Patent ID: 12257154

DETAILED DESCRIPTION OF THE INVENTION

Specific embodiments of the disclosed device, delivery system, and method will now be described with reference to the drawings. Nothing in this detailed description is intended to imply that any particular component, feature, or step is essential to the invention.

Described herein are therapeutic agent delivery systems that may be used in a knee joint, a hip joint, or any other joint. For example, the therapeutic agent delivery system may be used to treat a shoulder or ankle joint, or a portion of the spine. One of skill in the art will appreciate that other joints may also be treated with the systems, devices, and methods disclosed herein. Optionally in any embodiment, the therapeutic agent delivery system may comprise one or more intramedullary stems, configured to be disposed stably in a medullary canal of a bone. The intramedullary stem may be configured to deliver the therapeutic agent to the medullary canal, the joint space, or a combination thereof. Optionally, in any embodiment, an intramedullary stem is coupled to another component, such as another intramedullary stem or a femoral head, in a way that allows the distance between the stem and the other component to be adjusted to fit a patient, or the distance therebetween may be fixed.

The therapeutic agent delivered by the delivery systems described herein may comprise any fluid. For example, the therapeutic agent may comprise an antibiotic fluid such as a vancomycin or tobramycin, combinations thereof, or other antibiotics commonly used to treat implant-associated infections. One of skill in the art will appreciate that any therapeutic agent may be 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 canals being treated.

Therapeutic Agent Delivery System for Knee

FIGS.1A and1Bshow an exemplary therapeutic agent delivery system100for a knee.FIG.1Ashows the components of the delivery system assembled together, whileFIG.1Bshows the components of the delivery system disassembled and aligned for assembly. The delivery system100comprises a first intramedullary stem110, a second intramedullary stem120, and a coupling member130. Each of the two intramedullary stems110and120can be configured be disposed in a medullary canal of a bone. For example, the first intramedullary stem110can be configured to be disposed in the medullary canal of a femur of a patient, while a second intramedullary stem120can be configured to be disposed in the medullary canal of a tibia of the patient. The coupling member130, configured to be disposed in the joint space, can couple the two stems in a stable configuration, while maintaining a desired distance105between the two stems throughout the length of use of the therapeutic agent delivery system in a patient.

The first intramedullary stem110and the second intramedullary stem120may 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 comprise a first intramedullary stem specifically configured to engage a femur, and a second intramedullary stem specifically configured to engage a tibia. The two stems may differ in one or more dimensions, such as length, diameter, or degree of taper. Alternatively or in combination, the two stems may differ in one or more configurations or features as described herein (e.g., configuration of the stem channel, number, shape, and size of the protrusions, the fluted regions, and/or the outlet holes, etc.).

The coupling member130may comprise any coupling member as described herein, such as an adjustable height manifold or a fixed height wedge. In many embodiments of the delivery system100, the coupling member130can be configured to allow the distance105between the two stems to be adjusted, so as to accommodate the anatomy of the patient. The coupling member can be configured to fluidly couple to a source of a therapeutic agent and receive the therapeutic agent, and distribute the therapeutic agent to the intramedullary stems for delivery to the medullary canals.

The first stem110and the second stem120may be releasably coupled to the coupling member130. Each of the first stem and the second stem may be configured to couple to a stem connector132of the coupling member. The first stem may couple to a first stem connector132a, and the second stem may couple to a second stem connector132b. Various mechanisms for the connection between the stem and the coupling member are described herein, any of which may be incorporated into the coupling member130for coupling with the first stem or the second stem. The first stem and the second stem may couple to the first stem connector and the second stem connector, respectively, via identical mechanisms or via different mechanisms. Accordingly, the first stem connector132aand the second stem connector132bof the coupling member may be identical or different. In preferred embodiments, the first stem and the second stem are identical, such that the coupling member accordingly comprises two identical stem connectors configured to couple to the first stem and the second stem via identical mechanisms.

Intramedullary Stem

FIGS.2A-2Cshow an exemplary intramedullary stem200, suitable for incorporation with a therapeutic agent delivery system for a knee.FIG.2Ais a perspective view, andFIGS.2B and2Care side views of the intramedullary stem200. Each intramedullary stem200comprises an elongate body205having a longitudinal axis210, the elongate body having a first end215and a second end220opposite the first end. The first, or proximal, end may be configured to couple to a coupling member130, such as an adjustable height manifold or a fixed height wedge as described herein. The second, or distal, end may be disposed in the medullary canal of a bone. The elongate body205comprises a stem channel225extending between the first end215and the second end220, the stem channel configured to deliver the therapeutic agent through the stem and to the medullary canal. The first end215of the intramedullary stem200may be configured to couple the stem to a coupling member. The first end may comprise any mechanism for connecting the stem to the coupling member (e.g., flanged region, dovetail joints, snap buckle, winged nut, etc.), as described in further detail herein.

The intramedullary stem200may comprise a plurality of protrusions230, protruding radially outward from the elongate body205. The plurality of protrusions may comprise any number of protrusions having any appropriate shape, size, or configuration to engage the medullary canal in a stable fashion. For example, the protrusions may comprise elongate fins extending along the longitudinal length of the elongate body, as shown inFIGS.2A-2C. In one exemplary embodiment, the plurality of protrusions may comprise four fins, spaced equally at about 90° about the longitudinal axis210of the elongate body. The plurality of protrusions230and the elongate body205may be formed separately and coupled together. Alternatively or in combination, the plurality of protrusions230may be formed by removing material from the elongate body205, such that the plurality of protrusions and the elongate body are formed as a single member. Adjacent protrusions230may define one or more fluted regions235therebetween, the fluted regions radially recessed compared to the protrusions. The fluted regions may form a concave recessed region between adjacent protrusions.

The plurality of protrusions and fluted regions can be configured to minimize the surface area of the stem contacting the bone lining the medullary canal, such that the area of the bone flushed with the therapeutic agent may be maximized. For example, the plurality of protrusions and fluted regions can be configured such that less than 50% of the surface area of the stem is in contact with the bone lining the medullary canal. Of course this is not intended to be limiting and one of skill in the art will appreciate that any percentage of the surface area of the stem may contact the bone. The stem may comprise a plurality of identical fluted regions defined by a plurality of elongate fins, distributed symmetrically about the longitudinal axis210of the stem, as shown inFIGS.2A-2C. Alternatively, a plurality of fluted regions may be distributed asymmetrically about the longitudinal axis of the stem, and/or may have different shapes or sizes as described in further detail herein.

An intramedullary stem200may further comprise a plurality of outlet holes240in fluid communication with the stem channel225. The plurality of outlet holes240may be configured to deliver the therapeutic agent, distributed through the stem channel225, to the medullary canal, as well as adjacent tissue including the joint. The plurality of outlet holes may be disposed in a fluted region235, so as to deliver the therapeutic agent to the area of the bone not in contact with the intramedullary stem. The plurality of outlet holes may comprise any number of outlet holes having any appropriate size, shape, or distribution. For example, the plurality of outlet holes may include a plurality of equally sized and spaced holes that extend axially along a line substantially parallel to the longitudinal axis210of the stem, as shown inFIGS.2A-2C. The plurality of outlet holes may be arranged in various configurations, as described in further detail herein. The plurality of outlet holes may comprise holes having an identical shape and/or size, or holes having various shapes and/or sizes. Varying the hole size may allow further fluid control of therapeutic agent as it exits different regions of the stem.

The stem channel225may be a through hole that extends from the first end215to the second end220through both the first end and the second end, such that the elongate body comprises an open second or distal end. The system may further comprise a plug (not shown) configured to couple to the open second end of the stem, so as to close the second end and thereby create a blind channel. Alternatively, the stem channel225may be a blind channel, wherein the second end of the elongate body is closed. In configurations wherein the second end is open, the therapeutic agent may exit the stem channel into the medullary canal through the second end and/or through a plurality of outlet holes disposed along the elongate body205as described herein. If the stem comprises only the stem channel225extending through the first and second ends, without the plurality of outlet holes, the therapeutic agent may exit the stem channel only through the second end. In configurations wherein the second end of the stem is closed, the therapeutic agent may exit the stem channel into the medullary canal only through the plurality of outlet holes.

