Theragnostic Endoprosthetic Spacer

Abstract

Disclosed herein is an endoprosthetic spacer (100, 200, 300) for administering a therapeutic treatment, in particular a theragnostic treatment. The endoprosthetic spacer (100, 200, 300) comprises a body (102) that is configured to replace at least a part of a bone, a sensor assembly (104) comprising at least one sensor (104A, 104B, 104C), a communication module (108) configured to transmit a signal; and a controller (106) configured to read out a sensor signal from the at least one sensor (104A, 104B, 104C) and to transmit an output signal (110) via the communication module (108).

Claims

1. An endoprosthetic spacer for administering a therapeutic treatment, the endoprosthetic spacer comprising: a body that is configured to replace at least a part of a bone; a sensor assembly comprising at least one sensor; a communication module configured to transmit a signal; and a controller configured to read out a sensor signal from the at least one sensor and to transmit an output signal via the communication module.

2. The endoprosthetic spacer of claim 1, wherein the body comprises a transparent material and the at least one sensor is an optical sensor arranged in the transparent material.

3. (canceled)

4. The endoprosthetic spacer of claim 2, wherein the optical sensor comprises a camera.

5. The endoprosthetic spacer of claim 2, wherein the optical sensor is configured to perform a spectroscopic measurement.

6. The endoprosthetic spacer of claim 5, wherein the sensor assembly comprises a light source and the optical sensor is configured to adjust one or both of a wavelength of light emitted by the light source and a wavelength of light detected by the optical sensor to perform the spectroscopic measurement.

7. The endoprosthetic spacer of claim 1, wherein the sensor assembly comprises one or both of an ambient sensor that is configured to determine an ambient parameter, and a biomarker sensor that is configured to detect a biomarker.

8. The endoprosthetic spacer of claim 1, wherein the body is configured to replace at least a part of a joint.

9. (canceled)

10. The endoprosthetic spacer of claim 1, wherein the endoprosthetic spacer is configured to release one or both of a diagnostic substance and a pharmaceutical substance.

11. The endoprosthetic spacer of claim 10, further comprising a dispenser having a reservoir configured to store one or both of the diagnostic substance and the pharmaceutical substance, wherein the dispenser is configured to release one or both of a predetermined amount of the diagnostic substance and a predetermined amount of the pharmaceutical substance from the reservoir.

12. The endoprosthetic spacer of claim 1, further comprising a microfluidic circulation system that is configured to extract a fluid from an environment of the endoprosthetic spacer and to subsequently re-lease the extracted fluid to the environment of the endoprosthetic spacer.

13. The endoprosthetic spacer of claim 1, further comprising a light source configured to emit light wherein the therapeutic treatment comprises applying light using the light source.

14. (canceled)

15. The endoprosthetic spacer of claim 13, further comprising a light source configured to emit light, wherein the light source is configured to emit light in two different wavelength ranges.

16. The endoprosthetic spacer of claim 1, wherein the controller is configured to control administering of the therapeutic treatment based on one or both of the sensor signal and a command signal, wherein the communication module is configured to receive the command signal.

17. (canceled)

18. A computer-readable medium storing instructions that, when executed by a processor, cause the processor to: read out a sensor signal from a sensor in an endoprosthetic spacer; generate an output signal for transmission via a communication module of the endoprosthetic spacer, wherein the output signal is based on the sensor signal; and determine a control signal for controlling administering of a therapeu-tic treatment, by the endopros-thetic spacer.

19. The computer-readable medium of claim 18, wherein the control signal characterizes one or more of an amount of a diagnostic substance to be released from the endoprosthetic spacer an amount of a pharmaceutical substance to be released from the endoprosthetic spacer and an amount of light to be emitted from the endoprosthetic spacer.

20. (canceled)

21. A method of manufacturing an endoprosthetic spacer for administering a therapeutic treatment, the method comprising: providing at least one sensor; providing a controller that is configured to read out a sensor signal from the at least one sensor and to transmit an output signal via a communication module; and forming a body of the endoprosthetic spacer comprising the at least one sensor and the controller, wherein the body is configured to replace at least a part of a bone and to administer the therapeutic treatment.

22. The method of claim 21, wherein providing the at least one sensor comprises providing an optical sen-sor; the body comprises a transparent material; and forming the body comprises arranging the optical sensor in the transparent material.

23. The method of claim 21, wherein providing the at least one sensor comprises providing one or both of an optical sensor comprising a camera and an optical sensor configured to perform a spectroscopic measurement.

24. (canceled)

25. The method of claim 21, wherein forming the body comprises providing one or both of a diagnostic substance and a pharmaceutical substance in the body.

