Total joint replacement infection prevention device and method

Abstract

To provide suitable total joint replacement infection prevention devices and methods.SOLUTION: An orthopedic system for delivery of a therapeutic agent to a bone includes an elongate stem adapted to be inserted into an intramedullary canal, an inlet configured to receive the therapeutic agent, and one or more outlets configured to deliver the therapeutic agent to the bone. The elongate stem may comprise one or more protrusions to engage the bone and one or more channels extending longitudinally therein and fluidly coupled to the inlet. The therapeutic agent flows from the inlet through the one or more channels and exits into the intramedullary canal through the one or more outlets. The system may be configured to allow one or more dimensions of the system to be adjusted to be accommodated to the anatomy of a patient.SELECTED DRAWING: Figure 1B

Description

[Technical field]

[0001] (cross reference) This application is a PCT application of U.S. Patent Application No. 14 / 841,529, filed August 31, 2015 (Attorney Docket No. 44445-703.201), which is a nonprovisional application of and claims the benefit of U.S. Provisional Patent Application No. 62 / 180,986, filed June 17, 2015 (Attorney Docket No. 44445-703.101, formerly No. 44057-710.101), the entire contents of which are incorporated herein by reference.

[0002] Total joint replacement (TJR) is a medical procedure that involves the repair and replacement of joints, such as the hip and knee. In these surgical procedures, the bones in the hip or knee joint receive an orthopedic implant that mimics the structure of the joint being replaced.

[0003] In some cases, infection occurs, which can be a serious complication of TJR surgery. Unless the infection is properly diagnosed within the first 2-4 weeks after the original surgery, which is rare, the infected implant must be removed in combination with extensive debridement of the surrounding articular tissue and bone.

[0004] The current standard of care for the treatment of infected TJR in the United States typically involves a two-stage reimplantation process. In the first stage of the process, the infected components are surgically exposed through an incision. Scar tissue is then debulked, other soft tissues may be released, and sometimes osteotomy is performed. This stage also includes removal of all prosthetic components and foreign bodies, including, for example, acrylic bone cement. After extensive debridement of the infected soft tissue and bone, a spacer block consisting of a large amount of antibiotic bone cement is temporarily placed in the joint space. The purpose of the antibiotic bone cement is to sterilize the joint environment and act as an antibiotic delivery system. In addition, the bone cement acts as a spacer to preserve the joint space and maintain ligament length. However, the antibiotics released by the bone cement are uncontrollable and very costly to use. In addition, more operating room time is required to prepare the spacer material, which increases the cost of the surgery.

[0005] Following removal of the infected implant and insertion of an antibiotic bone cement spacer, the patient must generally wait 6-12 weeks before the second stage of the procedure can be performed. This time period is necessary so that the medical professional can be confident that the infection has been successfully eradicated. Only after the infectious condition has been eliminated can the second stage proceed. During the second stage, a new prosthesis is reimplanted.

[0006] In other countries, such as throughout Europe, a one-stage reimplantation process is common. This involves removal of the infected implant, followed by aggressive debridement, and then immediate reimplantation of a new implant, as noted above. Success rates for this technique are typically lower than for two-stage procedures. One-stage implantation processes are generally reserved for patients who are deemed too weak or too ill to undergo the traditional two-stage reimplantation process.

[0007] In some circumstances, both one and two stage procedures may have disadvantages. For example, as noted above, the two stage reimplantation process requires six to twelve weeks between surgeries. This is a very difficult time for the patient as they do not have a functional joint in place and it is typically very painful to move or walk with an antibiotic spacer. The articulating spacers are slightly better than static spacers, but are also more expensive and more difficult and time consuming to place during the original stage one procedure. From a health care perspective, the two stage procedure also requires two separate hospital stays. Finally, from the surgeon's perspective, a significant amount of scar tissue develops during the time span between the two procedures. This makes the second stage operation very difficult and time consuming. In addition, the two stage reimplantation process involves two very difficult and costly surgical procedures instead of one.

[0008] On the other hand, one-stage reimplantation surgical protocols require absolute identification of the infecting organism in order to proceed. Unfortunately, in the current health care system, this absolute identification is very difficult to achieve. In addition, one-stage reimplantation protocols require the use of fully cemented components. Fully cemented components are typically not favored by surgeons in the United States for revision surgery because they require large amounts of antibiotics that can structurally weaken the cement.

[0009] Furthermore, in both the one-stage and two-stage reimplantation surgical protocols, the release of antibiotics from the bone cement cannot be fully controlled, which is a significant disadvantage of both protocols and essentially acts to extend the time between the first and second surgical procedures in the two-stage reimplantation process.

[0010] Thus, there is a need for a device that can be employed during a reimplantation surgical procedure that can be used to deliver antibiotics or other therapeutic agents in a controlled and titratable manner directly into the synovial joint cavity and adjacent medullary canal as a means of eliminating infection following removal of a previous orthopedic implant.In addition, there is a need for such a device that can provide stability and maintain the physical dimensions of the joint space and normal soft tissue envelope in any joint that undergoes reimplantation of an orthopedic implant.In addition, there is a need for such a device that can be easily employed and that facilitates a reduction in the time required to perform a stage 1 reimplantation surgery and reduces the overall time between the first and second stages of a two-stage reimplantation surgical protocol.At least some of these will be addressed by the devices and methods described herein. [Background technology]

[0011] Other patents disclosing devices and methods for delivery of antibiotics to the intramedullary canal include US Pat. Nos. 8,900,323, 8,900,322, and 8,454,706. [Prior art documents] [Patent documents]

[0012] [Patent Document 1] U.S. Patent No. 8,900,323 [Patent Document 2] U.S. Patent No. 8,900,322 [Patent Document 3] U.S. Pat. No. 8,454,706 Summary of the Invention [Means for solving the problem]

[0013] The present invention relates generally to medical systems, devices and methods, and more specifically to orthopedic devices used to deliver therapeutic agents to the intramedullary canal in a joint or bone.

[0014] In one aspect of the invention, a therapeutic agent delivery system includes a first intramedullary stem configured to be positioned in a first medullary canal of a first bone, a second intramedullary stem configured to be positioned in a second medullary canal of a second bone, and a coupling member coupled to the first and second intramedullary stems. The first and second intramedullary stems each include an elongate body having a longitudinal axis, a first end, a second end opposite the first end, and a channel extending between the first and second ends. The first and second intramedullary stems each further include a plurality of projections extending radially outward from the elongate body, adjacent projections defining one or more grooved regions therebetween. The plurality of protrusions are configured to engage the first medullary canal in a stable manner, and the one or more exit holes are disposed within the one or more grooved regions, and the one or more exit holes are in fluid communication with the channel. The coupling member may be coupled to a first end of the first intramedullary stem and a first end of the second intramedullary stem, the coupling member holding the first and second intramedullary stems together and at a fixed distance. The coupling member may further include an inlet in fluid communication with the channel in the first and second intramedullary stems.

[0015] In some embodiments, the coupling member may include an adjustable height manifold configured to increase or decrease the distance between the first ends of the two intramedullary stems when the adjustable height manifold is actuated. The adjustable height manifold may include a housing with a central housing channel disposed therethrough, a rotating nut coupled to the housing, and an adjustable connector disposed within the housing channel. The adjustable connector may have an adjustable connector channel disposed therein. An inlet coupled to the housing may be fluidly coupled to the adjustable connector channel, and the adjustable connector channel may be fluidly coupled to a channel in the first stem or the second stem. Rotation of the nut may extend or retract the adjustable connector relative to the housing. The rotating nut may be threadably engaged with the adjustable connector, and the adjustable connector may be slidably disposed within the housing channel, and rotation of the rotating nut moves the adjustable connector up or down within the housing channel without rotation of the adjustable connector.

[0016] In some embodiments, the connecting member may include a wedge element, and placement of the wedge element between the first end of the first intramedullary stem and the first end of the second intramedullary stem adjusts the distance between the first ends of the two intramedullary stems.

[0017] The therapeutic agent delivery system may further comprise a source of therapeutic agent for delivery to the medullary canal from one or more exit holes in the grooved regions of one or more of the first and second stems. The therapeutic agent may be an antibiotic, which may include vancomycin, tobramycin, or a combination thereof.

[0018] In some embodiments, the first medullary canal can be in the femur and the first stem can be configured to be disposed therein, and the second medullary canal can be in the fibula and the second stem can be configured to be disposed therein.

[0019] In some embodiments, the coupling member may be releasably coupled to the first and second intramedullary stems.

[0020] In some embodiments, the first stem can be the same as the second stem.

[0021] In some embodiments, the first stem or the second stem may include four fins equally spaced around the circumference of the elongated body and extending along its longitudinal axis. The first stem or the second stem may further include a plurality of exit holes extending axially along a line generally parallel to its longitudinal axis.

[0022] In some embodiments, the coupling member may include a flanged region and a first end of the first or second stem may include a recessed region for receiving the flanged region, and rotation of the flanged region relative to the recessed region may releasably lock the first end with the coupling member. One or more pins may be disposed within the first end of the first or second stem and protrude therefrom to engage the flanged region and prevent further rotation of the first or second stem relative to the coupling member. In some embodiments, the coupling member may include a snap-fit ​​or dovetailed section for engaging a corresponding dovetailed or snap-fit ​​section on the first or second stem.

[0023] In some embodiments, the channel may extend from the first end to the second end of the first or second stem, and the channel may extend through both the first and second ends. The system may further include a plug disposed within the channel at the second end of the first or second stem. In some embodiments, the channel may be a dead-end channel in the first or second stem, and the dead-end channel may have a closed second end.

[0024] In some embodiments, the extension body of the first stem or the second stem may be tapered.

[0025] In some embodiments, the coupling member may include a housing, a first stem connector configured to engage a first end of a first intramedullary stem, and a second stem connector configured to engage a first end of a second intramedullary stem. The first and second stem connectors may be disposed on opposite sides of the housing. The first stem connector may have an orientation relative to the second stem connector, and the orientation may remain the same during actuation of the adjustable height manifold.

[0026] In some embodiments, the coupling member may include a housing with a recessed groove circumferentially disposed about at least a portion of the housing. The recessed groove may be sized to receive the tubing.

[0027] The therapeutic agent delivery system may further include a cover disposed over the first stem or the second stem, or a sponge disposed in at least some of the grooved regions of one or more of the first stem or the second stem, The cover or sponge may be configured to promote uniform distribution of the therapeutic agent therefrom into the first or second intramedullary canal.

[0028] The therapeutic agent delivery system may further include a pump configured to pump the therapeutic agent into the channel of the first or second stem.

[0029] The therapeutic agent delivery system may further include a vacuum pump configured to remove undesirable fluids from the first or second medullary canal via one or more exit holes or channels in the first stem or the second stem.

[0030] In some embodiments, multiple protrusions in the first stem or the second stem may be spirally arranged about its circumference, or one or more grooved regions in the first stem or the second stem may be spirally arranged about its circumference.

[0031] In some embodiments, the first stem or the second stem can have a surface area, and 50% or less of the surface area can be configured to contact bone within the first medullary canal or the second medullary canal.

[0032] The therapeutic agent delivery system may further include an outlet fluidly coupled to the first stem, the second stem, or the coupling member.

[0033] In another aspect of the invention, a method for treating a joint includes positioning a first intramedullary stem in a first medullary canal of a first bone, positioning a second intramedullary stem in a second medullary canal of a second bone, coupling the first intramedullary stem to the second intramedullary stem with a coupling member therebetween, and delivering a therapeutic agent to the first and second medullary canals.

[0034] In some embodiments, the coupling member may include an adjustable height manifold, and the method may further include actuating the adjustable height manifold, thereby adjusting a distance between the first end of the first intramedullary stem and the first end of the second intramedullary stem. Actuating the adjustable height manifold may include rotating a nut coupled to a housing of the adjustable height manifold, and rotating the nut may move an adjustable connector of the adjustable height manifold relative to the housing.

[0035] In some embodiments, the coupling member may include a wedge element having a fixed height, and the method may further include selecting a wedge element from a plurality of wedge elements having different fixed heights. Coupling the first stem to the second stem with the coupling member may include coupling the first intramedullary stem to the second intramedullary stem with the selected wedge element therebetween, thereby adjusting a distance between a first end of the first intramedullary stem and a first end of the second intramedullary stem.

[0036] In some embodiments, positioning the first intramedullary stem in the first medullary canal or the second intramedullary stem in the second medullary canal may include engaging multiple protrusions on the first or second stem with bone covering the respective first or second medullary canal.

[0037] In some embodiments, delivering a therapeutic agent may include delivering an antibiotic, which may include vancomycin, tobramycin, or a combination thereof.

[0038] In some embodiments, delivering the therapeutic agent may include delivering the therapeutic agent from one or more exit holes disposed within the grooved region of the first stem or the second stem.

[0039] In some embodiments, the first bone can be the femur and the second bone can be the fibula.

[0040] In some embodiments, the coupling step can include engaging a flanged region in the adjustable height manifold with a recessed region in the first stem or the first end of the second stem.

[0041] In some embodiments, delivering the therapeutic agent may include pumping the therapeutic agent from the first stem or the second stem into the respective first or second medullary canal.

[0042] The method may further include aspirating undesired fluid from the first or second medullary canal, the undesired fluid passing through one or more holes in the first stem or the second stem.

[0043] In some embodiments, positioning the first stem or the second stem may include positioning the first stem or the second stem within the respective medullary canal such that 50% or less of the surface area of ​​the first stem or the second stem contacts bone within the respective first or second medullary canal.

[0044] In another aspect of the invention, a therapeutic agent delivery system includes a femoral head configured to be positioned within the acetabulum and a femoral stem coupled to the femoral head, the femoral stem configured to be positioned within the femoral medullary canal. The system may further include an inlet coupled to the femoral stem and multiple outlets within the femoral head or femoral stem. A therapeutic agent may be introduced into the system from the inlet, and the therapeutic agent may be deliverable into the acetabulum or femoral canal from the multiple outlets.

[0045] In some embodiments, the femoral stem includes a threaded reduced diameter region that can be configured to be threadably engaged with the femoral head, thereby allowing adjustment of the distance between the femoral head and the femoral stem.

[0046] In some embodiments, the femoral stem may include a plurality of protrusions extending axially along the longitudinal axis of the femoral stem.

[0047] In some embodiments, the femoral stem includes an elongate channel extending therethrough, the channel may be fluidly coupled with an inlet and a plurality of outlets. The elongate channel may be a through hole, and one end of the femoral stem includes a plug.

