Patent Application
20080082168
Some embodiments of the disclosure may be understood by referring, in part, to the following description and the accompanying drawings, wherein:
Implanting a medical device in a subject's body may be correlated with an inflammatory and/or cytotoxic response. For example, a subject's body may produce fibrotic tissue that partially or completely encapsulates the foreign body. Such responses may be regarded as undesirable under some circumstances. For example, a subject in whom fibrotic tissue contacts a nerve following spinal surgery may experience significant back and/or leg pain. According to some embodiments of the present disclosure, however, these responses may be harnessed and/or enhanced for beneficial and/or desirable purposes. For example, formation of fibrotic tissue around an annular implant may repair an annular defect alone or in combination with the implant.
The present disclosure relates to apparatus, compositions, systems, and methods for treating a spinal condition (e.g., an annular defect). A variety of pathologic conditions may yield herniated nucleus pulposus, such as acute traumatic tears or cumulative delamination of the annular fibers. Cumulative damage may result from dehydration of the nucleus pulposus, which may change the loading environment of the posterior annulus. Thus, this desiccation may contribute to mechanical failure of the structure. Extrusion of the nucleus pulposus may occur if the annulus is compromised. Patients with radiographic evidence of tears and associated herniations may be asymptomatic. Radiculitis, however, may be an indication for surgical intervention, where the neuropathic symptom is secondary to mechanical impingement and autoimmune response to nucleus material. Structural changes in the posterior portion of the anterior column also may produce neovascularization and/or nociceptive changes, which may contribute to axiomechanical back pain. Surgeons frequently operate on leg pain or radiculopathy over axiomechanical back pain because the probability of success may be higher and long-term consequences of untreated neural compression exist. Discectomy may be the most common intervention for radiculopathy, wherein the offending fragment is removed. Regardless of the source, the pathology ultimately results from mechanical deficiency of the posterior annulus fibrosis. The extruded fragment may be surgically removed without addressing the annular defect, mechanical change, or inflammation.
A common zone for herniation may be in the posterolateral region. The posterior annulus may be relatively thin. The central region is reinforced by the posterior longitudinal ligament (PLL), thus discs may herniate posteriorly and lateral to the PLL. Anterior or direct lateral herniation may be rare.
An apparatus, according to some embodiments, may include a spinal implant (e.g., a scaffold implant) or a device for placing an implant (e.g., a scaffold implant) in a spine. For example, an apparatus may include a spinal implant configured and arranged for placement on, near, and/or adjacent to an annular defect. In some embodiments, an implant may include a scaffold (e.g., mesh and/or patch) having at least one tail configured and arranged to contact a vertebral body of the spine. For example, an implant may include one tail, two tails, three tails, four tails, or more than four tails. Tails may be spaced apart on an implant at desired intervals, regular intervals, and/or irregular intervals, according to some embodiments. A tail and a scaffold, in some embodiments, may be made from the same materials or different materials. In some embodiments where a tail and a scaffold have different compositions, a tail may include a wire.
An apparatus, according to some embodiments of the disclosure, may be sized according to the intended application. For example, the length of the tail(s), the size and shape of the scaffold, and the site of attachment between the tail(s) and the scaffold may be selected to accommodate the spine of the intended subject, whether a child or an adult, whether its morphology is regular or unusual. In some embodiments, an apparatus may include a scaffold having a generally oval shape (or a generally rectangular shape) and a total of two tails, one attached at either end of the scaffold. This scaffold may measure from about two millimeters (2 mm) to about thirty millimeters (30 mm) along its longest axis, from about two millimeters (2 mm) to about thirty millimeters (30 mm) along its shortest axis, and/or from about one micron (1 μm) to about ten millimeters (10 mm) at its point of maximum thickness. A scaffold may measure from about 2 mm to about 6 mm, from about 2 mm to about 8 mm, from about 2 mm to about 10 mm, from about 4 mm to about 10 mm, from about 4 mm to about 12 mm, from about 4 mm to about 18 mm, from about 4 mm to about 24 mm, and/or from about 6 mm to about 24 mm along its longest axis.
Tails may be sized to include a generous excess after being secured to a vertebral body. This excess may be trimmed as desired. A tail may be from about one centimeter (1 cm) to about fifteen centimeters (15 cm). In some embodiments, an apparatus may include a scaffold having a generally rectangular shape (or a generally oval shape) and a total of four tails, one attached at each corner. Where a scaffold includes more than one tail, the tails may be sized independently or identically as desired or required by the particular intended application.
According to some embodiments, an implant may include an annular scaffold (e.g., mesh and/or patch) that may be applied to a nucleus pulposus or nucleus of a disc in a spine. An implant may be secured to itself (e.g., the implant tails may be tied to the scaffold), rather than using rigid fasteners, such as screws, plugs, etc. in some embodiments.
As persons of ordinary skill in the art understand, a herniated disc may result in release of nucleus matter. A device, according to some embodiments, may partially or completely retain and/or contain herniated nucleus pulposus and/or prevent herniation (egg, an implantable obturator), thus avoiding potential contact to peripheral nerve roots. In some embodiments, a device may also support reintroduction of extruded nucleus pulposus materials into the disc space. A device may further retain and/or contain another device (e.g., a nucleus replacement implant). In contrast, an apparatus according to some embodiments may not form a barrier and may not itself contain herniated nucleus pulposus or obturate a tear in the annulus fibrosis. For example, an apparatus may serve as a scaffold for formation of new tissue (e.g., scar tissue) such that the new tissue repairs the defect. In some embodiments, a spinal implant may function to contain and/or prevent herniation for an initial period and subsequently biodegrade (e.g., once fibrous tissue has grown in).
