# Patent

## Title
System for use in bone cement preparation and delivery

## Abstract

A system for use in bone cement preparation can include a chamber for intermixing a liquid monomer and solid polymer components, a container, a vacuum channel, and a filter. The mixing chamber can be configured to hold a non-liquid, polymer powder component of a bone cement. The container can be configured to hold a liquid component of the bone cement. The system can have a first interface disposed between the mixing chamber and the container and a second interface disposed between the mixing chamber and the vacuum channel. The second interface can to receive and position the filter between the mixing chamber and the vacuum channel. The vacuum channel can direct a partial vacuum to draw the liquid component from the container into the non-liquid component in the mixing chamber to intermix the components and to thereby provide a settable bone cement.

## Background
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation of U.S. patent application Ser. No. 12/578,163, filed Oct. 13, 2009, which claims the benefit of priority under 35 U.S.C. § 119(e) of U.S. Provisional Application No. 61/104,979 filed Oct. 13, 2008. This application is related to the following U.S. patent application Ser. No. 12/427,531 filed Apr. 21, 2009, titled Bone Treatment Systems and Methods; and Provisional Application No. 61/124,916 filed Apr. 21, 2008, titled Bone Treatment Systems and Methods. The entire contents of all of the above applications are hereby incorporated by reference and should be considered a part of this specification.


