Fig. 3.

Cells are equipped with various mechanisms to sense surrounding biophysical cues and mechanical forces within its microenvironment. This can be exploited using various tissue engineering strategies, including gradient tissue-like structures, 3D scaffolds and organoids. Applied forces (in blue) can include compression, tensile strain and shear stress forces, which cause ciliary bending and Ca²⁺ influx, thereby inhibiting cAMP production. Other extracellular matrix properties (in red) include elasticity (stiffness), fibrous architecture (includes fibre orientation, ECM porosity and ligand density), and topographical cues. This ‘outside-in’ signalling is integrin-mediated: Integrin adhesion complexes bridge the extracellular matrix to the actin cytoskeleton and transduce signals in response to mechanical and chemical cues. Abbreviations: ECM, extracellular matrix; Ca²⁺, calcium ions; cAMP, cyclic adenosine monophosphate. [Created with BioRender.com].