Gianluca Tozzi

Computation of full-field displacements in a scaffold implant using digital volume correlation and finite element analysis

Measurements of three-dimensional displacements in a scaffold implant under uniaxial compression have been obtained by two digital volume correlation (DVC) methods, and compared with those obtained from micro-finite element models. The DVC methods were based on two approaches, a local approach which registers independent small volumes and yields discontinuous displacement fields; and a global approach where the registration is performed on the whole volume of interest, leading to continuous displacement fields. A customised mini-compression device was used to perform in situ step-wise compression of the scaffold within a micro-computed tomography (μCT) chamber, and the data were collected at steps of interest. Displacement uncertainties, ranging from 0.006 to 0.02 voxel (i.e. 0.12-0.4 μm), with a strain uncertainty between 60 and 600 με, were obtained with a spatial resolution of 32 voxels using both approaches, although the global approach has lower systematic errors. Reduced displacement and strain uncertainties may be obtained using the global approach by increasing the element size; and using the local approach by increasing the number of intermediary sub-volumes. Good agreements between the results from the DVC measurements and the FE simulations were obtained in the primary loading direction as well as in the lateral directions. This study demonstrates that volumetric strain measurements can be obtained successfully using DVC, which may be a useful tool to investigate mechanical behaviour of porous implants.

Compressive behaviour of bovine cancellous bone and bone analogous materials, microCT characterisation and FE analysis.

Compressive behaviour of bovine cancellous bone and three open-cell metallic foams (AlSi7Mg (30 ppi and 45 ppi); CuSn12Ni2 (30 ppi)) has been studied using mechanical testing, micro-focus computed tomography and finite element modelling. Whilst the morphological parameters of the foams and the bone appear to be similar, the mechanical properties vary significantly between the foams and the bone. Finite element models were built from the CT images of the samples and multi-linear constitutive relations were used for modelling of the bone and the foams. The global responses of the bone and foam samples were reasonably well captured by the FE models, whilst the percentage of yielded elements as a measure of damage evolution during compression seems to be indicative of the micro-mechanical behaviour of the samples. The damage evolution and distribution patterns across the bone and the foams are broadly similar for the strain range studied, suggesting possible substitution of trabecular bones with appropriate foams for biomechanical studies.

Bone–cement interfacial behaviour under mixed mode loading conditions

Interfacial behaviour of the bone-cement interface has been studied under tensile, shear and mixed mode loading conditions. Bovine cancellous bone was used to bond with acrylic bone cement to form bone-cement interface samples, which were mechanically tested under selected tensile, shear and mixed mode loading conditions. The influence of the loading angle and the extent of the cement penetration on the interfacial behaviour were examined. The failure mechanisms with regard to loading mode were examined using micro-focus computed tomography. The measured tensile and shear responses were utilized in a cohesive zone constitutive model, from which the pre-yield linear and the post-yield exponential strain softening behaviour under mixed mode loading conditions was predicted. The implications of the work on the studies of cemented joint replacements are also discussed.

Composite Hydrogels for Bone Regeneration

Over the past few decades, bone related disorders have constantly increased. Among all pathological conditions, osteoporosis is one of the most common and often leads to bone fractures. This is a massive burden and it affects an estimated 3 million people only in the UK. Furthermore, as the population ages, numbers are due to increase. In this context, novel biomaterials for bone fracture regeneration are constantly under development. Typically, these materials aim at favoring optimal bone integration in the scaffold, up to complete bone regeneration; this approach to regenerative medicine is also known as tissue engineering (TE). Hydrogels are among the most promising biomaterials in TE applications: they are very flexible materials that allow a number of different properties to be targeted for different applications, through appropriate chemical modifications. The present review will focus on the strategies that have been developed for formulating hydrogels with ideal properties for bone regeneration applications. In particular, aspects related to the improvement of hydrogels’ mechanical competence, controlled delivery of drugs and growth factors are treated in detail. It is hoped that this review can provide an exhaustive compendium of the main aspects in hydrogel related research and, therefore, stimulate future biomaterial development and applications.

The use of digital image correlation in the biomechanical area: a review

Abstract This paper offers an overview of the potentialities and limitations of digital image correlation (DIC) as a technique for measuring displacements and strain in biomechanical applications. This review is mainly intended for biomechanists who are not yet familiar with DIC. This review includes over 150 papers and covers different dimensional scales, from the microscopic level (tissue level) up to macroscopic one (organ level). As DIC involves a high degree of computation, and of operator-dependent decisions, reliability of displacement and strain measurements by means of DIC cannot be taken for granted. Methodological problems and existing solutions are summarized and compared, whilst open issues are addressed. Topics addressed include: preparation methods for the speckle pattern on different tissues; software settings; systematic and random error associated with DIC measurement. Applications to hard and soft tissues at different dimensional scales are described and analyzed in terms of strengths and limitations. The potentialities and limitations of DIC are highlighted, also in comparison with other experimental techniques (strain gauges, other optical techniques, digital volume correlation) and numerical methods (finite element analysis), where synergies and complementarities are discussed. In order to provide an overview accessible to different scientists working in the field of biomechanics, this paper intentionally does not report details of the algorithms and codes used in the different studies.

