Digital Multi-channel Tibial Implants in Orthopedic Medicine

Lead Research Organisation: University College London
Department Name: Institute of Orthopaedics

Abstract

Clinical and translational research to develop enhanced treatments for fractures would be greatly facilitated by the use of a valid and reliable measure of fracture healing. In preclinical studies, the gold standard is the measurement of bending or torsional stiffness; these are direct measures of the restitution of the key property of bone. This can only be performed in humans if the fracture is treated conservatively (without fixation) or by means of an external fixator. However the tibial shaft fracture (the fracture most likely to give problems clinically) is most often treated by intramedullary nailing. With an IM nail in situ, stiffness measurement is considered a waste of time, since it reflects the stiffness of the nail, as well as the bone, to an unknown extent. This project aims to overcome that problem by directly measuring strains in the nail in response to well-characterised loading of the bone-nail construct, thus allowing the stiffness of the bone itself to be deduced.The alternative approach to the monitoring of fracture healing is by radiographic imaging. With conventional radiographs this is apt to be misleading, though that is what clinicians use on a day-to-day basis. In this study, 3-D images from spiral CT will be processed by finite element analysis (FEA) to calculate the strength and stiffness of the healing fracture and this technique (which would not be realistic for routine use) will be used to validate the results obtained by the new telemetric method.We will take modified tibial nails, 11mm in diameter, supplied by our industrial partner and instrument them with 36 strain gauges distributed at three circumferential sites at three levels, together with the circuitry to read the strains and transmit them as radio waves. The electronics will be powered inductively through a coil enclosed in a ceramic ring on the end of the nail, preserving the cannulation of the whole nail which allows its insertion over a guide wire. Each instrumented nail will be calibrated to allow measurement of force with six degrees of freedom, and also bending deflection.Nails of several appropriate lengths will be instrumented for insertion into nine patients who are having surgery for delayed union of tibial shaft fractures, with a variety of fracture configurations at different levels in the tibia. The nails will be double-locked top and bottom with threaded screws so that the mechanical link between nail and bone will be rigid. At intervals following surgery we will examine the patients by gait analysis with simultaneous telemetric readings of strain from the nail. A 3D lower limb biomechanical model will be developed to allow the determination of forces acting on the tibia-nail construct, taking into account the forces generated in the construct by the patient's muscles. The forces and deflections experienced by the nail will be processed to yield the contribution of the bone to the whole construct. Simpler static loading protocols will also be explored. At the same time points, spiral CT images of 0.3mm slice thickness will be acquired and the datasets used to feed material properties of the bone and fracture callus into FEA software, excluding the nail, from which structural stiffness of the healing bone will be calculated. We will also apply validated scales of lower limb function.Using the FEA-derived structural properties of the bone as our comparator, we will validate the stiffness measurement based on analysis of the nail readout and loads. We will then use principal component analysis to determine the minimal strain gauge configuration and simplest loading protocols that yield sufficient information, in order to refine the system for commercialisation and clinical use. As well as providing an outcome measure for clinical trials, the system will be useful in routine treatment to guide rehabilitation and receive earlier warning of the need for secondary interventions such as bone graft.

Publications

10 25 50
 
Description We have developed a non-invasive method of measuring strains in fracture fixing bone nails.
Exploitation Route Commercialisation of the system by implant manufacturer
Sectors Healthcare,Manufacturing, including Industrial Biotechology

 
Description To help our commercial partner file a patent, initially
First Year Of Impact 2016
Sector Healthcare,Manufacturing, including Industrial Biotechology
 
Description Smith & Nephew
Amount £226,500 (GBP)
Organisation Smith and Nephew 
Sector Private
Country United Kingdom
Start 11/2010 
End 12/2012
 
Description Smith & Nephew
Amount £53,000 (GBP)
Funding ID RC831 
Organisation Smith and Nephew 
Sector Private
Country United Kingdom
Start 11/2010 
End 12/2013
 
Description SMD 
Organisation Strain Measurement Devices Ltd
Country United Kingdom 
Sector Private 
PI Contribution Awareness of medical markets and relevant products.
Collaborator Contribution Provision of strain gauging facilities and clean rooms.
Impact Within the SmartNail project, the outcomes are covered by the overall project outcomes. We also collaborate with SMD on other projects.
 
Description Smith&Nephew 
Organisation Smith and Nephew
Department Smith & Nephew Orthopaedics Ltd
Country United Kingdom 
Sector Private 
PI Contribution UCL brings expertise in designing instrumented implants. Technology know-how. S&N have gained valuable insight from UCL into the complexity of designing, developing and electrically testing off-the-shelf miniaturised wireless circuitry for orthopaedic applications.
Collaborator Contribution UCL have increased their internal capabilities for designing miniaturised electrical components and connections, which are suitable for integration into intramedullary nails. UCL have also gained valuable technical experience in the development of a pre-clinical ovine tibial nail model for monitoring fracture healing, which may be applicable to other research project conducted at their facilities. UCL post-graduate students contracted onto the project have also benefited from working with a commercial partner in terms of gaining a better understanding of the business environment.
Impact The consortium successfully designed two generations of instrumented biomechanical nails (Figure 1) for evaluation with an automated 6 degree of freedom calibration station in order to determine the following:- (a) suitable positions on the nail for attaching the wireless sensors, and (b) the most sensitive loading protocols and regenerate materials available for monitoring the early stage of fracture healing.