According to some embodiments, a scaffold may include pliable materials (e.g., mesh, fabric, felt) and lack a permanent structure (a “pliable scaffold”). A scaffold, in some embodiments, may include rigid and/or semi-rigid materials such that it retains or at least tends to retain its shape (a “rigid scaffold”), A rigid scaffold may be configured and arranged (either beforehand or in situ) to conform to the contours of the spine where it is to be placed. In addition, a rigid scaffold may be configured and arranged to nucleate and/or support formation of fibrotic tissue that conforms to the contours of the spine where the implant is to be placed and/or seals an annular defect. In some embodiments, a scaffold may be laterally reinforced by including, for example, a woven material having a more rigid weave in at least one dimension, a secondary element (e.g., a plastic insert), and/or a wire (e.g., a shape memory alloy).
An implant may include a permeable and/or an impermeable scaffold, according to some embodiments. A scaffold may include, in some embodiments, a releasable pharmaceutical agent and a polymer. A scaffold may be configured and arranged to be degradable (e.g., biodegradable) and/or non-degradable, A scaffold may include a pharmaceutical agent elution matrix configured and arranged to permit sustained, graduated, and/or, periodic release of a pharmaceutical agent. In some embodiments, surface characteristics of a scaffold material may be prepared and/or modified (e.g., by texturing) to support release of a pharmaceutical agent. For example, a scaffold may be nanotextured with tubules. A scaffold may be coated with a pharmaceutical agent in a suitable carrier configured and arranged to have desired release capabilities.
If desired or necessary, a pharmaceutical agent may include a binder to carry, load, of allow sustained release of the agent, such as but not limited to a suitable polymer or similar carrier. According to some embodiments of the disclosure, a polymer may include a product of a polymerization reaction inclusive of homopolymers, copolymers, terpolymers, etc., whether natural or synthetic, including random, alternating, block, graft, branched, cross-linked, blends, compositions of blends and variations thereof. A polymer may be in true solution, saturated, or suspended as particles or supersaturated in the therapeutic agent. A polymer may be biocompatible and/or biodegradable.
A polymeric material may include a phosphorylcholine linked macromolecule in some embodiments (a “PC polymer”). For example, a polymeric material may include a macromolecule containing pendant phosphorylcholine groups such as poly(MPCw:LMAx:HPMAy:TSMAz), where MPC is 2-methacryoyloxyethylphosphorylcholine, LMA is lauryl methacrylate, HPMA is hydroxypropyl methacrylate and TSMA is trimethoxysilylpropyl methacrylate, and w, x, y, and z are molar ratios of the monomers used in the feed. These values may be 23, 47, 25, and 5, respectively, but they are not necessarily the ratios that exist in the finished polymer.
A PC polymer may include, for example, 5% pendant trimethoxysilane groups, which may be used to crosslink the polymer after it is coated on a surface. These groups may also be used to chemically bond the material to a device having an appropriate surface chemistry. For example, where a scaffold that includes a Dacron mesh, the surface of the polyester may be hydrolyzed producing hydroxyl groups for reaction with trimethoxy silane. Alternatively, the Dacron may be formulated with impregnated fiber glass or glass powder. The glass may be the source of surface hydroxyl groups; however, it may change the mechanical properties of the Dacron.
A scaffold may include a polymer selected from the group consisting of alginate, aliphatic polyesters, bioglass, blood cells, bone-allograft or autograft, bone cement, carbohydrates, cellulose, cellulose derivatives (e.g., HPC), ceramics, chitin, chitosan, chitosan derivatives, collagen, collagen—native fibrous, collagen—recombinant derived, collagen—reconstituted fibrous, collagen—soluble, collagen—Types 1 to 20, copolymers of glycolide, copolymers of lactide, cyanoacrylate, dacron, demineralized bone, elastin, felt, fibrin, gelatin, glass, glycolide/1-lactide copolymers (PGA/PLLA), glycolide/trimethylene carbonate copolymers (PGA/TMC), glycosaminoglycans, gold, hyaluronic Acid, hyaluronic acid derivatives, hydrogel, hydroxy apatite, hydroxyethyl methacrylate, lactide/ε-capiolactone copolymers, lactide/σ-valerolactone copolymers, lactide/tetramethylglycolide copolymers, lactide/trimethlylene carbonate copolymers, 1-lactide/dl-lactide copolymers, polymethyl methacrylate (PMMA), polymethyl methacrylate-N-vinyl pyrrolidone copolymers, polymethyl methacrylate-styrene (MMA-styrene), nitinol, nylon-2, oligoethylenimine (OEI), OEI-HD (e.g., a condensation product of OEI with hexanedioldiacrylate), oxidized regenerated cellulose, PHBA/γ-hydroxyvalerate copolymers (PUBA/UVA), phosphate glasses, PLA/polyethylene oxide copolymers, PLA-polyethylene oxide (PELA), polyethylenimine (PEI), poly (amino acids), poly (trimethylene carbonates), poly hydroxyalkanoate polymers (PHA), poly(alkylene oxalates), poly(butylene diglycolate), poly(glycerol sebacate), poly(hydroxy butyrate) (PHB), poly(methacrylic acid), poly(n-vinyl pyrrolidone), poly(ortho esters), poly(styrene sulfonate), poly-β-alkanoic acids, poly-β-hydroxybutyrate (PBA), poly-β-hydroxypropionate (PHPA), poly-β-malic acid (PMLA), poly-ε-caprolactone (PCL), poly-σ-valerolactone, polyalkyl-2-cyanoacrylates, polyanhydrides, polycyanoacrylates, polydepsipeptides, polydihydropyrans, poly-DL-lactide (PDLLA), polyester, polyesteramides, polyester-polyallylene oxide block copolymers, polyesters of oxalic acid, polyethylene glycol—crosslinked, polyethylene glycol—poly(vinyl PEG), polyethylene glycol (PEG), polyethylene oxide, polyglycan esters, polyglycolide (PGA), polyiminocarbonates, polylactides (PLA), poly-1-lactide (PLLA), polymethyl methacrylate (PMMA), polyorthoesters, poly-p-dioxanone (PDO), polypeptides, polyphosphazenes, polysaccharides, polyurethanes (PU), polyvinyl alcohol (PVA), pseudo-poly(amino acids), radiopacifiers, salts, silicone, silk, starch, steel (e.g. stainless steel), synthetic cancellous bone void fillers, synthetic polymers, titanium, tricalcium phosphate, tyrosine based polymers, and combinations thereof. A scaffold may include a material selected from the group consisting of bone chips, calcium, calcium carbonate, calcium phosphate, calcium sulfate, liposomes, mesenchymal cells, osteoblasts, platelets, proteins (e.g., albumin, casein, whey proteins, plant proteins, and fish proteins), proteins modified, thrombin, trimethylene carbonate (TMC), and combinations thereof.
