Mapping the cell and tissue mechanical environment of early osteoarthritis by means of an optical image-based approach

Osteoarthritis (OA) is the most common chronic joint disease. Cartilage degeneration is the hallmark of OA, with associated changes in all other tissues of the joint. To date, OA is the leading cause of disability among elderly, resulting in pain, limited daily activities and a decreased quality of life. To date no known cure or proven strategy exists for reducing progression from early to end-stage OA. Mechanical loading is key regulator of cartilage homeostasis. The chondrocytes are surrounded by a specific zone of peri-cellular matrix (PCM). This acts as a communication zone with the wider extracellular matrix (ECM) environment, which provides the cartilage with its mechanical properties. Signals conveyed by the pericellular matrix are hypothesized to activate signaling cascades that fine-tune the synthesis of peri- and extracellular proteins and thus sustain or adapt the mechanical properties of the matrix, in order to maintain the chondrocyte’s metabolic activity or homeostasis. In early OA, cartilage homeostasis is challenged. Little is known about the mechanobiological response of the ’OA-challenged’ chondrocyte upon mechanical loading. In my PhD I will develop and apply optical image-based procedures and algorithms to quantify cell and matrix mechanical parameters in cartilage constructs, representative for healthy conditions and early OA disease conditions. In particular, I will develop and integrate Traction Force Microscopy (TFM) and Optical Coherence Tomography (OCT) to try to map the multiscale mechanical environment and its changes upon early OA induction.