Bony Tissue Delivery Systems and Methods

Abstract

A delivery system and method suitable for delivering a fluid to an interior of a bone and for removing fluid including bodily material from the interior of the bone. The delivery system includes a proximal portion graspable by a user and in fluid communication with a source of negative pressure and a delivery fluid. A delivery cannula has a length sufficient to extend from the proximal portion to a distal tip insertable into the interior of the bone to deliver the delivery fluid into the bone. A removal cannula has a length sufficient to extend from the proximal portion to a distal tip insertable into the interior of the bone to withdraw fluid including bodily material from the bone.

Claims

1. A delivery system suitable for delivering a fluid to an interior of a bone and for removing fluid including bodily material from the interior of the bone, comprising: a proximal portion graspable by a user and in fluid communication with a source of negative pressure and a delivery fluid; a delivery cannula having a length sufficient to extend from the proximal portion to a distal tip insertable into the interior of the bone to deliver the delivery fluid into the bone; and a removal cannula having a length sufficient to extend from the proximal portion to a distal tip insertable into the interior of the bone to withdraw fluid including bodily material from the bone.

2. The system of claim 1 wherein the delivery fluid includes cells capable of reducing inflammation.

3. The system of claim 1 wherein the proximal portion defines a first chamber containing the delivery fluid and a second chamber for generating the negative pressure and collecting the fluid including bodily material.

4. The system of claim 3 wherein the delivery fluid is delivered into the bone at the same time that fluid including bodily material is removed from the bone.

5. The system of claim 2 wherein the delivery fluid further includes a physical augmentation agent.

6. The system of claim 1 wherein the delivery cannula and the removal cannula are insertable into a vertebral body utilizing a transpedicular approach.

7. The system of claim 1 further including a guide sleeve having an interior diameter sufficient to accommodate the delivery cannula and the removal cannula.

8. The system of claim 1 wherein the removal cannula is movable axially independent of the delivery cannula.

9. The system of claim 1 wherein the removal cannula and the delivery cannula are disposed concentrically relative to each other.

10. A method for treating at least one of inflammation and pain in a bone, comprising: selecting a bone to be treated; selecting at least one delivery fluid including cells capable of reducing inflammation; and delivering the delivery fluid to an interior of the bone.

11. The method of claim 10 wherein the delivery fluid includes cells selected and qualified for their ability to repress inflammation.

12. The method of claim 10 wherein the delivery fluid further includes a physical augmentation agent.

13. The method of claim 10 further including withdrawing inflamed bodily material from the bone.

14. The method of claim 11 wherein the delivery fluid includes mesenchymal cells.

15. The method of claim 11 further including at least one additional agent such as an antibiotic, an anti-inflammatory drug, or an additional cell type.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In what follows, preferred embodiments of the invention are explained in more detail with reference to the drawings, in which:

[0028] FIG. 1 is a schematic side, partial cross-sectional view of a distal portion of a delivery device according to the present invention inserted into a vertebral body of a patient;

[0029] FIG. 1A is a view similar to FIG. 1 showing a proximal portion of one device construction according to the present invention

[0030] FIG. 2 is a schematic perspective view of a distal portion of a device according to the present invention having parallel fixed or sliding cannulas;

[0031] FIG. 3 is a view similar to FIG. 2 showing concentric cannulas;

[0032] FIG. 4 is a schematic illustration of a device according to the present invention having a single plunger to simultaneously deliver compounds or irrigation fluids and withdraw bodily material such as inflamed or damaged tissue;

[0033] FIG. 5 is a schematic perspective view of a dual chamber syringe having a suction chamber larger than a delivery chamber plus fixed inner and outer cannulas;

[0034] FIG. 6 is a view similar to FIG. 5 with an outer suction cannula that moves axially relative to a fixed inner cannula;

[0035] FIG. 7 is a schematic perspective view of another delivery device according to the present invention having a control valve which enables selective control of delivery and suction; and

[0036] FIGS. 8A-8C are enlarged schematic cross-sectional views of one construction of the control valve of FIG. 7.