[0048] In some embodiments, the femoral stem may be tapered.

[0049] In some embodiments, the multiple outlets may be disposed within the femoral head. The femoral head may include a central channel that may be fluidly coupled to the multiple outlets via multiple channels extending radially outward from the central channel.

[0050] The therapeutic agent delivery system may further include an outlet for fluid removal from the femoral head or femoral stem.

[0051] The therapeutic agent delivery system may further include an acetabular cup coupled to the femoral head, the therapeutic agent being delivered from the acetabular cup to the acetabulum.

[0052] In some embodiments, the multiple outlets may comprise multiple holes having varying diameters.

[0053] In some embodiments, the femoral head may be at least partially hollow.

[0054] The therapeutic agent delivery system may further include a locking mechanism for locking the femoral head with the femoral stem.

[0055] In another aspect of the invention, a method for treating a joint includes the steps of positioning a femoral stem in the medullary canal of the femur, coupling a femoral head to the femoral stem, positioning the femoral head in the acetabulum, and delivering a therapeutic agent to the medullary canal and the acetabulum.

[0056] In some embodiments, the coupling step can include adjusting a distance between the femoral head and the femoral stem. In some embodiments, the coupling step can include threadably engaging the femoral head with the femoral stem.

[0057] In some embodiments, positioning the femoral stem may include engaging a plurality of protrusions on the femoral stem with bone overlying the medullary canal.

[0058] In some embodiments, delivering a therapeutic agent may include delivering an antibiotic, which may include vancomycin, tobramycin, or a combination thereof.

[0059] In some embodiments, delivering the therapeutic agent may include delivering the therapeutic agent from one or more exit holes disposed within the grooved region of the femoral stem.

[0060] In some embodiments, delivering the therapeutic agent may include pumping the therapeutic agent from the femoral stem into the medullary canal or from the femoral head into the acetabulum.

[0061] The method may further include the step of aspirating undesirable fluid from the medullary canal or acetabulum.

[0062] In some embodiments, positioning the femoral stem may include positioning the femoral stem within the medullary canal such that 50% or less of the surface area of ​​the femoral stem contacts bone within the medullary canal.

[0063] In another aspect of the invention, a device for delivering a therapeutic agent to a joint in a patient includes an implant having multiple outlets for delivering a therapeutic agent to the joint, the joint being a shoulder joint, an ankle joint, or a spinal joint. The present invention provides, for example, the following: (Item 1) 1. A therapeutic agent delivery system comprising: a first intramedullary stem configured to be positioned within a first medullary canal of a first bone, an elongated body having a longitudinal axis, a first end, a second end opposite the first end, and a channel extending between the first end and the second end; a plurality of protrusions extending radially outward from the elongate body, adjacent protrusions defining one or more grooved regions therebetween; Equipped with a first stem, the plurality of protrusions configured to engage the first medullary canal in a stable manner, one or more exit holes disposed within the one or more grooved regions, the one or more exit holes in fluid communication with the channel; a second intramedullary stem configured to be positioned within a second medullary canal of a second bone, an elongated body having a longitudinal axis, a first end, a second end opposite the first end, and a channel extending between the first end and the second end; a plurality of protrusions extending radially outward from the elongate body, adjacent protrusions defining one or more grooved regions therebetween; Equipped with a second stem, the plurality of protrusions configured to engage the first medullary canal in a stable manner, one or more exit holes disposed within the one or more grooved regions, the one or more exit holes in fluid communication with the channel; a coupling member coupled to a first end of the first intramedullary stem and a first end of the second intramedullary stem, the coupling member holding the first intramedullary stem and the second intramedullary stem together and at a fixed distance, the coupling member further comprising an inlet in fluid communication with a channel in the first and second intramedullary stems; A system comprising: (Item 2) 2. The system of claim 1, wherein the connecting member comprises an adjustable height manifold configured to increase or decrease the distance between the first ends of the two intramedullary stems when the adjustable height manifold is actuated. (Item 3) the adjustable height manifold comprises a housing with a central housing channel disposed therethrough, a rotating nut coupled to the housing, and an adjustable connector disposed within the housing channel, the adjustable connector having an adjustable connector channel disposed therein; The inlet is coupled to the housing, the adjustable connector channel is fluidly coupled to the adjustable connector channel, the adjustable connector channel is fluidly coupled to a channel in the first or second stem, and rotation of the rotating nut extends or retracts the adjustable connector relative to the housing. Item 2. The system according to item 2. (Item 4) 4. The system of claim 3, wherein the rotating nut is threadably engaged with the adjustable connector, the adjustable connector is slidably disposed within the housing channel, and rotation of the rotating nut moves the adjustable connector up or down within the housing channel without rotation of the adjustable connector. (Item 5) 2. The system of claim 1, wherein the coupling member comprises a wedge element, and placement of the wedge element between the first end of the first intramedullary stem and the first end of the second intramedullary stem adjusts the distance between the first ends of the two intramedullary stems. (Item 6) 2. The system of claim 1, further comprising a source of the therapeutic agent for delivery to the medullary canal from one or more exit holes in one or more grooved regions of the first and second stems. (Item 7) 2. The system of claim 1, wherein the therapeutic agent is an antibiotic. (Item 8) 8. The system of claim 7, wherein the antibiotic comprises vancomycin, tobramycin, or a combination thereof. (Item 9) 2. The system of claim 1, wherein the first medullary canal is within a femur and the first stem is configured to be disposed therein, and the second medullary canal is within a tibia and the second stem is configured to be disposed therein. (Item 10) 2. The system of claim 1, wherein the coupling member is releasably coupled to the first and second intramedullary stems. (Item 11) 2. The system of claim 1, wherein the first stem is the same as the second stem. (Item 12) 2. The system of claim 1, wherein the first stem or the second stem comprises four fins equally spaced around the circumference of the elongated body and extending along its longitudinal axis. (Item 13) 2. The system of claim 1, wherein the first stem or the second stem includes a plurality of exit holes extending axially along a line generally parallel to its longitudinal axis. (Item 14) 2. The system of claim 1, wherein the coupling member comprises a flanged region, a first end of the first or second stem comprises a recessed region for receiving the flanged region, and rotation of the flanged region relative to the recessed region releasably locks the first end with the coupling member. (Item 15) Item 15. The system of item 14, wherein one or more pins are disposed within a first end of the first or second stem and protrude therefrom to engage the flanged region and prevent further rotation of the first or second stem relative to the coupling member. (Item 16) 2. The system of claim 1, wherein the coupling member comprises a snap-fit ​​or dovetailed section for engaging a corresponding dovetailed or snap-fit ​​section on the first stem or the second stem. (Item 17) 2. The system of claim 1, wherein the channel extends from a first end to a second end of the first or second stem, the channel extending through both the first end and the second end. (Item 18) Item 18. The system of item 17, further comprising a plug disposed in the channel at a second end of the first stem or the second stem. (Item 19) 2. The system of claim 1, wherein the channel is a dead-end channel in the first stem or the second stem, the dead-end channel having a closed second end. (Item 20) 2. The system of claim 1, wherein the extension body of the first stem or the second stem is tapered. (Item 21) 2. The system of claim 1, wherein the coupling member comprises a housing, a first stem connector configured to engage a first end of the first intramedullary stem, and a second stem connector configured to engage a first end of the second intramedullary stem, the first and second stem connectors being disposed on opposite sides of the housing, the first stem connector having an orientation relative to the second stem connector, and the orientation remaining the same during operation of an adjustable height manifold. (Item 22) Item 10. The system of item 1, wherein the coupling member comprises a housing, a recessed groove disposed circumferentially around at least a portion of the housing, the recessed groove being sized to receive tubing. (Item 23) 2. The system of claim 1, further comprising a cover disposed over the first stem or the second stem or a sponge disposed in at least some of the grooved regions of one or more of the first stem or the second stem, the cover or sponge configured to promote uniform distribution of the therapeutic agent therefrom into the first or second intramedullary canal. (Item 24) 2. The system of claim 1, further comprising a pump configured to pump the therapeutic agent into a channel of the first or second stem. (Item 25) 2. The system of claim 1, further comprising a vacuum pump configured to remove undesirable fluids from the first or second medullary canal via one or more exit holes or channels in the first stem or the second stem. (Item 26) 2. The system of claim 1, wherein a plurality of protrusions in the first stem or the second stem are spirally arranged about its circumference, or one or more grooved regions in the first stem or the second stem are spirally arranged about its circumference. (Item 27) 2. The system of claim 1, wherein the first stem or the second stem has a surface area, and 50% or less of the surface area is configured to contact bone within the first medullary canal or the second medullary canal. (Item 28) 2. The system of claim 1, further comprising an outlet fluidly coupled to the first stem, the second stem, or the coupling member. (Item 29) 1. A method for treating a joint, comprising: Positioning a first intramedullary stem in a first medullary canal of a first bone; positioning a second intramedullary stem in a second medullary canal of a second bone; coupling the first intramedullary stem to the second intramedullary stem with a coupling member therebetween; delivering a therapeutic agent to the first and second medullary canals; A method comprising: (Item 30) 30. The method of claim 29, wherein the coupling member comprises an adjustable height manifold, the method further comprising the step of actuating the adjustable height manifold, thereby adjusting the distance between a first end of the first intramedullary stem and a first end of the second intramedullary stem. (Item 31) Item 31. The method of item 30, wherein actuating the adjustable height manifold includes rotating a nut coupled to a housing of the adjustable height manifold, the rotating nut moving an adjustable connector of the adjustable height manifold relative to the housing. (Item 32) 30. The method of claim 29, wherein the coupling member comprises a wedge element having a fixed height, the method further comprising the step of selecting a wedge element from a plurality of wedge elements having different fixed heights, and the coupling step comprises the step of coupling the first intramedullary stem to the second intramedullary stem with the selected wedge element therebetween, thereby adjusting a distance between a first end of the first intramedullary stem and a first end of the second intramedullary stem. (Item 33) 30. The method of claim 29, wherein positioning a first intramedullary stem in the first medullary canal or positioning a second intramedullary stem in the second medullary canal includes engaging a plurality of protrusions on the first or second stem with bone covering the respective first or second medullary canal. (Item 34) 30. The method of claim 29, wherein the step of delivering a therapeutic agent comprises delivering an antibiotic. (Item 35) 35. The method of claim 34, wherein the antibiotic comprises vancomycin, tobramycin, or a combination thereof. (Item 36) 30. The method of claim 29, wherein delivering the therapeutic agent comprises delivering the therapeutic agent from one or more exit holes disposed within a grooved region of the first stem or the second stem. (Item 37) 30. The method of claim 29, wherein the first bone is the femur and the second bone is the tibia. (Item 38) 30. The method of claim 29, wherein the coupling step includes engaging a flanged region in an adjustable height manifold with a recessed region in the first stem or the first end of the second stem. (Item 39) 30. The method of claim 29, wherein the step of delivering the therapeutic agent comprises pumping the therapeutic agent from the first stem or the second stem into the respective first or second medullary canal. (Item 40) 30. The method of claim 29, further comprising the step of aspirating undesired fluid from the first or second medullary canal, wherein the undesired fluid passes through one or more holes in the first stem or the second stem. (Item 41) 30. The method of claim 29, wherein positioning the first stem or the second stem comprises positioning the first stem or the second stem in the respective first or second medullary canal such that 50% or less of a surface area of ​​the first stem or the second stem contacts bone in the respective first or second medullary canal. (Item 42) 1. A therapeutic agent delivery system comprising: a femoral head configured to be positioned within the acetabulum; a femoral stem coupled to the femoral head, the femoral stem configured to be positioned within the femoral medullary canal; an inlet coupled to the femoral stem; a plurality of outlets in the femoral head or the femoral stem; Equipped with the therapeutic agent is introduced into the system through the inlet; The system, wherein the therapeutic agent is deliverable from the multiple outlets into the acetabulum or the femoral medullary canal. (Item 43) Item 43. The system of item 42, wherein the femoral stem includes a threaded reduced diameter region configured to be threadably engaged with the femoral head, thereby allowing adjustment of the distance between the femoral head and the femoral stem. (Item 44) Item 43. The system of item 42, wherein the femoral stem includes a plurality of protrusions extending axially along a longitudinal axis of the femoral stem. (Item 45) Item 43. The system of item 42, wherein the femoral stem includes an elongated channel extending therethrough, the channel fluidly coupled with the inlet and the plurality of outlets. (Item 46) Item 46. The system of item 45, wherein the elongated channel is a through hole and one end of the femoral stem is provided with a plug. (Item 47) Item 43. The system of item 42, wherein the femoral stem is tapered. (Item 48) Item 43. The system of item 42, wherein the plurality of outlets are disposed within the femoral head, the femoral head comprising a central channel, the central channel fluidly coupled to the plurality of outlets via a plurality of channels extending radially outward from the central channel. (Item 49) Item 43. The system of item 42, further comprising an outlet for fluid removal from the femoral head or the femoral stem. (Item 50) Item 43. The system of item 42, further comprising an acetabular cup coupled to the femoral head, the therapeutic agent being delivered to the acetabulum from the acetabular cup. (Item 51) Item 43. The system of item 42, wherein the plurality of outlets comprises a plurality of holes having varying diameters. (Item 52) Item 43. The system of item 42, wherein the femoral head is at least partially hollow. (Item 53) Item 43. The system of item 42, further comprising a locking mechanism for locking the femoral head with the femoral stem. (Item 54) 1. A method for treating a joint, comprising: Positioning a femoral stem within the medullary canal of the femur; coupling a femoral head to the femoral stem; positioning the femoral head within the acetabulum; delivering a therapeutic agent to the medullary canal and to the acetabulum; A method comprising: (Item 55) 55. The method of claim 54, wherein the coupling step includes adjusting the distance between the femoral heads. (Item 56) Item 55. The method of item 54, wherein the coupling step includes threadingly engaging the femoral head with the femoral stem. (Item 57) 55. The method of claim 54, wherein positioning the femoral stem includes engaging a plurality of protrusions on the femoral stem with bone covering the medullary canal. (Item 58) 55. The method of claim 54, wherein the step of delivering a therapeutic agent comprises delivering an antibiotic. (Item 59) 59. The method of claim 58, wherein the antibiotic comprises vancomycin, tobramycin, or a combination thereof. (Item 60) 55. The method of claim 54, wherein delivering the therapeutic agent comprises delivering the therapeutic agent from one or more exit holes disposed within a grooved region of the femoral stem. (Item 61) 55. The method of claim 54, wherein the step of delivering the therapeutic agent comprises pumping the therapeutic agent from the femoral stem into the medullary canal or from the femoral head into the acetabulum. (Item 62) 55. The method of claim 54, further comprising the step of aspirating undesirable fluids from the medullary canal or the acetabulum. (Item 63) 55. The method of claim 54, wherein positioning the femoral stem comprises positioning the femoral stem in the medullary canal such that 50% or less of a surface area of ​​the femoral stem contacts bone in the medullary canal. (Item 64) 1. A device for delivering a therapeutic agent to a joint in a patient, comprising an implant having a plurality of outlets for delivering said therapeutic agent to said joint, said joint being a shoulder joint, an ankle joint, or a spinal joint.

