Nanoscale damage markers for early osteoarthritis detection in the bone-cartilage unit

Musculoskeletal disorders like osteoarthritis (OA) increase pain and reduce quality of life for millions of people worldwide, with 8 million people seeking treatment in the UK and hospital expenditures over $40 billion in the US alone.
As a progressive degenerative condition, it is critical to detect and treat OA early, but there are currently few reliable biomarkers. Though it is known that joint injury can lead to OA-development, it is unclear how this causes early tissue structural damage to develop at the nano- and microscale in the bone-cartilage unit - and lead to OA.
This project will discover the key damage and deformation processes initiated at the nanoscale in the tissue matrix of the bone-cartilage unit during injurious mechanical loading, and the dose-response thresholds at which nanoscale damage occurs. Using a destabilized meniscal model of osteoarthritis developed by collaborators at the ARUK-Kennedy Centre (Oxford), the project will analyse the load-induced structural changes in diarthroidal joints using high-resolution X-ray tomography (CT), small-angle X-ray scattering (SAXS) and cryo scanning-electron microscopy. We will develop a micro-compression rig for physiological loading of mouse bone which will be integrated into CT- and SAXS setups. By multiscale analyses of strain-concentrations in progressively-loaded joints, we will detect the presence of nanoscale structural damage and correlate it to initiation of OA. We will use state-of-the-art imaging and analysis techniques at Diamond Synchrotron (Harwell) and at our collaborators at the Max Planck Institute of Colloids and Interfaces (Potsdam).
This PhD project will discover novel nanoscale damage signatures of OA, which - via multiscale correlative imaging - could potentially be detected clinically.