BACKGROUND OF THE INVENTION
Field of the Invention
Embodiments of the present disclosure relate to bone cement injection systems, and in some embodiments provide a system for controlling the viscosity of injected bone cement to prevent extravasation.
Description of the Related Art
Osteoporotic fractures are prevalent in the elderly, with an annual estimate of 1.5 million fractures in the United States alone. These include 750,000 vertebral compression fractures (VCFs) and 250,000 hip fractures. The annual cost of osteoporotic fractures in the United States has been estimated at $13.8 billion. The prevalence of VCFs in women age 50 and older has been estimated at 26%. The prevalence increases with age, reaching 40% among 80-year-old women. Medical advances aimed at slowing or arresting bone loss from aging have not provided solutions to this problem. Further, the population affected will grow steadily as life expectancy increases. Osteoporosis affects the entire skeleton but most commonly causes fractures in the spine and hip. Spinal or vertebral fractures also cause other serious side effects, with patients suffering from loss of height, deformity and persistent pain which can significantly impair mobility and quality of life. Fracture pain usually lasts 4 to 6 weeks, with intense pain at the fracture site. Chronic pain often occurs when one vertebral level is greatly collapsed or multiple levels are collapsed.
Postmenopausal women are predisposed to fractures, such as in the vertebrae, due to a decrease in bone mineral density that accompanies postmenopausal osteoporosis. Osteoporosis is a pathologic state that literally means “porous bones”. Skeletal bones are made up of a thick cortical shell and a strong inner meshwork, or cancellous bone, of collagen, calcium salts and other minerals. Cancellous bone is similar to a honeycomb, with blood vessels and bone marrow in the spaces. Osteoporosis describes a condition of decreased bone mass that leads to fragile bones which are at an increased risk for fractures. In an osteoporosis bone, the sponge-like cancellous bone has pores or voids that increase in dimension making the bone very fragile. In young, healthy bone tissue, bone breakdown occurs continually as the result of osteoclast activity, but the breakdown is balanced by new bone formation by osteoblasts. In an elderly patient, bone resorption can surpass bone formation thus resulting in deterioration of bone density. Osteoporosis occurs largely without symptoms until a fracture occurs.
Vertebroplasty and kyphoplasty are recently developed techniques for treating vertebral compression fractures. Percutaneous vertebroplasty was first reported by a French group in 1987 for the treatment of painful hemangiomas. In the 1990's, percutaneous vertebroplasty was extended to indications including osteoporotic vertebral compression fractures, traumatic compression fractures, and painful vertebral metastasis. Vertebroplasty is the percutaneous injection of PMMA (polymethylmethacrylate) into a fractured vertebral body via a trocar and cannula. The targeted vertebrae are identified under fluoroscopy. A needle is introduced into the vertebrae body under fluoroscopic control, to allow direct visualization. A bilateral transpedicular (through the pedicle of the vertebrae) approach is typical but the procedure can be done unilaterally. The bilateral transpedicular approach allows for more uniform PMMA infill of the vertebra.
In a bilateral approach, approximately 1 to 4 ml of PMMA is used on each side of the vertebra. Since the PMMA needs to be forced into the cancellous bone, the techniques require high pressures and fairly low viscosity cement. Since the cortical bone of the targeted vertebra may have a recent fracture, there is the potential of PMMA leakage. The PMMA cement contains radiopaque materials so that when injected under live fluoroscopy, cement localization and leakage can be observed. The visualization of PMMA injection and extravasation are critical to the technique—and the physician terminates PMMA injection when leakage is evident. The cement is injected using syringes to allow the physician manual control of injection pressure.
Kyphoplasty is a modification of percutaneous vertebroplasty. Kyphoplasty involves a preliminary step consisting of the percutaneous placement of an inflatable balloon tamp in the vertebral body. Inflation of the balloon creates a cavity in the bone prior to cement injection. The proponents of percutaneous kyphoplasty have suggested that high pressure balloon-tamp inflation can at least partially restore vertebral body height. In kyphoplasty, some physicians state that PMMA can be injected at a lower pressure into the collapsed vertebra since a cavity exists, when compared to conventional vertebroplasty.
The principal indications for any form of vertebroplasty are osteoporotic vertebral collapse with debilitating pain. Radiography and computed tomography must be performed in the days preceding treatment to determine the extent of vertebral collapse, the presence of epidural or foraminal stenosis caused by bone fragment retropulsion, the presence of cortical destruction or fracture and the visibility and degree of involvement of the pedicles.
Leakage of PMMA during vertebroplasty can result in very serious complications including compression of adjacent structures that necessitate emergency decompressive surgery. See Groen, R. et al., “Anatomical and Pathological Considerations in Percutaneous Vertebroplasty and Kyphoplasty: A Reappraisal of the Vertebral Venous System,” Spine Vol. 29, No. 13, pp 1465-1471, 2004. Leakage or extravasation of PMMA is a critical issue and can be divided into paravertebral leakage, venous infiltration, epidural leakage and intradiscal leakage. The exothermic reaction of PMMA carries potential catastrophic consequences if thermal damage were to extend to the dural sac, cord, and nerve roots. Surgical evacuation of leaked cement in the spinal canal has been reported. It has been found that leakage of PMMA is related to various clinical factors such as the vertebral compression pattern, and the extent of the cortical fracture, bone mineral density, the interval from injury to operation, the amount of PMMA injected and the location of the injector tip. In one recent study, close to 50% of vertebroplasty cases resulted in leakage of PMMA from the vertebral bodies. See Hyun-Woo Do et al., “The Analysis of Polymethylmethacrylate Leakage after Vertebroplasty for Vertebral Body Compression Fractures,” J. of Korean Neurosurg. Soc., Vol. 35, No. 5 (May 2004), pp 478-82, (http://www.jkns.or.kr/htm/abstract.asp?no=0042004086).
Another recent study was directed to the incidence of new VCFs adjacent to the vertebral bodies that were initially treated. Vertebroplasty patients often return with new pain caused by a new vertebral body fracture. Leakage of cement into an adjacent disc space during vertebroplasty increases the risk of a new fracture of adjacent vertebral bodies. See Am. J. Neuroradiol., 2004 February; 25(2):175-80. The study found that 58% of vertebral bodies adjacent to a disc with cement leakage fractured during the follow-up period compared with 12% of vertebral bodies adjacent to a disc without cement leakage.
Another life-threatening complication of vertebroplasty is pulmonary embolism. See Bernhard, J. et al., “Asymptomatic Diffuse Pulmonary Embolism Caused by Acrylic Cement: An Unusual Complication of Percutaneous Vertebroplasty,” Ann. Rheum. Dis., 62:85-86, 2003. The vapors from PMMA preparation and injection also are cause for concern. See Kirby, B. et al., “Acute Bronchospasm Due to Exposure to Polymethylmethacrylate Vapors During Percutaneous Vertebroplasty,” Am. J. Roentgenol., 180:543-544, 2003.
In both higher pressure cement injection (vertebroplasty) and balloon-tamped cementing procedures (kyphoplasty), the methods do not provide for well controlled augmentation of vertebral body height. The direct injection of bone cement simply follows the path of least resistance within the fractured bone. The expansion of a balloon also applies compacting forces along lines of least resistance in the collapsed cancellous bone. Thus, the reduction of a vertebral compression fracture is not optimized or controlled in high pressure balloons as forces of balloon expansion occur in multiple directions.
In a kyphoplasty procedure, the physician often uses very high pressures (e.g., up to 200 or 300 psi) to inflate the balloon which crushes and compacts cancellous bone. Expansion of the balloon under high pressures close to cortical bone can fracture the cortical bone, typically the endplates, which can cause regional damage to the cortical bone with the risk of cortical bone necrosis. Such cortical bone damage is highly undesirable as the endplate and adjacent structures provide nutrients for the disc.
Kyphoplasty also does not provide a distraction mechanism capable of 100% vertebral height restoration. Further, the kyphoplasty balloons under very high pressure typically apply forces to vertebral endplates within a central region of the cortical bone that may be weak, rather than distributing forces over the endplate.
SUMMARY OF THE INVENTION
There is a general need to provide bone cements and methods for use in treatment of vertebral compression fractures that provide a greater degree of control over introduction of cement and that provide better outcomes. The present invention meets this need and provides several other advantages in a novel and nonobvious manner.
In certain embodiments, a bone cement preparation system can comprise a vacuum channel, a filter, a saturation chamber configured to hold a non-liquid component of a bone cement, and a container configured to hold a liquid component of the bone cement. The system can further have a first interface disposed between the chamber and the container and a second interface disposed between the chamber and the vacuum channel. In some embodiments, the second interface can be configured to receive and position the filter between the chamber and the vacuum channel. The vacuum channel can be configured to direct a partial vacuum to draw the liquid component from the container into the non-liquid component in the chamber to mix or combine the components and to thereby provide a settable bone cement.
In some embodiments, the filter can have a pore size between about 0.05 microns and 10 microns or the pore size can be approximately 0.2 microns.
In certain embodiments, a bone cement preparation system can further comprise a vacuum source. The vacuum source can be configured to couple to the vacuum channel and be actuatable to apply a partial vacuum through the vacuum channel to the chamber and container to draw the liquid into the chamber.
According to some embodiments, a system can comprise a chamber for holding a non-liquid component of a bone fill material, a container for holding a liquid component of the bone fill material, the container coupleable to the chamber at a first interface and a vacuum source. The vacuum source can be used to draw the liquid component into the non-liquid component to form bone fill material. The vacuum source can also couple to the chamber at a second interface.
The system may further have a filter. The filter can be positioned at the second interface and between the chamber and the vacuum source to allow gas to flow through the filter and to substantially inhibit the bone fill material from flowing through the filter. The filter can have a pore size between about 0.05 microns and 10 microns,
The system may still further include a bone fill material delivery device. This device can have a cannula for introducing bone cement into a bone and a driving system. The chamber can be configured to couple to the driving system to deliver bone cement from the chamber through the cannula and into a bone.
A method of bone cement preparation from bone cement precursors comprising a liquid monomer component and at least one non-liquid polymer component, according to certain embodiments can comprise many steps. They may include the following: disposing a non-liquid polymer in a chamber defined by a body; disposing a liquid monomer in a container coupleable to the chamber containing the non-liquid polymer; and applying a negative pressure via a vacuum source coupleable to the chamber. The pressure source can be configured to apply a negative pressure of −500 mmHg or greater to draw the liquid monomer from the container into contact with the non-liquid polymer component in the chamber. This can form a bone cement mixture and thereby provide a settable bone cement. There can be a filter separating the pressure source and the chamber. The filter can allow air flow therethrough but substantially inhibit flow of the mixture therethrough. The method can also include infiltrating and wetting surfaces of the non-liquid polymer component with the liquid monomer within the chamber thereby forming the settable bone cement.
These and other objects of the present invention will become readily apparent upon further review of the following drawings and specification.