[0064] These and other embodiments are described in further detail in the following description taken in conjunction with the accompanying drawings. Incorporation by Reference

[0065] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. [Brief description of the drawings]

[0066] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings.

[0067] [Figure 1A] FIG. 1A is a perspective view of an exemplary therapeutic agent delivery system for the knee.

[0068] [Figure 1B] FIG. 1B is an exploded view of the therapeutic agent delivery system of FIG. 1A.

[0069] [Figure 2A] FIG. 2A is a perspective view of an exemplary intramedullary stem.

[0070] [Figure 2B] 2B and 2C are side views of an exemplary intramedullary stem. [Figure 2C] 2B and 2C are side views of an exemplary intramedullary stem.

[0071] [Figure 3A] 3A and 3B show an alternative embodiment of an extension body of an intramedullary stem. [Figure 3B] 3A and 3B show an alternative embodiment of an extension body of an intramedullary stem.

[0072] [Figure 4A] FIG. 4A illustrates an exemplary embodiment of an adjustable height manifold in a collapsed configuration.

[0073] [Figure 4B] FIG. 4B shows the adjustable height manifold of FIG. 4A in an extended configuration.

[0074] [Diagram 5] FIG. 5 is an exploded view of the adjustable height manifold of FIG. 4A.

[0075] [Figure 6A] FIG. 6A is a perspective view of an exemplary embodiment of a housing of the adjustable height manifold of FIG. 4A.

[0076] [Figure 6B] FIG. 6B is a side view of the housing of FIG. 6A.

[0077] [Figure 6C] FIG. 6C is a top view of the housing of FIG. 6A.

[0078] [Figure 6D] FIG. 6D is a bottom view of the housing of FIG. 6A.

[0079] [Figure 6E] FIG. 6E is a vertical cross-sectional view of the housing of FIG. 6A.

[0080] [Figure 7A] FIG. 7A is a perspective view of an exemplary embodiment of a rotating nut of the adjustable height manifold of FIGS. 4A-4B.

[0081] [Figure 7B] FIG. 7B is a top view of the rotating nut of FIG. 7A.

[0082] [Figure 7C] FIG. 7C is a vertical cross-sectional view of the rotating nut of FIG. 7A.

[0083] [Figure 8A] FIG. 8A is a perspective view of an exemplary embodiment of an adjustable connector of the adjustable height manifold of FIGS. 4A-4B.

[0084] [Figure 8B] FIG. 8B is a bottom view of the adjustable connector of FIG. 8A.

[0085] [Figure 8C] 8C and 8D are side views of the adjustable connector of FIG. 8A. [Figure 8D] 8C and 8D are side views of the adjustable connector of FIG. 8A.

[0086] [Figure 9] FIG. 9 illustrates an exemplary embodiment of a manifold pin of the adjustable height manifold of FIGS. 4A-4B.

[0087] [Figure 10A] FIG. 10A is a top view of the assembled adjustable height manifold in the collapsed configuration as shown in FIG. 4A.

[0088] [Figure 10B] FIG. 10B is a side cross-sectional view of the assembled adjustable height manifold of FIG. 10A.

[0089] [Figure 11A] FIG. 11A is a perspective view of an exemplary embodiment of a fixed height wedge.

[0090] [Figure 11B] 11B and 11C are side views of the fixed height wedge of FIG. 11A. [Figure 11C] 11B and 11C are side views of the fixed height wedge of FIG. 11A.

[0091] [Figure 12-1] 12A-12H illustrate an exemplary mechanism for coupling the intramedullary stem to the coupling member. [Figure 12-2] 12A-12H illustrate an exemplary mechanism for coupling the intramedullary stem to the coupling member. [Figure 12-3] 12A-12H illustrate an exemplary mechanism for coupling the intramedullary stem to the coupling member. [Figure 12-4] 12A-12H illustrate an exemplary mechanism for coupling the intramedullary stem to the coupling member. [Figure 12-5] 12A-12H illustrate an exemplary mechanism for coupling the intramedullary stem to the coupling member. [Figure 12-6] 12A-12H illustrate an exemplary mechanism for coupling the intramedullary stem to the coupling member.

[0092] [Figure 13A] 13A-13C illustrate another exemplary mechanism for coupling the intramedullary stem to the coupling member. [Figure 13B] 13A-13C illustrate another exemplary mechanism for coupling the intramedullary stem to the coupling member. [Figure 13C] 13A-13C illustrate another exemplary mechanism for coupling the intramedullary stem to the coupling member.

[0093] [Figure 14A] 14A-14D illustrate another exemplary mechanism for coupling an intramedullary stem to a coupling member. [Figure 14B] 14A-14D illustrate another exemplary mechanism for coupling an intramedullary stem to a coupling member. [Figure 14C] 14A-14D illustrate another exemplary mechanism for coupling an intramedullary stem to a coupling member. [Figure 14D] 14A-14D illustrate another exemplary mechanism for coupling an intramedullary stem to a coupling member.

[0094] [Figure 15] FIG. 15 illustrates a method of treating a knee with a therapeutic agent delivery system.

[0095] [Figure 16] FIG. 16 illustrates a method of treating a knee with a therapeutic agent delivery system.

[0096] [Figure 17A] FIG. 17A is a perspective view of an exemplary therapeutic agent delivery system for a hip joint.

[0097] [Figure 17B] FIG. 17B is an exploded view of the therapeutic agent delivery system of FIG. 17A.

[0098] [Figure 18A] FIG. 18A is a perspective view of an exemplary embodiment of a femoral stem.

[0099] [Figure 18B] FIG. 18B is a side view of the femoral stem of FIG. 18A.

[0100] [Figure 18C] FIG. 18C is a side cross-sectional view of the femoral stem of FIG. 18A.

[0101] [Figure 18D] FIG. 18D is a bottom view of the femoral stem of FIG. 18A.

[0102] [Figure 19] FIG. 19 illustrates an exemplary embodiment of a stem plug.

[0103] [Figure 20A] FIG. 20A is a side view of an exemplary embodiment of a femoral head.

[0104] [Figure 20B] FIG. 20B is a side cross-sectional view of the femoral head of FIG. 20A.

[0105] [Figure 21A] 21A and 21B are side cross-sectional views of another exemplary embodiment of a femoral head. [Figure 21B] 21A and 21B are side cross-sectional views of another exemplary embodiment of a femoral head.

[0106] [Figure 22] FIG. 22 is a side view of another exemplary embodiment of the femoral head.

[0107] [Figure 23A] 23A and 23B show an exemplary mechanism for connecting the femoral head to the femoral stem. [Figure 23B] 23A and 23B show an exemplary mechanism for connecting the femoral head to the femoral stem.

[0108] [Figure 24A] 24A and 24B show an exemplary mechanism for locking a set distance between the femoral head and the femoral stem. [Figure 24B] 24A and 24B show an exemplary mechanism for locking a set distance between the femoral head and the femoral stem.

[0109] [Figure 24C] 24C-24F illustrate a method of assembling the locking mechanism of FIGS. 24A and 24B. [Figure 24D] 24C-24F illustrate a method of assembling the locking mechanism of FIGS. 24A and 24B. [Figure 24E] 24C-24F illustrate a method of assembling the locking mechanism of FIGS. 24A and 24B. [Figure 24F] 24C-24F illustrate a method of assembling the locking mechanism of FIGS. 24A and 24B.

[0110] [Figure 25A] 25A and 25B show an exemplary embodiment of a therapeutic agent delivery system having an acetabular cup. [Figure 25B] 25A and 25B show an exemplary embodiment of a therapeutic agent delivery system having an acetabular cup.

[0111] [Figure 26] FIG. 26 illustrates an exemplary embodiment of a therapeutic agent delivery system for the hip joint.

[0112] [Figure 27] FIG. 27 illustrates a method of treating a hip joint using a therapeutic agent delivery system.

[0113] [Figure 28A] 28A and 28B illustrate the use of negative pressure wound therapy with an intramedullary device. [Figure 28B] 28A and 28B illustrate the use of negative pressure wound therapy with an intramedullary device.

[0114] [Figure 29] FIG. 29 shows an optional cover for the intramedullary stem.

[0115] [Diagram 30] FIG. 30 illustrates an exemplary embodiment of a therapeutic agent delivery system.

[0116] [Figure 31A] 31A and 31B show an exemplary embodiment of a therapeutic agent delivery system with an inlet and an outlet. [Figure 31B] 31A and 31B show an exemplary embodiment of a therapeutic agent delivery system with an inlet and an outlet.

[0117] [Figure 32A] 32A and 32B illustrate an exemplary configuration for the interior channel of an intramedullary device. [Figure 32B] 32A and 32B illustrate an exemplary configuration for the interior channel of an intramedullary device.

[0118] [Figure 33A] 33A-33C illustrate another exemplary configuration for the interior channel of an intramedullary device. [Figure 33B] 33A-33C illustrate another exemplary configuration for the interior channel of an intramedullary device. [Figure 33C]33A-33C illustrate another exemplary configuration for the interior channel of an intramedullary device.

[0119] [Diagram 34] 34-36 show an exemplary embodiment of a therapeutic agent delivery system. [Diagram 35] 34-36 show an exemplary embodiment of a therapeutic agent delivery system. [Diagram 36] 34-36 show an exemplary embodiment of a therapeutic agent delivery system. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0120] Specific embodiments of the disclosed devices, delivery systems, and methods will now be described with reference to the drawings. The Detailed Description is not intended to imply that any particular component, feature, or step is essential to the invention.

[0121] Described herein is a therapeutic agent delivery system that can be used in the knee joint, hip joint, or any other joint. For example, the therapeutic agent delivery system can be used to treat the shoulder or ankle joint, or a portion of the spine. Those skilled in the art will understand that other joints can also be treated with the systems, devices, and methods disclosed herein. Optionally, in any embodiment, the therapeutic agent delivery system can include one or more intramedullary stems configured to be stably positioned within the medullary canal of a bone. The intramedullary stem can be configured to deliver therapeutic agents to the medullary canal, joint space, or a combination thereof. Optionally, in any embodiment, the intramedullary stem is coupled to another component, such as another intramedullary stem or femoral head, to allow the distance between the stem and the other component to be adjusted to fit the patient, or the distance between them can be fixed.

[0122] The therapeutic agent delivered by the delivery system described herein may consist of any fluid. For example, the therapeutic agent may consist of an antibiotic fluid, such as vancomycin, or tobramycin, combinations thereof, or other antibiotics commonly used to treat implant-associated infections. Those skilled in the art will appreciate that any therapeutic agent may also be delivered alone or in combination with an antibiotic or other therapeutic agent. Other exemplary therapeutic agents may include saline or other fluids used to irrigate the joint or medullary canal being treated.

[0123] Therapeutic delivery system for the knee - Patents.com 1A and 1B show an exemplary therapeutic agent delivery system 100 for a knee. FIG. 1A shows the components of the delivery system assembled together, while FIG. 1B shows the components of the delivery system disassembled and aligned for assembly. The delivery system 100 comprises a first intramedullary stem 110, a second intramedullary stem 120, and a coupling member 130. The two intramedullary stems 110 and 120 can each be configured to be placed within the medullary canal of a bone. For example, the first intramedullary stem 110 can be configured to be placed within the medullary canal of a patient's femur, while the second intramedullary stem 120 can be configured to be placed within the medullary canal of a patient's fibula. The coupling member 130, configured to be placed within the joint space, can couple the two stems in a stable configuration while maintaining a desired distance 105 between the two stems throughout the length of use of the therapeutic agent delivery system within the patient.

[0124] The first intramedullary stem 110 and the second intramedullary stem 120 may be any intramedullary stem as described herein. The two stems may be two identical stems, or they may be two different stems configured to have one or more differences in dimensions, configurations, or features. For example, the delivery system may include a first intramedullary stem specifically configured to engage the femur and a second intramedullary stem specifically configured to engage the fibula. The two stems may differ in one or more dimensions, such as length, diameter, or taper. Alternatively, or in combination, the two stems may differ in one or more configurations or features as described herein (e.g., stem channel configuration, protrusions, grooved areas, and / or number, shape, and size of exit holes, etc.).

[0125] The coupling member 130 may comprise any coupling member as described herein, such as an adjustable height manifold or a fixed height wedge. In many embodiments of the delivery system 100, the coupling member 130 can be configured to allow the distance 105 between the two stems to be adjusted to accommodate the patient's anatomy. The coupling member can be configured to fluidly couple to a source of therapeutic agent, receive the therapeutic agent, and distribute the therapeutic agent to the intramedullary stem for delivery to the medullary canal.

[0126] The first stem 110 and the second stem 120 may be releasably coupled to the coupling member 130. The first stem and the second stem may each be configured to couple to a stem connector 132 of the coupling member. The first stem may couple to the first stem connector 132a and the second stem may couple to the second stem connector 132b. Various mechanisms for connection between the stems and the coupling member are described herein, any of which may be incorporated into the coupling member 130 for coupling with the first or second stem. The first and second stems may couple to the first and second stem connectors, respectively, via the same mechanism or via different mechanisms. Thus, the first and second stem connectors 132a and 132b of the coupling member may be the same or different. In a preferred embodiment, the first stem and the second stem are the same, and therefore the coupling member optionally comprises two identical stem connectors configured to couple to the first stem and the second stem via the same mechanism.