Three-Dimensional Local Measurements of Bone Strain and Displacement: Comparison of Three Digital Volume Correlation Approaches

Different digital volume correlation (DVC) approaches are currently available or under development for bone tissue micromechanics. The aim of this study was to compare accuracy and precision errors of three DVC approaches for a particular three-dimensional (3D) zero-strain condition. Trabecular and cortical bone specimens were repeatedly scanned with a micro-computed tomography (CT). The errors affecting computed displacements and strains were extracted for a known virtual translation, as well as for repeated scans. Three DVC strategies were tested: two local approaches, based on fast-Fourier-transform (DaVis-FFT) or direct-correlation (DaVis-DC), and a global approach based on elastic registration and a finite element (FE) solver (ShIRT-FE). Different computation subvolume sizes were tested. Much larger errors were found for the repeated scans than for the virtual translation test. For each algorithm, errors decreased asymptotically for larger subvolume sizes in the range explored. Considering this particular set of images, ShIRT-FE showed an overall better accuracy and precision (a few hundreds microstrain for a subvolume of 50 voxels). When the largest subvolume (50-52 voxels) was applied to cortical bone, the accuracy error obtained for repeated scans with ShIRT-FE was approximately half of that for the best local approach (DaVis-DC). The difference was lower (250 microstrain) in the case of trabecular bone. In terms of precision, the errors shown by DaVis-DC were closer to the ones computed by ShIRT-FE (differences of 131 microstrain and 157 microstrain for cortical and trabecular bone, respectively). The multipass computation available for DaVis software improved the accuracy and precision only for the DaVis-FFT in the virtual translation, particularly for trabecular bone. The better accuracy and precision of ShIRT-FE, followed by DaVis-DC, were obtained with a higher computational cost when compared to DaVis-FFT. The results underline the importance of performing a quantitative comparison of DVC methods on the same set of samples by using also repeated scans, other than virtual translation tests only. ShIRT-FE provides the most accurate and precise results for this set of images. However, both DaVis approaches show reasonable results for large nodal spacing, particularly for trabecular bone. Finally, this study highlights the importance of using sufficiently large subvolumes, in order to achieve better accuracy and precision.

3D real-time micromechanical compressive behaviour of bone-cement interface: experimental and finite element studies

The integrity of bone-cement interface is essential for the long-term stability of cemented total joint arthroplasty. Although several studies have been carried out on bone-cement interface at continuum level, micromechanics of the interface has been studied only recently for tensile and shear loading cases. Fundamental studies of bone-cement interface at microstructural level are critical to the understanding of the failure processes of the interface, where multiple factors may contribute to failure. Here we present a micromechanical study of bone-cement interface under compression, which utilised in situ mechanical testing, time-lapsed microcomputed tomography (CT) and finite element (FE) modelling. Bovine trabecular bone was used to interdigitate with bone cement to obtain bone-cement interface samples, which were tested in step-wise compression using a custom-made loading stage within the μCT chamber. A finite element model was built from the CT images of one of the tested samples and loaded similarly as in the experiment. The simulated stress-displacement response fell within the range of the experimental responses, and the predicted local strain distribution correlated well with the failure pattern in the subject-specific experimental model. Damage evolution with load in the samples was monitored both experimentally and numerically. The results from the FE simulations further revealed the development of damage in the regions of interest during compression, which may be useful towards a micromechanics understanding of the failure processes at bone-cement interface.

