WO2011003133A1 - Surgical method and tool - Google Patents

Surgical method and tool Download PDF

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Publication number
WO2011003133A1
WO2011003133A1 PCT/AU2010/000856 AU2010000856W WO2011003133A1 WO 2011003133 A1 WO2011003133 A1 WO 2011003133A1 AU 2010000856 W AU2010000856 W AU 2010000856W WO 2011003133 A1 WO2011003133 A1 WO 2011003133A1
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Prior art keywords
plug element
cells
site
disc
surgical plug
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PCT/AU2010/000856
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French (fr)
Inventor
Tony Goldschlager
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Tony Goldschlager
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Priority to US22307609P priority Critical
Priority to US61/223,076 priority
Application filed by Tony Goldschlager filed Critical Tony Goldschlager
Publication of WO2011003133A1 publication Critical patent/WO2011003133A1/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/44Joints for the spine, e.g. vertebrae, spinal discs
    • A61F2/442Intervertebral or spinal discs, e.g. resilient
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/46Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor
    • A61F2/4603Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor for insertion or extraction of endoprosthetic joints or of accessories thereof
    • A61F2/4611Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor for insertion or extraction of endoprosthetic joints or of accessories thereof of spinal prostheses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/3094Designing or manufacturing processes
    • A61F2/30965Reinforcing the prosthesis by embedding particles or fibres during moulding or dipping
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/44Joints for the spine, e.g. vertebrae, spinal discs
    • A61F2/441Joints for the spine, e.g. vertebrae, spinal discs made of inflatable pockets or chambers filled with fluid, e.g. with hydrogel
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30316The prosthesis having different structural features at different locations within the same prosthesis; Connections between prosthetic parts; Special structural features of bone or joint prostheses not otherwise provided for
    • A61F2002/30535Special structural features of bone or joint prostheses not otherwise provided for
    • A61F2002/30581Special structural features of bone or joint prostheses not otherwise provided for having a pocket filled with fluid, e.g. liquid
    • A61F2002/30584Special structural features of bone or joint prostheses not otherwise provided for having a pocket filled with fluid, e.g. liquid filled with gas
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/44Joints for the spine, e.g. vertebrae, spinal discs
    • A61F2/442Intervertebral or spinal discs, e.g. resilient
    • A61F2002/444Intervertebral or spinal discs, e.g. resilient for replacing the nucleus pulposus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/44Joints for the spine, e.g. vertebrae, spinal discs
    • A61F2/442Intervertebral or spinal discs, e.g. resilient
    • A61F2002/4445Means for culturing intervertebral disc tissue
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2310/00Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00005The prosthesis being constructed from a particular material
    • A61F2310/00011Metals or alloys
    • A61F2310/00023Titanium or titanium-based alloys, e.g. Ti-Ni alloys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2310/00Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00005The prosthesis being constructed from a particular material
    • A61F2310/00011Metals or alloys
    • A61F2310/00035Other metals or alloys
    • A61F2310/00131Tantalum or Ta-based alloys

Abstract

This invention relates to a method and apparatus for treating a subject having an intervertebral disc with a defect comprising extruded, protruded or sequestered disc material. The apparatus involves a reversibly expandable plug element. The method involves administering chondrocytes and/or progenitor cells to a site within a disc, inserting an expandable surgical plug element into the site, expanding the expandable surgical plug element until this fills and/or seals the site so as to maintain the cells at the site, for at least a period sufficient for the cells to adhere to adjacent tissue. An associated surgical tool for positioning and controlling the apparatus is also disclosed.

Description

SURGICAL METHOD AND TOOL

FIELD OF THE INVENTION

The present invention relates to the field of spinal surgery and, more particularly, the surgical procedure known as a microdiscectomy.

