Transplantation of human fetal blood stem cells in the osteogenesis imperfecta mouse leads to improvement in multiscale tissue properties.

Osteogenesis imperfecta (OI or brittle bone disease) is a disorder of connective tissues caused by mutations in the collagen genes. We previously showed that intrauterine transplantation of human blood fetal stem/stromal cells in OI mice (oim) resulted in a significant reduction of bone fracture. This work examines the cellular mechanisms and mechanical bone modifications underlying these therapeutic effects, particularly examining the direct effects of donor collagen expression on bone material properties. In this study, we found an 84% reduction in femoral fractures in transplanted oim mice. Fetal blood stem/stromal cells engrafted in bones, differentiated into mature osteoblasts, expressed osteocalcin, and produced COL1a2 protein, which is absent in oim mice. The presence of normal collagen decreased hydroxyproline content in bones, altered the apatite crystal structure, increased the bone matrix stiffness, and reduced bone brittleness. In conclusion, expression of normal collagen from mature osteoblast of donor origin significantly decreased bone brittleness by improving the mechanical integrity of the bone at the molecular, tissue, and whole bone levels.

Ground improvement methods for liquefaction remediation

Soil liquefaction continues to be a major source of damage to buildings and infrastructure after major earthquake events. Ground improvement methods are widely used at many sites worldwide as a way of mitigating liquefaction damage. The relative success of these ground improvement methods in preventing damage after a liquefaction event and the mechanisms by which they can mitigate liquefaction continue to be areas of active research. In this paper the emphasis is on the use of dynamic centrifuge modelling as a tool to investigate the effectiveness of ground improvement methods in mitigating liquefaction risk. Three different ground improvement methods will be considered. First, the effectiveness of in situ densification as a liquefaction resistance measure will be investigated. It will be shown that the mechanism by which soil densification offers mitigation of the liquefaction risk can be studied at a fundamental level using dynamic centrifuge modelling. Second, the use of drains to relieve excess pore pressures generated during an earthquake event will be considered. It will be shown that current design methods can be further improved by incorporating the understanding obtained from dynamic centrifuge tests. Finally, the use of soil grouting to mitigate liquefaction risk will be investigated. It will be shown that by grouting the foundation soil, the settlement of a building can be reduced following earthquake loading. However, the grouting depth must extend the whole depth of the liquefiable layer to achieve this reduction in settlements.