26. The method of claim 25, wherein providing one or both of the diagnostic substance and the pharmaceutical substance comprises providing a dispenser with a reservoir storing one or both of the diagnostic substance and the pharmaceutical substance, wherein the dispenser is configured to release one or both of a predetermined amount of the diagnostic substance and a predetermined amount of the pharmaceutical sub-stance from the reservoir.

27. (canceled)

Description

LIST OF FIGURES

[0048] In the following, a detailed description of the invention and exemplary embodiments thereof is given with reference to the figures. The figures show schematic illustrations of

[0049] FIG. 1: an endoprosthetic spacer for administering a therapeutic treatment according to an exemplary embodiment of the invention;

[0050] FIG. 2: an endoprosthetic spacer for administering a therapeutic treatment in accordance with another embodiment of the invention;

[0051] FIG. 3a: an endoprosthetic spacer having an articulating member and a receiving member according to an exemplary embodiment of the invention;

[0052] FIG. 3b: an endoprosthetic spacer with a microfluidic circulation system according to an exemplary embodiment of the invention;

[0053] FIG. 4: a block diagram representing a computer-readable medium in accordance with an embodiment of the invention;

[0054] FIG. 5: a flow diagram illustrating a method of manufacturing an endoprosthetic spacer for administering a therapeutic treatment according to an exemplary embodiment of the invention;

[0055] FIG. 6: a prototype of an endoprosthetic spacer for administering a theragnostic treatment in accordance with an exemplary embodiment of the invention; and

[0056] FIG. 7: video images of an ex-vivo human knee recorded with the prototype of FIG. 6.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0057] FIG. 1 depicts a schematic illustration (not to scale) of a sectional view of an endoprosthetic spacer too for administering a therapeutic treatment according to an exemplary embodiment of the invention. In this example, a body 102 of the endoprosthetic spacer too is configured to replace the head of the femur, i.e. the lower part of the hip joint. In other examples, the body 102 may additionally comprise a second member that is configured to replace the acetabulum, i.e. the upper part of the hip joint. The body 102 comprises or consists of a transparent material, preferably polymethylmethacrylate (PMMA). To administer the therapeutic treatment, a pharmaceutical substance 103, e.g. an antibiotic and/or antiseptic, is admixed to the transparent material such that the pharmaceutical substance 103 is continuously released from the body 102 to the surrounding environment. Thereby, the pharmaceutical substance 103 may be applied to an infected joint in a targeted fashion.

[0058] The endoprosthetic spacer 100 comprises a sensor assembly 104 with a sensor 104A. The sensor 104A is embedded in the body 102 such that the sensor 104A is completely surrounded by the transparent material. In other examples, the sensor 104A may be arranged such that it is in contact with an environment of endoprosthetic spacer 100. In the example of FIG. 1, the sensor 104A is an optical sensor 104A, in a particular a camera that is configured to image an interface between the endoprosthetic spacer 100 and the acetabulum. Preferably, the camera 104A also comprises a light source that is configured to illuminate the region to be imaged. In other examples, the sensor 104A may be a different type of optical sensor, for example a photodiode or an optical sensor configured to perform a spectroscopic measurement, or may be an ambient sensor or a biomarker sensor.

[0059] The camera 104A is connected to a controller 106 that is configured to read out a sensor signal from the camera 104A. The sensor signal for example contains an image or video recorded by the camera 104A. The controller 106 is configured to control the camera 104A, e.g. to trigger exposure of an image or to initiate and stop recording of a video.

[0060] The controller 106 is a microcontroller that comprises a processor and a storage medium, e.g. a non-volatile memory like an EEPROM or flash memory. The storage medium stores instructions for execution by the processor to provide the functionality of the controller 106 described herein, in particular reading-out and processing the sensor signal. The storage medium may for example be the computer-readable medium 400 described below with reference to FIG. 4. The controller 106 additionally comprises a larger data storage or memory such as a flash memory for temporarily storing the sensor signal.

[0061] The controller 106 is connected to a communication module 108 that is configured to transmit a signal. In this example, the communication module 108 is a Bluetooth module that is configured to wirelessly communicate with other devices using the Bluetooth standard. The controller 106 is configured to transmit an output signal 110 via the communication module 108, wherein the output signal 110 may be used to transfer an image or video recorded by the camera 104A to an external computing device. The controller 106 is further configured to receive to an input signal via the communication module 108. The input signal may for example cause the controller 106 to record an image or video using the camera 104A or to initiate a data transfer of images or videos stored in the data storage. In this way, a physician may monitor the joint using the endoprosthetic spacer 100, e.g. to assess an effect of the therapeutic treatment.

[0062] The endoprosthetic spacer 100 may also comprise a battery (not shown) to provide power for the camera 104A, the controller 106 and the communication module 108. The endoprosthetic spacer 100 may further comprise additional elements (not shown), e.g. additional sensors, a dispenser or a light source as detailed below with reference to FIG. 3a.

