 30, which cooperate to further rotatably support the shaft 20 at a point between the oppositely directed pairs of teeth 22, 24 thereof.

The body may be comprised of two half portions 2a and 2b, as illustrated in Figures 4 and 6 respectively. One half portion of the body is an upper portion 2a, and the other, a lower portion 2b.

An actuator 40 may be removably attached (eg by way of a frangible joining portion) to one end 20a of the shaft 20 for the purpose of driving the shaft 20 and the teeth 26 which depend from this. The shaft end 20a to which the actuator 40 is attached extends beyond the higher of the end walls 4 of the body 2. The actuator 40 is a rectangular plate that is keyed to this end 20a of the shaft 20.

Referring now to Figures 7 through 8, the shaft 20 incorporates a collar shaped projection 46 toward but spaced apart from the end 20a thereof. The actuator 40 has a matching aperture 42 formed in one side thereof which is adapted to accept the end 20a of the shaft 20, and a collar portion 44 extending therefrom which is adapted to bear against the shaft's collar shaped projection 46. When the end 20a of shaft 20 is inserted into the aperture 42 in the actuator 40, the actuator can be rotated relative to the shaft 20 until ends of the two collars 44 and 46 meet. At this point, further rotation of the actuator 40 will effect rotation of the shaft. As the shaft 20 is rotated from its first position and toward its second position, the tips of teeth 26 are caused to pass through and extend out of the windows 14 in the top and bottom walls 8, 10 of the body 2 until the continued rotation of the shaft 20 brings the teeth 26 into contact with the medial portions 16 of the top and bottom walls 8, 10.

Referring to Figure 4, each of the medial portions 16 is equipped with a pair of spaced apart teeth- receiving recesses 50, which receive a portion of the teeth 26 therein so that these may extend from the body 2 to their fullest extent. Once nested in these recesses 50 (as illustrated in Figures 1 and 2), the teeth 26 are prevented from being rotated any further. At this point, the teeth 26 are in their extended position.

Adjacent to the surfaces of the first and second vertebral bodies, facing the intervertebral space, is the vertebral end plate that appears as a thin, smooth lining on the vertebral bodies (although the end plates actually form part of the IVD and are believed not to be attached to the subchondral bone of the vertebrae). When the vertebral body spacer 1 has been fitted to an intervertebral space, the one or more teeth 26 will therefore typically engage with the end plate(s) such that the vertebral body spacer 1 will be resistant to migration. However, in some instances of severe DDD, the end plates may be wholly or partially degraded, in which case the teeth 26 of the fitted vertebral body spacer 1 will engage with the vertebrae. Also, there may be instances when the surgeon chooses to remove the end plates along with the remainder of the degraded disc tissue (ie during discectomy), in which case, the teeth 26 of the fitted vertebral body spacer 1 will similarly engage with the vertebrae.

By securing the teeth 26 to the rotatable shaft 20, the vertebral body spacer 1 permits the surgeon to readily disengage the teeth 26 should he/she consider that the vertebral body spacer 1 is not properly positioned. During the fitting of the device, the discectomy-created invertebral space is maintained by the use of a retractor instrument (eg Caspar distraction pin) which is typically fastened to the adjacent vertebrae by screws. Even after the retractor has been removed, the vertebral body spacer 1 may be readily re-positioned if necessary, by re-applying the retractor and thereafter disengaging the teeth 26. In contrast, some of the vertebral body spacers of the prior art having means such as corrugations to prevent migration, can be difficult to remove and/or re-position even after a retractor has been re-applied.

In an embodiment of the present invention, one or more of the teeth 26 of the device may be provided with a duct, preferably coated with an anti-coagulating agent such as heparin, which may act, when the teeth 26 are engaged with the end plates and/or vertebral bodies, as a means to transport blood from vascularisation located at the vertebrae/end plate interface to the body 2 of the vertebral body spacer 1 to provide a source of oxygen and nutrition for new bone growth and/or generation of IVD-like tissue.