Start Year 2007
 
Title Low temperature encapsulate welding 
Description BACKGROUND [0002] 1. Technical Field [0003] This disclosure relates to various load-bearing medical implants with at least one electronic component that is sealed within a load-bearing structure of the implant to provide an impermeable bather to protect the electronic component from body fluids. Various methods are disclosed for hermetically sealing the electronic component within a metallic load-bearing implant structure by welding a weld plate over the cavity that accommodates the electronic component without causing thermal damage to the encapsulant or electronic component. Various techniques are also disclosed for encapsulating an electronic component within a cavity of a load-bearing implant, such as an IM nail that includes one or more electronic sensors for landmark identification. The encapsulation and welding techniques disclosed herein address the problems associated with load-bearing implants having shallow cavities for sensor or other components and shallow channels for wiring, wherein the sensor and encapsulant can be damaged by welding a cover plate in close proximity to the enscapsulant and sensor. [0004] 2. Description of the Related Art [0005] While most orthopedic implant developers are focused on improving current technologies, a handful are directed to developing "smart" or "intelligent" orthopedic implants equipped with implantable electronic components. Such electronically-equipped orthopedic implants provide real-time feedback to researchers, physicians or patients regarding how the implants are performing once they are placed inside a bone or joint. For example, orthopedic implants with electronic components can be used to detect poor bone in-growth, educate patients about safe post-operative activities, and improve surgical techniques. [0006] The implantable electronic circuits and components must be small to minimize the size of the implant and designed to last in a physiological environment for an extended period of time. A reliable hermetic barrier must be used to preventingress of body fluids to the implantable electronic components and to assure long term biocompatibility. Generally used methods for protecting electronic circuits from the bodily fluids or other damaging environments include both hermetic sealing and polymer encapsulation. [0007] Encapsulants, such as silicone elastomers, polyurethanes, silicone-urethane copolymer, polytetrafluoroethylene and epoxies have been used with implantable neuromuscular stimulators which rely on relatively simple circuits. However, polymers do not provide an impermeable barrier and therefore cannot be used for encapsulation of high density, high impedance electronic circuits. The moisture ingress will ultimately reach the electronic component resulting in electric shorting and degradation of leakage-sensitive circuitry. [0008] For radio frequency powered electronic components disposed within a medical implant, a combination of hermetic packaging and polymer encapsulation are used. Hermetic packaging, using metals, ceramics or glasses, provides the implant electronic circuitry with a long term protection from the ingress of body fluids. The primary role of the encapsulant is to stabilize the electronic components by acting as stress-relieving shock and vibration absorbers and providing electrical insulation. Electrical signals, such as power and stimulation, enter and exit the implant through hermetic through-holes, which are hermetically welded into the implant walls. The through-hole assembly utilizes a ceramic or glass insulator to allow one or more wires to exit the implant. [0009] In certain situations, electrical through-holes are not practical due to limited design space (e.g., <1 mm diameter) available for the parts in combination with the risk of fatigue failure of the connection due to cyclic loading of the implant. As a result, the role of the encapsulant as a secondary barrier to body fluid ingress becomes more important. Such devices include intramedullary (IM) nails, plates, rods and pedicle screws for orthopedic trauma application. In order to increase the body fluid barrier characteristics of the flexible impermeable encapsulant, the cavities that hold the electronic components need to be completely filled. This is difficult to achieve if the weld plate components have to be welded in close proximity with the encapsulant and the cavities are too long and narrow to allow adequate backfilling after hermetic sealing. [0010] Currently available medical grade silicone encapsulants are only suitable for short-term (e.g., <30 days) implantable applications, referred to as "restricted grade." However, some materials, such as MED3-4213 and ELAST-EONT™ developed by NuSil Silicone Technology (www.nusil.com) and AorTech (www.AorTech.com) respectively are unrestricted grades of silicone for long term implantation. Given that the onset temperature of thermal degradation for these types of materials is approximately 230° C., standard welding techniques, which generate local temperatures in the 400° C.-600° C. range, are not appropriate without the risk of degradation of either mechanical or optical properties the silicone. When exposed to high temperature conditions, the silicone will degrade leading to unpredictable performance. [0011] Scanning electron microscope (SEM) micrographs of cured MED3-4213 encapsulated in an implant before and after conventional welding techniques are shown in FIGS. 1A-1E. It is evident from FIGS. 1A-1E that performance degradation resulting from increases in optical absorption are noticeable in the form of a hazy or milky appearance that is apparent from a comparison of FIG. 1A, which shows a layer of undamaged silicone, and FIGS. 1B-1E. Furthermore, mechanical degradation takes the form of voids 22 (FIG. 1B), pitting 23 (FIG. 1C), degraded portions 24 of the polymer near the welding zones 25 (FIGS. 1D-1E), hardening/denaturizing, out gassing of volatiles, brittle structures, crazing, cracking, shrinking, melting, or delamination. Accordingly, all of these problems compromise biocompatibility and mechanical performance of the implant. [0012] There are no existing medical grade elastomers that can meet the high temperatures (400° C.