Microbiome-Bone Chip

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The recent recognition of the central role played by the microbiome in human health has lead to a paradigm shift in medicine, with ever-increasing awareness of how these host-specific communities of microorganisms can affect patient health. In the past decade, the gut microbiome has emerged as a contributor to disease processes throughout the body, but only recently has been shown to influence orthopaedic biomechanics. Early findings suggest that the microbiome may help answer questions in orthopaedic biomechanics that are not well addressed by current interventions and highlight the promise of the emerging field of "Musculoskeletal Microbiology".To date, analysis of gut-microbiome crosstalk has almost exclusively relied on the genomic or metagenomic analysis of samples collected from humans or animals. This is because no method exists to establish stable complex communities of gut commensal microorganisms in direct contact with intestinal epithelium and its overlying mucus layer in vitro. Although animal models have been used to analyse host-microbiome interactions and their contributions to pathophysiology, there are no in vitro systems available to verify these interactions in human cells cultured with a complex human microbiome. Thus, there is a great unmet need for experimental models that can sustain complex populations of human aerobic and anaerobic microbiota in contact with living human tissues to analyse dynamic and physiologically relevant human host-microbiome interactions.This project will bring together the Organ-on-a-Chip technology applied by Dr Verbruggen to develop a bone-chip model, with microbiome cultures and metabolomic data from an animal model developed by a founder of this new field of Musculoskeletal Microbiology, Prof Hernandez. With industrial support from the leading manufacturer of organ-chip technology, Emulate, and on-site expertise in 3D models of the microbiome, from Co-Investigator Dr Krishna Kumar, this project will build a proof-of-concept multi-organ chip system that links the gut microbiome with a bone-chip model. This chip model will provide a leap forward in drug discovery by providing a precision model to pick apart the important biological mechanisms, as well as providing a new technology to speed up drug testing while using less animals.