BACKGROUND TO THE INVENTION

Sciatica or sciatic neuritis refers to pain and/or numbness felt, most commonly, in the lower limb or lower back, caused by compression of the sciatic nerve or, more usually, one or more of the five nerve roots that give rise to the sciatic nerve (ie the lumbar nerves L4 or L5 and the sacral nerves Sl, S2 and S3). One common cause of this compression is spinal disc herniation (also known as a disc prolapse or "slipped disc"), wherein the fluid centre of an intervertebral disc (known as the nucleus pulposis; NP) bulges outwards, through the fibres of the external ring or "annulus" of cartilage (known as the annulus fibrosus; AF), such that it protrudes into the spinal canal and compresses the nerve root against the lamina or pedicle of an adjacent vertebral body (ie vertebra). This condition can, in many cases, resolve itself.

However, in more severe and chronic cases, some form of medical intervention will usually be required. For example, sciatica caused by spinal disc herniation is usually responsive to treatment or management with non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and diclofenac. In refractory cases however, only surgery will achieve a satisfactory outcome in terms of pain relief.

In a microdiscectomy, a small portion of the lamina over the nerve root is removed to gain access to the disc herniation, extrusion, protrusion or sequestered fragment. This disc material is removed so as to relieve the neural compression and provide space for the nerve to heal. This surgery is performed through a small keyhole incision in the midline of the low back and involves:

(i) first, elevating the back muscles (known as the erector spinae) off the lamina of the vertebra (nb. this does not typically require any cutting of the muscles since these run vertically up the back);

(ii) in a procedure known as a laminotomy, removing a small portion of the lamina of the vertebra with, for example, a pneumatic drill with a B5 dissecting tool and attachment (eg a Midas Rex® surgical tool; Medtronic, Inc., Fort Worth, TX, United States of America) to facilitate access and to relieve compression over the nerve root;

(iii) then removing the membrane (known as the ligamentum flavum) over the nerve root; and (iv) thereafter, retracting the nerve root to the side with a standard retractor, and removing the protruded, extruded or sequestered disc material (with a ronguer) from the vicinity of the nerve root. Since almost all of the bony structures, ligaments and muscles are left intact, microdiscectomy surgery can be performed on an outpatient or single overnight stay basis and, as the surgery is minimally invasive and generally well tolerated, patients are usually able to return quickly to their normal daily activities. However, while microdiscectomy is considered to be a highly successful surgical intervention (with success Tates of up to 90% typically quoted; Dietze D, 2009), improvements in the techniques and tools for microdiscectomy are sought so as to reduce the remaining risks and complications such as, for example, dural tear leading to cerebrospinal fluid leak (which may require the patient to remain reclined for one to two days to allow the leak to seal), nerve root damage, infection and so-called post-discectomy syndrome. PDS is the re-occurrence (eg after several months) of a number of symptoms that arise immediately following the microdiscectomy surgery, such as pain of variable intensity, which may radiate into the lower limbs (Ivanic GM et al., 2001). Further, the disruption to the disc, both from the original herniation and the microdiscectomy, may lead to further degeneration of the disc. In turn, this may lead to biomechanical and pathological changes manifesting in loss of disc height, structural changes in the disc, degeneration at other sites (such as the facet joints) and other pathological changes which are all potential causes of pain (McGirt MJ et al., 2009). Pain is also believed to be caused by nerve root irritation and polyradiculitis, resulting from inflammation (Mulleman D et al., 2006). Since microdiscectomy surgery presently does not seek to actually repair the disc damage, the present applicant now proposes a modification of the surgery wherein repair to the disc damage is initiated by the administration of suitable chondrocytes and/or progenitor cells (eg stem cells capable of differentiating into cells of the chondrogenic or notochordral lineage). Accordingly, the present invention is directed at a method of modified microdiscectomy and a surgical tool for use therefor.

SUMMARY OF THE INVENTION

Thus, in a first aspect, the present invention provides a method of treating a subject having an intervertebral disc with a defect comprising extruded, protruded or sequestered disc material, the method comprising the steps of:

(i) removing said extruded, protruded or sequestered disc material from said disc;

(ii) administering chondrocytes and/or progenitor cells to a site within said disc (such as a tear in the disc), and thereafter;

(iii) inserting an expandable surgical plug element into the site; and

(iv) expanding the expandable surgical plug element until this fills and/or seals the site; such that the expanded surgical plug element maintains the cells at the site, for at least a period sufficient for the cells to adhere to adjacent tissue. In one embodiment, the expandable surgical plug element is a reversibly expandable surgical plug elemέnt, in which case, the method further comprises the steps of:

(v) maintaining the expanded surgical plug element in situ so as to maintain the cells at the site, for at least a period sufficient for the cells to adhere to adjacent tissue; and

(vi) contracting the reversibly expandable surgical plug element and removing this from the site. In another embodiment, the expandable surgical plug element is intended to be maintained at the site for an extended period.

