Osteoarthritis (OA) affects over 8.75 million people in the UK creating the need for early stage interventions. Osteochondral (OC) grafting has been used to repair full thickness lesions but the efficacy of this therapy is questionable.

As a first step in developing a testing framework able to predict the potential and suitability of OC grafts for repair, here, we present experimental data to be used in informing boundary conditions, input parameters and testing sequences for developing and verifying an FE model of the interaction of OC grafts and surrounding host tissue.

Ten OC cylindrical grafts (height: 10mm; diameter: n=5–6.5mm; n=5–8.5mm) were harvested from adult porcine femurs (60–70kg). Unconfined compression tests were conducted using an Instron3365 with a 500N load cell and a BioBath filled with PBS at 37ºC. The OC grafts (prior to separation of cartilage and bone) and cartilage underwent four 5% strain (of cartilage layer) steps with displacement rate of 0.005mm/sec, each followed by a 45-minute relaxation. Final strain was 20%. Bone underwent a single displacement of 20% strain of bone at same displacement rate.

Young's moduli ranged from 6.2–42.0MPa, 0.7–3.9MPa, 46.8–123.7MPa for OC graft, cartilage and bone, respectively. The coefficient of variance between OC Grafts, cartilage and bone was 70.6%, 71.8%, and 25.2%, respectively.

Dispersion between samples was high. This may be due to intrinsic tissue variability but also due to the testing protocol: for cartilage in particular, the load was at the low end of the load cell capacity and the sample aspect ratio was poor for compressive testing. This work provides insight in understanding the effect of individual patient's and/or individual grafts used during osteochondral grafting. The results compel the need to accurately model these tissues when developing specimen-specific FE models for OC grafting.

Osteochondral (OC) grafting is one available method currently used to repair full thickness cartilage lesions with good results clinically when grafting occurs in patients with specific positive prognostic factors. However, there is poor understanding of the effect of individual patient and surgical factors. With limited tissue availability, development of Finite Element (FE) models taking into account these variations is essential. The aim of this study was to evaluate the effect of altering the material properties of OC grafts and their host environment through computer simulation.

A generic FE model (ABAQUS CAE 2017) of a push-out test was developed as a press-fit bone cylinder (graft) sliding inside a bone ring (host tissue). Press-fit fixation was simulated using an interference fit. Overlap between host and graft (0.01mm–0.05mm) and coefficient of friction (0.3–0.7) were varied sequentially. Bone Young's moduli (YM) were varied individually between graft and host within the range of otherwise derived tissue moduli (46MPa, 82MPa, 123MPa).

Increasing both overlap and frictional coefficient increased peak dislodging force independently (overlap: 490% & frictional coefficient: 176% across range tested). Increasing bone modulus also increased dislodging force, with host bone modulus (107%, 128%, and 140% increase across range, when Graft YM = 123MPa, 82 MPa, and 46MPa, respectively) having a greater influence than graft modulus (28%, 19% and 10% increase across range, when Host YM = 123 MPa, 82MPa and 46MPa, respectively).

As anticipated increasing overlap and friction caused an increase in force necessary to dislodge the graft. Importantly, differentially changing the graft and host material properties changed the dislodging force indicating that difference between graft and host may be an important factor in the success or failure clinically of osteochondral grafting.

The purpose of this study was to develop a novel, minimally invasive therapy for nucleus pulposus augmentation without the need for major surgical incision.

Two optimum patented self-assembling peptides based on natural amino acids were mixed with glycosaminoglycans (GAGs) to form reversible, tunable hydrogels that mimic the vital biological osmotic pumping action and aid in swelling pressure of the intervertebral disc (IVD). Separate peptide and GAG solutions can be switched from fluid to gel upon mixing inside the body. The gels were analysed using a series of complementary techniques (FTIR, TEM & rheometry) to determine their cross-length scale structure and properties. Approaches to developing a clinical product were then developed including the incorporation of a fluorescent probe and a CT contrast agents to aid visualization of the gels, and a semi-automatic syringe driver rig, incorporating a pressure sensor, for the delivery of the solutions into the intervertebral discs. The efficacy of the procedure in restoring disc height and biomechanics was examined using chemically degenerated bovine caudal samples.

It was found the presence of the GAGs stabilized the peptides forming stiffer gels, even upon injection through a long (∼10cm) small gauge needle. The injected gels were easily visualized post injection by microCT and by eye during dissection under visible and UV light. It was also noted that following injection, the disc height of the degenerated samples was restored to a similar level of that observed for native discs.

A hydrogel has been developed that is injected through a narrow bore needle using a semi-automatic delivery rig and forms a self-assembled gel in situ which has shown to restore the disc height. Further tests are now underway to examine their biomechanical performance across more physiological time periods.

Intervertebral disc (IVD) degeneration is one of the major causes of back pain. A number of emerging treatments for the condition have failed during clinical trial due to the lack of robust biomechanical testing during product development. The aim of this work was to develop improved in-vitro testing methods to enable new therapeutic approaches to be examined pre-clinically. It forms part of a wider programme of research to develop a minimally invasive nucleus augmentation procedure using self-assembling hydrogels.

Previous static testing on extracted IVDs have shown large inter-specimen variation in the measured stiffness when specimen hydration and fluid flow were not well controlled. In this work, a method of normalising the hydration state of IVDs prior-to and during compressive testing was developed.

Excised adult bovine IVDs underwent water-pik treatment and a 24-hour agitated bath in monosodium citrate solution to maximise fluid mobility. Specimens were submerged in a saline bath and held under constant pressure for 24 hours, after which the rate of change of displacement was low. Specimens were then cyclically loaded, from which the normalised specimen stiffness was determined. A degenerate disc model was developed with the use of enzymatic degeneration, allowing specimens to be tested sequentially in a healthy, degenerate, and then treated state. Self-assembling peptide-GAG hydrogels were tested using the developed method and the effect of treatment on stiffness and disc height were assessed.

