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J R Soc Interface. 2017 Aug;14(133). pii: 20170255. doi: 10.1098/rsif.2017.0255.

Hyaluronan supplementation as a mechanical regulator of cartilage tissue development under joint-kinematic-mimicking loading.

Author information

Institute for Biomechanics, ETH Zurich, Zurich, Switzerland
AO Research Institute, Davos, Switzerland.
Institute for Science and Technology in Medicine, Keele University, Stoke-on-Trent, UK.
Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
Department of Health Sciences, University of Potsdam, Potsdam, Germany.
Schön Klinik München Harlaching, Munich, Germany.
Paracelsus Private Medical University, Salzburg, Austria.


Articular cartilage plays an essential role in joint lubrication and impact absorption. Through this, the mechanical signals are coupled to the tissue's physiological response. Healthy synovial fluid has been shown to reduce and homogenize the shear stress acting on the cartilage surfaces due to its unique shear-thinning viscosity. As cartilage tissues are sensitive to mechanical changes in articulation, it was hypothesized that replacing the traditional culture medium with a healthy non-Newtonian lubricant could enhance tissue development in a cartilage engineering model, where joint-kinematic-mimicking mechanical loading is applied. Different amounts of hyaluronic acid were added to the culture medium to replicate the viscosities of synovial fluid at different health states. Hyaluronic acid supplementation, especially at a physiologically healthy concentration (2.0 mg ml-1), promoted a better preservation of chondrocyte phenotype. The ratio of collagen II to collagen I mRNA was 4.5 times that of the control group, implying better tissue development (however, with no significant difference of measured collagen II content), with a good retention of collagen II and proteoglycan in the mechanically active region. Simulating synovial fluid properties by hyaluronic acid supplementation created a favourable mechanical environment for mechanically loaded constructs. These findings may help in understanding the influence of joint articulation on tissue homeostasis, and moreover, improve methods for functional cartilage tissue engineering.


cartilage tissue engineering; hyaluronic acid supplementation; mechanical loading; non-Newtonian fluid; synovial fluid

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