The intramedullary stem200may be tapered to fit the medullary canal. For example, the elongate body205and/or the plurality of protrusions230may be tapered from the first end215to the second end220, as shown, so as 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, wherein the extent of the taper may be preferably in a range from about 0.1° to about 10°, more preferably about 0.5° to about 5°, and 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 a medullary canal of a specific type of bone.

The exemplary embodiment ofFIGS.2A-2Cmay comprise one or both of two intramedullary stems of a therapeutic agent delivery system for a knee as shown inFIGS.1A and1B. Preferably, the therapeutic agent delivery system for a knee comprises two identical intramedullary stems, such as the exemplary embodiment ofFIGS.2A-2C.

FIGS.3A and3Bshow alternative embodiments of the elongate body205of the intramedullary stem200ofFIGS.2A-2C.FIG.3Ashows an elongate body205comprising one or more protrusions231spirally disposed around the elongate body205along the longitudinal length of the body. Adjacent spiral or helical protrusions231define one or more fluted regions236therebetween, also spirally disposed around the elongate body.FIG.3Bshows an elongate body205comprising a plurality of protrusions232resulting from cutting away or otherwise removing portions of the spirally disposed protrusions231shown inFIG.3A. For example, as shown, a plurality of radial cuts may be made to elongate body to define the plurality of protrusions232. A plurality of fluted regions237may be defined between remaining portions of adjacent helical protrusions. Cutting away or removing portions of the spiral protrusions231as shown inFIG.3Bcan further decrease the contact area between the stem and the bone, thus allowing the therapeutic agent to flow more freely along the medullary canal.

In the embodiment ofFIG.3A, a plurality of outlet holes (not shown) may extend along a helical or spiral line, such as along the helical or spiral fluted regions236. In the embodiment shown inFIG.3B, the plurality of outlet holes240may disposed in the fluted regions237, such that the holes extend about a plurality of rings around the circumference of the elongate body.

Adjustable Height Manifold

FIGS.4A and4Bshow an adjustable height manifold300suitable for incorporation with a therapeutic agent delivery system for a knee such as inFIGS.1A-1B. The adjustable height manifold300is one example of a coupling member that can couple the 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 in a patient. The adjustable height manifold further enables the adjustment of the distance between the two stems, such that the delivery system may be configured to optimally accommodate the anatomy of the patient. The adjustable height manifold300may comprise a housing315, a rotating nut320, and an adjustable connector325. The rotating nut320and adjustable connector325may be coupled to the housing315, and configured so as to allow the manifold height305to be increased or decreased, based on the desired set distance between the two stems for a patient. Rotating the nut320in clockwise and counterclockwise directions can collapse or extend the manifold, by translating the adjustable connector along a longitudinal axis310of the manifold.FIG.4Ashows the adjustable height manifold300in a collapsed configuration, such that the manifold height305is relatively short and the manifold can thus fit a patient who requires a shorter set distance between the two knee stems.FIG.4Bshows the adjustable height manifold300in an extended configuration, such that the manifold height305is relatively long and the manifold can thus fit a patient who requires a longer set distance between the two knee stems.

The adjustable height manifold300further comprises a first stem connector342and a second stem connector344, disposed on opposite sides of the housing. The first stem connector342may be configured to couple to a first end of a first intramedullary stem, and the second stem connector344may be configured to couple to a first end of a second intramedullary stem. The first stem connector342may be coupled to the adjustable connector325, while the second stem connector344may be coupled to the housing315. Each stem connector may comprise a connection mechanism to couple to a corresponding connection mechanism disposed on the first end of the intramedullary stem. The first and second stem connectors may comprise different connection mechanisms, or they may comprise identical connection mechanisms. In preferred embodiments, the first and second stem connectors comprise identical connection mechanisms, 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 one another can allow proper and simultaneous coupling of the manifold to each stem during the implantation of the delivery system in a patient using the same actuation motion for both stems.

FIG.5is an exploded view of the adjustable height manifold300ofFIGS.4A-4B. The adjustable height manifold300comprises a housing315, a rotating nut320having a scalloped outer surface to provide gripping regions for an operator's fingers and internal threads, and an adjustable connector325, wherein the three components are axially aligned along a longitudinal axis310of the manifold. The manifold further comprises a manifold pin330, configured to secure the coupling of the adjustable connector the housing and control the range of motion of the adjustable connector. The adjustable connector comprises a first stem connector342, configured to couple to a first intramedullary stem. The housing comprises a second stem connector344, configured to couple to a second intramedullary stem. The housing further comprises an inlet335coupled thereto, the inlet configured to fluidly couple to a source of the therapeutic agent (not shown) to be delivered to the patient. The housing is configured to couple to the rotating nut and slidably receive the adjustable connector. The rotating nut is configured to threadably engage the adjustable connector, so as to cause the adjustable connector to extend outwards from housing along the longitudinal axis310, or retract inwards into the housing along the longitudinal axis when the nut is rotated.

FIGS.6A-6Eshow an exemplary embodiment of a housing315of the adjustable height manifold300ofFIGS.4A-4B.FIG.6Ais a perspective view,FIG.6Bis a side view,FIG.6Cis a top view,FIG.6Dis a bottom view, andFIG.6Eis a vertical cross sectional view (cross section A-A ofFIG.6B) of the housing315. The housing315comprises an inlet335to fluidly couple to a source of the therapeutic agent, and a housing channel340(best seen inFIG.6E) extending along the longitudinal axis310through the housing. The housing channel340is in fluid communication with the inlet335, such that the therapeutic agent added to the therapeutic agent delivery system through the inlet can be distributed to other components of the delivery system through the housing channel. The inlet335may comprise a barbed outer surface, to securely engage the inner surface of a tube (best seen inFIG.28A) supplying the therapeutic agent. The housing may further comprise a concave groove345, disposed at least partially or completely about the circumference of the housing thereby minimizing profile of the tubing/housing assembly. The groove can allow for placement of tubing supplying the therapeutic agent, coupled to the inlet335.

The housing315further comprises a second stem connector344, configured to couple to an intramedullary stem such as any intramedullary stem described herein. The housing channel340can extend through the stem connector344, such that the housing channel can be fluidly coupled to a stem channel of a stem coupled to the stem connector. The stem connector344may comprise any mechanism for connecting the coupling member to the stem (e.g., flanged region, dovetail joints, snap buckle, winged nut, etc.), as described in further detail herein.

The housing channel340may be configured to have a geometry that allows the adjustable connector disposed in the channel to slide axially along the longitudinal axis310, while preventing the adjustable connector from rotating within the channel. For example, the channel340may comprise two flat inner surfaces347disposed opposite one another, configured to interface with two flat side surfaces of the of adjustable connector. The channel may further comprise two rounded side inner surfaces349, configured to interface with two corresponding rounded surfaces of the adjustable connector. For example, the rounded inner surfaces347may comprise concave surfaces, while the rounded side surfaces of the adjustable connector may comprise convex surfaces. The interfacing of the flat inner surfaces of the housing channel with the flat side surfaces of the adjustable connector can prevent the adjustable connector from rotating therein, ensuring that the adjustable connector moves only slidably, not rotatably, within the housing channel. Preventing rotation of the adjustable connector, which comprises the first stem connector342, can ensure that the orientation of the second stem connector344remains fixed with respect to the orientation of the first stem connector, even when the rotating nut320is rotated. The fixed orientation of the first and second stem connectors with respect to one another can ensure that the manifold can easily couple to both the first stem and the second stem. 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 the implantation of the delivery system in a patient, by obviating the potential need to rotate one or more intramedullary stems after the stems have already been inserted into the patient's medullary cavities.

The housing may further comprise one or more prongs355, disposed about the periphery of the housing channel340and projecting longitudinally from housing. The prongs may comprise four prongs as shown inFIGS.6A-6E, each internal surface of the prong configured to engage each of the four sides of the adjustable connector to be disposed in the housing channel. Two of the prongs, disposed opposite one another, can be configured to have the flat inner surfaces347of the housing channel, while two of the remaining prongs, also disposed opposite one another, can be configured to have the rounded inner surfaces349of the housing channel. One or more of the prongs may further comprise an outward facing lip357disposed at the edge of the prong. The lip357may be configured to engage a corresponding manifold groove in the rotating nut as described in further detail herein, so as to securely couple the rotating nut to the housing and prevent axial movement of the rotating nut along the longitudinal axis310during rotation of the nut. The lip357may further comprise chamfers359, configured to facilitate the coupling of the rotating nut to the housing by guiding the lip into the manifold groove of the nut.

