Advancing Osteochondral Tissue Supply Chain Transport Conditions for Clinical Allografts

PhD project: “Advancing Osteochondral Tissue Supply Chain Transport Conditions for Clinical Allografts and Advanced Therapy Medicinal Products”

Application: 01/03/2023

Supervisors: Dr Karina Wright and Prof Martyn Snow

Patients with osteochondral defects will likely develop osteoarthritis is left untreated. One of the surgical procedures used to treat these defects is to implant donor cartilage and bone from fresh osteochondral allografts (OCA). For this surgical intervention to be successful it is important that OCA are implanted within 28 days of harvest from the human tissue donor. This is to ensure that the viability of cartilage cells (called chondrocytes) remains above 70%; the level demonstrated to correlate with good clinical outcomes in animal studies.

OCA was pioneered in the USA and due to it’s early success, the technique is now being used by orthopaedic surgeons across the globe and has recently been commissioned for use on the NHS. There is limited availability of grafts and consequently, there is great demand to transport OCA grafts via air carriers over long distances. Recent published data along with data from our preliminary investigations has shown that the viability of clinical OCA is well below industry standards. This in turn may have negative impacts on the clinical effectiveness of grafts which are transported internationally. There is a significant need to determine how individual and combined influences of supply chain transport conditions influence cell viability, tissue matrix integrity and the biomechanical properties of grafts in order to develop optimised processes for OCA supply.

This exciting project will involve a comprehensive study to investigate the effect of prolonged transport on allograft chondrocyte viability and the potential benefits of transport using alternative reagents and conditions. The project aims to optimise the storage and delivery of OCA and to explore the cryopreservation of grafts in order to prolong cell viability and increase graft availability for surgical use and as a source of cells for innovative cell-based therapies.

The successful applicant will work closely within a diverse multi-disciplinary team across a number of specialities and collaboratively with US industry partners. The highly desirable skills that will be developed through this PhD will span laboratory skills (including tissue culture, cryobiology and cellular analytic techniques e.g. flow cytometry, RNA and protein analysis, as well as tissue histological/immunohistochemical analysis, advanced tissue imaging techniques, biochemical analysis and biomechanical testing), as well as, developing a strong knowledge base in global tissue transport, human consenting/tissue handling procedures, supply chain logistics and manufacturing of cell-based therapies.

As part of this project, you will have the opportunity to provide a solution to an urgent clinical problem, which will have a potentially major, and quickly realised, impact on the quality of life of patients. The studentship will be based in the OSKOR group at the RJAH Orthopaedic Hospital in Oswestry. The OSKOR is an internationally recognised group with expertise in the manufacture and development of novel cell-based therapies aimed at treating osteochondral defects/OA. The studentship will also undertake work with specialists at other collaborating Universities including Birmingham, Exeter and Loughborough to explore the biomechanical and structural consequences of extended storage and to engage with specific cryobiology expertise.

This PhD is suitable for home students with a degree in the biological/natural sciences - minimum degree classification 2i. Non-UK/EU applicants will be considered if they are able to self-fund any additional tuition fees and costs that may exist and obtain a visa to study in the UK.

Funding Notes Funding is available to cover 100% UK student tuition fees and consumables for 3 years and a stipend for 3 years at Research Council rates (Stipend for 2022/3 is £17,668 per annum). Non-UK applicants will be considered if they are able to self-fund any additional tuition fees and costs that may exist and obtain a visa to study in the UK.

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