![]() The differentiation and morphogenesis of progenitor cells into functioning tissues is orchestrated through a diverse set of biochemical cues from neighboring cells and other elements of microenvironment. Mechanical force and mechanical signaling have been established as key to stem cell development and tissue behavior. Much of the work relating stem cell behavior to mechanical conditions, such as stiffness, geometry, and cell generated force, has been constrained to two-dimensional culture systems. Three-dimensional culture is more representative of in vivo conditions owing to increased cell-cell interactions and freedom for motility and reorganization, which are especially important in differentiation and morphogenesis. Compared with those on 2D, cells in 3D experience distinct mechanical stresses which influence their biological functions in embryonic development and tumor growth. ![]() As 3D culture platforms have become more widely utilized, those that more specifically address mechanical loading and signaling have also been developed. Since basic parameters, such as size, can affect cell and aggregate behavior, careful engineering is required to investigate cell response to a 3D environment. Microwell based platforms have emerged as a method to create large numbers of replicate multicellular structures for use in drug screening, disease modeling, and stem cell culture. Platforms involving ECM protein or hydrogel encapsulation have been used to demonstrate that geometry of an embedded 3D tissue can drive tube morphogenesis and cancer invasion through endogenous stress patterns. ![]()
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