The housing may further comprise a housing pin hole360, configured to receive a portion of the manifold pin. The pin hole360may be disposed on a prong355configured to engage the rotating nut, such that the pin hole360can be aligned with a nut pin hole in the rotating nut also configured to receive the manifold pin. When fully assembled, the manifold pin can be disposed partially in the housing and partially in slot in the adjustable connector disposed within the housing channel, to create a hard stop to prevent the manifold assembly from coming apart, as described in further detail herein. The housing pin hole360may be dimensioned to ensure the retention of the manifold pin within the pin hole. For example, the housing pin hole can have a diameter that is substantially equal to the diameter of the portion of the manifold pin configured to be disposed in the housing, such that the pin can be press fit into the housing pin hole.

FIGS.7A-7Cshow an exemplary embodiment of a rotating nut320of the adjustable height manifold300ofFIGS.4A-4B.FIG.7Ais a perspective view,FIG.7Bis a top view, andFIG.7Cis a vertical cross sectional view (cross section A-A ofFIG.7B) of the rotating nut320. The rotating nut320comprises a plurality of threads362disposed on a portion of its inner surface. The threads362may be configured to engage corresponding threads on a portion of the adjustable connector, such that rotation of the nut320about the adjustable connector can cause axial movement of the adjustable connector along the longitudinal axis of the manifold. The nut320may further comprise a manifold groove364disposed circumferentially about the inner surface of the nut. The manifold groove may be configured to receive one or more lips disposed on one or more prongs of the housing as described herein, so as to lock the nut onto the housing while still allowing rotation of the nut relative to the housing. The nut may further comprise chamfers366disposed below the manifold groove, extending circumferentially about the inner surface of the nut. The chamfers366can be configured to correspond to the chamfers of a housing lip, so as to guide the lip into the manifold groove. The nut may further comprise a nut pin hole368disposed on a portion of the nut below the threads362, the nut pin hole configured to receive the manifold pin therethrough. During assembly of the manifold, the manifold pin may be pushed into and completely through the body of the rotating nut, to dispose the pin partially within the housing and partially within the adjustable connector and thereby avoiding physical obstruction of the rotation of the nut by the pin. Accordingly, when the manifold is completely assembled, the manifold pin does not traverse any portion of the rotating nut, such that the rotating nut can rotate freely. The nut pin hole368may be dimensioned to facilitate the insertion of the manifold pin into and through the pin hole. For example, the nut pin hole can have a diameter that is greater than the diameter of the largest portion of the manifold pin, such that the pin can easily pass through the nut pin hole.

FIGS.8A-8Dshow an exemplary embodiment of an adjustable connector325of the adjustable height manifold300ofFIGS.4A-4B.FIG.8Ais a perspective view,FIG.8Bis a bottom view, andFIGS.8C and8Dare side views. The adjustable connector325comprises an adjustable connector channel370extending axially along the longitudinal axis310. The channel370extends through the length of the adjustable connector, and is configured to be in fluid communication with the housing channel340and hence with the inlet335fluidly coupled to the housing channel. The adjustable connector further comprises a first stem connector342, configured to couple to an intramedullary stem such as any intramedullary stem described herein. The connector channel370extends axially through the stem connector342, such that the channel370is in fluid communication with the stem channel of the stem coupled to the first stem connector342. The stem connector342may comprise any mechanism for connecting the coupling member to the stem (e.g., flanged region, dovetail joints, snap buckle, winged nut, etc.), as described in further detail herein.

The adjustable connector may further comprise threads372configured to engage corresponding threads of 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 comprise two flat side surfaces327and the two rounded side surfaces329, wherein the flat side surfaces may be configured to interface with the flat inner surfaces of the housing channel, and wherein the rounded side surfaces may be configured to interface with the rounded inner surfaces 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 hence the first stem connector342remains constant with respect to the orientation of the second stem connector. Moreover, this translates the rotational actuation of the nut into linear motion of the adjustable connector.

FIG.8Cshows the proximal flat side surface327aof the adjustable connector, configured to be oriented proximally with respect to the inlet of the housing. The proximal flat side surface can be configured to have an open slot374that extends through the bottom of the adjustable connector. The open slot374may be fluidly coupled to the adjustable connector channel370, as best seen inFIG.8Bshowing the bottom view of the adjustable connector. The open slot374may be configured such that when the assembled manifold is in the collapsed configuration as shown inFIG.4A, the open slot is aligned with the inlet so as to fluidly couple the inlet to the adjustable connector channel370. When the assembled manifold is in the extended position as shown inFIG.4B, the open bottom of the open slot374can ensure that the inlet remains in fluid communication with the housing channel, and thereby with the adjustable connector channel.

FIG.8Dshows the distal flat side surface327bof the adjustable connector, configured to be oriented distally with respect to the inlet of the housing. The distal flat side surface comprises a closed slot376, 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, rotating nut, and adjustable connector are assembled together. After full assembly, the manifold pin may be partially disposed in the housing, and partially disposed in the closed slot376of the adjustable connector. The manifold pin can be configured to remain engaged in the closed slot376during retraction or extension of the adjustable connector. The closed slot may be configured to have a width that is greater than the diameter of the portion of the manifold pin disposed in the slot, so as to facilitate the movement of the adjustable connector. When the assembled manifold is in the collapsed configuration as shown inFIG.4A, the manifold pin may be aligned with the top of the closed slot376. When the assembled manifold is in the extended configuration as shown inFIG.4B, the manifold pin may be aligned with the bottom of the closed slot376. The bottom of the closed slot376provides a hard stop to the extension of the adjustable connector from the housing, preventing the adjustable connector from extending any further. Thus, the closed slot376and the manifold pin can prevent the manifold assembly from coming apart.

FIG.9shows an exemplary embodiment of a manifold pin330of the adjustable height manifold300ofFIGS.4A-4B. The manifold pin330may comprise a small diameter portion332and a large diameter portion334. The small diameter portion332may be configured to engage the closed slot in the adjustable connector, while the large diameter portion334may be configured to be disposed in the manifold pin hole in the housing. As described herein, the manifold pin may be coupled to the manifold assembly by inserting the pin through the nut pin hole in the rotating nut. To facilitate the insertion of the manifold pin through the rotating nut, the large diameter portion334may have a diameter smaller than the diameter of the nut pin hole. To ensure the retention of the manifold pin within the housing, the large diameter portion334may have a diameter that is substantially equal to the diameter of the housing pin hole, such that the large diameter portion press fits into the housing pin hole. To facilitate translational motion of the adjustable connector within the housing channel, the small diameter portion322may have a diameter that is smaller than the width of the closed slot of the adjustable connector.

FIG.10Ais a top view andFIG.10Bis a vertical cross sectional view (cross section A-A ofFIG.10A) of the assembled adjustable height manifold300in the collapsed configuration, as shown inFIG.4A. The housing315is coupled to the rotating nut320via engagement of a lip357with a manifold groove364of the nut. The adjustable connector325is slidably disposed in the housing channel340, and threadably engaged with the rotating nut320. The large diameter portion334of the manifold pin330is disposed in the housing pin hole360, while the small diameter portion332is disposed within the closed slot376of 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 may be extended, by providing a hard stop when the pin hits the bottom of the closed slot376. The inlet335of the housing can be coupled to a source of a therapeutic agent to be delivered to the patient. The inlet can be fluidly connected to the housing channel340either directly or indirectly through the open slot374of the adjustable connector. When the manifold is in a collapsed configuration, the inlet can be fluidly coupled to the housing channel indirectly, through the open slot374of the adjustable connector. When the manifold is in an extended configuration, the inlet may be fluidly coupled directly to the housing channel. The housing channel can be fluidly connected to the adjustable connector channel370, so as to fluidly connect to the stem channel of the first stem, coupled to the first stem connector of the adjustable connector. The housing channel can also be fluidly connected to the stem channel of the second stem, coupled to the second stem connector of the housing. Thus, the therapeutic agent provided via the inlet335can be distributed to the first and second intramedullary stems coupled to the manifold.

