Scaffold Geometry Modulation of Mechanotransduction and its Influence on Epigenetics

Abstract

The dynamics of cell mechanics and epigenetic signatures direct cell behaviour and fate, thus influencing regenerative outcomes. In recent years, the utilisation of 2D geometric (square, triangle or round-shaped) substrates for investigating cell mechanics in response to the extracellular microenvironment have gained increasing interest in regenerative medicine due to their tunable physicochemical properties. In contrast, there is relatively limited knowledge of cell mechanobiology and epigenetics in the context of 3D biomaterial matrices, i.e., hydrogels and scaffolds. Scaffold’s geometry provides biophysical signals that trigger a nucleus response (regulation of gene expression) and modulates cell behaviour and function. In this review, we explore how scaffold geometries are achieved at different length scales by additive manufacturing techniques and discuss how scaffold geometry direct cell and nuclear mechanosensing. We further discuss how cell epigenetics, particularly DNA/histone methylation and histone acetylation, are modulated by scaffold features that lead to specific gene expression and ultimately influence the outcome of tissue regeneration. Overall, we highlight that harnessing scaffold multi-scale features via additive manufacturing can facilitate the assembly of cells and multicellular tissues into desired functional architectures through the mechanotransduction pathway.