Abstract:
This description relates to drug delivery devices ( 100 ), as well as related components, systems and methods.

Description:
TECHNICAL FIELD 
       [0001]    This description relates to drug delivery devices, as well as related components, systems and methods. 
       BACKGROUND 
       [0002]    Calcium phosphate-based cement is commonly used in many orthopedic and anaplastic surgical procedures. Various devices have been developed to prepare and/or deliver bone cement in such procedures. 
       SUMMARY 
       [0003]    This description relates to drug delivery devices, as well as related components, systems and methods. 
         [0004]    In various embodiments, the drug delivery devices, systems and methods can offer a reliable, repeatable, and/or consistent delivery of a predetermined volume of a liquid containing a therapeutic agent, such as an osteogenic agent. Prior to dissolution in the liquid, the therapeutic agent can be provided (stored) in the delivery device, for example, in solid (e.g., powder) form. Examples of therapeutic agents include proteins, such as a member of the transforming growth factor beta (TGF-β) family, at least one protein from the bone morphogenetic protein (BMP) family of proteins, or at least one protein from the growth/differentiation factor (GDF) family of proteins. In some embodiments, the therapeutic agent includes combinations of proteins, for example, combinations of any of the foregoing proteins. 
         [0005]    The compound can be secured in the device until reconstituted and administered to a patient to help control (e.g., prohibit) unintended usage. The components for reconstituting, mixing and agitating and delivery the admixture can be aseptically contained within a unitary system, thereby minimizing or eliminating contamination. The delivery device can also provide force enhancement to mix and prepare for injection reconstituted compounds which exhibit substantially viscous properties. 
         [0006]    In one aspect, a drug delivery system features a drug delivery device including a main body including a proximal end, a distal end, and a mixing chamber positioned between both ends, a rotary driver disposed at the proximal end of the main body, a main piston operably linked to the rotary driver, an agitator disposed with the mixing chamber and affixed to an agitator shaft, the agitator shaft operably linked to the main piston such that rotating the rotary drive imparts axial movement to agitator, and a piston end operably linked to the main piston. 
         [0007]    In another aspect, a drug delivery system features a delivery device, a reconstitution manifold and an air pump. The reconstitution manifold includes a first vial to contain a first substance, a second vial, in fluid communication with the first vial, to contain a second substance. The air pump is in fluid communication with the first and second vials and configured to operate in at least a first and second mode. While operating in the first mode, at least part of the first substance is combined with the second substance to form a resulting admixture. While operating in the second mode, the admixture is transferred from either the first or second vials to the delivery device. 
         [0008]    In another aspect, a method for preparing calcium phosphate-based cement includes reconstituting a BMP powder to form a BMP admixture in manifold, delivering the BMP admixture from the manifold to a delivery device releasably attached to the manifold, mixing the admixture with a CPM (calcium phosphate matrix) contained within the delivery device to form a third substance, and displacing a piston slidably disposed within the delivery device to eject the third substance from the delivery device. 
         [0009]    Features and advantages will be apparent from the description, drawings and claims. 
     
    
     
       DESCRIPTION OF DRAWINGS 
         [0010]      FIGS. 1A and 1B  are perspective and side views of an embodiment of a drug delivery device, respectively. 
           [0011]      FIGS. 2A and 2B  are perspective and side views of an embodiment of a drug delivery device, respectively. 
           [0012]      FIG. 3  is a partial sectional perspective view of the device of  FIGS. 1A and 1B . 
           [0013]      FIG. 4  is an exploded and partial sectional view of the device of  FIGS. 1A and 1B . 
           [0014]      FIGS. 5 and 6  are detailed perspective view of components disposed at the distal end of the device of  FIGS. 1A and 1B . 
           [0015]      FIG. 7  is a detailed perspective view of components disposed at the proximal end of the device of  FIGS. 2A and 2B . 
           [0016]      FIG. 8A  is a cross-sectional view of the device of  FIGS. 1A and 1B . 
           [0017]      FIG. 8B  is a detailed view of the area  8 B of  FIG. 8A . 
           [0018]      FIG. 9  is a cross-section of view of the device of  FIGS. 2A and 2B . 
           [0019]      FIG. 10  is a graphical depiction of the axial and rotation movement of components of the devices of  FIGS. 1A through 2B . 
           [0020]      FIG. 11  is a detailed view of an agitator of the devices of  FIGS. 1A through 2B . 
