Intervertebral fusion device with bone graft lumbar spine

Abstract

To provide an intervertebral fusion device with a suitable bone graft lumbar vertebra.SOLUTION: Intervertebral fusion devices and their methods of use are described herein. Also described herein are interbody device systems and methods of use thereof. In some embodiments, the disc space often needs to be distracted to restore the space between the vertebrae, both to increase the height of the intervertebral foramen and to create lordosis. The system can deliver sufficient force through the minimally invasive access port to enlarge the space for any connective tissue that may continue to connect the vertebrae. In addition, the bone distraction method minimizes point loading and prevents endplate fracture through better contact surface area.SELECTED DRAWING: Figure 9

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of U.S. Provisional Patent Application No. 63 / 082,255, filed September 23, 2020, and U.S. Provisional Patent Application No. 63 / 172,945, filed April 9, 2021, the entire disclosures of each of which are incorporated herein by reference.

[0002] Intervertebral fusion devices and methods for their use are described herein. Also described herein are interbody systems and methods for their use. [Background technology]

[0003] Degenerative joint disease in the spine usually involves tandem degeneration of the intervertebral disc and the two posterior facet joints, which act as a tripod to provide stabilization between the vertebrae of the spine. Degeneration of these joints is referred to as degenerative disc disease (DDD) or disc arthropathy, and facet joint degenerative disease or facet joint arthropathy, respectively. The result of DDD is often thinning of the intervertebral disc and collapse of the disc level. The openings through which spinal nerve roots travel as they leave the spinal column are called neural foramina, and the height of these foramina directly corresponds to the height of the disc. When there is collapse of the disc level, the natural height of the neural foramina is also collapsed, resulting in compression of the protruding nerve roots, which can cause neuralgia or radicular pain down the spinal column. Concomitantly, collapse of the disc level can cause ligamentous laxity and vertebral bulging. These ligaments, the posterior longitudinal ligament (PLL) and ligamentum flavum, surround the spinal cord and can bulge into the spinal canal as the disc level collapses. The result is compression of the entire spinal cord or thecal sac at the center of the spinal canal, which can result in radicular pain down the leg, in addition to leg weakness and fatigue, referred to as neurogenic claudication.

[0004] Surgical treatment of low back pain and sciatica involves determining the etiology of the pain, which can all arise from degenerative disc joint disease of the spine. These are:

[0005] Treatment of Spinal Mechanical Instability: Mechanical instability is the result of degeneration of both the intervertebral disc and / or the posterior facet joints. Mechanical instability causes painful arthritis or joint pain. Many spinal fusions are directed at reducing mechanical instability, thereby reducing the motion of arthritic joints, which become inflamed with movement. There are numerous methods for achieving spinal fusion using both anterior and posterior column fixation devices. The most popular spinal fusion method to date involves posterior screws used in combination with an interbody cage for anterior column support.

[0006] Treatment of Nerve Root Compression: As explained above, nerve root compression can occur externally, centered around the spinal cord or thecal sac, or around the protruding nerve root at the neural foramen. Pain from nerve root compression often follows the dermatomal distribution of the nerve root, causing radicular pain or sciatica. Spinal decompression aims to relieve neuralgia by removing pressure from the nerve root. This can be accomplished directly through removal of bone / ligament / disc compressing the nerve. It can also be accomplished indirectly by mechanically increasing the intervertebral height using an interbody or interlaminar spacer, thereby restoring neural foraminal height and reducing the bulging ligament / disc centered within the spinal canal.

[0007] Restoring the natural spinal alignment: One of the newer paradigms in spinal fixation and fusion is the restoration of sagittal balance using intervertebral spacers to restore the natural lordotic curvature of the spine. Restoring neutral spinal alignment enables patients to walk or stand with good posture rather than leaning forward. This reduces strain on the paraspinal muscles of the spine. Performing spinal fixation without restoring the natural spinal alignment often results in "flat back syndrome," in which patients suffer from chronic lower back pain due to muscle fatigue. Additionally, inducing natural sagittal balance using lordotic spacers has become a mainstay in preventing degeneration in the adjacent intervertebral spaces above and below the spinal fusion.

[0008] Vertebral interbody spacers have become an important part of spinal fusion for reasons related to the basis for treating back pain and neuralgia, as follows:

[0009] Intervertebral spacers improve the treatment of mechanical instability: Insertion of an intervertebral spacer provides more anterior support for spinal fusion, which helps stabilize mechanical instability. With their large footprint, some intervertebral spacers can be used as stand-alone fixation devices. They can also be used in conjunction with posterior spinal fixation to add anterior column support, allowing for more rigid stabilization, preventing loosening of the construct and fusion failure.

[0010] Intervertebral spacers improve the treatment of nerve root compression: Intervertebral spacers are used to increase the height of collapsed and degenerated disc spaces. This allows for indirect restoration of the height of the associated neural foramina, which can relieve compression of the protruding spinal nerve roots at that vertebral level. In addition, increasing the disc space height restores tension to the collapsed and bulging ligaments within the spinal canal, namely the PLL and ligamentum flavum. Restoring tension to these ligaments through bone distraction, known as ligament reduction, reduces the bulging of these ligaments into the spinal canal. The combination of decompression of the neural foramina and spinal canal reduces radicular sciatica and improves neurogenic claudication.

[0011] Intervertebral spacers improve the restoration of the spine's natural alignment: When the spine deviates from neutral global alignment, which primarily refers to forward curvature or deviation from sagittal alignment, patients will experience muscle pain and back strain throughout the day as they attempt to force themselves into a more neutral position. The lumbar spine is constructed in a natural lordosis, which allows for standing in an upright, neutral posture. As discs degenerate, thin, and collapse in height, the lumbar spine often loses its lordosis, which is why elderly patients are seen with degenerated spines that are rounded forward. The popularity of intervertebral spacers is driven by the fact that restoring disc height or anterior column height can help guide a patient's spine into a more neutral or lordotic position. In this way, spinal balance with fusion can be achieved. Indeed, there has been an increase in the use of lordotic and hyperlordotic intervertebral spacers, which further induce lordosis in the lumbar spine to help compensate for kyphosis at other degenerated levels. In the past, fusing the spine without the use of intervertebral spacers often resulted in spinal fixation in a flat or kyphotic position, which can leave patients with chronic pain, referred to as "flat back" syndrome. Fusion without the use of intervertebral spaces is gradually becoming obsolete. Also, currently, there are no existing percutaneous interbody systems that allow for prescribed lordotic correction of the spine. The percutaneous systems that exist today only enable parallel bone distraction of the intervertebral disc space.