Fixed Height Wedge

FIGS.11A-11Cshow a fixed height wedge400suitable for incorporation with a therapeutic agent delivery system for a knee.FIG.11Ashows a perspective view, andFIGS.11B and11Cshow side views of the wedge400. The fixed height wedge400is one example of a coupling member130that can couple the 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 in a patient. The wedge provides a relatively simpler connection between two intramedullary stems, wherein the wedge comprises a single, monolithic component rather than an assembly of a plurality of components. While the wedge height405of a wedge is fixed, the wedge may be provided in multiple sizes having various wedge heights, and the most appropriate size may be selected for each patient according to the patient's anatomy.

The fixed height wedge400comprises a first stem connector442configured to couple to a first intramedullary stem, and a second stem connector444configured 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 joints, snap buckle, winged nut, etc.), as described in further detail herein. The wedge further comprises an inlet435, configured to be coupled to a source of a therapeutic agent to be delivered to the patient. The inlet435can be fluidly connected to a wedge channel440extending along the longitudinal axis410of the wedge, through both the first stem connector and the second stem connector. Thus, the therapeutic agent provided through the inlet can be distributed via the wedge channel to the intramedullary stems coupled to the wedge.

The fixed height wedge400may additionally comprise one or more of any applicable structures and features described in relation to the adjustable height manifold300. For example, the wedge may comprise a concave groove445, analogous to the concave groove345described in relation to the housing of the adjustable height manifold. Similarly to the concave groove345, concave groove445may be disposed partially about the circumference of the wedge, so as to provide for placement of tubing coupled to the inlet.

Coupling Mechanisms

FIGS.12A-12Hillustrate an exemplary mechanism for coupling an intramedullary stem200to a coupling member130. The stem200may comprise any embodiment of an intramedullary stem as described herein, and the coupling member130may comprise any embodiment of a coupling member as described herein. The stem200comprises a first end215configured to engage the coupling member, and the coupling member130comprises a stem connector132configured to engage the first end of the stem. The stem connector132may be any stem connector coupled to any coupling member as described (e.g., stem connector342,344,442,444, etc.).FIG.12Ais a perspective view of the first end215of the intramedullary stem200.FIG.12Bis a perspective view of the stem connector132of the coupling member130.FIGS.12C and12Dare side views of a therapeutic agent delivery system100before assembly.FIG.12Eis a side view of an assembled delivery system100comprising two stems200and a coupling member130coupled together.FIG.12Fis an enlarged vertical cross sectional view of the portion of the assembled system100as indicated inFIG.12C.FIGS.12G and12Hare radial cross sections of the assembled system100along line A-A as indicated inFIG.12E, at different steps of the assembly.

As shown inFIG.12A, the first end215comprises a raised portion250disposed about a portion of the periphery of the first end. The raised portion250defines a rounded cavity251therein, configured to receive a flanged region150of the coupling member130as shown inFIG.12B. The raised portion250has a circumferential opening252configured to receive the flanged region150of the coupling member therethrough. The raised portion250further comprises a recessed lip253defining a recessed region254, as best seen inFIG.12F. The recessed region254can receive and retain the flanged region150, so as to limit axial movement of the coupling member along the longitudinal axis210of the stem. As shown inFIGS.12E and12F, the flanged region150can have a length154that is longer than the width152. The flanged region can further comprise two flat edges157extending along the length154of the flanged region, and two rounded edges159extending about the width152of the flanged region. The circumferential opening252may have a width that is greater than or equal to the width152of the flanged region150, but less than the length154of the flanged region, such that the flanged region can only enter the circumferential opening in the vertical orientation151with respect to the circumferential opening252, as shown inFIG.12G.

FIGS.12C and12Dshow the delivery system100before assembly, wherein the coupling member130is aligned for insertion into the space between two intramedullary stems200. The flanged regions150of the first stem connector132aand second stem connector132bare in the vertical orientation with respect to the circumferential openings252of the raised portions of the intramedullary stems. While aligned in this orientation, the coupling member may be pushed into the space between the two intramedullary stems such that the flanged regions are inserted through the circumferential openings of each stem, and captured into the recessed regions of the raised portions as shown inFIGS.12E,12F, and12G.

Once the flanged region150is placed within the rounded cavity251, the flanged region may be rotated in the direction shown by arrow155, as shown inFIG.12G. The flanged region may be rotated until the flanged region is disposed in the horizontal orientation153with respect to the circumferential opening252, as shown inFIG.12H. In the horizontal orientation, the flanged region can be prevented from sliding out of the rounded cavity through the circumferential opening, since the length154of the flanged region is greater than the size of the opening252. The first end215may further comprise one or more pins255disposed therein, configured to further secure the coupling between the stem and the stem connection. For example, the first end215may comprise two pins255, each pin angularly spaced at about 90° from the center of the circumferential opening252. Each rounded edge159of the flanged region150may comprise a smaller diameter edge159aand a larger diameter edge159b, such that a notch156is created at the intersection of edges159aand159b. As described, the flanged region150may be inserted through the opening252in the vertical orientation151as shown inFIG.12G, and subsequently rotated in the direction shown by arrow155, within the recessed region254of the first end215. As the flanged region rotates, the pin255can slide against the smaller diameter edge159a, until the pin hits the notch156created by the larger diameter edge159b. The pins may be configured, for example, to allow the flanged region to rotate by about 90° or a quarter turn before hitting the pins. The engagement of the notch156with the pin255can prevent further rotation of the stem relative to the coupling member. The pins255can thus provide a hard stop to the rotation of the flanged region, ensuring that the final orientation of the flanged region is the horizontal orientation153, which can prevent the flanged region from sliding out of the rounded cavity as described herein.

FIGS.13A-13Cillustrate another exemplary mechanism for coupling an intramedullary stem to a coupling member130.FIG.13Ashows a perspective view andFIG.13Bshows a top view of the coupling member130comprising the exemplary connection mechanism.FIG.13Cshows a side view of a portion of an assembled delivery system100, comprising two stems200and a coupling member130coupled together. The stem200may comprise any embodiment of an intramedullary stem as described herein, and the coupling member130may comprise any embodiment of a coupling member as described herein. The stem200comprises a first end215configured to engage the coupling member, and the coupling member130comprises a stem connector132configured to engage the first end of the stem. The stem connector132may be any stem connector coupled to any coupling member as described (e.g., stem connector342,344,442,444, etc.). Each stem connector132may comprise one or more dovetailed regions160, configured to engage one or more corresponding dovetailed regions260of the first end215of the stem200. Each stem connector132may further comprise a snap buckle162, configured to engage a corresponding snap buckle (not shown) disposed on the first end215of the stem. The snap buckle162can comprise flexible stems164that can tension centrally when the coupling member130is inserted slidingly into the stems200. The coupling member can snap into place when the coupling member is pushed past the notch166within the stems.

FIGS.14A and14Billustrate another exemplary mechanism for coupling an intramedullary stem200to a coupling member130.FIG.14Ashows the first step of assembly of the stems and the coupling member using the exemplary mechanism, andFIG.14Bshows the second step of the assembly. The stem200may comprise any embodiment of an intramedullary stem as described herein, and the coupling member130may comprise any embodiment of a coupling member as described herein. The stem200comprises a first end215configured to engage the coupling member, and the coupling member130comprises a stem connector132configured to engage the first end of the stem. The stem connector132may be any stem connector coupled to any coupling member as described (e.g., stem connector342,344,442,444, etc.). Each stem connector132may comprise one or more dovetailed regions160, configured to engage one or more corresponding dovetailed regions260of the first end215of the stem200.FIG.14Ashows the coupling member130aligned for insertion into the space between two intramedullary stems200, wherein the dovetailed regions160of the coupling member are aligned with the corresponding dovetailed regions260of the stems. The coupling member may be pushed into the space between the two stems such that the dovetailed regions160are engaged within the dovetailed regions260of the stems. Optionally, the first end215of each stem may comprise a raised portion with a circumferential opening similarly as in the embodiment ofFIGS.12A-12H, wherein the dovetailed region260is disposed within the rounded cavity defined within the raised portion. In such a configuration, the coupling member may be pushed into the space between the two stems until the dovetailed regions160hit a hard stop against the raised portions of the stems. The coupling member130or the intramedullary stem200may further comprise one or more turn stops176, configured to hold the coupling member in place once the coupling member is coupled to the stem.FIG.14Bshows the assembled delivery system100, wherein each stem200comprises a turn stop176configured to hold the coupling member130. Each turn stop can be rotatable, such that the position of the turn stop with respect to the stem and the coupling member can be adjusted. During the step of assembly as shown inFIG.14A, each turn stop may be rotated such that the turn stop does not extend beyond the first end215of each stem, thereby allowing the dovetailed region160of the coupling member slidingly engage the dovetailed region260of the stem without any physical obstruction from the turn stop. Once the coupling member is coupled to the stem, the turn stop may be rotated into the position shown inFIG.14B, such that the length of the turn stop extends over the junction between the stem and the coupling member. The turn stop can thus prevent the coupling member from sliding out of engagement with the intramedullary stem.