Preferably, the geometry of the body 2 corresponds to the geometry of the required intervertebral space between said first and second vertebral bodies. In this regard, it will be understood by persons skilled in the art that reference to first and second vertebral bodies is effectively a reference to any pair of vertebral bodies.

The size and shape of the vertebral body spacer 1 may vary from species to species and/or according to the position within the vertebral column. As such, the cross-sectional shape of the vertebral body spacer 1 will typically be square, rectangular or trapezoid, as discussed above. It may also have a lodortic curvature. Further, the end 4a of the vertebral body spacer 1 that, when fitted, is located at the anterior side of the intervertebral space, may be higher in dimension to the posterior end 4b; this may further assist in providing the vertebral body spacer 1 with resistance to migration, particularly anterior migration. Moreover, modification of the vertebral body spacer 1 may be made to adjust its size and shape to the gender, size and age of the subject or the requirements to relieve a particular type of DDD. However, preferably, the geometry of the vertebral body spacer 1 is selected to conform to an adult human subject for inserting into an intervertebral space between cervical, thoracic, lumbar or sacral vertebrae (ie at any one of a Cl to C7 position, Tl to Tl 2 position, Ll to L5 position and Sl to S5 position). The area of each of the top 8 and bottom 10 walls (ie the "footprint" of the vertebral body spacer 1) will, however, typically be in the range of 10-16mm², more preferably about 14mm², while the average thickness of the device will vary, generally, from about 4mm to about 10- 12mm.

The top 8 and/or bottom 10 walls of the of the vertebral body spacer 1 may be provided with corrugations and/or fins as are well known to persons skilled in the art, so as to provide the device with further resistance to migration.

Optionally, a suitable bonding material such as a bone cement (eg Kryptonite™ bone cement; Doctors Research Group, Inc.; Oxford, CT, United States of America) may be used to aid in maintaining the vertebral body spacer 1 in a fixed position within an intervertebral space. However, the device may also, optionally, comprise a fixing means (eg an orthopaedic pin, screw, wire, brace or plate) to aid in maintaining the vertebral body spacer 1 in a fixed position. A particularly preferred fixing means comprises a bioresorbable plate (eg a Hydrasorb™ plate; Medtronic Australasia Pry Ltd). However, preferably, the actuator 40 of the device is provided with, or is in the form of, a rectangular plate adapted to be secured to the first and second vertebral bodies to maintain them in alignment, and thereby clasp or clamp the vertebral body spacer 1 in a fixed, or substantially fixed, position. The plate of actuator 40 may be provided with apertures to receive screws or other suitable fixing devices to secure the plate to the vertebrae. Preferably, the plate is adapted to receive four screws (ie two for each of the first and second vertebral bodies), and the apertures preferably direct the orientation of the screws in the vertebrae. This arrangement can assist to avoid damage to vascularisation and neuronal tissue as a consequence of misplacement of the screws. The plate of actuator 40 may be provided with means to prevent backout of the screws. Further, the plate of actuator 40 may be a one level or two level plate such that it is secured to two and three vertebrae respectively. In one embodiment, the plate of actuator 40 is also adapted such that, when the teeth 26 are in the extended position, the plate is oriented in a substantially perpendicular position (relative to the footprint of the vertebral body spacer 1) and, consequently, in position to be secured to the first and second vertebral bodies using, preferably, screws. This arrangement can also assist the surgeon to avoid damage to vascularisation and neuronal tissue as a consequence of mis-placement of the screws. Further, when secured to the first and second vertebral bodies, the teeth are effectively locked in the extended position. The teeth can, however, alternatively be locked in the extended position, if necessary, by providing the device with a teeth locking means. Such teeth locking means may be of any form that would be readily apparent to persons skilled in the art such as, for example, a ratchet mechanism that permits rotation of the shaft 20 from its first position and toward its second position (the engagement position), while permitting only very limited rotation of the shaft in the opposite direction unless the ratchet mechanism is over-ridden by the surgeon. Such a ratchet mechanism may incorporate a series of teeth formed into a ring around the circumference of the shaft 20, and a pivoting finger

