Patent Description:
Spinal disorders such as degenerative disc disease, disc herniation, osteoporosis, spondylolisthesis, stenosis, scoliosis and other curvature abnormalities, kyphosis, tumor, and fracture may result from factors including trauma, disease and degenerative conditions caused by injury and aging. Spinal disorders typically result in symptoms including pain, nerve damage, and partial or complete loss of mobility.

Non-surgical treatments, such as medication, rehabilitation and exercise can be effective, however, may fail to relieve the symptoms associated with these disorders. Surgical treatment of these spinal disorders includes fusion, fixation, correction, discectomy, microdiscectomy, corpectomy, decompression, laminectomy, laminotomy, foraminotomy, facetectomy and implantable prosthetics. As part of these surgical treatments, spinal constructs including implants, such as, for example, bone graft, bone fasteners, spinal rods and interbody devices can be delivered to a surgical site for fixation with bone to immobilize a joint. The spinal constructs can be used to provide stability to a treated region and facilitate healing. This disclosure describes an improvement over these technologies.

<CIT> discloses a syringe in which one or more injectable materials are filled, comprises a cylinder or barrel in which a front partition stopper, and one or more intermediate partition stoppers are slidably disposed. In the simplest arrangement, a single intermediate partition stopper is disposed between the front partition stopper and a rear piston, to define first and second chambers within the cylinder in which first and second injectable materials can be respectively filled. An outer periphery of the intermediate partition stopper is provided with a plurality of circular lips between which at least one peripheral groove is defined. One of the first and second chambers is communicated with peripheral groove or grooves of the intermediate partition stopper by small passages to allow the first medicine, which is in liquid form, to enter and fill the groove or grooves and exclude air and bacteria therefrom. A transfer passage or passages are arranged in the wall of the cylinder to allow the first and second medicines to mix as the partition stopper is moved forward.

<CIT> discloses instruments and methods for controllably restoring vertebral body height by controlling the geometry of fill material introduced into cancellous bone. A method of treating bone includes injecting a volume of fill material into a bone and selectively modifying a viscosity of a selected portion of the bone filler to control the direction of flow of the fill material within the bone.

<CIT> discloses a product for delivering a material to an internal body part such as bone comprising a segmented plunger having a plurality of segments, where the plurality of cylindrical segments are sized for urging a material through an access member to thereby deliver the material to predetermined location in a subject's body.

<CIT> discloses a method for treating a vertebral bone comprises providing a gaseous substance and providing a flowable and settable bone filling material.

<CIT> discloses a multi-lumen mixing device that includes a first and second lumen constructed and arranged to separately pass a first and second reagent to a mixing chamber in the device, where the mixing chamber includes a mixing feature that mixes the first and second reagents.

<CIT> discloses a drug injection device which expels air which is mixed with the drug to be injected.

Provided is a surgical injection device for treating a selected site of a spine, the device comprising:.

The exemplary embodiments of the surgical system and related methods of use disclosed are discussed in terms of medical devices for the treatment of musculoskeletal disorders and more particularly, in terms of a surgical system and a method for treating a spine. spine (the methods are also described herein to aid understanding the invention. These methods do not form part of the claimed invention).

In some embodiments, the surgical system includes a surgical injection device, such as, for example, a syringe. The surgical injection device includes a selected amount of an agent, such as, for example, bone graft material and an amount of a evacuator, such as, for example, a flowable backfill material. The backfill material is configured to facilitate complete evacuation of the bone graft material from the syringe. In some embodiments, the syringe is configured for attachment with a cannula. The syringe, or barrel, is configured for attachment with a lumen, such as, for example, a tube. In some embodiments, the backfill material is packed behind the bone graft material in a series configuration with the syringe. In some embodiments, the backfill material is configured to facilitate filling of a lumen with bone graft material and facilitates full evacuation of the bone fill material from the lumen into a surgical site and/or an implant.

In some embodiments, the surgical injection device is configured to facilitate a surgical procedure and enable a surgeon to reliably place discrete amounts of bone graft material into a surgical site and/or an implant. In some embodiments, the surgical injection device provides a higher level of certainty to the surgeon as to an amount of bone graft material being injected with a surgical site. In some embodiments, the surgical injection device is configured to reduce waste of the bone graft material that remains in the syringe. In some embodiments, the agent may include allograft material.

In some embodiments, the surgical injection device includes dual chambers, one for the backfill material and the other for the bone graft material. In some embodiments, the dual chamber facilitates apportioning a certain amount for one area, then using backfill material to inject it, then apportioning a second amount for a second area and using the backfill material to eject it. In some embodiments, the surgical injection device includes one-way valves configured to prevent one chamber injecting material into another chamber and directs the bone graft material into the lumen. In some embodiments, the surgical injection device is configured for mixing the bone graft material for a portion of the injection and not mixing the bone graft material for another part of the injection.

In some embodiments, the surgical injection device is utilized for filling a void of a spinal implant, such as, for example, an interbody device. In some embodiments, the surgical injection device is utilized for filling bone cavities such as gutters during a posterior lateral fusion. In some embodiments, the surgical injection device is utilized for filling an interbody space surrounding and/or adjacent to an interbody spacer. In some embodiments, the surgical injection device may include alternating layers of backfill material and bone graft material. In some embodiments, the surgical injection device may include varying textures or types of bone graft material layered various types of backfill material. In some embodiments, the type of bone graft material is selected based on the surgical procedure and injected as needed, such as, for example, chunky bone graft material, then smooth bone graft material, then backfill material. In some embodiments, the injection process is repeated as necessary, such as, for example, for filling the gutters.

In some embodiments, the backfill material may include, such as, for example, glycerol, water, saline, oil or any polysaccharide; and/or material that is flowable and biocompatible. In some embodiments, the backfill material may include, such as, for example, cement to render the surgical injection device to be a single use or disposable device. In some embodiments, the backfill or bone graft material may include, or be formed in such a way to comprise solid chunks of fine, lubricious or smooth/ball-like material that, when injected, flow similar to a liquid.

In some embodiments, the bone graft material may include, such as, for example, autograft, allograft, MASTERGRAFT®, collagen, various sized beads or geometry that could approximate a flowing mechanism when injected. In some embodiments, a viscosity of the bone graft material and a viscosity of the backfill material may be equal.

In some disclosures, the backfill material is used to bulk up the bone graft material, such as with dual syringes. For example, the bone graft material may be too strong for a certain application, such as when using BMP in the cervical spine, and so the bone graft material can be diluted using a small amount or a large amount of the backfill material. The backfill material is therefore used for driving the bone graft into the surgical site and for reducing the potency of the bone graft.

In some embodiments, the bone graft material and the backfill material are visually similar where no difference in the materials can be discerned, or the materials are made to be visually different. One benefit is to ensure that the full amount of bone graft material or backfill material is fully injected before performing the next portion of the procedure.

In some embodiments, the bone graft material that can be placed in the surgical injection device can be demineralized bone material (e.g., fibers, chips, powder, or a combination thereof). In some embodiments, the demineralized bone fibers can be elongated and have an aspect ratio of at least from about <NUM>:<NUM> to about at least about <NUM>:<NUM>. In some embodiments, the elongated demineralized bone fibers are oriented along an axis of the device, such as, along the full length of the tube of the device. The elongated bone fibers can be obtained by any one of several methods, for example, by milling or shaving the surface of an entire bone or relatively large section of bone.

In other embodiments, the length of the fibers can be at least about <NUM> and have an average width from about <NUM> to about <NUM>. In various embodiments, the average length of the elongated fibers can be from about <NUM> to about <NUM> and the average width from about <NUM> to about <NUM>. In other embodiments, the elongated fibers can have an average length be from about <NUM> to about <NUM> and an average width from about <NUM> to about <NUM>.

In yet other embodiments, the diameter or average width of the elongated fibers is, for example, not more than about <NUM>, not more than <NUM> or not more than about <NUM>. In still other embodiments, the diameter or average width of the fibers can be from about <NUM> to about <NUM> or from about <NUM> to about <NUM>.

In another embodiment, the aspect ratio of the fibers can be from about <NUM>:<NUM> to about <NUM>:<NUM>, from about <NUM>:<NUM> to about <NUM>:<NUM>, from about <NUM>:<NUM> to about <NUM>:<NUM>, from about <NUM>:<NUM> to about <NUM>:<NUM>; or from about <NUM>:<NUM> to about <NUM>:<NUM>. Fibers according to this disclosure can advantageously have an aspect ratio from about <NUM>:<NUM> to about <NUM>:<NUM>, from about <NUM>:<NUM> to about <NUM>:<NUM>, from about <NUM>:<NUM> to about <NUM>:<NUM>, from about <NUM>:<NUM> to about <NUM>:<NUM>, from about <NUM>:<NUM> to about <NUM>:<NUM>, from about <NUM>:<NUM> to about <NUM>:<NUM>, from about <NUM>:<NUM> to about <NUM>:<NUM>, or from about <NUM>:<NUM> to about <NUM>:<NUM>.

In some embodiments, the bone chips can be used and they can be combined with bone fibers, where the chips to fibers ratio is about <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM> and/or <NUM>:<NUM>. In various embodiments, a surface demineralized bone chips to fibers ratio is about <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM> and/or <NUM>:<NUM> that can be used in the device. In some embodiments, a surface demineralized chips to fully demineralized fibers ratio is about <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM>, <NUM>:<NUM> and/or <NUM>:<NUM> that can be used in the device.

In some embodiments, a viscosity of the bone graft material and a viscosity of the backfill material may be different. In some embodiments, a viscosity of the backfill material would be less than a viscosity of the bone graft material. In some embodiments, the backfill material would be as thin as possible to reduce the resistance to injection.