FIGS.14C and14Dshow a variation of the embodiment shown inFIGS.14A and14B. Instead of turn stops, the coupling member130may comprise a winged nut170, rotatably fixed onto an anterior portion of the coupling member. The winged nut170can be configured to have a length174that is greater than the width172. The length174of the nut can be greater than the height135of the coupling member. During assembly, the coupling member130may be slidingly inserted into the stems200with the winged nut170in the horizontal orientation173as shown inFIG.14A. Subsequently, the winged nut170may be rotated to so as to be in the vertical orientation171as shown inFIG.14B, such that the length174of the nut extends over the junction between the dovetailed regions160and260. In the vertical orientation, the winged nut can prevent the coupling member130from sliding out of the stems200.

Method of Use of Therapeutic Agent Delivery System for Knee

FIG.15illustrates a method1500of treating a patient's knee using the therapeutic agent delivery system for a knee as described herein. In step1505, a first intramedullary stem is positioned in the medullary canal of the femur of the patient. In step1510, a second intramedullary stem is positioned in the medullary canal of the tibia of the patient. In step1515, the height of an adjustable height manifold is adjusted to fit the joint space between the first stem and the second stem. In step1520, the adjustable height manifold is coupled to the first stem and the second stem. The adjustable height manifold may be inserted in 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 stem connections with flanged regions as described herein, configured to engage corresponding rounded cavities of the stems, the adjustable height manifold may be inserted by leading with the two rounded edges of the flanged region. In step1525, the coupling between the adjustable height manifold and the first and second stems is further secured, via appropriate steps for the connection mechanism used. For example, if the adjustable height manifold comprises the flanged region as described herein, the manifold may be rotated to securely engage the flanged region into the corresponding cavity of the stems. If the adjustable height manifold and the stems comprise dovetailed regions with turn stops as described herein, the turn stops may be rotated to extend over the junction between the stem and the manifold, so as to prevent de-coupling of the manifold from the stems. In step1530, the therapeutic agent is delivered to the medullary canals of the femur and the tibia and the joint space.

FIG.16illustrates a method1600of treating a patient's knee using the therapeutic agent delivery system for a knee as described herein. In step1605, a first intramedullary stem is positioned in the medullary canal of the femur of the patient. In step1610, a second intramedullary stem is positioned in the medullary canal of the tibia of the patient. In step1615, a fixed height wedge with an appropriate height to fit the joint space between the first stem and the second stem is selected. In step1620, the fixed height wedge is coupled to the first stem and the second stem, wherein 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 stem connections with flanged regions as described herein, configured to engage corresponding rounded cavities of the stems, the fixed height wedge may be inserted by leading with the two rounded edges of the flanged region. In step1625, the coupling between the fixed height wedge and the first and second stems is further secured, via appropriate steps for the connection mechanism used. For example, if the fixed height wedge comprises the flanged region as described herein, the fixed height wedge may be rotated to securely engage the flanged region into the corresponding cavity of the stems. If the fixed height wedge and the stems comprise dovetailed regions with turn stops as described herein, the turn stops may be rotated to extend over the junction between the stem and the fixed height wedge, so as to prevent de-coupling of the fixed height wedge from the stems. In step1630, the therapeutic agent is delivered to the medullary canals of the femur and the tibia and the joint space.

The steps of methods1500and1600are provided as examples of methods of using a therapeutic agent delivery system in accordance with embodiments. A person of ordinary skill in the art will recognize many variations and modifications of methods1500and1600based 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 as illustrated inFIGS.15and16. Some of the steps may comprise sub-steps. Many of the steps may be repeated as many times as appropriate or necessary.

Therapeutic Agent Delivery System for Hip

FIGS.17A and17Bshow an exemplary therapeutic agent delivery system500for a hip.FIG.17Ais a perspective view of the assembled delivery system, whileFIG.17Bis an exploded perspective view of the system. The delivery system500comprises a femoral stem510and a femoral head520. The femoral stem510can be configured to disposed in a femoral medullary canal of a patient. The femoral head520can be configured to be disposed in an acetabulum of the patient. The femoral stem may comprise an inlet535configured to couple to a source of a therapeutic agent to be delivered to the patient. The inlet can be fluidly coupled to a channel in the femoral stem, so as to allow the therapeutic agent to be distributed in the femoral medullary canal. The femoral stem and the femoral head may be configured to removably couple together so as 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 in the acetabular joint space. The femoral stem and the femoral head may be configured to couple in a stable configuration, so as to maintain a desired distance between the femoral stem and the femoral head through the length of use of the therapeutic agent delivery system in the patient. Optionally, the femoral stem and the femoral head may be connected in a fashion that allows the distance between the stem and the head to be adjusted to fit the anatomy of the patient. The system500may further comprise a stem plug530, configured to couple to an end of the femoral stem.

Femoral Stem

FIGS.18A-18Dshow an exemplary femoral stem600suitable for incorporation with a therapeutic agent delivery system for a hip.FIG.18Ais a perspective view,FIG.18Bis a side view,FIG.18Cis a bottom view, andFIG.18Dis a side cross-sectional view of the femoral stem600. The femoral stem600comprises an elongate body605having a longitudinal axis610, the elongate body having a first end615and a second end620opposite the first end. The elongate body comprises a neck region650disposed near the first end615, wherein the neck region may be configured to couple to the femoral head. The second end620may be configured be disposed in the femoral medullary canal. The femoral stem600further comprises an inlet535, configured to be coupled to a source of the therapeutic agent. The inlet535is in fluid communication with a stem channel625extending between the first end615and the second end620, as best seen inFIG.18D. The stem channel can be configured to deliver the therapeutic agent through the stem and to the medullary canal. Further, the stem channel can be configured to fluidly couple to one or more channels in the femoral head.

The elongate body605may have one or more structures or features that are similar to the intramedullary stem200described previously. For example, the femoral stem600may comprise a plurality of protrusions630, protruding radially outward from the elongate body605. The plurality of protrusions may comprise any number of protrusions having any appropriate shape, size, or configuration to engage the medullary canal in a stable fashion. For example, the protrusions may comprise elongate fins extending along the longitudinal length of the elongate body, as shown inFIGS.18A-18D. In one exemplary embodiment, the plurality of protrusions may comprise four fins, spaced equally at about 90° about the longitudinal axis610of the elongate body. Of course this is not intended to be limiting, and the number of fins may be any number, such as three fins spaced approximately 120 degrees apart, five fins spaced approximately 72 degrees apart, etc. The plurality of protrusions630and the elongate body605may be formed separately and coupled together. Alternatively or in combination, the plurality of protrusions630may be formed by removing material from the elongate body605, such that the plurality of protrusions and the elongate body are formed as a single member. Adjacent protrusions630may define one or more fluted regions635therebetween, the fluted regions radially recessed compared to the protrusions.

The plurality of protrusions and fluted regions can be configured to minimize the surface area of the stem contacting the bone lining the medullary canal, such that the area of the bone flushed with the therapeutic agent may be maximized. For example, the plurality of protrusions and fluted regions can be configured such that less than 50% of the surface area of the stem is in contact with the bone lining the medullary canal. Of course this is not intended to be limiting and one of skill in the art will appreciate that any percentage of surface area of the stem may contact the bone. The stem may comprise a plurality of identical fluted regions defined by a plurality of elongate fins, distributed symmetrically about the longitudinal axis610of the stem, as shown inFIGS.18A-18D. Alternatively, a plurality of fluted regions may be distributed asymmetrically about the longitudinal axis of the stem, and/or may have different shapes or sizes. For example, the elongate body605may comprise protrusions and fluted regions as described in relation toFIGS.3A and3B.