In a second aspect, the present invention provides a reversibly expandable surgical plug element adapted to be both selectively expanded to fill and seal an aperture or cavity and contracted for removal therefrom.

In a third aspect, the present invention provides a surgical tool for positioning and controlling a reversibly expandable surgical plug element adapted to be both selectively expanded to fill and seal an aperture or cavity and contracted for removal therefrom, the surgical tool comprising means for positioning the surgical plug element, and means for remotely controlling the expansion and contraction of the surgical plug element.

In a fourth aspect, the present invention provides an expandable surgical plug element adapted to be selectively expanded to fill and seal an aperture or cavity.

The expandable surgical plug element of the fourth aspect is preferably composed of a bioresorbable material.

BRIEF DESCRIPTION OF THE ACCOMPANYING FIGURES

Figure 1 provides a representation of (a) a surgical tool according to the present invention comprising a reversibly expandable surgical plug element, and (b) the same surgical tool when attached to a syringe and showing the surgical plug element in expanded form.

DETAILED DESCRIPTION OF THE INVENTION

Since microdiscectomy surgery presently does not seek to actually repair the disc damage, and may in fact add to degeneration, the present applicant proposes a modification of the surgery wherein repair to the disc damage is initiated by the administration of suitable chondrocytes and/or progenitor cells. Thus, in a first aspect, the present invention provides a method of treating a subject having an intervertebral disc with a defect comprising extruded, protruded or sequestered disc material, the method comprising the steps of: (i) removing said extruded, protruded or sequestered disc material from said disc;

(ii) administering chondrocytes and/or progenitor cells to a site within said disc (such as a tear in the disc), and thereafter; (iii) inserting an expandable surgical plug element into the site; and

(iv) expanding the expandable surgical plug element until this fills and/or seals the site; such that the expanded surgical plug element maintains the cells at the site, for at least a period sufficient for the cells to adhere to adjacent tissue.

The method of the present invention provides the possibility of a substantially complete repair of the disc defect (eg a tear in the cartilage of a herniated disc) by providing a "supply" of chondrocytes and/or progenitor cells thereof which are capable of generating disc-like tissue (such as AF-like tissue). To achieve this, it is essential that following administration, the cells are maintained at the site and not, otherwise, lost through the washing effect of blood and/or serous fluid at the surgical site. This can be exacerbated when, immediately following the surgery, the subject is lying on his/her back thereby creating gravitational pressures and strains which would tend to extrude the administered cells from the site within the intervertebral disc. Accordingly, the method of the present invention seeks to address this problem by applying an expandable surgical plug element to maintain the cells at the site, at least for a period sufficient for the cells to adhere to adjacent tissue.

Step (i) of the method may be conducted in accordance with the standard techniques used in

microdiscectomy surgery and as are well known to persons skilled in the art. Typically, this will involve, first, elevating the back muscles off the lamina of the vertebra, then removing the ligamentum flavum over the nerve root, subsequently performing a laminotomy to facilitate access to the disc and to relieve compression over the nerve root, and thereafter moving the nerve root to the side with a standard retractor before removing the extruded, protruded or sequestered disc material with a suitable tool such as a ronguer.

