Accurate measurement of local strain in heterogeneous and anisotropic bone tissue is fundamental to understand the pathophysiology of musculoskeletal diseases, to evaluate the effect of interventions from preclinical studies, and to optimize the design and delivery of biomaterials. Digital volume correlation (DVC) can be used to measure the three-dimensional displacement and strain fields from micro-computed tomography (μCT) images of loaded specimens. However, this approach is affected by the quality of the input images, by the morphology and density of the tissue under investigation, by the correlation scheme, and by the operational parameters used in the computation. Therefore, for each application, the precision of the method should be evaluated. In this paper, we present the results collected from datasets analyzed in previous studies as well as new data from a recent experimental campaign for characterizing the relationship between the precision of two different DVC approaches and the spatial resolution of the outputs. Different bone structures scanned with laboratory source μCT or synchrotron light μCT (SRμCT) were processed in zero-strain tests to evaluate the precision of the DVC methods as a function of the subvolume size that ranged from 8 to 2,500 µm. The results confirmed that for every microstructure the precision of DVC improves for larger subvolume size, following power laws. However, for the first time, large differences in the precision of both local and global DVC approaches have been highlighted when SRμCT or in vivo μCT images were used instead of conventional ex vivo μCT. These findings suggest that in situ mechanical testing protocols applied in SRμCT facilities should be optimized to allow DVC analyses of localized strain measurements. Moreover, for in vivo μCT applications, DVC analyses should be performed only with relatively course spatial resolution for achieving a reasonable precision of the method. In conclusion, we have extensively shown that the precision of both tested DVC approaches is affected by different bone structures, different input image resolution, and different subvolume sizes. Before each specific application, DVC users should always apply a similar approach to find the best compromise between precision and spatial resolution of the measurements.

Injuries of bone and cartilage constitute important health issues costing the National Health Service billions of pounds annually, in the UK only. Moreover, these damages can become cause of disability and loss of function for the patients with associated social costs and diminished quality of life. The biomechanical properties of these two tissues are massively different from each other and they are not uniform within the same tissue due to the specific anatomic location and function. In this perspective, tissue engineering (TE) has emerged as a promising approach to address the complexities associated with bone and cartilage regeneration. Tissue engineering aims at developing temporary three-dimensional multicomponent constructs to promote the natural healing process. Biomaterials, such as hydrogels, are currently extensively studied for their ability to reproduce both the ideal 3D extracellular environment for tissue growth and to have adequate mechanical properties for load bearing. This review will focus on the use of two manufacturing techniques, namely electrospinning and 3D printing, that present promise in the fabrication of complex composite gels for cartilage and bone tissue engineering applications.

A micromechanical characterization of biomaterials for bone tissue engineering is essential to understand the quality of the newly regenerated bone, enabling the improvement of tissue regeneration strategies. A combination of microcomputed tomography in conjunction with in situ mechanical testing and digital volume correlation (DVC) has become a powerful technique to investigate the internal deformation of bone structure at a range of dimensional scales. However, in order to obtain accurate three-dimensional strain measurement at tissue level, high-resolution images must be acquired, and displacement/strain measurement uncertainties evaluated. The aim of this study was to optimize imaging parameters, image postprocessing and DVC settings to enhance computation based on 'zero-strain' repeated high-resolution synchrotron microCT scans of trabecular bone and bone-biomaterial systems. Low exposures to SR X-ray radiation were required to minimize irradiation-induced tissue damage, resulting in the need of advanced three-dimensional filters on the reconstructed images to reduce DVC-measured strain errors. Furthermore, the computation of strain values only in the hard phase (i.e. bone, biomaterial) allowed the exclusion of large artefacts localized in the bone marrow. This study demonstrated the suitability of a local DVC approach based on synchrotron microCT images to investigate the micromechanics of trabecular bone and bone-biomaterial composites at tissue level with a standard deviation of the errors in the region of 100 microstrain after a thorough optimization of DVC computation. LAY DESCRIPTION: Understanding the quality of newly regenerated bone after implantation of novel biomaterials is essential to improve bone tissue engineering strategies and formulation of biomaterials. The relationship between microstructure and mechanics of bone has been previously addressed combining microcomputed tomography with in situ mechanical testing. The addition of an image-based experimental technique such as digital volume correlation (DVC) allows to characterize the deformation of materials in a three-dimensional manner. However, in order to obtain accurate information at the micro-scale, high-resolution images, obtained for example by using synchrotron radiation microcomputed tomography, as well as optimization of the DVC computation are needed. This study presents the effect of different imaging parameters, image postprocessing and DVC settings for as accurate investigation of trabecular bone structure and bone-biomaterial interfaces. The results showed that when appropriate image postprocessing and DVC settings are used DVC computation results in very low strain errors. This is of vital importance for a correct understanding of the deformation in bone-biomaterial systems and the ability of such biomaterials in producing new bone comparable with the native tissue they are meant to replace.

The use of synchrotron radiation micro-computed tomography (SR-microCT) is becoming increasingly popular for studying the relationship between microstructure and bone mechanics subjected to in situ mechanical testing. However, it is well known that the effect of SR X-ray radiation can considerably alter the mechanical properties of bone tissue. Digital volume correlation (DVC) has been extensively used to compute full-field strain distributions in bone specimens subjected to step-wise mechanical loading, but tissue damage from sequential SR-microCT scans has not been previously addressed. Therefore, the aim of this study is to examine the influence of SR irradiation-induced microdamage on the apparent elastic properties of trabecular bone using DVC applied to in situ SR-microCT tomograms obtained with different exposure times. Results showed how DVC was able to identify high local strain levels (> 10,000 µε) corresponding to visible microcracks at high irradiation doses (~ 230 kGy), despite the apparent elastic properties remained unaltered. Microcracks were not detected and bone plasticity was preserved for low irradiation doses (~ 33 kGy), although image quality and consequently, DVC performance were reduced. DVC results suggested some local deterioration of tissue that might have resulted from mechanical strain concentration further enhanced by some level of local irradiation even for low accumulated dose.

Osteoregenerative biomaterials for the treatment of bone defects are under much development, with the aim of favoring osteointegration up to complete bone regeneration. A detailed investigation of bone–biomaterial integration is vital to understand and predict the ability of such materials to promote bone formation, preventing further bone damage and supporting load-bearing regions. This study aims to characterize the ex vivo micromechanics and microdamage evolution of bone–biomaterial systems at the tissue level, combining high-resolution synchrotron microcomputed tomography, in situ mechanics and digital volume correlation. Results showed that the main microfailure events were localized close to or within the newly formed bone tissue, in proximity to the bone–biomaterial interface. The apparent nominal compressive load applied to the composite structures resulted in a complex loading scenario, mainly due to the higher heterogeneity but also to the different biomaterial degradation mechanisms. The full-field strain distribution allowed characterization of microdamage initiation and progression. The findings reported in this study provide a deeper insight into bone–biomaterial integration and micromechanics in relation to the osteoregeneration achieved in vivo for a variety of biomaterials. This could ultimately be used to improve bone tissue regeneration strategies.