           [0021]      FIG. 12  is a schematic view of a drug delivery system including the drug delivery device of  FIGS. 1A and 1B  and a reconstitution manifold. 
           [0022]      FIG. 13  is a perspective view of a drug delivery system. 
           [0023]      FIGS. 14A and 14B  are partial sectional perspective views of the drug delivery system of  FIG. 13 . 
           [0024]      FIG. 15  is a perspective view of the internal components of the reconstitution manifold of  FIG. 13 . 
           [0025]      FIG. 16  is a cross-sectional view of internal components of the reconstitution manifold of  FIG. 13 . 
       
    
    
       [0026]    Like reference symbols in the various drawings indicate like elements. 
       DETAILED DESCRIPTION  
       [0027]    In certain embodiments, a drug delivery system reconstitutes a first substance, mixes and agitates the reconstituted first substance with a second substance to form a third substance and delivers, by injection, the third substance to a patient. 
         [0028]    In some embodiments, the first substance is a therapeutic agent, such as an osteogenic agent. A therapeutic agent can be provided, for example, in solid (e.g., powder) form. Examples of therapeutic agents include proteins, such as members of the TGF-β family (e.g., one or more members of the BMP family of proteins, one or more members of the GDF family of proteins). Examples of osteogenic agents are disclosed, for example in U.S. Pat. Nos. 6,719,968, 6,027,919, 5,658,882, 5,618,924 and 5,013,649, which are hereby incorporated by reference. In certain embodiments, the osteogenic agent is BMP-2, BMP-12 or MP52. In some embodiments, multiple therapeutic (e.g., osteogenic) agents can be used. In certain embodiments, the second substance is a CPM powder. 
         [0029]    In general, the first substance is reconstituted and transferred to a delivery device containing the second substance wherein the reconstituted BMP powder and CPM are mixed to form a third substance. The third substance is then ejected from the delivery device and administered to a patient by injection, for example. 
         [0030]    In some embodiments, the drug delivered system is configured for preparing a homogeneous third substance, which includes the first and second substances, and has physical properties such as viscosity, density and specific gravity well suited for delivery to a patient by injection, for example. In some embodiments, the device is configured for use with BMP-2. 
         [0031]      FIGS. 1A and 1B  show a delivery device  100  having a proximal end  102  and a distal end  104  and including a main body front  105  joined to an axially extending main body rear  110 . The delivery device can be dimensioned to administer a suitable quantity, such as 5-ml or 1-ml of a material, such as a bone cement, to a patient. A rotary drive  115  is threadably attached at the proximal end  102  of the main body rear  110  and an outer front  120  is threadably attached to the main body front  105 . The outer front  120  includes a luer connection  123  configured to receive a needle or reconstitution manifold (described below). In certain embodiments, the main body front  105  includes a window  125  to display the position of the interior components of the device  100  and the contents therein. In some embodiments, the main body rear  115  includes laterally extending fins  130 . 
         [0032]    In some embodiments, as shown in  FIGS. 2A and 2B , the delivery device  100  can include a piston end  132  extending along a concentric bore in the rotary drive  115  and protrudes beyond a proximal end  133  of the drive  115 . 
         [0033]      FIGS. 3 through 9  show the internal components of the delivery device  100  including a syringe barrel  135  disposed within the main body front  105 . A piston shaft  140  extends axially along the length of the device between the proximal and distal ends  102 ,  104 . An agitator shaft  145  concentrically receives a portion of the piston shaft  140 . The syringe barrel  135  includes a frustoconical wall  147  ( FIGS. 8A and 8B ) to define a mixing chamber  150  through which the piston shaft  140  extends. The syringe barrel  135  can include a circumferentially extending vent (not shown) to allow evolved gases within the barrel to escape while the mixing chamber  150  is filled and/or during the mixing and/or ejection of the contents contained therein (described below). The vent can be formed from a sintered material wrapped with a high density polyethylene, such as polytetrafluoroethylene (PTFE), for example. 
         [0034]    The piston shaft  140  includes a piston head  151  and an axial central bore  152  extending along the piston shaft  140  from a port  153  located at a distal end of the piston head  151 , toward the mixing chamber  150 , when the piston shaft  140  is in a filly distal position. The central bore  152  can includes transverse ports  154 , such that when the piston head  151  is in a filly distal position, the luer connection  123  is in fluid communication with the mixing chamber  150 . 