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS

[0037] Delivery devices according to the present invention are described in more detail below in relation to FIGS. 1-8C. The anti-inflammatory treatment of this invention consists of injecting or otherwise placing certain cell types in bone suspected of having an inflamed area. If cells that are known for being anti-inflammatory agents are placed in an inflamed site within bone according to the present invention, the inflammation decreases almost immediately. This is regardless of the cause of the inflammation. The exact mechanism by which inflammation is suppressed is unknown, but cytokines and other secretory bio-molecules known to affect inflammation and inflammation signalling are suspected to play an important role. Examples of cells with anti-inflammatory properties are mesenchymal stem cells (MSCs), derived from bone marrow, stromal vascular stem cells, and any engineered or isolated cells yet to be developed that have appropriate anti-inflammatory properties.

[0038] One key advantage of using living cells as the anti-inflammatory agent is that the cells are used as miniature bioactive manufacturing systems, which upon implantation will provide a sustained and long-term production of those anti-inflammation bio-molecules. Certain types of stem cells such as MSCs are further known to be immune-privileged, meaning that they can evade immune rejection for a while, conferring them with an even longer benefit. This also means that allogenic MSCs (cells from another person) can be effective as well as autogenic or autologous cells (cells from the patient). Longer lasting cells will provide longer-term bioactive secretion modulating or decreasing inflammation-causing pain. Living cells such as MSCs can also secrete combinations of inflammation modulating biomolecules, which can act in additive or synergistic fashion to provide better activity than purified anti-inflammatory drugs.

[0039] Even if the inflammation is secondary to another cause such as infection or a tissue injury, it is still advantageous to treat the inflammation as well as the primary cause. As was mentioned earlier, one possible source of inflammation in diseased spines is a bacterial infection. Although antibiotics can treat infections, it can take up to a year to finally get relief. The invention can give relief at the same time the antibiotic treatment is started, or anytime during and after the course of the antibiotic treatment, in cases where an infection is the suspected cause of the inflammation.

[0040] Cells utilized according to the present invention can be sourced from the patient (autogenic or autologous) or from another person (allogenic). For safety, the patient's own cells are preferred since there is little to no risk of transmitting diseases that the patient has not been already exposed to. Collecting the cells intraoperatively avoids the costs and problems associated with keeping the cells alive outside of the body for an extended period. The most abundant source of such autogenic cells are the MSCs which are found in many tissues including bone marrow, circulating in blood, and also in fat deposits (adipose tissue). Harvesting these cells can be carried out by a variety of means (usually involving aspiration), but they are always initially mixed with other cells. It is desirable to separate or enrich the MSCs from other cells as much as possible in order to get a more predictable effect. There are several means of doing so, involving, for example, antibodies, enzymes, mechanical means, or a combination of methods. Purely mechanical means, especially by centrifugation, are preferred since there are no foreign substances introduced.

[0041] Alternatively, for added convenience, and enhanced bioactivity, cells that have been isolated from a donor(s), amplified with various tissue or cell culture techniques, banked, and qualified for their ability to tame inflammation could be used. Such cells can be prepared in very large batches and frozen into therapeutic doses until needed for use. At the time, the health provider can thaw the cells and prepare for delivery. Large cell banks can be carefully studied and selected for their potency, absence of adventitious agents and provide for safe and effective cell source at the point of care without the need for the additional procedures of harvesting donor bone marrow or adipose tissue and a time consuming processing of isolating and enriching MSCs before injections.

[0042] During the process of propagation and selection of allogenic cells, further manipulation could be considered which would provide additional benefits or enhanced anti-inflammatory activity. For example, MSC or other cells could be engineered by introducing a gene known to modulate inflammation. The product of such a gene could be a cytokine or hormone that would act locally on the inflamed tissue, or remotely by recruiting and signalling the host immune cells to migrate to the inflammation area and decrease the inflammation. Many ways of introducing genes in cells are known to people who are skilled in the art and include but are not limited to: lipid mediated transfer, viral transduction, chemical transfection and electroporation.

