Abstract
Geometrical cues provided by the intrinsic architecture of tissues and implanted biomaterials have a high relevance in controlling cellular behavior. Knowledge of how cells sense and subsequently respond to complex geometrical cues of various sizes and origins is needed to understand the role of the architecture of the extracellular environment as a cell-instructive parameter. This is of particular interest in the field of tissue engineering, where the success of scaffold-guided tissue regeneration largely depends on the formation of new tissue in a native-like organization in order to ensure proper tissue function. A well-considered internal scaffold design (i.e., the inner architecture of the porous structure) can largely contribute to the desired cell and tissue organization. Advances in scaffold production techniques for tissue engineering purposes in the last years have provided the possibility to accurately create scaffolds with defined macroscale external and microscale internal architectures. Using the knowledge of how cells sense geometrical cues of different size ranges can drive the rational design of scaffolds that control cellular and tissue architecture. This concise review addresses the recently gained knowledge of the sensory mechanisms of cells towards geometrical cues of different sizes (from the nanometer to millimeter scale) and points out how this insight can contribute to informed architectural scaffold designs.
Highlights
In vivo, tissues have specific geometrical properties that contribute to their physiological functions.For instance, bone tissue has a hierarchical structure that is critical for its mechanical properties [1,2,3].Tendons and ligaments have highly aligned collagen fibers that endow these tissues with the ability to withstand mechanical loading and thereby prevent tissue damage [4]
Tissuethan engineering produced by particular, we focus on the sensing of substrate curvature, an important parameter in 3D tissue engineering scaffolds produced by additive manufacturing
Anisotropic focal adhesions (FAs) placement and force-dependent FA maturation and stabilization followed by leading edge protrusion in line with the oriented adhesions are suggested to underlie the cellular response towards contact guidance cues smaller than cell size
Summary
Tissues have specific geometrical properties that contribute to their physiological functions. Studies employing two-dimensional (2D) or pseudo-3D two-and-a-half-dimensional (2.5D) relief structures with highly controlled geometrical cues have demonstrated that cells respond to a wide variety of geometrical cues in the form of ridges, lines, pillars, pits or other shapes in sizes ranging from nanometer to millimeter scale (reviewed by [38,40]) These fabricated geometrical cues are designed to resemble the geometrical cues that cells are subjected to in vivo, in the form of both native tissue and biomimetic scaffolds, which are known to influence various cellular responses. We propose several promising research directions to further advance our knowledge on the cellular geometry sensing and response in complex environments and describe how this could contribute to smart scaffold design
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