When viewed from the top, one may observe that bulge 110 may come in contact with, or exert pressure to surrounding structures or tissues. For example, bulge 110 may compress neural element 115. As a result, the patient may experience pain, discomfort, or loss of function. In the case of a tear, the leakage of nucleus pulposus may result in a variety of problems and complications, as persons of ordinary skill in the art understand.
One may repair a disc defect (e.g., annular tear) by applying an embodiment of a scaffold implant of the disclosure
Scaffold 200 attaches to vertebral body 100A through perforation 210A, and to vertebral body 100B through perforation 210B. The respective positions of perforation 210A and perforation 210B depend on a number of factors, including the desired placement of scaffold 200.
A practitioner (erg, a surgeon) may position scaffold 200 in a defective or damaged area of the disc, e.g., over an annular tear. In one embodiment, perforation 210A and perforation 210B reside in the posterior margins of vertebral body 100A and vertebral body 100B, respectively. In other embodiments, one may select the precise positions of perforation 210A and perforation 210B depending on factors such as the desired position of scaffold 200, a patient's anatomy, the nature of the defect in the disc, etc., as persons of ordinary skill in the art who have the benefit of the instant disclosure understand
An implant, according to some embodiments, may include a composition to elicit a specific biologic response. In some embodiments, an implant may include a composition formulated to enhance annular defect repair (e.g., by augmenting and/or inhibiting one or more biological processes) according to some embodiments. For example, an implant may include a releasable pharmaceutical agent that enhances or impedes fibrosis, A pharmaceutical agent may include, for example, an anti-inflammatory agent, an anti-adhesive agent, and/or a pro-adhesive agent.
In some embodiments, a pharmaceutical agent may result in adhesion and/or fibrosis in one or more surrounding tissues. Production of fibrotic tissue at or near the site of a disc defect may enhance defect repair and/or treatment. For example, new fibrotic tissue that partially and/or completely surrounds an implant or defect may at least partially contain the nucleus pulposus, thereby augmenting the native annular fibrosis. A scaffold, in some embodiments, may include an anti-adhesion compound (ergo, on a portion of the scaffold that may contact a nerve root to minimize or avoid painful tethering of scar tissue to a nerve root).
According to some embodiments, a composition including a pharmaceutical agent may be carried on and/or eluted by at least a portion of an implant. Thus, a scaffold may have one or more portions that include a therapeutic composition and one or more portions that lack a therapeutic composition. For example, a scaffold may have a domain or domains configured and arranged to confer structure (e.g., shape, rigidity, resilience, etch) and a domain or domains containing a pharmaceutical agent. In a non-limiting example, a scaffold may include opposing surfaces, one of which includes biocompatible polymers for structure and the other of which includes a pharmaceutical agent. One of ordinary skill in the art having the benefit of the present disclosure will understand that determining which surface faces the annular defect and which surface faces away from the annular defect will depend, at least in part on what pharmaceutical agent(s) are used, the shape of the scaffold, the nature of the adjoining tissue. In another non-limiting example, a scaffold may include a sheath of a biocompatible polymer for structure and a core comprising a bioactive agent. The sheath may be configured and arranged to be biodegradable and/or bioresorbable (e.g., to permit the scaffold to function as a barrier for an initial period).