BRIEF DESCRIPTION OF THE DRAWINGS
In order to better understand the invention and to see how it may be carried out in practice, some preferred embodiments are next described, by way of non-limiting examples only, with reference to the accompanying drawings, in which like reference characters denote corresponding features consistently throughout similar embodiments in the attached drawings.
FIG. 1 is a perspective view of a system for bone cement preparation by vacuum saturation mixing of a polymer powder with a liquid monomer in accordance with some embodiments.
FIG. 2A is a sectional perspective view of a seal membrane in a first position.
FIG. 2B is a sectional perspective view of the seal membrane of FIG. 2A in a second position.
FIG. 3 is a perspective view of a component of FIG. 1 combined with additional components of a bone cement injection system.



DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
For purposes of understanding the principles of the invention, reference will now be made to the embodiments illustrated in the drawings and the accompanying text. As background, a vertebroplasty procedure using the system of FIG. 3 could insert parts of the system through a pedicle of a vertebra, or in a parapedicular approach, for accessing the osteoporotic cancellous bone. The initial aspects of the procedure can be similar to a conventional percutaneous vertebroplasty wherein the patient is placed in a prone position on an operating table. The patient is typically under conscious sedation, although general anesthesia is an alternative. The physician injects a local anesthetic (e.g., 1% Lidocaine) into the region overlying the targeted pedicle or pedicles as well as the periosteum of the pedicle(s). Thereafter, the physician can use a scalpel to make a 1 to 5 mm skin incision over each targeted pedicle. Thereafter, an introducer can be advanced through the pedicle into the anterior region of the vertebral body, which typically is the region of greatest compression and fracture. The physician can confirm the introducer path posterior to the pedicle, through the pedicle and within the vertebral body by anteroposterior and lateral X-Ray projection fluoroscopic views or by other methods. The introduction of infill material as described below can be imaged several times, or continuously, during the treatment depending on the imaging method.
Definitions
“Bone cement, bone fill or fill material, infill material or composition” includes its ordinary meaning and is defined as any material for infilling a bone that includes an in-situ hardenable material or that can be infused with a hardenable material. The fill material also can include other “fillers” such as filaments, microspheres, powders, granular elements, flakes, chips, tubules and the like, autograft or allograft materials, as well as other chemicals, pharmacological agents or other bioactive agents.
“Flowable material” includes its ordinary meaning and is defined as a material continuum that is unable to withstand a static shear stress and responds with an irrecoverable flow (a fluid)—unlike an elastic material or elastomer that responds to shear stress with a recoverable deformation. Flowable material includes fill material or composites that include a fluid (first) component and an elastic or inelastic material (second) component that responds to stress with a flow, no matter the proportions of the first and second component, and wherein the above shear test does not apply to the second component alone.
“Substantially” or “substantial” mean largely but not entirely. For example, substantially may mean about 50% to about 99.999%, about 80% to about 99.999% or about 90% to about 99.999%.
“Vertebroplasty” includes its ordinary meaning and means any procedure wherein fill material is delivered into the interior of a vertebra.
“Osteoplasty” includes its ordinary meaning and means any procedure wherein fill material is delivered into the interior of a bone.
FIG. 1 is illustrative of a bone cement preparation system 100 according to certain aspects of the disclosure. In particular, FIG. 1 shows how various bone cement precursors can be connected in a bone cement preparation system 100. The bone cement precursors can include a first polymer non-liquid component 110 and a second liquid monomer component 115. Each component can be provided and maintained in separate containers prior to combination. After combination of the components, an admixture can be provided that self cures into a settable bone cement, such as a PMMA cement. In other embodiments, the components can be combined to form other materials. In addition, liquid 115 and non-liquid 110 components can include respectively, one or more liquid and/or non-liquid component. For example, the non-liquid component can include two or three components as discussed in co-pending U.S. patent application Ser. No. 12/427,531, filed 21 Apr. 2009, which is incorporated by reference in its entirety and should be considered a part of this specification.
Referring to FIG. 1, the polymer non-liquid component 110 can be provided, shipped, and/or otherwise introduced prior to use, in a chamber 120 in a cement-carrying body 122. The cement-carrying body 122 can in one embodiment also be used as a delivery component for delivering bone cement into bone, as will be described in more detail below. The cement-carrying body 122 can in one embodiment be of a transparent plastic. The body 122 extends along an axis 175 from a proximal end 172 to a distal end 174 with the chamber 120 or interior space in between. The proximal end 172 of the cement-carrying body 122 can have a fitting, such as, for example, a threaded fitting 136a, for connecting various other devices such as a pressurization mechanism or a receiving body 130 to the structure. The distal end 174 of the structure 122 can also have a fitting 158b (e.g., a Luer fitting) for connecting various other devices such as a delivery device, a filter, and/or a vacuum source to the structure 122 as will be described further below.
The length of the cement-carrying body 122 can in some embodiments range from about 5 cm to 20 cm, to provide an interior volume of from about 2 cc to 20 cc. In other embodiments, the cement-carrying body 122 can have other dimensions to provide other desired interior volumes. In some embodiments, the body 122 is transparent to allow viewing of monomer saturation described below. In use in a vertebroplasty procedure, one or more cement-carrying bodies 122 can be used, as a treatment of a vertebral compression fracture can use from about 2 cc to 8 cc of bone cement.
The liquid monomer component 115 can be carried in a source 125, such as an ampule. The liquid monomer component 115 can be poured or otherwise placed into an inner space 132 in receiving body 130 as indicated in FIG. 1. In some embodiments, the source 125 can include at least a part of the body 130. In some embodiments, the receiving body 130 can be a funnel.
The volume of the receiving body 130 can be sized to contain a selected volume of monomer 115 required to saturate a volume of polymer powder 110 in the cement-carrying body 122. The receiving body 130 can in one embodiment be fabricated of a clear plastic.
The receiving body 130 and the cement-carrying body 122 can couple to provide a first interface 135 wherein the liquid monomer 115 can interface with the polymer component 110. In one embodiment, the receiving body 130 is detachably coupled to body 122 by cooperating threaded fitting portions 136a and 136b. The receiving body 130 can form a fluid-tight fitting with the body 122, such as with an o-ring.