[0063] FIG. 2 depicts a schematic illustration (not to scale) of a sectional view of an endoprosthetic spacer 200 for administering a therapeutic treatment in accordance with another embodiment of the invention. Similar to the endoprosthetic spacer 100, the endoprosthetic spacer 200 comprises a body 102, a sensor assembly 104 with a sensor 104A, a controller 106 and a communication module 108. In contrast to the example of FIG. 1, the body 102 of the endoprosthetic spacer 200 is a support structure that may for example comprise a metal alloy such as a titanium alloy and/or polyethylene, in particular ultra-high molecular weight polyethylene (UHMW-PE). Accordingly, the shape and size of the body 102 resemble the bone to be replaced only approximately. The sensor 104A, the controller 106 and the communication module 108 are integrated in or attached to the body 102. The body 102 is configured to be embedded in a modeling layer 202, which may for example comprise or consist of a thermoplastic material like PMMA. In the example of FIG. 2, the body 102 is completely enclosed in the modeling layer 202. The shape and size of the modeling layer 202 closely resemble the bone to be replaced. The modeling layer 202 may for example be added before or during surgery, allowing for a flexible adjustment of the size and shape of the endoprosthetic spacer 200. The modeling layer 202 or the body 102 may comprise a pharmaceutical substance (not shown) similar to the example of FIG. 1. In other examples, the modeling layer 202 or the body 102 may additionally or alternatively comprise a diagnostic substance, e.g. a fluorophore-labelled antibody for diagnostic monitoring.

[0064] FIG. 3a shows a schematic illustration (not to scale) of a sectional view of an endoprosthetic spacer 300 with a body 102 having two members, an articulating member 102A and a receiving member 102B that is configured to movably receive the articulating member 102A. In the example of FIG. 3a, the endoprosthetic spacer 300 is configured to serve as a knee joint replacement, i.e. the articulating member 102A is configured to at least partially replace the distal end of the femur and the receiving member 102B is configured to at least partially replace the proximal end of the tibia. A distal surface of the receiving member 102B and a proximal surface of the articulating member 102A face each other across an interface volume 302 and are shaped such that the body 102 is configured to mimic the motional degrees of freedom of the human knee joint, e.g. such that the articulating member 102A may rotate with respect to the receiving member 102B around a rotation axis that is parallel to the horizontal x axis in FIG. 3a. In some examples, additional elements may be arranged in the interface volume 302, e.g. a joint liner or articulating surface (not shown). Similar to the endoprosthetic spacer 100, the body 102 is formed of a transparent thermoplastic material, preferably PMMA, and contains a pharmaceutical substance 103 that is admixed to the thermoplastic material. When implanted in a patient, the pharmaceutical substance 103 may slowly be released from the body 102 to the environment of the endoprosthetic spacer 300.

[0065] Similar to the endoprosthetic spacers 100 and 200, the endoprosthetic spacer 300 comprises a sensor assembly 104, a controller 106 and a communication module 108, each of which is embedded in the body 102, in particular in the receiving member 102B. In the example of FIG. 3a, the sensor assembly 104 comprises a plurality of sensors, namely a camera 104A, an ambient sensor 104B, and a biomarker sensor 104C.

[0066] The camera 104A comprises a camera sensor, e.g. a CMOS sensor (not shown) and imaging optics (not shown) configured to image a field of view 304 of the camera 104A onto the camera sensor. The camera 104A is fully enclosed by the thermoplastic material of the body 102 and is oriented such that the field of view 304 of the camera 104A faces the interface volume 302 between the articulating member 102A and the receiving member 102B. The camera 104A may additionally comprise a light source (not shown) that is configured to illuminate the field of view 304, for example one or more light emitting diodes. The camera 104A is connected with the controller 106, which is configured to control operation of the camera 104A and to read out a sensor signal from the camera 104A.

[0067] The ambient sensor 104B is a temperature sensor that is configured to measure a temperature at the position of the ambient sensor 104B. The ambient sensor 104B is arranged such that a detection surface of the ambient sensor 104B is in contact with the environment of the endoprosthetic spacer 300, e.g. to facilitate thermal equilibration. The ambient sensor 104B is connected with the controller 106, which is configured to read out a sensor signal from the ambient sensor 104B. The ambient sensor 104B may for example comprise a thermocouple and the controller 106 may be configured to measure a voltage across the thermocouple to determine the temperature. Alternatively, the ambient sensor 104B may for example comprise a thermistor and the controller 106 may be configured to measure a resistance of the thermistor to determine the temperature. In some examples, the ambient sensor 104C may comprise electronic circuits for generating a sensor signal that characterizes the measured temperature, e.g. a digital sensor signal.