(hereinafter referred to as a pawl) which is pivotally attached to the body 2 and which is biased into engagement with the teeth formed into the shaft 20. When the shaft 20 is rotated from its first position and toward its second position, the pawl slides up and over each tooth in turn, and a biasing means forces the pawl back into engagement with the next tooth. When the shaft 20 is rotated in the opposite direction, the pawl catches against the tooth and prevents rotation in that direction unless the surgeon manually releases the shaft 20 from the pawl thereby permitting such rotation. Alternatively, the teeth locking means may take the form of an aperture passing through a portion of each of the body 2 and shaft 20, wherein these two apertures align when the shaft reaches its second position (the engagement or teeth extended position), so that a pin (or fastener, such as a screw) may be passed through the aligned apertures thereby locking the shaft 20 in position.

The device of the present invention may be used to treat DDDs including those identified by observing the presence of degenerated discs, bulging discs, herniated discs, thinning discs, collapsed discs, the formation of osteophytes, spontaneous or post-traumatic tears of the disc tissue and other observable disc irregularities. The device may, however, also be used to treat any condition where fusion of vertebral bodies is desired (eg for fracture stabilisation or treatment of malignancy). Further, the device of the present invention may be adapted for use following corpectomy or multilevel corpectomy.

In the context of treating DDDs, the device may be accordingly used, for example, for fusion procedures such as anterior cervical discectomy and fusion (ACDF) and anterior lumbar interbody fusion (ALIF) procedures. Further, the device can also be used in regenerative procedures for treating DDDs. For example, the vertebral body spacer 1 of the device may be provided with suitable cells to achieve, following surgery, in situ generation of intervertebral (IVD)-like tissue between the vertebrae, which tissue may mimic the functionality of the FVD and thereby provide vertebral stabilisation without the alteration of spine biomechanics observed in fusion surgeries. Suitable cells include those that are capable of differentiating into disc cartilage-type cells and/or IVD-like tissue. Examples of such cells are stem cells including mesenchymal stem cells³, chondrocyte progenitor cells and amnion epithelial cells (as described in International Patent Specification No WO 2010/012025, which is hereby incorporated by reference). The cells may be autologous.

Accordingly, the device of the present invention may be used for the delivery of cells capable of differentiating into disc cartilage-type cells and/or IVD-like tissue to an intervertebral space in a human or vertebrate animal subject. In particular, the device may be provided with a therapeutically effective amount of cells in combination with a pharmaceutical ly-acceptable carrier, conveniently within cavity 12 of the body 2. Optionally, the cells may be retained in the cavity 12 with, for example, a substance such as fibrin glue (eg Tisseel; Baxter International Inc, Deerfield, IL, United States of America), Gelfoam® (Pharmacia & Upjohn Company, New York, NY, United States of America) or other biocompatible scaffold or matrix material, or a thin film of biodegradable material. Otherwise, the pharmaceutically- acceptable carrier can be adapted to retain the cells in the cavity 12. In this manner, the device acts as a cell delivery vehicle whereby the cells are retained within the cavity until, at least, the vertebral body spacer 1 is placed between the first and second vertebral bodies. The term "intervertebral (FVD)-like tissue" as used herein in relation to a device or method of the present invention is to be understood as referring to any tissue suitable for the repair or replacement of FVD tissue or a part thereof. The repair of IVD tissue may include, for example, the substitution of diseased components of FVD tissue, for instance dysfunctional NP cells. An IVD-like tissue may be characterised by, for instance, a demonstrated increase in the presence of FVD tissue cells (eg an increase in the presence of cells displaying surface markers of FVD tissue or disc cartilage-type cells such as, for example, those of the chondrogenic lineage), or by the presence of tissue exhibiting an improvement in at least one biomechanical characteristic of the FVD-like tissue in comparison with an equivalent tissue that could be expected to be generated during fusion (eg an increase in the compressibility of an FVD-like tissue may be such an improved biomechanical characteristic).

