Multiscale patient-specific modelling of articular chondrocyte biochemical regulation Multiscale patient-specific modelling of articular chondrocyte biochemical regulation

Osteoarthritis (OA) is a highly prevalent and disabling joint pathology that affects mostly the knee joint, and more specifically the articular cartilage. One of the first signs of cartilage degeneration is the change of biochemical composition, e.g. loss of proteoglycans. On the one hand, such loss affects directly the mechanical response of the tissue to the external stimuli, e.g. internal pressure. Yet, concomitant synovitis seems to lead the way in which articular chondrocytes are chronically stimulated in OA, independently on the mechanical environment or drug treatment, thereof highlighting the important to duly capture the complex biochemical regulation of articular chondrocytes.

 

This project specifically targets the modelling and patient-specific simulations of collective chondrocyte behaviour in a representative tissue volume. At the cell level, validated network models will be used and a full cartilage thickness agent-based model (ABM) will allow the individual network models to cooperate over the modelled tissue volume. Cooperation will depend on both initial and boundary biochemical conditions, established respectively at the network and ABM boundary levels. These conditions will be defined according to patient-specific data that are readily available and consist in proteomics measurements of synovial fluid and chondrocyte gene expressions, in a cohort of OA patients, explored at the Hospital del Mar. Technological developments will first focus on establishing a suitable computational framework through the code Repast HPC. Eventually, patient-specific simulated data will be mined together with real world data, to achieve a biochemical-based stratification of patients in relation to pain.  

 

Supervisors: Jérôme Noailly, Maria Segarra-Queralt, Laura Tio (IMIM)