Surgical injection system and method

A surgical injection device includes at least one tubular element defining a passageway. The passageway is configured for disposal of a selected volume of an agent and an evacuator disposed within the passageway. An actuator is engageable with the evacuator to entirely expel the selected volume of the agent from the passageway to a selected site. Spinal constructs, implants, systems and methods are disclosed.

TECHNICAL FIELD

The present disclosure generally relates to medical devices for the treatment of musculoskeletal disorders, and more particularly to a surgical system and a method for treating a spine.

BACKGROUND

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.

SUMMARY

In one embodiment, a surgical injection device is provided. The surgical injection device includes at least one tubular element defining a passageway. The passageway is configured for disposal of a selected volume of an agent and an evacuator disposed within the passageway. An actuator is engageable with the evacuator to entirely expel the selected volume of the agent from the passageway to a selected site. In some embodiments, spinal constructs, implants, systems and methods are disclosed.

DETAILED DESCRIPTION

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.

In some embodiments, the surgical system includes a surgical injection device, such as, for example, a syringe. In some embodiments, 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. In some embodiments, 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. In some embodiments, the syringe 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 embodiments, 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 50:1 to about at least about 1000:1. 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 3.5 cm and have an average width from about 20 mm to about 1 cm. In various embodiments, the average length of the elongated fibers can be from about 3.5 cm to about 6.0 cm and the average width from about 20 mm to about 1 cm. In other embodiments, the elongated fibers can have an average length be from about 4.0 cm to about 6.0 cm and an average width from about 20 mm to about 1 cm.

In yet other embodiments, the diameter or average width of the elongated fibers is, for example, not more than about 1.00 cm, not more than 0.5 cm or not more than about 0.01 cm. In still other embodiments, the diameter or average width of the fibers can be from about 0.01 cm to about 0.4 cm or from about 0.02 cm to about 0.3 cm.

In another embodiment, the aspect ratio of the fibers can be from about 50:1 to about 950:1, from about 50:1 to about 750:1, from about 50:1 to about 500:1, from about 50:1 to about 250:1; or from about 50:1 to about 100:1. Fibers according to this disclosure can advantageously have an aspect ratio from about 50:1 to about 1000:1, from about 50:1 to about 950:1, from about 50:1 to about 750:1, from about 50:1 to about 600:1, from about 50:1 to about 350:1, from about 50:1 to about 200:1, from about 50:1 to about 100:1, or from about 50:1 to about 75:1.

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 90:10, 80:20, 70:30, 60:40, 50:50, 40:60, 30:70, 20:80 and/or 10:90, In various embodiments, a surface demineralized bone chips to fibers ratio is about 90:10, 80:20, 70:30, 60:40, 50:50, 40:60, 30:70, 20:80 and/or 10:90 that can be used in the device. In some embodiments, a surface demineralized chips to fully demineralized fibers ratio is about 90:10, 80:20, 70:30, 60:40, 50:50, 40:60, 30:70, 20:80 and/or 10:90 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 3 cubic centimeter (cc). In some embodiments, the surgical injection device includes a lumen having a volume of 3 cc. In some embodiments, the surgical injection device is filled with 3 cc of bone graft material and 3 cc of backfill material such that the backfill material evacuates the entire 3 cc of bone graft material into the 3 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 embodiments, 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 embodiments, the bone graft material syringe is activated to fill a void. In some embodiments, a filling tube is attached with the dual syringe device. In some embodiments, the bone graft material is configured to fill the filling tube. In some embodiments, 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 embodiments, 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 embodiments, the backfill material syringe is activated to evacuate the bone graft material from the filling tube into the implant. In some embodiments, the bone graft material syringe can be activated again to fill a second void. In some embodiments, the bone graft material syringe and the backfill material syringe can be simultaneously activated. In one embodiment, 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 0.1 cc of the radiopaque marker material in between each 1 cc 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 embodiments, 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 3 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.

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.

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 toFIGS. 1-7, there are illustrated components of a surgical system10including a surgical injection device12.