The term "disc cartilage-type cell" as used herein in relation to a device or method of the present invention is to be understood as referring to cells suitable for FVD repair or replacement, which may include cells that generate IVD or FVD-like tissue or IVD tissue cells (disc cartilage-type cells such as, for example, those of the chondrogenic lineage). Disc cartilage-type cells may be characterised by, for instance, the presence of a disc cartilage cell morphology, disc cartilage cell surface markers or disc cartilage cell molecular markers. This may, particularly, include the characterisation of disc cartilage-type cells by the presence of distinctive NP and/or AF cell characteristics.

The term "therapeutically effective amount" as used herein is to be understood as referring to an amount of the cells (ie a cell number) that is viably sufficient for the in situ generation of intervertebral (FVD)-like tissue between the vertebrae. Such an amount may vary considerably depending upon a range of factors such as the mode of administration, and the age and/or body weight of the subject. However, typically, the amount will be in the range of about 1 x 10⁵ to 1 x 10¹⁰, more preferably, 1 x 10⁸ to 1 x 10¹⁰ cells.

The term "pharmaceutically-acceptable carrier" as used herein is to be understood as referring to any substance that aids the delivery of the cells, for example by providing physical properties that prevent cellular extrusion from the body 2 of the vertebral body spacer 1, any substance that assists in maintaining the viability of the cells prior to or following administration, any substance that provides a structural scaffold or guidance template or that provides the requisite surface properties for cellular placement or growth, any substance that aids in the three dimensional immobilisation of the cells, any substance that assists in directing the cells into disc cartilage-type cells and/or FVD-like tissue (eg the substance may comprise one or more biologically active agents for stimulating differentiation of the cells into a disc cartilage-type cell such as those which stimulate chondrogenesis in stem cells such as TGF-β3 and BMP- 7/OP-l which are known to commit certain cells to the chondrogenic lineage), or any substance that assists in the delivery of growth and/or morphogenic factors. Said substance is, further, to be understood as being well tolerated and biocompatible with the subject to which it is delivered. Suitable pharmaceutically-acceptable carriers may be selected from materials that function as suitable cellular scaffolds or act as functional templates that guide the cellular remodelling process. Preferred materials create an environment that is conducive to cell adhesion, cell proliferation, the necessary gene expression for FVD-like tissue, generation or function, differentiation towards a disc cartilage-type cell phenotype (eg of the chondrogenic lineage), or that temporarily provides cells with protection from unfavourable local implantation environments.

Particular examples of preferred pharmaceutically-acceptable carriers include those comprising bioresorbable polymers, including naturally-derived or synthetically synthesised polymers such as hyaluronan, fibrin, collagen, alginate, chitosan or a combination thereof. Hyaluronan, collagen and chitosan are particularly preferred carriers for use in IVD-like tissue generation as they may provide initial mechanical stability, promote three-dimensional immobilisation of cells, support a homogenous distribution of cells, and maintain the phenotype of disc cartilage-type cells. Carriers comprising hyaluronan, in particular, may be preferred since hyaluronan is a highly hydrophilic, high molecular weight biopolymer that is a key component of cartilage extracellular matrix.

Preferred pharmaceutically-acceptable carriers may, further, be adapted to retain cells within a cavity 12 in the vertebral body spacer 1 and, as such, may take the form of a gel, sponge or fibrous substance (particularly wherein the carrier is highly porous and/or comprises an interconnected network of pores) fully or partially occupying the cavity 12.

In one embodiment, the pharmaceutically-acceptable carrier may comprise a bioresorbable hydrogel or cross-linked polymeric system capable of absorbing large volumes of aqueous solutions such as water, since the normal water content of cartilage is high and IVD-like tissue formation tends to increase in hydrophilic conditions. However, as such hydrogels or cross-linked polymeric systems may display poor structural properties, the network density of a carrier may be modulated by altering the cross-linking density. Particular examples include glycol polymer (eg Pluronics®; BASF, Ludwigshafen, Germany), collagens, extracellular matrix extracts (eg Matrigel™; BD Biosciences, San Jose, CA, United States of America), and fibrin glue.