         [0035]    The outer front  120  can include a substantially cylindrical ejection chamber  155  which receives a front seal  157 . The ejection chamber  155  and front seal  157  are sized to receive the piston head  151  of the piston shaft  140 . In some embodiments, the mixing chamber  150  is preloaded with the second component, such as, for example, a CPM powder, for mixing with the first component, such as, for example, a reconstituted BMP liquid that is introduced through the luer connection  123 , along the central bore  152 , out of the transverse ports  154  and into the syringe barrel  135 . 
         [0036]    In some embodiments, the transverse ports  154  include a circular seal (not shown), such as an o-ring, for example, which permits the passage of fluid from the central bore  152  to the mixing chamber  150  but substantially impedes the reverse flow of fluid from the mixing chamber  150  to the central bore  152 . In certain embodiments, the circular seals allow a reconstituted BMP-2 liquid to flow into the mixing chamber  150  via the transverse ports  154  and prevents the BMP-2 liquid from flowing back into the central bore  152  during the mixing and ejection of the BMP-2 liquid with the CPM. The port  153  at the distal end of the piston head  151  can also include a plug (not shown) of sintered material which is configured to allow the passage of a liquid, such as, for example, the flow of reconstituted BMP-2 through the luer connection  123  and into the central bore  152 , but substantially impedes the flow of a paste, such as, for example, a mixture of reconstituted BMP-2 and CPM. 
         [0037]    An agitator  158  and an agitator seal  160  which seated proximally to the agitator  158  and can be frustoconical, for example, are contained within the mixing chamber  150  and are attached to the piston shaft  140 . A piston end  132  ( FIGS. 8A and 8B ) is attached to a proximal end of the piston shaft  140  with a fastener  134 . 
         [0038]    In certain embodiments, shown in  FIG. 9 , an agitator and an agitator seal integrally form an agitator assembly  163 . The agitator assembly  163  engages the frustoconical wall  147  of the syringe barrel  135  to form a seal therewith. The proximal end  164  of the piston shaft  140  extends and connects with the fastener  134 . A piston end spring  165   a  and main piston spring  165   b  bias the piston shaft  140  distally to improve contact between the piston head  151  with the front seal  157  during mixing. 
         [0039]    The piston end  132  is configured for axial (translational) movement and the rotary drive  115  is configured for rotational movement. A main piston  166 , an inner ratchet  168 , a drive inner  170  and a drive outer  172  are concentrically arranged along the piston shaft  140  between the agitator shaft  145  and the main body rear  110  to translate the rotary movement of the rotary drive  115  to the agitator  158  and the axial movement of the piston end  132  to the main piston  166  as described below. 
         [0040]    A cam track  173  extends around the agitator shaft  145  and receives a cam follower  175  mounted to an inner surface of the syringe barrel  135 . The rotary drive  115  is keyed directly to the main piston  166  proximate the piston end  132  ( FIGS. 8A and 8B ). Accordingly, rotation of rotary drive  115  rotates the main piston  166 . The main piston  166  is keyed to the agitator shaft  145 , such that as the main piston  166  rotates, engagement of the cam follower  175  with the cam track  173  imparts axial movement of the agitator shaft  145  and the attached agitator  158  within the mixing chamber  150 . The cam track  173  can describe a helical path, for example, about the agitator shaft  145 . A retainer ring  177 , a drive runner  180 , and a drive runner stop ring  185  are concentrically arranged along the drive outer  172  between the main body rear  110  and the rotary drive  115 . 
         [0041]    In operation, in certain embodiments, the agitator shaft  145  and attached agitator  158 , follow a reciprocating motion within the mixing chamber  150  to mix the paste. Referring to  FIG. 10 , one prescribed motion includes 120-degrees rotation of the rotary drive  150 ; a 240-degrees helical motion with 30-mm axial movement towards the distal end  104 ; a 120-degrees rotation; and 240-degrees helical motion with 30 mm axial movement towards the proximal end  102 . The agitator  158  thus returns to its starting point every two revolutions of the rotary drive  115 . 