Various components of surgical system10may have material composites, including the above materials, to achieve various desired characteristics such as strength, rigidity, elasticity, compliance, biomechanical performance, durability and radiolucency or imaging preference. The components of surgical system10, individually or collectively, may also be fabricated from a heterogeneous material such as a combination of two or more of the above-described materials. The components of surgical system10may be monolithically formed, integrally connected or include fastening elements and/or instruments, as described herein.

The components of surgical system10including surgical injection device12can 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 system10may 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 device12includes a plurality of tubular elements, such as, for example, a syringe barrel14and tubing16that define a passageway P. An evacuator, such as, for example, a flowable backfill material32is engageable with a selected volume V of an agent, such as, for example, bone graft material30within passageway P to entirely expel selected volume V of bone graft30from passageway P to a void of a selected site, as described herein. In some embodiments, surgical injection device12can include a single tubular element, or a plurality of tubular elements that are integrally connected or monolithically formed.

In some embodiments, bone graft30is configured for disposal into barrel14in a dry state. In some embodiments, surgical injection device12is configured for withdrawing blood or liquid via suction or vacuum from a selected site (e.g., disc space) to hydrate dry bone graft30. In some embodiments, after bone graft30is hydrated, it is injected into the selected site.

In some embodiments, bone graft30can be withdrawn from a selected site. In some embodiments, when bone graft30is injected into the wrong site, or if bone graft30has been injected into a site due to an emergency, surgical injection device12is configured to withdraw bone graft30from the site via suction or vacuum.

Barrel14extends between a proximal end18and a distal end20. End18defines an opening22configured for disposal of an actuator, such as, for example, a plunger42, as described herein. End20defines an opening24and is configured for connection with tubing16, as described herein. In some embodiments, end20includes a tip having a taper, nozzle, valve and/or luer lock connection for connecting with tubing16. In some embodiments, end20includes a pressure fit, friction fit or threaded connection for connecting with tubing16. In some embodiments, end20is integrally connected or monolithically formed with tubing16.

In some embodiments, barrel14includes 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 barrel14is transparent to provide a visual indication of the amount of material that remains in barrel14.

Tubing16is configured for attachment with a tip of barrel14adjacent opening24. Tubing16extends between an end60and an end62. End60includes a surface64. Surface64is connected with the tip of barrel14in various configurations, such as, for example, luer lock connection, friction fit, pressure fit, locking protrusion/recess, locking keyway and/or adhesive. End62is configured for disposal adjacent a void of the selected site, as described herein, as bone graft30is entirely expelled from passageway P.

Tubing16includes a surface66that defines a cavity, such as, for example, a passageway68. Tubing16is attached with the tip of barrel14adjacent opening24to connect passageway28with passageway68to form passageway P. Passageway68is configured for passage of bone graft30and backfill32such that selected volume V of bone graft30is entirely expelled from passageway P to the void of the selected site, as described herein. In some embodiments, passageway68may 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 tubing16can be any length depending on the surgical procedure.

In some embodiments, tubing16includes 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 tubing16is transparent to provide a visual indication of the amount of material that remains in tubing16.

In some embodiments, radiopaque markers are positioned on the tip and tubing16is 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 surface64can 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 tubing16can 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 tubing16can 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 graft30is configured to flow through passageway P into a selected site. In some embodiments, bone graft30includes a viscosity configured to reduce resistance with surface26and facilitate flow within passageway P. In some embodiments, bone graft30includes a lubricating material. In some embodiments, bone graft30may 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 graft30comprises 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 graft30comprises 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 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. WO90/11092, the disclosure of which is herein incorporated by reference in its entirety). 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 U.S. Pat. Nos. 5,593,972, 5,589,466, and 5,580,859, the disclosures of which are herein incorporated by reference in their entireties.

Gene therapy vectors further comprise suitable adenoviral vectors including, but not limited to for example, those described in U.S. Pat. No. 5,652,224, which is herein incorporated by reference.

