A Novel in Vitro and in Silico System for Analysing Complex Mechanobiological Behaviour of Chondrocytes in 3D Hydrogel Constructs.

Physiological loading is essential for the maintenance of articular cartilage through regulation of tissue remodelling. To correctly understand the behaviour of chondrocytes in their native environment, cell stimulating devices/bioreactors have been developed to examine the effect of mechanical stimuli on chondrocytes. This study describes the design and validation of a novel system for analysing chondrocyte deformation patterns. This involves an in vitro mechanical device that applies multiaxial-loading regimes to chondrocyte-seeded agarose constructs and in silico models for analysing chondrocyte deformation patterns. The computer-controlled device precisely applies compressive, tensile and shear strains to hydrogel constructs using a customisable macro-based programme. The synchronisation of the displacements is shown to be accurate with a 1.2% error and is highly reproducible. The device design allows housing for up to 8 novel designed free-swelling 3D hydrogel constructs. Constructs include mesh ends and optimised to withstand the application of up to 7% mechanical tensile and 15% shear strains. Constructs were characterised through mapping the strain within as mechanical load was applied and was validated using microscopy methods, chondrocyte viability using live/dead imaging and cell deformation strains. Images were analysed to determine the complex deformation strain patterns of chondrocytes under a range of dynamic mechanical stimulations. This is one of the first systems that have characterised construct strains to cellular strains. The features in this device make the system ideally suited for a systematic approach for investigation of the response of chondrocytes to a complex physiologically relevant deformation profile.