Compared to previous static tests, the improved method reduced the variation in the normalised specimen stiffness. In addition, statistically significant differences were seen before and after enzymatic degradation to simulate degeneration, thus providing controls against which to evaluate treatments. The augmentation of the nucleus with the hydrogel intervention reduces the stiffness of the degenerate disc towards that of the healthy disc. This method is now being used to further investigate nucleus augmentation devices.

The clinical uptake of minimally invasive interventions for intervertebral disc, such as nucleus augmentation, is currently hampered by the lack of robust pre-clinical testing methods that can take into account the large variation in the mechanical behaviour of the tissues. Using computational modelling to develop new interventions could be a way to test scenarios accounting for variation. However, such models need to have been validated for relevant mechanical function, e.g. compressive, torsional or flexional stiffness, and local disc deformations.

The aim of this work was to use a novel in-vitro imaging method to assess the validity of computational models of the disc that employed different degrees of sophistication in the anatomical representation of the nucleus.

Bovine caudal bone-disc-bone entities (N=6) were dissected and tested in uniaxial compression in a custom-made rig. Forty glass markers were placed on the surface of each disc. The specimens were scanned both with MRI and micro-CT before and during loading. Specimen-specific computational models were built from CT images to replicate the compression test. The anatomy of the nucleus was represented in three ways: assuming a standard diameter ratio, assuming a cylindrical shape with its volume matching that measured from MRI, and deriving the shape directly from MRI. The three types of models were calibrated for force-displacement. The radial displacement of the glass markers were then compared with their experimental displacement derived from CT images.

For a similar accuracy in modelling overall force-displacement, the mean error on the surface displacement was 35% for standard ratio nucleus, 38% for image-based cylindrical nucleus, and 32% for MRI-based nucleus geometry.

This work shows that, as long as consistency is kept to develop and calibrate image-based computational models, the complexity of the nucleus geometry does not influence the ability of a model to predict surface displacement in the intervertebral disc.

There are a number of periprosthetic femoral fracture (PFF) fixation failures. In several cases the effect of fracture configuration on the performance of the chosen fixation method has been underestimated. As a result, fracture movement within the window that seems to promote callus formation has not been achieved and fixations ultimately failed.

This study tested the hypothesis that: PFF configuration and the choice of plate fixation method can be detrimental to healing.

A series of computational models were developed, corroborated against measurements from a series of instrumented laboratory models and in vivo case studies. The models were used to investigate the fixation of different fracture configurations and plate fixation parameters. Surface strain and fracture movement were compared between the constructs.

A strong correlation between the computational and experimental models was found. Computational models showed that unstable fracture configurations increase the stress on the plate fixation. It was found that bridging length plays a pivotal role in the fracture movement. Rigid fixations, where there is clinical evidence of failure, showed low fracture movement in the models (<0.05mm); this could be increased with different screw and plate configurations to promote healing.

In summary our results highlighted the role of fracture configuration in PFF fixations and showed that rigid fixations that suppress fracture movement could be detrimental to healing.

Purpose: Subject-specific computational models of anatomical components can now be generated from image data and used in the assessment of orthopaedic interventions. Whilst such models are becoming more commonplace, there are few studies that have investigated the effects of element size or the level of morphological detail that is required to model complex hierarchical structures such as trabecular bone [1,2]. The purpose of this study was to investigate the modelling of the mechanical properties of a trabecular-like material under compression, and in particular to evaluate the relationship between the grey-scale dependent density, determined from microCT, and the elastic modulus at different levels of mesh density.

Materials and Methods: A specific open cell rigid foam (pcf 7.5, Sawbone, Sweden), with a porosity over 95% and cell size between 1.5 and 2.5 mm, was chosen to represent human cancellous bone. Five cylindrical specimens (24 mm diameter, 19 mm height) were compressed under a maximum displacement of 0.35 mm in a materials testing machine. All the specimens were imaged by microCT (ƒÝCT80, Scanco Medical, Switzerland) before the test to provide the geometry and greyscale distribution. Corresponding finite element models of each specimen were generated using proprietary software (ScanFE, Simpleware, UK) with an element size of 1.5 mm. The elastic modulus of each element was based on the image greyscale using a conversion factor that was determined, through trial-and-error, by matching the predicted displacement with the experimental measurement in the linear region (> 0.2 mm). For each specimen, models of higher and lower mesh densities were constructed by down-sampling the microCT output to different levels. The smallest element size was limited to 0.5 mm due to computational restrictions, however a smaller 8 mm cube of the material was also analysed, with element sizes down to 0.25 mm.

Results: From the experimental tests, the mean apparent elastic modulus of the specimens was found to be 15 MPa, as compared with 18 MPa specified by the manufacturer. For the computational models, the predicted elastic modulus of the whole specimen models was found to decrease with decreasing element size. In particular, there was a large drop in the predicted values when the element size was of the same order as the cell size. With larger elements, the results indicated some convergence and there was reasonable agreement with the experimental results. For the cube model with smaller element sizes, the predicted moduli values again appeared to converge as the element size was reduced to 0.25 mm.

Conclusion: The results of this study show that the optimum conversion factor from an image greyscale value to an elastic modulus varies with element size. If the finite element method is to be used effectively to model bone, then the mesh size must either be sufficiently large to use a continuum approach or sufficiently small to capture the behaviour of the individual trabeculae. Different conversion factors will be required to determine the material properties from the image greyscale in each case.