In FIG. 1, it can further be seen that a first interface surface 140 can be provided intermediate the polymer non-liquid component 110 and the liquid monomer component 115. The first interface surface 140 can control the interface 135 of the liquid 115 and polymer 110 components. The first interface surface 140 can be a seal, valve, filter etc. Where the first interface surface 140 is a seal or a valve, it can be opened in various ways including via the application of negative pressure as will be described below. The seal 140 can allow the liquid 115 to be introduced and maintained in the receiving body 130 for short or long periods of time. Thus, a practitioner may begin to prepare the bone cement independent of other activities, such as varied back table activities in the operating theatre as the physician is attending to the patient prior to the procedure.
Some embodiments do not include an interface surface 140 between the chamber 120 and the receiving body 130.
Still referring to FIG. 1, a vacuum source 150 is shown which can include a syringe body 152 and retractable plunger 154, or can alternatively include any other vacuum line, evacuated cartridge or the like that can produce the vacuum described below. The vacuum source 150 can be detachably coupled to the cement-carrying body 122. This can be for suctioning the liquid monomer component 115 into and through the non-liquid polymer powder component 110 disposed in chamber 120 in the body 122. The saturation of the polymer powder 110 with the monomer 115 can thus cause the biomaterial column to begin polymerization and set in post-mixing (or post-saturation) time intervals that are described further below.
The terms wetting and saturating are used interchangeably herein to describe the process of thoroughly or completely exposing the non-liquid polymer powder component to the liquid monomer component, in other words to unite the two components to thereafter cause a polymerization reaction between at least two portions of the biomaterials.
Where the vacuum source 150 connects to the cement-carrying body 122 a second interface 155 is established. This interface 155 is between the volume of polymer beads 110 and the vacuum source. The vacuum source 150 can be connected to body 122 either directly or by a fitting 156. The connection can be with, for example, cooperating screw or press-fit coupling portions indicated at 158a and 158b. The vacuum source 150 or fitting 156 can optionally include a pressure relief valve 160, and/or a valve 165 for selectively closing channel 146. In some embodiments, the pressure relief valve 160 can limit the amount of negative pressure in the syringe 152.
In some embodiments, the vacuum source 150 can include a canister pre-packaged with a suitable level of vacuum therein to provide a negative pressure source for saturating the biomaterial column with the liquid monomer. For example, the vacuum source 150 can be a vacuum/gas cartridge, similar to a CO2 cartridge but with a partial vacuum inside. The vacuum canister can be coupled to cement-carrying body directly or by a fitting 156. The vacuum source 150 or the fitting 156 can have a valve 165 such as an open/close stopcock valve.
In some embodiments, the vacuum source 150 can comprise a syringe. For example, the syringe can comprise a 20 cc to 60 cc syringe and more particularly a 30 cc syringe. It has been found that a 30 cc syringe can provide a negative pressure of −500 mmHg or greater. The size of the syringe and the amount of desired negative pressure of certain embodiments can vary greatly and can depend on many factors. These factors can include the amount of bone cement to be prepared, the cross-section and length of the mixing chamber and the volume and dimensions of the polymer beads.
Similar to the first interface 135, the second interface 155 can have a second interface surface 170. FIG. 1 illustrates a second interface surface 170 that is a filter, but it can alternatively be a valve, seal, etc. intermediate the polymer powder or bead component 110 and the vacuum source 150. The second interface surface 170 can be configured to allow evacuated air to flow therethrough under the negative pressure but substantially prevent the flow of liquid monomer therethrough when the monomer 115 has saturated the polymer 110. Thus, in some embodiments, both the first interface 135 and the second interface 155 of the polymer component can include a valve-like mechanism to allow and/or limit fluid flows to controllably saturate the powder component with the monomer in a controlled time interval to provide a predetermined monomer/polymer ratio.
In some embodiments, where the second interface surface 170 is a filter, such as shown in FIG. 1, the filter can include a plastic (e.g., high density polyethylene) mesh filter. In some embodiments, the filter can be a metal or ceramic microporous material. The filter can in some embodiments have a mean pore dimension of about 0.05 to 10 microns. In some embodiments, the filter has a mean pore dimension of about 0.1 to 0.5 microns. In some embodiments, the filter has a mean pore dimension of about 0.2 microns. The filter pores can be configured to allow air extraction from the volume of polymer powder 110 in body 122 by initial application of a vacuum from the vacuum source 150. The liquid monomer component 115 when suctioned through the polymer powder 110 in chamber 120 can create a higher viscosity mixture akin to wet sand. The filter 170 can be configured to prevent the mixture from passing through the filter 170. The filter 170 can also function to limit liquid monomer 115 losses from the saturated mixture. This can result in a desired (e.g., an exact) volume of liquid monomer 115 being drawn by vacuum into the chamber 120 for saturating the polymer powder volume 110.
The filter 170 can advantageously facilitate the operation of the bone cement preparation system 100 according to some embodiments. This is because, the filter 170 can allow sufficient negative pressure to pass through the filter 170 to pull the liquid monomer 115 into the non-liquid 110 component, while also preventing the liquid monomer from simply passing through the chamber and into the vacuum source. For example, in some embodiments, the filter can clog to prevent flow of the liquid monomer. In some embodiments, the cement mixture can clog the filter to prevent flow of the liquid monomer. In other embodiments, the filter may swell or polymerize once contacted by the liquid monomer to prevent flow through the filter.
If an insufficient amount of liquid monomer 115 is mixed with the non-liquid 110 polymer component, the mixture will be starved, i.e. it will have insufficient liquid monomer to begin the curing process in all regions of the mixture. For example, some embodiments of the system advantageously produce a de-aerated, non-clumped and homogeneous bone cement admixture. The exact ratio for the monomer and polymer components can be provided by the packaging of these components, and the system described above can insure that substantially none of the liquid monomer escapes the system.
In some embodiments, the bone cement precursors can be combined to form a self-curing bone cement as a result of a chemical reaction when a polymer component and liquid monomer component interact, along with activators and initiators. For example, some embodiments include the mixing of a PMMA bone cement that can be provided for a treatment, such as, treating a vertebral compression fracture, setting an artificial joint, etc.
In some embodiments, the polymer component 110 is provided in a formulation of bead sizes to cooperate with the monomer volume 115 and negative pressure from the vacuum source to insure that all surfaces of the polymer beads or powder are wetted or saturated. This can be done so that the admixture does not create a polymerizing volume or other volume that clogs the intra-bead spaces to prevent monomer 115 migration from the superior region of the polymer bead volume 110 to the inferior region of the polymer beads.
