Multi-axial mechanical stimulation of tissue engineered cartilage: Review

Abstract

The development of tissue engineered cartilage is a promising new approach for the repair of damaged or diseased tissue. Since it has proven difficult to generate cartilaginous tissue with properties similar to that of native articular cartilage, several studies have used mechanical stimuli as a means to improve the quantity and quality of the developed tissue. In this study, we have investigated the effect of multi-axial loading applied during in vitro tissue formation to better reflect the physiological forces that chondrocytes are subjected to in vivo. Dynamic combined compression-shear stimulation (5% compression and 5% shear strain amplitudes) increased both collagen and proteoglycan synthesis (76 ± 8% and 73 ± 5%, respectively) over the static (unstimulated) controls. When this multiaxial loading condition was applied to the chondrocyte cultures over a four week period, there were significant improvements in both extracellular matrix (ECM) accumulation and the mechanical properties of the in vitro-formed tissue (3-fold increase in compressive modulus and 1.75-fold increase in shear modulus). Stimulated tissues were also significantly thinner than the static controls (19% reduction) suggesting that there was a degree of ECM consolidation as a result of long-term multi-axial loading. This study demonstrated that stimulation by multi-axial forces can improve the quality of the in vitro-formed tissue, but additional studies are required to further optimize the conditions to favour improved biochemical and mechanical properties of the developed tissue.