[0043] The cells whether autologous or allogenic can be delivered to the site of inflammation as suspension by means of a cannula such as a hollow hypodermic needle or a catheter, as discussed in more detail below. Open surgery is also possible, but it is much less desirable. The cells can also be delivered suspended in a formulation, which would enhance their viability through the injection procedure or post-injection at the site of implantation. Such a formulation could include many different soluble chemical preparations maintaining proper physiological condition prior, during or after the injection. Furthermore, the formulation could also include alone or in combination with various soluble factors, soluble or insoluble biomaterials which would act at minimizing sheer stress on the cells during the injection, or help stabilize the cells prior to, or after the injection. Formulations according to the present invention can include cell carriers such as one or more of collagen, gelatin, hyaluronic acid, saline or Ringer's solution, Agar, or similar solutions or physical augmentation material. Such a formulation could also be helpful in maintaining cell viability while the cells are frozen for storage and transportation. Formulation with various soluble and insoluble factors and biomaterials could also facilitate injection and help in the retention of the cells at the site optimal for treatment without loss due to dilution because of the presence of various body fluids such as blood, serum etc, or surgical fluids such as saline washes. Certain formulations could include natural bone graft fragments, a synthetic scaffold set in situ to further increase retention at the injection site. Additional formulations could include biomaterials to improve injection and retention and include only the secreted factors from the cells either purified or not, enriched or concentrated or not without the cells themselves, combined with the formulation for injection. Additional therapeutic agents can be added such as antibiotics, anti-inflammatory compounds, nano silver and/or ionic silver, and/or marker material to enhance visualization via fluoroscopy or other imaging or visualization technique.

[0044] Certain formulations in conjunction with conventional physical augmentation techniques could be injected in a specific sequence to allow mechanical stabilization of certain bone structures such as the end plate or the vertebral pedicle, or to plug a needle or trocar access point to the bone, once the delivery of the therapy is complete. The inflammation modulating cells could be injected immediately after, or just before the delivery of the conventional physical augmentation technique.

[0045] Physical augmentation material can include scaffold material including one or more of DBM (demineralized bone material), collagen, bone particles, synthetic particles such as PEEK (polyether ether ketone), calcium phosphate cement. Traditional bone cement generally may have a negative impact on cells, but could be injected after cleaning out inflammation residues and before cells are injected according to the present invention. It may be desirable to increase porosity of the cement by combining it with gelatin fibers, fast resorbing PLA (polylactic acid) fibers, or water-soluble glass such as described by James Walls in U.S. Pat. No. 8,673,018.

[0046] In cases where the treatment site is also physically compromised (such as a fractured vertebral body), conventional physical augmentation techniques can be used in conjunction with, or before or after the cells are delivered. Even if there is no mechanical/physical compromise to the treatment site, an augmentation material can be used before, in conjunction with, or after the cells are delivered. It is preferable, of course, that the augmentation technique and material is compatible with cells so as not to render the cells non-viable. For example, if an acrylic bone cement is used, then the cells should not be inserted until the cement mass has cooled below about 40 degrees C. With more biocompatible materials, the cells can be formulated with the material (such as a calcium phosphate cement) as described above and injected together, or the biomaterial can be implanted before or after the cells are injected. The cells could also be modified to incorporate a tracking dye, imaging enhancer/tracer, or gene or other reporter which could facilitate traceability, localization or persistence once injected.

[0047] Cells can be delivered to the site with little or no preparation of the site, or with more extensive preparation. Certainly, in the case of infection it is desirable to eliminate the infection before the cells are delivered. It is also desirable to eliminate as much of the inflamed tissue as possible by physically removing it by, for example, suction or washing. The method chosen cannot be 100% precise and efficient because it is not possible to image the inflamed area during the procedure. MRI is the standard detection method, but it is unsuitable for use during an operative procedure. So any method needs to be robust. However, MRI can provide a guide to the location and volume of inflamed tissue to be removed.

[0048] It is desirable if the aspiration apparatus allows a sample of the inflamed tissue to be collected for examination and characterization. Such characterization may allow a better understanding of the cause of the disease and provide information that can be used augment the basic anti-inflammatory treatment.