Step (ii) of the method preferably involves administering an "effective amount" of chondrocytes and/or progenitor cells. The term "effective amount" is to be understood as referring to an amount of the cells (ie a cell number) that will lead to a substantially complete repair of the disc following surgery within, for example, 3-6 months of the surgery; wherein a substantially complete repair may be regarded as a repair wherein the thickness of the annulus tissue has been substantially restored to that of the undamaged regions of this tissue in the disc and/or of the NF. Such an effective amount of the cells may vary considerably depending upon a range of factors such as the mode of administration, type of cell(s) administered, the age and/or body weight of the subject, and the severity of the damage being treated. However, typically, the amount will be in the range of about 1 x 105 to 1 x 1010, more preferably, 0.5 x 106 to 5 x 106 cells. An effective amount of the cells may also provide anti-inflammatory factors which may decrease radiculopathy or discogenic or other pain or degeneration.

The chondrocytes and/or progenitor cells may be administered to the site within the defect (eg tear in the cartilage of a herniated disc) by any of the methods well known to persons skilled in the art for delivering cells to a specific desired site for tissue regeneration such as, for example, by injecting the cells into the site using a suitable syringe and needle (eg a ImI syringe with a 27 gauge needle), pipette or other suitable device. Alternatively, the cells might be administered to the desired site via a lumen provided in a surgical tool comprising the expandable surgical plug element.

The cells may be administered in combination with a suitable pharmaceutically-acceptable carrier. The term "pharmaceutically-acceptable carrier" 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 site of administration, 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 the conversion of progenitor cells (if administered) to cells of 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. As such, 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 AF-like tissue or cells, NP-like tissue or cells, disc-like tissue or cells, notochordal-like tissue or cells, generation or function, differentiation of progenitor cells (if administered) towards cells of the chondrogenic or other suitable lineage, or that temporarily provides cells with protection from unfavourable local implantation environments, and/or provide for an anti-inflammatory or anti-fibrotic effect. 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 AF-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 cells of the chondrogenic lineage. 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, take the form of a gel, gel foam, sponge or fibrous substance particularly wherein the carrier is highly porous and/or comprises an interconnected network of pores.

Chondrocytes suitable for use in the method may be isolated from a suitable source (eg disc tissue and/or other cartilage tissue) or, more preferably, may be generated in vitro from suitable progenitor cells. In vitro methodologies for differentiating suitable progenitor cells into cells of the chondrogenic lineage have been described in, for example, Chung WA, 2009 and Hiyama A, 2008; the entire contents of both being hereby incorporated by reference. Such differentiated (and expanded) cells may optionally be stored for later use. Preferred methods of storage include cryopreservation in suitable storage media (eg in animal free or serum substitutes optionally comprising dimethylsulphoxide (DMSO), such as Cryostor™; BioLife Solutions, Inc., Bothell, WA, United States of America). When required, the cells can be prepared for immediate administration to the subject by, for example, isolating the cells from the culture/storage media and thereafter resuspending the cells in a pharmaceutically-acceptable carrier. Progenitor cells suitable for use in the method may be of any stem cell type capable of differentiating into cells of the chondrogenic lineage or notochordal lineage, and may therefore be selected from stem cells of adult, foetal or embryonic origin. An example of a preferred progenitor cell type for use in the method are mesenchymal stem cells (MSCs) (Risbud MV et al, 2004; Jeong JH et al, 2009) isolated from, for example, bone marrow and other suitable sources (eg dental pulp, adipose tissue, disc tissue, placental membranes etc). Such cells may be dispersed/expanded and, optionally, stored for later use by, for example, cryopreservation as described above. When required, the progenitor cells can be prepared for immediate administration to the subject by, for example, isolating the cells from the culture/storage media and thereafter resuspending the cells in a pharmaceutically-acceptable carrier. Preferably, the method of the present invention utilises progenitor cells rather than fully differentiated chondrocytes, although in some embodiments, the progenitor cells may be partially or wholly substituted with derivative cells; that is, in the case of multipotent MSCs, cells which have been at least partially differentiated from the MSCs (ie the invention may utilise "pre-differentiated" cells). Such MSC derivative cells (eg cells of the chondrogenic lineage) may be produced, for example, by culturing MSCs in a suitable medium (eg DMEM-HG with 40μg/ml proline, 10 ng/ml TGF-β 1 , 10OnM DMSO, 1 % ITS- X, 1% penicillin/streptomycin and lOOμg/ml sodium pyruvate) under suitable conditions optionally in combination with fibrin and thrombin. Further, the progenitor cells and/or derivative cells therefrom, may be supplemented with one or more other (ie non-derivative) cell types (including one or more other stem cell types), tissue fragments (preferably intervertebral disc (FVD) tissue fragments) and/or biologically active agents such as inflammatory inhibitors, antibiotics, cytokines and/or morphogenic factors, particularly factors that direct progenitor cells and/or derivative cells therefrom towards cells of the chondrogenic lineage (eg preferably fibrin and/or thrombin, but also members of the TGF-β superfamily, in particular TGF-β3 and BMP-7/OP-1 which are known to commit certain cells to the chondrogenic lineage; eg BMP-7 is known to elevate matrix synthesis in NP cells), and agents that facilitate the slow or controlled release of these or other bioactive molecules. Step (iii) of the method typically involves positioning the expandable surgical plug element into the site of the defect (eg a tear in the annulus of the herniated disc), preferably to no more than a depth of 1 to 30 mm from the outer surface of the annulus of the disc.