The femoral stem600may further comprise a plurality of outlet holes640in fluid communication with the stem channel625. The plurality of outlet holes640may be configured to deliver the therapeutic agent, distributed through the stem channel625, to the femoral medullary canal, as well as adjacent tissue including the joint. The plurality of outlet holes may be disposed in a fluted region635, so as to deliver the therapeutic agent to the area of the bone not in contact with the femoral stem. The plurality of outlet holes may comprise any number of outlet holes having any appropriate size, shape, or distribution. For example, the plurality of outlet holes may include a plurality of equally sized and spaced holes that extend axially along a line substantially parallel to the longitudinal axis610of the stem, as shown inFIGS.18A-18D. Alternatively, the plurality of outlet holes may extend along a helical or spiral line as shown inFIG.3A, or the holes may extend about a plurality of rings around the circumference of the elongate body, as shown inFIG.3B. The plurality of outlet holes may comprise holes having an identical shape and/or size, or holes having various shapes and/or sizes. Varying the hole size may allow further fluid control of therapeutic agent as it exits different regions of the stem.

The stem channel625may be a through hole that extends from the first end615to the second end620through both the first end and the second end, such that the elongate body comprises an open second or distal end. The system may further comprise a plug, shown inFIG.19, configured to couple to the open second end of the stem, so as to close the second end and thereby create a blind channel. Alternatively, the stem channel625may be a blind channel, wherein the second end of the elongate body is closed. In configurations wherein the second end is open, the therapeutic agent may exit the stem channel into the medullary canal through the second end and/or through a plurality of outlet holes disposed along the elongate body605as described herein. If the stem comprises only the stem channel625extending through the first and second ends, without the plurality of outlet holes, the therapeutic agent may exit the stem channel only through the second end. In configurations wherein the second end of the stem is closed, the therapeutic agent may exit the stem channel into the medullary canal only through the plurality of outlet holes.

The neck region650extends along a neck axis655, disposed at an angle660with respect to the longitudinal axis610of the elongate body605. The angle660may be in a range from about 120° to about 160°, about 130° to about 150°, about 140° to about 150°, or about 145°. The neck region may comprise one or more connection mechanisms or features to couple to the femoral head. For example, as shown, the neck region may comprise a plurality of threads670, configured to threadably engage complementary threads on the femoral head.

The femoral stem600may be tapered to fit the medullary canal. For example, the elongate body605and/or the plurality of protrusions630may be tapered from the first end615to the second end620, as shown, so as 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, wherein the extent of the taper may be in a range from about 0.1° to about 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 a medullary canal of a specific type of bone.

FIG.19shows a stem plug530suitable for incorporation with any therapeutic agent delivery system as described herein. The stem plug530may comprise a smaller diameter region535and a larger diameter region540. The smaller diameter region may be configured to be press-fit into an open second end of an elongate body of any intramedullary stem or hip stem as described herein.

Femoral Head

FIGS.20A and20Bshow an exemplary embodiment of a femoral head700, suitable for incorporation with a therapeutic agent delivery system for a hip.FIG.20Ais a side view, andFIG.20Bis a side cross-sectional view of the femoral head700, along line A-A as shown inFIG.20A. The femoral head700can comprise the shape of a truncated sphere, wherein the truncated base715of the head is configured to couple to the femoral stem. The femoral head700comprises a head central channel725, extending axially along a central axis710of the femoral head. The central channel725is configured couple to the neck of the femoral stem, and thereby be in 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 outlet holes740, fluidly coupled to the central channel725. The outlet holes may be configured to extend radially outwards from the central channel. Thus, a therapeutic agent may be supplied to the delivery system via an inlet of the femoral stem, move through the stem channel into the central channel725of the femoral head, and exit into the acetabular joint space through the outlet holes740.

The base715may comprise one or more mechanisms for coupling the femoral head to the neck region of the femoral stem. For example, as shown, a portion of the central channel725near the base715may comprise a plurality of threads770, configured to threadably engage a plurality of complementary threads of the femoral stem neck. A threaded connection between the femoral head and the femoral stem neck can 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 be further configured to receive one or more set screws near the base, wherein the set screws can fix the distance between the femoral head and the femoral stem once the distance is appropriately set. For example, as shown inFIG.20B, the base may comprise two set screw receiving regions780, wherein each set screw receiving region comprises a plurality of threads785to engage a set screw having complementary threads. The set screw receiving regions can extend radially outwards from the central channel, such that the ends of the set screws can be directly or indirectly coupled to the neck of the femoral stem disposed within the central channel. WhileFIG.20Bshows two set screw receiving regions radially offset from one another by about 180°, the femoral head may comprise any number of set screws distributed in any appropriate configuration. For example, the femoral head may comprise three set screw receiving regions radially offset from one another by about 120°, or four set screw receiving regions radially offset from one another by about 90°.

FIGS.21A and21Bshow another exemplary embodiment of a femoral head800, suitable for incorporation with a therapeutic agent delivery system500for a hip. The femoral head800is partially hollowed, so as to reduce the material mass and weight of the femoral head. The femoral head800comprises a central channel825, configured to be in fluid communication with the stem channel of the femoral stem as described herein. The femoral head further comprises an inner shell830and an outer shell835, wherein the inner and outer shells are thin, truncated spherical shells disposed about the periphery of the femoral head. The inner shell830is connected to the material disposed about and defining the central channel825. The outer shell835is connected to the inner shell830via a plurality of support struts845extending between the inner shell and the outer shell. The inner shell defines an inner cavity855between the inner shell and the material defining the central channel. The inner cavity855is hollow, and configured to be sealed against the central channel and the inner shell, such that no fluid can enter the inner cavity during use of the delivery system. The inner shell and the outer shell define an outer cavity850therebetween, wherein the outer cavity850is fluidly coupled to the central channel825. The outer shell comprises a plurality of outlet holes840, such that fluid in the outer cavity850can exit the femoral head through the outlet holes. Thus, the therapeutic agent supplied through an inlet of a femoral stem can move through the stem channel into the central channel825of the femoral head800, into the outer cavity850, and through the outlet holes840into the acetabular joint space. Components of the femoral head800may be formed via3D printing or laser sintering.

FIG.22shows another exemplary embodiment of a femoral head900, suitable for incorporation with a therapeutic agent delivery system for a hip. The femoral head900comprises a central channel925, configured to be in fluid communication with the stem channel of the femoral stem as described herein. The femoral head further comprises a plurality of hollow tubes940extending radially outwards from the central channel925and fluidly coupled to the central channel. The femoral head further comprises an outer shell935, a thin, truncated spherical shell disposed about the periphery of the femoral head. The outer shell935is coupled to the plurality of hollow tubes940, such that the hollow tubes940extend through the thickness of the outer shell. The hollow tubes, the outer shell, and the material disposed about defining the central channel together define a plurality of inner cavities855, which are hollow and configured to be fluidly sealed, such that no fluid can enter the inner cavities during use of the delivery system. Thus, the therapeutic agent supplied through an inlet of a femoral stem can move through the stem channel into the central channel925of the femoral head900, into the plurality of hollow tubes940, and into the acetabular joint space. The internal diameter of the hollow tubes and/or the thickness of the hollow tubes may be varied to control the flow of fluid within the femoral head, and to adjust the amount of support provided by the hollow tubes to the outer shell to protect the integrity of the outer shell.

Coupling Mechanisms

FIGS.23A and23Bshow exemplary mechanisms for coupling a femoral head520to a femoral stem510. The femoral head520may comprise any femoral head as described herein, such as femoral heads700,800, and900described in relation toFIGS.20A-22. The femoral stem510may comprise any femoral stem as described herein, such as any embodiment of the femoral stem600described herein.FIG.23Ais a side cross sectional view of a femoral head520coupled fixedly to a femoral stem510. The neck region650of the stem is fixedly coupled to a portion of the central channel725of the femoral head, such that the length540of the neck that engages the femoral head is fixed. For example, the neck650may be press-fitted into the central channel725, such that the neck advances into the central channel by a pre-determined length. The neck650may comprise regions having different diameters so as to create a notch between the regions, wherein the notch can provide a stop against the femoral head surface when the neck650has been advanced into the central channel by the pre-determined length. In a delivery system incorporating such a connection mechanism, the distance between the femoral head and the femoral stem is fixed.FIG.23Bis a side cross sectional view of a femoral head520coupled adjustably to a femoral stem510. The neck region650of the stem is adjustably coupled to a portion of the central channel725, for example via engagement of threads670disposed on the neck650of the stem with complementary threads770disposed on a portion of the central channel725. The length540of the neck that engages the central channel can thereby be increased or decreased by threadably rotating the femoral head about the femoral stem. As the femoral head is rotated to axially translate the head farther away from the femoral stem, the length540decreases, and the distance between the femoral head and the femoral stem increases such that the delivery system can 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 length540increases, and the distance between the femoral head and the femoral stem decreases such that the delivery system can be suitable for patients requiring a shorter set distance between the femur and the acetabulum. In a delivery system incorporating such a connection mechanism, the distance between the femoral head and the femoral stem can be thus adjusted to accommodate the anatomy of a patient.