The device of the present invention may be wholly or partially composed of a bioresorbable material such as a polylactide or polyglycolic acid (PGA). Particularly preferred are bioresorbable materials which comprise a polylactic acid-based material (PLA); since polylactic acid-based materials may be gradually degraded and resorbed such that vertebral bodies, being supported by the vertebral body spacer 1, may be maintained in position until new IVD-like tissue has formed and functionally substitutes the vertebral body spacer 1. Accordingly, it will generally be preferred that a bioresorbable material is selected such that the device (or, at least, the vertebral body spacer 1) is slowly degraded and resorbed over, for example, a period of 12 to 24 months.

Otherwise, the device of the present invention may be composed of a biocompatible material such as titanium, tantulum, Trabecular Metal™ material (Zimmer, Inc., Warsaw, IN, United States of America), carbon fibre, a polymer such as polyether ether ketone (PEEK) well known to persons skilled in the art, or a combination thereof (particularly, a combination of carbon fibre and PEEK).

The vertebral body spacer 1 may also be coated with a composition comprising one or more biologically active agents for stimulating differentiation of cells into a disc cartilage-type cell. For example, the biologically active agents may include those which stimulate chondrogenesis in stem cells such as TGF- β3 and BMP-7/OP-l .

In further aspects of the present invention, there is provided a method of fusing a first vertebral body and a second vertebral body comprising surgically inserting a device of the present invention within an intervertebral space created between said first and second vertebral bodies, and a method of generating IVD-like tissue between a first vertebral body and a second vertebral body comprising surgically inserting a device of the present invention within an intervertebral space created between said first and second vertebral bodies.

EXAMPLES

Example 1

A prototype device was designed to provide immediate post-discectomy stability to a spine by providing support between the vertebrae and by assisting in maintaining the intervertebral space between the vertebrae. The cavity of the device can be provided with bone graft material, a bone graft substitute material or cells capable of differentiating into disc cartilage-type cells and/or FVD-like tissue.

Materials and Methods Preparation of a vertebral body spacer for cervical discectomy

A prototype device as illustrated in Figures 1 to 9 was produced using polyvinyl chloride (PVC).

Surgical procedures

The device was tested on mature aged ewes. Before surgery, the animals were starved for 24 hours. Following anaesthesia by intravenous injection (and maintained with isofluorane inhalation), the ewes were positioned onto their backs on the operating table and the right side of the neck shaved and prepared with antiseptic wash. Initially, X-ray imaging was undertaken to confirm the location of IVD tissue damage. For spinal disc removal, a 5cm transverse incision was made between the carotid artery and trachea toward the spine, and a surgical plane developed to expose the region where the damaged disc was located. A 21 gauge spinal needle was then bayoneted and inserted into the disc space. The spinal needle position can be confirmed with intraoperative fluoroscopy. A Caspar distraction pin was then secured to the vertebral bodies either side of the disc, and then the Caspar distraction pin gently retracted apart to open up the disc cavity. An interoperative X-ray can be used to confirm the correct spinal level. A total discectomy was performed leaving the cartilaginous end plates intact. The vertebral body spacer was then opened on the sterile field, and then Mastergraft® granules (Medtronic Australasia Pry Ltd) mixed with autologous blood was then packed into the cavities of the device. Following insertion into the disc space, the actuator of the device was rotated clockwise to extend the teeth of the device to engage with the end plates. The distraction apparatus was then removed and the vertebral body spacer tested to ensure that it was securely in place. The wound can be closed in layers using Vicryl sutures (Ethicon, Inc., Somerville, NJ, United States of America) specifically to the platysma muscle in the neck. A sterile dressing was also placed on the wound. Finally, analgesia can be administered immediately postoperatively using a Fentanyl patch (Ortho-McNeil-Janssen Pharmaceuticals, Inc., Titusville, NJ, United States of America) and a further local anaesthetic applied, as required. There was no "extrusion" of the device from the disc space over the period that they remained implanted in the animals.