Step (iv) of the method involves expanding the expandable surgical plug element until this fills and/or seals the site such that loss of the administered chondrocytes and/or progenitor cells into, for example, blood and/or serous fluid in the spinal canal, is substantially prevented. Thus, where the expandable surgical plug element has, during step (iii), been positioned at a depth of no more than 1 to 30 mm from the outer surface of the annulus, the expansion of the expandable surgical plug element results in the filling and sealing of the site adjacent to the outer surface of the annulus. This effectively creates a pore behind the expanded surgical plug element within the tissue of the disc, wherein the administered chondrocytes and/or progenitor cells may be contained and allowed to adhere.

In one embodiment of the method of the first aspect, the expandable surgical plug element is a reversibly expandable surgical plug element, in which case, the method further comprises the steps of:

(v) maintaining the expanded surgical plug element in situ so as to maintain the cells at the site, for at least a period sufficient for the cells to adhere to adjacent tissue; and

(vi) contracting the reversibly expandable surgical plug element and removing this from the site

Step (v) of the method involves maintaining the expanded surgical plug element in situ so as to maintain the chondrocytes and/or progenitor cells at the site of administration, for at least a period sufficient for the cells to adhere to adjacent tissue. Preferably, this period will be in the range of 2 to 36 hours, more preferably in the range of about 8 to about 24 hours. Finally, step (vi) of the method involves contracting the reversibly expandable surgical plug element and removing this from the site, in a manner similar to removing a wound drain.

In another embodiment of the method of the first aspect, the expandable surgical plug element is intended to be maintained at the site for an extended period. Such an expandable surgical plug element is preferably composed of a bioresorbable material.

In a second aspect, the present invention provides a reversibly expandable surgical plug element adapted to be both selectively expanded to fill and seal an aperture or cavity and contracted for removal therefrom.

In one embodiment, the reversibly expandable surgical plug element is an inflatable element of elastomeric material positioned over and secured to the end of a conduit, so that fluid (eg air) may be supplied to or removed from the inflatable element via the conduit for the purpose of expansion or contraction. The inflatable element may be a balloon. The conduit may take a form similiar to that of a drain tube, Foley or Fogarty catheter or other such device.

In a third aspect, the present invention provides a surgical tool for positioning and controlling a reversibly expandable surgical plug element adapted to be both selectively expanded to fill and seal an aperture or cavity and contracted for removal therefrom, the surgical tool comprising means for positioning the surgical plug element, and means for remotely controlling the expansion and contraction of the surgical plug element.

In one embodiment, the reversibly expandable surgical plug element of the tool is a balloon positioned over and secured to the end of a conduit, and the tool further comprises a syringe connected to the end of the conduit distal from the balloon, the arrangement being such that fluid (eg air) may be supplied to and/or removed from the conduit and balloon via the syringe.

Where the reversibly expandable surgical plug element is a balloon, it may be preferable to provide a tab depending from the balloon, wherein the tab fills or covers an aperture provided in the balloon so that separation of the tab from the balloon will open this aperture permitting deflation of the balloon.