         [0042]    In certain embodiments, as shown in  FIG. 11  and, the agitator  158  includes a plurality of blades  186  extended substantially radially from the agitator shaft  145 . The blades  186  can be made from a variety of material including, for example, polycarbonate, Santoprene® (Monsanto Corporation, Delaware), polyester elastomer, polypropylene, or polyethylene. The blades  186  can be formed from a flexible material and configured to mix and agitate the contents of the mixing chamber  150  to form a homogeneous paste. The blades  186  can be configured to deform when the agitator shaft  145  is moved rotationally and remain radially extended when the agitator shaft  145  is moved axially. 
         [0043]    As the agitator  158  or agitator assembly  163  ( FIG. 9 ) operates, the drive inner  170  and drive outer  172  components will also rotate within the main body front  105 . The rotary drive  115  is keyed to a drive runner  180 , which engages threads  187  on the main body rear  110 . As the rotary drive  115  is turned, the drive runner  180  moves along the main body rear until it contacts the drive runner stop ring  185 . The retainer ring  177  includes two tabs  188  configured to engage slots  189  disposed in the main body rear  110  proximal to the fins  130 , to prevent the rotary drive  115  from moving axially relative to the main rear body  110 . The drive runner stop ring  185  is pinned to the main body rear  110  and secured in place. 
         [0044]    The drive runner stop ring  185  includes circumferentially located bosses  190  sized and configured to engage circumferentially located recesses  193  on the drive runner  180 . As the rotary drive  115  and agitator  158  are turned to mix the contents of the mixing chamber  115 , the drive runner  180  advances axially along threads  187  a predetermined distance until the drive runner is proximate the drive runner stop ring  185 . The bosses  190  along the drive runner stop ring  185  engage the recesses  193  along the drive runner  180  locking the drive runner  180  against further rotation. In some embodiments, after about 16-turns of the rotary drive  115  and a satisfactory mix of the contents of the mixing chamber  150  is achieved, the drive runner  180  is locked to the drive runner stop ring  185 . 
         [0045]    After the contents of the mixing chamber  150  are sufficiently mixed, the rotary drive  115  is locked against rotation by the driver runner stop ring  185 . The agitator shaft  145  is therefore prevented from rotating in the main body front  105 . The piston end  132  is released by rotating it clockwise relative to the rotary drive  115  (when viewed from the proximal end  102 ), which unlatches a bayonet arrangement (not shown) between these two parts. The piston end  132  and the main piston  166  are then urged back (towards the proximal end) by about 30 mm under the action of a spring (not shown). 
         [0046]    The drive inner  170  is configured to rotate and be fixed axially by an radially extending flange  194  disposed between the main body front  105  and the rotary drive  115 . The drive inner  170  connects to the main piston  166  by a two start 120-mm pitch thread, and therefore rotates by 90-degrees counterclockwise as the main piston  166  moves back. The drive outer  172  carries a set of ratchet arms  195  ( FIG. 4 ) that permit only clockwise rotation within the main body front  105  and is threaded to the drive inner  170  via a single start 3-mm pitch thread. Therefore, as the drive inner  170  rotates counterclockwise, the drive outer  172  is forced to rotate 90-degrees relative to the drive inner  170 , and is pushed 0.75 mm towards the distal end of the device. 
         [0047]    After the piston end  132  is depressed a full stroke by the user (in the distal direction), the piston end  132  then moves back toward its original position (in the proximal direction) to complete a return stroke under the action of the a spring (not shown) located in an annular region between piston end  132  and the rotary drive  115 . As the piston end  132  is depressed by the operator, the drive outer  172  bears directly on the syringe barrel  135  such that the syringe barrel  135  is forced 0.75-mm towards the distal end  104  of the device. The operator can use the laterally extending fins  130  ( FIGS. 1A through 2B ) for improved leverage in depressing the piston end  132 . 
         [0048]    In some embodiments, a full return stroke of the piston end  132  in the proximal direction, 30-mm, for example, translates into an axial movement of the syringe barrel  135  of only 0.75-mm, while increasing the transmitted axial force by a factor of 40 (30 /0.75-mm). Such force enhancement decreases the static and dynamic force requirements for mixing and displacing the contents of the syringe barrel. This is particularly advantageous when the syringe barrel  135  contains a substantially viscous fluid. The force enhancement and corresponding axial advancement of the syringe barrel  135  can be modified to suit various operator force requirements and fluid viscosities. 
         [0049]    The piston end  132  is pushed against the load of the spring (not shown) and the drive inner  170  rotates 90 degrees clockwise. The drive outer  172  is connected to the drive inner  170  via a set of ratchet arms that permit the drive outer  172  to only rotate clockwise relative to the drive inner  170 . Therefore, as the drive inner  170  rotates clockwise it carries the drive outer  172  with it, rotating in the main body front  105 . 
