Engineered cancer in vitro model to demultiplex biophysical cues in metastasis

Breast cancer is the most common cancer in women in the UK. Whilst prognosis for patients with low grade disease continually improves, 70% of patients with advanced breast cancer develop incurable bone metastases. The mechanisms driving targeted metastases are complex, requiring changes in both the primary tumour and the metastatic niche. A significant risk factor for breast cancer incidence and prognosis is breast density. How this links with biological cascade that underpins the ability of breast cancer cells metastasise and colonise the bone is unknown.

We have developed alginate-based biomaterials, functionalised to mimic the stiffness of distinct stages of breast cancer progression, and bioactive hydrogels that mimic the bone microenvironment. Encapsulation of breast cancer/bone cell populations offers the possibility of generating physiologically relevant 3D tissue engineered models through the combination of materials and cells. Further, the inclusion of 3D models in a microfluidic system will mimic the blood vessels that cancer cells use as passage way for metastasis, hence enable the interconnection and modelling of the breast-to-bone dissemination.

There are numerous beneficiaries of this Advanced Biomedical Materials CDT. Firstly and of short term impact are the PhD students themselves. They will receive extensive research specific and professional/transferable skills training throughout the 4 years of the programme. They will have access to state of the art facilties and world leading academics, industry and clinicians. The training and potential placements are designed to maximise the impact of their research in terms of dissemination and movement of their research along the translation pathway.

Longer term benefits are that this distinct cohort will become the future UK Biomedical Materials leaders and be able to use their bespoke training and network within the cohort to collaborate on future worldwide funding opportunities and drive UK research in this area.

UK and international academics will benefit as they will gain the next generation of highly skilled postdoctoral researchers with knowledge and expertise not only in their specific research area but of industry, regulatory and clinical aspects.

UK and international industry will benefit - in the short term they will gain academic based research to further develop products and in the longer term have a pool of highly skilled graduates.

Clinicians will benefit from collaborative research and also the development of new and novel products to enhance the treatment of a variety of trauma and disease based needs from biomaterials.

The public will benefit as end users as patients that will have their quality of life improved from the products developed in the CDT and will be educated in novel technologies and materials to repair the human body. The UK economy will benefit from the reduced healthcare costs associated with the new and improved medical products developed in this CDT and subsequently from the trained graduates. The UK economy will also benefit from the increased revenue from medical sales products from the UK industrial partners we will be working with.

The impact of this CDT will be realised by direct academic, clinical and industrial engagement with the students allowing efficient and state of the at training and fast translation of developing products. Students will also be trained in knowledge exchange and will use these skills to disseminate their research to, and liaise with, the key stakeholders - the academic, industrial, clinical and public sectors. We will ensure widening participation routes are addressed in this CDT in order to include equality and diversity not only in our initial CDT student cohort but in future researcher generations to come.