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REPORT

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2

Sarah E. Grieshaber, Amit K. Jha, Alexandra J. E. Farran, and Xinqiao Jia

Contents 2.1 2.2 2.3

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Basic Concepts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Hydrogel Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 2.3.1 Chemical Crosslinking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 2.3.2 Physical Crosslinking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 2.4 Modulating Hydrogel Microstructure and Mechanical Properties . . . . . . . . . . . . . . . . . . . . . . . . 26 2.4.1 Modulating Hydrogel Microstructure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 2.4.2 Engineering Hydrogels with Robust Mechanical Properties . . . . . . . . . . . . . . . . . . . . . . . 28 2.5 Biodegradable and Bioactive Hydrogels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 2.5.1 Biodegradable Hydrogels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 2.5.2 Engineering Bioactive Hydrogels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 2.6 Conclusion and Future Directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

Abstract The successful engineering of synthetic hydrogels that exhibit key features of the natural extracellular matrices has led to significant advances in the field of tissue engineering. Various chemical and physical approaches have been developed for hydrogel synthesis. While the chemical methods rely on the presence of readily addressable functional groups for the formation of covalent bonds at the crosslinking points, the physical approaches utilize weak and reversible interactions for gelation purposes. In many cases, physical gels need to be covalently stabilized for their long term applications in tissue engineering. Over the past decade, hydrogels have evolved from passive scaffolding materials to bioactive and cellresponsive matrices that play a defining role in the regulation of cellular functions and tissue growth. Novel hydrogels with tunable microstructures, mechanical properties, and degradation rates have been engineered. Biological motifs or soluble factors have been successfully incorporated in the hy