We will investigate the biochemical properties of living human articular cartilage tissue so as to optimise the conditions for storing osteochondral allograft tissue used in transplantation.
Articular cartilage is an avascular tissue found on the surface of bones, which enables smooth articulation of the joint. Localised damage to articular cartilage as a result of injury or disease impairs articulation, causing pain and immobility, and if left untreated can progress to chronic diseases such as osteoarthritis. Osteochondral allograft transplantation (OAT) involves the transplant of donor tissue into the host joint to replace and repair the area of damage. This procedure is considered to be the gold standard treatment for localised cartilage damage but its use is restricted by availability of suitable tissue. Currently donor OAT tissue is provided to surgeons by tissue banks with the limiting factor being the length of time the tissue can be stored due to the decreasing viability of chondrocyte cells that make up and maintain the OAT tissue. The aim of the project is to improve upon existing storage conditions in order to increase the viability of chondrocyte cells within the OAT and therefore the length of time the OAT tissue can be stored.
Central hypothesis: Optimisation of OAT tissue storage conditions will increase the length of time that it can be stored by tissue banks and will increase the supply of suitable donor tissue to surgeons.
Aims and objectives: i) To develop and characterise protocols for measuring chondrocyte and hence OAT viability in storage. Techniques will include gene and protein expression analyses, live dead staining and measures of mitochondrial function, redox status and nutrient turnover. ii) To investigate the effect of nutrient and gaseous tension on the viability of OAT cells during storage.
The project brings together a multi-disciplinary team of supervisors with expertise in chondrocyte biology, cell physiology and chemistry. The student will receive specific training in the molecular and cellular characterisation of chondrocytes and OAT tissue, assays relating to nutrient turnover, mitochondrial function and cellular redox status. In addition the student will be enrolled of the Liverpool Doctoral College project to develop skills in scientific communication, mathematical analyses and commercialisation of research. The project will also be closely linked with NHS partners at Liverpool. The Department houses the newly awarded MRC-ARUK Centre for Integrated research into Musculoskeletal Ageing which is a collaboration with Newcastle University and the University of Sheffield.
The Institute of Ageing and Chronic Disease is fully committed to promoting gender equality in all activities. In recruitment we emphasize the supportive nature of the working environment and the flexible family support that the University provides. The Institute holds a silver Athena SWAN award in recognition of on-going commitment to ensuring that the Athena SWAN principles are embedded in its activities and strategic initiatives.
Open to students worldwide
The project is open to both home and overseas students, it is UNFUNDED and applicants are encouraged to contact the Principal Supervisor directly to discuss their application and the project.
The successful applicant will be expected to provide the funding for registration, tuition fees, all their own living expenses and research costs (bench fees) of £15,000 per year to cover charges associated with purchasing laboratory consumables. Details of costs can be found on the University website
1) Chui K, Jeys L, Snow M. (2015) Knee salvage procedures: The indications, techniques and outcomes of large osteochondral allografts. World Journal of Orthopaedics 6, 340-350.
2) McNicholas MJ and Oldershaw RA. Cartilage Regeneration: How Do We Meet the Increasing Demands of an Ageing Population?. SM J Orthop. 1, 1010.
3) Collins JA, Moots RJ, Winstanley R, Clegg PD and Milner PI. (2013) Oxygen and pH-sensitivity of human osteoarthritic chondrocytes in 3-D alginate bead culture system. Osteoarthritis and Cartilage 21(11): 1790-1978
4) Lamari FN, Theocharis AD, Asimakopoulou AP, Malavaki CJ and Karamanos NK. (2006) Metabolism and biochemical/physiological roles of chondroitin sulfates: analysis of endogenous and supplemental chondroitin sulfates in blood circulation Biomed. Chromatogr. 20: 539-550.
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