Restoration of chondrocytic phenotype on a two-dimensional micropatterned surface

Chondrocytes within mature cartilage reside in a 3D matrix and adopt a distinctive round morphology. A vast 2D-culture surface is well-known to induce chondrocyte dedifferentiation characterized by the loss of spherical morphology and ceased expression of chondrogenic markers. Methods to restore chondrogenesis so far only occur on a certain level producing varied cell subpopulations and inferior cartilage matrix; the critical parameters, especially for the pericellular microenvironment, are still to be precisely determined. In this study, arrays of 2D circular micropatterns were designed to hold single subcultured chondrocytes with stable adhesion. The chondrocytes rounded up forming a 3D architecture; they remodeled their cytoskeleton to resemble in-situ chondrocytes and expressed collagen II instead of collagen I or fibronectin. This technique suggested that pure physical constraints can induce chondrocytic phenotype restoration on a 2D surface; it also provides a new design pathway to precisely control the microenvironment surrounding every chondrocyte therefore to unify the redifferentiation level of individual cell.