Preferably, a portion of the tab distal from the balloon aperture-filling or -covering portion may be secured to a site surrounding the aperture or cavity to be filled and sealed by the balloon by way of a securement means such as a surgical staple and/or suture (which may be composed of a bioresorbable material). This provides a safety means in the event, albeit an unlikely event, of inadvertent removal of the inflated balloon; that is, the deflation caused by the separation of the tab from the balloon should minimise the possibility of the removed plug element contacting and/or otherwise injuring a nearby nerve root or o'ther structure.

In a further aspect, the present invention provides a reversibly inflatable surgical plug element adapted to be both selectively inflated to fill and seal an aperture or cavity and deflated for removal therefrom, the inflatable plug element having a tab depending therefrom, said tab filling or covering an aperture in the inflatable plug element so that separation of the tab from the inflatable plug element will open this aperture permitting deflation of the inflatable plug element. In a fourth aspect, the present invention provides an expandable surgical plug element adapted to be selectively expanded to fill and seal an aperture or cavity.

The expandable surgical plug element of the fourth aspect is preferably composed of a bioresorbable material.

Finally, it will be appreciated by persons skilled in the art that an expandable surgical plug element according to the present invention may also consist in a mechanism having a forward most head that is adapted to reversibly or irreversibly expand to fill and/or seal an aperture or cavity (eg a defect in the annulus of a herniated disc). For example, such a mechanism may comprise a head which reversibly or irreversibly expands and contracts in a manner similar to an umbrella. This may be made from bioresorbable materials and left in situ over an extended period until resorption occurs.

Referring now to Figure Ia, where there is illustrated an example of a surgical tool 100 for positioning and controlling a reversibly expandable surgical plug element 102. The reversibly expandable surgical plug element 102 is adapted to be both selectively expanded to fill an aperture or cavity (eg a defect in the intervertebral disc) and contracted for removal therefrom. The reversibly expandable plug element 102 is an inflatable balloon of elastomeric material positioned over and secured to the end of a conduit 104, so that a fluid (such as air or sterilised water) may be supplied to or removed from the inflatable balloon 102 via the conduit 104 for the purpose of expanding or contracting the balloon 102. Where adapted for filling a tear in the annulus of a herniated disc, it is envisaged that the balloon 104 would be expanded to a diameter of no more than about 0.5 to 30 mm. The fluid is supplied to the conduit 104 and balloon 102 via a syringe 110 connected to the end of the conduit 104 distal from the balloon 102. There is a tab 106 depending from the balloon 102, the tab filling or covering an aperture 108 in the balloon 102 so that separation of the tab 106 from the balloon 102 will open this aperture 108 permitting deflation of the balloon 102. A portion of the tab 106a distal from the aperture 108 filling or covering portion 106b may be secured to a site surrounding the aperture or cavity 108 to be filled by the balloon 102 by a surgical staple 109. In this way, as the conduit 104 and balloon 102 are withdrawn, the tab 106 remains in place and so the tab 106 is separated from the balloon 102 thereby opening aperture 108 and causing deflation of the balloon 102.

In use, the balloon 102 may be positioned in a defect in the intervertebral disc by a surgeon holding the syringe 110 equipped end of the conduit 104, as illustrated in Figure Ib. The surgeon will then use the syringe 1 10 to pump fluid through the conduit 104 so that this fills the balloon 102, causing the balloon 102 to fill and seal the tear. Tab 106 will then be secured to a nearby site (eg to an adjacent vertebra) with a surgical staple 109. When the balloon 102 is to be removed, the surgeon withdraws the conduit 104, but the tab 106 remains in place (due to staple 109) and so it is separated from the balloon 102, opening aperture 108 and causing deflation of the balloon 102. This assists in the removal of the surgical tool 100.

