Mechanotransduction in tissue engineering: Insights into the interaction of stem cells with biomechanical cues

Stem cells in their natural microenvironment are exposed to biochemical and biophysical cues emerging from the extracellular matrix (ECM) and neighboring cells. In particular, biomechanical forces modulate stem cell behavior, biological fate, and early developmental processes by sensing, interpreting, and responding through a series of biological processes known as mechanotransduction. Local structural changes in the ECM and mechanics are driven by reciprocal activation of the cell and the ECM itself, as the initial deposition of matrix proteins sequentially affects neighboring cells. Recent studies on stem cell mechanoregulation have provided insight into the importance of biomechanical signals on proper tissue regeneration and function and have shown that precise spatiotemporal control of these signals exists in stem cell niches. Against this background, the aim of this work is to review the current understanding of the molecular basis of mechanotransduction by analyzing how biomechanical forces are converted into biological responses via cellular signaling pathways. In addition, this work provides an overview of advanced strategies using stem cells and biomaterial scaffolds that enable precise spatial and temporal control of mechanical signals and offer great potential for the fields of tissue engineering and regenerative medicine will be presented.