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., U.S. Pat. No. 6,552,170 and European Pat. No. 0,401,384 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 graft30are sterile. In a non-limiting method, sterility is readily accomplished for example by filtration through sterile filtration membranes (e.g., 0.2 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-1, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-15, BMP-16, BMP-17, BMP-18 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-1; BMP-2; BMP-3; BMP-4; BMP-5; BMP-6; BMP-7; BMP-8; BMP-9; BMP-10; BMP-11; BMP-12; BMP-13; BMP-15; BMP-16; BMP-17; or BMP-18; 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, 5-lipoxygenase inhibitors such as those described in U.S. Pat. Nos. 5,534,524 and 6,455,541 (the contents of which are herein incorporated by reference in their entireties), heterocyclic compounds such as those described in U.S. Pat. No. 5,658,935 (herein incorporated by reference in its entirety), 2,4-dioxoimidazolidine and imidazolidine derivative compounds such as those described in U.S. Pat. Nos. 5,397,796 and 5,554,594 (the contents of which are herein incorporated by reference in their entireties), sulfonamide derivatives such as those described in U.S. Pat. No. 6,313,119 (herein incorporated by reference in its entirety), or acylguanidine compounds such as those described in U.S. Pat. No. 6,492,356 (herein incorporated by reference in its entirety).

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-1, CTGF-2, CTGF-4 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-1, TGF-beta-2, TGF-beta-3, 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-1, GDF-2, GDF-3, GDF-7, GDF-10, GDF-11, and GDF-15. For example, GDFs useful as isolated osteoinductive agents include, but are not limited to, the following GDFs: GDF-1 polynucleotides or polypeptides corresponding to GenBank Accession Numbers M62302, AAA58501, and AAB94786, as well as mature GDF-1 polypeptides or polynucleotides encoding the same. GDF-2 polynucleotides or polypeptides corresponding to GenBank Accession Numbers BC069643, BC074921, Q9UK05, AAH69643, or AAH74921, as well as mature GDF-2 polypeptides or polynucleotides encoding the same. GDF-3 polynucleotides or polypeptides corresponding to GenBank Accession Numbers AF263538, BC030959, AAF91389, AAQ89234, or Q9NR23, as well as mature GDF-3 polypeptides or polynucleotides encoding the same. GDF-7 polynucleotides or polypeptides corresponding to GenBank Accession Numbers AB158468, AF522369; AAP97720, or Q7Z4P5, as well as mature GDF-7 polypeptides or polynucleotides encoding the same. GDF-10 polynucleotides or polypeptides corresponding to GenBank Accession Numbers BC028237 or AAH28237, as well as mature GDF-10 polypeptides or polynucleotides encoding the same.

GDF-11 polynucleotides or polypeptides corresponding to GenBank Accession Numbers AF100907, NP_005802 or 095390, as well as mature GDF-11 polypeptides or polynucleotides encoding the same. GDF-15 polynucleotides or polypeptides corresponding to GenBank Accession Numbers BC008962, BC000529, AAH00529, or NP004855, as well as mature GDF-15 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-1, CDMP-2, LMP-1, LMP-2, or LMP-3.

CDMPs and LMPs useful as isolated osteoinductive agents include, but are not limited to, the following CDMPs and LMPs: CDMP-1 polynucleotides and polypeptides corresponding to GenBank Accession Numbers NM_00557, U13660, NP_000548 or P43026, as well as mature CDMP-1 polypeptides or polynucleotides encoding the same. CDMP-2 polypeptides corresponding to GenBank Accession Numbers or P55106, as well as mature CDMP-2 polypeptides. LMP-1 polynucleotides or polypeptides corresponding to GenBank Accession Numbers AF345904 or AAK30567, as well as mature LMP-1 polypeptides or polynucleotides encoding the same. LMP-2 polynucleotides or polypeptides corresponding to GenBank Accession Numbers AF345905 or AAK30568, as well as mature LMP-2 polypeptides or polynucleotides encoding the same. LMP-3 polynucleotides or polypeptides corresponding to GenBank Accession Numbers AF345906 or AAK30569, as well as mature LMP-3 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 some embodiments, a statin may be used as the growth factor. Statins include, but is not limited to, atorvastatin, simvastatin, pravastatin, cerivastatin, mevastatin (see U.S. Pat. No. 3,883,140, the entire disclosure is herein incorporated by reference), velostatin (also called synvinolin; see U.S. Pat. Nos. 4,448,784 and 4,450,171 these entire disclosures are herein incorporated by reference), fluvastatin, lovastatin, rosuvastatin and fluindostatin (Sandoz XU-62-320), dalvastain (EP Appln. Publn. No. 738510 A2, the entire disclosure is herein incorporated by reference), 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 1:1 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 (2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonic acid), MES (2-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 1 mM to 100 mM.