[0012] Interbody fusion implants can be placed into the disc space through either a posterior, lateral, or anterior approach trajectory. Two posterior approaches are posterior lumbar interbody fusion (PLIF), in which the interbody fusion implant is placed through a laminectomy, and transforaminal lumbar interbody fusion (TLIF), in which the facet joint is resected and the interbody fusion implant is placed through a posterolateral trajectory. The lateral approach to the spine for placement of the interbody fusion implant is called lateral lumbar or extralateral lumbar interbody fusion (LLIF / XLIF). Two anterior approaches to the lumbar spine are a direct anterior open approach, called anterior lumbar interbody fusion (ALIF), or an anterolateral approach, called oblique lumbar interbody fusion (OLIF). All of these approaches, except ALIF, can be performed through either an open or minimally invasive approach using retractors. This approach is depicted in Figure 1. Current percutaneous interbody fusion implants utilize an oblique posterolateral approach with a similar trajectory to TLIF, but because the facet joints are typically not removed with these approaches, but rather they extend across the disc space within Kambin's triangle, necessitating a slightly more lateral trajectory to get underneath the facet joints while targeting Kambin's triangle.

[0013] A drawback of inserting an interbody cage is that there is still a significant amount of dissection and tissue trauma using open or minimally invasive approaches to gain access to the disc space, which corresponds to greater postoperative pain and longer recovery times. The advent of less invasive retractors allows for less tissue trauma, but still involves tissue retraction, which can result in non-trivial postoperative pain. Current approaches using less invasive retractors also result in the use of smaller interbody implants that penetrate through the access port. However, a drawback of using smaller implants is that there is little surface area of ​​contact with the vertebrae above and below, leading to weak support, which increases the risk of the implant itself settling into the adjacent vertebrae. Percutaneous approaches to the spine using tubular dilators are an approach used to even further limit tissue dissection and retraction, but adoption has been limited due to poor visualization of the protruding nerves in Kambin's triangle and the risk of nerve injury when attempting dilation within a collapsed intervertebral foramen, where the safety margin of Kambin's triangle is even narrower. Figure 2 is an illustration of Kambin's triangle, which is the approach taken for current endoscopic or percutaneous approaches to the spine. In addition, current percutaneous techniques are unfamiliar to many surgeons and require additional training, and unfamiliarity can often increase procedure time.

[0014] Current developments in interbody fusion devices and techniques, in addition to minimizing the approach, also focus on restoring disc height and lordosis to restore spinal alignment. Existing open and minimally invasive techniques employ the use of instrumentation such as rasps, curettes, shavers, and dilators to widen the disc space, release vertebral ligamentous attachments, and effect intervertebral space distraction. When used in endoscopic or minimally invasive approaches, many of these instruments are hampered by the inability of the system instrumentation to enable the surgeon to properly prepare the disc space for the deployed geometry of the implant because access is restricted during the procedure.

[0015] There are several existing options for interbody fusion devices. The original interbody fusion devices were static PEEK or metal cages. To effect improved lordosis correction, these static cages were either shaped with built-in lordosis angulation or inserted and packed over the anterior majority of the vertebral body, with screws compressing posteriorly to induce lordosis. However, drawbacks of both static and expandable posteriorly inserted cages remain, such as subsidence due to their small footprint and / or contact surface area on the vertebral endplates, along with the fact that they often do not conform well to the vertebral body, leading to point loading and endplate fracture. Expandable cages are more susceptible to causing endplate fracture, particularly because expansion at the anterior wall can create lordosis, but this can also reduce the overall contact surface area by lifting the vertebra away from the more posterior portion of the rigid implant structure.

[0016] Although lateral and anteriorly placed cages possess more surface area and therefore improved endplate coverage, they still require separate incisions and dissections for access. Currently, endoscopically inserted interbody fusion devices can provide increased height.

[0017] Lumbar intervertebral fusion devices are indicated for use in skeletally mature patients with discoid disc degeneration at one or two consecutive levels from L2 to L5. DDD is defined as low back pain of discogenic origin accompanied by disc degeneration, confirmed through medical history and radiological examination. Patients with DDD may also suffer from up to Grade I spondylolisthesis at the involved level. Intervertebral devices are indicated for use in conjunction with a complementary fixation system and autograft bone. Intervertebral fusion devices aim to restore disc height and lumbar lordosis. Several insertion methods exist for these devices, and limitations vary across different approaches to insertion. All insertion methods employ either an anterior or posterior approach, but anterior insertion carries a greater risk of complications but achieves superior restoration of height and lumbar lordosis.

[0018] Due to the nature of the dissection and complications associated with anterior insertion of intervertebral devices, surgeons are turning to posterior insertion methods. Specifically, the transforaminal lumbar interbody fusion (TLIF) approach has become dominant in the field of interbody fusion. Insertion at the posterolateral angle imposes limitations on footprint size. A small insertion window limits the size of the interbody body. A method that circumvents this limitation employs an expandable approach, thereby increasing the footprint after insertion.

[0019] The interbody devices described herein can employ shapes and expansions that can increase the contact points and contact surface area between the vertebral endplates and the device to more evenly distribute compressive forces applied to the interbody device. By increasing contact between the vertebral endplates and the interbody device, the incidence of subsidence can be effectively reduced. Increasing contact can mean increasing the contact surface area, increasing the distance between contact points, increasing contact with stiffer portions of the anatomy, increasing conformal contact, etc. Enlargement can also minimize the access window required to reduce the invasiveness of the procedure while still allowing engagement with the peripheral area of ​​the vertebral endplates. Engaging the periphery of the vertebral bodies can allow force distribution near the more compact and dense cortical bone. Furthermore, by distributing compressive forces across a larger surface area of ​​the vertebral endplates, migration is reduced. Greater contact with native bone structure better promotes bony fusion, thus reducing the likelihood of revision surgery due to interbody failure.

[0020] The devices described herein can employ expandable footprints, adjustable heights, and / or adjustable lordosis. By allowing multiple degrees of adjustment, disc height can be virtually restored and load-bearing configurations can be optimized while minimizing complications and the need for revision surgery. The devices described herein can employ expanded footprints, heights, and / or lordosis. The devices described herein can increase the surface area of ​​contact resulting from an increased number of contact points.

