An overview of substrate stiffness guided cellular response and its applications in tissue regeneration

Cell-matrix interactions play a critical role in tissue repair and regeneration. With gradual uncovering of substrate mechanical characteristics that can affect cell-matrix interactions, much progress has been made to unravel substrate stiffness-mediated cellular response as well as its underlying mechanisms. Yet, as a part of cell-matrix interaction biology, this field remains in its infancy, and the detailed molecular mechanisms are still elusive regarding scaffold-modulated tissue regeneration. This review provides an overview of recent progress in the area of the substrate stiffness-mediated cellular responses, including 1) the physical determination of substrate stiffness on cell fate and tissue development; 2) the current exploited approaches to manipulate the stiffness of scaffolds; 3) the progress of recent researches to reveal the role of substrate stiffness in cellular responses in some representative tissue-engineered regeneration varying from stiff tissue to soft tissue. This article aims to provide an up-to-date overview of cell mechanobiology research in substrate stiffness mediated cellular response and tissue regeneration with insightful information to facilitate interdisciplinary knowledge transfer and enable the establishment of prognostic markers for the design of suitable biomaterials.