[0127] Intramedullary stem 2A-2C show an exemplary intramedullary stem 200 suitable for incorporation with a therapeutic agent delivery system for a knee. FIG. 2A is a perspective view of the intramedullary stem 200, and FIGS. 2B and 2C are side views thereof. Each intramedullary stem 200 includes an elongated body 205 having a longitudinal axis 210, the elongated body having a first end 215 and a second end 220 opposite the first end. The first or proximal end may be configured to couple to a coupling member 130, such as an adjustable height manifold or a fixed height wedge as described herein. The second or distal end may be disposed within the medullary canal of the bone. The elongated body 205 includes a stem channel 225 extending between the first end 215 and the second end 220, the stem channel configured to deliver a therapeutic agent through the stem and into the medullary canal. The first end 215 of the intramedullary stem 200 may be configured to couple the stem to a coupling member. The first end may include any mechanism for connecting the stem to a coupling member (e.g., a flanged region, a dovetail joint, a snap buckle, a wing nut, etc.), as described in further detail herein.

[0128] The intramedullary stem 200 may include a plurality of protrusions 230 that protrude radially outward from the extension body 205. The plurality of protrusions may include any number of protrusions having any suitable shape, size, or configuration for engaging the medullary canal in a stable manner. For example, the protrusions may include extension fins that extend along the longitudinal length of the extension body, as shown in FIGS. 2A-2C. In one exemplary embodiment, the plurality of protrusions may include four fins equally spaced about 90° apart about the longitudinal axis 210 of the extension body. The plurality of protrusions 230 and the extension body 205 may be formed separately and joined together. Alternatively, or in combination, the plurality of protrusions 230 may be formed by removing material from the extension body 205 such that the plurality of protrusions and the extension body are formed as a single member. Adjacent protrusions 230 define one or more grooved regions 235 therebetween, which may be radially recessed relative to the protrusions. The grooved regions may form concave recessed regions between adjacent protrusions.

[0129] The protrusions and grooved regions can be configured to minimize the surface area of ​​the stem that contacts the bone overlying the medullary canal, and thus the area of ​​bone rich in therapeutic agent can be maximized. For example, the protrusions and grooved regions can be configured such that less than 50% of the surface area of ​​the stem contacts the bone overlying the medullary canal. Of course, this is not intended to be limiting, and one skilled in the art will understand that any percentage of the surface area of ​​the stem can contact the bone. The stem can include a plurality of identical grooved regions defined by a plurality of elongated fins that are symmetrically distributed about the longitudinal axis 210 of the stem, as shown in Figures 2A-2C. Alternatively, the grooved regions can be asymmetrically distributed about the longitudinal axis of the stem, and / or have different shapes or sizes, as described in more detail herein.

[0130] The intramedullary stem 200 may further comprise a plurality of exit holes 240 in fluid communication with the stem channel 225. The plurality of exit holes 240 may be configured to deliver the therapeutic agent dispensed through the stem channel 225 to the medullary canal as well as adjacent tissues, including the joint. The plurality of exit holes may be disposed within the grooved region 235 to deliver the therapeutic agent to areas of the bone that are not in contact with the intramedullary stem. The plurality of exit holes may comprise any number of exit holes having any suitable size, shape, or distribution. For example, the plurality of exit holes may include a plurality of equally sized and spaced holes extending axially along a line generally parallel to the longitudinal axis 210 of the stem, as shown in FIGS. 2A-2C. The plurality of exit holes may be arranged in various configurations, as described in further detail herein. The plurality of exit holes may comprise holes having the same shape and / or size or holes having various shapes and / or sizes. Varying hole sizes may allow for further fluid control of the therapeutic agent as it exits different regions of the stem.

[0131] The stem channel 225 may be a through hole extending through both the first end and the second end from the first end 215 to the second end 220, such that the elongated body includes an open second or distal end. The system may further include a plug (not shown) configured to couple to the open second end of the stem to close the second end, thereby creating a dead-end channel. Alternatively, the stem channel 225 may be a dead-end channel, and the second end of the elongated body is closed. In a configuration in which the second end is open, the therapeutic agent may exit the stem channel through the second end and / or through multiple exit holes disposed along the elongated body 205 as described herein into the medullary canal. If the stem includes only the stem channel 225 extending through the first and second ends without multiple exit holes, the therapeutic agent may exit the stem channel only through the second end. In a configuration in which the second end of the stem is closed, the therapeutic agent may exit the stem channel into the medullary canal only through the multiple exit holes.

[0132] The intramedullary stem 200 may be tapered to fit into the medullary canal. For example, the elongated body 205 and / or the plurality of projections 230 may be tapered from the first end 215 to the second end 220, as shown, to have a smaller radial cross-sectional area at the second end than at the first end. For example, the taper may comprise a gradual taper, and the degree of taper may preferably be within the range of about 0.1° to about 10°, more preferably about 0.5° to about 5°, even more preferably about 1° to about 5°, or about 1° to about 4°, or about 2°, or about 3°. The taper may be adjusted to accommodate the medullary canal of a particular type of bone.

[0133] The exemplary embodiment of Figures 2A-2C may include one or both of the two intramedullary stems of a therapeutic agent delivery system for a knee such as that shown in Figures 1A and 1 B. Preferably, a therapeutic agent delivery system for a knee includes two identical intramedullary stems such as the exemplary embodiment of Figures 2A-2C.

[0134] 3A and 3B show alternative embodiments of the extension body 205 of the intramedullary stem 200 of FIGS. 2A-2C. FIG. 3A shows the extension body 205 with one or more protrusions 231 spirally arranged around the extension body 205 along the longitudinal length of the body. Adjacent spiral or helical protrusions 231 also define one or more grooved regions 236 therebetween that are spirally arranged around the extension body. FIG. 3B shows the extension body 205 with multiple protrusions 232 resulting from cutting or otherwise removing a portion of the spirally arranged protrusion 231 shown in FIG. 3A. For example, as shown, multiple radial cuts can be made in the extension body to define multiple protrusions 232. Multiple grooved regions 237 can be defined between the remaining portions of adjacent helical protrusions. Cutting or removing a portion of the spiral protrusion 231 as shown in FIG. 3B can further reduce the contact area between the stem and the bone, thus allowing the therapeutic agent to flow more freely along the medullary canal.

[0135] In the embodiment of Figure 3A, multiple exit holes (not shown) may extend along a spiral or helical line, such as along a spiral or helical grooved region 236. In the embodiment shown in Figure 3B, multiple exit holes 240 may be disposed within grooved region 237 such that the holes extend about multiple rings around the circumference of the elongated body.

[0136] Adjustable Height Manifold 4A-4B show an adjustable height manifold 300 suitable for incorporation with a therapeutic agent delivery system for a knee such as in FIGS. 1A-1B. The adjustable height manifold 300 is one example of a coupling member that can couple two intramedullary stems in a stable configuration while maintaining a desired distance between the two stems throughout the length of use of the therapeutic agent delivery system within the patient. The adjustable height manifold further allows for adjustment of the distance between the two stems so the delivery system can be configured to optimally accommodate the patient's anatomy. The adjustable height manifold 300 can include a housing 315, a rotating nut 320, and an adjustable connector 325. The rotating nut 320 and the adjustable connector 325 can be coupled to the housing 315 and configured to allow the manifold height 305 to be increased or decreased based on a desired set distance between the two stems for the patient. Rotating the nut 320 in a clockwise and counterclockwise direction can collapse or extend the manifold by translating the adjustable connector along the manifold's longitudinal axis 310. Figure 4A shows the adjustable height manifold 300 in a collapsed configuration such that the manifold height 305 is relatively short so that the manifold can therefore accommodate patients who require a shorter set distance between the two knee stems. Figure 4B shows the adjustable height manifold 300 in an extended configuration such that the manifold height 305 is relatively long so that the manifold can therefore accommodate patients who require a longer set distance between the two knee stems.

[0137] The adjustable height manifold 300 further includes a first stem connector 342 and a second stem connector 344 disposed on opposite sides of the housing. The first stem connector 342 may be configured to couple to a first end of a first intramedullary stem, and the second stem connector 344 may be configured to couple to a first end of a second intramedullary stem. The first stem connector 342 may be coupled to the adjustable connector 325, while the second stem connector 344 may be coupled to the housing 315. Each stem connector may include a connection mechanism for coupling to a corresponding connection mechanism disposed on the first end of the intramedullary stem. The first and second stem connectors may include different connection mechanisms, or they may include the same connection mechanism. In a preferred embodiment, the first and second stem connectors include the same connection mechanism and have a fixed orientation relative to one another, such that the orientation remains the same during actuation of the adjustable height manifold to adjust the manifold height. The fixed orientation of the two stem connectors relative to each other can enable proper and simultaneous coupling of the manifold to each stem during implantation of the delivery system into the patient using the same actuation motion for both stems.

[0138] FIG. 5 is an exploded view of the adjustable height manifold 300 of FIGS. 4A-4B. The adjustable height manifold 300 comprises a housing 315, a rotating nut 320 having a scalloped exterior surface and internal threads to provide a gripping area for an operator's fingers, and an adjustable connector 325, the three components being axially aligned along the longitudinal axis 310 of the manifold. The manifold further comprises a manifold pin 330 configured to ensure coupling of the adjustable connector to the housing and control the range of motion of the adjustable connector. The adjustable connector comprises a first stem connector 342 configured to couple to a first intramedullary stem. The housing comprises a second stem connector 344 configured to couple to a second intramedullary stem. The housing further comprises an inlet 335 coupled thereto, the inlet configured to fluidly couple to a source of therapeutic agent (not shown) to be delivered to the patient. The housing is configured to couple to the rotating nut and to slidably receive the adjustable connector. The rotating nut is configured to threadably engage the adjustable connector such that, when the nut is rotated, it causes the adjustable connector to extend outwardly from the housing along the longitudinal axis 310 or retract inwardly into the housing along the longitudinal axis.

[0139] 6A-6E show an exemplary embodiment of the housing 315 of the adjustable height manifold 300 of FIGS. 4A-4B. FIG. 6A is a perspective view of the housing 315, FIG. 6B is a side view thereof, FIG. 6C is a top view thereof, FIG. 6D is a bottom view thereof, and FIG. 6E is a vertical cross-sectional view thereof (section AA in FIG. 6B). The housing 315 comprises an inlet 335 for fluidly coupling to a source of therapeutic agent and a housing channel 340 (best seen in FIG. 6E) that extends through the housing along the longitudinal axis 310. The housing channel 340 is in fluid communication with the inlet 335, so that therapeutic agent added to the therapeutic agent delivery system through the inlet can be distributed through the housing channel to other components of the delivery system. The inlet 335 may comprise a barbed outer surface to securely engage the inner surface of a tube (best seen in FIG. 28A) that supplies the therapeutic agent. The housing may further include a recessed groove 345 disposed at least partially or completely about the circumference of the housing, thereby minimizing the profile of the tubing / housing assembly. The groove may be coupled to the inlet 335 and allow for placement of tubing to deliver a therapeutic agent.

[0140] The housing 315 further comprises a second stem connector 344 configured to couple to an intramedullary stem, such as any of the intramedullary stems described herein. The housing channel 340 can extend through the stem connector 344 such that the housing channel can be fluidly coupled to a stem channel of a stem coupled to the stem connector. The stem connector 344 can comprise any mechanism for connecting a coupling member to a stem (e.g., a flanged region, a dovetail joint, a snap buckle, a wing nut, etc.), as described in further detail herein.

[0141] The housing channel 340 can be configured to have a geometry that allows an adjustable connector disposed within the channel to slide axially along the longitudinal axis 310 while preventing the adjustable connector from rotating within the channel. For example, the channel 340 can include two flat inner surfaces 347 disposed opposite one another and configured to interface with two flat sides of the adjustable connector. The channel can further include two rounded inner surfaces 349 configured to interface with two corresponding rounded surfaces of the adjustable connector. For example, the rounded inner surfaces 347 can include concave surfaces while the rounded sides of the adjustable connector can include convex surfaces. The interface of the flat inner surfaces of the housing channel with the flat sides of the adjustable connector can prevent the adjustable connector from rotating therein, ensuring that the adjustable connector does not rotate but only slidably moves within the housing channel. Preventing rotation of the adjustable connector, which includes the first stem connector 342, can ensure that the orientation of the second stem connector 344 remains fixed relative to the orientation of the first stem connector, even when the rotating nut 320 is being rotated. The fixed orientation of the first and second stem connectors relative to each other can ensure that the manifold can easily couple to both the first and second stems. For example, the manifold can be inserted into the space between the first and second stems and then rotated in one direction to couple to both stems. Such a configuration of the stem connectors can facilitate implantation of the delivery system into a patient by eliminating the potential need to rotate one or more intramedullary stems after the stems have already been inserted into the patient's medullary cavity.

[0142] The housing may further include one or more protrusions 355 disposed about the periphery of the housing channel 340 and projecting longitudinally from the housing. The protrusions may include four protrusions as shown in FIGS. 6A-6E, with each inner surface of the protrusion configured to engage with each of the four sides of the adjustable connector to be disposed within the housing channel. Two of the protrusions disposed opposite one another may be configured to have a flat inner surface 347 of the housing channel, while the remaining two of the protrusions disposed opposite one another may be configured to have a rounded inner surface 349 of the housing channel. One or more of the protrusions may further include an outwardly facing edge 357 disposed at an edge of the protrusion. The edge 357 may be configured to engage a corresponding manifold groove in the rotating nut as described in further detail herein to securely couple the rotating nut to the housing and prevent axial movement of the rotating nut along the longitudinal axis 310 during rotation of the nut. The edge 357 may further include a chamfer 359 configured to facilitate coupling of the rotating nut to the housing by guiding the edge into the manifold groove of the nut.

[0143] The housing may further include a housing pin hole 360 ​​configured to receive a portion of the manifold pin. The pin hole 360 ​​may be disposed on a protrusion 355 configured to engage the rotating nut, such that the pin hole 360 ​​may also be aligned with a nut pin hole in the rotating nut configured to receive the manifold pin. When fully assembled, the manifold pin may be partially disposed within the housing and partially disposed within a slot in an adjustable connector disposed within the housing channel, as described further herein, to create a hard stop to prevent the manifold assembly from being disassembled. The housing pin hole 360 ​​may be dimensioned to ensure retention of the manifold pin within the pin hole. For example, the housing pin hole may have a diameter substantially equal to a diameter of a portion of the manifold pin configured to be disposed within the housing, such that the pin may be press fit into the housing pin hole.