In some embodiments, the surgical injection device is configured to fill a void in an interbody spacer having a volume of <NUM> cubic centimeter (cc). In some embodiments, the surgical injection device includes a lumen having a volume of <NUM> cc. In some embodiments, the surgical injection device is filled with <NUM> cc of bone graft material and <NUM> cc of backfill material such that the backfill material evacuates the entire <NUM> cc of bone graft material into the <NUM> cc void of the interbody spacer. The volumes stated herein are for reference only, and any volume that is appropriate in relation to the size of the devices being used and filled can be applied.

In some non-claimed disclosures, the surgical injection device includes a dual syringe device including one syringe to dispense a specific amount of bone graft material and a second syringe configured to dispense a specific amount of backfill material. In some non-claimed disclosures, the bone graft material syringe is activated to fill a void. In some non-claimed disclosures, a filling tube is attached with the dual syringe device. In some non-claimed disclosures, the bone graft material is configured to fill the filling tube. In some non-claimed disclosures, a positive pressure is applied to the backfill material syringe to resist and/or prevent bone graft material from entering into the backfill material syringe. In some non-claimed disclosures, the dual syringe device includes a one-way valve to resist and/or prevent one material from entering into the syringe of the other material.

In some non-claimed disclosures, the backfill material syringe is activated to evacuate the bone graft material from the filling tube into the implant. In some non-claimed disclosures, the bone graft material syringe can be activated again to fill a second void. In some non-claimed disclosures, the bone graft material syringe and the backfill material syringe can be simultaneously activated. In one non-claimed disclosure, the backfill syringe is filled with radiopaque material such that at certain intervals, the surgeon can see how much bone graft material has been injected. In one embodiment, the surgeon injects <NUM>. 1cc of the radiopaque marker material in between each 1cc apportioning of bone graft material such that as the device fills, each radiopaque marker layer indicates the amount of bone graft material that has entered the interbody device. In some non-claimed disclosures, the surgical injection device may include more than two syringes to provide various bone graft materials having different material properties. In some embodiments, the system may comprise <NUM> or more syringes.

In some embodiments, the surgical injection device includes a tube prepackaged with bone graft material. In some embodiments, the tube is configured for connection with a pressure applying device, such as, for example, a syringe to evacuate the bone graft material from the tube. In some embodiments, the bone graft material is enclosed within the tube by a cap at one or both ends. In some embodiments, the tube includes a stopper. In some embodiments, the tube is attachable with a luer lock connector. In some embodiments, the tube includes an end configured for connection with an irrigation instrument.

In some embodiments, a method for utilizing the prepackaged tube includes the step of removing the caps from one or both ends. In some embodiments, a method for utilizing the prepackaged tube includes attaching the tube to an implant (these methods do not form part of the claimed invention).

In some embodiments, the surgical injection device includes plugs configured to be internal or substantially internal within the tube. In some embodiments, the plugs are configured for implantation with the bone graft material, eliminating the need to remove the plugs prior to applying the bone graft material.

In some embodiments, one or all of the components of the surgical system are disposable, peel-pack, pre-packed sterile devices that can be used with an implant. One or all of the components of the surgical system may be reusable. The surgical system may be configured as a kit with multiple sized and configured components.

In some embodiments, the present disclosure may be employed to treat spinal disorders such as, for example, degenerative disc disease, disc herniation, osteoporosis, spondylolisthesis, stenosis, scoliosis and other curvature abnormalities, kyphosis, tumor and fractures. In some embodiments, the present disclosure may be employed with other osteal and bone related applications, including those associated with diagnostics and therapeutics. In some embodiments, the disclosed surgical system and methods (these methods do not form part of the claimed invention). may be alternatively employed in a surgical treatment with a patient in a prone or supine position, and/or employ various surgical approaches to the spine, including anterior, posterior, posterior mid-line, direct lateral, postero-lateral, and/or antero-lateral approaches, and in other body regions. The present disclosure may also be alternatively employed with procedures for treating the lumbar, cervical, thoracic and pelvic regions of a spinal column. The system and methods (these methods do not form part of the claimed invention). of the present disclosure may also be used on animals, bone models and other non-living substrates, such as, for example, in training, testing and demonstration.

The present disclosure may be understood more readily by reference to the following detailed description of the disclosure taken in connection with the accompanying drawing figures, which form a part of this disclosure. It is to be understood that this disclosure is not limited to the specific devices, methods, conditions or parameters described and/or shown herein, and that the terminology used herein is for the purpose of describing particular embodiments by way of example only and is not intended to be limiting of the claimed disclosure. In some embodiments, as used in the specification and including the appended claims, the singular forms "a," "an," and "the" include the plural, and reference to a particular numerical value includes at least that particular value, unless the context clearly dictates otherwise. Ranges may be expressed herein as from "about" or "approximately" one particular value and/or to "about" or "approximately" another particular value. Similarly, when values are expressed as approximations, by use of the antecedent "about," it will be understood that the particular value forms another embodiment. It is also understood that all spatial references, such as, for example, horizontal, vertical, top, upper, lower, bottom, left and right, are for illustrative purposes only and can be varied within the scope of the disclosure. For example, the references "upper" and "lower" are relative and used only in the context to the other, and are not necessarily "superior" and "inferior".

Methods of treatment are not part of the invention. However, the claimed device is suitable for treating a selected site of a spine. As used in the specification and including the appended claims, "treating" or "treatment" of a disease or condition refers to performing a procedure that may include administering one or more drugs to a patient (human, normal or otherwise, or other mammal), in an effort to alleviate signs or symptoms of the disease or condition. Alleviation can occur prior to signs or symptoms of the disease or condition appearing, as well as after their appearance. Thus, treating or treatment includes preventing or prevention of disease or undesirable condition (e.g., preventing the disease from occurring in a patient, who may be predisposed to the disease but has not yet been diagnosed as having it). In addition, treating or treatment does not require complete alleviation of signs or symptoms, does not require a cure, and specifically includes procedures that have only a marginal effect on the patient. Treatment can include inhibiting the disease, e.g., arresting its development, or relieving the disease, e.g., causing regression of the disease. For example, treatment can include reducing acute or chronic inflammation; alleviating pain and mitigating and inducing re-growth of new ligament, bone and other tissues; as an adjunct in surgery; and/or any repair procedure. Also, as used in the specification and including the appended claims, the term "tissue" includes soft tissue, ligaments, tendons, cartilage and/or bone unless specifically referred to otherwise.

The following discussion includes a description of a surgical system and related methods of employing the surgical system in accordance with the principles of the present disclosure. Alternate embodiments are also disclosed. Reference is made in detail to the exemplary embodiments of the present disclosure, which are illustrated in the accompanying figures. Turning to <FIG>, there are illustrated components of a surgical system <NUM> including a surgical injection device <NUM>.

The components of surgical system <NUM> can be fabricated from biologically acceptable materials suitable for medical applications, including metals, synthetic polymers, ceramics and/or their composites. For example, the components of surgical system <NUM>, individually or collectively, can be fabricated from materials such as stainless steel alloys, commercially pure titanium, titanium alloys, Grade <NUM> titanium, super-elastic titanium alloys, cobalt-chrome alloys, superelastic metallic alloys (e.g., Nitinol, super elasto-plastic metals, such as GUM METAL®), ceramics and composites thereof such as calcium phosphate (e.g., SKELITE™), thermoplastics such as polyaryletherketone (PAEK) including polyetheretherketone (PEEK), polyetherketoneketone (PEKK) and polyetherketone (PEK), carbon-PEEK composites, PEEK-BaSO<NUM> polymeric rubbers, polyethylene terephthalate (PET), fabric, silicone, polyurethane, silicone-polyurethane copolymers, polymeric rubbers, polyolefin rubbers, hydrogels, semi-rigid and rigid materials, elastomers, rubbers, thermoplastic elastomers, thermoset elastomers, elastomeric composites, rigid polymers including polyphenylene, polyamide, polyimide, polyetherimide, polyethylene, epoxy, partially resorbable materials, such as, for example, composites of metals and calcium-based ceramics, composites of PEEK and calcium based ceramics, composites of PEEK with resorbable polymers, totally resorbable materials, such as, for example, calcium based ceramics such as calcium phosphate, tri-calcium phosphate (TCP), calcium sulfate, or other resorbable polymers such as polylactide, polyglycolide, polytyrosine carbonate, polycaroplaetohe and their combinations.

The components of surgical system <NUM> including surgical injection device <NUM> can be employed, for example, with percutaneous surgical implantation, minimally invasive surgery, mini-open and open surgical techniques to prepare a surgical site including tissue in connection with a surgical procedure, introduction of surgical instrumentation and/or delivery and introduction of one or more biomaterials and/or an implant, such as, for example, spinal implants, rods, fasteners, connectors, plates, an intervertebral implant, interbody devices and arthroplasty devices at a surgical site within a body of a patient, for example, a section of a spine. In some embodiments, surgical system <NUM> may be employed with surgical procedures, such as, for example, decompression, corpectomy and discectomy, which can include fusion and/or fixation treatments that employ implants.

Surgical injection device <NUM> includes a plurality of tubular elements, such as, , a syringe barrel <NUM> and tubing <NUM> that define a passageway P. An evacuator, such as, a flowable backfill material <NUM> is engageable with a selected volume V of an agent, such as, bone graft material <NUM> within passageway P to entirely expel selected volume V of bone graft <NUM> from passageway P to a void of a selected site, as described herein. In some embodiments, surgical injection device <NUM> can include a single tubular element, or a plurality of tubular elements that are integrally connected or monolithically formed.