-600° C.) needed for conventional welding which is used to provide a hermetic seal in the form of a weld plate over the cavity accommodating electronic component. As a result, a more cost-effective solution would be to optimize the existing methods of hermetic sealing. Consequently, there is a need for improved methods of packaging electronic components within an encapsulant that overcomes the thermal degradation issue caused by conventional welding techniques used to provide a hermetic seal. This need applies to medical implants and other unrelated applications. SUMMARY OF THE DISCLOSURE [0013] A load-bearing medical implant is disclosed that comprises a metallic load-bearing structure. The load-bearing structure comprises an outer surface and a cavity extending into the outer surface. The cavity accommodates an electronic component that is held in a fixed position in the cavity by an encapsulant. The cavity is covered by a plate that is welded over the cavity in close proximity to the electronic component and encapsulant to provide a seal over the cavity and the electronic component. [0014] In a refinement, the encapsulant is substantially free of thermal damage despite the close proximity of the encapsulant to the welded plate. [0015] In another refinement, the barrier is a silicone encapsulant that is temperature stable below about 150°. In a further refinement of this concept, the silicone encapsulant fills the cavity without substantial void spaces. [0016] In another refinement, the load-bearing structure may also include a channel that extends from the cavity and along the outer surface of the structure. In such a refinement, the channel can be used to accommodate a wire, wire bundle or wire bus connected to the electronic component. In such an embodiment, the wire may extend through the channel and outside the implant as the encapsulant is used to form a barrier that prevents body fluids from entering the cavity and reaching the electronic component. [0017] In a refinement, a single plate is also welded over the channel and the cavity without damage to the encapsulant or electronic component. [0018] In another refinement, the metallic load-bearing structure further comprises a landmark, such as a screw hole of an IM nail, and the electronic component is a spatial sensor used to identify a location of the landmark in a patient's body during installation of the IM nail. [0019] In designing the IM nails and implants discussed above, special attention is paid to the issue of potential damage to the encapsulant and possible the sensor for implants that have shallow cavities for the sensor and shallow channels for the wiring or wire bus. Damage to the encapsulant and possibly the sensor becomes an issue as the welding area is in close proximity to the encapsulant and sensor. [0020] Therefore, techniques are disclosed for encapsulating an electronic component within a cavity of a load-bearing implant that must also be welded. The disclosed techniques may include one or more of the following concepts: (a) post-curing treatment of the encapsulant to minimize the thermal degradation of the encapsulant during the welding process; (b) encapsulation techniques that reduce or eliminate void spaces in the encapsulant or cavity for long-term protection of the electronic component from body fluids; (c) optimization of the laser welding conditions such as pulse energy, duration, and repetition rate, traverse speed, degree of overlap of the of the laser weld spots during pulse mode and penetration of the weld spots to limit the exposure of the encapsulant to heat; (d) improved designs of the weld plate geometry and cavity assembly; and (e) application of heat sinks to limit the heat transferred from the weld location to the encapsulant. [0021] In one disclosed method, a hermetic seal is formed by a combination of: (i) potting or encapsulating the electronic component in a cavity of the implant with little or no void space; and (ii) pulsed laser welding of a weld plate over the cavity that provides a hermetic seal and that minimizes the thermal degradation of the encapsulant. Such a method may include: providing an implant and weld plate configured to provide offset weld lines around the periphery of the recess; injecting encapsulant at a first temperature and, prior to the welding of the weld plate to the device; exposing the cured encapsulant to an elevated second temperature; using pulsed laser welding parameters selected from the group consisting of: a pulse energy of in the range of from about 1 to about 3 J, a pulse duration in the range of from about 2 to about 8 msec, a pulse repetition in the range of from about 2 to about 8 Hz, a traverse speed in the range of from about 50 to about 150 mm/min, shield gas delivered at a rate ranging from about 10 to about 30 l/min at a pressure ranging from about 2 to about 4 bar, weld spot overlap ranging from about 35 to about 80%, weld penetration ranging from about 30 to about 85% and combinations thereof. [0022] In a refinement, the welding parameters may be controlled to produce a desired overlap of the weld spots that can range from about 35 to about 80%, more preferably from about 70 to about 80%, while maintaining the temperature inside the cavity below about 150° C. to avoid thermal damage to the encapsulant. [0023] In another refinement, the welding parameters may be controlled to produce a desired weld penetration that can range from about 30% to about 85%, more preferably from about 35% to about 50%, while maintaining the temperature inside the cavity below about 150° C. One specific, but non-limiting example, utilizes a pulse energy of about 2 J, a pulse duration of about 5 msec, a pulse repetition of about 5 Hz, a traverse speed of about 100 mm/min, argon shield gas delivered at a rate of about 20 l/min at 3 bar, weld overlap of greater than 50% and weld penetration of greater than 35%, while maintaining the temperature of the cavity below 150° C. Obviously, these parameters will vary depending upon the size, structure and materials of construction of the implant or device that will accommodate the electronic component(s) as well as the particular encapsulant used and the particular electronic component(s) that is being hermetically sealed in the implant. [0024] In a refinement, the encapsulant is applied with a needle and pressurized syringe. [0025] In another refinement, the encapsulant is also injected into the cavity of the implant that houses the electronic device or sensor using a sealed mold. In such a refinement, the silicone may be cured in the mold. [0026] In a refinement, an implantable medical device is manufactured according to the disclosed methods. In a further refinement, improved IM nails are manufactured according to the disclosed methods. [0027] The offset weld lines help minimize the amount of heat dissipated into the encapsulant during the welding step. A suitable offset for the weld lines ranges from about 250 to about 750 microns from the peripheral edges of the cavity. In one specific, but non-limiting example, the offset is about 500 microns. Obviously, this parameter will vary greatly, depending upon the particular implant. [0028] Heat sinks can be located in the inner bore of the device and/or as an external sleeve