Development of in vitro models of common cancers of the urological system to investigate the effects on the tumour microenvironment

The cellular microenvironment (which includes matrix rigidity, soluble factors, cell-cell and cell-extracellular matrix (ECM) interactions) is instrumental to the response of cancer cells to treatment. Low oxygen tension (hypoxia) within the tumour and surrounding tissues greatly reduces the effectiveness of radiotherapy for prostate and bladder cancer patients.
Cancer cells cultured in 3D can recapitulate the in vivo tumours to a significantly higher degree when compared to monolayer cultures. The proliferation of tumour cells cultured in 3D is typically slower and hence more physiologically relevant than that of monolayer cultures.
In this project 3D tumour models will be developed that better recapitulate the tumour microenvironment and improve the in vitro assessment of cancer therapeutics modalities.
We have established fibrous scaffolds and 3D cancer models using synthetic (self-assembling peptides) and natural (alginate, collagen) hydrogels that better mimic the fibrous component of tumours. Here, we aim to develop 3D models with tumour cells seeded within the biomaterials to bridge the gap between flat 2D in vitro culture and in vivo experiments. These will be cultured in a perfusion bioreactor with modifiable oxygen delivery or in the presence of hypoxia inducers to mimic the hypoxic environment seen in solid tumours to allow us to assess the role of hypoxia in treatment resistance, and more specifically in radiation response.

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.