[0144] 7A-7C show an exemplary embodiment of the rotating nut 320 of the adjustable height manifold 300 of FIGS. 4A-4B. FIG. 7A is a perspective view of the rotating nut 320, FIG. 7B is a top view thereof, and FIG. 7C is a vertical cross-sectional view thereof (section AA in FIG. 7B). The rotating nut 320 includes a plurality of threads 362 disposed on a portion of its inner surface. The threads 362 may be configured to engage corresponding threads on a portion of the adjustable connector such that rotation of the nut 320 about the adjustable connector can cause axial movement of the adjustable connector along the longitudinal axis of the manifold. The nut 320 may further include a manifold groove 364 disposed circumferentially about the inner surface of the nut. The manifold groove may be configured to receive one or more edges disposed on one or more protrusions of the housing as described herein to lock the nut onto the housing while still allowing rotation of the nut relative to the housing. The nut may further include a chamfer 366 disposed below the manifold groove and extending circumferentially about the inner surface of the nut. The chamfer 366 may be configured to correspond to the chamfer of the housing edge to guide the edge into the manifold groove. The nut may further include a nut pin hole 368 disposed on a portion of the nut below the threads 362, the nut pin hole being configured to receive a manifold pin therethrough. During assembly of the manifold, the manifold pin may be pushed completely into and through the body of the rotating nut, disposing the pin partially within the housing and partially within the adjustable connector, thereby avoiding physical obstruction of the rotation of the nut by the pin. Thus, when the manifold is fully assembled, the manifold pin does not traverse any portion of the rotating nut, and therefore the rotating nut may rotate freely. The nut pin hole 368 may be sized to facilitate insertion of the manifold pin into and through the pin hole. For example, the nut pin hole can have a diameter greater than the diameter of the largest portion of the manifold pin so that the pin can easily pass through the nut pin hole.

[0145] 8A-8D show an exemplary embodiment of the adjustable connector 325 of the adjustable height manifold 300 of FIGS. 4A-4B. FIG. 8A is a perspective view, FIG. 8B is a bottom view, and FIGS. 8C and 8D are side views. The adjustable connector 325 comprises an adjustable connector channel 370 extending axially along the longitudinal axis 310. The channel 370 extends through the length of the adjustable connector and is configured to be in fluid communication with the housing channel 340 and thus with the inlet 335 that is fluidly coupled to the housing channel. The adjustable connector further comprises a first stem connector 342 that is configured to couple to an intramedullary stem, such as any of the intramedullary stems described herein. The connector channel 370 extends axially through the stem connector 342 such that the channel 370 is in fluid communication with the stem channel of the stem that is coupled to the first stem connector 342. The stem connector 342 may include any mechanism for connecting a coupling member to a stem (eg, a flanged region, a dovetail joint, a snap buckle, a wing nut, etc.), as described in further detail herein.

[0146] The adjustable connector may further include threads 372 configured to engage corresponding threads on the rotating nut, such that rotation of the nut can cause vertical movement of the adjustable connector into or out of the housing. The adjustable connector may include two flat sides 327 and two rounded sides 329, where the flat sides may be configured to interface with a flat inner surface of the housing channel and the rounded sides may be configured to interface with a rounded inner surface of the housing channel. As described herein, such a configuration can prevent the adjustable connector from rotating when the rotating nut is rotated, ensuring that the orientation of the adjustable connector, and thus the first stem connector 342, remains constant relative to the orientation of the second stem connector. This further translates the rotational actuation of the nut into linear motion of the adjustable connector.

[0147] 8C shows the proximal flat side 327a of the adjustable connector configured to be oriented proximally relative to the inlet of the housing. The proximal flat side can be configured to have an open slot 374 extending through the bottom of the adjustable connector. The open slot 374 can be fluidly coupled to the adjustable connector channel 370, as best seen in FIG. 8B, which shows a bottom view of the adjustable connector. The open slot 374 can be configured to be aligned with the inlet such that when the assembled manifold is in a collapsed configuration, as shown in FIG. 4A, the open slot fluidly couples the inlet to the adjustable connector channel 370. When the assembled manifold is in an extended position, as shown in FIG. 4B, the open bottom of the open slot 374 can ensure that the inlet remains in fluid communication with the housing channel, and thereby the adjustable connector channel.

[0148] FIG. 8D shows the distal flat side 327b of the adjustable connector configured to be oriented distally relative to the inlet of the housing. The distal flat side includes a closed slot 376 configured to engage a portion of the manifold pin retained in the housing. As described herein, the manifold pin may be coupled to the manifold assembly after the housing, the rotating nut, and the adjustable connector are assembled together. After full assembly, the manifold pin may be partially disposed in the housing and partially disposed in the closed slot 376 of the adjustable connector. The manifold pin may be configured to remain engaged in the closed slot 376 during retraction or extension of the adjustable connector. The closed slot may be configured to have a width that exceeds the diameter of the portion of the manifold pin disposed in the slot to facilitate movement of the adjustable connector. When the assembled manifold is in the collapsed configuration as shown in FIG. 4A, the manifold pin may be aligned with an upper portion of the closed slot 376. When the assembled manifold is in the extended configuration as shown in FIG. 4B, the manifold pins may be aligned with the bottom of the closure slots 376. The bottom of the closure slots 376 provides a hard stop to the extension of the adjustable connector from the housing, preventing the adjustable connector from extending any further. Thus, the closure slots 376 and the manifold pins may prevent the manifold assembly from disassembly.

[0149] FIG. 9 illustrates an exemplary embodiment of a manifold pin 330 of the adjustable height manifold 300 of FIGS. 4A-4B. The manifold pin 330 may include a small diameter portion 332 and a large diameter portion 334. The small diameter portion 332 may be configured to engage a closed slot in the adjustable connector, while the large diameter portion 334 may be configured to be disposed within a manifold pin hole in the housing. As described herein, the manifold pin may be coupled to the manifold assembly by inserting the pin through a nut pin hole in the rotating nut. To facilitate insertion of the manifold pin through the rotating nut, the large diameter portion 334 may have a diameter smaller than the diameter of the nut pin hole. To ensure retention of the manifold pin within the housing, the large diameter portion 334 may have a diameter substantially equal to the diameter of the housing pin hole, such that the large diameter portion is press-fit into the housing pin hole. To facilitate translational movement of the adjustable connector within the housing channel, the small diameter portion 322 may have a diameter smaller than the width of the closed slot of the adjustable connector.

[0150] FIG. 10A is a top view of the assembled adjustable height manifold 300 in a collapsed configuration as shown in FIG. 4A, and FIG. 10B is a vertical cross-sectional view (section AA in FIG. 10A) thereof. The housing 315 is coupled to the rotating nut 320 via engagement of the edge 357 with the manifold groove 364 of the nut. The adjustable connector 325 is slidably disposed within the housing channel 340 and threadingly engaged with the rotating nut 320. The large diameter portion 334 of the manifold pin 330 is disposed within the housing pin hole 360, while the small diameter portion 332 is disposed within the closed slot 376 of the adjustable connector. When the rotating nut is rotated clockwise or counterclockwise, the adjustable connector can slide up or down within the housing channel without rotating. The manifold pin can control the extent to which the adjustable connector can be extended by providing a hard stop when the pin hits the bottom of the closed slot 376. The inlet 335 of the housing can be coupled to a source of therapeutic agent to be delivered to the patient. The inlet can be fluidly connected to the housing channel 340 either directly or indirectly through the open slot 374 of the adjustable connector. When the manifold is in the collapsed configuration, the inlet can be fluidly connected to the housing channel indirectly through the open slot 374 of the adjustable connector. When the manifold is in the extended configuration, the inlet can be fluidly connected directly to the housing channel. The housing channel can be fluidly connected to the adjustable connector channel 370 to fluidly connect to a stem channel of a first stem that is coupled to the first stem connector of the adjustable connector. The housing channel can also be fluidly connected to a stem channel of a second stem that is coupled to the second stem connector of the housing. Thus, the therapeutic agent provided via the inlet 335 can be distributed to the first and second intramedullary stems that are coupled to the manifold.

[0151] Fixed Height Wedge 11A-11C show a fixed height wedge 400 suitable for incorporation with a therapeutic agent delivery system for a knee. FIG. 11A shows a perspective view of the wedge 400, and FIGS. 11B and 11C show side views thereof. The fixed height wedge 400 is an example of a coupling member 130 that can couple two intramedullary stems in a stable configuration while maintaining a desired distance between the two stems throughout the length of use of the therapeutic agent delivery system within the patient. The wedge provides a relatively simple connection between the two intramedullary stems, and the wedge comprises a single monolithic component rather than an assembly of multiple components. Although the wedge height 405 of the wedge is fixed, the wedge can be provided in multiple sizes with various wedge heights, and the most appropriate size can be selected for each patient according to the patient's anatomy.

[0152] The fixed height wedge 400 comprises a first stem connector 442 configured to couple to a first intramedullary stem and a second stem connector 444 configured to couple to a second intramedullary stem. The first and second stem connectors may comprise any mechanism for connecting the stem to the coupling member (e.g., flanged region, dovetail joint, snap buckle, wing nut, etc.) as described in further detail herein. The wedge further comprises an inlet 435 configured to be coupled to a source of therapeutic agent to be delivered to the patient. The inlet 435 can be fluidly connected to a wedge channel 440 that extends through both the first stem connector and the second stem connector along the longitudinal axis 410 of the wedge. Thus, a therapeutic agent provided through the inlet can be distributed via the wedge channel to an intramedullary stem coupled to the wedge.

[0153] Fixed height wedge 400 may additionally include one or more of any applicable structures and features described in connection with adjustable height manifold 300. For example, wedge may include recessed groove 445 similar to recessed groove 345 described in connection with the housing of the adjustable height manifold. Similar to recessed groove 345, recessed groove 445 may be located partially about the circumference of the wedge to provide for placement of tubing coupled to the inlet.

[0154] Coupling mechanism 12A-12H illustrate an exemplary mechanism for coupling an intramedullary stem 200 to a coupling member 130. The stem 200 may comprise any embodiment of an intramedullary stem as described herein, and the coupling member 130 may comprise any embodiment of a coupling member as described herein. The stem 200 comprises a first end 215 configured to engage the coupling member, and the coupling member 130 comprises a stem connector 132 configured to engage the first end of the stem. The stem connector 132 may be any stem connector (e.g., stem connectors 342, 344, 442, 444, etc.) coupled to any coupling member as described. FIG. 12A is a perspective view of the first end 215 of the intramedullary stem 200. FIG. 12B is a perspective view of the stem connector 132 of the coupling member 130. FIGS. 12C and 12D are side views of the therapeutic agent delivery system 100 prior to assembly. Figure 12E is a side view of the assembled delivery system 100 with two stems 200 and coupling member 130 coupled together. Figure 12F is an enlarged vertical cross-sectional view of a portion of the assembled system 100 as shown in Figure 12C. Figures 12G and 12H are radial cross-sections of the assembled system 100 along line AA as shown in Figure 12E at different steps of assembly.

[0155] As shown in FIG. 12A, the first end 215 includes a raised portion 250 that is centered about a portion of the periphery of the first end. The raised portion 250 defines a rounded cavity 251 therein that is configured to receive the flanged region 150 of the coupling member 130 as shown in FIG. 12B. The raised portion 250 has a circumferential opening 252 that is configured to receive the flanged region 150 of the coupling member therethrough. The raised portion 250 further includes a recessed edge 253 that defines a recessed region 254, as best seen in FIG. 12F. The recessed region 254 can receive and retain the flanged region 150 to limit axial movement of the coupling member along the longitudinal axis 210 of the stem. As shown in FIGS. 12E and 12F, the flanged region 150 can have a length 154 that is greater than a width 152. The flanged region may further include two flat edges 157 extending along the length 154 of the flanged region and two rounded edges 159 extending about the width 152 of the flanged region. The circumferential opening 252 may have a width greater than or equal to the width 152 of the flanged region 150, but less than the length 154 of the flanged region, as shown in FIG. 12G, such that the flanged region can only enter the circumferential opening in a perpendicular orientation 151 relative to the circumferential opening 252.

[0156] 12C and 12D show the delivery system 100 prior to assembly, with the coupling member 130 aligned for insertion into the space between the two intramedullary stems 200. The flanged regions 150 of the first stem connector 132a and the second stem connector 132b are in a perpendicular orientation to the circumferential openings 252 of the raised portions of the intramedullary stems. While aligned in this orientation, the coupling member can be pushed into the space between the two intramedullary stems, as shown in FIGS. 12E, 12F, and 12G, such that the flanged regions are inserted through the circumferential openings of each stem and captured within the recessed regions of the raised portions.

[0157] Once the flanged region 150 is positioned within the round cavity 251, it may be rotated in the direction indicated by arrow 155, as shown in FIG. 12G. The flanged region may be rotated until it is positioned horizontally 153 relative to the circumferential opening 252, as shown in FIG. 12H. In the horizontal orientation, the flanged region may be prevented from sliding out of the round cavity through the circumferential opening because the length 154 of the flanged region exceeds the size of the opening 252. The first end 215 may further include one or more pins 255 disposed therein that are configured to further secure the coupling between the stem and the stem connection. For example, the first end 215 may include two pins 255, each pin spaced angularly apart about 90° from the center of the circumferential opening 252. Each rounded edge 159 of the flanged region 150 may include a smaller diameter edge 159a and a larger diameter edge 159b such that a notch 156 is created at the intersection of the edges 159a and 159b. As described, the flanged region 150 may be inserted through the opening 252 in a vertical orientation 151 as shown in FIG. 12G and subsequently rotated in the direction indicated by the arrow 155 within the recessed region 254 of the first end 215. As the flanged region rotates, the pin 255 may slide against the smaller diameter edge 159a until the pin strikes the notch 156 created by the larger diameter edge 159b. The pin may be configured, for example, to allow the flanged region to rotate approximately 90° or a quarter turn before striking the pin. Engagement of the notch 156 with the pin 255 may prevent further rotation of the stem relative to the coupling member. The pin 255 can thus provide a hard stop to the rotation of the flanged region to ensure that the final orientation of the flanged region is in a horizontal orientation 153, which can prevent the flanged region from sliding out of the round cavity as described herein.

