Viscoelasticity in natural tissues and engineered scaffolds for tissue reconstruction

[Display omitted] Viscoelasticity of living tissues plays a critical role in tissue homeostasis and regeneration, and its implication in disease development and progression is being recognized recently. In this review, we first explored the state of knowledge regarding the potential application of tissue viscoelasticity in disease diagnosis. In order to better characterize viscoelasticity with local resolution and non-invasiveness, emerging characterization methods have been developed with the potential to be supplemented to existing facilities. To understand cellular responses to matrix viscoelastic behaviors in vitro, hydrogels made of natural polymers have been developed and the relationships between their molecular structure and viscoelastic behaviors, are elucidated. Moreover, how cells perceive the viscoelastic microenvironment and cellular responses including cell attachment, spreading, proliferation, differentiation and matrix production, have been discussed. Finally, some future perspective on an integrated mechanobiological comprehension of the viscoelastic behaviors involved in tissue homeostasis, cellular responses and biomaterial design are highlighted. Tissue- or organ-scale viscoelastic behavior is critical for homeostasis, and the molecular basis and cellular responses of viscoelastic materials at micro- or nano-scale are being recognized recently. We summarized the potential applications of viscoelasticity in disease diagnosis enabled by emerging non-invasive characterization technologies, and discussed the underlying mechanism of viscoelasticity of hydrogels and current understandings of cell regulatory functions of them. With a growing understanding of the molecular basis of hydrogel viscoelasticity and recognition of its regulatory functions on cell behaviors, it is important to bring the clinical insights on how these characterization technologies and engineered materials may contribute to disease diagnosis and treatment. This review explains the basics in characterizing viscoelasticity with our hope to bridge the gap between basic research and clinical applications.