Throughout this specification the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

All publications mentioned in this specification are herein incorporated by reference. Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed in Australia or elsewhere before the priority date of each claim of this application.

It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive. REFERENCES

1. O'Halloran DM, and Pandit AS, Tissue-Engineering Approach to Regenerating the Intervertebral Disc. Tissue Engineering 13(8): 1927- 1954 (2007).

2. Magne D, Vinatier C, Julien M, Weiss P, and Guicheux J, Mesenchymal stem cell therapy to rebuild cartilage. Trends in Molecular Medicine 11(1 1):519-526 (2005).

3. Richardson SM, Curran JM, Chen R, Vaughan-Thomas A, Hunt JA, Freemont AJ, and Hoy land JA, The differentiation of bone marrow mesenchymal stem cells into chondrocyte-like cells on poly-L-lactic acid (PLLA) scaffolds. Biomaterials 27:4069-4078 (2006).

Claims

1. An orthopaedic device comprising a vertebral body spacer capable of being placed between a first vertebral body and a second vertebral body of a human or vertebrate animal subject such that said vertebral body spacer forms or occupies an intervertebral space between said first and second vertebral bodies, and wherein said vertebral body spacer comprises a body housing at least one tooth therein, where the, or each, tooth is adapted to be driven from this housed position to a position where the tooth extends beyond the body.

2. An orthopaedic device for the delivery of cells capable of differentiating into disc cartilage-type cells and/or IVD-like tissue to an intervertebral space in a human or vertebrate animal subject, said device comprising a vertebral body spacer capable of being placed between a first vertebral body and a second vertebral body of said subject such that said vertebral body spacer forms or occupies an intervertebral space between said first and second vertebral bodies, wherein the vertebral body spacer comprises a body housing at least one tooth therein, where the, or each, tooth is adapted to be driven from this housed position to a position where the tooth extends beyond the body, and wherein said vertebral body spacer is provided with a therapeutically effective amount of cells in combination with a pharmaceutically-acceptable carrier.

3. The device of claim 1 or 2, wherein the vertebral body spacer comprises a pair of oppositely directed teeth.

4. The device of any one of the preceding claims, wherein the vertebral body spacer comprises an actuator adapted to assist the driving of the, or each, tooth from the housed position to the extended position.

5. The device of any one of the preceding claims, wherein the body of the vertebral body spacer rotatably supports a shaft to which the, or each, tooth is secured, so that rotation of the shaft causes the, or each, tooth to be both driven to and from the housed position within the body.

6. The device of any one of claims 1 to 3, wherein the vertebral body spacer comprises an actuator adapted to assist the driving of the, or each, tooth from the housed position to the extended position, wherein the actuator is attached to an end of a shaft to which the, or each, tooth is secured, said shaft being rotatably supported by the body of the vertebral body spacer.

7. The use of the device of any one of claims 1 to 6 in the treatment of DDD.

8. The use of the device of any one of claims 1 to 6 for the delivery of cells capable of differentiating into disc cartilage-type cells and/or FVD-like tissue to an intervertebral space in a human or vertebrate animal subject, wherein said device is provided with a therapeutically effective amount of said cells in combination with a pharmaceutically-acceptable carrier.

9. A method of fusing a first vertebral body and a second vertebral body comprising surgically inserting the device of any one of claims 1 to 6 within an intervertebral space created between said first and second vertebral bodies

10. A method of generating IVD-like tissue between a first vertebral body and a second vertebral body comprising surgically inserting the device of any one of claims 1 to 6 within an intervertebral space created between said first and second vertebral bodies, wherein said device is provided with a therapeutically effective amount of said cells in combination with a pharmaceutically-acceptable carrier.