A pharmaceutical agent suitable for inclusion in a scaffold of the disclosure, in some embodiments, may include a protein (e.g., peptide (e.g., adhesion peptide), enzyme, antibody, receptor, receptor ligand), a carbohydrate (e.g., monosaccharide, disaccharide, polysaccharide (linear or branched)), a lipid (e.g., prostaglandin, eicosanoid, steroid), a nucleic acid (e.g., DNA, RNA, siRNA, microRNA, ribozyme, virus, vector, coding sequence, antisense sequence, nucleotide), and/or combinations thereof. In some embodiments, a pharmaceutical agent may include one or more of the compounds listed in TABLE 1 and/or analogues and derivatives thereof. For example, a pharmaceutical agent may include alpha-interferon, an amino acid, an angiogenic agent, an anti-allergic agent, an anti-angiogenic agent, an antiarrhythmic agent, an antibiotic, an anti-coagulant agent, an anti-fibrin agent, an anti-fungal agent, an anti-inflammatory agent, an anti-neoplastic agent, an antioxidant, an anti-platelet agent, an anti-proliferative agent, an anti-rejection agent, an anti-thrombotic agent, an anti-viral drug, bioactive RGD, a blood clotting agent, a cell, a chemotherapeutic agent, a fibrosis-inducing agent, a fibrosis-inhibiting agent, a growth factor, a hormone, a nitric oxide or a nitric oxide donor, nitroprusside, a phosphodiesterase inhibitor, a proliferative agent, a prostaglandin inhibitor, a proteoglycan, a radioactive material, a serotonin blocker, a super oxide dismutase, a super oxide dismutase mimetic, suramin, a thioprotease inhibitor, thiazolopyrimidine, a tyrosine kinase inhibitor, a vasodilator, and/or a vitamin. In some embodiments, a pharmaceutical agent may include a compound selected from the group consisting of 1-α-25 dihydroxyvitamin D3, alcohol, all-trans retinoic acid (ATRA), angiotensin II antagonists, anti-tumor necrosis factor, beta-blocker, carcinogens, chondroitin, clopidegrel, collagen inhibitors, colony stimulating factors, coumadin, cyclosporine A, cytokines, dentin, diethylstibesterol, etretinate, glucosamine, glycosaminoglycans, growth factor antagonists or inhibitors, heparin sulfate proteoglycan, immoxidal, immune modulator agents (e.g., immunosuppressant agents), inflammatory mediator, insulin, isotretinoin (13-cis retinoic acid), lipid lowering agents (e.g., cholesterol reducers, HMC-CoA reductase inhibitors (statins)), lysine (e.g., polylysine), methylation inhibitors, N[G]-nitro-L-arginine methyl ester (L-NAME), plavix, polyphenol, PR39, prednisone, signal transduction factors, signaling proteins, somatomedins, thrombin, thrombin inhibitor, ticlid, and combinations thereof.
A fibrosis-inducing agent may include, according to some embodiments, an adhesive, an arterial vessel wall irritant, bleomycin, a bone morphogenic protein (BMP), connective tissue growth factor (CTGF), an extracellular matrix component, an inflammatory cytokine, leptin, a polymer, and/or vinyl chloride (including a polymer of vinyl chloride). In some embodiments, a fibrosis-inducing agent may include analogues and/or derivatives of the foregoing compounds. An adhesive may include, for example, crosslinked poly(ethylene glycol)-methylated collagen and/or cyanoacrylates. An arterial vessel wall irritant may include, for example, crystalline silicates, copper, ethanol, metallic beryllium and oxides thereof, neomycin, quartz dust, silica, silk, talc, talcum powder, and/or wool. A bone morphogenic protein (BMP) may include, for example, bone morphogenic protein-2, bone morphogenic protein-3, bone morphogenic protein-4, bone morphogenic protein-5, bone morphogenic protein-6, and/or bone morphogenic protein-7. An extracellular matrix component may include, for example, collagen, fibrin, fibrinogen, and/or fibronectin. An inflammatory cytokine may include, for example, basic fibroblast growth factor (bFGF), granulocyte-macrophage colony stimulating factor (GM-CSF), growth hormones, insulin growth factor-1 (IGF-1), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), nerve growth factor (NGF) platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), tumor necrosis factor α (TNF-α), and/or vascular endothelial growth factor (VEGF). A polymer may include, for example, chitosan, N-carboxybutylchitosan, a poly(alkylcyanoacrylate), poly(ethylene-co-vinylacetate), poly(ethylene terephthalate), a polylysine, polytetrafluoroethylene (PTFE), a polyurethane, and/or an ROD protein.
A pharmaceutical agent, in some embodiments, may include any compound, mixture of compounds, or composition of matter consisting of a compound, which produces a therapeutic or useful result in at least one subject. A pharmaceutical agent may include a polymer, a marker; such as a radiopaque dye or particles, or may include a drug, including pharmaceutical and therapeutic agents, or an agent including inorganic or organic drugs without limitation. According to some embodiments, a pharmaceutical agent may be in various forms such as an uncharged molecule, a component of a molecular complex, and/or a pharmacologically acceptable salt (e.g., hydrochloride, hydrobromide, sulfate, laurate, palmitate, phosphate, nitrate, borate, acetate, maleate, tartrate, oleate, and salicylate).
In some embodiments, a water insoluble pharmaceutical agent may be included in a scaffold of the disclosure. In other embodiments, a water-soluble derivative of a water insoluble pharmaceutical agent may be included in a scaffold (e.g., to effectively serve as a solute). Once in a subject's body, a water-soluble derivative of a water insoluble pharmaceutical agent may be converted (e.g., by enzymes, hydrolyzed by body pH, or metabolic processes) to a biologically active form. Additionally, a pharmaceutical agent formulation may include various known forms such as solutions, dispersions, pastes, particles, granules, emulsions, suspensions and powders. The drug or agent may or may not be mixed with polymer or a solvent as desired.
