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 (ECM) structure and zonal heterogeneity. Furthermore, it is understood that the presence of native ECM 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 microscale. 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. Decellularized scaffolds, which retain the native tissue macro- and microstructure 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. Impact statement Physiological cartilage function is a key criterion in the success of a cartilage tissue engineering solution. The in situ performance is dependent on the initial scaffold design as well as extracellular matrix deposition by endogenous or exogenous cells. Both biological and biomechanical stimuli serve as key regulators of cartilage homeostasis and maturation of the resulting tissue-engineered graft. An improved understanding of the influence of biomechanics on cellular function and consideration of the final biomechanical and tribological performance will help in the successful development and translation of tissue-engineered grafts to restore natural joint function postcartilage trauma or osteoarthritic degeneration, delaying the requirement for prosthetic intervention.