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The development of biomaterials with temporally controlled properties has advanced our understanding of healing and disease in vitro and widened the number of tools available for regenerative medicine applications. This chapter focuses on the description of various coupling and degradation chemistries used to dynamically modulate the properties of mimics of the native extracellular matrix (ECM) in the context of hydrogel-based biomaterials. These chemistries can be used to control the biophysical and biochemical properties of synthetic matrices to capture in vitro the dynamic changes that occur in the native ECM in vivo, such as remodeling during wound healing. Biologically relevant reaction kinetics and spatial resolutions are achievable providing a range of time and size scales for designing spatiotemporally controlled synthetic biomaterials. In situ characterization techniques have also been developed, allowing the observation of biophysical and biochemical properties as they change in time, to help researchers identify key cues in the environment that direct cell fate. Understanding how changes in the ECM direct cellular functions within an in vitro synthetic mimic can provide researchers with information on critical cues responsible for healing or disease with applications in designing new treatments.

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