         [0050]    The syringe barrel  135  remains stationary relative to the main body front  105  during the forward stroke of the main piston  166 , and the front of the main piston  166  moves into a reduced diameter section of the outer front  120 , which serves as a small diameter paste dispensing syringe. 
         [0051]    In certain embodiments, the volume occupied by mixed paste contained within the mixing chamber  150  is less than that occupied by the CPM powder, so there is a void within the mixing chamber at the end of the mixing process. The first 10 to 15 strokes of the piston end  132  and the main piston  166  serve to take up the void space. 
         [0052]    After the void is filled by the movement of the syringe barrel  135  relative to the outer front  120 , the reducing volume of the mixing chamber  150  causes the contents of the mixing chamber  150 , such as a paste for example, to flow into the reduced diameter bore in the outer front seal  157 , as the main piston  166  is withdrawn. On the subsequent advance of the main piston  166 , this paste is forced out of the luer connection  123  on the front of the outer front  120 , and into an injection needle attached to the luer connection  123 . In certain embodiments, the volume of paste ejected from the device is from about 0.1 ml to about 0.3 ml per stroke of the main piston  166 . 
         [0053]    The outer front  120  is connected to the main body front  105  and slides within the syringe barrel  135 , so the effect of the movement of the syringe barrel  135  is to reduce the axial length of the mixing chamber  150 . The movement of the outer front  120  at the distal end of the mixing chamber  150 , addresses a phenomenon referred to as filter pressing, whereby the liquid in a multiphase composition, such as a calcium phosphate cement, for example, separates from the solid at the point where the load is applied, thereby leaving the solid portion behind, during ejection from a syringe, for example. In certain embodiments, the application of the load by the movement of the syringe barrel  135  relative to the outer front  120  proximate the outlet of the mixing chamber  150 , i.e., the luer connection  123 , helps the portion of the paste proximate the luer connection  123  to remain dry and the general body of the paste retain a sufficiently high water content for subsequent ejection and delivery through the luer connection  123 . 
         [0054]    Referring generally to  FIGS. 12-16 , the delivery device  100  can be used as a component in a drug delivery system  200  which also includes a reconstitution manifold  205  and a syringe  210  which can also include an air pump or other pressure source. In certain embodiments, the manifold  205  includes two vials, a water for injection (WFI) vial  215  and a concentrate vial  220 . The contents of the vials  215 ,  220  form an admixture to be delivered through an exit port  223  which is releasably attached to the luer connection  123  of the outer front  120  of the device  100 . The WFI vial  215  includes a vent  225  extending generally upwards and terminating in a catch-pot (not shown) which is open to ambient and has a volumetric capacity substantially equal to the volume of the vent  225 . 
         [0055]      FIG. 13  depicts a unitary system  300  including components of the drug delivery system  200 . The drug delivery device  100  and/or the syringe  210  can be releasably attached to the reconstitution manifold  205  during varying stages of use of the drug delivery system  200 . 
         [0056]    With specific reference to  FIGS. 14A through 15 , the manifold  205  can include a cover  230  slidably disposed within the manifold  205  and configured to position vials  215  and  220  above concentric needles  235  in a raised position. In one embodiment, the vials  215 ,  220  are locked inside of the cover  230  to limit access and the unintended use of the vial contents, before transfer to the delivery device  200  as described below. The cover  230  can be substantially transparent to reveal the enclosed vials  215  and  220 . When the cover  230  is pushed toward a lowered position, the vials  215  and  220  are pierced by the concentric needles  235  for evacuation of the vial contents during operation of the manifold  205 . 
         [0057]    The cover  230  can include vial guides  232 ,  234  ( FIG. 15 ) to center the vials  215 ,  220  on the concentric needles  235 . The manifold  205  can include a manifold assembly  305  to support the vials  215 ,  220  as the cover  230  is moved to the lowered position. The delivery device  100  is attached to the manifold  205  at a device connector  310  ( FIGS. 14A and 14B ). The syringe  210  is attached to the manifold  205  at an air pump connector  315 . In certain embodiments, all components of the manifold  205 , including the vials  215 ,  220  are self-contained by an external housing  320  which can be configured to be tamper-evident or tamper-proof. A connection shutter  325  is slideably disposed proximate the device connector  310  and configured to be normally held open against the bias of a spring (not shown) by the luer connection  123  when the delivery device  100  engages the manifold  205 . When the delivery device  100  is removed from the manifold  205 , the connection shutter  325  springs closed and passes into a groove (not shown) configured such that the shutter  325  can not subsequently be reopened. This configuration minimizes the possibility of extraction of the contents of the vials  215 ,  220  from the manifold  205  by premature removal of the delivery device  100 . 