In some embodiments, the BMP-2 is provided in a vehicle (including a buffer) containing sucrose, glycine, L-glutamic acid, sodium chloride, and/or polysorbate80.

In some embodiments, bone graft30comprises therapeutic agents. Exemplary therapeutic agents include but are not limited to IL-1 inhibitors, such Kineret® (anakinra), which is a recombinant, non-glycosylated form of the human inerleukin-1 receptor antagonist (IL-1Ra), or AMG 108, which is a monoclonal antibody that blocks the action of IL-1. 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-1 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-11 (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.

Backfill32is configured to flow through passageway P to expel selected volume V of bone graft30into a selected site. In some embodiments, a viscosity of backfill32facilitates driving bone graft30from passageway28, through passageway68and into a selected site. In some embodiments, the viscosity of backfill32is lower than the viscosity of bone graft30to facilitate movement of bone graft30through passageway P. In some embodiments, the viscosity of bone graft30is equal to the viscosity of backfill32. 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, backfill32may 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, backfill32may include, such as, for example, cement to render surgical injection device12to be a single use device and/or disposable. In some embodiments, backfill32may include, such as, for example, solid chunks of material that, when injected, flow similar to a liquid.

Plunger42actuates movement of backfill32and bone graft30within passageway P. Plunger42extends between an end44and an end46. End44includes a handle48configured for manipulation to translate plunger42relative to the wall of barrel14within passageway28. End46includes a plunger seal50that slidably engages the wall of barrel14such that plunger42is movably disposed with opening22. Plunger seal50is configured to resist and/or prevent backfill32and/or bone graft30from exiting opening22.

Plunger seal50is configured to translate within passageway28and contact backfill32. Plunger42translates relative to barrel14between an initial orientation, as shown inFIG. 5, and a fully or entirely expelled orientation, as shown inFIG. 7. In the initial orientation, plunger42is disposed adjacent backfill32. Plunger42translates, in the direction shown by arrow A inFIG. 5, such that plunger seal50applies a force to backfill32. The force applied by plunger seal50causes backfill32to compress bone graft30. Compression of bone graft30causes bone graft30to flow from passageway28through opening24. Further translation of plunger42causes backfill32to force bone graft30into passageway68, as shown by inFIG. 6. Translation of plunger42to the entirely expelled orientation causes backfill32to flow into passageway68forcing bone graft30through passageway68to entirely expel selected volume V of bone graft30into a selected site, for example, as shown inFIG. 7.

In some embodiments, bone graft30is disposed in a series configuration with backfill32within passageway P such that selected volume V of bone graft30can be entirely expelled by backfill32. In some embodiments, entirely expelling the entire selective volume V of bone graft30includes particulate and/or residue of bone graft30remaining on the surfaces that define passageway P. In some embodiments, bone graft30and backfill32are disposed in layers, such as, for example, alternating layers of bone graft30and backfill32within passageway28. In some embodiments, an alternating layer configuration of bone graft30and backfill32is configured to facilitate selective filling of the selected site S with bone graft30and backfill32. In some embodiments, the surgeon adds 2 cc of bone graft30at the base of at least one bone fastener, and adds 1 cc of backfill32to facilitate confirmation of full injection of bone graft30. In some embodiments, barrel14comprises multiple layers of 2 cc of bone graft30interspersed with 1 cc layers of backfill32.

In some embodiments, the selected site includes, for example, an interbody implant80. In some embodiments, interbody implant80includes a surface82. Surface82defines a void84. Void84is configured to receive the selected volume V of bone graft30. In some embodiments, the cross-section geometry of interbody implant80may 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 system10, similar to the systems and methods described herein, includes surgical injection device12and 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 implant80. Surgical system10may 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 implant80.