[0049] One cleaning method is to use an aspiration needle and a delivery needle to alternately suck out the inflamed marrow utilizing the aspiration needle and rinse it with saline utilizing the delivery needle. Pre-shaped needles, made of nitinol (memory alloy) in some constructions, may facilitate the procedure. The equipment may also be combined into a single apparatus with dual needles and chambers such that a flow can be set up with saline injection occurring simultaneously with marrow aspiration. A continuous flow system can also be developed where the syringe chambers are replaced with pumps and reservoirs, as described in more detail below regarding FIGS. 7-8C. A system where the second needle deploys such that it is facing the first needle may facilitate, especially, a continuous flow technique.

[0050] Preferably, devices according to the present invention are suitable to both remove fluids including particulate matter, especially inflammatory materials, from bone such as a vertebral body as well as to deliver fluids including formulations with living cells, anti-inflammatories, augmentation materials, and/or antimicrobial compositions including antibiotics. It is preferable to be able to access most of the interior of the vertebral body with flushing fluids, suction, and delivery of therapeutic materials. Several constructions for accomplishing this will be detailed below. If a needle of a delivery device according to the present invention is inserted directly in the bone it is unlikely that the needle can be moved around much inside the vertebral body so flushing would probably depend on a strong flow of saline that would extend well beyond the end of the delivery needle to loosen and liquefy the bad materials. For maximum effectiveness, the suction should be shut off during the saline delivery phase.

[0051] If a guide tube, also referred to as an outer cannula, is inserted in the bone before delivery/suction devices are inserted, then the fluid deliver/suction devices could be moved around somewhat inside of the vertebral body. This could help the efficiency and possibly simultaneous suction and delivery could be used. This is especially true if the suction and delivery needles could slide relative to each other.

[0052] Initial incision and placement of a distal portion of a device according to the present invention typically would follow conventional kyphoplasty and/or vertebroplasty techniques. In certain techniques according to the present invention, individual needles or catheters may be inserted for each procedure sequentially or in parallel, thus a needle for withdrawing inflammatory components, a needle for delivering saline, a needle for the cells, etc.

[0053] A distal portion 12, FIG. 1, of a dual-cannula delivery device 10 according to the present invention is shown inserted via a transpedicular (through the pedicle) approach into the interior 20 of a vertebral body VB.sub.2 of a patient. Vertebral body VB.sub.2 is separated from vertebral bodies VB.sub.1 and VB.sub.3 by discs D.sub.1 and D.sub.2, respectively. An inner delivery cannula 14 and an outer withdrawal cannula 16, also referred to as removal cannula 16, are passed through a guide sleeve 18, such as a needle or catheter having an inner diameter which is greater than the outer diameter of withdrawal cannula 16. Inner delivery cannula 14 has a distal tip 22 through which fluids are delivered as indicated by arrows 24. Removal cannula 16 has a distal tip 26 which draws fluids into it as indicated by arrows 28. Guide sleeve 18 remains in position to guide the delivery cannula 14 and withdrawal cannula 16 into the interior 20 of vertebral body VB2, and then is removed at the end of the procedure. The distal portion 12 can then be moved distally and proximally relative to guide sleeve 18 to effectively clean the inside of vertebral body In another technique, the delivery cannula 14 and withdrawal cannula 16 are inserted together directly into the bone without a guide sleeve.

[0054] The proximal portion of the delivery devices according to the present invention can have various constructions as described in more detail below. Delivery device 10a, FIG. 1A, has a distal portion 12a that is similar to distal portion 12, FIG. 1, and a proximal portion 30a with a handpiece 32, inlet portion 34 communication with a delivery cannula 14a, and a removal portion 36 communicating with a removal cannula 16a such as described below in relation to FIG. 7 for a pump/pneumatic system to deliver fluids to bone and withdraw unwanted fluids and materials. A flexible section 40 enables removal cannula 16a to be moved axially relative to fixed delivery cannula 14a. Both cannulas 14a and 16a are axially movable independently relative to guide sleeve 18a.