[0021] The geometry of the devices described herein can be conformed to the geometry of the vertebral endplates, with the dome-shaped shape defining the contours of the enlarged upper surface of the device and the flat surface defining the lower surface of the device. Summary of the Invention [Means for solving the problem]

[0022] Interbody systems and methods of use thereof are described herein.

[0023] The interbody systems described herein have the capability to perform procedures (disc preparation, implant delivery, implant deployment / expansion, final conformal implant locking and disconnection, and instrument removal) through minimally invasive or percutaneous access. In some embodiments, the interbody systems allow access through the following approaches: posteriorly via a laminectomy, through a facet joint resection, or through Kambin's triangle, or through the superior endplate just below Kambin's triangle, a transpedicular approach with access through a transforaminal approach, through an endplate, through a lateral approach, or through other approach trajectories enabled by minimally invasive access, etc. These approaches are depicted by FIG. 1.

[0024] In some embodiments, the interbody systems described herein can be configured to perform disc preparation. The remaining disc between the vertebrae can be resected or reamed to enable decompression of the disc space and placement and deployment of an interbody implant. The instrumentation used for disc preparation can be configured to penetrate through a minimally invasive access window. The system can be configured to allow for directional clearance of soft tissue. In some embodiments, the system can also be configured to allow for circumferential resection to further enable distraction of the intervertebral space.

[0025] FIG. 7 illustrates disc space distraction 100 using a balloon 102. The disc distraction 100 utilizes the balloon 102 to compact or disrupt the annulus 104, as illustrated by FIG. 8. The balloon can be a high-pressure balloon. In some embodiments, the balloon can be expanded to restore foraminal height, as depicted by FIG. 9. The balloon can be expanded to maximize surface area contact with the vertebral endplates, as shown in FIG. 10.

[0026] In some embodiments, the disc space often needs to be distracted to restore intervertebral space, both to increase foraminal height and to create lordosis, as depicted in FIG. 9 . The system described herein can deliver sufficient force through a minimally invasive access port to enlarge the space against any connective tissue that may continue to connect the vertebrae. In addition, the distraction method minimizes point loads and prevents endplate fracture through better contact surface area. The system provides user feedback to alert the user when the vertebral bodies are sufficiently distracted or, as depicted in FIG. 14 , when the ligamentous connections between the vertebral bodies are disrupted. Such feedback can be in the form of a pressure indicator. The distraction can be directional, allowing for selective distraction of the anterior versus posterior half of the interbody space (as illustrated in FIGS. 13 and 15 ).

[0027] Implant Sizing: A "try-in" system can measure the optimal desired size of the implant through a minimally invasive access port with the aid of fluoroscopy and / or pressure feedback. The system can size the optimal height, width, and lordosis angle using this percutaneous "try-in" method. Optimal sizing can be determined by the measured amount of expansion that produces the desired pressure reading. Optimal sizing can also be determined by the conformance of the implant to the adjacent vertebral endplates or the desired distraction visualized using radiography. The try-in system can also provide feedback to the user to determine when the optimal distraction of the space has occurred.

[0028] In some embodiments, the interbody implant can be placed / positioned through a minimally invasive access window, as depicted in FIG.

[0029] Interbody Deployment to maximize contact surface area and maintain the desired height and lordosis angle of the intervertebral space: The interbody body can be deployed by the user once it is past the minimally invasive access window and at the target site, as shown in Figure 18. The interbody body can be retractable and reversible.

[0030] Interbody deployment can be aided by an internal balloon, which can push the contact surface of the interbody body to conform to the adjacent vertebral endplates. The interbody implant itself can stabilize the balloon from sliding or increase the strength of the balloon wall itself. A curved trocar can be used to change the angle of the implant to prevent migration of the balloon or implant.

[0031] The interbody implant can remain anchored in place while in the deployed configuration.

[0032] The interbody implant can be locked into a final conformal state in which it remains stable. The interbody implant can also be filled with a material that provides load-bearing properties or that can enable bone ingrowth.

[0033] In some embodiments, the interbody implant is capable of withstanding the weight of the patient. The present invention provides, for example, the following. (Item 1) 1. A method of deploying an interbody implant in an intervertebral disc space, the method comprising: inserting an inflatable balloon into the disc space, the inflatable balloon configured to expand into the disc space, thereby widening the disc space; expanding the inflatable balloon to restore foraminal height; withdrawing the inflatable balloon from the disc space; directing the interbody implant into the disc space through a minimally invasive access window; deploying the interbody implant into the disc space; A method comprising: (Item 2) Item 10. The method of item 1, wherein the interbody implant is a tensile filament. (Item 3) Item 10. The method of item 1, wherein the trocar is attached to an additional fixation point that is affixed to bone. (Item 4) 4. The method of claim 3, wherein the additional fixation point is a pedicle screw. (Item 5) Item 10. The method of item 1, wherein the trocar is curved. (Item 6) Item 10. The method of item 1, wherein the trocar is inserted from the outside. (Item 7) Item 10. The method of item 1, wherein the trocar is inserted posteriorly. (Item 8) Item 10. The method of item 1, wherein the inflatable balloon further comprises an outer sleeve. (Item 9) 9. The method of claim 8, wherein the outer sleeve includes a roughened surface to widen the disc space and effect further expansion. (Item 10) Item 10. The method of item 1, further comprising one or more load-bearing structures. (Item 11) Item 11. The method of item 10, wherein the one or more load-bearing structures are filled with a load-bearing material. (Item 12) 12. The method of claim 11, wherein the load-bearing material is cement, demineralized bone putty, epoxy, rigid particles, small metal particles, bone chips, or a combination thereof. (Item 13) Item 10. The method of item 1, wherein the trocar further comprises one or more sensors. (Item 14) Item 14. The method of item 13, wherein the one or more sensors are a pressure sensor, an impedance sensor, an ultrasonic sensor, or a combination thereof. (Item 15) Item 10. The method of item 1, wherein the interbody implant includes a closure mechanism. (Item 16) Item 16. The method of item 15, wherein the closure mechanism prevents extrusion of the inner material. (Item 17) Item 17. The method of item 16, wherein the closure mechanism is a mechanical crimp, an electrostatic closure, a screw cap, a plug, or a combination thereof. (Item 18) Item 10. The method of item 1, wherein the inflatable balloon is inserted over a trocar. (Item 19) 1. An interbody system comprising: an interbody implant including an expansion balloon; Trocar and Equipped with The interbody implant is inserted through the trocar. Interbody system. (Item 20) 20. The interbody system of item 19, wherein the interbody implant is an extensible filament. (Item 21) 20. The interbody system of item 19, wherein the interbody implant comprises a braided structure, a woven structure, a knitted structure, a mesh structure, or a combination thereof. [Brief explanation of the drawings]

[0034] [Figure 1] FIG. 1 depicts all of the posterior, posterolateral, lateral, anterolateral, and anterior approaches to the spine for insertion of an interbody device.

