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Hydrogel biomaterials generated from sources such as extracellular matrix (ECM) and other natural materials are being used extensively in regenerative medicine. Within many of these applications, the chosen biomaterials have gravitated towards soft hydrogels because they resemble the endogenous ECM and its innate properties. Such materials have several important advantages over other materials, such as (1) the capability of mimicking the mechanical properties of soft tissues in the body, and (2) possessing biological properties beneficial for interactions with cells that are lacking in synthetic materials. Examples of naturally derived hydrogel materials include, but are not limited to, collagens, hyaluronic acid, alginate, fibrin, and their derivatives. Through chemical modification, thereby tailoring specific properties of these materials, scientists can create a variety of polymerization techniques to generate a vast quantity of distinct hydrogel types. Their range of attainable mechanical properties, their bioactivity, and the many options for crosslinking approaches facilitate their use in a wide range of applications, as varied as two- and three-dimensional tissue culture, propagation and differentiation of stem cells, maintenance of primary cells, wound healing, cell therapy, generation of tissue models for in vitro testing, and biofabrication technologies such as bioprinting. This chapter explores the uses of various natural hydrogel types and technologies within the context of some of the aforementioned applications that have potential to make substantial impacts in the field of regenerative medicine.

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