[0158] 13A-13C illustrate another exemplary mechanism for coupling an intramedullary stem to a coupling member 130. FIG. 13A shows a perspective view and FIG. 13B shows a top view of a coupling member 130 with an exemplary connection mechanism. FIG. 13C shows a side view of a portion of an assembled delivery system 100 with two stems 200 and a coupling member 130 coupled together. The stems 200 may comprise any embodiment of an intramedullary stem as described herein, and the coupling member 130 may comprise any embodiment of a coupling member as described herein. The stems 200 comprise a first end 215 configured to engage the coupling member, and the coupling member 130 comprises a stem connector 132 configured to engage the first end of the stem. The stem connector 132 may be any stem connector (e.g., stem connectors 342, 344, 442, 444, etc.) coupled to any coupling member as described. Each stem connector 132 may include one or more dovetailed regions 160 configured to engage one or more corresponding dovetailed regions 260 of the first end 215 of the stem 200. Each stem connector 132 may further include a snap buckle 162 configured to engage a corresponding snap buckle (not shown) disposed on the first end 215 of the stem. The snap buckle 162 may include a flexible stem 164 that may be pulled to its center when the coupling member 130 is slidably inserted into the stem 200. The coupling member may snap into place when the coupling member is pushed past a notch 166 in the stem.

[0159] 14A and 14B illustrate another exemplary mechanism for coupling an intramedullary stem 200 to a coupling member 130. FIG. 14A shows a first step of assembly of the stem and coupling member using the exemplary mechanism, and FIG. 14B shows a second step of assembly. The stem 200 may comprise any embodiment of an intramedullary stem as described herein, and the coupling member 130 may comprise any embodiment of a coupling member as described herein. The stem 200 comprises a first end 215 configured to engage the coupling member, and the coupling member 130 comprises a stem connector 132 configured to engage the first end of the stem. The stem connector 132 may be any stem connector (e.g., stem connector 342, 344, 442, 444, etc.) coupled to any coupling member as described. Each stem connector 132 may include one or more dovetailed regions 160 configured to engage one or more corresponding dovetailed regions 260 of the first end 215 of the stem 200. FIG. 14A shows the coupling member 130 aligned for insertion into the space between two intramedullary stems 200, with the dovetailed region 160 of the coupling member aligned with the corresponding dovetailed region 260 of the stem. The coupling member may be pushed into the space between the two stems, such that the dovetailed region 160 is engaged within the dovetailed region 260 of the stem. Optionally, the first end 215 of each stem may include a raised portion with a circumferential opening, similar to the embodiment of FIGS. 12A-12H, with the dovetailed region 260 disposed within a rounded cavity defined within the raised portion. In such a configuration, the coupling member can be pushed into the space between the two stems until the dovetailed region 160 hits a hard stop against the raised portion of the stem. The coupling member 130 or intramedullary stem 200 can further include one or more rotation stops 176 configured to hold the coupling member in place once it is coupled to the stem. FIG. 14B shows an assembled delivery system 100, with each stem 200 including a rotation stop 176 configured to hold the coupling member 130. Each rotation stop can be rotatable so that the position of the rotation stop relative to the stem and coupling member can be adjusted.During the step of assembly as shown in Figure 14A, each rotation stop may be rotated so that it does not extend beyond the first end 215 of each stem, thereby allowing the dovetailed region 160 of the coupling member to slidingly engage the dovetailed region 260 of the stem without any physical obstruction from the rotation stop. Once the coupling member is coupled to the stem, the rotation stop may be rotated to the position shown in Figure 14B such that the length of the rotation stop extends across the junction between the stem and coupling member. The rotation stop may thus prevent the coupling member from sliding out of engagement with the intramedullary stem.

[0160] 14C and 14D show a variation of the embodiment shown in FIGS. 14A and 14B. Instead of a rotation stop, the coupling member 130 may include a wing nut 170 rotatably secured on a forward portion of the coupling member. The wing nut 170 may be configured to have a length 174 that exceeds a width 172. The nut length 174 may exceed the coupling member height 135. During assembly, the coupling member 130 may be slidingly inserted into the stem 200 with the wing nut 170 in a horizontal orientation 173 as shown in FIG. 14A. The wing nut 170 may then be rotated to a vertical orientation 171 as shown in FIG. 14B such that the nut length 174 extends across the junction between the dovetailed regions 160 and 260. In the vertical orientation, the wing nut may prevent the coupling member 130 from sliding off the stem 200.

[0161] Methods of using a therapeutic agent delivery system for the knee FIG. 15 illustrates a method 1500 of treating a patient's knee using a therapeutic agent delivery system for the knee as described herein. In step 1505, a first intramedullary stem is positioned in the medullary canal of the patient's femur. In step 1510, a second intramedullary stem is positioned in the medullary canal of the patient's fibula. In step 1515, a height of the adjustable height manifold is adjusted to fit into the joint space between the first stem and the second stem. In step 1520, the adjustable height manifold is coupled to the first stem and the second stem. The adjustable height manifold may be inserted into the joint space between the first stem and the second stem in a specific orientation appropriate for the connection mechanism used. For example, if the adjustable height manifold comprises a stem connection with a flanged region as described herein configured to engage a corresponding rounded cavity of the stem, the adjustable height manifold may be inserted by leading the two rounded edges of the flanged region. In step 1525, the coupling between the adjustable height manifold and the first and second stems is further secured via steps appropriate for the connection mechanism used. For example, if the adjustable height manifold includes a flanged region as described herein, the manifold may be rotated to securely engage the flanged region into a corresponding cavity in the stem. If the adjustable height manifold and stem include a dovetailed region with a rotation stop as described herein, the rotation stop may be rotated to extend across the junction between the stem and manifold to prevent uncoupling of the manifold from the stem. In step 1530, a therapeutic agent is delivered to the medullary canals and joint spaces of the femur and fibula.

[0162] FIG. 16 illustrates a method 1600 of treating a patient's knee using a therapeutic agent delivery system for the knee as described herein. In step 1605, a first intramedullary stem is positioned in the medullary canal of the patient's femur. In step 1610, a second intramedullary stem is positioned in the medullary canal of the patient's fibula. In step 1615, a fixed height wedge with an appropriate height is selected to fit into the joint space between the first and second stems. In step 1620, the fixed height wedge is coupled to the first and second stems, and the fixed height wedge may be inserted into the joint space between the first and second stems in a specific orientation appropriate for the connection mechanism used. For example, if the fixed height wedge comprises a stem connection with a flanged region as described herein configured to engage a corresponding rounded cavity of the stem, the fixed height wedge may be inserted by leading the two rounded edges of the flanged region. In step 1625, the coupling between the fixed height wedge and the first and second stems is further secured via steps appropriate for the connection mechanism used. For example, if the fixed height wedge includes a flanged region as described herein, the fixed height wedge may be rotated to securely engage the flanged region into a corresponding cavity in the stem. If the fixed height wedge and stem include a dovetailed region with a rotation stop as described herein, the rotation stop may be rotated to extend across the junction between the stem and the fixed height wedge to prevent uncoupling of the fixed height wedge from the stem. In step 1630, a therapeutic agent is delivered to the medullary canals and joint spaces of the femur and fibula.

[0163] The steps of methods 1500 and 1600 are provided as examples of methods of using a therapeutic agent delivery system according to embodiments. Those skilled in the art will recognize many variations and modifications of methods 1500 and 1600 based on the disclosure provided herein. For example, some steps may be added or removed. One or more steps may be performed in a different order than illustrated in Figures 15 and 16. Some of the steps may include sub-steps. Many of the steps may be repeated multiple times, as appropriate or necessary.

[0164] Therapeutic delivery system for the hip joint - Patent application 17A and 17B show an exemplary therapeutic agent delivery system 500 for a hip joint. FIG. 17A is a perspective view of an assembled delivery system, while FIG. 17B is an exploded perspective view of the system. The delivery system 500 includes a femoral stem 510 and a femoral head 520. The femoral stem 510 can be configured to be positioned within the femoral medullary canal of a patient. The femoral head 520 can be configured to be positioned within the acetabulum of a patient. The femoral stem can include an inlet 535 configured to couple to a source of therapeutic agent to be delivered to the patient. The inlet can be fluidly coupled to a channel in the femoral stem to allow the therapeutic agent to be distributed within the femoral canal. The femoral stem and femoral head can be configured to be removably coupled together to fluidly connect the femoral stem channel to one or more channels in the femoral head, such that the therapeutic agent can also be distributed within the acetabular joint space. The femoral stem and femoral head may be configured to mate in a stable configuration to maintain a desired distance between the femoral stem and the femoral head throughout the length of use of the therapeutic agent delivery system within the patient. Optionally, the femoral stem and the femoral head may be connected in a manner that allows the distance between the stem and the head to be adjusted to fit the patient's anatomy. The system 500 may further include a stem plug 530 configured to mate to the end of the femoral stem.

[0165] Femoral stem 18A-18D show an exemplary femoral stem 600 suitable for incorporation with a therapeutic agent delivery system for a hip joint. FIG. 18A is a perspective view, FIG. 18B is a side view, FIG. 18C is a bottom view, and FIG. 18D is a side cross-sectional view of the femoral stem 600. The femoral stem 600 includes an elongate body 605 having a longitudinal axis 610, the elongate body having a first end 615 and a second end 620 opposite the first end. The elongate body includes a reduced diameter region 650 disposed proximate the first end 615, which may be configured to couple to a femoral head. The second end 620 may be configured to be disposed within the femoral medullary canal. The femoral stem 600 further includes an inlet 535 configured to be coupled to a source of therapeutic agent. The inlet 535 is in fluid communication with a stem channel 625 that extends between the first end 615 and the second end 620, as best seen in FIG. 18D. The stem channel can be configured to deliver a therapeutic agent through the stem and into the medullary canal. Additionally, the stem channel can be configured to fluidly couple to one or more channels in the femoral head.

[0166] The extension body 605 may have one or more structures or features similar to the intramedullary stem 200 previously described. For example, the femoral stem 600 may include a plurality of projections 630 projecting radially outward from the extension body 605. The plurality of projections may include any number of projections having any suitable shape, size, or configuration for engaging the medullary canal in a stable manner. For example, the projections may include extension fins extending along the longitudinal length of the extension body, as shown in FIGS. 18A-18D. In one exemplary embodiment, the plurality of projections may include four fins equally spaced about 90° apart about the longitudinal axis 610 of the extension body. Of course, this is not intended to be limiting, and the number of fins may be any number, such as three fins spaced about 120 degrees apart, five fins spaced about 72 degrees apart, etc. The plurality of projections 630 and the extension body 605 may be formed separately and coupled together. Alternatively, or in combination, the plurality of protrusions 630 may be formed by removing material from the elongated body 605 such that the plurality of protrusions and the elongated body are formed as a unitary member. Adjacent protrusions 630 may define one or more grooved regions 635 therebetween, the grooved regions having a radial recession compared to the protrusions.

[0167] The protrusions and grooved regions can be configured to minimize the surface area of ​​the stem that contacts the bone overlying the medullary canal, and thus the area of ​​bone rich in therapeutic agent can be maximized. For example, the protrusions and grooved regions can be configured such that less than 50% of the surface area of ​​the stem contacts the bone overlying the medullary canal. Of course, this is not intended to be limiting, and one skilled in the art will understand that any percentage of the surface area of ​​the stem can contact the bone. The stem can include a plurality of identical grooved regions defined by a plurality of elongated fins that are distributed symmetrically about the longitudinal axis 610 of the stem, as shown in FIGS. 18A-18D. Alternatively, the grooved regions can be distributed asymmetrically about the longitudinal axis of the stem and / or have different shapes or sizes. For example, the elongated body 605 can include the protrusions and grooved regions as described in connection with FIGS. 3A and 3B.

[0168] The femoral stem 600 may further comprise a plurality of exit holes 640 in fluid communication with the stem channel 625. The plurality of exit holes 640 may be configured to deliver the therapeutic agent dispensed through the stem channel 625 to the femoral medullary canal as well as adjacent tissues, including the joint. The plurality of exit holes may be disposed within the grooved region 635 to deliver the therapeutic agent to areas of the bone that are not in contact with the femoral stem. The plurality of exit holes may comprise any number of exit holes having any suitable size, shape, or distribution. For example, the plurality of exit holes may include a plurality of equally sized and spaced holes extending axially along a line generally parallel to the longitudinal axis 610 of the stem, as shown in FIGS. 18A-18D. Alternatively, the plurality of exit holes may extend along a helix or spiral as shown in FIG. 3A, or the holes may extend about a plurality of rings around the circumference of the elongated body as shown in FIG. 3B. The multiple exit holes may comprise holes having the same shape and / or size or holes having various shapes and / or sizes. Varying hole sizes may allow for further fluid control of the therapeutic agent as it exits different regions of the stem.

[0169] The stem channel 625 may be a through hole extending through both the first and second ends from the first end 615 to the second end 620, such that the elongated body includes an open second or distal end. The system may further include a plug, as shown in FIG. 19, configured to couple to the open second end of the stem to close the second end, thereby creating a dead-end channel. Alternatively, the stem channel 625 may be a dead-end channel, and the second end of the elongated body is closed. In a configuration in which the second end is open, the therapeutic agent may exit the stem channel through the second end and / or through multiple exit holes disposed along the elongated body 605 as described herein into the medullary canal. If the stem includes only the stem channel 625 extending through the first and second ends without multiple exit holes, the therapeutic agent may exit the stem channel only through the second end. In a configuration in which the second end of the stem is closed, the therapeutic agent may exit the stem channel into the medullary canal only through the multiple exit holes.

[0170] The neck region 650 extends along a neck axis 655 that is disposed at an angle 660 relative to the longitudinal axis 610 of the elongated body 605. The angle 660 can be within a range of about 120° to about 160°, about 130° to about 150°, about 140° to about 150°, or about 145°. The neck region can include one or more connection mechanisms or features for coupling to the femoral head. For example, as shown, the neck region can include a plurality of threads 670 configured to threadably engage complementary threads on the femoral head.

[0171] The femoral stem 600 may be tapered to fit into the medullary canal. For example, the extension body 605 and / or the plurality of projections 630 may be tapered from the first end 615 to the second end 620, as shown, to have a smaller radial cross-sectional area at the second end than at the first end. For example, the taper may comprise a gradual taper, and the degree of taper may be within the range of about 0.1° to 10°, about 0.5° to about 5°, about 1° to about 5°, about 1° to about 4°, or about 2°, or about 3°. The taper may be adjusted to accommodate the medullary canal of a particular type of bone.

[0172] 19 illustrates a stem plug 530 suitable for incorporation with any therapeutic agent delivery system as described herein. The stem plug 530 may include a smaller diameter region 535 and a larger diameter region 540. The smaller diameter region may be configured to be press fit into the open second end of the extension body of any intramedullary or hip stem as described herein.