It can also be important to consider the bead size of the polymer component 110 when determining the pore size of the filter 170. If the bead size is too small compared to the pore size, the initial application of negative pressure to the mixing chamber can clog the filter so that the negative pressure cannot draw the needed liquid monomer into the mixing chamber. This may occur immediately or before sufficient monomer has been drawn into the mixing chamber. If this occurs, it is unlikely that the correct monomer to polymer ratio will be obtained without some further mixing action, such as hand mixing the remaining liquid into the polymer.
The systems and methods described herein can provide many benefits such as not requiring hand mixing. The system can be faster than mixing by hand, and can minimize or eliminate clumping resulting in more uniform cement. For example, in certain embodiments the system can uniformly combine the liquid monomer and the non-liquid polymer in less than about 20 seconds, in about 10 seconds or in only a few seconds. In addition, the system can contain the fumes created by the chemical reaction when the liquid and non-liquid components are combined. For example, the fumes can be contained within the mixing chamber 120 and/or the receiving body 130. In some embodiments, at least a portion of the fumes can be drawn into the vacuum source 150.
In addition, the use of negative pressure to draw the liquid into the non-liquid can also provide certain benefits. For example, vacuum can remove the air or gas from the non-liquid. This space can be filled with the liquid to get a more even and uniform mixture. Where the liquid to be forced into the non-liquid, such as by injecting the liquid, the air is not necessarily removed. Injection can also, in some instances, result in air pockets, clumps, and other areas of non-uniformity. Hand mixing can result in similar problems. In some embodiments, the use of vacuum can substantially, if not completely, remove these problems.
Example functions of the various components are described next to illustrate how certain objectives of the disclosure are accomplished. With further reference to FIG. 1, it can be understood that the physician or nurse can first pour a predetermined volume of polymer beads 110 into chamber 120. Next, the operator can assemble and/or screw the monomer-receiving body 130, here a funnel, (together with optional seal 140) onto the top of cement-carrying body 122. Next, the vacuum source 150 can be coupled to the fitting 156 with a filter 170 and a stopcock valve 165. The fitting 156 with vacuum source 150 can then be attached to the cement-carrying body 122. In some embodiments, the connection between the assemblies are fluid-tight screw fittings.
Next, the operator can close the stopcock valve 165 and pull the syringe plunger 154 (or actuates another type of vacuum source) to provide a pre-determined negative pressure in bore 176 of syringe body 152. It has been found that high quality, commercially available 20 cc to 60 cc syringes can be actuated to provide about a negative pressure of −250 mmHg to −750 mmHg which can remain in the syringe for several minutes or indefinitely in some instances. Then, the operator can open a monomer source 125 (such as breaking a monomer ampule), and can pour the predetermined volume of monomer 115 into the inner space 132 of the funnel 130. The assembly 100 can be placed in a stand (not shown) to maintain the assembly in an upright position—i.e., with the axis 175 of the assembly being vertical so that the monomer 115 does not spill from the funnel 130.
As discussed previously, some embodiments of the cement preparation system include an optional seal 140. With the monomer 115 loaded in inner space 132, the optional seal or valve 140 can prevent the monomer from reaching the interface 135 or superior surface of the polymer powder 110. The entire assembly can remain in this condition indefinitely. One embodiment of the seal or valve 140 is shown in FIGS. 2A and B, and can include one or more silicon thin film layers 180 with slits 182 therein. The slits 182 can be configured to hold the liquid monomer 115—but when a suction source is applied the slits can open (indicated at 182′ in FIG. 2B) to allow fluid flow therethrough to wet and saturate the polymer beads 110. For example, negative pressures in the range −250 mmHg or greater, −400 mm/Hg or greater, or −500 mmHg or greater can open the slits 182 in seal 140.
Returning now to a method of use, with the system 100 assembled including the bone cement precursors, the operator can open the stock-cock valve 155 to expose the vacuum to the inferior interface 156 of the polymer beads 110. The negative pressure can then extend through the spaces between the polymer beads 110 to thus draw the liquid monomer 115 through the volume of beads. In some embodiments, this can be done in an interval ranging between about 5 seconds and 60 seconds. It has been found that negative pressures in the range of −250 mmHg or greater, −400 mm/Hg or greater, or −500 mmHg or greater can be used to controllably saturate the volume of polymer beads 110 utilizing one embodiment of cement and monomer described in the following paragraphs.
Thus, a method of bone cement preparation can include providing a body defining a chamber for receiving bone cement precursors including a liquid monomer component 115 and at least one non-liquid polymer component 110, disposing the non-liquid component in the chamber, disposing the liquid component at a first interface with the non-liquid component, and applying a negative pressure in the range −250 mmHg or greater, −400 mm/Hg or greater, or −500 mmHg or greater to a second interface with the non-liquid component thereby causing the monomer liquid to infiltrate, saturate and wet the surfaces of the non-liquid component 110. In this method, the first interface 135 is vertically superior to the second interface 155—as the pressures can be selected to cooperate with gravity and not work against gravity.
In the embodiment described in the above method, the volume of polymer component 110 is between about 10 cc and 14 cc. The length of chamber 120 that carries the polymer component 110 is less than about 10 cm, 8 cm and 6 cm with a diameter of between 8 mm and 15 mm. In this embodiment, the volume of monomer component 115 is between about 2 cc and 4 cc. Other embodiments can have other dimensions and can use other negative pressure ranges.
In one embodiment, the polymer/monomer ratio is between 2:1 and 5:1. In some embodiments, the negative pressure can cause monomer saturation of the polymer within less that 45 seconds or less than 30 seconds.
In another aspect of the invention, the second interface surface 170 can be a polymer filter member that allows unimpeded gas or air flow at the negative pressures described above but prevents substantial flows of a liquid or monomer-polymer mixture therethrough. In one embodiment, the filter 170 can be a polymer filter with micron scale porosities ranging between 0.05 microns and 10.0 microns, and usually between 0.1 microns and 5.0 microns. In operation, the wetted filter 170 can clog and prevent liquid flows therethrough.
The filter 170 can help ensure that the polymer to monomer ratio within the chamber 120 remains in a very tight range. This is not possible with systems where the vacuum pulls too much monomer through the chamber and then out of the volume of polymer beads. As disclosed, in a preferred embodiment, the entire monomer volume remains in chamber 120 to saturate the polymer beads 110.
