Abstract

Microfabrication Technologies for Engineering a Joint on Chip

Marcel Karperien, Professor, Developmental BioEngineering, MIRA Institute for Biomedical Technology & Technical Medicine, University of Twente

Osteoarthritis is a degenerative joint disease affecting more than 300.000.000 patients world-wide. Despite tremendous efforts in the past, the etiology of the disease is still poorly understood and cannot be cured. While initially considered as a disease of cartilage it is now clear that the disease involves all tissues in the joint. Furthermore a disease trigger in each of these tissues can initiate the onset of disease. Despite the different origin they culminate over time in a similar disease presentation. It has also become clear that currently used animal models poorly reflect the complexity of human disease nor do allow the detailed study of the complex interactions between the different joint tissues at various stages of disease. To address these shortcomings my group has started the development of a joint-on-chip. The joint-on-chip has a modular chip design. We are engineering chips for each individual tissue, i.e. cartilage, subchondral bone, synovium, ligament and/or meniscus which together form the joint. The individual chips are connected to each other through blood vessel mimicking microfluidic channels  as well as with a chip mimicking the intra-articular space. This latter chip will contain features allowing non-invasive imaging / sensing of inter tissue communication. Since movement is a critical and an essential feature in every joint, the individual chips can all be independently actuated mimicking both compression and shear stress. Prototype chips of the synovium and the cartilage including actuation have become available and we have shown that these devices can be used for studying critical biological processes in the healthy and diseased joint. Additionally we developed various strategies for introducing cell laden membranes composed of natural polymers and/or tissue constructs in the chip. Finally, we have developed SPRi based sensors for assessing the secretion of cytokines over time and dedicated sensors that can be used to locally assess matrix metalloproteinase activity, a key factor driving joint degeneration on chip. In my presentation I will discuss various engineering aspects of our microfabrication technology platforms needed for recreating a representative and functional human joint and show our efforts to functionally characterize these devices and will illustrate how we use these devices to further our understanding of a healthy and diseased human joint.