RT Journal Article SR Electronic T1 Longitudinal in vivo micro-CT-based approach allows spatio-temporal characterization of fracture healing patterns and assessment of biomaterials in mouse femur defect models JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.10.02.324061 DO 10.1101/2020.10.02.324061 A1 Esther Wehrle A1 Duncan C Tourolle né Betts A1 Gisela A Kuhn A1 Erica Floreani A1 Malavika H Nambiar A1 Bryant J Schroeder A1 Sandra Hofmann A1 Ralph Müller YR 2021 UL http://biorxiv.org/content/early/2021/01/15/2020.10.02.324061.abstract AB Thorough preclinical evaluation of functionalized biomaterials for treatment of large bone defects is essential prior to clinical application. Using in vivo micro-computed tomography (micro-CT) and mouse femoral defect models with different defect sizes, we were able to detect spatio-temporal healing patterns indicative of physiological and impaired healing in three defect sub-volumes and the adjacent cortex. The time-lapsed in vivo micro-CT-based approach was then applied to evaluate the bone regeneration potential of functionalized biomaterials using collagen and BMP-2. Both collagen and BMP-2 treatment led to distinct changes in bone turnover in the different healing phases. Despite increased periosteal bone formation, 87.5% of the defects treated with collagen scaffolds resulted in non-unions. Additional BMP-2 application significantly accelerated the healing process and increased the union rate to 100%. This study further shows potential of time-lapsed in vivo micro-CT for capturing spatio-temporal deviations preceding non-union formation and how this can be prevented by application of functionalized biomaterials.This study therefore supports the application of longitudinal in vivo micro-CT for discrimination of normal and disturbed healing patterns and for the spatio-temporal characterization of the bone regeneration capacity of functionalized biomaterials.Competing Interest StatementThe authors have declared no competing interest.