Final Report Summary - BONEMECHBIO (Frontier research in bone mechanobiology during normal physiology, disease and for tissue regeneration)
The BoneMechBio project conducted frontier research to delineate specific aspects of bone mechanobiology during normal physiology, disease and for tissue regeneration purposes. Through specific work packages, this ERC funded research project delivered significant advances in the understanding of the mechanical regulation of bone during normal physiology and osteoporosis. Furthermore the fundamental understanding obtained from these studies was applied to develop novel approaches for regeneration of bone tissue for treatment of bone pathologies. Theme 1 discovered new information on how bone cells sense and respond to the mechanical environment in their natural environment (in vivo) and also in the same cells grown in the laboratory environment. Together the studies in Theme 1 significantly progressed understanding of bone physiology. Theme 2 developed a multidisciplinary approach, employing (1) the most advanced computational modelling techniques and (2) a novel experimental loading and imaging device, to predict the mechanical stimuli that different bone cells experience under in vivo loading. These methods were applied to predict the local strain environment of osteocytes in variations locations within bone. Together these multidisciplinary studies significantly advanced the field of bone mechanobiology by evolving the understanding of the mechanical environment of bone cells in vivo and in vitro. Furthermore the results of these studies were applied to inform the design of the bone tissue regeneration approaches to apply loading regimes that are analogous to those experienced in vivo (further described below for Theme 5). Theme 3 designed and validated fluid flow chambers suitable for long term flow studies. Using these systems we quantified the role of integrin receptors, primary cilia and adhesion junctions, for mechanosensing in bone cells in vitro. We also investigated the role of extracellular mechanical and physical cues for dictating bone biology. Theme 4 provided evidence that estrogen deficiency, a condition existing in osteoporotic patients, (a) disrupts mechanosensory proteins, (b) alters biochemical responses and (c) mechanical stimuli. These findings have significantly advanced current understanding of osteoporosis by shedding light on fundamental changes in bone mechanobiology, a process that is crucial in healthy bone but previously not considered during disease. Theme 5 used a combination of computational fluid dynamics (CFD) and fluid structure interaction (FSI) methods to predict the mechanical stimuli generated in tissue engineering scaffolds within a bioreactor. We used this approach to optimise the design of a bioreactor to produce physiologically realistic cellular stimulation. This theme provided information that might lead to a novel regenerative treatment for large bone defects, as well as addressing the major limitation of core degradation and construct failure. Further information on the research conducted through the ERC and the work of Professor Laoise McNamara's gorup can be found at www.mechanobiology.ie