Reproducing the biomechanical environment of the chondrocyte for cartilage tissue engineering

It is well known that the biomechanical and tribological performance of articular cartilage is inextricably linked to its extracellular matrix structure and zonal heterogeneity. Furthermore, it is understood that the presence of native extracellular matrix components such as collagen II and aggrecan promote healthy homeostasis in the resident chondrocytes. What is less frequently discussed is how chondrocyte metabolism is related to the extracellular mechanical environment, at both the macro and micro scale. The chondrocyte is in immediate contact with the pericellular matrix of the chondron, which acts as a mechanocoupler, transmitting external applied loads from the ECM to the chondrocyte. Therefore, components of the pericellular matrix also play essential roles in chondrocyte mechanotransduction and metabolism. Recreating the biomechanical environment through tuning material properties of a scaffold and/or the use of external cyclic loading can induce biosynthetic responses in chondrocytes. Decellularised scaffolds which retain the native tissue macro and micro-structure also represent an effective means of recapitulating such an environment. The use of such techniques in tissue engineering applications can ensure the regeneration of skeletally mature articular cartilage with appropriate biomechanical and tribological properties to restore joint function. Despite the pivotal role in graft maturation and performance, biomechanical and tribological properties of such interventions is often underrepresented. This review outlines the role of biomechanics in relation to native cartilage performance and chondrocyte metabolism, and how application of this theory can enhance the future development and successful translation of biomechanically relevant tissue engineering interventions.