A pharmaceutical agent, in some embodiments, may include a solvent. A solvent may be any single solvent or a combination of solvents. For example, a solvent may include water, aliphatic hydrocarbons, aromatic hydrocarbons, alcohols, ketones, dimethyl sulfoxide, tetrahydrofuran, dihydrofuran, dimethylacetamide, acetates, and/or combinations thereof. According to some embodiments, a solvent is ethanol, A solvent is isobutanol in some embodiments. According to some embodiments, two or more pharmaceutical agents may be dissolved or dispersed in the same solvent. For example, dexamethasone, estradiol, and paclitaxel may be dissolved in isobutanol. Alternatively, dexamethasone, estradiol, and paclitaxel may be dissolved in ethanol. In yet another example, dexamethasone, estradiol, and ABT-578, i.e., the rapamycin analog, 3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)9,10,12,13,14,21,22,23,24, 25,26,27,32,33,34,34a—Hexadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-3-methoxy-4-tetrazol-1-yl)cyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-2-3,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone; 23,27-Epoxy-3H-pyrido[2,1-c]i[1,4]oxaazacyclohentriacontin-e-1,5,11,28,29(4H,,6H,31H)-pentone, may be dissolved together in one solvent (e.g., ethanol or isobutanol).
According to some embodiments of the disclosure, a pharmaceutical agent may be a gene therapy agent. For example, a pharmaceutical agent may include a viral or retroviral vector (e.g., adenovirus) having a therapeutic nucleic acid (e.g., a sense or antisense sequence). A pharmaceutical agent may include, for example, a small interfering RNA (siRNA). A siRNA may include a 21 base pair double stranded RNA and may, for example, reduce production of BMP's (e.g., to prevent spinal fusion) or reduce production of cytokines and/or other proteins (e.g., to reduce inflammation and/or promote healing), A siRNA may be complexed with a transfection agent or carrier.
A method of repairing an annular defect in a spine may include placing a scaffold implant (e.g., having at least one tail) on, near, and/or adjacent to the defect according to some embodiments. For example, a practitioner (e.g., a surgeon) may choose peri-annular placement or sub-annular placement. In some embodiments, a placement technique may not rely exclusively on the annular fibers to retain the device. Rather, a practitioner may use positive anchoring in the tissues, as allowed by a patient's anatomy. Anchoring may include anchoring directly to the bone of the vertebral endplates and/or anchoring to posterior elements of the vertebra(e). Thus, a method may include, in some embodiments, contacting the at least one thread with a vertebral body of the spine. For example, a method may include threading a tail through a perforation in a vertebral body of the spine. According to some embodiments, a method may also include contacting one or more additional tails through one or more additional perforations in the same and/or another vertebral body of the spine.
To attach a scaffold to vertebral bodies, a practitioner (e.g., a surgeon) may use a tunneling approach, as persons of ordinary skill in the art who have the benefit of the instant disclosure understand. Tunneling in the posterior vertebral endplate anchors the tails of scaffold 200 (as described below), which in turn, anchors the scaffold over the defect. As noted, the scaffold provides reinforcement, which retains the extruded nucleus material.
More specifically, a practitioner may make perforation 210A in an endplate of vertebral body 100A. Similarly, a practitioner may make perforation 210B in an endplate of vertebral body 100B.
A practitioner may use a variety of techniques and instruments to make perforation 210A and perforation 210B. For example, a practitioner may use a drill, a trochar, or a punch, as desired.
According to the embodiment shown in
Similarly, a practitioner uses trochar 220B to make perforation 210B in an endplate of vertebral body 100B. A practitioner may make perforation 210B at a desired position, size, and angle. If desired, a practitioner may make perforation 210A and perforation 210B at complementary angles with respect to a horizontal (anterior-posterior or top or transverse) plane of annulus 105.
The size, angle, and location of perforation 210A and perforation 210B depend on a variety of factors, as persons of ordinary skill in the art who have the benefit of the instant disclosure understand. The factors include the desired location of scaffold 200 with respect to annulus 105, vertebral body 100A and vertebral body 100B, the patient's anatomy, and the particular geometry and characteristics of scaffold 200 and its tails (as described below).
After performing the perforation procedure above, a practitioner may attach an implant. More specifically, a practitioner may secure one end or region of scaffold 200 to vertebral body 100A by using one or more knots 205A. Likewise, a practitioner may use one or more knots 205B to attach another end of scaffold 200 to vertebral body 100B. As described below in detail, scaffold 200 couples to a pair of tails. A practitioner may use a respective tail to tie knot 205A and knot 205B.
Note that knots constitute just one technique for securing the scaffold implant in a desired location. One may use a variety of techniques to secure the scaffold implant, as persons of ordinary skill in the art who have the benefit of the instant disclosure understand, and as desired. As one example, one may use a crimping tool to crimp a sleeve or other suitable structure in order to secure the implant. As other examples, one may use fraction fits, braids, or cam locks, as desired.
Once attached, an implant may retain the nucleus pulposus, help avoid extrusion of the nucleus pulposus, and/or provide a pharmaceutical (e.g., therapeutic) agent, as described above. An implant may also serve as a scaffold for scar tissue growth, further securing the implant in place.
As noted above, a practitioner may place or implant scaffold 200 in a variety of positions with respect to annulus 105. For example, a practitioner may use a peri-annular placement or an intra-annular placement for scaffold 200 and the implant generally.
In some cases of contained herniated nucleus pulposus, peri-annular placement of the scaffold construct reinforces the posterior annulus without accessing the inter-disc space. This method of placement may protect surrounding material from harmful substances contained in the nucleus matter.
Furthermore, some methods of the disclosure may avoid worsening the annular defect, because, for example, a practitioner may place the scaffold on top of the defect. In fact, under some circumstances, a practitioner may even be able to push back the extruded nucleus matter into the defect. In cases where a disc bulge exists, a patch will reinforce the defective area without exposing the body to the nucleus pulposus.
