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Optimisation of biomaterials for an organ-on-a-chip model of breast cancer bone metastases

   Department of Materials Science and Engineering

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  Dr Stefaan Verbruggen, Prof G Reilly, Prof Fred Claeyssens  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

To apply for this programme, please visit Informal enquiries are welcome, to [Email Address Removed].

ABM CDT A common site for breast cancer metastases is bone, affecting about 80% of patients. Once metastasis to bone has occurred the five-year survival rate drops from 99% to 29%. How breast cancer metastasises to bone is not well understood, partly because of a lack of appropriate human model systems. Thus, there is an unmet clinical need to develop models that recapitulate the extracellular material properties and mechanical stimulation in the bone metastatic niche, which can be applied to better understand the metastatic cascade and accelerate discovery of new therapeutic targets.

Likewise, the testing of new cancer drugs presents a pressing clinical problem, as cancer treatments have the lowest success rate of any therapeutic field, with only 5.1% of oncology drugs entering Phase I clinical trials being approved by the FDA. This often occurs due to drug candidates proving effective in animals but not humans, or due to effective treatments for humans being ruled out as ineffective by animal studies. Even with promising pre-clinical data,bringing a single drug to FDA market-approval can take more than 10 years and $2.5 billion, with about two-thirds of this cost occurring in the clinical trial phases.

Therefore, there is a clear need to develop novel microfluidic technologies to provide a leap forward in our ability to accurately identify lead candidates and screen for safety in humans, which would save resources, reduce human risk and accelerate clinical translation.

Main questions to be answered:

Fundamental to the development of a reproducible microfluidic model of the metastatic microenvironment is understanding how the underlying extracellular matrix material in bone regulates the development of the metastatic niche, and how these properties change as the niche develops. This requires us to engineer an in vitro organ-on-a-chip model of invasive ductal breast carcinomas, where metastasis to bone is common and associated with a poor prognosis. Careful tuning of both the chemical properties (e.g. mineral content) and the mechanical properties (e.g. stiffness) of the substrate material to be placed in the chip will pinpoint the optimum biomaterial to be applied in this device. A particular substrate which will be tested is a novel type of jelly-fish sourced collagen produced by our collaborative industrial partner Jellagen, and which preliminary analysis by the Supervisory Team suggests is more conducive to osteogenesis than traditional sources of collagen, and may thus better replicate the in vivo microenvironment. Jellagen will be combined with the co-supervisors’ already established technologies to produce multi-scale porous scaffolds from synthetic polymers. This will lead to new knowledge and technology which may be used to identify and test novel drug targets that disrupt metastasis.

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