In some embodiments, bone graft <NUM> is configured for disposal into barrel <NUM> in a dry state. In some embodiments, surgical injection device <NUM> is configured for withdrawing blood or liquid via suction or vacuum from a selected site (e.g., disc space) to hydrate dry bone graft <NUM>. In some embodiments, after bone graft <NUM> is hydrated, it is injected into the selected site.

In some embodiments, bone graft <NUM> can be withdrawn from a selected site. In some embodiments, when bone graft <NUM> is injected into the wrong site, or if bone graft <NUM> has been injected into a site due to an emergency, surgical injection device <NUM> is configured to withdraw bone graft <NUM> from the site via suction or vacuum.

Barrel <NUM> extends between a proximal end <NUM> and a distal end <NUM>. End <NUM> defines an opening <NUM> configured for disposal of an actuator, such as, a plunger <NUM>, as described herein. End <NUM> defines an opening <NUM> and is configured for connection with tubing <NUM>, as described herein. In some embodiments, end <NUM> includes a tip having a taper, nozzle, valve and/or luer lock connection for connecting with tubing <NUM>. In some embodiments, end <NUM> includes a pressure fit, friction fit or threaded connection for connecting with tubing <NUM>. In some embodiments, end <NUM> is integrally connected or monolithically formed with tubing <NUM>.

Barrel <NUM> defines a longitudinal axis X1, as shown in <FIG>. In some embodiments, barrel <NUM> may have cross section configurations, such as, for example, oval, cylindrical, triangular, square, polygonal, irregular, uniform, non-uniform, offset, staggered, undulating, arcuate, variable and/or tapered. In some embodiments, a wall of barrel <NUM> can be flexible, elastic, semi-rigid or rigid.

Barrel <NUM> includes a surface <NUM>. Surface <NUM> defines a cavity, such as, for example, a passageway <NUM>. Passageway <NUM> defines a portion of passageway P, as described herein. Passageway <NUM> extends along axis X1 between ends <NUM>, <NUM>. Passageway <NUM> is configured for disposal of bone graft <NUM> and backfill <NUM>, as described herein. In some embodiments, passageway <NUM> may have cross section configurations, such as, for example, oval, cylindrical, triangular, square, polygonal, irregular, uniform, non-uniform, offset, staggered, undulating, arcuate, variable and/or tapered.

In some embodiments, barrel <NUM> includes a visual indicia, such as, gradations on an outer surface configured to provide a visual indication of the amount of material injected. In some embodiments, a portion or the entire barrel <NUM> is transparent to provide a visual indication of the amount of material that remains in barrel <NUM>.

Tubing <NUM> is configured for attachment with a tip of barrel <NUM> adjacent opening <NUM>. Tubing <NUM> extends between an end <NUM> and an end <NUM>. End <NUM> includes a surface <NUM>. Surface <NUM> is connected with the tip of barrel <NUM> in various configurations, such as, for example, luer lock connection, friction fit, pressure fit, locking protrusion/recess, locking keyway and/or adhesive. End <NUM> is configured for disposal adjacent a void of the selected site, as described herein, as bone graft <NUM> is entirely expelled from passageway P.

Tubing <NUM> includes a surface <NUM> that defines a cavity, such as, for example, a passageway <NUM>. Tubing <NUM> is attached with the tip of barrel <NUM> adjacent opening <NUM> to connect passageway <NUM> with passageway <NUM> to form passageway P. Passageway <NUM> is configured for passage of bone graft <NUM> and backfill <NUM> such that selected volume V of bone graft <NUM> is entirely expelled from passageway P to the void of the selected site, as described herein. In some embodiments, passageway <NUM> may have cross section configurations, such as, for example, oval, cylindrical, triangular, square, polygonal, irregular, uniform, non-uniform, offset, staggered, undulating, arcuate, variable and/or tapered. It will be understood that the tubing <NUM> can be any length depending on the surgical procedure.

In some embodiments, tubing <NUM> includes a visual indicia, such as, gradations on an outer surface configured to provide a visual indication of the amount of material injected. In some embodiments, a portion or the entire tubing <NUM> is transparent to provide a visual indication of the amount of material that remains in tubing <NUM>.

In some embodiments, radiopaque markers are positioned on the tip and tubing <NUM> is made from a radiolucent material. In some embodiments, the tube comprises a steering member that allows the tip to be steerable so that the angle of surface <NUM> can be changed and the magnitude. In some embodiments, the steerable tip utilizes similar technology as a steerable catheter (e.g., multiple lumens, with one being used for a wire to pull the tip). In some embodiments, end of tubing <NUM> can be closed or have an opening and the surface of tubing can have one or a plurality of openings or fenestrations for dispensing graft material and/or fluid. In some embodiments, these openings can be disposed at an angle and/or orientation for dispensing the graft material and/or fluid to the desired site or sites. In some embodiments, the plurality of fenestrations can also be oriented along the tube to give a line of dispensing, rather than a point of dispensing. In some embodiments, the plurality of fenestrations can be approximated by a single long opening.

In some embodiments, the surface of tubing <NUM> can have one or a plurality of openings for dispensing graft material and/or fluid and the device can include a handle for orienting the openings. The handle can be rotated, translated or pivoted to the proper orientation for delivery of the graft material and/or fluid.

Selected volume V of bone graft <NUM> is configured to flow through passageway P into a selected site. In some embodiments, bone graft <NUM> includes a viscosity configured to reduce resistance with surface <NUM> and facilitate flow within passageway P. In some embodiments, bone graft <NUM> includes a lubricating material. In some embodiments, bone graft <NUM> may include, such as, for example, bone material including autograft, allograft, xenograft, MASTERGRAFT®, collagen or transgenic cortical and/or corticocancellous bone, and tissue growth or differentiation factors, partially resorbable materials, such as, for example, composites of metals and calcium-based ceramics, composites of PEEK and calcium based ceramics, composites of PEEK with resorbable polymers, totally resorbable materials, such as, for example, calcium based ceramics such as calcium phosphate, TCP, HA-TCP, calcium sulfate, or other resorbable polymers such as polylactide, polyglycolide, polytyrosine carbonate, polycaprolactone and their combinations.

In some embodiments, bone graft <NUM> comprises demineralized bone material. The demineralized bone material can be comprise demineralized bone, powder, chips, triangular prisms, spheres, cubes, cylinders, shards, fibers or other shapes having irregular or random geometries. These can include, for example, "substantially demineralized," "partially demineralized," or "fully demineralized" cortical and cancellous bone. These also include surface demineralization, where the surface of the bone construct is substantially demineralized, partially demineralized, or fully demineralized, yet the body of the bone construct is fully mineralized.

In some embodiments, bone graft <NUM> comprises at least one growth factor. These growth factors include osteoinductive agents (e.g., agents that cause new bone growth in an area where there was none) and/or osteoconductive agents (e.g., agents that cause in growth of cells into and/or through the allograft). Osteoinductive agents can be polypeptides or polynucleotides compositions. Polynucleotide compositions of the osteoinductive agents include, but are not limited to, isolated Bone Morphogenetic Protein (BMP), Vascular Endothelial Growth Factor (VEGF), Connective Tissue Growth Factor (CTGF), Osteoprotegerin, Growth Differentiation Factors (GDFs), Cartilage Derived Morphogenic Proteins (CDMPs), Lim Mineralization Proteins (LMPs), Platelet derived growth factor, (PDGF or rhPDGF), Insulin-like growth factor (IGF) or Transforming Growth Factor beta (TGF-beta) polynucleotides. Polynucleotide compositions of the osteoinductive agents include, but are not limited to, gene therapy vectors harboring polynucleotides encoding the osteoinductive polypeptide of interest. Gene therapy methods (these methods do not form part of the claimed invention) often utilize a polynucleotide which codes for the osteoinductive polypeptide operatively linked or associated to a promoter or any other genetic elements necessary for the expression of the osteoinductive polypeptide by the target tissue. Such gene therapy and delivery techniques are known in the art, (See, for example, International Publication No. <CIT>. Suitable gene therapy vectors include, but are not limited to, gene therapy vectors that do not integrate into the host genome. Alternatively, suitable gene therapy vectors include, but are not limited to, gene therapy vectors that integrate into the host genome.

In some embodiments, the polynucleotide is delivered in plasmid formulations. Plasmid DNA or RNA formulations refer to polynucleotide sequences encoding osteoinductive polypeptides that are free from any delivery vehicle that acts to assist, promote or facilitate entry into the cell, including viral sequences, viral particles, liposome formulations, lipofectin, precipitating agents or the like. Optionally, gene therapy compositions can be delivered in liposome formulations and lipofectin formulations, which can be prepared by methods well known to those skilled in the art. General methods are described, for example, in <CIT>, <CIT>, and<CIT>.

Gene therapy vectors further comprise suitable adenoviral vectors including, but not limited to for example, those described in <CIT>.

Polypeptide compositions of the isolated osteoinductive agents include, but are not limited to, isolated Bone Morphogenetic Protein (BMP), Vascular Endothelial Growth Factor (VEGF), Connective Tissue Growth Factor (CTGF), Osteoprotegerin, Growth Differentiation Factors (GDFs), Cartilage Derived Morphogenic Proteins (CDMPs), Lim Mineralization Proteins (LMPs), Platelet derived growth factor, (PDGF or rhPDGF), Insulin-like growth factor (IGF) or Transforming Growth Factor beta (TGF-beta707) polypeptides. Polypeptide compositions of the osteoinductive agents include, but are not limited to, full length proteins, fragments or variants thereof.