[0173] Thigh Head 20A-20B show an exemplary embodiment of a femoral head 700 suitable for incorporation with a therapeutic agent delivery system for a hip joint. FIG. 20A is a side view of the femoral head 700, and FIG. 20B is a side cross-sectional view thereof along line AA as shown in FIG. 20A. The femoral head 700 can comprise a truncated sphere shape, with a truncated base 715 of the head configured to couple to a femoral stem. The femoral head 700 comprises a head central channel 725 extending axially along a central axis 710 of the femoral head. The central channel 725 is configured to couple to a reduced diameter portion of the femoral stem, thereby providing fluid communication with the hip stem channel when the femoral head is connected to the femoral stem. The femoral head further comprises a plurality of exit holes 740 fluidly coupled to the central channel 725. The exit holes can be configured to extend radially outward from the central channel. Thus, a therapeutic agent may be fed into the delivery system via an inlet in the femoral stem, travel through the stem channel into the central channel 725 of the femoral head, and exit through the exit hole 740 into the acetabular joint space.

[0174] The base 715 may include one or more mechanisms for coupling the femoral head to the reduced diameter region of the femoral stem. For example, as shown, a portion of the central channel 725 proximate the base 715 may include a plurality of threads 770 configured to threadably engage a plurality of complementary threads on the femoral stem reduced diameter. The threaded connection between the femoral head and the femoral stem reduced diameter may allow the distance between the femoral head and the femoral stem to be adjusted to fit the patient's anatomy. Optionally, the femoral head may further be configured to receive one or more set screws proximate the base that can fix the distance between the femoral head and the femoral stem once the distance is properly set. For example, as shown in FIG. 20B, the base may include two set screw receiving regions 780, each set screw receiving region including a plurality of threads 785 for engaging a set screw having a complementary thread. The set screw receiving areas can extend radially outward from the central channel, such that the ends of the set screws can be directly or indirectly coupled to a reduced diameter portion of the femoral stem disposed within the central channel. Although FIG. 20B shows two set screw receiving areas radially offset from one another by approximately 180°, the femoral head can include any number of set screws distributed in any suitable configuration. For example, the femoral head can include three set screw receiving areas radially offset from one another by approximately 120° or four set screw receiving areas radially offset from one another by approximately 90°.

[0175] 21A-21B show another exemplary embodiment of a femoral head 800 suitable for incorporation with a therapeutic agent delivery system 500 for a hip joint. The femoral head 800 is partially hollowed out to reduce the material mass and weight of the femoral head. The femoral head 800 comprises a central channel 825 configured to be in fluid communication with a stem channel of a femoral stem as described herein. The femoral head further comprises a medial shell 830 and an lateral shell 835, the medial and lateral shells being thin truncated spherical shells centered about the periphery of the femoral head. The medial shell 830 is centered about and connected to the material defining the central channel 825. The lateral shell 835 is connected to the medial shell 830 via a number of support struts 845 extending between the medial shell and the lateral shell. The medial shell defines an inner cavity 855 between the medial shell and the material defining the central channel. The inner cavity 855 is hollow and configured to be sealed against the central channel and the inner shell, so that no fluid can enter the inner cavity during use of the delivery system. The inner and outer shells define an outer cavity 850 therebetween, which is fluidly coupled to the central channel 825. The outer shell includes a plurality of exit holes 840, so that fluid within the outer cavity 850 can exit the femoral head through the exit holes. Thus, a therapeutic agent delivered through an inlet of the femoral stem can travel through the stem channel into the central channel 825 of the femoral head 800, into the outer cavity 850, and through the exit holes 840 into the acetabular joint space. The components of the femoral head 800 can be formed via 3D printing or laser sintering.

[0176] 22 illustrates another exemplary embodiment of a femoral head 900 suitable for incorporation with a therapeutic agent delivery system for a hip joint. The femoral head 900 comprises a central channel 925 configured to be in fluid communication with a stem channel of a femoral stem as described herein. The femoral head further comprises a plurality of hollow tubes 940 extending radially outward from the central channel 925 and fluidly coupled to the central channel. The femoral head further comprises an outer shell 935, which is a thin truncated spherical shell centered about the periphery of the femoral head. The outer shell 935 is coupled to the plurality of hollow tubes 940 such that the hollow tubes 940 extend through the thickness of the outer shell. The hollow tubes, the outer shell, and the material centered about and defining the central channel together define a plurality of inner cavities 855, which are hollow and configured to be fluidly sealed such that no fluids can enter the inner cavities during use of the delivery system. Thus, a therapeutic agent supplied through the inlet of the femoral stem can travel through the stem channel into the central channel 925 of the femoral head 900, into the plurality of hollow tubes 940, and into the acetabular joint space. The inner diameter of the hollow tubes and / or the thickness of the hollow tubes can be varied to control the flow of fluid within the femoral head, adjust the amount of support provided by the hollow tubes to the outer shell, and protect the integrity of the outer shell.

[0177] Coupling mechanism 23A and 23B show an exemplary mechanism for coupling the femoral head 520 to the femoral stem 510. The femoral head 520 may comprise any femoral head as described herein, such as femoral heads 700, 800, and 900 described in connection with FIGS. 20A-22. The femoral stem 510 may comprise any femoral stem as described herein, such as any embodiment of the femoral stem 600 described herein. FIG. 23A is a side cross-sectional view of the femoral head 520 fixedly coupled to the femoral stem 510. The stem's reduced diameter region 650 is fixedly coupled to a portion of the femoral head's central channel 725, and thus the reduced diameter length 540 that engages the femoral head is fixed. For example, the reduced diameter portion 650 may be press-fit into the central channel 725, and thus the reduced diameter portion advances into the central channel by a predetermined length. The reduced diameter portion 650 may include regions having different diameters to create a notch between the regions, which can provide a stop against the femoral head surface once the reduced diameter portion 650 is advanced into the central channel a predetermined length. In a delivery system incorporating such a connection mechanism, the distance between the femoral head and the femoral stem is fixed. FIG. 23B is a side cross-sectional view of a femoral head 520 adjustably coupled to a femoral stem 510. The reduced diameter portion region 650 of the stem is adjustably coupled to a portion of the central channel 725, for example, via engagement of threads 670 disposed on the reduced diameter portion 650 of the stem with complementary threads 770 disposed on a portion of the central channel 725. The length 540 of the reduced diameter portion that engages the central channel can thereby be increased or decreased by threading and rotating the femoral head about the femoral stem. As the femoral head is rotated to axially translate the head further away from the femoral stem, the length 540 decreases and the distance between the femoral head and the femoral stem increases, and thus the delivery system may be suitable for patients requiring a longer set distance between the femur and the acetabulum.As the femoral head is rotated to axially translate the head closer to the femoral stem, the length 540 increases and the distance between the femoral head and the femoral stem decreases, and thus the delivery system may be suitable for patients requiring a shorter set distance between the femur and the acetabulum. In delivery systems incorporating such a connection mechanism, the distance between the femoral head and the femoral stem can therefore be adjusted to accommodate the patient's anatomy.

[0178] 24A and 24B show an exemplary mechanism for locking a set distance between a femoral head 520 and a femoral stem 510 of a therapeutic agent delivery system for a hip joint. The femoral head 520 may comprise any femoral head as described herein, such as femoral heads 700, 800, and 900 described in connection with FIGS. 20A-22. The femoral stem 510 may comprise any femoral stem as described herein, such as any embodiment of the femoral stem 600 described herein. FIG. 24A is a perspective view of the femoral head 520 with an exemplary connection mechanism, and FIG. 24B is a bottom view thereof. As described herein, the femoral head 520 may comprise a pair of set screw receiving regions 780 proximate the base 715 of the head, which may receive a pair of set screws configured to engage a femoral stem reducer disposed within a central channel 725 of the femoral head to fix the position of the stem reducer therein. The femoral head may further include a pair of blocks 550 disposed within the set screw receiving area 780 adjacent the central channel 725. Each block may be coupled with a set screw 554, and the blocks may include a rounded cavity for receiving an end of the set screw, which may rotate freely within the rounded cavity. Two dowel pins 552 may be coupled to the block-set screw assembly to limit the translational movement of the set screw relative to the blocks. Rotation of the set screw within the set screw receiving area may cause the block coupled thereto to translate radially inward or outward. The block may be translated radially inward until it engages and presses against the reduced diameter area of ​​the stem disposed within the central channel, thereby preventing further rotation of the femoral head about the femoral stem. The block may distribute the force between the reduced diameter and the set screw across a larger surface to more effectively lock the position of the reduced diameter. Although FIGS. 24A-24F show pairs of set screw receiving areas that are radially offset from one another by approximately 180°, the locking mechanism may include any number of set screws distributed in any suitable configuration.For example, the femoral head may include three set screw receiving regions radially offset from one another by approximately 120° or four set screw receiving regions radially offset from one another by approximately 90°.

[0179] 24C-24F illustrate a method of assembling the locking mechanism of FIGS. 24A and 24B. FIG. 24C shows the femoral head 520 and components of the locking mechanism prior to assembly. As previously described, the femoral head may include one or more set screw receiving areas 780 extending radially outward from a central channel 725. Each set screw receiving area may be configured to receive a set screw 554, a block 550, and a pair of dowel pins 552. FIG. 24D shows a first step in the assembly of the locking mechanism, in which a block 550 is coupled to the femoral head 520. The femoral head may include a block receiving area 556 adjacent the central channel 725, into which a block may be inserted from the base 715 of the femoral head. As best seen in FIG. 24B, the block 550 may have a concave surface 551 on a first end and a rounded recess 553 on a second end opposite the first end. As shown in FIG. 24C, the block may be inserted into the femoral head with the concave surface oriented radially inward, facing the central channel, and the rounded recess oriented radially outward. FIG. 24E illustrates a second step in the assembly of the locking mechanism, where a set screw 554 is coupled to the femoral head 520. As best seen in FIG. 24B, the set screw receiving area 780 includes set screw threads 785 configured to engage a threaded area of ​​a set screw. The set screw may be threadably engaged with the set screw threads in the set screw receiving area to translate the set screw radially inward within the set screw receiving area. As best seen in FIG. 24D, the set screw includes a set screw head 555, where the unthreaded region of the set screw can have a smaller diameter than the threaded region of the set screw. During the step shown in FIG. 24E, the set screw can be translated radially inward until the set screw head is located within the rounded recess 553 of the block 550 (as best seen in FIG. 24B). FIG. 24F shows the final step in the assembly of the locking mechanism, where the dowel pin 552 is coupled to the femoral head. The two dowel pins can be pressed into the block 550 with an interference fit.When the dowel pin is pushed fully into the block, the tip of the pin can engage the set screw head 555, thus preventing the set screw from separating from the block. For example, the screw head can include a recessed groove 557 (as best seen in FIGS. 24B and 24D) that extends about the circumference of the set screw head 555. The tip of the dowel pin can be configured to engage the recessed groove when the pin is pushed fully into the block (as best seen in FIG. 24B), thus preventing the set screw from separating from the block.

[0180] Optional Features 25A and 25B show an exemplary embodiment of a therapeutic agent delivery system 500 for a hip joint further comprising an acetabular cup 560. FIG. 25A is a perspective view of the system 500 and FIG. 25B is a side cross-sectional view thereof. The delivery system 500 may further comprise a separate acetabular cup 560 configured to be inserted into the acetabular space of the hip joint. The femoral head 520 thus interfaces with the acetabular cup rather than directly with the patient's acetabulum. The acetabular cup may comprise a plurality of grooved exterior structures 565 through which fluid may flow to reach the acetabulum.

[0181] FIG. 26 illustrates an exemplary embodiment of a therapeutic agent delivery system 500 for a hip joint. The therapeutic agent delivery system 500 as described herein may be configured to function as a final implant rather than as a temporary implant intended for the first stage of a two-stage reimplantation procedure. The system 500 may include a femoral stem 510, such as any of the femoral stems described herein, a femoral head 520, such as any of the femoral heads described herein, and a stem plug 530. In addition, the system 500 may further include a liner 570 and an acetabular cup 560 configured to be implanted between the femoral head 520 and the patient's acetabulum. Fluid may flow through the femoral head, out of the liner and acetabular cup, and into the joint space and acetabulum. Optionally, as an alternative to or in combination with the inlet 535 of the femoral stem 510, the acetabular cup 560 may include a separate inlet through which a therapeutic agent may be delivered.

[0182] Methods of using a therapeutic agent delivery system for the hip joint FIG. 27 illustrates a method 1700 of treating a patient's hip joint using a therapeutic agent delivery system for the hip joint as described herein. In step 1705, a femoral stem is positioned within the medullary canal of the patient's femur. In step 1710, a femoral head is coupled to the femoral stem. In optional step 1715, the distance between the femoral stem and the femoral head is adjusted to best fit the delivery system to the patient's anatomy. For example, if the femoral head is coupled to the femoral stem via a threaded connection mechanism as described herein, the distance between the femoral stem and the head can be adjusted by threading and rotating the femoral head about the stem. Step 1715 may further include locking the distance between the femoral head and the femoral stem, for example, via a set screw mechanism as described in connection with FIGS. 24A-24F. In step 1720, the femoral head is positioned within the patient's acetabulum. In step 1725, a therapeutic agent is delivered to the medullary canal and acetabulum via the delivery system.

[0183] The steps of method 1700 are provided as examples of methods of using a therapeutic agent delivery system according to embodiments. Those skilled in the art will recognize many variations and modifications of method 1700 based on the disclosure provided herein. For example, some steps may be added or removed. Some of the steps may include sub-steps. Many of the steps may be repeated multiple times, as appropriate or necessary. One or more steps may be performed in a different order than illustrated in FIG. 27. For example, a femoral head and a femoral stem may be coupled together, and if necessary, the distance between the head and stem is adjusted before the assembled device is positioned within the patient's femur and acetabulum.

[0184] Additional Features of Therapeutic Delivery Systems In any of the therapeutic agent delivery systems described herein, the flow of fluid within the system can be adjusted by modifying the dimensions or configuration of one or more of the channels and / or exit holes. For example, the diameter of the channels and / or exit holes can be increased or decreased, or the channels can be configured to have variable diameters along the length of the assembly to bias the flow of fluid in a particular direction. The angles at the junctions between channels can also be varied to bias the flow of fluid within the system.