[0068] The biomarker sensor 104C is configured to measure a concentration of a biomarker in the environment of the endoprosthetic spacer 300. Preferably, the biomarker is a biomarker associated with an immune response, for example an inflammation marker such as C-reactive protein (CRP). The biomarker sensor 104C is arranged in the body 102 such that a detection surface of the biomarker sensor 104C is in contact with the environment of the endoprosthetic spacer 300. The detection surface of the biomarker sensor 104C may for example comprise a plurality of field effect transistors (FETs) with CRP antibodies for immobilizing CRP in the vicinity of the field effect transistors (FETs) such that the presence of CRP can be inferred from a source-drain current of a FET. In other examples, different antibodies may be used for detecting other biomarkers. In particular, a plurality of different types of antibodies may be employed to simultaneously detect a plurality of biomarkers. The biomarker sensor 104C is also connected to the controller 106, which is configured to read out a sensor signal from the biomarker sensor 104C. The sensor signal may e.g. be an average source-drain current of the plurality of FETs. In other examples, the biomarker sensor 104C may comprise electronic circuits for generating a sensor signal that characterizes the biomarker concentration, e.g. a digital sensor signal.

[0069] In addition to and/or instead of the sensors shown in FIG. 3a, the sensor assembly 104 may comprise other sensors. The ambient sensor 104B may for example be a pH sensor that is configured to measure a pH value in the environment of the endoprosthetic spacer 300, e.g. via electrodes arranged on the detection surface, or may be a combined temperature and pH sensor that is configured to measure a temperature as well as a pH value. The sensor assembly 104 may also comprise an optical sensor that is configured to perform a spectroscopic measurement. The spectroscopic sensor may for example comprise a broadband or tunable light source, e.g. in the visible and/or near-infrared spectrum, and a detector configured to measure an intensity of light transmitted through or scattered and/or reflected by the environment of the endoprosthetic spacer 300, e.g. the interface volume 302 or surrounding tissue. The light source may be spectrally tunable and/or the detector may be configured to measure a spectrally resolved intensity. The controller 106 may be configured to determine spectra using the spectroscopic sensor, which may be transmitted via the communication module 108 and may for example be used to assess a tissue hydration or a hemoglobin concentration.

[0070] The endoprosthetic spacer 300 further comprises a dispenser 306 with a reservoir 308 that is configured to store a pharmaceutical substance, in particular a fluid containing the pharmaceutical substance (not shown). The pharmaceutical substance may be the same as the pharmaceutical substance 103 in the body 102 or may be different from the pharmaceutical substance 103. The volume of the reservoir 308 may for example be between 0.1 ml and 5 ml. The dispenser 306 is connected to the controller 106 and is configured to release a predetermined amount of the pharmaceutical substance from the reservoir to the environment of the endoprosthetic spacer 300, e.g. the interface volume 302. For this, the dispenser 306 comprises a microfluidic channel system 310 having a plurality of openings in fluid communication with the environment of the endoprosthetic spacer. The microfluidic channel system 310 may comprise a pump and/or a valve for releasing the pharmaceutical substance, e.g. in response to a control signal received from the controller 106. In other examples, the reservoir 308 may additionally or alternatively store a diagnostic substance, e.g. a dye or a fluorophore-labelled substance for diagnostic monitoring.

[0071] The endoprosthetic spacer 300 also comprises a light source 312 configured to emit light into an illumination cone 314, which in the example of FIG. 3a is oriented towards the interface volume 302. The light source is an ultraviolet (UV) light source configured to emit UV light, e.g. light between 200 nm and 380 nm. In other examples, the light source 312 may additionally or alternatively emit light in other wavelength ranges, for example in the visible range for illuminating the field of view 304 of the camera 104A or to excite a fluorophore. A maximum output power of the light emitted by the light source 312 may e.g. be between 0.1 mW and 10 mW. The light source 312 may be configured to adjust the output power, e.g. be tween 0 mW and the maximum output power. The light source 312 is connected to the controller 106 and is configured to receive a control signal from the controller 106, e.g. to switch the light source 312 on or off or to adjust the output power of the light source 312. The light source 312 may be a continuous-wave light source or may be a pulsed light source.

[0072] In other embodiments, the components of the endoprosthetic spacer 300 described above may be arranged differently. Some or all of the components may be arranged in the articulating member 102A. Components in different members of the body 102 may be connected via a cable between the members and/or a wireless communication link. The pharmaceutical substance 103 may be contained in the articulating member 102A and/or in the receiving member 102B. In some examples, the endoprosthetic spacer 300 may be similar to the endoprosthetic spacer 200 shown in FIG. 2, i.e. the body 102 may be a support structure that e.g. consists of or comprises a metal alloy and/or polyethylene and is configured to sup port a surrounding modelling layer, e.g. consisting of or comprising PMMA. The other components of the endoprosthetic spacer 300 may be embedded in or attached to the support structure as shown in FIG. 2. In some examples, the endoprosthetic spacer 300 may also be configured to replace a different joint or bone, e.g. the hip joint, wherein the receiving member 102B is shaped to at least partially replace the acetabulum and the articulating member 102A is shaped to at least partially replace the upper part of the femur.

