Disc and Cartilage Biology

Traumatic and degenerative damage to the articular joint and intervertebral disc (IVD) are major causes of acute and chronic pain. However, the factors that contribute to the loss of function and the underlying pathophysiology are still poorly understood. In addition, present medical and surgical approaches do not address the underlying pathology and are often unsatisfactory. We investigate potential mechanisms leading to cartilage and IVD damage and identify tissue and systemic biomarkers of degeneration, which may serve as diagnostic and therapeutic targets; we then evaluate novel biological treatments for repair and regeneration.

We have established a whole IVD organ culture system with the ability to maintain entire discs alive for several weeks under controlled nutrient and mechanical loading conditions. Within this IVD-specific bioreactor, we are investigating the beneficial or detrimental effects of nutrition, mechanical load, and/or biochemical factors on disc cell viability and metabolic activity.

Our ex-vivo IVD defect and degeneration models allow us to design and evaluate appropriate biological treatment strategies, including implantation/ homing of stem cells, delivery of anabolic, anti-catabolic or anti-inflammatory molecules, new biomaterials or combinations thereof. Data from ex vivo models are correlated to in vivo observations and clinical data to identify molecular markers of dysfunction. The goal is to develop functional therapies which, depending on the type of damage, will maintain or restore the mechanical properties of the disc, while cellular components will enhance the endogenous regenerative process.

To study the potential of new therapies for articular cartilage repair and regeneration, we have developed cartilage-specific bioreactor system applying multiaxial load to tissue-engineered constructs or osteochondral explants. The bioreactor mimics the load and motion characteristics of an articulating joint. Chondral and osteochondral defect and disease models enable us to test tailored treatments under physiologically relevant, mechanically loaded ex-vivo conditions. Cell- and material-based therapies as well as chondrogenic and anti-inflammatory factors are under investigation for cartilage repair and preservation.