[0185] Any of the therapeutic agent delivery systems as described herein may further include a pump operably coupled to the inlet. The pump may be configured to pump the therapeutic agent into one or more channels of the system.

[0186] Any of the therapeutic agent delivery systems as described herein may optionally include a vacuum pump, which may be coupled to an inlet or outlet of the system. The vacuum pump may be configured to remove any undesirable or excess fluids from the patient's body prior to introducing a therapeutic agent into the body using the delivery system.

[0187] Any of the therapeutic agent delivery systems as described herein may optionally include a subcutaneous port coupled to an inlet or outlet of the delivery system, which may be accessed via a needle or syringe, as appropriate.

[0188] 28A and 28B illustrate the use of negative pressure wound therapy with a therapeutic agent delivery system for a knee. Negative pressure wound therapy can optionally be used in conjunction with a therapeutic agent delivery system to further improve the outcome of the treatment. The patient's wound can be filled with a sponge 90 and optionally covered with a wound dressing 85 coupled to a vacuum pump 80. Activation of the vacuum pump can then draw blood and nutrients into the infected area. As shown in FIG. 28B, the optional sponge for negative pressure wound therapy can also be provided as a strip of sponge 95 configured to be placed along the intramedullary stem 200 of the delivery system 100. The strip of sponge can be trimmed to fit into the space along the grooved region 235 of any intramedullary stem 200. The negative pressure wound therapy can draw material through the sponge, into the stem's multiple exit holes, into the stem channel, and out of the body through the inlet or outlet of the system. Although a delivery system for the knee is shown in Figures 28A and 28B, negative pressure wound therapy may be used in conjunction with any therapeutic agent delivery system as described herein, including delivery systems for joints other than the knee.

[0189] FIG. 29 illustrates an optional cover 75 for the intramedullary stem 200 suitable for incorporation with any of the therapeutic agent delivery systems described herein. The cover 75 may comprise a thin conical sponge configured to fit inside the medullary canal as an interface between the bone and the intramedullary stem 200. The cover can be configured to cover substantially all of the stem's elongated body 205 and thus interface uniformly with the intramedullary bone. When covered with the cover 75, the therapeutic agent can disperse within the cover and reach the corresponding surface of the medullary canal regardless of the shape of the intramedullary stem (e.g., the shape, size, number, or configuration of the protrusions and grooved regions). This exemplary configuration may also be used in conjunction with negative pressure wound treatment as previously described.

[0190] 30 illustrates an exemplary embodiment of a therapeutic agent delivery system 1000. The delivery system 1000 may include an intramedullary stem 1010, which may be any intramedullary stem as described herein, such as intramedullary stem 110, 120, or 200 or femoral stem 510 or 600. The stem 1010 may include a stem channel 1025 extending through both a first end 1015 and a second end 1020 of the stem. Instead of receiving the therapeutic agent from a coupling member coupled to the stem, the stem 1010 may be configured to receive a catheter 1030 that supplies the therapeutic agent through the first end 1015. The therapeutic agent may be delivered to the medullary canal through the second end 1020.

[0191] 31A and 31B show an exemplary embodiment of a therapeutic agent delivery system with an inlet and an outlet. FIG. 31A shows an exemplary embodiment of a therapeutic agent delivery system 100 for a knee as described herein. The delivery system 100 may include an inlet 140 configured to couple to a source of therapeutic agent. The inlet 140 may be fluidly coupled to one or more channels of the coupling member 130, which may be fluidly coupled to a stem channel in the stem 200. Optionally, the system may further include an outlet 145 configured to remove the therapeutic agent and / or any other fluids from the body. The stem and coupling member may include internal channels configured to direct fluid between the inlet and the stem channel and between the stem channel and the outlet. Other aspects of the system may generally take the same form as previously described. FIG. 31B shows an exemplary embodiment of a therapeutic agent delivery system 500 for a hip joint as described herein. The delivery system 500 may include an inlet 535 configured to couple to a source of therapeutic agent. The inlet 535 may be fluidly coupled to a channel in the femoral stem 510, and the stem channel may be fluidly coupled to a central channel in the femoral head 520 that is coupled to the femoral stem. Optionally, the system may further include an outlet 545 configured to remove the therapeutic agent and / or any other fluids from the body. The femoral stem and femoral head may include internal channels configured to direct fluid between the inlets and channels of the stem and the head, and between the outlets and channels of the stem and the head. Other aspects of the system may generally take the same form as previously described.

[0192] 32A and 32B illustrate example configurations for the internal channels of an intramedullary stem. FIG. 32A is a cross-sectional view of an intramedullary stem 1100 with multiple separate internal flow channels, and FIG. 32B is a cross-sectional view thereof. The stem 1100 may comprise any intramedullary stem as described herein, such as the intramedullary stems 110, 120, or 200 or the femoral stems 510 or 600. The stem 1100 may comprise a first internal channel 1110 centrally disposed along the longitudinal axis of the stem and a second internal channel 1120 centrally disposed about the periphery of the first internal channel (the second internal channel may form the shape of a cylindrical shell surrounding the first internal channel). The first internal channel may be fluidly coupled to a first plurality of exit holes 1115, each of which may extend from the first internal channel through a second internal channel to an outer wall of the stem (such as the grooved region 1135 of the stem). The second internal channel may be fluidly coupled to a second plurality of exit holes 1125, each of which may extend directly from the second internal channel to the outer wall of the stem. The first internal channel and the second internal channel may be fluidically sealed to one another, and each of the first plurality of exit holes 1115 may cross the second internal channel 1120 through a side channel that is fluidically sealed to the second internal channel. Thus, the first internal channel and the second internal channel may form two separate internal flow paths, each of which may be used to deliver fluid to or remove fluid from tissue. As shown in FIG. 32B, the first plurality of outlet holes 1115 and the second plurality of outlet holes 1125 may be linearly arranged along the length of the stem in an alternating manner such that every other hole is in fluid communication with a different internal flow path.

[0193] 33A-33C illustrate another exemplary configuration for the internal channels of an intramedullary stem. FIG. 33A is a perspective view, FIG. 32B is a vertical cross-sectional view, and FIG. 33C is a horizontal cross-sectional view of an intramedullary stem 1200 with multiple separate internal flow paths. The stem 1200 may comprise any intramedullary stem as described herein, such as the intramedullary stems 110, 120, or 200 or the femoral stems 510 or 600. The stem 1200 may comprise a first internal channel 1210 extending along the length of the stem and a second internal channel 1220 adjacent to the first internal channel, also extending along the length of the stem. The first and second internal channels may be fluidly sealed to one another, such that each channel forms a separate internal flow path. The first internal channel may be fluidly coupled to a first plurality of exit holes 1215, each of which may extend from the first internal channel to an outer wall of the stem (such as the grooved region 1235 of the stem) without crossing the second internal channel. The second internal channel may be fluidly coupled to a second plurality of exit holes 1225, each of which may extend from the second internal channel to an outer wall of the stem without crossing the first internal channel. Thus, the first internal channel and the second internal channel may form two separate internal flow paths, each of which may be used to deliver fluid to or remove fluid from tissue. As shown in FIG. 33A, the first plurality of exit holes 1215 and the second plurality of exit holes 1225 may be arranged along the length of the stem in an alternating manner, such that every other hole is in fluid communication with a different internal flow path.

[0194] An intramedullary stem with two or more separate internal flow paths as shown in Figures 32A-33C can be used to simultaneously deliver fluid to tissue and remove fluid from tissue without cross-contaminating the fluid to be delivered with the fluid to be removed. For example, a first internal channel can be fluidly coupled to an inlet (such as inlet 140 in Figure 31A or inlet 535 in Figure 31B) configured to receive a therapeutic agent from a source, while a second internal channel can be fluidly coupled to an outlet (such as outlet 145 in Figure 31A or outlet 545 in Figure 31B) configured to remove fluid from tissue. In this configuration, the first multiple outlet holes can deliver a therapeutic agent to tissue, while the second multiple outlet holes can remove fluid from tissue, thereby allowing simultaneous delivery of a therapeutic agent and removal of fluid from tissue without cross-contamination between the therapeutic agent and the fluid to be removed. In another exemplary configuration, the first internal channel may be fluidly coupled to a first inlet configured to receive a first therapeutic agent, while the second internal channel may be fluidly coupled to a second inlet configured to receive a second therapeutic agent different from the first therapeutic agent. In this configuration, simultaneous delivery of two different therapeutic agents may be achieved without cross-contamination between the two therapeutic agents before they reach the tissue.

[0195] 34-36 show exemplary embodiments of therapeutic agent delivery systems adapted for use in various joints. Although the description of the therapeutic agent delivery systems is primarily directed to systems to be used in the knee or hip, systems with similar components and features may be used to treat any other joint. FIG. 34 shows an exemplary embodiment of a delivery system 1200 for the shoulder, FIG. 35 shows an exemplary embodiment of a delivery system 1300 for the ankle, and FIG. 36 shows an exemplary embodiment of a delivery system 1400 for the spine. In the illustrated embodiment, the delivery systems 1200, 1300, and 1400 include an inlet 140 through which the therapeutic agent may be supplied and a plurality of outlet holes 240 through which the therapeutic agent may be delivered to individual locations of the body. Any of the delivery systems 1200, 1300, and 1400 may incorporate any other structure or feature disclosed herein in connection with the delivery systems for the knee and hip.

[0196] The components of the therapeutic agent delivery system as described herein may be formed from one or more of many materials commonly used in orthopedic implants, including, but not limited to, titanium alloy Ti 6Al-4V, polyetheretherketone (PEEK), polymethylmethacrylate (PMMA), and ultra-high molecular weight polyethylene (UHMWPE). The materials may incorporate an antibiotic-impregnated outer layer, such as an antibiotic-impregnated PMMA outer layer. The surfaces of the components may be polished to prevent bone growth and biofilm formation. Alternatively, the surfaces of the components may incorporate one or more of a hyaluronic acid (HA) coating, a silver coating, or an antibiotic carrier coating that is grit blasted or plasma sprayed, or passivated and irradiated to form a hydrophilic nanostructure. The delivery system as described herein may comprise one or more of a machined or sintered portion.

[0197] While preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will hereafter occur to those skilled in the art without departing from the invention. It is understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. The following claims define the scope of the invention, and it is intended that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

1. A therapeutic agent delivery system, comprising: a femoral head, said femoral head comprising a first channel and a first plurality of outlets; a femoral stem comprising a proximal portion adapted to be coupled to the femoral head and a distal portion configured to be disposed within the femoral medullary canal, the distal portion comprising a second channel and a second plurality of outlets, the proximal portion comprising a third channel, the third channel fluidly coupled to the first channel when the femoral stem is coupled to the femoral head; an inlet, when the femoral stem is coupled to the femoral head, the inlet being fluidly coupled to the first plurality of outlets of the femoral head via the first channel and the third channel and to the second plurality of outlets of the femoral stem via the second channel, and further, when a source of therapeutic agent is coupled to the inlet and the therapeutic agent is introduced into the system via the inlet, the therapeutic agent is deliverable to the hip joint space via the first plurality of outlets in the femoral head and to the femoral medullary canal via the second plurality of outlets in the femoral stem; A system comprising:

2. The delivery system of claim 1, wherein the femoral head is configured to be positioned within the acetabulum.

3. The delivery system of claim 2, wherein the femoral head is configured to be positioned within an acetabular cup positioned within the acetabulum.

4. The delivery system of claim 1, wherein the femoral head further comprises a plurality of channels, each outlet of the first plurality of outlets being fluidly coupled to one of the channels, and each channel of the plurality of channels being fluidly coupled to the first channel.

5. The delivery system of claim 1, wherein the femoral head is rotatably coupled to the proximal portion of the femoral stem.

6. The delivery system of claim 1, wherein the femoral head is adjustably coupled to the proximal portion of the femoral stem.

7. A delivery system as described in claim 6, wherein the femoral head is adjustably coupled to the proximal portion of the femoral stem to accommodate the anatomical dimensions of a patient.

8. The delivery system of claim 1, wherein the femoral head further comprises a locking mechanism for securing the femoral head to the femoral stem at a fixed distance from the femoral stem.

9. The delivery system of claim 8, wherein the locking mechanism includes a locking screw.

10. A delivery system as described in claim 1, wherein the femoral head further comprises a plurality of fluidly sealed cavities within the femoral head.

11. The delivery system of claim 1, wherein the proximal portion of the femoral stem includes the inlet.

12. A therapeutic agent delivery system, comprising: a head, the head comprising a first channel and a first plurality of outlets; a stem comprising a proximal portion adapted to be coupled to the head and a distal portion configured to be disposed within a medullary canal of a bone, the distal portion comprising a second channel and a second plurality of outlets, the proximal portion comprising a third channel, the third channel fluidly coupled to the first channel when the stem is coupled to the head; an inlet, when the stem is coupled to the head, the inlet fluidly coupled to the first plurality of outlets of the head via the first channel and the third channel and to the second plurality of outlets of the stem via the second channel, and further, when a source of therapeutic agent is coupled to the inlet and the therapeutic agent is introduced into the system via the inlet, the therapeutic agent is deliverable to the shoulder joint space via the first plurality of outlets in the head and also to the medullary canal of the bone via the second plurality of outlets in the stem; A system comprising:

13. The delivery system of claim 12, wherein the head is configured to be positioned within the glenohumeral joint of the shoulder and the bone is the humerus.

14. The delivery system of claim 12, wherein the head further comprises a plurality of channels, each outlet of the first plurality of outlets being fluidly coupled to one of the channels, and each channel of the plurality of channels being fluidly coupled to the first channel.

15. A delivery system as described in claim 12, wherein the head is rotatably coupled to the proximal portion of the stem.

16. A delivery system as described in claim 12, wherein the head is adjustably coupled to the proximal portion of the stem.

17. A delivery system as described in claim 16, wherein the head is adjustably coupled to the proximal portion of the stem to accommodate the anatomical dimensions of a patient.

18. A delivery system as described in claim 12, wherein the head further comprises a locking mechanism for securing the head to the stem at a fixed distance from the stem.

19. The delivery system of claim 18, wherein the locking mechanism includes a locking screw.

20. A delivery system as described in claim 12, wherein the head further comprises a plurality of fluidly sealed cavities within the head.

21. A delivery system as described in claim 12, wherein the proximal portion of the stem includes the inlet.

22. The delivery system of claim 12, wherein the proximal portion of the stem further comprises a third plurality of outlets fluidly coupled to the inlet.

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