with aperture to limit the heat transferred from the weld location to the encapsulant. The heat sinks can made from thermal conductors such as copper, silver or aluminum alloys. [0029] To combine the advantages of aluminum and copper, heat sinks can be made of aluminum and copper bonded together. Thermally conductive grease may be used to ensure optimal thermal contact. If utilized, the thermally conductive grease may contain ceramic materials such as beryllium oxide and/or aluminum nitride, but may also or alternatively contain finely divided metal particles, e.g. colloidal silver. The heat sinks may be designed to have a substantial surface area with optional fins. In a refinement, a clamping mechanism, screws, or thermal adhesive may be used to hold the heat sink tightly onto the component to maximize thermal conductivity, without crushing or damaging the implant or electronic component. The heat sink can be modular in design enabling different size implants in terms of length and/or diameter to be fitted during the welding operation. [0030] Silicone encapsulants may be typically cured at about 80° C. for a time period ranging from about 1 to about 2 hours or according to the manufacturer specifications. Post-curing of the encapsulant at an elevated temperature will enhance the physical and performance properties of the silicone by increasing cross-link density, mitigating out-gassing, removing volatile agents by diffusion and evaporation and allowing the material to become conditioned to the service temperature of the welding operation. [0031] Following a normal cure cycle for a silicone, the silicone can be exposed to mild heat (from about 160 to about 180° C.) for a time period ranging from about 4 to about 8 hours. Lower temperature ranges can be used in a range of from about 100 to about 120° C. over longer periods (-24 hours). Insufficient curing can result in bubbling and production of potentially toxic monomers. On the other hand, increasing the temperature above 180° C. has been shown to have an adverse effect on the encapsulated electronic components. [0032] The disclosed methods are useful for devices in which electronic components may be in close proximity with the parts to be welded and require a sealed environment. For example, the disclosed methods are useful in fabricating orthopedic, dental and maxillofacial devices and implants as well as a host of other non-medical applications. [0033] The disclosed low-temperature pulsed laser welding methods are compatible with many soft elastomers in combination with an electronics module. In a refinement, the encapsulant is a soft elastomer. In another refinement, particularly for the fabrication of medical implants, the encapsulant may be a medical grade silicone. In other refinements, conformable potting materials, such as a bio-inert polymer, e.g. polyurethane, epoxy resin, and polyetheretherketone (PEEK) can be used as an encapsulant material. [0034] The encapsulant may be used in combination with a biocompatible primer to promote adhesion to the implant base metal minimizing void formation within the cavity. [0035] Other advantages and features will be apparent from the following detailed description when read in conjunction with the attached drawings. 
IP Reference WO2010088531 
Protection Patent granted
Year Protection Granted 2013
Licensed No
Impact A method for hermetically sealing an electronic component in a load-bearing implant, the method comprising: providing a load-bearing implant with a cavity for accommodating the electronic component; providing a weld plate configured to cover the cavity with an offset margin extending around a periphery of the cavity; encapsulating the electronic component in the cavity within an encapsulant; curing the encapsulant at a first temperature; heat treating the cured encapsulant to a second temperature; and welding a weld plate over the cavity along the offset margin without causing substantial thermal damage to the encapsulant so the weld plate provides a seal over the cavity.
 
Title Telemetric orthopaedic implant 
Description FIELD OF THE INVENTION The invention relates generally to orthopaedic implants, and more particularly to orthopaedic implants having data acquisition capabilities and their use in monitoring and diagnosing fracture healing. BACKGROUND TO THE INVENTION Fractures of long bones are a prevalent problem, accounting for 10% of non-fatal injuries in the USA (Kanakaris 2007). Of these, the most common are fractures of the tibial shaft, approximated to result in 77,000 hospitalisations a year in the USA (Schmidt et al 2003). The epidemiology and aetiology of tibial shaft fractures indicates a relation with risk behaviour. This type of fracture appears to be most prevalent in young men (Grutter 2000). A study by Court-Brown, 1995 found the mean age of patients witfh tibial shaft fractures to be 37 years, with the highest incidence occurring amongst teenage males. The two most common causes being; sports related injuries and road traffic accidents. There are several classifications described for fractures of the tibia, perhaps the most widely accepted of long bone fracture classifications in the AO/OTA classification (Arbeitsgemeinschaft fur Osteosynthesefragen/ Orthopaedic Trauma Association). This classification system looks solely at the pattern of fracture, not taking into consideration the local soft tissue damage (Fig1). Associated soft tissue injury may be classified according to the Tscherne and Gotzen classification (Schmidt et al 2003) for closed tibial fractures, and according to the Gustilo Anderson classification (Gustilo & Anderson 1976) for open fractures. For an in-vitro biomechanical study of an instrumented nail, used for strain telemetry, the most useful of these classifications is the AO classification. This is an alphanumeric classification system for all long bone fractures. An example of a fracture classified in this way is 42-C2. "4" represents the tibia, whilst the "2" tells us this is a fracture of the diaphysis. Having described the location, the letters A, B or C are assigned to indicate the fracture type and increasing complexity. Subgroups of these, in increasing severity, are assigned by the addition of the numbers 1 ,2 or 3 (Grutter 2000). Further subdivisions of these groups may be made, to indicate the number of fragments. Of the various fracture, 42-A3 appears to be the most common, accounting for 23.9% of tibial diaphyseal fractures (Court-Brown 1995). Treatment of these fractures is broadly divided into two categories, conservative and surgical. Conservative therapy involved the use of a plaster-cast or functional bracing. Surgical treatment can involve either open-reduction and internal fixation (ORIF) of intramedullary (IM) nailing. A