In another embodiment, a method for combining a liquid monomer component 115 and a non-liquid polymer component 110 of a settable bone cement includes disposing the non-liquid component 110 in a chamber 120 of a body 122 wherein the non-liquid component 110 includes a group of polymer beads without exposed or “free” benzoyl peroxide (BPO) or any other activator or initiator components. In some embodiments, all BPO (and/or other activator/initiator components) is within the polymer particles or beads, thus no BPO is free or instantly available to initiate any chemical reaction at the moment the monomer is drawn into and through the polymer bead volume. In another configuration, to eliminate free BPO a radiopacifier (such as zirconium dioxide) is milled onto the PMMA particle or bead surfaces which prevents rapid access of a monomer-polymer reaction to the BPO (and/or other activator/initiator components). These configurations of the polymer component 110 can thus allow complete monomer saturation of the polymer bead volume 110. The polymer particles are unable to react with the monomer so as to clump or clog during monomer flow therethrough within the time interval described to draw the liquid monomer into the second interface 155 with second interface surface 170.
In one embodiment, the system is configured for using a polymer powder to monomer liquid ratio of between 2:1 and 5:1 wherein the non-liquid component 110 is designed to provide no free BPO for at least 30 seconds and the vacuum saturation of the polymer component by the monomer can be accomplished with a negative pressure in the range −250 mmHg or greater, −400 mm/Hg or greater, or −500 mmHg or greater.
In another embodiment, a method for combining a liquid monomer component 115 and a non-liquid polymer component 110 of a settable bone cement can include disposing the non-liquid component 110 in a chamber 120 of a body 122 wherein the non-liquid component 110 includes a first group of beads having a first mean diameter and a second group of beads having a second mean diameter, disposing the liquid component 115 at a first interface 135 with the non-liquid component 110; and applying a negative pressure in the range −250 mmHg or greater, −400 mm/Hg or greater, or −500 mmHg or greater to a second interface 155 thereby causing wetting of the non-liquid component 110 with the liquid component 115. The first and second bead diameters can be selected to cooperate with the pressure to allow the wetting in less than about 50 seconds, 40 seconds or 30 seconds. In one embodiment, the first and second groups of beads have mean diameters, respectively of 110 microns and 35 microns. The bead diameters can be important in that the small diameter beads can be limited in volume to prevent migration and clogging of intra-bead spaces among the larger beads as the monomer is drawn rapidly through the polymer volume.
In another embodiment, the bone cement used in the system can include a monomer component and polymer component, wherein the polymer component includes a first volume of beads having a first average wt. % of benzoyl peroxide (BPO) on the basis of the total weight of the first volume and a second volume of beads having a second average wt. % of BPO on the basis of the total weight of the second volume. In this bone cement embodiment, the first group of beads can have an average cross section of less than about 100 microns, 80 microns, 60 microns or 40 microns. The second group of beads can have an average cross section of greater than about 40 microns, 60 microns, 80 microns and 100 microns. In some embodiments, the first volume has less than 0.5 wt. % of BPO and the second volume has greater than 0.5 wt. % of BPO. In some embodiments, the combined first and second volumes have less than a 5.0 wt. % of BPO or less than a 2.5 wt. % of BPO. In some embodiments, the combined first and second volumes have greater than a 0.5 wt. % of BPO or greater than a 1.0 wt. % of BPO. In other embodiments, at least a portion of the first volume is without BPO or at least a portion of the second volume is without BPO.
In another embodiment, the bone cement includes a monomer component and polymer component, wherein the polymer component includes a volume of beads carrying from 0.2% and 0.6% of BPO on the basis of the total weight of the volume, wherein at least 80% of the BPO is carried on a sub-volume of beads, the beads having a mean cross section of greater than 100 microns, and wherein less than 20% of the BPO is carried on a sub-volume of beads, the beads having a mean cross section of less than 100 microns.
In another embodiment, the bone cement includes a monomer component and polymer component, wherein the polymer component includes a volume of beads carrying from 0.2% and 0.6% of BPO on the basis of the total weight of the volume, wherein 100% of the BPO is carried on a portion of the bead volume where the beads have a mean cross section of greater than 100 microns, and wherein no BPO is carried on a portion of the bead volume where the beads have a mean cross section of less than 100 microns.
In another embodiment, the bone cement includes a monomer component and polymer component, wherein the polymer component includes a volume of beads of at least one polymeric material, wherein the polymer component carries from 0.2% and 3.0% BPO on the basis of the total weight of the volume, wherein a first portion of the bead volume carries BPO in a surface coating and wherein a second portion of the bead volume carries BPO intermixed in the at least one polymeric material.
In another embodiment, the bone cement includes a monomer component and polymer component, wherein the polymer component includes a volume of beads of at least one polymeric and from 0.2% and 3.0% BPO on the basis of the total weight of the volume, and wherein the BPO is provided in at least two of the following forms: as a surface coating on beads, as BPO particles, as BPO in microcapsules, as BPO particles within beads of a polymeric material, and as BPO in microcapsules within beads of a polymeric material.
In another method, a bone cement can be provided including a mixture of a liquid monomer component and polymer component of particles which includes distributing BPO within the mixture to provide a selected BPO availability to be wetted by the monomer component over first and second intervals, wherein the BPO availability per second over the first interval is substantially greater than the BPO availability per second over the second interval. Thereafter, the liquid monomer component and polymer component can be intermixed and then injected into bone. In this method, the selected BPO availability can be provided by at least two different particles having differing BPO configurations therein. In one embodiment, the selected BPO availability is provided by a differential BPO exposure in a surface area of the particles. In another embodiment, the selected BPO exposure is provided in part by particles having a mixed polymeric material and BPO. In yet another embodiment, the selected BPO exposure is provided in part by particles having a surface coating of BPO. In another embodiment, the selected BPO exposure is provided in part by microencapsulated BPO. In another embodiment, the selected BPO exposure is provided by particles having layers of polymeric materials and BPO.
