Two PhD positions at the Department of Developmental BioEngineering

PhD position 1: The effect of biomechanical loading on joint tissues in health and disease.

Exposure of joint tissues to biomechanical loading is a key characteristic of the moving knee joint and is essential for normal joint health. Indeed patients suffering from osteoarthritis are advised to keep on moving and consequently loading their joint. However excessive loading of the joint can also increase joint deterioration in osteoarthritis. It is unclear what healthy loading of an osteoarthritic knee joint entails and what is pathophysiological loading worsening disease. More in dept knowledge is needed to understand the impact of biomechanical loading on healthy and diseased joint tissues at the molecular and cellular level. In previous research we have engineered a cartilage-on-chip and synovial membrane-on-chip model and we have developed prototypes of Hoffa’s fatpad and a ligament-on-chip in which the engineered joint tissues can be mechanically stimulated. The purpose of this project is to use these models for increasing our understanding of the impact of mechanical loading on the cellular and molecular level in the healthy and osteoarthritic joint. In this project the PhD student is expected to closely collaborate with partners in the Erasmus Medical Center and the Leiden University Medical Center.

PhD position 2: Point-of-care diagnostic device for the early assessment of osteoarthritis.
Diagnostic tools enabling the early detection of osteoarthritis and the endotyping of osteoarthritic patient groups in different subgroups are still not available. This is considered one of the main reasons why no disease modifying osteoarthritic drugs are on the market. The goal of this project is to identify dearly needed biomarkers in synovial fluid and / or serum in the early osteoarthritis patient group with asymptomatic disease. We will use VHH antibody technology in combination with next generation sequencing to identify differentially binding VHH to synovial fluid and serum specimens of healthy, early and late osteoarthritic patients. Differential binders will be characterized and antigens will be identified using pool down assays and mass spectrometry. Discriminating VHHs will be used to establish a multiplex assay for early diagnosis of osteoarthritis using surface plasmon resonance imaging as a read out. The device will be tested using serum and synovial fluid samples of previously established patient cohorts. The candidate is expected to establish a vibrant collaboration with companies, hospitals and other consortium partners. In this project the PhD candidate will closely collaborate with the companies IBIS Technologies and Ssens.