Variants of the isolated osteoinductive agents include, but are not limited to, polypeptide variants that are designed to increase the duration of activity of the osteoinductive agent in vivo. Embodiments of variant osteoinductive agents include, but are not limited to, full length proteins or fragments thereof that are conjugated to polyethylene glycol (PEG) moieties to increase their half-life in vivo (also known as pegylation). Methods of pegylating polypeptides are well known in the art (See, e.g., <CIT> and <CIT> as examples of methods of generating pegylated polypeptides). In some embodiments, the isolated osteoinductive agent(s) are provided as fusion proteins. In one embodiment, the osteoinductive agent(s) are available as fusion proteins with the Fc portion of human IgG. In another embodiment, the osteoinductive agent(s) are available as hetero- or homodimers or multimers. Examples of some fusion proteins include, but are not limited to, ligand fusions between mature osteoinductive polypeptides and the Fc portion of human Immunoglobulin G (IgG). Methods of making fusion proteins and constructs encoding the same are well known in the art.

In some embodiments, isolated osteoinductive agents that are included in bone graft <NUM> are sterile. In a non-limiting method (these methods do not form part of the claimed invention) sterility is readily accomplished for example by filtration through sterile filtration membranes (e.g., <NUM> micron membranes or filters). In one embodiment, the isolated osteoinductive agents include one or more members of the family of Bone Morphogenetic Proteins ("BMPs"). BMPs are a class of proteins thought to have osteoinductive or growth-promoting activities on endogenous bone tissue, or function as pro-collagen precursors. Known members of the BMP family include, but are not limited to, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM> as well as polynucleotides or polypeptides thereof, as well as mature polypeptides or polynucleotides encoding the same.

BMPs utilized as osteoinductive agents comprise one or more of BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; BMP-<NUM>; or BMP-<NUM>; as well as any combination of one or more of these BMPs, including full length BMPs or fragments thereof, or combinations thereof, either as polypeptides or polynucleotides encoding the polypeptide fragments of all of the recited BMPs. The isolated BMP osteoinductive agents may be administered as polynucleotides, polypeptides, full length protein or combinations thereof.

In another embodiment, isolated osteoinductive agents include osteoclastogenesis inhibitors to inhibit bone resorption of the bone tissue surrounding the site of implantation by osteoclasts. Osteoclast and osteoclastogenesis inhibitors include, but are not limited to, osteoprotegerin polynucleotides or polypeptides, as well as mature osteoprotegerin proteins, polypeptides or polynucleotides encoding the same. Osteoprotegerin is a member of the TNF-receptor superfamily and is an osteoblast-secreted decoy receptor that functions as a negative regulator of bone resorption. This protein specifically binds to its ligand, osteoprotegerin ligand (TNFSF11/OPGL), both of which are key extracellular regulators of osteoclast development.

Osteoclastogenesis inhibitors further include, but are not limited to, chemical compounds such as bisphosphonate, <NUM>-lipoxygenase inhibitors such as those described in <CIT> and <NUM>,<NUM>,, heterocyclic compounds such as those described in <CIT>, <NUM>,<NUM>-dioxoimidazolidine and imidazolidine derivative compounds such as those described in <CIT> and <CIT>, sulfonamide derivatives such as those described in <CIT>, or acylguanidine compounds such as those described in <CIT>.

In another embodiment, isolated osteoinductive agents include one or more members of the family of Connective Tissue Growth Factors ("CTGFs"). CTGFs are a class of proteins thought to have growth-promoting activities on connective tissues. Known members of the CTGF family include, but are not limited to, CTGF-<NUM>, CTGF-<NUM>, CTGF-<NUM> polynucleotides or polypeptides thereof, as well as mature proteins, polypeptides or polynucleotides encoding the same.

In another embodiment, isolated osteoinductive agents include one or more members of the family of Vascular Endothelial Growth Factors ("VEGFs"). VEGFs are a class of proteins thought to have growth-promoting activities on vascular tissues. Known members of the VEGF family include, but are not limited to, VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E or polynucleotides or polypeptides thereof, as well as mature VEGF-A, proteins, polypeptides or polynucleotides encoding the same.

In another embodiment, isolated osteoinductive agents include one or more members of the family of Transforming Growth Factor-beta genes ("TGF-betas"). TGF-betas are a class of proteins thought to have growth-promoting activities on a range of tissues, including connective tissues. Known members of the TGF-beta family include, but are not limited to, TGF-beta-<NUM>, TGF-beta-<NUM>, TGF-beta-<NUM>, polynucleotides or polypeptides thereof, as well as mature protein, polypeptides or polynucleotides encoding the same.

In another embodiment, isolated osteoinductive agents include one or more Growth Differentiation Factors ("GDFs"). Known GDFs include, but are not limited to, GDF-<NUM>, GDF-<NUM>, GDF-<NUM>, GDF-<NUM>, GDF-<NUM>, GDF-<NUM>, and GDF-<NUM>. For example, GDFs useful as isolated osteoinductive agents include, but are not limited to, the following GDFs: GDF-<NUM> polynucleotides or polypeptides corresponding to GenBank Accession Numbers M62302, AAA58501, and AAB94786, as well as mature GDF-<NUM> polypeptides or polynucleotides encoding the same. GDF-<NUM> polynucleotides or polypeptides corresponding to GenBank Accession Numbers BC069643, BC074921, Q9UK05, AAH69643, or AAH74921, as well as mature GDF-<NUM> polypeptides or polynucleotides encoding the same. GDF-<NUM> polynucleotides or polypeptides corresponding to GenBank Accession Numbers AF263538, BC030959, AAF91389, AAQ89234, or Q9NR23, as well as mature GDF-<NUM> polypeptides or polynucleotides encoding the same. GDF-<NUM> polynucleotides or polypeptides corresponding to GenBank Accession Numbers AB158468, AF522369, AAP97720, or Q7Z4P5, as well as mature GDF-<NUM> polypeptides or polynucleotides encoding the same. GDF-<NUM> polynucleotides or polypeptides corresponding to GenBank Accession Numbers BC028237 or AAH28237, as well as mature GDF-<NUM> polypeptides or polynucleotides encoding the same.

GDF-<NUM> polynucleotides or polypeptides corresponding to GenBank Accession Numbers AF100907, NP_005802 or <NUM>, as well as mature GDF-<NUM> polypeptides or polynucleotides encoding the same. GDF-<NUM> polynucleotides or polypeptides corresponding to GenBank Accession Numbers BC008962, BC000529, AAH00529, or NP004855, as well as mature GDF-<NUM> polypeptides or polynucleotides encoding the same.

In another embodiment, isolated osteoinductive agents include Cartilage Derived Morphogenic Protein (CDMP) and Lim Mineralization Protein (LMP) polynucleotides or polypeptides. Known CDMPs and LMPs include, but are not limited to, CDMP-<NUM>, CDMP-<NUM>, LMP-<NUM>, LMP-<NUM>, or LMP-<NUM>.

CDMPs and LMPs useful as isolated osteoinductive agents include, but are not limited to, the following CDMPs and LMPs: CDMP-<NUM> polynucleotides and polypeptides corresponding to GenBank Accession Numbers NM_000557, U13660, NP_000548 or P43026, as well as mature CDMP-<NUM> polypeptides or polynucleotides encoding the same. CDMP-<NUM> polypeptides corresponding to GenBank Accession Numbers or P55106, as well as mature CDMP-<NUM> polypeptides. LMP-<NUM> polynucleotides or polypeptides corresponding to GenBank Accession Numbers AF345904 or AAK30567, as well as mature LMP-<NUM> polypeptides or polynucleotides encoding the same. LMP-<NUM> polynucleotides or polypeptides corresponding to GenBank Accession Numbers AF345905 or AAK30568, as well as mature LMP-<NUM> polypeptides or polynucleotides encoding the same. LMP-<NUM> polynucleotides or polypeptides corresponding to GenBank Accession Numbers AF345906 or AAK30569, as well as mature LMP-<NUM> polypeptides or polynucleotides encoding the same.

In another embodiment, isolated osteoinductive agents include one or more members of any one of the families of Bone Morphogenetic Proteins (BMPs), Connective Tissue Growth Factors (CTGFs), Vascular Endothelial Growth Factors (VEGFs), Osteoprotegerin or any of the other osteoclastogenesis inhibitors, Growth Differentiation Factors (GDFs), Cartilage Derived Morphogenic Proteins (CDMPs), Lim Mineralization Proteins (LMPs), or Transforming Growth Factor-betas (TGF-betas), TP508 (an angiogenic tissue repair peptide), as well as mixtures or combinations thereof.

In another embodiment, the one or more isolated osteoinductive agents useful in bone graft <NUM> are selected from the group consisting of BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, BMP-<NUM>, or any combination thereof; CTGF-<NUM>, CTGF-<NUM>, CGTF-<NUM>, CTGF-<NUM>, or any combination thereof; VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, or any combination thereof; GDF-<NUM>, GDF-<NUM>, GDF-<NUM>, GDF-<NUM>, GDF-<NUM>, GDF-<NUM>, GDF-<NUM>, or any combination thereof; CDMP-<NUM>, CDMP-<NUM>, LMP-<NUM>, LMP-<NUM>, LMP-<NUM>, and or combination thereof; Osteoprotegerin; TGF-beta-<NUM>, TGF-beta-<NUM>, TGF-beta-<NUM>, or any combination thereof; or any combination of one or more members of these groups.

