Lab-based produced vascularised tissue for in vitro lab on a chip models of healthy and diseased tissue

Lead Research Organisation: University of Sheffield
Department Name: Materials Science and Engineering

Abstract

An important research strand in biomaterials is the development of in-lab grown organs, which are increasingly mimicking the structural and biological complexity of human organs. These organs-on-a-chip are increasingly developed as an alternative to the use of animals in pharmaceutical testing. However the lack of perfusion through vascularisation remains an obstacle in the development of physiological tissue-on-a-chip models. Current models using microfluidic perfusion lack sufficient scale and complexity. Ex-vivo tissue slice cultures are also only suitable for very short-term culture. The project will utilise in house developed technology to build an in vitro model of vascularised tissue. This technology incorporates a prototype vascular network in a porous material and allows for vascular outgrowth to occur in a hydrogel-based well where we can place cells, cell spheroids or even small biopsies. We will use perfusion bioreactors to study the vascular outgrowth within the scaffolds to obtain a lab-on-a-chip device that can be used for long term observation of vascularisation in healthy and diseased tissue models. This will be developed to present an in vitro alternative to in vivo testing platforms, such as the mouse dorsal skin fold model.1 This in vitro model will be used to explore the vascularisation of healthy and diseased tissue models. We aim to explore healthy and cancer tissue models. If successful, this device will fill an important unmet need as an in vitro testing platform.

Planned Impact

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.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S022201/1 01/04/2019 30/09/2027
2262871 Studentship EP/S022201/1 01/10/2019 30/09/2023 Caitlin Jackson