The reversibly expandable surgical plug element 102, tab 106 and/or the staple 109 used to fix the tab 106, may be wholly or partially composed of a bioresorbable material such as a polylactide or polyglycolic acid (PGA) (eg Vicryl™, Ethicon, Inc., Somerville, NJ, United States of America), which may be gradually degraded and resorbed over, for example, a period of 3 to 6 months. Otherwise, the reversibly expandable surgical plug element 102, tab 106 and/or staple 109 may be composed of a biocompatible material such as, but not limited to, titanium, tantulum, Trabecular Metal™ material (Zimmer, Inc., Warsaw, IN, United States of America), carbon fibre, a polymer such as poly ether ether ketone (PEEK) well known to persons skilled in the art, or a combination thereof (particularly, a combination of carbon fibre and PEEK).

The present invention is hereinafter further described by way of the following, non-limiting example(s) and accompanying figure(s). EXAMPLE(S)

Example 1 Stem cell retention in microdiscectomy wound in sheep

A study was conducted with sheep to assess the improvement in maintenance of exogenous stem cells at the site of a microdiscectomy wound with and without the use of an expandible surgical plug element in accordance with the present invention. In order to provide a more meaningful model for the human spine (when, post-microdiscectomy, the patient is lying on his/her back), the study used sheep having undergone microdiscectomy surgery in the anterior cervical intervertebral disc, since it was considered that the pressures and strains including gravitational forces, placed on the vertebra and damaged disc (including stem cells administered into the defect of the intervertebral disc) of the standing sheep in the cervical spine would be similar to that placed on the vertebra and damaged disc of a patient lying on his/her back. Moreover, the washing effect of blood and/or serous fluid at the surgical site was expected to be" very similiar.

An identical microdiscectomy was performed at C3/4 and C4/5 in sheep. A standardised amount of disc was removed and 1 x 106 adipose-derived ovine mesenchymal stem cells (MSCs) labelled with a fluorescent cell marker, Cell Trace CSFE (Invitrogen Corpration, San Diego, CA, United States of America) were injected into both disc defects. The viability of the cells, assessed by standard Trypan Blue Exclusion tests, was found to be greater than 85%. One defect was closed using the expandible surgical plug element of the present invention, whilst the other defect was left open. Sheep were sacrificed at intervals after the procedure including 2 hours and 24 hours. Biopsies from within the defect of each of the intervertebral discs, were taken and frozen histological sections prepared. Three levels, with a distance of 100 microns each, were taken from each biopsy and three 5 micron sections from each level were prepared on slides. Each entire slide was scanned with the Olympus dot slide System (with BX51 Microscope), at x20 magnification using a U-MNIBA3 filter, Peltier-cooled high sensitivity camera, and a consistent exposure. The images were then uploaded into the Metamorph quantitative analysis software program (version 7.6; Molecular Devices Corporation, Sunnyvale, CA, United States of America). The program measured intensity per unit area, which is proportional to the number of CSFE-labelled MSCs, thereby giving an objective measure of the cells retained at different levels within each site of the disc defect injected with cells. The results of this experiment showed that there was significantly more MSCs in the site of the disc defect where the expandible surgical plug element was used to contain the cells (p =0.0003).

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

Chung WA et al. Differentiation of rodent bone marrow mesenchymal stem cells into intervertebral disc- like cells following co-culture with rat disc tissue. Tissue Eng Part A, 3 February 2009.

Dietze Jr, DD. Evolution of Spine Surgery (http://www.back.com/articles-evolution.html), 17 April 2009.

Hiyama A et al. Stem cell applications in intervertebral disc repair. Cell MoI Biol 54(l):24-32 (2008). Ivanic, GM et al. The post-discectomy syndrome: aetiolgy, diagnosis, treatment, prevention. Arch Orthop Trauma Surg 121 :494-500 (2001).

Jeong, JH et al. Human mesenchymal stem cells implantation into the degenerated coccygeal disc of the rat. Cytotechnology 59(l):55-64 (2009).

McGirt MJ et al. Recurrent disc herniation and long-term back pain after primary lumbar discectomy: review of outcomes reported for limited versus aggressive disc removal. Neurosurgery 64(2):338-344 (2009). Mulleman D et al. Pathophysiology of disk-related sciatica. I.— Evidence supporting a chemical component. Joint Bone Spine 73(2):151-158 (2006).