FIGS.24A and24Bshow an exemplary mechanism for locking a set distance between a femoral head520and a femoral stem510of a therapeutic agent delivery system for a hip. The femoral head520may comprise any femoral head as described herein, such as femoral heads700,800, and900described in relation toFIGS.20A-22. The femoral stem510may comprise any femoral stem as described herein, such as any embodiment of the femoral stem600described herein.FIG.24Ais a perspective view andFIG.24Bis a bottom view of a femoral head520comprising the exemplary mechanism. As described herein, a femoral head520may comprise a pair of set screw receiving regions780near the base715of the head, which can receive a pair of set screws configured to engage the femoral stem neck disposed in the central channel725of the femoral head, so as to fix the position of the stem neck therein. The femoral head may further comprise a pair of blocks550disposed within the set screw receiving regions780, adjacent to the central channel725. Each block can be coupled with a set screw554, wherein the block may comprise a rounded cavity to receive the end of the set screw, and wherein the end of the set screw may be free to rotate within the rounded cavity. Two dowel pins552may be coupled to the block-set screw assembly so as to limit the translational motion of the set screw relative to the block. Rotation of the set screw within the set screw receiving region can cause the block coupled thereto to translate radially inwards or outwards. The block may be translated radially inwards until the block engages and pushes against the neck region of the stem disposed within the central channel, thereby preventing further rotation of the femoral head about the femoral stem. The block can distribute the forces between the neck and the set screw across a broader surface, to more effectively lock the position of the neck. WhileFIGS.24A-24Fshow a pair of set screw receiving regions radially offset from one another by about 180°, the locking mechanism may comprise any number of set screws distributed in any appropriate configuration. For example, the femoral head may comprise three set screw receiving regions radially offset from one another by about 120°, or four set screw receiving regions radially offset from one another by about 90°.

FIGS.24C-24Fillustrate a method of assembling the locking mechanism ofFIGS.24A and24B.FIG.24Cshows the femoral head520and components of the locking mechanism before assembly. As described previously, the femoral head may comprise one or more set screw receiving regions780extending radially outwards from the central channel725. Each set screw receiving region can be configured to receive a set screw554, a block550, and a pair of dowel pins552.FIG.24Dshows the first step of assembly of the locking mechanism, wherein the block550is coupled to the femoral head520. The femoral head may comprise a block receiving region556adjacent the central channel725, and the block may be inserted into block receiving region from the base715of the femoral head. As best seen inFIG.24B, the block550may have a concave surface551on a first end and a round indent553on a second end opposite the first end. As shown inFIG.24C, the block may be inserted into the femoral head with the concave surface directed radially inwards, facing the central channel, and the round indent directed radially outwards.FIG.24Eshows the second step of assembly of the locking mechanism, wherein the set screw554is coupled to the femoral head520. As best seen inFIG.24B, the set screw receiving region780comprises set screw threads785, configured to engage the thread region of the set screw. The set screw may be threadably engaged with the set screw threads within the set screw receiving region, to translate the set screw radially inwards within the set screw receiving region. As best seen inFIG.24D, the set screw can comprise a set screw head555, an unthreaded region of the set crew having a smaller diameter than the threaded region of the set screw. During the step shown inFIG.24E, the set screw can be translated radially inwards until the set screw head is disposed within the round indent553of the block550(as best seen inFIG.24B).FIG.24Fshows the final step of assembly of the locking mechanism, wherein the dowel pins552are coupled to the femoral head. The two dowel pins may be pressed into the block550with an interference fit. When the dowel pins are pressed completely into the block, the leading ends of pins can engage the set screw head555, such that the pins prevent the set screw from separating from the block. For example, the screw head may comprise a concave groove557(as best seen inFIGS.24B and24D) extending about the circumference of the set screw head555. The leading ends of the dowel pins may be configured to engage the concave groove when the pins are pressed completely into the block (as best seen inFIG.24B) such that the set screw cannot separate from the block.

Optional Features

FIGS.25A and25Bshow an exemplary embodiment of a therapeutic agent delivery system500for a hip, further comprising an acetabular cup560.FIG.25Ais a perspective view andFIG.25Bis a side cross sectional view of the system500. The delivery system500may further comprise a separate acetabular cup560, configured to be inserted into the acetabular space of the hip joint. The femoral head520thus interfaces with the acetabular cup, rather than interfacing directly with the acetabulum of the patient. The acetabular cup may comprise a plurality of fluted external structures565, through which fluid may flow to reach the acetabulum.

FIG.26shows an exemplary embodiment of a therapeutic agent delivery system500for a hip. The therapeutic agent delivery system500as described herein may be configured to function as the final implant, rather than as a temporary implant intended for the first stage of a two-stage re-implantation procedure. The system500may comprise a femoral stem510such as any femoral stem described herein, a femoral head520such as any femoral head described herein, and a stem plug530. In addition, the system500may further comprise a liner570and an acetabular cup560configured to be implanted between the femoral head520and the acetabulum of the patient. Fluid may flow through the femoral head and out the liner and acetabular cup, into the joint space and the acetabulum. Optionally, alternatively to or in combination with the inlet535of the femoral stem510, the acetabular cup560may comprise a separate inlet, through which the therapeutic agent may be supplied.

Method of Use of Therapeutic Agent Delivery System for Hip

FIG.27illustrates a method1700of treating a patient's hip using a therapeutic agent delivery system for a hip as described herein. In step1705, a femoral stem is positioned in the medullary canal of the patient's femur. In step1710, a femoral head is coupled to the femoral stem. In step1715, which is optional, the distance between the femoral stem and the femoral head is adjusted such that the delivery system best fits 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 head may be adjusted by threadably rotating the femoral head about the stem. Step1715may further comprise locking the distance between the femoral head and the femoral stem, for example via the set screw mechanism described in relation toFIGS.24A-24F. In step1720, the femoral head is positioned in the patient's acetabulum. In step1725, the therapeutic agent is delivered to the medullary canal and the acetabulum via the delivery system.

The steps of method1700are provided as examples of a method of using a therapeutic agent delivery system in accordance with embodiments. A person of ordinary skill in the art will recognize many variations and modifications of the method1700based on the disclosure provided herein. For example, some steps may be added or removed. Some of the steps may comprise sub-steps. Many of the steps may be repeated as many times as appropriate or necessary. One or more steps may be performed in a different order than as illustrated inFIG.27. For example, the femoral head and the femoral stem may be coupled together and, if necessary, the distance between the head and stem adjusted, before the assembled device is positioned in the patient's femur and acetabulum.

Additional Features of Therapeutic Agent Delivery Systems

In any of the therapeutic agent delivery systems described herein, the flow of fluid within the system may be adjusted by modifying one or more dimensions or configurations of the channels and/or outlet holes. For example, the diameter of the channels and/or outlet holes may be increased or decreased, or channels may be configured to have varying diameters along the length of the assembly, to bias the flow of fluid in a particular direction. Angles at junctures between the channels may also be varied to bias fluid flow within the system.

Any therapeutic agent delivery system as described herein may further comprise a pump, operatively coupled to the inlet. The pump may be configured to pump the therapeutic agent into one or more channels of the system.

Any therapeutic agent delivery system as described herein may optionally comprise a vacuum pump that may be coupled to an inlet or an outlet of the system. The vacuum pump may be configured to remove any unwanted or excess fluids from the body of the patient, before introducing the therapeutic agent to the body using the delivery system.

Any therapeutic agent delivery system as described herein may optionally comprise a port under the skin that is coupled to an inlet or outlet of the delivery system. The port may be accessed via a needle or syringe as necessary.

