Interaction-tailored cell aggregates in alginate hydrogels for enhanced chondrogenic differentiation.

Controlling cell-matrix interactions is critical when transferring cells into the body using a scaffold, which can be elaborately tailored to successfully engineer the desired tissue. In this study, ATDC5 cells were encapsulated within alginate hydrogels and their chondrogenic differentiation was investigated in vitro. Cell-matrix interactions were introduced using RGD peptides, which improved the viability of encapsulated cells and enhanced the formation of condensed structures similar to a chondrogenic nodule. When N-cadherin of ATDC5 cells was blocked, the encapsulated cells did not form an aggregate, and chondrogenic differentiation could not be induced. Preformed cell aggregates with defined cell numbers in RGD-modified alginate gels retained adequate N-cadherin-mediated cell-cell interactions and increased chondrogenic marker gene expression, compared with the homogeneously dispersed cells in the gels. This approach may be useful to promote chondrogenesis with relatively few cells if they are encapsulated into a scaffold as a form of aggregates.