As noted above, scaffold 200 is attached to a pair of tails, shown as tail 230A and tail 230B in
Tail 230A and tail 230B allow a practitioner to secure scaffold 200 in a desired location. A practitioner may use tail 230A and tail 230B to tie the implant onto itself. In this manner, a practitioner may avoid using rigid fasteners (e.g., bone screws). Rigid materials may have one or more undesirable effects, such as contact with sensitive nearby tissues or injury to nerves.
In peri-annular placement, tail 230A and tail 230B enter perforation 210A and 210B, respectively, from the posterior direction of respective vertebral body 100A and vertebral body 100B. In contrast, in intra-annular placement, a practitioner threads tail 230A and 230B so that they enter, respectively, perforation 210A and 210B from near annulus 105 and exit the posterior aspect of vertebral body 100A and vertebral body 100B, respectively.
More specifically, after making perforation 210A, a practitioner may thread tail 230A through perforation 210A, starting with the end of perforation 210A nearer annulus 105. Thus, the free end (i.e., the end not coupled to scaffold 200 before placement of the implant) of tail 230A enters perforation 210A near annulus 105, and exits perforation 210A at the posterior aspect of vertebral body 100A.
After threading through perforation 210A, a practitioner uses the free end of tail 230A to tie knot 205A. A practitioner may pull tail 230A to a desired degree of tension before or during the tying of knot 205A. Once a practitioner has finished tying knot 205A, a practitioner may cut off any excess portion of tail 230A.
Similarly, after making perforation 210B, a practitioner threads tail 230B through perforation 210B. A practitioner begins the threading from an end of perforation 210A that is closer to annulus 105. Thus, the free (i.e., the end not coupled to scaffold 200 before placement of the implant) end of tail 230B enters perforation 210B near annulus 105. After threading, the end of tail 230B exits perforation 210A at the posterior of vertebral body 100B.
After threading through perforation 210B, a practitioner uses the free end of tail 230B to tie knot 205B. As noted above, a practitioner may pull tail 230B to a desired degree of tension before or during the tying of knot 205B. A practitioner may cut off any excess portion of tail 230B after finishing the tying of knot 205B.
Scaffold 200 may be attached to tail 230A and tail 230B, for example, via loop 240A and loop 240B, respectively, or without them. Optional integral loop 240A and loop 240B facilitate the tying of knot 205A and 205B (see
As noted, scaffold 200 may cover a herniated region or area of the disc or annulus 105. Scaffold 200 may be permeable or impermeable, as desired. In some embodiments, scaffold 200 may not need to be impermeable. Because scaffold 200 buttresses and supports the herniated region, it may prevent, or tend to prevent, the leakage and release of nucleus material. Furthermore, the patient's body will scar over during the healing process and thus, help to isolate and contain the nucleus material. Thus, a two-stage process may occur in which a permeable scaffold may act to seal the annulus: (1) the permeable scaffold may buttress the insufficient tissue allowing the body to (2) create an impermeable fibrous scar. This configuration may also provide stability to the level (e.g., where the scaffold is able to resist significant tensile forces).
As noted above, a scaffold implant may optionally include needles or guides 250A and 250B coupled to an end of each respective tail (230A and 230B). Needle 250A and needle 250B facilitate threading respective tail 230A and/or tail 230B, tying respective knot 205A and/or knot 205B, and/or both threading and tying.
Once a practitioner has performed the threading, a practitioner may detach (e.g., cut off or otherwise uncouple) needle 250A before tying knot 205A (see
Similarly, once a practitioner has threaded tail 230B, a practitioner may detach (e.g., cut off or otherwise uncouple) needle 250B before tying knot 205B (see
One may tie knots 205A and 205B in a variety of ways, as persons of ordinary skill in the art who have the benefit of the instant disclosure understand. As one example,
To tie the knot, a practitioner threads the free end of tail 230B through loop 240B in the direction of arrow 260. After the first threading operation, a practitioner then may thread the end of tail 230B one or more times through loop 240B in order to produce a tighter or more secure knot. After the last threading, a practitioner may tie the free end of tail 230B using a conventional knot or surgical knot, as desired.
One may thread tails 230A and 230B through perforations or openings 210A and 210B, respectively, by using a manual approach, or by using an instrument-assisted approach.
In the technique illustrated, a practitioner uses trochar 220 and a plate or guide 300. Trochar 220A has an opening or hole 310A. Likewise, plate 300 has an opening or hole 305. Openings 310A and 305 facilitate the threading of tail 230A. Tail 230B of the scaffold implant is similarly threaded
Referring to
Subsequently, a practitioner withdraws plate 300 from the patient's body, using a motion generally in the direction of arrow 360. As plate 300 moves in the direction shown by arrow 360, it pulls or withdraws tie fee end of tail 230A from the patient's body. Once a practitioner has sufficiently withdrawn plate 300, he or she will have access to the free end of tail 230A. A practitioner may then use the retrieved free end of tail 230A to tie a knot and thus secure one end of scaffold 200 in a desired location.
A practitioner may repeat the above technique for the other tail, i.e., tail 230B. Once a practitioner has retrieved tail 230B, he or she may tie another knot, thus securing the second end of scaffold 200 in a desired location. At the conclusion of this procedure, scaffold 200 may be positioned in a desired location with respect to the defect in annulus 105. As one alternative, a practitioner may thread both tail 230A and tail 230B through perforation 305 and retract both tails in direction 360 to secure them.