FIGS.28A and28Billustrate the use of negative pressure wound therapy with a therapeutic agent delivery system for a knee. Negative pressure wound therapy may optionally be used in tandem with the therapeutic agent delivery system, in order to further improve the prognosis of the treatment. The wound of the patient can be packed with sponges90and optionally covered with a wound dressing85coupled to a vacuum pump80. Actuation of the vacuum pump can then draw blood and nutrients to infected areas. As shown inFIG.28B, optional sponges for negative pressure wound therapy may also be provided as strips95of sponges configured to be disposed along the intramedullary stems200of the delivery system100. The strips of sponges may be trimmed to fit the space along the fluted regions235of any intramedullary stem200. Negative pressure wound therapy can pull material through the sponge and into the plurality of outlet holes of the stem, into the stem channel, and out of the body through the inlet or outlet of the system. While a delivery system for a knee is shown inFIGS.28A and28B, negative pressure wound therapy may be used with any therapeutic agent delivery system as described herein, including delivery systems for joints other than the knee.

FIG.29shows an optional cover75for an intramedullary stem200, suitable for incorporation with any therapeutic agent delivery system described herein. The cover75may comprise a thin, cone-shaped sponge, configured to fit inside the medullary canal as an interface between the bone and the intramedullary stem200. The cover can be configured to cover the substantially all of the elongate body205of the stem, and thus evenly interface with the intramedullary bone. When covered with the cover75, 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., shape, size, number, or configuration of protrusions and fluted regions). This exemplary configuration may also be used in conjunction with the negative pressure wound therapy previously described.

FIG.30shows an exemplary embodiment of a therapeutic agent delivery system1000. The delivery system1000may comprise an intramedullary stem1010which may be any intramedullary stem as described herein, such as intramedullary stems110,120, or200, or femoral stems510or600. The stem1010may comprise a stem channel1025that extends through both the first end1015and the second end1020of the stem. Instead of receiving the therapeutic agent from a coupling member coupled to the stem, the stem1010may be configured to receive a catheter1030supplying the therapeutic agent through the first end1015. The therapeutic agent may be delivered to the medullary canal through the second end1020.

FIGS.31A and31Bshow exemplary embodiments of therapeutic agent delivery systems with inlets and outlets.FIG.31Ashows an exemplary embodiment of a therapeutic agent delivery system100for a knee, as described herein. The delivery system100may comprise an inlet140, configured to couple to a source of the therapeutic agent. The inlet140may be fluidly coupled to one or more channels of a coupling member130, and the one or more channels of the coupling member may be fluidly coupled to the stem channels in the stems200. Optionally, the system may further comprise an outlet145, configured to remove the therapeutic agent and/or any other fluid from the body. The stems and the coupling member may comprise 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.31Bshows an exemplary embodiment of a therapeutic agent delivery system500for a hip, as described herein. The delivery system500may comprise an inlet535, configured to couple to a source of the therapeutic agent. The inlet535may be fluidly coupled to a channel of the femoral stem510, and the stem channel may be fluidly coupled to a central channel of the femoral head520coupled to the femoral stem. Optionally, the system may further comprise an outlet545, configured to remove the therapeutic agent and/or any other fluid from the body. The femoral stem and the femoral head may comprise internal channels configured to direct fluid between the inlet and the channels of the stem and the head, and between the outlet and the channels of the stem and the head. Other aspects of the system may generally take the same form as previously described.

FIGS.32A and32Billustrate an exemplary configuration for the internal channels of an intramedullary stem.FIG.32Ais a sectional view andFIG.32Bis a cross sectional view of an intramedullary stem1100comprising a plurality of separate internal fluid paths. Stem1100may comprise any intramedullary stem as described herein, such as intramedullary stems110,120, or200, or femoral stems510or600. Stem1100may comprise a first internal channel1110centrally disposed along the longitudinal axis of the stem, and a second internal channel1120disposed about the periphery of the first internal channel (the second internal channel can 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 outlet holes1115, each of the first plurality of outlet holes extending from the first internal channel, through the second internal channel, to an outer wall of the stem (such as a fluted region1135of the stem). The second internal channel may be fluidly coupled to a second plurality of outlet holes1125, each of the second plurality of outlet holes extending from the second internal channel directly to an outer wall of the stem. The first internal channel and the second internal channel may be fluidly sealed against one another, and each of the first plurality of outlet holes1115may cross over the second internal channel1120through a side channel that is fluidly sealed against the second internal channel. Therefore, the first internal channel and the second internal channel can form two separate internal fluid paths, each of which can be used to deliver fluid to the tissue or remove fluid from the tissue. As shown inFIG.32B, the first plurality of outlet holes1115and the second plurality of outlet holes1125may 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 fluid path.

FIGS.33A-33Cillustrate another exemplary configuration for the internal channels of an intramedullary stem.FIG.33Ais a perspective view,FIG.33Bis a vertical cross sectional view, andFIG.33Cis a horizontal cross sectional view of an intramedullary stem1200comprising a plurality of separate internal fluid paths. Stem1200may comprise any intramedullary stem as described herein, such as intramedullary stems110,120, or200, or femoral stems510or600. Stem1200may comprise a first internal channel1210running along the length of the stem, and a second internal channel1220adjacent the first internal channel, also running along the length of the stem. The first and second internal channels may be fluidly sealed against one another, such that each channel forms a separate internal fluid path. The first internal channel may be fluidly coupled to a first plurality of outlet holes1215, each of the first plurality of outlet holes extending from the first internal channel to an outer wall of the stem (such as a fluid region1235of the stem), without cutting through the second internal channel. The second internal channel may be fluidly coupled to a second plurality of outlet holes1225, each of the second plurality of outlet holes extending from the second internal channel to an outer wall of the stem, without cutting through the first internal channel. Therefore, the first internal channel and the second internal channel can form two separate internal fluid paths, each of which can be used to deliver fluid to the tissue or remove fluid from the tissue. As shown inFIG.33A, the first plurality of outlet holes1215and the second plurality of outlet holes1225may 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 fluid path.

An intramedullary stem comprising two or more separate internal fluid paths as shown inFIGS.32A-33Cmay be used to simultaneously deliver fluid to and remove fluid from the tissue, without cross-contaminating the fluid to be delivered with the fluid to be removed. For example, a first internal channel may be fluidly coupled to an inlet (such as inlet140ofFIG.31Aor inlet535ofFIG.31B) configured to receive a therapeutic agent from a source, while the second internal channel may be fluidly coupled to an outlet (such as outlet145ofFIG.31Aor outlet545ofFIG.31B) configured to remove fluid from the tissue. In this configuration, the first plurality of outlet holes can deliver the therapeutic agent to the tissue, while the second plurality of outlet holes can remove fluid from the tissue, thereby allowing simultaneous delivery of therapeutic agent and removal of fluid from the 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 can be achieved, without cross-contamination between the two agents before the agents reach the tissue.

FIGS.34-36show exemplary embodiments of therapeutic agent delivery systems adapted for use in various joints. While descriptions of the therapeutic agent delivery systems are primarily directed to systems to be used in the knee or in the hip, systems comprising similar components and features may be used to treat any other joint.FIG.34shows an exemplary embodiment of a delivery system1200for a shoulder,FIG.35shows an exemplary embodiment of a delivery system1300for an ankle, andFIG.36shows an exemplary embodiment of a delivery system1400for a spine. In the embodiments shown, the delivery systems1200,1300, and1400comprise an inlet140through which the therapeutic agent may be supplied, and a plurality of outlet holes240through which the therapeutic agent may be delivered to the respective location of the body. Any of the delivery systems1200,1300, and1400may incorporate any other structures or features disclosed herein in relation to delivery systems for the knee and the hip.

Components of the therapeutic agent delivery systems 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, polyether ether ketone (PEEK), polymethyl methacrylate (PMMA), and ultra high molecular weight polyethylene (UHMWPE). The materials may incorporated an antibiotic-impregnated outer layer, such as an antibiotic-impregnated PMMA outer layer. The surface of the components may be polished to prevent bone growth and formation of biofilms. Alternatively, the surface of the components may be grit-blasted or plasma-sprayed, incorporate one or more of an hyaluronic acid (HA) coating, silver coating, or antibiotic carrier coating, or be passivated and irradiated to form a hydrophilic nanostructure. The delivery systems as described herein may comprise one or more of machined parts or sintered parts.

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