[0055] A dual-cannula device according to the present invention has a parallel configuration in some constructions and a concentric configuration in other constructions, as illustrated schematically in FIGS. 2 and 3. The geometrical relationship of the cannulas is fixed relative to each other in certain constructions or the cannulas slide independently. Distal portion 12b, FIG. 2, has parallel sliding cannulas 14b and 16b that deliver fluid, arrows 24b, or withdraw fluid, arrows 28b. Arrows 50 indicate the relative axial movement of cannulas 14b and 16b. Distal portion 12c, FIG. 3, has concentric cannulas 14c and 16c which move concentrically relative to each other as indicated by arrows 60 before, during or after delivery of fluid, arrows 24c, and removal of fluid, arrows 28c, respectively.

[0056] In certain constructions, the proximal portion includes dual chamber syringes to feed the cannulas. They would be arranged such that when a common plunger is pushed, one chamber would suck out liquid by generating negative pressure and the other chamber would feed liquid into a delivery cannula. A dual chamber syringe 70, FIG. 4, defines chambers 72 and 74 to be the same diameter and arranged in-line with each other. Arrow 76 schematically illustrates fluid including bodily material such as inflamed or damaged tissue being drawn into removal cannula 78 and then into chamber 74 when a single plunger 82 is depressed, while simultaneously delivering fluid under positive pressure from chamber 72 through delivery cannula 80 and into a patient.

[0057] FIG. 5 is a schematic perspective view of a dual chamber syringe device 90 having parallel syringe bores 92, 94 defining a suction chamber 96 larger than a delivery chamber 98 plus fixed inner and outer cannulas 100, 102 having distal tips 104 and 106 for discharging and withdrawing fluids, respectively. Suction chamber 96 includes (1) a collection volume 110 on the proximal side of a piston 126 that communicates with withdrawal cannula 102 via a conduit 107 and (2) a gas volume 112 on the distal side of piston 126 that is filled with a gas such as air that is vented out a port 114. Delivery chamber 98 includes (1) a delivery volume 116 on the distal side of a piston 128 and (2) an empty volume 118 that communicates with the atmosphere.

[0058] As plunger 120 is depressed, plunger rods 122 and 124 transfer force to pistons 126 and 128. Fluid in delivery volume 116 is forced into delivery cannula 100 while bodily fluids and material are simultaneously aspirated into collection volume 110. In one construction, conduit 107 includes a check valve 109, shown in phantom, to inhibit backflow of fluid toward distal tip 106 of cannula 102.

[0059] Device 90a, FIG. 6, is similar to device 90, FIG. 5, plus has the capability to axially move the removal cannula 102a relative to the delivery cannula 100a. Conduit 107a includes a flexible section 130 to enable axial movement of removal cannula 102a. A finger grip or projection can be added to the distal portion of conduit 107a or to removal cannula 102a independent of movement of plunger 120a. In some constructions, chambers 96a and 98a are the same size in diameter and volume for both the in-line and parallel chamber designs and, in other constructions, the chambers differ in size from each other. The cannulas of devices 90 and 90a can be utilized with or without guide sleeves or catheters as described elsewhere in this application.

[0060] Instead of self-contained devices shown in FIGS. 4-6, it is also possible to use separate pumps, one for suction and one for fluid delivery. The pumps could run together, but it is best to be able to control suction and delivery separately. A preferred operating sequence is to first suck out some material, then deliver a saline flush, then shut off the saline and suck it out along with loosened inflammatory material. This cycle could be repeated several times before finally injecting therapeutic material(s). Instead of pumps, a vacuum collection reservoir could be used for suction and a pressure reservoir could be used for fluid delivery. It is also possible to provide a control system that automatically cycles between fluid deliver and suction, possibly with the time intervals being settable by the surgeon.

[0061] Delivery system 140, FIG. 7, shows a pump arrangement with a manual fluid control valve 146 between a delivery pumps 148, a suction pump 150 and associated fluid reservoirs (not shown) and the delivery cannula 142 and withdrawal cannula 144. An electric switch that turns the pumps on and off as needed could also be used as well as a pneumatic control valve that controls suction and pressurized air to suction and fluid delivery reservoirs.

