This article summarizes recent progress in the design and synthesis of hydrogels as tissue-engineering scaffolds. Hydrogels are attractive scaffolding materials due to their highly swollen network structure, ability to encapsulate cells and bioactive molecules, and efficient mass transfer. Various polymers, including natural, synthetic, and natural/synthetic hybrid polymers, have been used to make hydrogels via chemical or physical crosslinking. Bioactive synthetic hydrogels have emerged as promising scaffolds because they can provide molecularly tailored biofunctions and adjustable mechanical properties, as well as an extracellular matrix-like microenvironment for cell growth and tissue formation. Hydrogels are water-swollen polymeric networks that can swell but do not dissolve in water. They have a 3D network structure, crosslinked either physically or chemically, allowing effective immobilization and release of active agents and biomolecules. Hydrogels resemble natural soft tissue more than any other type of polymeric biomaterials. They are biocompatible, highly permeable for oxygen, nutrients, and other water-soluble metabolites, and are attractive scaffolds for cell encapsulation. Hydrogels can be classified into physical and chemical hydrogels based on their cross-linking mechanism. Physical crosslinks include entangled chains, hydrogen bonding, hydrophobic interaction, and crystallite formation. Chemical crosslinks are permanent junctions formed by covalent bonds. Hydrogel networks may include both permanent and semipermanent junctions. The type and degree of crosslinking influence network properties such as swelling, elastic modulus, and transport of molecules. The control of the hydrogel network structure allows for the proper design and characterization of degradation, diffusion of bioactive molecules, and migration of cells through the network. Four important swelling parameters define the network structure of hydrogels, including swelling ratio, polymer volume fraction in the swollen state, number average molecular weight between cross-links, and network mesh size. Hydrogels have been used as an important class of tissue-engineering scaffolds because they can provide a soft tissue-like environment for cell growth and allow diffusion of nutrients and cellular waste through the elastic hydrogel network. They have advantages over other types of polymeric scaffolds, such as easy control of structural parameters, high water content, promising biocompatibility, and adjustable scaffold architecture. The article summarizes recent progress in the design and synthesis of hydrogel scaffolds for tissue engineering. It begins with an overview of the properties of polymers used for designing and fabricating hydrogel scaffolds, then briefly describes the use of the natural extracellular matrix (ECM) as a design model for engineering bioactive hydrogels, followed by highlighting three types of ECM-mimetic hydrogels, including cell-adhesive, enzyme-sensitive, and growth factor (GF)-bearing hydrogels. Finally, five-year perspectives and key issues are provided regarding the applications of hydrogel tissue-engineering scaffThis article summarizes recent progress in the design and synthesis of hydrogels as tissue-engineering scaffolds. Hydrogels are attractive scaffolding materials due to their highly swollen network structure, ability to encapsulate cells and bioactive molecules, and efficient mass transfer. Various polymers, including natural, synthetic, and natural/synthetic hybrid polymers, have been used to make hydrogels via chemical or physical crosslinking. Bioactive synthetic hydrogels have emerged as promising scaffolds because they can provide molecularly tailored biofunctions and adjustable mechanical properties, as well as an extracellular matrix-like microenvironment for cell growth and tissue formation. Hydrogels are water-swollen polymeric networks that can swell but do not dissolve in water. They have a 3D network structure, crosslinked either physically or chemically, allowing effective immobilization and release of active agents and biomolecules. Hydrogels resemble natural soft tissue more than any other type of polymeric biomaterials. They are biocompatible, highly permeable for oxygen, nutrients, and other water-soluble metabolites, and are attractive scaffolds for cell encapsulation. Hydrogels can be classified into physical and chemical hydrogels based on their cross-linking mechanism. Physical crosslinks include entangled chains, hydrogen bonding, hydrophobic interaction, and crystallite formation. Chemical crosslinks are permanent junctions formed by covalent bonds. Hydrogel networks may include both permanent and semipermanent junctions. The type and degree of crosslinking influence network properties such as swelling, elastic modulus, and transport of molecules. The control of the hydrogel network structure allows for the proper design and characterization of degradation, diffusion of bioactive molecules, and migration of cells through the network. Four important swelling parameters define the network structure of hydrogels, including swelling ratio, polymer volume fraction in the swollen state, number average molecular weight between cross-links, and network mesh size. Hydrogels have been used as an important class of tissue-engineering scaffolds because they can provide a soft tissue-like environment for cell growth and allow diffusion of nutrients and cellular waste through the elastic hydrogel network. They have advantages over other types of polymeric scaffolds, such as easy control of structural parameters, high water content, promising biocompatibility, and adjustable scaffold architecture. The article summarizes recent progress in the design and synthesis of hydrogel scaffolds for tissue engineering. It begins with an overview of the properties of polymers used for designing and fabricating hydrogel scaffolds, then briefly describes the use of the natural extracellular matrix (ECM) as a design model for engineering bioactive hydrogels, followed by highlighting three types of ECM-mimetic hydrogels, including cell-adhesive, enzyme-sensitive, and growth factor (GF)-bearing hydrogels. Finally, five-year perspectives and key issues are provided regarding the applications of hydrogel tissue-engineering scaff