The components of surgical system10including surgical injection device12are employed to augment the surgical treatment. In some embodiments, surgical injection device12can introduce or deliver a selected volume V of bone graft30into interbody implant80prior, during and/or subsequent to disposal of interbody implant80with vertebrae at selected surgical site S. In some embodiments, surgical injection device12can inject selected volume V of bone graft30into interbody implant80in vivo. In some embodiments, surgical injection device12can inject selected volume V of bone graft30directly adjacent or into the vertebrae at selected surgical site S.

Surgical injection device12is provided with a selected volume V, such as, for example, 3 cc of bone graft30, as shown inFIG. 5. Surgical injection device12is provided with a volume of backfill32, such as, for example, 3 cc of backfill32. End62of tubing16is disposed adjacent void84of interbody implant80. In some embodiments, void84is configured to receive 3 cc of bone graft30.

From the initial orientation, a force is applied to plunger42and/or plunger42is manipulated such that plunger42translates in the direction shown by arrow A inFIG. 5. Plunger seal50applies a force to backfill32to compress bone graft30adjacent opening24, as described herein. Continued manipulation of plunger42causes bone graft30to flow from passageway28through opening24such that backfill32forces bone graft30into passageway68, as shown by inFIG. 6. As plunger42is further manipulated, backfill32flows into passageway68forcing bone graft30through passageway68to entirely expel selected volume V of bone graft30from passageway P into void84at selected site S, as shown inFIG. 7.

In some embodiments, surgical system10comprises 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 system10are removed and the incision is closed. The components of surgical system10can 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 system10.

In some embodiments, the components of surgical system10contain 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 graft30to 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 embodiment, as shown inFIGS. 8-11, surgical system10, similar to the systems and methods described above with regard toFIGS. 1-7, includes a surgical injection device112, similar to surgical injection device12described herein. Surgical injection device112includes a syringe barrel114, a syringe barrel214and tubing116. Barrel114extends between an end118and an end120. End118defines an opening122configured for disposal of an actuator, such as, for example, a plunger142, similar to plunger42described herein. End120defines an opening124and a tip configured for connection with tubing116, similar to that described herein. Barrel114defines a longitudinal axis X2, as shown inFIG. 8.

Barrel114includes a surface126. Surface126defines a passageway128. Passageway128defines a portion of a fluid passageway P1, similar to that described herein. Passageway128extends along axis X2between ends118,120. Passageway128is configured for disposal of a selected volume V1of bone graft material130, similar to that described herein.

Plunger142is movably disposed with opening122. Plunger142is configured to actuate movement of bone graft130within passageway128. Plunger142includes a plunger seal150that slidably engages the wall of barrel114such that plunger142is movably disposed with opening122. Plunger seal150is configured to resist and/or prevent bone graft130from exiting opening122.

Plunger seal150is configured to translate within passageway128and contact bone graft130. Plunger142is configured to translate relative to barrel114between an initial orientation, as shown inFIG. 9, and a dispensing orientation, as shown inFIG. 10. In the initial orientation, plunger142is disposed adjacent bone graft130. Plunger142is configured for translation, in the direction shown by arrow B inFIG. 10, such that plunger seal150applies a force to bone graft130. The force applied by plunger seal150causes bone graft130to flow from passageway128through opening124into tubing116, similar to that described herein.

Barrel214extends between an end218and an end220. End218defines an opening222configured for disposal of a plunger242, similar to plunger42described herein. End220defines an opening224and a tip configured for connection with tubing116, similar to that described herein. Barrel214defines a longitudinal axis X3, as shown inFIG. 8. In some embodiments, axis X3is disposed parallel to axis X2. In some embodiments, axis X3may be disposed at alternate orientations relative to axis X2, such as, for example, transverse and/or other angular orientations, such as, acute or obtuse.

Barrel214includes a surface226. Surface226defines a passageway228. Passageway228defines a portion of fluid passageway P1. Passageway228extends along axis X3between ends218,220. Passageway228is configured for disposal of backfill material232, similar to that described herein.

Plunger242is movably disposed with opening222. Plunger242is configured to actuate movement of bone fill232within passageway228. Plunger242includes a plunger seal250that slidably engages the wall of barrel214such that plunger242is movably disposed with opening222. Plunger seal250is configured to resist and/or prevent backfill232from exiting opening222.