[0073] FIG. 3b depicts a schematic illustration (not to scale) of a sectional view of an endoprosthetic spacer 320. The endoprosthetic spacer 320 is similar to the endoprosthetic spacer 300 of FIG. 3a and also comprises a body 102 with an articulating member 102A and a receiving member 102B as well as a sensor assembly 104, a controller 106 and a communication module 108, each of which is embedded in the body 102.

[0074] The endoprosthetic spacer 320 comprises a microfluidic circulation system 322 with an inlet 322A formed by two openings, which may e.g. be arranged such that the openings are located suprapatellar when the endoprosthetic spacer 320 is implanted in a knee joint. The microfluidic circulation system 322 further comprises an outlet 322B, which may e.g. be arranged such that the opening is located retropatellar or intercondylar and faces the interface volume 302 when the endoprosthetic spacer 320 is implanted in a knee joint. The microfluidic circulation system 322 further comprises a pump (not shown) that is configured to pump fluid from the inlet 322 to the outlet as indicated by the arrows.

[0075] The microfluidic circulation system 322 additionally comprises a filter 324 that is arranged in a flow path between the inlet 322A and the outlet 322B. The filter 324 may e.g. be a bacterial filter that is configured to filter out bacteria and/or parts of bacteria from the fluid pumped by the microfluidic circulation system. The filter 324 may further be coated with an antibiotic and/or dye. In the example of FIG. 3b, the filter 324 is arranged in the field of view 304 of a camera 104A, which may e.g. be used to monitor material absorbed by the filter.

[0076] The endoprosthetic spacer 320 may comprises additional elements, e.g. as described above for the endoprosthetic spacer 300. In particular, the endoprosthetic spacer 320 may comprise a dispenser (not shown) with a reservoir and a microfluidic channel system. The microfluidic channel system may e.g. be coupled with the microfluidic circulation system through a microvalve. The dispenser and the microfluidic circulation system 322 may share a pump can be used for circulating fluid through the microfluidic channel system and for releasing fluid from the reservoir and/or may share one or more openings.

[0077] FIG. 4 schematically illustrates a computer-readable medium 400 in accordance with an embodiment of the invention. The computer-readable medium 400 comprises sets of ma chine-readable instructions for execution by a processor. Any of the sets of instructions referred to herein may be embodied by a corresponding software module. In other words, each of the blocks 402-406C may resemble a software module. The computer-readable medium 400 may for example be connected to or part of the controller 106 of the endoprosthetic spacer 100, 200 or 300, e.g. such that a processor of the controller 106 executes instructions stored on the computer-readable medium 400 to provide the functionality described in the following or at least a part thereof. Alternatively, the computer-readable medium 400 may for example be provided to copy instructions from the computer-readable medium 400 to an internal storage medium of one of the endoprosthetic spacers 100, 200 or 300. In the following, the computer-readable medium 400 is described with reference to FIG. 3a using the endoprosthetic spacer 300 as a non-limiting example.

[0078] The computer-readable medium 400 comprises a set of instructions 402 that, when executed by a processor, cause the processor to read out a sensor signal from a sensor in the endoprosthetic spacer 300, e.g. the camera 104A, the ambient sensor 104B and/or the biomarker sensor 104C. Accordingly, the set of instructions 402 may also be referred to as the sensor read-out instructions 402.

[0079] The sensor read-out instructions 402 additionally comprise instructions for performing a measurement, e.g. to send trigger signals to the camera 104A for initiating and terminating recording of a video, to the biomarker sensor 104C to initiate and terminate a biomarker concentration measurement or to a sub-module of the controller to initiate and terminate a voltage or resistance measurement of the temperature sensor 104B. The measurements are performed based on a measurement plan for the sensor assembly 104, which may e.g. be stored on the computer-readable medium 400 or the internal memory of the controller 106. The measurement plan specifies parameters of a measurement, e.g. how and when to perform a measurement. The measurement plan may for example define that an image is to be taken with the camera every 30 minutes or that a temperature measurement is to be performed every 30 seconds.