META-analysis comparing conservative treatment to ORIF found that despite significantly decreased risk of superficial wound infection, casting resulted in a lower rate of union at 20 weeks (p=0.008) (Littenburg et al. 1998). Additionally casting is limited by the severity of the fracture and deformity, with initial moderate or severe displacement increasing the rate of delayed of non-union from 9% to as much as 27% (Schmidt et al 2003). IM nailing appears to be the preferred method of treatment for the majority of tibial fractures (Schmidt et al 2003). This suggestion is supported by a Randomised Control Trial (RCT) which shows IM nailing to result in faster union and a decrease in the rates of malunion, in comparison to conservative treatment (Hooper GJ 1991). Delayed or non-union are a major concern with tibial fractures. On a "best case scenario" calculation the cost of one tibial non-union is estimated to be £16,330, with 20% being direct costs of treatment and 80% due to indirect costs (Kanakaris 2007). The reported incidence of delayed union shows a great degree of variability due to the arbitrary definitions used. Generally delayed union of the tibia is recognised at 20 weeks, however, earlier detection may be possible. One could think of delayed union as the point at which altering the treatment may be considered, in order to achieve union (Phieffer & Goulet 2006). The definition of non-union is broadly accepted as the presence of no radiographic evidence of healing for three consecutive months, in a fracture of at least 9 months of age. The prevalence of delayed and non-union is reported to be 4.4% and 2.5% respectively. However, in open fractures, delayed union may be as high as 41 %, requiring further treatment before union is achieved (Phieffer & Goulet 2006). Treatment for delayed union varies in light of the cause. This can, broadly speaking, involve stabilisation, re-nailing, bone-grafts, adjunct therapy such as electrical stimulation, ultrasound or biological adjuncts such as Bone Morphogenic Protein (BMP). However timing is key to success as early diagnosis and treatment of delayed union can save the patient from considerable periods of disability and pain (Phieffer & Goulet 2006), whilst also having an impact on health economics due to a reduction in morbidity. Various methods have been used to ascertain the end point of healing of fractures. This is fundamental knowledge to clinicians so as to advise patients on appropriate load bearing in the injured limb or to diagnose the risk of delayed or non-unions. Currently there is a lack of a gold standard method which supplies sensitive data, good repeatability as well as ease of use. Serial radiographs and manual manipulation, often used in conjunction, are subjective and show inter-clinician variability. The inaccuracy and complexity of using dexa-scans, vibrational analysis, scintigraphy and ultrasound has also eliminated them as potential measurement tools. TELEMETRY An IM nail acts to provide stability, whilst transmitting rotational, bending and compressive forces across the fracture site and maintaining anatomical alignment of the bone. The IM nail also acts as a load sharing device, gradually shifting the load to the bone, as it heals. Telemetry enables the direct measurement of strain and load carried by an appropriately instrumented IM and hence gives an indication of the progress of fracture repair without disrupting fracture healing. An example of a telemetric orthopaedic system is disclosed in WO 2007/025191, which is herein incorporated in its entirety. In addition to its clinical use, such methodology proves to be of great benefit toward increasing our understanding of fracture healing and its biomechanics. It allows optimisation of postoperative patient care, assessing the role of different activities on skeletal loads to identify which are most appropriate for providing the desired mechanical environment (Schneider E, 2001). Strain gauges, which enable the direct measurement of the load applied to the nail, are conventionally located in multiple recesses in the outer wall of the nail and hence have the potential to cause changes in the biomechanical properties of the nail. This in turn could lead to local weakening or stress concentration. We have identified redundancy associated with the provision of strain gauges at multiple locations on a nail and have identified: firstly an optimal position for a recess comprising a plurality of strain gauges and secondly an optimal orientation of the strain gauges relative to the longitudinal axis of the nail. The strain gauges are capable of monitoring the strain in a nail when it experiences either off-set axial compression, torsional forces or three/four point bending forces. The identification of the optimal positioning and orientation of the strain gauges will facilitate the generation of a single commercial design of an IM nail which can be used with varying fracture patterns. RADIOSTEREOMETRIC ANALYSIS (RSA) In vivo measurement of three-dimensional (3D) displacement of prosthetics or body parts was pioneered by Goran Selvik in 1974 (Bragdon et al 2002). RSA is also referred to as radiostereometry or roentgen stereophotogrammic analysis. RSA measurements can be obtained using pairs of simultaneous radiographs taken repeatedly over time. Tantalum bead markers are implanted into the body part or implant segment under study with at least three non- colinear beads needed to define each rigid body subject to scrutiny (Valstar et al. 2005). A 3D coordinate system is achieved by way of a calibration cage embedded with tantalum beads in well defined, immoveable positions. Two radiographs placed side-by-side, in a uniplanar arrangement or at a 90 degree angle to each other, in the case of a bi-planar arrangement (Valstar et al. 2005) are used to establish the 3D coordinates of the markers, and displacement between the rigid bodies can be calculated (Madanat et al. 2006) using commercially available RSA software systems. Whilst RSA is a "gold standard" technique for assessing fixation and migration of joint replacements and determining micromotion of the bone, this technique has not be considered for measuring inter-fragmentary movement in long bone fractures fixated with an orthopaedic fixation device. We have identified that RSA can be used accurately and precisely to measure interfragmentary movement in a long bone, such as a tibia, fixated with an IM nail before and after reduction of the fracture. SUMMARY OF THE INVENTION According to a first aspect of the invention there is provided a telemetric orthopaedic implant system, the system comprising: (a) an orthopaedic implant, the orthopaedic implant having a longitudinal axis and comprising (i) a strain gauge orientated at