TISSUE REGENERATION

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Bone tissue engineering and regenerative medicine are promising strategies for treating bone diseases and reconstructing bone defects. For many years research has been dedicated to understanding the biochemical environment that is required to encourage bone regeneration and the desired properties of biocompatible scaffold materials. These studies demonstrate the potential for stem cell based therapies for bone regeneration. However the field of tissue regeneration is faced with the specific challenge to develop novel tissue regeneration approaches to produce tissue that can simultaneously support loading, but is also porous to allow for cell migration and diffusion of nutrients into the regenerated tissue to maintain viability. Prof. McNamara’s research group develop mechanobiology based approaches (compression, vibration, fluid flow and hydrostatic bioreactors) for bone tissue regeneration and apply these methods to overcome limitations of biomaterial based in vitro approaches for bone tissue regeneration.

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Experimental and computational studies have sought to understand the role of bone composition and organisation in regulating the biomechanical behaviour of bone.  However, due to the complex hierarchical arrangement of the constituent materials, the reported experimental values for the elastic modulus of trabecular and cortical tissue have conflicted greatly. Furthermore finite element studies of bone have largely made the simplifying assumption that material behaviour was homogeneous or that tissue variability only occurred at the microscale based on grey values from micro-CT scans. Osteocytes are composed of an elastic cell membrane that deforms in response to the external fluid flow imposed by mechanical loading. This represents a most challenging multi-physics problem in which fluid and solid domains interact and as such no previous study has accounted for this complex behaviour.

 

Prof. McNamara’s group employ fluid-structure interaction (FSI) modelling to investigate the complex mechanical environment of osteocytes in vivo. Fluorescent staining of osteocytes is performed in order to visualise their native environment and develop geometrically accurate models of the osteocyte in vivo. This involves a three-scale finite element homogenisation scheme to enable prediction of homogenised effective properties of tissue level bone from its fundamental nanoscale constituents of hydroxyapatite mineral crystals and organic collagen proteins. This approach could provide a preclinical tool to predict bone mechanics following prosthetic implantation or bone fracture during disease. These are the first computational FSI models to simulate the complex multi-physics mechanical environment of osteocyte in vivo and provide a deeper understanding of bone mechanobiology.