A method of repairing an annular defect in a spine may include, according to some embodiments, placing a scaffold implant (e.g., having at least one tail) on, near, and/or adjacent to the defect and irradiating the tissue adjacent to the scaffold implant. Irradiation may include ionizing radiation (e.g., beta particles, neutrons, alpha particles, X-rays and photons) and/or proton beams. Gratings, lenses and/or filters may be used to deliver the radiation to a specific site of interest. As one of ordinary skill will understand, the dosing and frequency of irradiation may be adjusted to customize the formation of fibrotic tissue to a particular subject and/or a specific application.
A method of preparing a spinal implant having a scaffold and at least one tail may include, according to some embodiments, providing a scaffold having a bare surface; mixing at least one pharmaceutical agent and at least one polymer in a solvent to form a mixture; and applying the mixture to at least a portion of the bare surface of the scaffold to form a coating thereon. A mixture, in some embodiments, may be applied to the bare surface of the scaffold by spraying, dipping, jetting and/or any other application techniques. According to some embodiments, at least one polymer may be a crosslinkable polymer (e.g., phosphorylcholine-linked methacrylate polymer). The at least one polymer may include a trimethoxysilane functional group in some embodiments. The at least one polymer and at least one pharmaceutical agent may be mixed using ethanol as the solvent. A mixture may be uniformly applied to at least a portion of the scaffold. Also, the at least one pharmaceutical agent may be uniformly distributed in the coating, layered or otherwise disbursed or dissolved in or on the coating or coatings. A coating may have a thickness of about 5 to about 6 microns.
A method, according to some embodiments, may include curing a coating. Curing a coating may include heating the coating, either independently or by way of another processing step in the overall manufacture of a product. Also, a base coating may not be necessary. In some embodiments, a method may further include applying an overcoating to at least a portion of the scaffold.
A coated scaffold may be mounted to a delivery device and/or sterilized, in some embodiments. Sterilization of a coated scaffold may include irradiating the coating. Prior to being sterilized, a coated scaffold may be cured, dried, and/or otherwise processed in accordance with a desired end product. According to some embodiments, a sterilizing step may facilitate crosslinking of the polymer coating. A sterilizing step may include exposing a coated scaffold to at least one cycle of ethylene oxide and/or beat.
A coated scaffold, in some embodiments, may include at least one pharmaceutical agent. For example, a coated scaffold may include about 10 to about 13 micrograms of a pharmaceutical agent along a linear millimeter of the coated scaffold length or as needed to obtain an effective tissue concentration for the required length of time, for the desired end product.
Any dose that leads to a desired or required effective tissue concentration may be used in some embodiments. Effective tissue concentration limits may be known for many drugs. In some such cases, it may be possible to predict the effective tissue concentration when the drug is release from a device. In others, routine dosing experiments may be performed to determine the right dose or desired dose. Concentration of a drug in the tissue may vary with distance from the device and/or may vary in relation to fluid dynamics near the device, e.g., (lymphatic) drainage.
In some embodiments, a scaffold of the present disclosure may include a pharmaceutical agent in any amount desired by a practitioner. One of ordinary skill in the art having the benefit of the present disclosure understands that the exact selection and dose of a pharmaceutical depends on a variety of factors including without limitation, one or more aspects of a subject's medical history (e.g., health, allergies, weight), the intended location of the scaffold, the condition being treated, and the intended course of therapy. A scaffold may include a certain weight of pharmaceutically active agent per unit surface area of device placed in contact with the tissue of interest in order to obtain an effective tissue concentration for the required time. For example, a scaffold may include from about 0.01 micrograms to about 10 milligrams of a pharmaceutical agent along a linear millimeter of the coated scaffold length. For example, a scaffold may include from about 0.01 micrograms to about 0.1 micrograms, from about 0.1 micrograms to about 1.0 micrograms, from about 1.0 micrograms to about 10 micrograms, from about 10 micrograms to about 100 micrograms, from about 100 micrograms to about 1.0 milligram, and/or from about 1.0 milligram to about 10 milligrams of a pharmaceutical agent along a linear millimeter of the coated scaffold length. In some embodiments, these ranges may apply to a scaffold that includes a pharmaceutical agent in its fibers (e.g., rather than as a coating) and/or in domains.
A coated scaffold may include 30% by weight of a therapeutic agent relative to the polymer or as needed for the desired end product. A scaffold, according to some embodiments, may include a pharmaceutical agent in any amount relative to the weight of the scaffold desired by a practitioner. For example, a scaffold may include from about 0.01% by weight to about 0.1% by weight, from about 0.1% by weight to about 1.0% by weight, from about 1.0% by weight to about 10% by weight, from about 1.0% by weight to about 10% by weight, from about 10% by weight to about 20% by weight, from about 20% by weight to about 30% by weight, from about 30% by weight to about 40% by weight, from about 40% by weight to about 50% by weight, and/or more than about 50% by weight of a pharmaceutical agent.
A coating, in some embodiments, may include a uniform matrix of therapeutic agent and polymer; binder, and/or carrier.
One may fabricate scaffold 200, tail 230A and tail 230B, and optional loop 240A and optional loop 240B from a variety of materials, as desired, and as persons of ordinary skill in the art who have the benefit of the instant disclosure understand. The choice of material depends on the desired characteristics of those components, and the particular desired properties of the resulting implant.
Scaffold 200 (and tails 230A and 230B and loops 240A and 240B, as desired) may be fabricated from a natural or synthetic pliable material. The material should be biocompatible and relatively pliable, although one may use a relatively rigid or semi-rigid material, as desired. Furthermore, the materials should encourage fibrous tissue encapsulation.
