Applications of X-ray computed tomography for the evaluation of biomaterial-mediated bone regeneration in critical-sized defects.

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 with osteoregenerative biomaterials constantly under development aiming at promoting and enhancing bone healing. X-ray computed tomography (XCT) has become a standard and essential tool for quantifying structure-function relationships in bone and biomaterials, facilitating the development of novel bone tissue engineering strategies. This paper presents recent advancements in XCT analysis of biomaterial-mediated bone regeneration. As a noninvasive and nondestructive technique, XCT allows for qualitative and quantitative evaluation of three-dimensional (3D) scaffolds and biomaterial microarchitecture, bone growth into the scaffold as well as the 3D characterisation of biomaterial degradation and bone regeneration in vitro and in vivo. Furthermore, in combination with in situ mechanical testing and digital volume correlation (DVC), XCT demonstrated its potential to better understand the bone-biomaterial interactions and local mechanics of bone regeneration during the healing process in relation to the regeneration achieved in vivo, which will likely provide valuable knowledge for the development and optimisation of novel osteoregenerative biomaterials. LAY DESCRIPTION: Bone, being a dynamically adaptable material, displays excellent regenerative properties following fracture. However, the self-healing capacity of bone becomes more difficult with large bone defects. Those defects are common and occur in many clinical situations; hence, biomaterials are mostly used to restore both bone structure and function in the defect site. X-ray computed tomography (XCT) is a powerful tool to evaluate bone regeneration in critical-sized defects after the implantation of biomaterials, allowing to an improved understanding of the regeneration process following different bone tissue engineering approaches. This paper focuses on recent advancements in XCT analysis to characterise biomaterial-mediated bone regeneration in critical-sized defects. XCT supports three-dimensional (3D) analysis of biomaterials, scaffolds and regenerated bone microarchitecture, as well as bone ingrowth into the scaffold. As a nondestructive technique, XCT allows for a 3D characterisation of biomaterial degradation and bone regeneration over time. In addition, XCT combined with in situ mechanical experiments and digital volume correlation (DVC) provides a 3D evaluation and quantification of bone-biomaterial interactions and deformation mechanisms during the regeneration process. This remains essential for the development and enhancement of novel biomaterials able to produce bone that is comparable with the native tissue they aim to replace.