[0080] The sensor read-out instructions 402 also comprise instructions for processing the sensor signal, e.g. to average, filter and/or compress the sensor signal to reduce an amount of data to be transferred. The sensor read-out instructions 402 in particular comprise instructions for extracting measurement values characterized by the sensor signal from the sensor signal, e.g. converting a measured voltage or resistance from the temperature sensor 104B to a temperature using a predetermined calibration curve. Additionally, the sensor read-out instructions 402 also comprise instructions for analyzing the sensor signal, e.g. by comparing the sensor signal or a measurement value characterized by the sensor signal to a predetermined reference value or a predetermined reference range. The sensor read-out instructions 402 further comprise instructions for temporarily storing the sensor signal or the processed sensor signal on an internal memory of the controller 106, e.g. until an external computing device is coupled with the communication module 108.

[0081] The computer-readable medium 400 further comprises a set of instructions 404 that, when executed by a processor, provide capabilities for communication via the communication module 108, e.g. for communicating with an external computing device connected to the communication module 108 by a wireless communication link. Accordingly, the set of instructions 404 may also be referred to as the communication instructions 404. The communication instructions 404 comprise a subset of instructions 404A for transmitting signals via the communication module 108, also referred to as output instructions 404A, and a subset of instructions 404 B for receiving signals via the communication module 108, also referred to as input instructions 404B.

[0082] The output instructions 404A, when executed by a processor, cause the processor to generate an output signal for transmission via the communication module 108. The output instructions 404A are configured to generate different types of output signals. Some types of output signals are based on the sensor signal that is read out using the sensor read-out instructions 402. One type of output signal contains the sensor signal or a processed sensor signal. There may be different output signals for each of the sensors 104A-104C of the sensor assembly 104 or one output signal based on the sensors signals from all of the sensors 104A-104C. Another type of output signal is a warning signal, which indicates that a measurement value is below or above the predetermined reference value or outside of the predetermined reference range. Yet another type of output signal contains information regarding the status of the endoprosthetic spacer 300, e.g. a filling level of the reservoir 308, a treatment plan for the dispenser 306 and/or the light source 312, a measurement plan for the sensor assembly 104 and/or a charging status of a battery of the endoprosthetic spacer 300.

[0083] The input instructions 404B control the handling of input signals received by the communication module. The input instructions 404B are configured to handle different types of input signals. The input instructions 404B handle command signals for altering settings of the endoprosthetic spacer 300 or a component thereof or for controlling operation of a component of the endoprosthetic spacer 300. The command signal may e.g. contain a new measurement plan or a new treatment plan that is to replace a current measurement or treatment plan, respectively. Alternatively, the command signal may control one of the sensors 104A-104C, e.g. may trigger recording of a video by the camera 104C, or may directly control administering of the therapeutic treatment, e.g. by switching on the light source 312 or releasing pharmaceutical substance from the reservoir 308.

[0084] The computer-readable medium 400 further comprises a set of instructions 406 that, when executed by a processor, determine a control signal for controlling administering of a therapeutic treatment. The set of instructions 406 may also be referred to as the treatment instructions 406. The endoprosthetic spacer 300 is configured to administer two types of therapeutic treatments: application of the pharmaceutical substance via the dispenser 306 and application of UV light via the light source 312. In the following, the application of the pharmaceutical substance via the dispenser 306 is used as an example for illustration purposes. Application of UV light may be controlled by the treatment instructions 406 in a similar way.

[0085] The treatment instructions 406 comprise three subsets of instructions, a set of instructions 406A for processing a command signal, a set of instructions 406B for processing a sensor signal and a set of instructions 406C to determine the control signal based on the output of the two sets of instructions 406A and 406B. The control signal characterizes an amount of the pharmaceutical substance to be released from the reservoir 308. Subsequently, the controller 106 sends the control signal to the dispenser 306 to administer the therapeutic treatment. The control signal may for example be a trigger signal that opens a valve and/or switches on a pump in the microfluidic channel system 310.

[0086] The set of instructions 406A are configured to process a command signal. As described above, a command signal may contain information related to a treatment plan that determines administering of the therapeutic treatment and may be stored in the memory of the controller 106. The treatment plan defines parameters based on which the pharmaceutical substance is released by the dispenser 306, in particular a rate at which the pharmaceutical substance or the fluid containing the pharmaceutical substance is released. The treatment plan may for example specify a continuous flow rate from the reservoir 306 such as 1 μl to 50 μl per hour. Alternatively, the treatment plan may specify a predetermined fluid volume to be released from the reservoir and a repetition rate how often the predetermined fluid volume is to be released, e.g. 1 μl to 10 μl every hour. The treatment plan also contains parameters regarding the determination of the control signal based on the sensor signal as described below. A command signal may also directly control administering of the therapeutic treatment and may e.g. specify an amount of fluid that is to be released instantaneously as a one-off treatment.