In some embodiments of a method, the mixable bone cement can be configured to have a selected interval in which the release or exposure of BPO or other initiator is controlled. This can provide a slope of a free BPO curve over time which is positive or flat (or non-negative) for an interval post-mixing of at least 2 minutes, 4 minutes, 6 minutes, 8 minutes and 10 minutes. In another embodiment, the free BPO curve can be controlled in slope over the post-mixing period to flatten, increase in slope or decrease in slope in either direction but controlling the free BPO. By the term free BPO, it is meant the volume of BPO or other initiator that is available or exposed to the liquid monomer post-mixing.
In one specific formulation of a PMMA cement, the solid or powder component of the bone cement includes: polymethylmethacrylate polymer (PMMA) by weight of 49.6% with the nominal allowable range between 45%-55%; benzoyl peroxide (BPO) by weight is 0.40% with a nominal allowable range between 0.30-0.80%; and zirconium dioxide by weight is 50.0% with a nominal allowable range 45%-55%. In this cement formulation, the liquid component of the bone cement includes: methylmethacrylate (MMA) by weight of 99.5% with an allowable range of 98.0-99.9%; N,N-dimethyl-p-toluidine (DMPT) by weight of 0.50% with an allowable range of 0.15-0.95%; and hydroquinone (HQ) of 75 ppm with an allowable range of 30-150 ppm. In this cement formulation, the powder PMMA component as described above consists of a blend of three (3) subgroups of powders 1, 2 and 3 which are mixed in a ratio as follows: powder 1=44.28%; powder 2=36.86% and powder 3=18.86%. The nominal range of powder 1 can be from 40%-50%. The nominal range of powder 2 can be from 30%-40%. The nominal range of powder 3 can be from 40%-50%. Powder 1 consists of a target particle size of 110 microns and an allowable range between 100 and 120 microns with a molecular weight of 350,000 and an allowable range of 250,000 to 450,000; and benzoyl peroxide (BPO) at 1.0% by weight with an allowable range of 0.9% to 1.1%. Powder 2 consists of a target particle size of 80 microns and an allowable range between 70 and 90 microns with a molecular weight of 400,000 and an allowable range of 300,000 to 500,000; and benzoyl peroxide (BPO) at 1.2% by weight with an allowable range of 1.1% to 1.3%. Powder 3 consists of a target particle size of 35 microns and an allowable range between 25 and 45 microns with a molecular weight of 250,000 and an allowable range of 250,000 to 350,000; and benzoyl peroxide (BPO) at 0.0%.
The systems of some embodiments can further include a bone cement delivery assembly or ejection mechanism for ejecting bone cement into bone. Looking now to FIG. 3, in some embodiments, the cement-carrying body 122 can be de-coupled from the bone cement preparation system 100 and coupled to a bone cement delivery assembly 200. The bone cement delivery assembly 200 can include a bone cement injector 240 that may extend into bone, such as, cancellous bone of a vertebra, and a cement activation component 215 which may include an emitter 220 for applying energy to bone cement. The bone cement delivery assembly 200 can also include a cement ejection mechanism. As shown in FIG. 3, the cement ejection mechanism can include a piston or driving shaft 205 and a driving system 210. The piston 205 can be inserted into the chamber 120 to ultimately drive the bone cement through a needle 124 and into bone. The driving system 210 can actuate the piston 205. It should be appreciated that the driving system 210 can be any hand-operated syringe, hydraulic or pneumatic actuated syringe, wire-cable actuated syringe or the like. For example, the driving system 210 can include a manually advanced plunger assembly, any type of hydraulic system, CO2 gas cartridge system, pneumatic system, cable drive system, screw drive system, a spring system or other pump system; any of which can be computer controlled with a microprocessor that executes one or more control algorithms for delivering the curable bone cement at desired flow parameters (e.g., flow rate, temperature, pressure) into a treatment site (e.g., into naturally-occurring cavities in uncompressed cancellous bone of a bone, such as a vertebral body).
As mentioned, some embodiments of bone cement delivery assembly 200 can include an emitter 220. The emitter 220 may apply thermal energy to a flow of bone cement delivered to the cement activation component 215 from chamber 120 of source 122. The thermal energy can cause the viscosity of the cement to increase to a selected, higher viscosity value as the cement exits the needle 124 into bone. The controlled application of energy to bone cement may enable the physician to select a setting rate for the cement to reach a selected polymerization endpoint as the cement is being introduced into the vertebra, thus allowing a high viscosity that will be prevent unwanted cement extravasation.
The cement delivery system can include the cement heating system as disclosed in U.S. patent application Ser. No. 12/062,337, filed Apr. 3, 2008, and the other following related applications: U.S. patent application Ser. No. 11/469,764 filed Sep. 1, 2006; Ser. No. 11/165,652 filed Jun. 24, 2005; App. No. 60/713,521 filed Sep. 1, 2005; Ser. No. 11/209,035 filed Aug. 22, 2005; App. No. 60/929,936 filed Apr. 30, 2007; App. No. 60/899,487 filed Feb. 5, 2007; Ser. No. 12/024,969 filed Feb. 1, 2008; App. No. 60/907,467 filed Apr. 3, 2007; App. No. 60/907,468 filed Apr. 3, 2007; App. No. 60/907,469 filed Apr. 3, 2007; and App. No. 60/929,416 filed Jun. 26, 2007. The entire contents of all of the above applications are hereby incorporated by reference and should be considered a part of this specification.
The above description is intended to be illustrative and not exhaustive. In addition, particular characteristics, features, dimensions and the like are presented in the dependent claims. These can be combined in various embodiments and fall within the scope of the disclosure. It should be understood that various additional embodiments encompass the dependent claims as if they were alternatively written in a multiple dependent claim format with reference to other independent claims. Specific characteristics and features of the embodiments of the systems and methods are described in relation to some figures and not in others, and this is for convenience only. While certain principles have been made clear in the exemplary descriptions and combinations, it will be obvious to those skilled in the art that modifications may be utilized in practice which are particularly adapted to specific environments and operative requirements without departing from the principles espoused herein.
Of course, the foregoing description is that of certain features, aspects and advantages, to which various changes and modifications can be made without departing from the spirit and scope of the disclosure. Moreover, the bone treatment systems and methods need not feature all of the objects, advantages, features and aspects discussed above. Thus, for example, those skill in the art will recognize that the systems and methods can be embodied or carried out in a manner that achieves or optimizes one advantage or a group of advantages as taught herein without necessarily achieving other objects or advantages as may be taught or suggested herein. In addition, while a number of variations have been shown and described in detail, other modifications and methods of use, which are within the scope of the disclosure, will be readily apparent to those of skill in the art based upon this disclosure. It is contemplated that various combinations or subcombinations of these specific features and aspects of embodiments may be made and still fall within the scope of the disclosure. Accordingly, it should be understood that various features and aspects of the disclosed embodiments can be combined with or substituted for one another in order to form varying modes of the discussed bone treatment systems and methods.