about +45° and/or at about -45° relative to the longitudinal axis of the implant; (ii) a recess adapted to receive said strain gauge(s); (iii) an electronic component electrically connected to at least a power supply, a first transmitter, a first receiver, and a first microprocessor; (iv) a recess adapted to receive said electronic components; (v) potting material to seal said recess; (vi) a power source electrically connected to said electronic component. (b) a control unit, the control unit comprising; (i) a second microprocessor (ii) a second transmitter electrically connected to said second microprocessor, the second transmitter adapted to send a signal to said first receiver of said electronic component; and (iii) a second receiver electrically connected to said second microprocessor, the second receiver adapted to receive data from said transmitter of said electronic component. The gauges orientated at about +45° or at about -45° relative to the longitudinal axis of the orthopaedic implant have been identified as being optimally positioned to measure strain associated with either torque and also three- or four-point bending. The relative location of the gauges to the fracture site has been found to be unimportant when measuring strain upon application of torque. In embodiments of the invention further strain gauges are provided which are orientated either at about 0° or about 90° relative to the longitudinal axis of the orthopaedic implant. Such orientation has been identified as being optimal for measuring strain associated with offset-axial loading. However, the relative location of the gauges to the fracture site has been found to be important and there is a significant diminishment in sensitivity in strain measurement when the fracture site is distal to the gauge. It is therefore desirable in a commercial embodiment of a nail to provide gauges which are capable of measuring strain regardless of fracture type and location and to provide healthcare personnel with options relating to the mechanical loading regime to be utilised. For example, off-set axial compression loading requires the patient to be ambulatory. Whilst a commercial IM nail could therefore be provided with gauges orientated at about +45° and'or about -45° relative to the longitudinal axis of the orthopaedic implant this would limit the loading regime to torque, which may not be satisfactory or possible with some patients. The potential for an IM nail to offer an alternative to torque loading ie. off-set axial compression or three- or four point bending by the provision of differently orientated gauges in one recess is therefore viewed as an attractive commercial offering that will not prejudice the mechanical integrity of the IM nail. Commercial embodiments of the nail have a recess which comprises a strain gauge orientated at about +45° and a strain gauge orientated at about 0°, or a strain gauge orientated at about +45° and a strain gauge orientated at about 90°, or a strain gauge orientated at about -45° and a strain gauge orientated at about 0°, or strain gauge orientated at about -45° and a strain gauge orientated at about 90°. In embodiments of the invention the recess comprises a strain gauge orientated at +45°, a strain gauge orientated at about -45° and a strain gauge located at about 0°, or a strain gauge orientated at about +45°, a strain gauge orientated at about -45° and a strain gauge orientated at about 90°, or a strain gauge orientated at about +45°, a strain gauge orientated at about 0° and a strain gauge orientated at about 90°, or a strain gauge orientated at about -45°, a strain gauge orientated at about 0° and a strain gauge orientated at about 90°. In embodiments of the invention the recess comprises a strain gauge orientated at about +45°, a strain gauge orientated at about -45 °, a strain gauge orientated at about 0° and a strain gauge orientated at about 90°. Examples of suitable mechanical strain gauges include foil, thin film, or semiconductor strain gauges. Alternatively, the sensors may be load cells used to directly measure mechanical load. In embodiments of the invention a lid is optionally associated with the recess to provide electrical shielding for the circuitry therein. According to a second aspect of the invention there is provided a telemetric orthopaedic implant comprising; (i) a strain gauge orientated at about +45° and/or -45° relative to a longitudinal axis of the implant; (ii) a recess adapted to receive said strain gauge(s); (iii) an electronic component electrically connected to at least a power supply, a first transmitter, a first receiver, and a first microprocessor; (iv) a recess adapted to receive said electronic components; (v) potting material to seal said recesses; (vi) a power source electrically connected to said electronic component. In embodiments of the second aspect of the invention at least one further strain gauge is orientated at about 0° and/or at about 90° relative to the longitudinal axis of the implant. In embodiments of the invention a lid is optionally associated with the recess to provide electrical shielding for the circuitry therein. In embodiments according to the first and second aspects of the invention the orthopaedic implant is an IM nail. A telemetric IM nail has been previously disclosed in WO 2007/025191 which is herein incorporated, by reference, in its entirety. Suitable materials and methodology for the instrumentation of a nail and examples of suitable peripheral components for use in communication and for storing information received from the nail are disclosed in WO 2007/025191. In embodiments of the invention the telemetric orthopaedic implant, more specifically an IM nail is provided with a single recess for receiving the strain gauges. In specific embodiments of the invention this single recess is located in the proximal portion of the nail. In specific embodiments of the invention this single recess comprises or consists of strain gauges orientated about +45° and about 0° or about -45° and about 0° relative to the longitudinal axis of the nail. In alternative embodiments of the invention the recess in which the strain gauges are provided is located substantially mid-way along the length of the longitudinal axis of the IM nail. In an alternative embodiment of the invention the strain gauge recess is located substantially mid-way along the length of the longitudinal axis and extending into the tapered proximal region of the nail. The wall thickness of the proximal region in some designs of an IM nail is slightly thicker and the provision of a recess which retains the strain gauges and the associated electronic components has less effect on the mechanical integrity of the nail than if the recess was located in other regions of the nail. In