ETH Zürich Swiss Federal Institute of Technology in Zürich- ENDOTARGET Project Partner

Marcy Zenobi-Wong’s Tissue Engineering and Biofabrication (TEB) laboratory in the Department of Health Science and Technology at ETH Zurich focuses on tissue engineering and advanced biofabrication strategies.  The lab has a strong interest in cartilage and in finding treatments for articular cartilage defects and pathologies.  Most recently, the lab has started to work on therapeutic approaches to osteoarthritis (OA), ranging from gene engineering to make cartilage cells less susceptible to inflammation, to developing materials that help lubricate the surface of cartilage and prevent further damage. For example, we use CRISPR-Cas9 to achieve target genomic modification of human chondrocytes.  The combination of such an efficient gene editing protocol with tissue engineering enables the design of engineered cartilage that is resistant to, e.g., inflammation, calcification, or cellular senescence.

At TEB, we are also exploring the potential of zwitterionic polymers for both therapeutic and diagnostic applications in the context of OA.  Zwitterionic polymers carry both positive and negative charges in equal number and are therefore extremely hydrophilic.  This gives them excellent biocompatibility and leads to the formation of a thin water film on surfaces that have been treated with these polymers. In one related project, we were able to show that by applying our materials to cartilage explants, we can restore the beneficial lubrication properties that are lost in OA patients.  We are also exploring these polymers for sustained delivery of anti-inflammatory drugs.  By enzymatically crosslinking our zwitterionic polymers after application to OA cartilage, we can also create an interpenetrating network that both restores the initial mechanical strength of the tissue and acts as a sealant to prevent pro-inflammatory factors from entering the cartilage and triggering cartilage breakdown.  Finally, we are also developing novel contrast agents based on these materials, which we can use to visualize the cartilage tissue with computed tomography, thus providing insights into tissue compositional changes which take place during OA development.

In Endotarget we are leading the strategies for the design of small animal experiments to test the role of endotoxins and other microbial products in the progression of osteoarthritis.  Rodents, mainly mice and rats, are biologically and genetically very similar to humans and have been successfully used to study many human diseases and conditions.  Our investigation with rodents aims to understand how poor gut health affects arthritis, and vice versa.  Deciphering the association between the gut and the joints can help us develop innovate treatments that can significantly impact human health and well-being.  We are also involved in several other activities, such as analysing the human arthritic microbiome in several patient cohorts and analysing the endotoxins present in synovial fluid of arthritis patients.