X-ray biomechanical imaging and digital volume correlation of bone : from regeneration to structure

Bone as such displays an intrinsic regenerative potential following fracture; however, this capacity is limited with large bone defects that cannot heal spontaneously. The management of critical-sized bone defects remains a major clinical and socioeconomic need; thus, osteoregenerative biomaterials are constantly under development aiming at promoting and enhancing bone healing. Measuring the biomechanical response of regenerated bone at different dimensional scales is crucial in order to assess its mechanical performance and overall structural response, ultimately validating different treatments applied to restore bone within the defect site. The major aim of this PhD project was to combine high-resolution X-ray micro-computed tomography (microCT) biomechanical imaging and digital volume correlation (DVC) to newly formed bone structures in order to provide a detailed characterisation of bone formation, mechanical competence and deformation mechanisms at tissue level following use of different biomaterials in critical-sized bone defects. A methodological approach was developed to extract full-field deformation of bone at tissue level based on synchrotron radiation (SR)-microCT. This was achieved through an optimisation of image postprocessing and DVC settings that provided reliable displacement and strain measurements at tissue level to investigate the micromechanics of trabecular bone structures and bone-biomaterial systems. In addition, the effect of SR on bone integrity was assessed and experimental protocols were established for a safer and more reliable application of in situ SR-microCT experiments aiming at minimising the irradiation-induced tissue damage. The defined methods were then used for the investigation of the micromechanics of bone-biomaterial systems and newly formed bone in vivo after the application of osteoconductive and osteoinductive biomaterials. Microdamage initiation and propagation at the bone-biomaterial interface was identified, indicating that the resorption rate and osteoinduction properties of bone grafts may be as beneficial as the original stiffness of the scaffolds for an efficient micromechanics in vivo. Furthermore, the mechanical adaptation of bone structure at an early stage of bone regeneration was demonstrated irrespective of the implanted biomaterial in the bone defect. In conclusion, the experimental approaches herein presented have shown to be advantageous for investigating the local mechanics of bone tissue during the healing process in relation to the regeneration achieved in vivo for a variety of biomaterials. Moreover, results suggest that enhanced osteoinductive biomaterials offering a controlled release of growth factors could be successfully adopted for the treatment of critical-sized bone defects.