[0062] Manual fluid control valve 146, FIG. 7, is shown in operation in FIGS. 8A-8C. A plunger 160 defines first and second passages 162 and 164 and is biased by a spring 166 within block 170 to an off position as shown in FIG. 8A. Block 170 defines first and second channels 172 and 174 which are in fluid communication with removal cannula 144 and delivery cannula 142, respectively. In this construction, initial force applied to plunger 160 causes first passage 162 to align with first channel 172 to pass bodily materials as indicated by arrow 180, FIG. 8B, through suction pump 150, FIG. 7. Further depression of plunger 160 causes second passage 164, FIG. 8C, to align with channel 174, also referred to as a saline passage, to enable delivery of fluid as indicated by arrow 182.

[0063] Therapy could be delivered through the saline passage with suction turned off in the case of a free-flowing therapeutic material such as cells in a carrier or possibly a liquid self-setting calcium phosphate cement. In the case of a particulate augmentation material it may be preferred to remove the twin needle device and replace it with a larger diameter catheter.

[0064] Cells and physical augmentation product can be delivered sequentially. There may be an advantage to deliver the physical scaffold first, then the cells onto the scaffold. It is also possible to mix cells and scaffold/augmentation material together before delivery if the augmentation material is cell friendly.

[0065] Individual syringes can be used for specialized delivery (or suction) with the twin needle devices used for routine operations such as flushing. Delivery needles/catheters can have more than two passages, maybe three or four passages would be useful for some indications. But in general, it is best to use a guide catheter and separate delivery devices if the delivery needs cannot be met with a two lumen delivery device.

[0066] Any other equipment, either existing or to be developed in the future, for delivering or aspirating fluids intraoperatively, may be adapted to the technique. Also, there are many options for the operative approach. Any technique that the treating physician is comfortable with is probably satisfactory. When it comes to the spine, the most common technique is expected to be the transpedicular (through the pedicle) approach used with kyphoplasty and vertebral augmentation. Examples of other techniques are a direct lateral approach and an approach through the disc into the endplate. These examples are not meant to be limiting.

[0067] If there is obvious involvement of bone inflammation on both sides of the joint or damaged disc, then the anti-inflammatory treatment should be applied to both bone areas. Even if only one bone (or vertebral body) shows obvious inflammation, the opposite bone can be treated with the anti-inflammatory cells as a prophylactic measure.

[0068] In a preferred embodiment of this invention, a surgeon or interventional radiologist would insert a needle or small trocar in the pedicule vertebral body, and through fluoro-guidance, would push the needle/trocar until it reaches the vertebral body, guide the needle to the zone of inflammation from prior diagnostic imaging, and inject MSCs at the site of inflammation. The MSCs injection could be performed after a quantity of inflamed marrow was removed by suction from the same needle or through a different one place in the vicinity from another port or access. The surgeon or radiologist would then remove the needle(s) and standard post intervention procedures for tending the soft tissue puncture site would be follow. In another embodiment of the invention, the inflamed tissue removed from the site could be characterized for diagnostic or other clinical use.

[0069] An open technique can also be used, if desired. This might be advantageous in cases where severe infection is present and open debridement is needed to remove the infected tissue.

[0070] Although specific features of the present invention are shown in some drawings and not in others, this is for convenience only, as each feature may be combined with any or all of the other features in accordance with the invention. While there have been shown, described, and pointed out fundamental novel features of the invention as applied to a preferred embodiment thereof, it will be understood that various omissions, substitutions, and changes in the form and details of the devices illustrated, and in their operation, may be made by those skilled in the art without departing from the spirit and scope of the invention. For example, it is expressly intended that all combinations of those elements and/or steps that perform substantially the same function, in substantially the same way, to achieve the same results be within the scope of the invention. Substitutions of elements from one described embodiment to another are also fully intended and contemplated. It is also to be understood that the drawings are not necessarily drawn to scale, but that they are merely conceptual in nature.

[0071] It is the intention, therefore, to be limited only as indicated by the scope of the claims appended hereto. Other embodiments will occur to those skilled in the art and are within the following claims.