[0035] [Figure 2] Figure 2 is an illustration of Kambin's triangle.

[0036] [Figure 3] 3 illustrates an exemplary embodiment of the system described herein, namely, "Exemplary Embodiment 1: Structure Combined with Mesh." The figure depicts the collapsed and expanded positions.

[0037] [Figure 4] 4 illustrates an exemplary embodiment of the system described herein, namely, "Exemplary Embodiment 2: Structure with Tapered Leading Edge." FIG. 4 depicts an enlarged configuration in one plane.

[0038] [Figure 5] Figure 5 illustrates an example of a matrix structure in an insertion configuration that is transitioned to an expanded configuration. Figure 5 depicts only one plane of the structure.

[0039] [Figure 6]6 illustrates an example of an approach trajectory and trocar access that can be visualized under radiographic imaging and includes the ability to drill through cortical bone. The trocar can have sensors such as, but not limited to, neuromonitoring sensors, pressure sensors, impedance sensors, and the like, and / or combinations thereof.

[0040] [Figure 7] FIG. 7 illustrates an example of balloon-assisted disc space distraction.

[0041] [Figure 8] FIG. 8 illustrates an example of disc space distraction utilizing a balloon to compact or disrupt the annulus.

[0042] [Figure 9] FIG. 9 illustrates an example of disc space distraction with an expanding balloon to restore foraminal height.

[0043] [Figure 10] FIG. 10 illustrates disc space clearance and distraction with the balloon expanding to maximize surface area contact with the vertebral endplates.

[0044] [Figure 11] 11 illustrates the balloon being inserted through the trocar and pivoted away from the insertion trajectory, and deployed past the valve annulus.

[0045] [Figure 12] FIG. 12 illustrates the step of expanding a balloon with a texture to provide friction against sliding, which enlarges and ruptures the annulus, enabling further expansion.

[0046] [Figure 13]13 illustrates the use of a multi-chamber balloon to effect selective enlargement and / or distraction of the anterior versus posterior portion of the interbody space. The chambers can be enlarged synchronously or independently. Enlargement to create lordosis and disrupt the anterior portion of the annulus is shown.

[0047] [Figure 14] 14 depicts selective distraction osteogenesis in the anterior portion of the disc space to disrupt the anterior wall of the annulus using instrumentation including inflation pressure and / or volume feedback to the user. The balloon can be filled with a liquid or gas.

[0048] [Figure 15] 15 illustrates a pre-shaped balloon configured to expand more in the anterior portion to create lordosis. The balloon is removed and left in place.

[0049] [Figure 16] 16 illustrates an interbody implant placed through a minimally invasive access window after the initial dilation balloon has been removed from the space. A containment device is depicted that is both braided and load-bearing. The containment device can also be braided, woven, knitted, or the like.

[0050] [Figure 17] FIG. 17 illustrates a pouch-like containment device filled with a load-bearing filler material.

[0051] [Figure 18] FIG. 18 illustrates an interbody implant deployed to maximize contact surface area and maintain the desired height and lordosis angle.

[0052] [Figure 19] FIG. 19 illustrates an interbody implant deployed in an off-axis trajectory of the insertion angle, which prevents sliding of the implant back out through the access trajectory.

[0053] [Figure 20] Figure 20 illustrates an expanding scaffold structure that is locked into place. This is an example of a locking mechanism.

[0054] [Figure 21] FIG. 21 illustrates the structure of a compacted, initially bent tubule that can be expanded into a straightened tubule.

[0055] [Figure 22] FIG. 22 illustrates the mesh expanded to a longitudinally shortened but radially expanded state and elongated for delivery.

[0056] [Figure 23] FIG. 23 illustrates a load-bearing structure deployed by a pump to further enlarge the disc space using a fixation mechanism.

[0057] [Figure 24] FIG. 24 illustrates a multiple balloon or multi-chamber balloon that enables expansion in multiple directions into preconfigured or adjustable geometries.

[0058] [Figure 25] FIG. 25 illustrates multiple magnification mechanisms that effect magnification in different directions.

[0059] [Figure 26] FIG. 26 illustrates the twisted end of the containment device as a closure mechanism.

[0060] [Figure 27] FIG. 27 illustrates the crimped end of the containment device as a closure mechanism.

[0061] [Figure 28]FIG. 28 illustrates a containment device filled with larger interlocking particles that create greater porosity and trabecular formation.

[0062] [Figure 29] FIG. 29 illustrates a containment device that is filled with smaller particles that create less porosity and trabeculation. DETAILED DESCRIPTION OF THE INVENTION

[0063] Detailed Description Prior to insertion, the devices described herein can exist in a collapsed state that minimizes overall footprint, height, and lordosis. Once the disc is resected or an insertion path is created, the device can be inserted using a specialized hammer, which allows for manipulation of the insertion angle. Once the tool is inserted into the disc space, the hammer can be used to expand the device to the desired height, lordosis, and / or footprint. Additional methods can be used to dissect the disc space while the device is being expanded. The expandable footprint increases contact points and increases peripheral contact with the vertebral endplates, thereby distributing compression forces and reducing the probability of fracture. Furthermore, a greater amount of contact points can encourage a greater range of bony fusion, thereby minimizing the risk of cage migration.