In some embodiments, a statin may be used as the growth factor. Statins include, but is not limited to, atorvastatin, simvastatin, pravastatin, cerivastatin, mevastatin (see <CIT>, velostatin (also called synvinolin; see <CIT> and <NUM>,<NUM>, fluvastatin, lovastatin, rosuvastatin and fluindostatin (Sandoz XU-<NUM>-<NUM>), dalvastain (<CIT> eptastatin, pitavastatin, or pharmaceutically acceptable salts thereof or a combination thereof. In various embodiments, the statin may comprise mixtures of (+)R and (-)-S enantiomers of the statin. In various embodiments, the statin may comprise a <NUM>:<NUM> racemic mixture of the statin.

The growth factor may contain inactive materials such as buffering agents and pH adjusting agents such as potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium acetate, sodium borate, sodium bicarbonate, sodium carbonate, sodium hydroxide or sodium phosphate; degradation/release modifiers; drug release adjusting agents; emulsifiers; preservatives such as benzalkonium chloride, chlorobutanol, phenylmercuric acetate and phenylmercuric nitrate, sodium bisulfate, sodium bisulfite, sodium thiosulfate, thimerosal, methylparaben, polyvinyl alcohol and phenylethyl alcohol; solubility adjusting agents; stabilizers; and/or cohesion modifiers. In some embodiments, the growth factor may comprise sterile and/or preservative free material.

These above inactive ingredients may have multi-functional purposes including the carrying, stabilizing and controlling the release of the growth factor and/or other therapeutic agent(s). The sustained release process, for example, may be by a solution-diffusion mechanism or it may be governed by an erosion-sustained process.

In some embodiments, the growth factor is supplied in an aqueous buffered solution. Exemplary aqueous buffered solutions include, but are not limited to, TE, HEPES (<NUM>-[<NUM>-(<NUM>-hydroxyethyl)-<NUM>-piperazinyl]ethanesulfonic acid), MES (<NUM>-morpholinoethanesulfonic acid), sodium acetate buffer, sodium citrate buffer, sodium phosphate buffer, a Tris buffer (e.g., Tris-HCL), phosphate buffered saline (PBS), sodium phosphate, potassium phosphate, sodium chloride, potassium chloride, glycerol, calcium chloride or a combination thereof. In various embodiments, the buffer concentration can be from about <NUM> to <NUM>.

In some embodiments, the BMP-<NUM> is provided in a vehicle (including a buffer) containing sucrose, glycine, L-glutamic acid, sodium chloride, and/or polysorbate <NUM>.

In some embodiments, bone graft <NUM> comprises therapeutic agents. Exemplary therapeutic agents include but are not limited to IL-<NUM> inhibitors, such Kineret® (anakinra), which is a recombinant, non-glycosylated form of the human inerleukin-<NUM> receptor antagonist (IL-<NUM> Ra), or AMG <NUM>, which is a monoclonal antibody that blocks the action of IL-<NUM>. Therapeutic agents also include excitatory amino acids such as glutamate and aspartate, antagonists or inhibitors of glutamate binding to NMDA receptors, AMPA receptors, and/or kainate receptors. Interleukin-<NUM> receptor antagonists, thalidomide (a TNF-α release inhibitor), thalidomide analogues (which reduce TNF-α production by macrophages), quinapril (an inhibitor of angiotensin II, which upregulates TNF-α), interferons such as IL-<NUM> (which modulate TNF-α receptor expression), and aurin-tricarboxylic acid (which inhibits TNF-α), may also be useful as therapeutic agents for reducing inflammation. It is further contemplated that where desirable a pegylated form of the above may be used. Examples of still other therapeutic agents include NF kappa B inhibitors such as antioxidants, such as dilhiocarbamate, and other compounds, such as, for example, sulfasalazine.

Examples of therapeutic agents suitable for use also include, but are not limited to an anti-inflammatory agent, analgesic agent, or osteoinductive growth factor or a combination thereof. Anti-inflammatory agents include, but are not limited to, apazone, celecoxib, diclofenac, diflunisal, enolic acids (piroxicam, meloxicam), etodolac, fenamates (mefenamic acid, meclofenamic acid), gold, ibuprofen, indomethacin, ketoprofen, ketorolac, nabumetone, naproxen, nimesulide, salicylates, sulfasalazine [<NUM>-hydroxy-<NUM>-[-<NUM>-[C2-pyridinylamino)sulfonyl]azo]benzoic acid, sulindac, tepoxalin, and tolmetin; as well as antioxidants, such as dithiocarbamate, steroids, such as cortisol, cortisone, hydrocortisone, fludrocortisone, prednisone, prednisolone, methylprednisolone, triamcinolone, betamethasone, dexamethasone, beclomethasone, fluticasone or a combination thereof.

Suitable analgesic agents include, but are not limited to, acetaminophen, bupivicaine, fluocinolone, lidocaine, opioid analgesics such as buprenorphine, butorphanol, dextromoramide, dezocine, dextropropoxyphene, diamorphine, fentanyl, alfentanil, sufentanil, hydrocodone, hydromorphone, ketobemidone, levomethadyl, mepiridine, methadone, morphine, nalbuphine, opium, oxycodone, papaveretum, pentazocine, pethidine, phenoperidine, piritramide, dextropropoxyphene, remifentanil, tilidine, tramadol, codeine, dihydrocodeine, meptazinol, dezocine, eptazocine, flupirtine, amitriptyline, carbamazepine, gabapentin, pregabalin, or a combination thereof.

In some embodiments, bone graft <NUM> includes at least one antimicrobial. Antimicrobial includes, for example, antibiotics, antifungal, antiviral agents or the like. Antimicrobial agents to treat infection include by way of example and not limitation, antiseptic agents, antibacterial agents; quinolones and in particular fluoroquinolones (e.g., norfloxacin, ciprofloxacin, lomefloxacin, ofloxacin, etc.), aminoglycosides (e.g., gentamicin, tobramycin, etc.), glycopeptides (e.g., vancomycin, etc.), lincosamides (e.g., clindamycin), cephalosporins (e.g., first, second, third generation) and related beta-lactams, macrolides (e.g., azithromycin, erythromycin, etc.), nitroimidazoles (e.g., metronidazole), penicillins, polymyxins, tetracyclines, or combinations thereof.

