Scaffold stiffness influences cell behavior: opportunities for skeletal tissue engineering.

Skeletal defects resulting from trauma, tumors, or abnormal development frequently require surgical treatment to restore normal tissue function. To overcome the limitations associated with conventional surgical treatments, several tissue engineering approaches have been developed. In particular, the use of scaffolds enriched with stem cells appears to be a very promising strategy. A crucial issue in this approach is how to control stem cell behavior. In this respect, the effects of growth factors, scaffold surface characteristics, and external 'active' loading conditions on stem cell behavior have been investigated. Recently, it has become clear that the stiffness of a scaffold is a highly potent regulator of stem cell differentiation. In addition, the stiffness of a scaffold affects cell migration, which is important for the infiltration of host tissue cells. This review summarizes current knowledge on the role of the scaffold stiffness in the regulation of cell behavior. Furthermore, we discuss how this knowledge can be incorporated in scaffold design which may provide new opportunities in the context of orthopedic tissue engineering.