[0064] The terms "interbody body," "interbody device," and "interbody implant" are used interchangeably throughout this specification. In some embodiments, the interbody device can be a stent. Exemplary embodiment 1: Hydraulic bone in a pouch

[0065] This embodiment involves a collapsed structure attached to a mesh enclosure. Upon insertion, the device is locked into place as it expands within the disc space using a hydraulic mechanism, such as a fluid- or gas-filled balloon. Once the desired expansion is achieved, the mesh is filled with bone graft until it abuts the vertebral endplates, increasing the contact area. Exemplary Embodiment 2: Tapered Insertion Geometry with Assisted Disc Expansion

[0066] This embodiment utilizes a tapered geometry in multiple planes at the leading edge of the device to reduce the required insertion force. The device consists of multiple bodies. Upon insertion, the disc space is opened using a hydraulic mechanism, such as, but not limited to, a fluid-filled balloon. The upper body is expanded about the pivot and locked into place when the desired height and lordosis is met. The bodies may be attached to a mesh that is filled with bone graft until the mesh contours to the vertebral endplates and increases the contact area. Exemplary embodiment 3: matrix structure

[0067] This embodiment involves a structure with multiple cells. The cells are formed with multiple connecting branches. In a collapsed state, the structure is nested in a compacted configuration. The structure contains additional bodies that contact multiple cells. Upon insertion, the additional bodies mechanically engage with the structure and lock into place to expand the structure. The structure expands until the cell connections contact the vertebral endplates at multiple contact points, thereby distributing compressive forces. Exemplary embodiment 4: peacock tail

[0068] This embodiment involves expansion around a pivot, where multiple bodies rotate to expand the footprint. When in the collapsed configuration, the bodies can nest together and upon insertion, open up and expand to create one larger structure. This structure can promote better bone fusion and stability by increasing the contact surface area and engaging a larger portion of the endplates. Example embodiment 5: Nested scaffolds

[0069] This embodiment involves an expansion method in which multiple bodies nest within one another while in a collapsed state, in a manner similar to Russian dolls. Upon insertion, pieces located within the parent piece can be pulled out and locked into an expanded conformal shape to increase the contact surface area. Exemplary Embodiment 6: Deployment of Plates Prior to Insertion of Constructs

[0070] This embodiment uses a temporary method to expand the disc space prior to insertion of the disc device. The insertion of endplates coupled with the expansion mechanism increases the stability of the restored disc height and establishes more contact points, thus evenly distributing compression forces. Exemplary Embodiment 7: Augmentation

[0071] This embodiment involves adding multiple pieces of the same size to the initial piece after installation of the initial piece is completed. The initial piece is inserted to establish positioning, and then additional pieces are added to the originally inserted piece to increase the contact surface area and evenly distribute the compressive forces exerted on the interbody device.

[0072] In some embodiments, the interbody implants (devices) described herein can include a trocar, which can be minimally invasively placed into the target intervertebral space to confirm trajectory via radiographic imaging, as depicted in Figure 11. In other embodiments, the trocar can inject a dye or tracer solution that penetrates part or all of the intervertebral space to allow the surgeon to visualize the space.

[0073] In some embodiments, the trocar can also function as an intraoperative neuromonitoring probe or sensor to ensure the insertion trajectory remains on an acceptable and safe path. The trocar can be attached to a stereotactic system for navigation or fixation points, such as pedicle screws or bone, to provide mechanical stability or leverage. In other embodiments, the trocar can have stereotactic fiducials for integration with the navigation system.

[0074] The trocar can be curved, steerable, or have any shape memory to enable access to the target site in a non-straight manner.

[0075] In some embodiments, the trocar can have components or geometries that enable drilling through cortical bone, as depicted in FIG. 6 . In other embodiments, the trocar can have geometries that will enable access through a transpedicular approach aimed from above to gain access to the disc space through the end plates of the vertebral bodies. In some embodiments, the trocar can have geometries that enable access through a lateral or oblique-lateral approach, in which the trocar can enter the disc space below Kambin's triangle through the lateral vertebral body wall and the superior end plate below Kambin's triangle. In other embodiments, the trocar can have geometries that enable access into the disc space through an approach that proceeds through the superior articular process of the facet joint.

[0076] In some embodiments, the trocar can include one or more sensors that can be used to characterize the type of tissue the trocar is traversing. The one or more sensors can be, but are not limited to, a pressure sensor, an impedance sensor, an ultrasound sensor, and the like, and / or combinations thereof.

[0077] In other embodiments, the trocar can have a shim-like bullet-head geometry that allows for blunt access to be gained into the tight disc space without having sharp edges that could impinge on the endplates or inadvertently cut the dura.

[0078] In other embodiments, the trocar can employ a mechanism to prevent it from backing out. This mechanism can include an enlarged radius at the distal end. Alternatively, the trocar can be coupled to a screw anchoring mechanism that anchors it to the bone it traverses.

[0079] In some embodiments, the interbody devices described herein can include disc preparation instrumentation that can be used to dissect, cut, or resect tissue or bone within the disc space through a minimally invasive access trajectory. Disc preparation instruments can include, but are not limited to, augers, drills, cutters, bites, scrapers, perforators, and the like, and / or combinations thereof. The disc preparation instrumentation can be enlarged to allow inter-endplate contact. The instrumentation can have a steerable working tip. In some embodiments, the tip can be articulated in one or more directions. Steering can be achieved through couplings, gear mechanisms, cable mechanisms, shape memory properties, and the like. In some embodiments, the disc preparation instrumentation can be used to enlarge the disc space.

[0080] In other embodiments, the system can include an expansion balloon, pouch, bladder, or the like. The expansion balloon, pouch, bladder, or the like can be inserted over, through, or through a passageway created by a trocar, as depicted in FIG. 6 . The balloon can be used to apply pressure to connective tissue within the target disc space. In some embodiments, the expansion force can be used to break, stretch, or separate connective tissue or bone compressing the space. In other embodiments, the expansion force can be used to compact connective tissue or bone to create a void for the implant to be deployed. In some embodiments, the expansion force can be used to shift, move, or push connective tissue or bone to create a space for the implant to be deployed.

[0081] The balloon can include a surface treatment to provide friction for sliding, including, but not limited to, metal traces on the outer surface, roughened surfaces, grids, adhesives, and the like.

[0082] In some embodiments, the balloon can be deployed within another device that can be used to dilate a space or cut tissue. The instrumentation can pivot the balloon so that it is no longer aligned with the insertion trajectory once it is delivered to the target space. This can place the balloon in a more favorable position for dilation. This can also prevent the balloon from sliding out of the insertion path when it encounters opposing forces during dilation, as depicted in FIG. 11.

[0083] In other embodiments, the balloon can include one or more sensors to indicate its deployment status and provide safety feedback to the surgeon or control system, as depicted in FIG. 14 . In some embodiments, the sensor can be a strain gauge on the surface of the balloon to measure the degree of expansion. Multiple strain gauges on the surface of the balloon can determine the three-dimensional expansion direction of the balloon. In other embodiments, the sensor can be a pressure gauge to provide feedback regarding the force being exerted or the rate of expansion. This can be used as information for the surgeon regarding the magnitude of compression. This can also be used to provide safety protection against overexpansion and potential rupture of the balloon. A sudden drop in pressure can be used to indicate connective tissue rupture. In some embodiments, the sensor can be configured for volumetric measurement, allowing feedback regarding the size and volume of the available disc space.

