Mechanobiologically mimetic model systems for study of Bone disease (MEMETic)

ongoing

Despite immense efforts to develop therapies for osteoporosis, conventional drugs that target bone loss only prevent osteoporotic fractures in 50% of sufferers, and the worldwide economic burden of treatment is projected to reach $132 billion by 2050. Recently our research has (1) identified important tissue-level changes in osteoporotic bone and (2) provided evidence that the biological mechanisms by which the cells normally respond to their mechanical environment are altered. However, no existing therapeutic approach has been developed to account for these. It is timely to build upon our important research findings and significantly advance the state of the art in the field of mechanobiology to understand osteoporosis aetiology and ultimately inform effective therapies. A particular challenge for the international research field, has been that most current understanding of bone biology and pathophysiology has been derived either using 2D cell culture, which fails to capture vital biomechanical aspects of bone that govern bone biology, or animal studies, whose biology differs from that of humans. So, existing approaches cannot fully capture, or account for both human biological and mechanical factors, and this project seeks to address this challenge. The global objective of the MEMETic project is to provide a paradigm change for studies of bone disease and therapeutics by consolidating, and significantly advancing, our novel approaches to develop advanced ex vivo models that recreate in vivo biomechanical cues in a living and multicellular 3D environment to replicate the mechanobiological function of bone. The MEMETic models will be applied to advance understanding of osteoporosis and a new osteoporosis therapy (sclerostin antibody). A unique multidisciplinary approach, combining cell and molecular biology with biomechanical and mechanobiological techniques, will enable these important advances, and consolidate a world leading mechanobiology research program.