Risbud, MV et al. Stem cell regeneration of the nucleus pulposus. The Spine Journal 4(6 Suppl):348S- 353S (2004).

Claims

1. A method of treating a subject having an intervertebral disc with a defect comprising extruded, protruded or sequestered disc material, the method comprising the steps of:
(i) removing said extruded, protruded or sequestered disc material from said disc;
(ii) administering chondrocytes and/or progenitor cells to a site within said disc, and thereafter;
(iii) inserting an expandable surgical plug element into the site; and
(iv) expanding the expandable surgical plug element until this fills and/or seals the site; such that the expanded surgical plug element maintains the cells at the site, for at least a period sufficient for the cells to adhere to adjacent tissue.
2. The method of claim 1, wherein the expandable surgical plug element is a reversibly expandable surgical plug element, and said method further comprises the steps of:
(v) maintaining the expanded surgical plug element in situ so as to maintain the cells at the site, for at least a period sufficient for the cells to adhere to adjacent tissue; and
(vi) contracting the reversibly expandable surgical plug element and removing this from the site.
3. The method of claim 1, wherein the expandable surgical plug element is intended to be
maintained at the site for an extended period.
4. The method of any one of claims 1 to 3, wherein the intervertebral disc defect is a herniated disc.
5. A reversibly expandable surgical plug element adapted to be both selectively expanded to fill and seal an aperture or cavity and contracted for removal therefrom.
6. A surgical tool for positioning and controlling a reversibly expandable surgical plug element adapted to be both selectively expanded to fill and seal an aperture or cavity and contracted for removal therefrom, the surgical tool comprising means for positioning the surgical plug element, "and means for remotely controlling the expansion and contraction of the surgical plug element.
7. An expandable surgical plug element adapted to be selectively expanded to fill and seal an
aperture or cavity.
8. The expandable surgical plug element of claim 7 composed of a bioresorbable material.
PCT/AU2010/000856 2009-07-06 2010-07-05 Surgical method and tool WO2011003133A1 (en)

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US61/223,076 2009-07-06

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999004720A1 (en) * 1997-07-11 1999-02-04 Reprogenesis Inc. Repair of intervertebral disks
US20020111688A1 (en) * 1999-10-20 2002-08-15 Cauthen Joseph C. Intervertebral disc annulus stent
US20030078579A1 (en) * 2001-04-19 2003-04-24 Ferree Bret A. Annular repair devices and methods
WO2003039328A2 (en) * 2001-08-27 2003-05-15 Thomas James C Jr Implant for partial disc and cancellous bone replacement
US20050049604A1 (en) * 2002-05-16 2005-03-03 Singer Deron J. Device for treating intervertebral disc herniations
US20050149046A1 (en) * 2003-12-24 2005-07-07 Friedman Craig D. Repair of spinal annular defects and annulo-nucleoplasty regeneration
US20070255285A1 (en) * 2006-04-27 2007-11-01 Warsaw Orthopedic, Inc. Devices, Apparatus, and Methods for Disc Augmentation

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999004720A1 (en) * 1997-07-11 1999-02-04 Reprogenesis Inc. Repair of intervertebral disks
US20020111688A1 (en) * 1999-10-20 2002-08-15 Cauthen Joseph C. Intervertebral disc annulus stent
US20030078579A1 (en) * 2001-04-19 2003-04-24 Ferree Bret A. Annular repair devices and methods
WO2003039328A2 (en) * 2001-08-27 2003-05-15 Thomas James C Jr Implant for partial disc and cancellous bone replacement
US20050049604A1 (en) * 2002-05-16 2005-03-03 Singer Deron J. Device for treating intervertebral disc herniations
US20050149046A1 (en) * 2003-12-24 2005-07-07 Friedman Craig D. Repair of spinal annular defects and annulo-nucleoplasty regeneration
US20070255285A1 (en) * 2006-04-27 2007-11-01 Warsaw Orthopedic, Inc. Devices, Apparatus, and Methods for Disc Augmentation

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