P2RX7 Purinoceptor::a therapeutic target for ameliorating the symptoms of Duchenne muscular dystrophy

Background Duchenne muscular dystrophy (DMD) is the most common inherited muscle disease, leading to severe disability and death in young men. Death is caused by the progressive degeneration of striated muscles aggravated by sterile inflammation. The pleiotropic effects of the mutant gene also include cognitive and behavioral impairments and low bone density. Current interventions in DMD are palliative only as no treatment improves the long-term outcome. Therefore, approaches with a translational potential should be investigated, and key abnormalities downstream from the absence of the DMD product, dystrophin, appear to be strong therapeutic targets. We and others have demonstrated that DMD mutations alter ATP signaling and have identified P2RX7 purinoceptor up-regulation as being responsible for the death of muscles in the mdx mouse model of DMD and human DMD lymphoblasts. Moreover, the ATP–P2RX7 axis, being a crucial activator of innate immune responses, can contribute to DMD pathology by stimulating chronic inflammation. We investigated whether ablation of P2RX7 attenuates the DMD model mouse phenotype to assess receptor suitability as a therapeutic target. Methods and Findings Using a combination of molecular, histological, and biochemical methods and behavioral analyses in vivo we demonstrate, to our knowledge for the first time, that genetic ablation of P2RX7 in the DMD model mouse produces a widespread functional attenuation of both muscle and non-muscle symptoms. In dystrophic muscles at 4 wk there was an evident recovery in key functional and molecular parameters such as improved muscle structure (minimum Feret diameter, p < 0.001), increased muscle strength in vitro (p < 0.001) and in vivo (p = 0.012), and pro-fibrotic molecular signatures. Serum creatine kinase (CK) levels were lower (p = 0.025), and reduced cognitive impairment (p = 0.006) and bone structure alterations (p < 0.001) were also apparent. Reduction of inflammation and fibrosis persisted at 20 mo in leg (p = 0.038), diaphragm (p = 0.042), and heart muscles (p < 0.001). We show that the amelioration of symptoms was proportional to the extent of receptor depletion and that improvements were observed following administration of two P2RX7 antagonists (CK, p = 0.030 and p = 0.050) without any detectable side effects. However, approaches successful in animal models still need to be proved effective in clinical practice. Conclusions These results are, to our knowledge, the first to establish that a single treatment can improve muscle function both short and long term and also correct cognitive impairment and bone loss in DMD model mice. The wide-ranging improvements reflect the convergence of P2RX7 ablation on multiple disease mechanisms affecting skeletal and cardiac muscles, inflammatory cells, brain, and bone. Given the impact of P2RX7 blockade in the DMD mouse model, this receptor is an attractive target for translational research: existing drugs with established safety records could potentially be repurposed for treatment of this lethal disease.

Microdamage assessment of bone-cement interfaces under monotonic and cyclic compression.

Bone-cement interface has been investigated under selected loading conditions, utilising experimental techniques such as in situ mechanical testing and digital image correlation (DIC). However, the role of bone type in the overall load transfer and mechanical behaviour of the bone-cement construct is yet to be fully quantified. Moreover, microdamage accumulation at the interface and in the cement mantle has only been assessed on the exterior surfaces of the samples, where no volumetric information could be obtained. In this study, some typical bone-cement interfaces, representative of different fixation scenarios for both hip and knee replacements, were constructed using mainly trabecular bone, a mixture of trabecular and cortical bone and mainly cortical bone, and tested under static and cyclic compression. Axial displacement and strain fields were obtained by means of digital volume correlation (DVC) and microdamage due to static compression was assessed using DVC and finite element (FE) analysis, where yielded volumes and strains (εzz) were evaluated. A significantly higher load was transferred into the cement region when mainly cortical bone was used to interdigitate with the cement, compared with the other two cases. In the former, progressive damage accumulation under cyclic loading was observed within both the bone-cement interdigitated and the cement regions, as evidenced by the initiation of microcracks associated with high residual strains (εzz_res).

Digital volume correlation can be used to estimate local strains in natural and augmented vertebrae: an organ-level study

Digital Volume Correlation (DVC) has become popular for measuring the strain distribution inside bone structures. A number of methodological questions are still open: the reliability of DVC to investigate augmented bone tissue, the variability of the errors between different specimens of the same type, the distribution of measurement errors inside a bone, and the possible presence of preferential directions. To address these issues, five augmented and five natural porcine vertebrae were subjected to repeated zero-strain micro-CT scan (39μm voxel size). The acquired images were processed with two independent DVC approaches (a local and a global one), considering different computation sub-volume sizes, in order to assess the strain measurement uncertainties. The systematic errors generally ranged within ±100 microstrain and did not depend on the computational sub-volume. The random error was higher than 1000 microstrain for the smallest sub-volume and rapidly decreased: with a sub-volume of 48 voxels the random errors were typically within 200 microstrain for both DVC approaches. While these trends were rather consistent within the sample, two individual specimens had unpredictably larger errors. For this reason, a zero-strain check on each specimen should always be performed before any in-situ micro-CT testing campaign. This study clearly shows that, when sufficient care is dedicated to preliminary methodological work, different DVC computation approaches allow measuring the strain with a reduced overall error (approximately 200 microstrain). Therefore, DVC is a viable technique to investigate strain in the elastic regime in natural and augmented bones.