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      Viscoelastic hydrogels for 3D cell culture

      1 , 2 , 3 , 4
      Biomaterials Science
      Royal Society of Chemistry (RSC)

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          Abstract

          This mini-review discusses newly developed approaches to tuning hydrogel viscoelasticity and recent studies demonstrating an impact of viscoelasticity on cells.

          Abstract

          In tissues, many cells are surrounded by and interact with a three-dimensional soft extracellular matrix (ECM). Both the physical and biochemical properties of the ECM play a major role in regulating cell behaviours. To better understand the impact of ECM properties on cell behaviours, natural and synthetic hydrogels have been developed for use as synthetic ECMs for 3D cell culture. It has long been known that ECM and tissues are viscoelastic, or display a time-dependent response to deformation or mechanical loading, exhibiting stress relaxation and creep. However, only recently have there been efforts made to understand the role of the time-dependent aspects of the ECM mechanics on regulating cell behaviours using hydrogels for 3D culture. Here we review the characterization and molecular basis of hydrogel viscoelasticity and plasticity, and describe newly developed approaches to tuning viscoelasticity in hydrogels for 2D and 3D culture. Then we highlight several recent studies finding a potent impact of hydrogel stress relaxation or creep on cell behaviours such as cell spreading, proliferation, and differentiation of mesenchymal stem cells. The role of time-dependent mechanics on cell biology remains largely unclear, and ripe for further exploration. Further elucidation of this topic may substantially advance our understanding of cell–matrix interactions during development, homeostasis, wound healing, and disease, and guide the design of biomaterials for regenerative medicine.

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          Most cited references54

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          Atomic Force Microscope

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            Tensional homeostasis and the malignant phenotype.

            Tumors are stiffer than normal tissue, and tumors have altered integrins. Because integrins are mechanotransducers that regulate cell fate, we asked whether tissue stiffness could promote malignant behavior by modulating integrins. We found that tumors are rigid because they have a stiff stroma and elevated Rho-dependent cytoskeletal tension that drives focal adhesions, disrupts adherens junctions, perturbs tissue polarity, enhances growth, and hinders lumen formation. Matrix stiffness perturbs epithelial morphogenesis by clustering integrins to enhance ERK activation and increase ROCK-generated contractility and focal adhesions. Contractile, EGF-transformed epithelia with elevated ERK and Rho activity could be phenotypically reverted to tissues lacking focal adhesions if Rho-generated contractility or ERK activity was decreased. Thus, ERK and Rho constitute part of an integrated mechanoregulatory circuit linking matrix stiffness to cytoskeletal tension through integrins to regulate tissue phenotype.
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              Hydrogels for tissue engineering.

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                Author and article information

                Journal
                BSICCH
                Biomaterials Science
                Biomater. Sci.
                Royal Society of Chemistry (RSC)
                2047-4830
                2047-4849
                2017
                2017
                : 5
                : 8
                : 1480-1490
                Affiliations
                [1 ]Department of Mechanical Engineering
                [2 ]Stanford University
                [3 ]Stanford
                [4 ]USA
                Article
                10.1039/C7BM00261K
                28584885
                fac7c32a-8ce0-41b0-8251-c0dc9020789c
                © 2017
                History
                Product
                Self URI (article page): http://xlink.rsc.org/?DOI=C7BM00261K

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