Our research

Musculoskeletal Mechanobiology and Materials for Regeneration

Our research focus is to delineate the importance of mechanics in musculoskeletal physiology and utilise this fundamental information to inform the development of novel therapeutics, biomaterials, and biofabrication technologies to treat orthopedic defects and/or diseases such as osteoporosis

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Mechano-biology & Mechano-immunology

Our lab is interested in understanding the mechanisms by which mechanical loading is potent driver of tissue formation, particularly in the context of bone and immune resposnes. Utilising tibia and ulna compressive loading models, coupled with transgenic mouse models, we are hoping to identify the role of numerous cell types, including skeletal stem cells (red cells in image), in bone mechanoadaptation. Moreover, using these models we hope to identify key mechanosensitive mechanisms mediating this bone forming response to loading, which we can then target therapeutically to enhance bone regeneration in defects and disease.

Selected papers below:

Loss of Adenylyl Cyclase 6 in Leptin Receptor-Expressing Stromal Cells Attenuates Loading-Induced Endosteal Bone Formation

Mechanical signals promote osteogenic fate through a primary cilia-mediated mechanism

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Cellular Mechanotransduction

Our lab is interested in understanding how cells sense and transduce biophysical stimuli into biochemical signal responses (mechanotransduction) in bone. In particular we have completed numerous studies investigating the role of the primary cilium (red linear structure in image) in cellular mechanotransduction and have identified several cilia associated molecular mechanisms mediating this response. We have also completed studies investigating the role of cytoskeletal elements such as actin, intermediate filaments, and focal adhesions in bone cell mechanotransduction and how this is altered in disease.

Selected papers below:

Primary cilium-mediated MSC mechanotransduction is dependent on Gpr161 regulation of hedgehog signalling

Pressure‐induced mesenchymal stem cell osteogenesis is dependent on intermediate filament remodeling

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Cell-Cell communication

Bone contains a network of osteocytes throughout the tissue that maintains tissue homeostasis via the coordination of effector cell types such as osteoblasts and osteoclasts. Our lab is interested in understanding how osteocytes coordinate these cell types, particularly in response to mechanical loading. In particular, we have identified that osteocytes secrete extracellular vesicles and that the cargo of these EVs are altered by mechanics.

Selected papers below:

Human bone marrow stem/stromal cell osteogenesis is regulated via mechanically activated osteocyte‐derived extracellular vesicles

Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

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Biofabrication

Melt electrowriting is an emerging technology which enables the accurate deposition of micron scale fibres that mirror the scale of the extracellular matrix in many tissues. Our lab is utilising this approach to understand how cells respond to different fibrous substrate architectures and use this knowledge and technology to develop novel scaffolds and grafts for both skeletal and vascular applications.

Selected papers below:

Mediating human stem cell behaviour via defined fibrous architectures by melt electrospinning writing

Scaffold microarchitecture regulates angiogenesis and the regeneration of large bone defects

Organ on Chip

Combining the knowledge obtained through the above research areas, we have recently started to develop organ on chip systems to better model human tissue physiology, with particular attention paid to the synovial joint tissues (Bone, Cartilage and Synovium).

Selected papers below:

Biofabrication of vasculature in microphysiological models of bone