MechAscan - A novel online mechanical assessment tool for manufacturing engineered tissues in regenerative medicine and drug discovery.

The proportion of people around the world aged over 60 years is growing faster than any other age group, as a result of longer life expectancy. This population ageing can be seen as a success story for public health policies and for socioeconomic development, but it places a challenge on medicine and, within the UK, the NHS to maximize the health and functional capacity of older people. Regenerative Medicine is one potential solution for this longer life and healthy lifestyle, providing cell based therapies which can replace damaged or diseased tissues. Growing replacement tissues is bringing exciting novel solutions which now require new manufacturing methods and processes to enable the translation to the clinic. Bioreactors are mechanical devices that provide controlled growth environments for engineered tissues and mimic the physical forces cells and tissues experience in the body. Monitoring the maturation of tissue implants during culture, and prior to implantation into the patient, is important for defining optimum manufacturing criteria and for their clinical success. Key properties that tissue engineered implants must display include strength and durability. To infer material properties from imaging, new non-destructive, three-dimensional imaging techniques are needed, that can be used to provide accurate results efficiently at both the manufacturing site and the clinic. In this proposal, our partners have linked the imaging technique, optical coherence elastography, with a hydrostatic pressure bioreactor to create a novel imaging solution, MechAscan, which allows real-time mechanical characterisation and simultaneous physical stimulation of engineered tissue implants. MechAscan will provide a clear advantage over currently available traditional mechanical testing approaches and elastography techniques, which require direct contact of the mechanical load with the sample and are destructive. Additionally, MechAscan can be used for real-time monitoring of mechanical properties as the construct is grown in culture in a sterile growth environment. Our aim is to develop a novel technology platform allowing real-time and non-destructive monitoring of tissue engineered products in a sterile growth environment to avoid construct to construct variation during manufacturing and allow the translation of regenerative medicine constructs with known properties into the clinic. To facilitate uptake in use of the technology and translation to the clinic, we propose to fully test and validate the MechAscan technology in an interdisciplinary approach combining bioreactor technology, biomaterials science, physics and mathematics.

Patients: Improvements in quality control of Regenerative Medicine Implant Manufacturing will directly benefit patients. Well characterised tissue implants will eliminate tissue to tissue variability and minimise patient risk. Furthermore, regular monitoring of implant maturation on line throughout manufacture will lead to an improved therapy which will impact on clinical outcomes and therefore improve quality of life.

NHS: Our technology will increase the efficiency of therapy and recovery and will yield to improved service and cost reduction for the NHS.

Industry: To maintain the development process for future treatments, industry is constantly in need of a pipeline of ideas, such as the MechAscan technology. Currently, there are no commercially available elastography techniques that maintain sterility and allow for simultaneous maturation of engineered implants. There are multiple potential commercial routes with companies such as Thorlabs, TA Instruments, and Cell Scale where the MechAscan will meet a need for imaging of their bioreactor instruments. We will exploit these commercialisation opportunities. Combining bioreactor technology with optical imaging modalities underpinned by mathematical modelling will provide the platform for the development of new characterisation equipment, produced and sold by UK companies. This will aid the establishment of Regenerative Medicine Manufacturing as a UK leading global industry.

Manufacturing and Regulatory: The "Comparability: Manufacturing, Characterisation and Controls Workshop" organised by the UKRMP-Pluripotent Stem Cell Platform has 'comparability' as a regulatory requirement for cell-based products. The European Medicine Agency (EMA) and the UK Medicine and Healthcare products Regulatory Agency (MHRA) regard this difficult for cell-based products as characterisation, standardisation and quality control of cell-therapy medicines remain key challenges. In order to translate engineered tissues into the clinic, the manufacture of tissue constructs need to be controlled, constructs need to be characterised and their manufacture standardised. This project will develop a new tool that will aid the identification and monitoring of quality control criteria for the performance of tissue constructs, aid the standardisation of their manufacture and characterise tissue implants and hence addresses translational challenges