Plunger seal250is configured to translate within passageway228and contact backfill232. Plunger242is configured to translate relative to barrel214between an initial orientation, as shown inFIG. 9and a fully or entirely expelled orientation, as shown inFIG. 11. In the initial orientation, plunger242is disposed adjacent backfill232. Plunger242is configured for translation, in the direction shown by arrow C inFIG. 11, such that plunger seal250applies a force to backfill232. The force applied by plunger seal250causes backfill232to flow from passageway228through opening224. Further translation of plunger242causes backfill232to flow into tubing116, similar to that described herein.

Tubing116extends between an end160and an end162. Tubing116is configured for connection with openings124,224, as described herein. In some embodiments, end160includes a bifurcated extension164having a part166and a part168. Part166includes a surface170. In some embodiments, surface170is connected with the tip of barrel114, similar to that described herein. Part166includes a surface174that defines a passageway176. Part166is connected with barrel114to orient passageway176in communication with passageway128.

Part168includes a surface172. In some embodiments, surface172is connected with the tip of barrel214, similar to that described herein. Part168includes a surface178that defines a passageway180. Part168is connected with barrel214to orient passageway180in communication with passageway228. Passageways176,180merge into a passageway192. In some embodiments, passageways176,180merge at a juncture, such as, for example, a mixing chamber182, which may be employed to selectively combine one or more agents and backfill, as described herein.

Tubing116includes a surface190. Surface190defines passageway192. Passageway192is in communication with passageways176,180to form a portion of passageway P1. Passageway192is configured for passage of selected volume V of bone graft130and backfill232. End162is configured for engagement with selected site S1to direct the flow of selected volume V1of bone graft130into selected site S1, similar to that described herein.

Backfill232is configured to force bone graft130through chamber182, as shown by inFIG. 11. Translation of plunger242into the fully or entirely expelled orientation causes backfill232to flow into chamber182forcing bone graft130through passageway192to entirely expel selected volume V1of bone graft130into selected site S1, as shown inFIG. 11and similar to that described herein.

In some embodiments, barrel114is disposed in a side by side configuration with barrel214. In this configuration, selected volume V of bone graft130is injected into tubing116prior to injection of backfill232into tubing116. In some embodiments, bone graft130and backfill232are injected into tubing116in stages to form layers, such as, for example, alternating layers of bone graft130and backfill232within selected site S1. In some embodiments, barrel114includes a one way valve disposed adjacent end120that is configured to resist and/or prevent backflow of bone graft130into passageway128. In some embodiments, barrel214includes a one way valve disposed adjacent end220that is configured to resist and/or prevent backflow of backfill232into passageway228.

In some embodiments, barrel114and barrel214are the same size. In some embodiments, barrel114and barrel214are different sizes depending on the desired number of applications of bone graft130, volume of lumen and selected site S1.

In one embodiment, as shown inFIGS. 12-19, surgical system10, similar to the systems and methods described herein, includes a surgical injection device312, similar to the surgical injection devices described herein. Surgical injection device312includes a tubular element, such as, for example, a tube314and a syringe barrel414, as described herein. Tube314extends between an end318and an end320. End318includes a luer lock connection352, as shown inFIG. 15. In some embodiments, luer lock352is configured to facilitate attachment of barrel414with tube314, as described herein. In some embodiments, end318includes a flange362. Flange362is configured for engagement with barrel414to resist and/or prevent separation of barrel from tube314, as shown inFIG. 18. End320defines an opening324configured for connection with a selected site S2. Tube314defines a longitudinal axis X4, as shown inFIG. 18.

In some embodiments, end318is configured for connection with a tip325, as shown inFIG. 15. In some embodiments, tip325is configured to facilitate connection with an irrigation instrument. In some embodiments, tip325is configured to facilitate connection with an irrigation instrument. In some embodiments, tube314is prepackaged with a selected volume V2of bone graft330, similar to that described herein. In some embodiments, tube314includes a cap326engageable with end318to prevent bone graft330from exiting opening322, as shown inFIG. 13. In some embodiments, tube314includes a cap328engageable with end320to prevent bone graft from exiting opening324.