As an example of one material, one may use polyester to take advantage of its property of encouraging fibrous tissue encapsulation. Various methods are known to persons of ordinary skill in the art for using polyester to encourage tissue in growth. As a specific example, one may use Dacron. One may also coat (e.g., dry coat), impregnate, or micro-texture (or otherwise include or embed into), the material, for example, with therapeutic or medicated agents, to elicit a desired response.
Examples of other materials or therapeutic or medicated agents that may be used include anti-inflammatory agents, anti-adhesive agents (to eliminate or reduce scar tissue), and/or pro-adhesive agents. Examples of anti-inflammatory agents are described in detail in U.S. patent application Ser. No. 11/455,401, titled “Improved Method of Treating Degenerative Spinal Disorders”, filed on Jun. 19, 2006, and incorporated herein by reference). Note, however, that in addition or instead one may use other suitable materials, as persons of ordinary skill in the art who have the benefit of the instant disclosure understand. Furthermore, one may use a single material or agent or a combination of several materials or agents, as desired.
A system, according to some embodiments, may include a scaffold implant, together with a tool and/or instrument for positioning or implanting the scaffold implant within a subject's spine. In some embodiments, a tool and/or instrument for positioning or implanting the scaffold implant within a subject's spine may include, for example, a first handle having a channel, a body having a channel, a hollow shaft or tube that connects the channel of the first handle to the channel of the body to form an inserter track, an elongate inserter slidably contained in the inserter track, wherein the inserter has a body end proximal to the body and a first handle end proximal to the first handle, and wherein the body end comprises an opening configured and arranged to receive a spinal implant tail, a second handle attached to the inserter at its first handle end and operable to slide the inserter back and forth along the inserter track, and a pair of articulating needles or guides configured and arranged to contact a spinal implant tail and thread it through a perforation in a vertebral body.
An apparatus, in some embodiments, may include a plate configured to slide within the body, and at least one member configured to thread at least one tail of the scaffold implant. For example,
Handle 420 provides a mechanism for a practitioner to hold and manipulate instrument 400. Handle 420 couples to shaft 440. Shaft 440 in turn couples to body 450. Thus, handle 420, shaft 440, and body 450 provide a channel through which plate 430 may slide back and forth.
Handle 410 couples to plate 430. Plate 430 may slide through handle 420 of the instrument, through shaft 440, and through body 450. Plate 430 has an opening 435. Tail 230A or tail 230B of the scaffold implant may pass through opening 435.
Handle 410 provides a way for a practitioner to manipulate plate 430. By pushing in or pulling out handle 410, a practitioner may slide plate 430 through body 450. Pushing in handle 410 causes the end of plate 430 to protrude from body 450. Pulling out handle 410 causes the end of plate 430 to retract into body 450.
Needles 470A and 470B provide a mechanism for threading tails 230A and 230B (not shown in
Note that
A practitioner also retracts plate 430 into body 450. A practitioner then inserts needle 470A (along with tail 230A) into perforation 210A (not shown explicitly) of vertebral body 100A (not shown explicitly) by pushing in body 450 in a posterior-to-anterior direction. Similarly, a practitioner inserts needle 470B (along with tail 230B) into perforation 210B (not shown explicitly) of vertebral body 100B (not shown explicitly).
Subsequently, a practitioner slides plate 430 in a posterior-to-anterior direction such that opening 435 of plate 430 becomes aligned or approximately aligned with openings 475A and 475B of needles 470A and 470B, respectively. By pushing needles 470A and 470B through, respectively, perforations 210A and 210B (not shown explicitly), a practitioner causes the threading of tails 230A and 230B through opening 435 of plate 430.
Once tails 230A and 230B thread through opening 435, a practitioner retracts needles 470A and 470B by pulling body 450 in an anterior-to-posterior direction. Needles 470A and 470B consequently retract from perforations 210A and 210B, leaving tails 230A and 230B threaded in opening 435 of plate 430.
A practitioner may then pull handle 410 (not shown in
As will be understood by those skilled in the art who have the benefit of the instant disclosure, other equivalent or alternative devices, systems, and methods for spinal implantation at or near an injured and/or damaged annulus fibrosis can be envisioned without departing from the essential characteristics thereof. Accordingly, the manner of carrying out the disclosure as shown and described are to be construed as illustrative only.
Persons skilled in the art may make various changes in the shape, size, number, and/or arrangement of parts without departing from the scope of the instant disclosure. For example, a scaffold may have any regular or irregular curvilinear shape (e.g., triangle, rectangle, square, or other polygon, a circle, an oval, or an ellipse). Also, where ranges have been provides, the disclosed endpoints may be treated as exact and/or estimates as desired or demanded by the particular embodiment. In addition, it may be desirable in some embodiments to mix and match range endpoints. Tail ends may or may not be joined with each other (e.g., using a knot) and/or may be adhered to the bone (tunnel end) using an adhesive material. A pharmaceutical agent may be deposited on a scaffold by any available method. For example, a pharmaceutical agent may be coated (e.g., sprayed or spray-dried) onto a scaffold. These equivalents and alternatives along with obvious changes and modifications are intended to be included within the scope of the present disclosure. Accordingly, the foregoing disclosure is intended to be illustrative, but not limiting, of the scope of the disclosure as illustrated by the following claims.
This application is a continuation-in-part of U.S. patent application Ser. No. 11/541,356 filed Sep. 29, 2006, the contents of which are incorporated herein in their entirety by reference.
| Number | Date | Country | |
|---|---|---|---|
| Parent | 11541356 | Sep 2006 | US |
| Child | 11831802 | US |