embodiments of the invention the recess is dimensioned such that the pocket extends along the longitudinal axis of the nail and has a length greater than its width. In embodiments of the invention the recess has a length of between about 10 and 150mm, or between about 10 and 130 mm, or between about 100mm and 150mm, or between about 100mm and 140mm, or between about 100mm and 130mm, or between about 120mm and 140mm. In embodiments of the invention the recess has a length of about 130mm. The recess has a mid-way point along its length. In embodiments of the invention the mid-way point along the length of the recess is located approximately mid-way along the longitudinal axis of the IM nail. In embodiments of the invention the mid-way point along the length of the recess is offset from the mid-way point of the longitudinal axis of the nail, by up to the length of the pocket. For example, the length of the recess can be defined as having a first end and a second end, and either of these ends can be located at the mid-way point along the longitudinal axis of the nail. An example of an IM nail is the TRIGEN META NAIL® (Smith & Nephew). Due to the design constraints of the TRIGEN META NAIL®, the recess is located in the proximal region of the nail. In embodiments of the invention the IM nail comprises or consists of the design of the 8 or 9 pocket nail disclosed in Table 1 In embodiments of the invention the IM nail is for use in repairing fractures of the long bones, for example tibial or femoral fractures. Alternative embodiments include incorporation of the strain gauges and the other electronic components within other implantable trauma products, such as a plate, a bone screw, a cannulated screw, a pin, a rod, a staple, and a cable. Further, the instrumentation described herein is extendable to joint replacement implant, such as total knee replacements (TKR) and total hip replacements (THR), dental implants, and craniomaxillofacial implants. According to a .third aspect of the invention there is provided the use of a telemetric orthopaedic implant according to the second aspect of the invention in the system according to the first aspect of the invention. While immobilization and surgery may facilitate bone healing, the healing of a fracture still requires adequate physiological healing which can be achieved through continuously monitoring changes in the in situ load distribution between the implant and the surrounding bone using sensors and a biotelemetry system. The mass and architecture of bone are known to be influenced by mechanical loading applied to them. In the absence of appropriate loading due to stress shielding caused by poor management of internal orthopaedic fixation systems, bone mass is reduced, resulting in compromised healing of the fracture. The primary function of a telemetric orthopaedic implant is to carry load immediately after surgical placement. For example, the telemetric orthopaedic nail carries the load immediately after surgical placement in the intrameduallary canal. With progression of fracture healing, the load sharing between the implant and the bone changes. This can be tracked by using strain gauges which are optimally positioned within the orthopaedic implant regardless of the location of the fracture is. This has the advantage that a single design of nail can be used for a range of fracture types and fracture locations. The strain gauges are used to monitor the progress of union in the case of fracture by either continuously or intermittently monitoring the load component of the healing bone in all spatial components, which is unobtainable from X-rays. Periodic follow-up will provide a graph that shows the gradual decrease of relative motion of the fragments until union occurs. Each fracture patient generates his or her own healing curve; however the general shape of the healing curve indicates whether the fracture will progress to either a union condition, delayed union condition or a non-union condition. The healing curve generated from a patient is dependent on a number of factors including the type and location of the fracture, health status (underlying disease), age, activity, rehabilitation, and time to reach weight bearing. According to a fourth aspect of the present invention there is provided a method of measuring applied mechanical load across an orthopaedic implant, said method comprising the steps of; (i) positioning a subject having a telemetric orthopaedic implant according to the second aspect of the invention in a position suitable for applying a desired mechanical load; (ii) applying the mechanical load to the implant; and (iii) interrogating at least one strain gauge provided within the implant. The load measured by the strain gauge can then by compared with hypothetical load vs. healing time curves showing the load distribution between an instrumented nail and the surrounding bone for (i) fractures that progress to a union condition, (iii) fractures that are a delayed non-union and (iii) fractures that maintain a non-union condition. Although fracture healing results in a reduction in implant load, the remaining load of the nail can be significant and are expected to increase with patient activity. It has been suggested that loading of the bone may increase up to 50% after implant removal. The load measured in the adjacent bone can be determined by subtracting the implant load from the load exerted through the limb, which is determined using either a force plate or balance. The clinician can also measure the load acting through the contra-lateral limb in order to provide a reference measurement for a fully functional limb. If the surgeon observes that the strain on the implant is decreasing over time, this implies that the surrounding hard tissue (for example the callus) is accepting some of the load and thus, the fracture is healing. However, if the strain on the implant is unchanged with time and at the approximate level as when the patient was discharged from hospital or other health care facility, this implies that the surrounding hard tissue is not bearing the load and, therefore the fracture is not healing. In embodiments of the method according to the fourth aspect of the invention there is provided a method of measuring the mechanical load across an implanted telemetric orthopaedic implant upon application of a torsional force, said method comprising the steps of; (i) positioning a subject having the telemetric orthopaedic implant either in a stance or supine position; (ii) applying a torsional force on the telemetric orthopaedic implant; and (iii) interrogating a strain gauge in the about +45° and/or about -45° orientation. In embodiments of the method according to the fourth aspect of the invention there is provided a method of