[0084] In some embodiments, the balloon can be pressurized with a gas or liquid. In other embodiments, the balloon is removed from the patient before the next step. In some embodiments, the balloon can be removed and left in the patient before the next step.

[0085] The balloon may be radiopaque or filled with a radiopaque material so that it can be inflated to conform to the prepared disc space and visualized by radiography or the like. The balloon or a device connected to the balloon may enable the user to extrapolate the expansion volume of the balloon and the height of the anterior, posterior, or lateral boundaries.

[0086] The balloon can incorporate multiple chambers that enable expansion in different directions or shapes. FIG. 13 depicts a balloon with multiple chambers 302 and 302′. The balloon can be composed of one or more chambers. The number of chambers can depend on the different directions and / or shapes desired. In some embodiments, the balloon can be pre-shaped to enable directional or preferential expansion of different sections of the intervertebral space, as depicted in FIG. 15. The balloon can be deployed past the annulus from the outside or anteriorly, as depicted in FIG. 11. The balloon can incorporate multiple chambers that can be expanded together or independently, as depicted in FIG. 13.

[0087] The system can include one or more load-bearing structures that can be deployed at the target site following space preparation. The use of an expansion balloon prior to deploying the load-bearing structure enables the use of a structure that, when deployed, has a low expansion force but a high static load-bearing capacity. One example is an expandable scaffold structure that is locked in place to withstand static forces, as depicted by FIG. 20 . The locking mechanism can be a ratchet mechanism, a catch mechanism, a pin or equivalent engagement, and / or a combination thereof. Another example is a structure made of a shape-memory material in which the canaliculus is initially bent to form a compacted and collapsed configuration for insertion, which then returns to a straightened canaliculus to provide robust static load-bearing capacity, as depicted by FIG. 21 . Another example includes a penetrable mesh having a proximal end, a distal end, a radially constrained elongated state configured for delivery within a catheter lumen or trocar, and an expanded state with a longitudinally shortened configuration relative to the radially constrained state, as depicted by FIG. 22 , and a plurality of elongated filaments woven together to form the mesh.

[0088] The use of an expansion balloon reduces the expansion force required to deploy the load-bearing structure, but deployment of the load-bearing structure can also continue to expand the disc space. Deployment of the load-bearing structure can be used to drive fixation features into the vertebrae above and below the space. In some embodiments, the fixation features can include nails, screws, spikes, lattices, meshing, grit, or the like at the interface surface to the vertebral endplates. Expansion forces can be used to drive these fixation features into adjacent connective tissue and / or bone. The expansion means can be pneumatic, hydraulic, mechanical, shape-memory, gas-expansion, via chemical reaction or thermal expansion, and the like.

[0089] An alternative or supplement to deploying a load-bearing structure can be to deploy a containment pouch, mesh, braid, woven fabric, knitted fabric, balloon, or the like, and fill the containment device with a load-bearing filler material. Using a containment device that conforms to the disc space and adjacent vertebral endplates can maximize the load-bearing surface area. Some advantages of this include greater durability and reduced or prevented subsidence and the like. The containment device can be load-bearing by itself, as depicted in FIG. 17, or can be filled with a load-bearing filler material. The containment device can have a closure mechanism after filling is complete, as depicted in FIG. 24. The closure mechanism can be a cap, a crimp closure of an open end, a twist closure of a malleable portion, adhesive, a screw cap, and the like, and / or a combination thereof.

[0090] In some embodiments, the load-bearing structure and / or containment device can be filled with a material. The material can be a load-bearing filler material to provide additional load-bearing capacity. The filler material can be, but is not limited to, a liquid, gas, solid, particulate, or the like, and / or a combination thereof, with various properties. The material can include, but is not limited to, compressive strength, tensile strength, adhesion, promotion of bone ingrowth, phase change, solidification, and / or combinations thereof. The filler material can be, but is not limited to, cement, demineralized bone putty, epoxy, rigid particles, small metal particles, bone chips, and / or combinations thereof. Some filler materials, such as, but not limited to, cement, epoxy, putty, may allow for pressure injection, which can be controlled to reach a certain pressure to ensure it is load-bearing. A filler material that is in a liquid state can remain liquid or can be hardened, set, or consolidated into a more solid-like structure. Smaller particle fillers, such as, but not limited to, sand-like particles of demineralized bone, biomaterials, silica particles, ceramic particles, metal particles, bone particles, and / or combinations thereof, can be tamped and packed to ensure load-bearing, as depicted by FIG. 28. Similarly, larger rigid particles can be tamped and packed into a containment device. When these larger rigid particles are packed together, their physical characteristics can interlock to fracture the rigid structure, as depicted by FIG. 23. Combinations of different types of filler materials can also be used. When using a hardener, a relatively longer hardening time, such as about 1-2 hours, can enable removal of the implant during the procedure.

[0091] One feature of different filler material configurations is the resulting porosity and trabecular formation of the load-bearing material. Smaller filler material particles lead to a denser bulk with lower porosity. Larger filler material particles lead to a less dense bulk with higher porosity. Various combinations of particle sizes can be used to achieve the desired density and porosity.

[0092] The filler material or additive may also have additional properties to promote bone ingrowth. In some embodiments, BMP2, collagen, hydroxyapetite, or other or combinations of such additives may be used. In other embodiments, the filler material has inherent properties that promote bone ingrowth, such as tantalum surfaces and the like.

[0093] In some embodiments, a method of deploying an interbody implant into an intervertebral disc space includes inserting an inflatable balloon into the intervertebral disc space, the inflatable balloon configured to expand into the intervertebral disc space, thereby widening the disc space; inflating the inflatable balloon to restore foraminal height; withdrawing the inflatable balloon from the disc space; guiding the interbody implant into the disc space through a minimally invasive access window; and deploying the interbody implant into the disc space.

[0094] The interbody implant can be a tensile filament. In other embodiments, the trocar is attached to an additional fixation point that is affixed to the bone. The additional fixation point can be a pedicle screw. In some embodiments, the trocar is curved. The trocar can be inserted from the lateral or posterior side. In other embodiments, the inflatable balloon further comprises an outer sleeve. The outer sleeve can include a roughened surface to widen the disc space and facilitate further expansion.