## Claims

1. A bone cement preparation system comprising:
a liquid container configured to receive a liquid component of a bone cement from an external source and further configured to release the liquid component therefrom;
a mixing chamber configured to receive through a first opening and hold therein a non-liquid component of the bone cement from an external source, wherein the first opening is disposed at a first end of the mixing chamber and is further configured to couple to the liquid container to receive and hold the liquid component released therefrom to form a settable bone cement mixture comprising the liquid component and the non-liquid component, the mixing chamber further having a second opening that is disposed at a second end of the mixing chamber; and
a filter configured to couple to the second opening of the mixing chamber, wherein the filter comprises a plurality of pores that are configured to prevent passage of the bone cement mixture therethrough while allowing passage of air or gas therethough,
wherein the system comprises a flow path that extends from the liquid container through the first opening of the mixing chamber to the second opening of the mixing chamber, wherein the direction of the flow path is linear.

2. The bone cement preparation system of claim 1, wherein the pores are configured to swell upon coming into contact with the bone cement to prevent the passage of the bone cement mixture therethrough while allowing the passage of air or gas therethough.

3. The bone cement preparation system of claim 1, wherein the pores have an average pore size between about 0.05 microns and about 10 microns.

4. The bone cement preparation system of claim 1, further comprising a pressure source configured to apply a pressure to the liquid component in the liquid container to cause the liquid component to be transferred into the mixing chamber and combine with the non-liquid component, while causing air in the mixing chamber to be removed through the filter.

5. The bone cement preparation system of claim 4, wherein the pressure source is a negative pressure source comprising a vacuum source.

6. The bone cement preparation system of claim 5, wherein the vacuum source is configured to be coupled to the mixing chamber through the filter, wherein the vacuum source comprises a vacuum channel configured to form a partial vacuum therein to draw the liquid component from the liquid container into the mixing chamber.

7. The bone cement preparation system of claim 1, further comprising the non-liquid component and the liquid component combinable to form the settable bone cement.

8. The bone cement preparation system of claim 7, wherein the non-liquid component comprises polymer particles and initiators, wherein the liquid component comprises monomers, and wherein the settable bone cement is configured to initiate setting at least in part by polymerization of monomers initiated by the initiators.

9. The bone cement preparation system of claim 8, wherein an average pore size of the filter is smaller than an average diameter of the polymer particles.

10. The bone cement preparation system of claim 1, wherein the liquid container comprises a funnel.

11. A system comprising:
a liquid container configured to receive a liquid component of a settable bone fill material from an external source and further configured to release the liquid component therefrom;
a mixing chamber configured to receive through a first opening and hold therein a non-liquid component of the bone fill material from an external source, wherein the first opening is disposed at a first end of the mixing chamber and is further configured to couple to the liquid container to receive and hold the liquid component released therefrom to form a settable bone fill material comprising the liquid component and the non-liquid component, the mixing chamber further having a second opening that is disposed at a second end of the mixing chamber;
a pressure source configured to apply a pressure to the liquid component in the liquid container to transfer the liquid component from the liquid container into the mixing chamber to mix with the non-liquid component to form the settable bone fill material; and
a filter configured to couple to the second opening of the mixing chamber and configured to allow gas to pass therethrough, while being configured to inhibit the bone fill material from passing therethrough,
wherein the system comprises a flow path that extends from the liquid container through the first opening of the mixing chamber to the second opening of the mixing chamber, wherein the direction of the flow path is linear.

12. The system of claim 11, further comprising a bone fill material delivery device comprising:
a cannula for introducing the bone fill material into a bone;
and a driving system, wherein the mixing chamber is configured to couple to the driving system to deliver the bone fill material from the mixing chamber through the cannula and into a bone.

13. The system of claim 11, wherein the pressure source is a negative pressure source comprising a vacuum channel configured to be coupled to the mixing chamber, wherein the vacuum channel is configured to form a partial vacuum therein to draw the liquid component from the liquid container into the mixing chamber to combine with the non-liquid component.

14. The system of claim 13, further comprising a stopcock valve between the filter and the vacuum channel and configured to control application of negative pressure from the vacuum source to the chamber and container.

15. The system of claim 11, further comprising a pressure relief valve configured to limit the amount of the pressure applied to the liquid component.