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Abstract
Natural cellular microenvironment consists of spatiotemporal gradients of multiple physical (e.g. extracellular matrix stiffness, porosity and stress/strain) and chemical cues (e.g. morphogens), which play important roles in regulating cell behaviors including spreading, proliferation, migration, differentiation and apoptosis, especially for pathological processes such as tumor formation and progression. Therefore, it is essential to engineer cellular gradient microenvironment incorporating various gradients for the fabrication of normal and pathological tissue models in vitro. In this article, we firstly review the development of engineering cellular physical and chemical gradients with cytocompatible hydrogels in both two-dimension and three-dimension formats. We then present current advances in the application of engineered gradient microenvironments for the fabrication of disease models in vitro. Finally, concluding remarks and future perspectives for engineering cellular gradients are given.
Declaration of interest
This work was financially supported by the National Natural Science Foundation of China (11372243, 81300696), China Postdoctoral Science Foundation (2014M552463), the Major International Joint Research Program of China (11120101002), the Key (Key grant) Project of Chinese Ministry of Education (313045) and International Science & Technology Cooperation Program of China (2013DFG02930). FX was also partially supported by the China Young 1000-Talent Program and Program for New Century Excellent Talents in University (NCET-12-0437). BP-M received funding from the Ministry of Higher Education (MOHE), Government of Malaysia under the high impact research (UM.C/HIR/MOHE/ENG/44).