Some exemplary antimicrobial agents include, by way of illustration and not limitation, acedapsone; acetosulfone sodium; alamecin; alexidine; amdinocillin; amdinocillin pivoxil; amicycline; amifloxacin; amifloxacin mesylate; amikacin; amikacin sulfate; aminosalicylic acid; aminosalicylate sodium; amoxicillin; amphomycin; ampicillin; ampicillin sodium; apalcillin sodium; apramycin; aspartocin; astromicin sulfate; avilamycin; avoparcin; azithromycin; azlocillin; azlocillin sodium; bacampicillin hydrochloride; bacitracin; bacitracin methylene disalicylate; bacitracin zinc; bambermycins; benzoylpas calcium; berythromycin; betamicin sulfate; biapenem; biniramycin; biphenamine hydrochloride; bispyrithione magsulfex; butikacin; butirosin sulfate; capreomycin sulfate; carbadox; carbenicillin disodium; carbenicillin indanyl sodium; carbenicillin phenyl sodium; carbenicillin potassium; carumonam sodium; cefaclor; cefadroxil; cefamandole; cefamandole nafate; cefamandole sodium; cefaparole; cefatrizine; cefazaflur sodium; cefazolin; cefazolin sodium; cefbuperazone; cefdinir; cefepime; cefepime hydrochloride; cefetecol; cefixime; cefmenoxime hydrochloride; cefmetazole; cefmetazole sodium; cefonicid monosodium; cefonicid sodium; cefoperazone sodium; ceforanide; cefotaxime sodium; cefotetan; cefotetan disodium; cefotiam hydrochloride; cefoxitin; cefoxitin sodium; cefpimizole; cefpimizole sodium; cefpiramide; cefpiramide sodium; cefpirome sulfate; cefpodoxime proxetil; cefprozil; cefroxadine; cefsulodin sodium; ceftazidime; ceftibuten; ceftizoxime sodium; ceftriaxone sodium; cefuroxime; cefuroxime axetil; cefuroxime pivoxetil; cefuroxime sodium; cephacetrile sodium; cephalexin; cephalexin hydrochloride; cephaloglycin; cephaloridine; cephalothin sodium; cephapirin sodium; cephradine; cetocycline hydrochloride; cetophenicol; chloramphenicol; chloramphenicol palmitate; chloramphenicol pantothenate complex; chloramphenicol sodium succinate; chlorhexidine phosphanilate; chloroxylenol; chlortetracycline bisulfate; chlortetracycline hydrochloride; cinoxacin; ciprofloxacin; ciprofloxacin hydrochloride; cirolemycin; clarithromycin; clinafloxacin hydrochloride; clindamycin; clindamycin hydrochloride; clindamycin palmitate hydrochloride; clindamycin phosphate; clofazimine; cloxacillin benzathine; cloxacillin sodium; chlorhexidine, cloxyquin; colistimethate sodium; colistin sulfate; coumermycin; coumermycin sodium; cyclacillin; cycloserine; dalfopristin; dapsone; daptomycin; demeclocycline; demeclocycline hydrochloride; demecycline; denofungin; diaveridine; dicloxacillin; dicloxacillin sodium; dihydrostreptomycin sulfate; dipyrithione; dirithromycin; doxycycline; doxycycline calcium; doxycycline fosfatex; doxycycline hyclate; droxacin sodium; enoxacin; epicillin; epitetracycline hydrochloride; erythromycin; erythromycin acistrate; erythromycin estolate; erythromycin ethylsuccinate; erythromycin gluceptate; erythromycin lactobionate; erythromycin propionate; erythromycin stearate; ethambutol hydrochloride; ethionamide; fleroxacin; floxacillin; fludalanine; flumequine; fosfomycin; fosfomycin tromethamine; fumoxicillin; furazolium chloride; furazolium tartrate; fusidate sodium; fusidic acid; ganciclovir and ganciclovir sodium; gentamicin sulfate; gloximonam; gramicidin; haloprogin; hetacillin; hetacillin potassium; hexedine; ibafloxacin; imipenem; isoconazole; isepamicin; isoniazid; josamycin; kanamycin sulfate; kitasamycin; levofuraltadone; levopropylcillin potassium; lexithromycin; lincomycin; lincomycin hydrochloride; lomefloxacin; lomefloxacin hydrochloride; lomefloxacin mesylate; loracarbef; mafenide; meclocycline; meclocycline sulfosalicylate; megalomicin potassium phosphate; mequidox; meropenem; methacycline; methacycline hydrochloride; methenamine; methenamine hippurate; methenamine mandelate; methicillin sodium; metioprim; metronidazole hydrochloride; metronidazole phosphate; mezlocillin; mezlocillin sodium; minocycline; minocycline hydrochloride; mirincamycin hydrochloride; monensin; monensin sodiumr; nafcillin sodium; nalidixate sodium; nalidixic acid; natainycin; nebramycin; neomycin palmitate; neomycin sulfate; neomycin undecylenate; netilmicin sulfate; neutramycin; nifuiradene; nifuraldezone; nifuratel; nifuratrone; nifurdazil; nifurimide; nifiupirinol; nifurquinazol; nifurthiazole; nitrocycline; nitrofurantoin; nitromide; norfloxacin; novobiocin sodium; ofloxacin; onnetoprim; oxacillin and oxacillin sodium; oximonam; oximonam sodium; oxolinic acid; oxytetracycline; oxytetracycline calcium; oxytetracycline hydrochloride; paldimycin; parachlorophenol; paulomycin; pefloxacin; pefloxacin mesylate; penamecillin; penicillins such as penicillin g benzathine, penicillin g potassium, penicillin g procaine, penicillin g sodium, penicillin v, penicillin v benzathine, penicillin v hydrabamine, and penicillin v potassium; pentizidone sodium; phenyl aminosalicylate; piperacillin sodium; pirbenicillin sodium; piridicillin sodium; pirlimycin hydrochloride; pivampicillin hydrochloride; pivampicillin pamoate; pivampicillin probenate; polymyxin b sulfate; porfiromycin; propikacin; pyrazinamide; pyrithione zinc; quindecamine acetate; quinupristin; racephenicol; ramoplanin; ranimycin; relomycin; repromicin; rifabutin; rifametane; rifamexil; rifamide; rifampin; rifapentine; rifaximin; rolitetracycline; rolitetracycline nitrate; rosaramicin; rosaramicin butyrate; rosaramicin propionate; rosaramicin sodium phosphate; rosaramicin stearate; rosoxacin; roxarsone; roxithromycin; sancycline; sanfetrinem sodium; sarmoxicillin; sarpicillin; scopafungin; sisomicin; sisomicin sulfate; sparfloxacin; spectinomycin hydrochloride; spiramycin; stallimycin hydrochloride; steffimycin; streptomycin sulfate; streptonicozid; sulfabenz; sulfabenzamide; sulfacetamide; sulfacetamide sodium; sulfacytine; sulfadiazine; sulfadiazine sodium; sulfadoxine; sulfalene; sulfamerazine; sulfameter; sulfamethazine; sulfamethizole; sulfamethoxazole; sulfamonomethoxine; sulfamoxole; sulfanilate zinc; sulfanitran; sulfasalazine; sulfasomizole; sulfathiazole; sulfazamet; sulfisoxazole; sulfisoxazole acetyl; sulfisboxazole diolamine; sulfomyxin; sulopenem; sultamricillin; suncillin sodium; talampicillin hydrochloride; teicoplanin; temafloxacin hydrochloride; temocillin; tetracycline; tetracycline hydrochloride; tetracycline phosphate complex; tetroxoprim; thiamphenicol; thiphencillin potassium; ticarcillin cresyl sodium; ticarcillin disodium; ticarcillin monosodium; ticlatone; tiodonium chloride; tobramycin; tobramycin sulfate; tosufloxacin; trimethoprim; trimethoprim sulfate; trisulfapyrimidines; troleandomycin; trospectomycin sulfate; tyrothricin; vancomycin; vancomycin hydrochloride; virginiamycin; zorbamycin; or combinations thereof.

Antiviral agents can include, but are not limited to, vidarabine, acyclovir, famciclovir, valacyclovir, gancyclovir, valganciclovir, nucleoside-analog reverse transcriptase inhibitors (such as AZT (zidovudine), ddl (didanosine), ddC (zalcitabine), d4T (stavudine), and 3TC (lamivudine)), nevirapine, delavirdine, protease inhibitors (such as, saquinavir, ritonavir, indinavir, and nelfinavir), ribavirin, amantadine, rimantadine, neuraminidase inhibitors (such as zanamivir and oseltamivir), pleconaril, cidofovir, foscarnet, and/or interferons.

Backfill <NUM> is configured to flow through passageway P to expel selected volume V of bone graft <NUM> into a selected site. In some embodiments, a viscosity of backfill <NUM> facilitates driving bone graft <NUM> from passageway <NUM>, through passageway <NUM> and into a selected site. In some embodiments, the viscosity of backfill <NUM> is lower than the viscosity of bone graft <NUM> to facilitate movement of bone graft <NUM> through passageway P. In some embodiments, the viscosity of bone graft <NUM> is equal to the viscosity of backfill <NUM>. In some embodiments, the evacuator may include a solid, liquid or gaseous substance, and/or include a mechanical element such as a gasket, disc, stopper or plunger.

In some embodiments, backfill <NUM> may include, such as, for example, sterile water, glycerol, saline, oil or any polysaccharide; and/or material that is flowable and biocompatible, such as, for example, blood, or blood components including plasma, platelet-rich plasma, buffy coat. In some embodiments, backfill <NUM> may include, such as, for example, cement to render surgical injection device <NUM> to be a single use device and/or disposable. In some embodiments, backfill <NUM> may include, such as, for example, solid chunks of material that, when injected, flow similar to a liquid.

Plunger <NUM> actuates movement of backfill <NUM> and bone graft <NUM> within passageway P. Plunger <NUM> extends between an end <NUM> and an end <NUM>. End <NUM> includes a handle <NUM> configured for manipulation to translate plunger <NUM> relative to the wall of barrel <NUM> within passageway <NUM>. End <NUM> includes a plunger seal <NUM> that slidably engages the wall of barrel <NUM> such that plunger <NUM> is movably disposed with opening <NUM>. Plunger seal <NUM> is configured to resist and/or prevent backfill <NUM> and/or bone graft <NUM> from exiting opening <NUM>.

Plunger seal <NUM> is configured to translate within passageway <NUM> and contact backfill <NUM>. Plunger <NUM> translates relative to barrel <NUM> between an initial orientation, as shown in <FIG>, and a fully or entirely expelled orientation, as shown in <FIG>. In the initial orientation, plunger <NUM> is disposed adjacent backfill <NUM>. Plunger <NUM> translates, in the direction shown by arrow A in <FIG>, such that plunger seal <NUM> applies a force to backfill <NUM>. The force applied by plunger seal <NUM> causes backfill <NUM> to compress bone graft <NUM>. Compression of bone graft <NUM> causes bone graft <NUM> to flow from passageway <NUM> through opening <NUM>. Further translation of plunger <NUM> causes backfill <NUM> to force bone graft <NUM> into passageway <NUM>, as shown by in <FIG>. Translation of plunger <NUM> to the entirely expelled orientation causes backfill <NUM> to flow into passageway <NUM> forcing bone graft <NUM> through passageway <NUM> to entirely expel selected volume V of bone graft <NUM> into a selected site, for example, as shown in <FIG>.

According to the invention, bone graft <NUM> is disposed in a series configuration with backfill <NUM> within passageway P such that selected volume V of bone graft <NUM> can be entirely expelled by backfill <NUM>. In some embodiments, entirely expelling the entire selective volume V of bone graft <NUM> includes particulate and/or residue of bone graft <NUM> remaining on the surfaces that define passageway P. In some embodiments, bone graft <NUM> and backfill <NUM> are disposed in layers, such as, for example, alternating layers of bone graft <NUM> and backfill <NUM> within passageway <NUM>. In some embodiments, an alternating layer configuration of bone graft <NUM> and backfill <NUM> is configured to facilitate selective filling of the selected site S with bone graft <NUM> and backfill <NUM>. In some embodiments, the surgeon adds 2cc of bone graft <NUM> at the base of at least one bone fastener, and adds <NUM> cc of backfill <NUM> to facilitate confirmation of full injection of bone graft <NUM>. In some embodiments, barrel <NUM> comprises multiple layers of 2cc of bone graft <NUM> interspersed with 1cc layers of backfill <NUM>.

In some embodiments, the selected site includes, for example, an interbody implant <NUM>. In some embodiments, interbody implant <NUM> includes a surface <NUM>. Surface <NUM> defines a void <NUM>. Void <NUM> is configured to receive the selected volume V of bone graft <NUM>. In some embodiments, the cross-section geometry of interbody implant <NUM> may have various configurations, such as, for example, cylindrical, round, oval, oblong, triangular, polygonal having planar or arcuate side portions, irregular, uniform, non-uniform, consistent, variable, horseshoe shape, U-shape or kidney bean shape.