measuring the mechanical load across an orthopaedic implant upon application of an off-set axial compressive force, said method comprising the steps of; (i) positioning a subject having the telemetric orthopaedic implant in a stance position; (ii) applying an off-set axial compressive force on the telemetric orthopaedic implant; and (iii) interrogating a strain gauge in the about 0c and/or about 90° orientation. In embodiments of the method according to the fourth aspect of the invention there is provided a method of measuring the mechanical load across an orthopaedic implant upon application of a three or four point bending force, said method comprising the steps of; (i) positioning a subject having the telemetric orthopaedic implant in a stance or supine position; (ii) applying a three or four point bending force on the telemetric orthopaedic implant; and (iii) interrogating a strain gauge in the about +45°, about -45°, about 0° and/or about 90° orientation. According to a fifth aspect of the present invention there is provided a method of monitoring fracture healing in a subject, said method comprising the steps of; (i) positioning a subject having a telemetric orthopaedic implant according to the second aspect of the invention in a position suitable for applying a desired mechanical load; (ii) applying the mechanical load; (iii) interrogating at least one strain gauge provided within the implant; (iv) correlating the strain with a reference fracture healing curve. In embodiments according to the fifth aspect of the invention the mechanical load is selected from the group consisting of; off-set axial compression, torque, three point bending or four point bending, wherein the subjecting is optionally positioned in the stance or supine phase. The IM nail can be used to detect changes in fracture callus stiffness and determine healing status of the patient. The IM nail can detect changes of at least 4.1 Nm/0 in callus stiffness. It is therefore envisaged that the nail can detect delayed or non-union fracture within one month of tibial fracture fixation based on callus stiffness measurements. According to a sixth aspect of the invention there is provided the use of radiostereometric analysis for the measurement of inter-fragmentary movement within a bone fracture, wherein the bone fracture is fixed with an orthopaedic fixation device. In embodiments of the invention RSA can be used to differentiate between intact, reduced and non-reduced fractures. According to a seventh aspect of the invention there is provided the use of RSA to differentiate between intact, reduced and non-reduced fractures. According to an eighth aspect of the invention there is provided a method of measuring inter-fragmentary movement within a bone fracture, wherein the bone fracture is fixed with a fracture fixation device, said method comprising; i) associating of a plurality of radio-opaque markers with the fractured bone and/or the fracture fixation device; ii) positioning a calibration cage comprising a plurality of radio-opaque markers at known locations in relation to the fracture site; iii) undertaking a radiographic examination of the fracture site, wherein the fracture site and the calibration cage are simultaneously x-rayed from at least two angles; iv) generating a three-dimensional co-ordinate system based upon the location of the radio-opaque markers in the calibration cage; v) comparing the three-dimensional location of the radio-opaque markers associated with the fractured bone and/or the fracture fixation device with the three-dimensional co-ordinate system. In embodiments of the invention the fracture is of the long bones, for example the tibia or femur. The orthopaedic device can be for example, an intrameduallary nail, bone plate or external fixator, such as an llazorov frame. In a specific embodiment of the invention RSA is used to accurately and precisely monitor inter-fragmentary movement in a tibial shaft fracture fixed with an IM nail. An example of a suitable radio-opaque marker is a tantalum bead, although alternative radio-opaque makers which are suitable for use in RSA are envisaged. Alternatively, the solder joints associated with the electronic components can be utilised as reference points for monitoring inter-fragmentary bone movement. The radio-opaque markers are preferably associated with the proximal and distal segments of the fracture, thereby defining the rigid body segments. At least 3 radio-opaque markers are associated with the proximal and distal segments of the fracture. The radio-opaque markers are preferably associated with the bone and/or implant in a scattered pattern. The orthopaedic device can be selected from, for example, an IM nail, bone plate or external fixator, such as an llazorov frame. RSA is capable of measuring micromotion of the bone as a result of positional change of the implant (through loosening or dynamization of the screws), variations of the forces acting on the implant (inducible displacements) and is also capable of indirectly measuring callus stiffness. Thus, RSA can be used post-operatively to assess both implant stability and fracture reduction. It is further envisaged that RSA can be used as an intra-operative tool for trauma fixation. The utilisation of this technique will enable the surgeon to correct implant malposition or malalignment and to ensure that the fracture is adequately reduced. It is envisaged in further embodiments of the invention that the inventions according to one or more aspects of the invention can be combined. For example, a fracture can be fixed with an appropriately instrumented IM nail, allowing both the telemetric and radiostereometric assessment of fracture healing. Advantageously the instrumented IM nail used and the system comprising the IM nail is as defined according to the first and second aspects of the invention. According to a ninth aspect of the invention there is provided the use of a system according to the first aspect of the invention or a telemetric orthopeadic implant according to the second aspect of the invention in the in vitro analysis of fracture healing, for example biomechanical models of fracture healing, including animal models. According to a tenth aspect of the invention there is provided a methods, devices and systems as substantially herein described with reference to the accompanying Examples, Tables and Figures. Further features, aspects, and advantages of the present invention, as well as the structure and operation of various embodiments of the present invention, are described in detail below with reference to the accompanying drawings. 
IP Reference WO2011004151 
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Year Protection Granted 2014
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