Design and validation of an in vitro loading system for the combined application of cyclic compression and shear to 3D chondrocytes-seeded agarose constructs.

Physiological loading is essential for the maintenance of articular cartilage by regulating tissue remodelling, in the form of both catabolic and anabolic processes. To promote the development of tissue engineered cartilage which closely matches the long term functionality of native tissue, bioreactors have been developed to provide a combination of loading modalities, which reflect the nature of normal physiological loads. This study describes the design and validation of an in vitro mechanical system for the controlled application of bi-axial loading regimes to chondrocyte-seeded agarose constructs. The computer-controlled system incorporates a robust gripping system, which ensures the delivery of precise values of cyclic compressive and shear strain to 3D cell-seeded constructs. Sample prototypes were designed, optimised using finite element analysis and validated performing compressive and shear fatigue mechanical tests. The horizontal and vertical displacements within the bioreactor are precisely controlled by a dedicated programme that can be easily implemented. The synchronisation of the orthogonal displacements was shown to be accurate and reproducible. Constructs were successfully loaded with a combined compressive and shear loading regimen at 1 Hz for up to 48 h with no appreciable loss of cell viability or mechanical integrity. These features along with the demonstrated high consistency make the system ideally suitable for a systematic investigation of the response of chondrocytes to a complex physiologically relevant deformation profile.