[0095] In some embodiments, the interbody system further comprises one or more load-bearing structures. There may be one, two, three, four, or more load-bearing structures. The one or more load-bearing structures may be filled with a load-bearing material. The load-bearing material may include, but is not limited to, cement, demineralized bone putty, epoxy, rigid particles, small metal particles, bone chips, or a combination thereof.

[0096] In other embodiments, the trocar further comprises one or more sensors. The one or more sensors can be a pressure sensor, an impedance sensor, an ultrasound sensor, or a combination thereof. In some embodiments, the interbody implant can include a closure mechanism. The closure mechanism can prevent extrusion of the inner material. The closure mechanism can be a mechanical crimp, an electrostatic closure, a screw cap, a plug, or a combination thereof. In other embodiments, an inflatable balloon can be inserted onto, within, or over the trocar. In some embodiments, the inflatable balloon can be configured to attach to the trocar in a desired configuration to enlarge and / or widen the intervertebral disc space.

[0097] In some embodiments, a method of implanting an interbody implant into an intervertebral disc space includes inserting an inflatable balloon into the intervertebral disc space, the inflatable balloon configured to expand into the intervertebral disc space, thereby widening the disc space; inflating the inflatable balloon to restore foraminal height; withdrawing the inflatable balloon from the disc space; guiding the interbody implant into the disc space through a minimally invasive access window; and implanting the interbody implant into the disc space.

[0098] In some embodiments, the degree of vertebral body space expansion is between about 0 degrees and about 30 degrees, between about 0 degrees and about 10 degrees, between about 0 degrees and about 20 degrees, between about 10 degrees and about 20 degrees, between about 10 degrees and about 30 degrees, between about 20 degrees and about 30 degrees, 0 degrees, 1 degree, 2 degrees, 3 degrees, 4 degrees, 5 degrees, 6 degrees, 7 degrees, 8 degrees, 9 degrees, 10 degrees, 11 degrees, 12 degrees, 13 degrees, 14 degrees, 15 degrees, 16 degrees, 17 degrees, 18 degrees, 19 degrees, 20 degrees, 21 degrees, 22 degrees, 23 degrees, 24 degrees, 25 degrees, 26 degrees, 27 degrees, 28 degrees, 29 degrees, 30 degrees, 31 degrees, 32 degrees, 33 degrees, 34 degrees, 35 degrees, 36 degrees, 37 degrees, 38 degrees, 39 degrees, 40 degrees, 41 degrees, 42 degrees, 43 degrees, 44 degrees, 45 degrees, 46 degrees, 47 degrees, 48 ​​degrees, 49 degrees, 50 degrees, 51 degrees, 52 degrees, 53 degrees, 54 degrees, 55 degrees, 56 degrees, 57 degrees, 58 degrees, 59 degrees, 60 degrees, 61 degrees, 62 degrees, 63 degrees, 64 degrees, 65 degrees, 66 degrees, 67 degrees, 68 degrees, 69 degrees, 70 degrees, 71 degrees, 72 degrees, 73 degrees, 74 degrees, 75 degrees, 76 degrees, 77 degrees, 78 degrees, 79 degrees, 80 degrees, 81 degrees, 82 degrees, 83 degrees, 84 degrees, 85 degrees, The angle can be in the range of 27 degrees, 28 degrees, 29 degrees, 30 degrees, about 0 degrees, about 1 degree, about 2 degrees, about 3 degrees, about 4 degrees, about 5 degrees, about 6 degrees, about 7 degrees, about 8 degrees, about 9 degrees, about 10 degrees, about 11 degrees, about 12 degrees, about 13 degrees, about 14 degrees, about 15 degrees, about 16 degrees, about 17 degrees, about 18 degrees, about 19 degrees, about 20 degrees, about 21 degrees, about 22 degrees, about 23 degrees, about 24 degrees, about 25 degrees, about 26 degrees, about 27 degrees, about 28 degrees, about 29 degrees, or about 30 degrees. In other embodiments, the angle range can be prior to the step of deploying / implanting the interbody implant. In some embodiments, the angle range can be after the step of deploying / implanting the interbody implant.

[0099] In another embodiment, a method of deploying an interbody implant into an intervertebral disc space includes inserting an inflatable balloon into the intervertebral disc space, the inflatable balloon configured to expand into the intervertebral disc space, thereby enlarging the intervertebral disc space; inflating the inflatable balloon to restore foraminal height; withdrawing the inflatable balloon from the disc space; guiding the interbody implant into the intervertebral disc space through a minimally invasive access window; and deploying the interbody implant into the disc space.

[0100] In some embodiments, the interbody system includes an interbody implant including an expansion balloon and a trocar, through which the interbody implant is inserted. The interbody implant can be an expandable filament. In other embodiments, the interbody implant can include a braided structure, a woven structure, a knitted structure, a mesh structure, or a combination thereof. In some embodiments, the interbody system can further include a device or multiple devices / instrumentation for disc preparation. Disc preparation can include reaming any tissue space and / or expanding the space to create a void for the interbody implant. In other embodiments, the interbody system can further include one or more load-bearing structures.

[0101] In some embodiments, the systems described herein are utilized for spinal interbody implant procedural techniques. The interbody implant can be an expandable filamentary interbody device. A trocar is advanced into the intervertebral space. The intervertebral space can be identified using injection of a dye, which should penetrate through the empty or degenerated disc space and into the vertebral body. With respect to the disc space, this can identify a dense intervertebral space.

[0102] The balloon can be inserted with angulation to prevent the balloon from backing out through its initial trajectory at high pressure, given that the disc tends to slide against the bone.

[0103] Possible auditory or visual feedback can signal the absolute pressure and the rate of pressure change to the operator, which can assist the operator in assessing whether the disc or the entire intervertebral space has "snapped."

[0104] Intraoperative neuromonitoring over the trocar itself can be useful for percutaneous transforaminal approaches through Kambin's triangle.

[0105] In some embodiments, the trocar can be attached to additional fixation points that are affixed to bone (such as, but not limited to, one or more pedicle screws or equivalent, a facet joint, or a lamina) to prevent it from backing out.

[0106] For better direct balloon and implant deployment, deploy the balloon over a curved trocar with either a varying curvature or adjustable curvature. The purpose of deploying over a curved trocar is to prevent retraction of the lifting balloon and implant.