[0087] The set of instructions 406B are configured to process a sensor signal or a processed sensor signal provided by the sensor read-out instructions 402. The instructions 406B implement a feedback loop that is configured to adjust administering of the therapeutic treatment based on the sensor signal. In particular, the instructions 406B adjust parameters of the treatment plan based on the sensors signal. As an example, the sensor signal may characterize a concentration of C-reactive protein (CRP) determined by the biomarker sensor 104C, which may serve as an indicator of inflammation. Accordingly, the instructions 406B increase or decrease a flow rate or predetermined fluid volume and repetition rate specified by the treatment plan depending on the concentration of CRP. The treatment plan may contain an upper and/or lower bound to specify a range within which the flow rate or predetermined fluid volume and repetition rate may be adjusted based on the sensor signal. In one example, the treatment plan may specify that the flow rate can be adjusted between 50% and 200% of a predetermined value.

[0088] FIG. 5 shows a flowchart of a method 500 of manufacturing an endoprosthetic spacer in accordance with an embodiment of the invention. The method 500 may for example be executed during surgery to form a custom-built endoprosthetic spacer for subsequent implantation in a patient. Alternatively, the method 500 may be executed to manufacture pre-built endoprosthetic spacers, e.g. based on patient-specific designs or as a core structure to be adapted for a patient during surgery. In the following, the method 500 is described with reference to FIGS. 2 and 3 using the endoprosthetic spacers 200 and 300 as non-limiting examples. The flowchart of FIG. 5 illustrates one example for an order of execution of the method 500. But the method 500 is not limited to this particular order of execution. As far as technically feasible, the steps of method 500 may be executed in an arbitrary order and also simultaneously at least in part.

[0089] In step 502, at least one sensor is provided. In the example of FIG. 3a, a camera 104A, an ambient sensor 104B and a biomarker sensor 104C are provided. The sensors may be pro vided as fully functional pre-built units or may be assembled during step 502, e.g. by combining a light source and a camera to build the light-source-equipped camera 104A.

[0090] In step 504, the controller 106 is provided that is configured to read out a measurement signal from the sensors 104A-104C and to transmit an output signal via the communication module 108. In some examples, step 504 also comprises programming the controller 106, e.g. by providing or employing the computer-readable medium 400. The instructions stored on the computer-readable medium 400 or a part thereof may for example be copied to a storage medium of the controller 106. In other examples, the controller 106 may already be provided including the computer-readable medium 400. Step 504 further comprises providing the communication module 108, either as part of the controller 106 or as an independent device. Step 504 may also comprise providing a measurement plan and a treatment plan, e.g. via the communication module 108 or on the computer-readable medium 400.

[0091] The method 500 also comprises, in step 506, providing the light source 312 and, in step 508, providing the dispenser 306. The light source 312 and/or the dispenser may be pro vided as fully functional pre-built units or may be assembled during step 502, e.g. by connecting the reservoir 308 to the microfluidic channel system 310. The dispenser 306 may be pro vided with an empty reservoir 308 or the reservoir 308 may be filled with a pharmaceutical substance or a mixture of pharmaceutical substances in step 508.

[0092] In step 510, the body 102 of the endoprosthetic spacer is formed. The body 102 of the endoprosthetic spacer 300 of FIG. 3a is for example formed from a thermoplastic material, preferably polymethylmethacrylate (PMMA), which is also referred to as bone cement. The bone cement is e.g. provided as a two-component system of a liquid containing methyl methacrylate (MMA) monomers and a powder containing pre-polymerized PMMA. The two components are mixed to initiate polymerization. One or more pharmaceutical substances 103 are provided by admixing the substances to the liquid and/or powder or adding the substances when mixing the two components. Subsequently, as the polymerization proceeds and the bone cement hardens, the articulating member 102A and the receiving member 102B are formed from the bone cement and adapted to the patient, e.g. based on the shape of a permanent prosthesis previously removed from the patient. The sensors 104A-104C of the sensor assembly 104, the controller 106, the communication module 108, the dispenser 306 and the light source 312 are connected to each other as described above with reference to FIG. 3a and, together with a power source, are embedded in the hardening bone cement, e.g. such that some or all of components are fully surrounded by bone cement and/or such that some or all of the components are arranged at an outer surface of the body 102. Subsequently, when the bone cement is completely or almost completely polymerized, the endoprosthetic spacer 300 may be implanted in the patient.

[0093] The body 102 of the endoprosthetic spacer 200 of FIG. 2, on the other hand, is for example formed from a metal alloy, polyethylene or a combination thereof. The body 102 may e.g. be formed by molding, milling, 3D printing or a combination thereof. The body 102 is shaped to roughly resemble the form of the bone to be replaced such that the shape of the endoprosthetic spacer 200 can be adapted to a specific patient later on, e.g. by surrounding the body 102 by the modelling layer 202. The body 102 may comprise cavities or recesses configured to receive components such as the sensor 104A, the controller 106 and the communication module 108 as well as additional components, e.g. a power source, a dispenser, a light source and/or other sensors. Alternatively, some or all of these components may be attached to outer surfaces of the body 102. The components may be glued to the body 102 or may be fastened using screws, clips or hooks. In some examples, step 510 may also comprise forming at least a part of the modeling layer 202, e.g. as described above using bone cement.

