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Designing degradable hydrogels for orthogonal control of cell microenvironments

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      Abstract

      This review provides insight into emerging degradable and cell-compatible hydrogels for understanding and modulating cell behavior for various bioengineering applications.

      Abstract

      Degradable and cell-compatible hydrogels can be designed to mimic the physical and biochemical characteristics of native extracellular matrices and provide tunability of degradation rates and related properties under physiological conditions. Hence, such hydrogels are finding widespread application in many bioengineering fields, including controlled bioactive molecule delivery, cell encapsulation for controlled three-dimensional culture, and tissue engineering. Cellular processes, such as adhesion, proliferation, spreading, migration, and differentiation, can be controlled within degradable, cell-compatible hydrogels with temporal tuning of biochemical or biophysical cues, such as growth factor presentation or hydrogel stiffness. However, thoughtful selection of hydrogel base materials, formation chemistries, and degradable moieties is necessary to achieve the appropriate level of property control and desired cellular response. In this review, hydrogel design considerations and materials for hydrogel preparation, ranging from natural polymers to synthetic polymers, are overviewed. Recent advances in chemical and physical methods to crosslink hydrogels are highlighted, as well as recent developments in controlling hydrogel degradation rates and modes of degradation. Special attention is given to spatial or temporal presentation of various biochemical and biophysical cues to modulate cell response in static ( i.e., non-degradable) or dynamic ( i.e., degradable) microenvironments. This review provides insight into the design of new cell-compatible, degradable hydrogels to understand and modulate cellular processes for various biomedical applications.

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      Matrix elasticity directs stem cell lineage specification.

      Microenvironments appear important in stem cell lineage specification but can be difficult to adequately characterize or control with soft tissues. Naive mesenchymal stem cells (MSCs) are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity. Soft matrices that mimic brain are neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. During the initial week in culture, reprogramming of these lineages is possible with addition of soluble induction factors, but after several weeks in culture, the cells commit to the lineage specified by matrix elasticity, consistent with the elasticity-insensitive commitment of differentiated cell types. Inhibition of nonmuscle myosin II blocks all elasticity-directed lineage specification-without strongly perturbing many other aspects of cell function and shape. The results have significant implications for understanding physical effects of the in vivo microenvironment and also for therapeutic uses of stem cells.
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        Integrins: bidirectional, allosteric signaling machines.

        In their roles as major adhesion receptors, integrins signal across the plasma membrane in both directions. Recent structural and cell biological data suggest models for how integrins transmit signals between their extracellular ligand binding adhesion sites and their cytoplasmic domains, which link to the cytoskeleton and to signal transduction pathways. Long-range conformational changes couple these functions via allosteric equilibria.
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          Hydrogels for tissue engineering.

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            Author and article information

            Affiliations
            [a ] Department of Materials Science and Engineering , University of Delaware , Newark , DE 19716 , USA . Email: kiick@ 123456udel.edu ; Email: akloxin@ 123456udel.edu
            [b ] Biomedical Engineering , University of Delaware , Newark , DE 19716 , USA
            [c ] Delaware Biotechnology Institute , University of Delaware , Newark , DE 19716 , USA
            [d ] Department of Chemical and Biomolecular Engineering , University of Delaware , Newark , DE 19716 , USA
            Journal
            Chem Soc Rev
            Chem Soc Rev
            Chemical Society Reviews
            Royal Society of Chemistry
            0306-0012
            1460-4744
            5 August 2013
            7 September 2013
            : 42
            : 17
            : 7335-7372
            23609001 3762890 c3cs60040h 10.1039/c3cs60040h
            This journal is © The Royal Society of Chemistry 2013

            This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

            Categories
            Chemistry

            Chemistry

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