Abstract
In their natural environment, cells are constantly exposed to a cohort of biochemical and biophysical signals that govern their functions and fate. Therefore, materials for biomedical applications, either in vivo or in vitro, should provide a replica of the complex patterns of biological signals. Thus, the development of a novel class of biomaterials requires, on the one side, the understanding of the dynamic interactions occurring at the interface of cells and materials; on the other, it requires the development of technologies able to integrate multiple signals precisely organized in time and space. A large body of studies aimed at investigating the mechanisms underpinning cell-material interactions is mostly based on 2D systems. While these have been instrumental in shaping our understanding of the recognition of and reaction to material stimuli, they lack the ability to capture central features of the natural cellular environment, such as dimensionality, remodelling and degradability. In this work, we review the fundamental traits of material signal sensing and cell response. We then present relevant technologies and materials that enable fabricating systems able to control various aspects of cell behavior, and we highlight potential differences that arise from 2D and 3D settings.
Highlights
For a long time, cell-culturing substrates, like glass, plastic and metal, were considered as passive supports
Their system elegantly demonstrated that gel remodelling is essential in driving cell differentiation: even in a ‘morphologically’ spread state, cell were not able to launch an osteogenic program, owing to the low traction forces generated in a restrictive, non-degradable matrix
These examples demonstrated that matrix stiffness alone is not sufficient to predict stem cell differentiation in 3D, but it is rather the dynamic variation of stiffness and degradation that plays a crucial role in affecting cell fate
Summary
Cell-culturing substrates, like glass, plastic and metal, were considered as passive supports. Tissue engineering and regenerative medicine failed in having a dramatic impact on modern clinics, despite their undeniable potentialities This is mainly caused by a lack of knowledge on the effects of exogenous stimuli and in particular those presented by culturing materials, in the generation of fully-functional tissues in vitro or in vivo. Signals presented to stem cells in their niche dictate fate and functions, i.e., whether they have to remain quiescent, proliferate or differentiate [9] In this context, one of the greatest challenges is to develop materials able to display a set of stimuli that tightly control stem cell behavior. One of the greatest challenges is to develop materials able to display a set of stimuli that tightly control stem cell behavior This requires designing and fabricating perfectly-controlled physical/chemical environments in which the effect of specific material signals on cell functions can be precisely assessed. We provide examples on controlling cell functions and fate with -engineered systems
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