         [0058]    As shown in  FIG. 16 , the concentric needles  235  can include a core needle  330  substantially surrounded by an outer sheath  335  to define annular space between the core needle  330  and the sheath  335  for passage of the contents of the vials to the manifold  205 . The core needle  330  is open at a needle tip  340  and connected to an air conduit  345  to provide for passage of air and between the vial  215  and the air pump  210  and between the vial  220  and the vent  225 . Transverse ports  340  extend from the sheath  335  to provide fluid communication between the vials  210 ,  215  and the manifold  205 . 
         [0059]    In use, an operator pushes the cover  230  of the manifold  205  downward thereby penetrating the vials  215 ,  220  with concentric needles  235 . The syringe  210  is first pulled out to draw the WFI from the vial  215  through a first one-way valve  227  and into the concentrate vial  220 , facilitated by the vent  225 . The manifold  205  is then gently agitated to reconstitute the contents of the concentrate vial  220 . The syringe  210  is then pushed in to force the reconstituted mixture from the concentrate vial  220  through a second one-way valve  229  and into the delivery device  100 . The delivery device  100  can be removed from the manifold  205  by rotating the delivery device  100 , for example, and detaching the luer connection  123  from the device connector  310 . The connection shutter  325  closes to limit access to the remaining contents of the concentrate vial  220 . Both of the return valves  227 ,  229  and the luer connection  123  can be contained with a valve manifold  350 . 
         [0060]    The operator then rotates the rotary drive  115  clockwise (as viewed from the proximal end  102 ) about 15 or 16-full rotations, for example, to form a paste in the mixing chamber  150  of the delivery device  100  and lock the rotary drive  115 . Accordingly, the paste can be consistently, uniformly and aseptically mixed within the mixing chamber  150  before delivery to the ejection chamber  155  and passage through the luer connection  123 . A delivery needle (not shown), such as a Tuohy needle with an obdurator, for example, is connected to the luer connection  123  of the delivery device  100 . The delivery needle can be positioned within a patient before or after connection with the delivery device  100 , using a fluoroscope, for example, and directed at a treatment site, such as a wrist or hip, for delivery of the contents of the mixing chamber  150  of the delivery device  100 . 
         [0061]    The rotary driver  115  or the piston end  132  protruding from the rotary drive  115  ( FIGS. 8A ,  8 B, and  9 ) is rotated clockwise (as viewed from the proximal end  102 ) 15 to 20-degrees, for example, to release the bayonet and force the piston end  132  in a proximal direction under the bias of the springs  165   a  and  165   b  ( FIGS. 7 , and  9 ). The piston end  132  rotates independently of the rotary drive  115 . 
         [0062]    The operator then depresses the piston end  132  in a distal direction 10 to 15 full strokes, for example, before the paste is available for ejection from the ejection chamber  155 , through the luer connection  123  and the connected delivery needle, and injection to the treatment site. In some embodiments, the delivery device  100  is configured for one-time usage. 
         [0063]    While certain embodiments have been described, others are possible. 
         [0064]    As an example, while certain dimensions have been disclosed, in general any desired dimensions can be used. 
         [0065]    As another example, while formulation and delivery of bone cement have been described, other mixtures can also be formed and/or delivered. 
         [0066]    As a further example, while certain applications of systems and devices have been described, in general, the devices and systems can be used in any desired application. As an example, the devices and systems can be used in tissue (e.g., bone, cartilage, tendon, meniscus, ligament) treatment and/or repair. In some embodiments, the devices and systems can be used in bone-to-bone repair. In certain embodiments, the devices and systems can be used in cartilage regeneration. In some embodiments, the devices and systems can be used in bone fracture repair. Additionally or alternatively, the devices and systems can be used in implant treatment and/or repair. As an example, the devices and systems can be used to grout one or more implants. 
         [0067]    Other embodiments are in the claims.