[0094] FIG. 6 depicts a prototype of an endoprosthetic spacer 600 for administering a theragnostic treatment in accordance with an exemplary embodiment of the invention during various stages of manufacture. The endoprosthetic spacer 600 may for example be manufactured using a method of manufacturing an endoprosthetic spacer according to the invention, e.g. the method 500 of FIG. 5 described above.

[0095] The endoprosthetic spacer 600 comprises a body 102 with a base shown in FIG. 6A and a cover (not shown) for the base. The body 102 consists of PMMA and was formed by 3D printing. The shape of the body 102 is formed to resemble the tibia plateau of the human tibia for implanting the endoprosthetic spacer 600 into a human knee. One or more diagnostic and/or pharmaceutical substances may be admixed to the PMMA before or when forming the body 102.

[0096] The body 102 comprises a hollow core that is configured to receive other components of the endoprosthetic spacer 600 as illustrated in FIGS. 6B and 6C. In particular, the endoprosthetic spacer 600 comprises a printed-circuit board 602, a battery 604, and a sensor assembly with a camera 104A. A microcontroller and a wireless communication module are arranged on the printed-circuit board 602, wherein the microcontroller is configured to read out a video stream from the camera 104A and to transmit an output signal via the wireless communication module, e.g. to an external computing device such as a computer or a smartphone. The battery 604 is configured to power the printed-circuit board 602 as well as the camera 104A. In other examples, the endoprosthetic spacer 600 may comprise additional components, in particular a light source and/or a dispenser as described above.

[0097] The camera 104A, the printed-circuit board 602, and the battery 604 are arranged in the base of the body 102 such that the camera 104A faces through a transparent sidewall of the base to record images from the environment of the endoprosthetic spacer 600. In addition, filler material 606 such as solid foam, e.g. a polymeric foam, is arranged within the body 102 to align the camera 104A and to secure the camera 104A in place. Subsequently, the body 102 is closed by attaching the cover to the base and placed in a sterile enclosure as shown in FIG. 6D.

[0098] FIG. 7 depicts exemplary video images of a human knee recorded with the endoprosthetic spacer 600 of FIG. 6 and transmitted to a smartphone. For this, the endoprosthetic spacer 600 was implanted into an ex-vivo human knee, a video stream was recorded with the camera 104A and transmitted to the smartphone via the wireless communication module. The images show the tissue and the synovia surrounding the endoprosthetic spacer 600.

[0099] The embodiments of the present invention disclosed herein only constitute specific examples for illustration purposes. The present invention can be implemented in various ways and with many modifications without altering the underlying basic properties. Therefore, the present invention is only defined by the claims as stated below.

LIST OF REFERENCE SIGNS

[0100] 100—endoprosthetic spacer [0101] 102—body of the endoprosthetic spacer [0102] 102A—articulating member [0103] 102B—receiving member [0104] 103—pharmaceutical substance [0105] 104—sensor assembly [0106] 104A—optical sensor [0107] 104B—ambient sensor [0108] 104C—biomarker sensor [0109] 106—controller [0110] 108—communication module [0111] 200—endoprosthetic spacer [0112] 202—modelling layer [0113] 300—endoprosthetic spacer [0114] 302—interface volume [0115] 304—camera field of view [0116] 306—dispenser [0117] 308—reservoir [0118] 310—microfluidic channel system [0119] 312—light source [0120] 314—illumination cone [0121] 320—endoprosthetic spacer [0122] 322—microfluidic circulation system [0123] 322A—inlet of the microfluidic circulation system [0124] 322B—outlet of the microfluidic circulation system [0125] 324—filter [0126] 400—computer-readable medium [0127] 402—sensor read-out instructions [0128] 404—communication instructions [0129] 404A—output instructions [0130] 404B—input instructions [0131] 406—treatment instructions [0132] 406A—instructions for processing of command signal [0133] 406B—instructions for processing of sensor signal [0134] 406C—instructions for determining the control signal [0135] 500—method of manufacturing an endoprosthetic spacer [0136] 502—step of providing a sensor [0137] 504—step of providing a controller [0138] 506—step of providing an ultra-violet light source [0139] 508—step of providing a dispenser [0140] 510—step of forming a body of the endoprosthetic spacer [0141] 600—endoprosthetic spacer [0142] 602—printed-circuit board [0143] 604—battery [0144] 606—filler material