Transduction of strain to cells seeded onto scaffolds exposed to uniaxial stretching: A three dimensional finite element study

When preparing tissue engineering and regenerative medicine constructs, a commonly encountered problem is the failure of seeded cells to infiltrate the scaffold. In an increasing number of cases, constructs are being mechanically preconditioned with the expectation that preconditioning will enhance the construct's maturation and effectiveness by pre-exposing seeded cells to stimuli the tissue of interest experiences in vivo. However, whether or not mechanostimulation of a scaffold actually results in transmission of stimuli to the seeded cells remains poorly understood. The purpose of this research was to develop a model that quantifies how strain is transmitted to cells layered on a scaffold's surface compared to cells embedded within a scaffold. Three-dimensional finite element models representative of these conditions were created. When 10% strain was applied to the construct, embedded cells received the full imposed strain. However, cells growing on top of the scaffold received 5% strain within the first layer of cells, and the strain transmitted to cells in subsequent layers decreased exponentially with increasing distance from the scaffold's surface. When experimentally testing the model, strain-induced biological responses were muted in conditions where cell to scaffold contact was reduced. This research illustrates the importance of achieving cellular penetration and cell-to-scaffold contacts when mechanically conditioning tissue engineering constructs.