Tube314includes a surface342. Surface342defines a passageway344. Passageway344defines a portion of a fluid passageway P2, similar to that described herein. Passageway344extends along axis X4between ends318,320. Passageway344is configured for disposal of a selected volume V2of bone graft material330, similar to that described herein. Selected volume V2of bone graft330is configured to flow through passageway P2into selected site S2.

Barrel414includes a surface426. Surface426defines passageway428. Passageway428defines a portion of a fluid passageway P2, as described herein. Passageway428extends along axis X4. Passageway428is configured for disposal of backfill432configured for actuation by a plunger442, as described herein.

Plunger442includes a plunger seal450. Plunger seal450is configured to apply a force to backfill432causing bone graft330to be expelled from tubing314, as described herein. Plunger442is configured for translation relative to the wall of barrel414within passageway428. In some embodiments, plunger442is configured to translate relative to barrel414, in the direction shown by arrow E inFIG. 19, to engage backfill432to entirely expel selected volume V2of bone graft330from passageway P2into selected site S2, similar to that described herein.

In some embodiments, tube314includes 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 tube314is transparent to provide a visual indication of the amount of material that remains in tube314.

In some embodiments, a surgical instrument, such as, for example, an inserter370including a cannula for disposal of surgical injection device312is employed to facilitate connection with selected site S2, as shown inFIG. 18. Inserter370is configured to facilitate introduction and/or delivery of the components of surgical system10to a surgical site, as described herein, and/or engage selected site S2. In some embodiments, inserter370may include one or more needles, trocars, sheaths and/or minimally invasive instruments. In some embodiments, inserter370may include a cutting surface that can be extended and retracted to cut and/or sever tissue and/or components of surgical system10. In some embodiments, inserter370may be guided via imaging guidance, as described herein. In some embodiments, inserter370includes a handle372configured to facilitate manipulation and positioning of surgical injection device312.

In one embodiment, as shown inFIGS. 20-23, surgical system10, similar to the systems and methods described herein, includes a surgical injection device512, similar to the surgical injection devices described herein. Surgical injection device512includes a tubular element, such as, for example, a tube514and a plunger552, similar to that described herein. Tube514extends between an end518and an end520.

Tube514includes a surface542. Surface542defines a passageway544. Passageway544defines a portion of a fluid passageway P3, similar to that described herein. Passageway544extends along axis X5between ends518,520. Passageway544is configured for disposal of a selected volume V3of bone graft material530, similar to that described herein. Selected volume V3of bone graft530is configured to flow through passageway P3into selected site S3. In some embodiments, tube514is prepackaged with a selected volume V3of bone graft530, similar to that described herein. In some embodiments, tube514includes a cap526engageable with end520to prevent bone graft530from exiting tube514, as shown inFIG. 20.

In some embodiments, tube514includes an evacuator, such as, for example, a stopper532that is disposed adjacent end518. In some embodiments, stopper532includes a biocompatible material, similar to that described herein, and is configured for disposal with selected site S3. In some embodiments, stopper532is configured to facilitate expelling the entire selected volume V3of bone graft530from tube514, similar to that described herein.

Plunger552is engageable with tube514and translatable relative to a wall of tube514to entirely expel bone graft530from passageway P3, as described herein. Plunger552extends between an end554and an end556. End554includes a handle557configured for manipulation to translate plunger552within passageway544. Plunger552includes a plunger seal558configured to apply a force to stopper532and/or bone graft530, similar to that described herein. In some embodiments, plunger552is configured to translate relative to tube514, as shown inFIGS. 22 and 23, such that plunger seal558engages stopper523, which entirely expels selected volume V3of bone graft530from passageway P3into selected site S3, for example, a void of an interbody implant, similar to that described herein.

In some embodiments, tube514includes 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 tube514is transparent to provide a visual indication of the amount of material that remains in tube514.

In some embodiments, an inserter370including a cannula for disposal of surgical injection device512is employed to facilitate connection with selected site S3, as shown inFIGS. 21-23. In some embodiments, inserter570includes a handle572configured to facilitate manipulation and positioning of surgical injection device512.