[0107] In some embodiments, trocar insertion can be posterior, including but not limited to percutaneous or endoscopic via Kambin's triangle, open or MIS incision after a hemi-laminectomy (tubular approach), transpedicular, or intended to proceed through the superior articular process.

[0108] In other embodiments, trocar insertion can be from the outside. External can include, but is not limited to, an incision through an external retractor with a monitored trocar inserted through the psoas muscle without disrupting it. An advantage of this procedure is that the psoas muscle is not disrupted or torn for disc preparation or insertion because there is no large implant being pushed through the psoas muscle.

[0109] In some embodiments, for the second stage after expanding the disc space, an implant with an internal expansion balloon can be deployed prior to or during the step of filling with cement or demineralized bone putty to confirm positioning, provide additional expansion, and maintain the expanded position. Interbody lifting balloon + disc preparation

[0110] In some embodiments, an inflatable balloon is used to widen the disc space. The inflatable balloon can include an outer sleeve over the lifting balloon with a roughened or lattice-like surface that, upon expansion, helps widen the disc space. This can also allow for roughening of the bone without impinging on the endplates, which may promote fusion. The sleeve can also provide additional friction within the disc space to prevent backing out.

[0111] In other embodiments, the inflatable balloon can induce angulation in the orientation of the vertebral bodies via preformed dimensions for lordosis / kyphosis correction or correction of coronal misalignment.

[0112] In some embodiments, the balloon side has a shape with a greater anterior height to allow for various sizes to align with the endplates or advance past the endplates on the lateral or anterior surfaces of the vertebral bodies to loosen or rupture the anterior longitudinal ligament or lateral osteophytes, or to reposition the vertebral body alignment.

[0113] In some embodiments, the balloon includes attachments that enable directional bone / disc clearance. In other embodiments, the balloon includes a pressure indicator that reads pressure and / or rate of pressure increase per cc of fluid to provide a rate of pressure change.

[0114] In some embodiments, the balloon includes the option of stereotactic guidance for use with a stereotactic guidance system or an augmented reality platform. Radiopacity of the balloon wall or the use of contrast agents can be present to visualize deployment.

[0115] In some embodiments, there can be a mesh of pressure cages as a sleeve over the balloon to provide information on load distribution and expansion direction. The trocar can have a tapered "shim profile" to aid in sliding it into the tight intervertebral space.

[0116] An endoscopic tool or removal obturator to effectuate disc space widening, with or without attachment to a bony medium as a fixation point. Spinal extensible filamentary interbody implant with internal expansion balloon

[0117] Described herein is a spinal extensible filamentary interbody implant with an internal expanding balloon. The interbody implant can be an implantable filamentary device, including a braided, woven, knitted, meshed, or any other structure that can be press-fit into bone and integrated with it.

[0118] In some embodiments, the filamentous interbody device can have inherent properties in the metal that allow for bone ingrowth. In other embodiments, the metal can be surface treated to allow for bone ingrowth, such as, but not limited to, titanium spray deposition of hydroxyapetite. In other embodiments, the expandable implant can be "tri-sized" and reversible. The implant can be sized to satisfy angulation, size, and alignment by deploying a balloon within the implant to ensure it fits.

[0119] In some embodiments, the filamentary interbody device is reversible and can be removed while simultaneously moving the filler material out of the intervertebral space.

[0120] In some embodiments, the implant can include a shape with a leading edge of greater height. In other embodiments, the implant can maximize implant expansion to the outer edge of the endplate. In some embodiments, the implant can include an inner mesh with strain gauges to read out the distribution of forces on the implant. The implant can be expanded sufficiently to have an even distribution of load. In some embodiments, the implant is a stent.

[0121] In some embodiments, the implant can be "closable" following backfilling to prevent extrusion of the inner material. Other embodiments can include mechanical crimping, electrostatic closure, screw caps, plugs, or other types of closure mechanisms.

[0122] Unless otherwise indicated, all numerical values ​​used in the specification and claims, expressing properties such as quantities of ingredients, molecular weights, reaction conditions, and the like, are to be understood in all instances as modified by the term "about." Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and appended claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should, at the very least, be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values ​​set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their individual testing measurements.

[0123] As used in the context of describing the present invention (particularly in the context of the claims that follow), the terms "a," "an," and "the," and similar referents, should be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The recitation of ranges of values ​​herein is intended merely to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each separate value is incorporated herein as if it were individually listed herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or clearly contradicted otherwise by context. The use of any and all examples or exemplary language (e.g., "such as") provided herein is intended merely to better elucidate the invention and does not pose a limitation on the scope of the invention as otherwise claimed. No language herein should be construed as indicating any non-claimed element essential to the practice of the invention.

[0124] Although the use of the term "or" in the claims is used to mean "and / or" unless expressly indicated to refer to alternatives only or unless the alternatives are mutually exclusive, the present disclosure supports a definition that refers to alternatives only and "and / or."

[0125] Groups of alternative elements or embodiments of the invention disclosed herein should not be construed as limiting. Members of each group may be referenced and claimed individually or in any combination with other members of the group or other elements found herein. It is anticipated that one or more members of a group may be included in or deleted from a group for reasons of convenience and / or patentability. When any such inclusion or deletion occurs, the specification herein includes the group as modified and is thus deemed to fulfill the written description of all Markush groups used in the appended claims.

[0126] Preferred embodiments of the present invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations on these preferred embodiments will, of course, become apparent to those skilled in the art upon perusal of the foregoing description. The inventors anticipate that skilled artisans will employ such variations as necessary, and the inventors intend for the invention to be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Furthermore, any combination of the above-described elements in all possible variations thereof is covered by the invention unless otherwise indicated herein or clearly contradicted by context.

[0127] Specific embodiments disclosed herein may be further limited in the claims using the terms "consisting of" or "consisting essentially of." When used in a claim, whether as filed or added through an amendment, the transitional term "consisting of" excludes any element, step, or ingredient not recited in the claim. The transitional term "consisting essentially of" limits the scope of the claim to the recited materials or steps and those that do not materially affect the basic and novel characteristics. Embodiments of the invention so claimed are inherently or explicitly described and enabled herein.

[0128] Furthermore, it is to be understood that the embodiments of the invention disclosed herein are illustrative of the principles of the invention. Other modifications that may be employed are within the scope of the invention. Thus, by way of example, and not of limitation, alternative configurations of the invention may be utilized in accordance with the teachings herein. Therefore, the invention is not limited to that precisely as shown and described.

Claims

[Claim 1] The invention described in this specification.

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