Design and Fabrication of Viscoelastic Hydrogels as Extracellular Matrix Mimicry for Cell Engineering

The extracellular matrix (ECM) performs both as a static scaffold and as a dynamic, viscoelastic milieu that actively participates in cell signaling and mechanical feedback loops. Recently, biomaterials with tunable viscoelastic properties have been utilized to mimic the native ECM in the fields of tissue engineering and regenerative medicines. These materials can be designed to support cell attachment, proliferation, and differentiation, facilitating the repair or replacement of damaged tissues. Moreover, viscoelasticity modulation of ECM mimicry helps to develop therapeutic strategies for diseases involving altered mechanical properties of tissues such as fibrosis or cancer. The study of biomaterial viscoelasticity thus intersects with a broad spectrum of biological and medical disciplines, offering insights into fundamental cell biology and practical solutions for improving human health. This review delves into the design and fabrication strategies of viscoelastic hydrogels, focusing particularly on two major viscoelastic parameters, mechanical strength and stress relaxation, and how the hydrogel mechanics influence the interactions between living cells and surrounding microenvironments. Meanwhile, this review discusses current bottlenecks in hydrogel-cell mechanics studies, highlighting the challenges in viscoelastic parameter decoupling, long-term stable maintenance of viscoelastic microenvironment, and the general applicability of testing standards and conversion protocols.