In assembly, operation and use, surgical system <NUM>, similar to the systems described herein, includes surgical injection device <NUM> and is employed to treat an affected section of a patient body, such as, for example, vertebrae with a spinal implant, such as, for example, interbody implant <NUM>. Surgical system <NUM> may be used with surgical methods or techniques including open surgery, mini-open surgery, minimally invasive surgery and percutaneous surgical implantation, whereby vertebrae are accessed through a mini-incision, or sleeve that provides a protected passageway to a surgical site. Once access to the surgical site is obtained, a surgical treatment, similar to those described herein and for example, a spinal stabilization procedure can be performed for treating a spine disorder. In some embodiments, a diseased and/or damaged portion of the vertebrae can be removed and an intervertebral space is prepared for interbody implant <NUM>.

The components of surgical system <NUM> including surgical injection device <NUM> are employed to augment the surgical treatment. In some embodiments, surgical injection device <NUM> can introduce or deliver a selected volume V of bone graft <NUM> into interbody implant <NUM> prior, during and/or subsequent to disposal of interbody implant <NUM> with vertebrae at selected surgical site S. In some embodiments, surgical injection device <NUM> can inject selected volume V of bone graft <NUM> into interbody implant <NUM> in vivo. In some embodiments, surgical injection device <NUM> can inject selected volume V of bone graft <NUM> directly adjacent or into the vertebrae at selected surgical site S.

Surgical injection device <NUM> is provided with a selected volume V, such as, for example, <NUM> cc of bone graft <NUM>, as shown in <FIG>. Surgical injection device <NUM> is provided with a volume of backfill <NUM>, such as, for example, <NUM> cc of backfill <NUM>. End <NUM> of tubing <NUM> is disposed adjacent void <NUM> of interbody implant <NUM>. In some embodiments, void <NUM> is configured to receive <NUM> cc of bone graft <NUM>.

From the initial orientation, a force is applied to plunger <NUM> and/or plunger <NUM> is manipulated such that plunger <NUM> translates in the direction shown by arrow A in <FIG>. Plunger seal <NUM> applies a force to backfill <NUM> to compress bone graft <NUM> adjacent opening <NUM>, as described herein. Continued manipulation of plunger <NUM> causes bone graft <NUM> to flow from passageway <NUM> through opening <NUM> such that backfill <NUM> forces bone graft <NUM> into passageway <NUM>, as shown by in <FIG>. As plunger <NUM> is further manipulated, backfill <NUM> flows into passageway <NUM> forcing bone graft <NUM> through passageway <NUM> to entirely expel selected volume V of bone graft <NUM> from passageway P into void <NUM> at selected site S, as shown in <FIG>.

In some embodiments, surgical system <NUM> comprises a kit including a plurality of interbody devices, connectors, plates, bone fasteners and/or fixation elements, which may be employed with a single vertebral level or a plurality of vertebral levels. Upon completion of the procedure, the surgical instruments, assemblies and non-implanted components of surgical system <NUM> are removed and the incision is closed. The components of surgical system <NUM> can be made of radiolucent materials such as polymers. Radiomarkers may be included for identification under x- ray, fluoroscopy, CT or other imaging techniques. In some embodiments, the use of surgical navigation, microsurgical and image guided technologies may be employed to access, view and repair spinal deterioration or damage, with the aid of surgical system <NUM>.

In some embodiments, the components of surgical system <NUM> contain radiomarkers and/or radioopacity enhancing agents. In some embodiments, the radiomarkers and/or radioopacity enhancing agents enable the surgeon the ability to visualize (e.g., via c-arm radiography) the delivery of bone graft <NUM> to the site and assess the quality of fill at the intended delivery site. In some embodiments, the radiomarkers include, but are not limited to, barium, calcium phosphate, bismuth, iodine, tantalum, tungsten, and/or metal beads or particles.

In one non-claimed disclosure, as shown in <FIG>, surgical system <NUM>, similar to the systems and methods described above with regard to <FIG>, includes a surgical injection device <NUM>, similar to surgical injection device <NUM> described herein. Surgical injection device <NUM> includes a syringe barrel <NUM>, a syringe barrel <NUM> and tubing <NUM>. Barrel <NUM> extends between an end <NUM> and an end <NUM>. End <NUM> defines an opening <NUM> configured for disposal of an actuator, such as, for example, a plunger <NUM>, similar to plunger <NUM> described herein. End <NUM> defines an opening <NUM> and a tip configured for connection with tubing <NUM>, similar to that described herein. Barrel <NUM> defines a longitudinal axis X2, as shown in <FIG>.

Barrel <NUM> includes a surface <NUM>. Surface <NUM> defines a passageway <NUM>. Passageway <NUM> defines a portion of a fluid passageway P1, similar to that described herein. Passageway <NUM> extends along axis X2 between ends <NUM>, <NUM>. Passageway <NUM> is configured for disposal of a selected volume V1 of bone graft material <NUM>, similar to that described herein.

Plunger <NUM> is movably disposed with opening <NUM>. Plunger <NUM> is configured to actuate movement of bone graft <NUM> within passageway <NUM>. Plunger <NUM> includes a plunger seal <NUM> that slidably engages the wall of barrel <NUM> such that plunger <NUM> is movably disposed with opening <NUM>. Plunger seal <NUM> is configured to resist and/or prevent bone graft <NUM> from exiting opening <NUM>.

Plunger seal <NUM> is configured to translate within passageway <NUM> and contact bone graft <NUM>. Plunger <NUM> is configured to translate relative to barrel <NUM> between an initial orientation, as shown in <FIG>, and a dispensing orientation, as shown in <FIG>. In the initial orientation, plunger <NUM> is disposed adjacent bone graft <NUM>. Plunger <NUM> is configured for translation, in the direction shown by arrow B in <FIG>, such that plunger seal <NUM> applies a force to bone graft <NUM>. The force applied by plunger seal <NUM> causes bone graft <NUM> to flow from passageway <NUM> through opening <NUM> into tubing <NUM>, similar to that described herein.

Barrel <NUM> extends between an end <NUM> and an end <NUM>. End <NUM> defines an opening <NUM> configured for disposal of a plunger <NUM>, similar to plunger <NUM> described herein. End <NUM> defines an opening <NUM> and a tip configured for connection with tubing <NUM>, similar to that described herein. Barrel <NUM> defines a longitudinal axis X3, as shown in <FIG>. In some non-claimed disclosures, axis X3 is disposed parallel to axis X2. In some non-claimed disclosures, axis X3 may be disposed at alternate orientations relative to axis X2, such as, for example, transverse and/or other angular orientations, such as, acute or obtuse.

Barrel <NUM> includes a surface <NUM>. Surface <NUM> defines a passageway <NUM>. Passageway <NUM> defines a portion of fluid passageway P1. Passageway <NUM> extends along axis X3 between ends <NUM>, <NUM>. Passageway <NUM> is configured for disposal of backfill material <NUM>, similar to that described herein.

Plunger <NUM> is movably disposed with opening <NUM>. Plunger <NUM> is configured to actuate movement of bone fill <NUM> within passageway <NUM>. Plunger <NUM> includes a plunger seal <NUM> that slidably engages the wall of barrel <NUM> such that plunger <NUM> is movably disposed with opening <NUM>. Plunger seal <NUM> is configured to resist and/or prevent backfill <NUM> from exiting opening <NUM>.

Plunger seal <NUM> is configured to translate within passageway <NUM> and contact backfill <NUM>. Plunger <NUM> is configured to translate relative to barrel <NUM> between an initial orientation, as shown in <FIG> and a fully or entirely expelled orientation, as shown in <FIG>. In the initial orientation, plunger <NUM> is disposed adjacent backfill <NUM>. Plunger <NUM> is configured for translation, in the direction shown by arrow C in <FIG>, such that plunger seal <NUM> applies a force to backfill <NUM>. The force applied by plunger seal <NUM> causes backfill <NUM> to flow from passageway <NUM> through opening <NUM>. Further translation of plunger <NUM> causes backfill <NUM> to flow into tubing <NUM>, similar to that described herein.

Tubing <NUM> extends between an end <NUM> and an end <NUM>. Tubing <NUM> is configured for connection with openings <NUM>, <NUM>, as described herein. In some non-claimed disclosures, end <NUM> includes a bifurcated extension <NUM> having a part <NUM> and a part <NUM>. Part <NUM> includes a surface <NUM>. In some non-claimed disclosures, surface <NUM> is connected with the tip of barrel <NUM>, similar to that described herein. Part <NUM> includes a surface <NUM> that defines a passageway <NUM>. Part <NUM> is connected with barrel <NUM> to orient passageway <NUM> in communication with passageway <NUM>.

Part <NUM> includes a surface <NUM>. In some non-claimed disclosures, surface <NUM> is connected with the tip of barrel <NUM>, similar to that described herein. Part <NUM> includes a surface <NUM> that defines a passageway <NUM>. Part <NUM> is connected with barrel <NUM> to orient passageway <NUM> in communication with passageway <NUM>. Passageways <NUM>, <NUM> merge into a passageway <NUM>. In some non-claimed disclosures, passageways <NUM>, <NUM> merge at a juncture, such as, for example, a mixing chamber <NUM>, which may be employed to selectively combine one or more agents and backfill, as described herein.

Tubing <NUM> includes a surface <NUM>. Surface <NUM> defines passageway <NUM>. Passageway <NUM> is in communication with passageways <NUM>, <NUM> to form a portion of passageway P1. Passageway <NUM> is configured for passage of selected volume V of bone graft <NUM> and backfill <NUM>. End <NUM> is configured for engagement with selected site S1 to direct the flow of selected volume V1 of bone graft <NUM> into selected site S1, similar to that described herein.

