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Mechancis and dynamics of cell death after impact injury of articular cartilage

Related publication

Bartell, et al., 2015. Measuring microscale strain fields in articular cartilage during rapid impact reveals thresholds for chondrocyte death and a protective role for the superficial layer. Journal of Biomechanics.

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Background

Articular cartilage is a heterogeneous soft tissue in joints (e.g. your knee). More specifically, cartilage covers the end of long bones in mammals and its function is (1) to provide a very low-friction surface for joint motion and to (2) to dissipate and distribute load in the joint. Cartilage is a unique tissue because it has very few cells or vasculature, and the cells (known as chondrocytes) that do exist have very low metabolism. Instead of cells, cartilage is primarily composed of extra-cellular matrix, which has a complex and heterogeneous multi-scale mechanical behavior. As a material, cartilage is quite robust and can withstand decades of normal loading. However, cartilage is susceptible to damage from loading at high rates or magnitudes. In part, this is because cartilage lacks the cells and vasculature necessary for a rapid and effective healing response. 

Osteoarthritis (OA) is a degenerative joint disease which involves degradation of the articular cartilage, leading to pain and disability. OA affects over 27 million adults in the US and is a leading cause of disability in developed nations, but there is no cure and few effective treatments. OA is associated with age and obesity, and can be brought on gradually by normal wear-and-tear. However, approximately 12% of clinical osteoarthritis is associated with a traumatic event (e.g. sports injury) and is labeled as post-traumatic osteoarthritis (PTOA). Despite decades of research, mechanisms of OA initiation after trauma remain poorly understood.

Knowledge-gap

Understanding PTOA initiation has proven difficult, due in part to the complexities of cartilage material properties and the scope of the disease. From the materials perspective, cartilage is homogenous and has important mechanical variation on the scale of tens-of-microns (e.g. cartilage has a distinct superficial layer which is more compliant than the bulk). From the clinical perspective, a traumatic, event can deliver forces over a fraction of a second (10-3 s) while a patient may not present with symptoms for years (108 s). Current methods are unable to address both mechanics and biology at high spatial and temporal resolutions.

Method

Thus, we developed a method to simultaneously study the mechanics and biology of cartilage at high resolution in both space and time. To do this, we combined fast-camera video with confocal microscopy and used the method to study cell death in bovine cartilage after a localized impact, achieving approximately 85 µm spatial resolution and 1 ms temporal resolution.

Results and significance

Our results showed that, at these high rates, strain (in particular, its tensor norm) and the probability of cell death were highly correlated (p<0.001) with a threshold of 8% microscale strain norm before any cell death occurred. Additionally, cell death had developed by two hours after impact, suggesting an important time-window for targeted clinical therapeutics. Moreover, when the superficial layer was removed, strain – and subsequently cell death – penetrated deeper into the samples (p<0.001). This suggests a protective role for the surface layer of articular cartilage. Combined, these results provide insight regarding the detailed biomechanics that drive early chondrocyte damage after trauma and emphasize the importance of understanding cartilage and its mechanics on the microscale.

Cartilage Impact