Recreating functional tissues through bioengineering strategies requires steering of complex cell fate decisions. Notch, a juxtacrine signaling pathway, regulates cell fate and controls cellular organization with local precision. The engineering-friendly characteristics of the Notch pathway provide handles for engineering tissue patterning and morphogenesis. We discuss the physiological
significance and mechanisms of Notch signaling with an emphasis on its potential use for engineering complex tissues. We highlight the current state of the art of Notch activation and provide a view on the design aspects, opportunities, and challenges in modulating Notch for tissue-engineering strategies. We propose that finely tuned control of Notch contributes to the generation of tissues with accurate form and functionality.
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