Backfill <NUM> is configured to force bone graft <NUM> through chamber <NUM>, as shown by in <FIG>. Translation of plunger <NUM> into the fully or entirely expelled orientation causes backfill <NUM> to flow into chamber <NUM> forcing bone graft <NUM> through passageway <NUM> to entirely expel selected volume V1 of bone graft <NUM> into selected site S1, as shown in <FIG> and similar to that described herein.

In some non-claimed disclosures, barrel <NUM> is disposed in a side by side configuration with barrel <NUM>. In this configuration, selected volume V of bone graft <NUM> is injected into tubing <NUM> prior to injection of backfill <NUM> into tubing <NUM>. In some non-claimed disclosures, bone graft <NUM> and backfill <NUM> are injected into tubing <NUM> in stages to form layers, such as, for example, alternating layers of bone graft <NUM> and backfill <NUM> within selected site S1. In some non-claimed disclosures, barrel <NUM> includes a one way valve disposed adjacent end <NUM> that is configured to resist and/or prevent backflow of bone graft <NUM> into passageway <NUM>. In some non-claimed disclosures, barrel <NUM> includes a one way valve disposed adjacent end <NUM> that is configured to resist and/or prevent backflow of backfill <NUM> into passageway <NUM>.

In some non-claimed disclosures, barrel <NUM> and barrel <NUM> are the same size. In some non-claimed disclosures, barrel <NUM> and barrel <NUM> are different sizes depending on the desired number of applications of bone graft <NUM>, volume of lumen and selected site S1.

In one non-claimed disclosure, as shown in <FIG>, surgical system <NUM>, similar to the systems and methods described herein, includes a surgical injection device <NUM>, similar to the surgical injection devices described herein. Surgical injection device <NUM> includes a tubular element, such as, for example, a tube <NUM> and a syringe barrel <NUM>, as described herein. Tube <NUM> extends between an end <NUM> and an end <NUM>. End <NUM> includes a luer lock connection <NUM>, as shown in <FIG>. In some non-claimed disclosures, luer lock <NUM> is configured to facilitate attachment of barrel <NUM> with tube <NUM>, as described herein. In some non-claimed disclosures, end <NUM> includes a flange <NUM>. Flange <NUM> is configured for engagement with barrel <NUM> to resist and/or prevent separation of barrel from tube <NUM>, as shown in <FIG>. End <NUM> defines an opening <NUM> configured for connection with a selected site S2. Tube <NUM> defines a longitudinal axis X4, as shown in <FIG>.

In some non-claimed disclosures, end <NUM> is configured for connection with a tip <NUM>, as shown in <FIG>. In some non-claimed disclosures, tip <NUM> is configured to facilitate connection with an irrigation instrument. In some non-claimed disclosures, tip <NUM> is configured to facilitate connection with an irrigation instrument. In some non-claimed disclosures, tube <NUM> is prepackaged with a selected volume V2 of bone graft <NUM>, similar to that described herein. In some non-claimed disclosures, tube <NUM> includes a cap <NUM> engageable with end <NUM> to prevent bone graft <NUM> from exiting opening <NUM>, as shown in <FIG>. In some embodiments, tube <NUM> includes a cap <NUM> engageable with end <NUM> to prevent bone graft from exiting opening <NUM>.

Tube <NUM> includes a surface <NUM>. Surface <NUM> defines a passageway <NUM>. Passageway <NUM> defines a portion of a fluid passageway P2, similar to that described herein. Passageway <NUM> extends along axis X4 between ends <NUM>, <NUM>. Passageway <NUM> is configured for disposal of a selected volume V2 of bone graft material <NUM>, similar to that described herein. Selected volume V2 of bone graft <NUM> is configured to flow through passageway P2 into selected site S2.

Barrel <NUM> includes a surface <NUM>. Surface <NUM> defines passageway <NUM>. Passageway <NUM> defines a portion of a fluid passageway P2, as described herein. Passageway <NUM> extends along axis X4. Passageway <NUM> is configured for disposal of backfill <NUM> configured for actuation by a plunger <NUM>, as described herein.

Plunger <NUM> includes a plunger seal <NUM>. Plunger seal <NUM> is configured to apply a force to backfill <NUM> causing bone graft <NUM> to be expelled from tubing <NUM>, as described herein. Plunger <NUM> is configured for translation relative to the wall of barrel <NUM> within passageway <NUM>. In some non-claimed disclosures, plunger <NUM> is configured to translate relative to barrel <NUM>, in the direction shown by arrow E in <FIG>, to engage backfill <NUM> to entirely expel selected volume V2 of bone graft <NUM> from passageway P2 into selected site S2, similar to that described herein.

In some embodiments, tube <NUM> includes a visual indicia, such as, gradations on an outer surface configured to provide a visual indication of the amount of material injected. In some non-claimed disclosures, a portion or the entire tube <NUM> is transparent to provide a visual indication of the amount of material that remains in tube <NUM>.

In some non-claimed disclosures, a surgical instrument, such as, for example, an inserter <NUM> including a cannula for disposal of surgical injection device <NUM> is employed to facilitate connection with selected site S2, as shown in <FIG>. Inserter <NUM> is configured to facilitate introduction and/or delivery of the components of surgical system <NUM> to a surgical site, as described herein, and/or engage selected site S2. In some non-claimed disclosures, inserter <NUM> may include one or more needles, trocars, sheaths and/or minimally invasive instruments. In some non-claimed disclosures, inserter <NUM> may include a cutting surface that can be extended and retracted to cut and/or sever tissue and/or components of surgical system <NUM>. In some non-claimed disclosures, inserter <NUM> may be guided via imaging guidance, as described herein. In some embodiments, inserter <NUM> includes a handle <NUM> configured to facilitate manipulation and positioning of surgical injection device <NUM>.

In one non-claimed disclosure, as shown in <FIG>, surgical system <NUM>, similar to the systems and methods described herein, includes a surgical injection device <NUM>, similar to the surgical injection devices described herein. Surgical injection device <NUM> includes a tubular element, such as, for example, a tube <NUM> and a plunger <NUM>, similar to that described herein. Tube <NUM> extends between an end <NUM> and an end <NUM>.

Tube <NUM> includes a surface <NUM>. Surface <NUM> defines a passageway <NUM>. Passageway <NUM> defines a portion of a fluid passageway P3, similar to that described herein. Passageway <NUM> extends along axis X5 between ends <NUM>, <NUM>. Passageway <NUM> is configured for disposal of a selected volume V3 of bone graft material <NUM>, similar to that described herein. Selected volume V3 of bone graft <NUM> is configured to flow through passageway P3 into selected site S3. In some non-claimed disclosures, tube <NUM> is prepackaged with a selected volume V3 of bone graft <NUM>, similar to that described herein. In some non-claimed disclosures, tube <NUM> includes a cap <NUM> engageable with end <NUM> to prevent bone graft <NUM> from exiting tube <NUM>, as shown in <FIG>.

In some non-claimed disclosures, tube <NUM> includes an evacuator, such as, for example, a stopper <NUM> that is disposed adjacent end <NUM>. In some non-claimed disclosures, stopper <NUM> includes a biocompatible material, similar to that described herein, and is configured for disposal with selected site S3. In some non-claimed disclosures, stopper <NUM> is configured to facilitate expelling the entire selected volume V3 of bone graft <NUM> from tube <NUM>, similar to that described herein.

Plunger <NUM> is engageable with tube <NUM> and translatable relative to a wall of tube <NUM> to entirely expel bone graft <NUM> from passageway P3, as described herein. Plunger <NUM> extends between an end <NUM> and an end <NUM>. End <NUM> includes a handle <NUM> configured for manipulation to translate plunger <NUM> within passageway <NUM>. Plunger <NUM> includes a plunger seal <NUM> configured to apply a force to stopper <NUM> and/or bone graft <NUM>, similar to that described herein. In some non-claimed disclosures, plunger <NUM> is configured to translate relative to tube <NUM>, as shown in <FIG>, such that plunger seal <NUM> engages stopper <NUM>, which entirely expels selected volume V3 of bone graft <NUM> from passageway P3 into selected site S3, for example, a void of an interbody implant, similar to that described herein.

In some non-claimed disclosures, tube <NUM> includes a visual indicia, such as, gradations on an outer surface configured to provide a visual indication of the amount of material injected. In some embodiments, a portion or the entire tube <NUM> is transparent to provide a visual indication of the amount of material that remains in tube <NUM>.

In some non-claimed disclosures, an inserter <NUM> including a cannula for disposal of surgical injection device <NUM> is employed to facilitate connection with selected site S3, as shown in <FIG>. In some non-claimed disclosures, inserter <NUM> includes a handle <NUM> configured to facilitate manipulation and positioning of surgical injection device <NUM>.

Claim 1:
A surgical injection device (<NUM>) for treating a selected site of a spine, the device (<NUM>, <NUM>) comprising:
a plurality of tubular elements (<NUM>, <NUM>), wherein the plurality of tubular elements include a syringe barrel (<NUM>) defining a barrel passageway (<NUM>), and tubing (<NUM>) defining a tubing passageway (<NUM>), the tubing (<NUM>) connected with a distal end of the barrel (<NUM>), such that barrel passageway (<NUM>) connects with tubing passageway (<NUM>) to define a passageway (P);
an agent (<NUM>, <NUM>) and an evacuator (<NUM>) disposed within the passageway (P), the plurality of tubular elements being configured for disposal of a selected volume (V) of the agent (<NUM>); and
an actuator, characterized in that
the agent (<NUM>) and the evacuator (<NUM>) are disposed in series within the barrel passageway (<NUM>);
and the actuator is engageable with the evacuator (<NUM>) to entirely expel the selected volume (V) of the agent (<NUM>) from the passageway (P) to the selected site.