2D imprinted substrates and 3D electrospun scaffolds revolutionize biomedicine.

Abstract

Momentous advances in engineering in the 1980s and 1990s reduced significantly the manufacturing cost of equipment that can produce nano to low microscale materials. This was a key milestone in the field of biomedicine, as from the early 2000s, we entered the era of nanobiomedicine. Essentially, with very low capital cost, every laboratory in the world could develop cell culture substrates and/or implantable devices with morphological features down to the nanometer scale. The rationale of using such small dimensional features derives from the fact that the extracellular space is comprised of nanoto microscale supramolecular assemblies. Further, cells employ probing filopodia extensions and contractile intracellular machinery to gather topographical, spatial, mechanical and chemical information from the extracellular environment, which consequently determines cell functionality, lineage commitment and fate. Among the various fabrication technologies, lithography constitutes the most popular 2D top-down method, while electrospinning represents the most widely used 3D bottomup method [1–7]. The produced 2D and 3D constructs have enabled the study of cell and tissue responses at previously economical and technological prohibiting small scales and the rational design thereof for a specific application/clinical indication. Key to the design tenant is that topographical features and morphological structures should promote cellular polarization and organized extracellular matrix assembly, resembling the natural conformation of tissues. Using photolithography back in 1983, microscale V-shape grooves were created to study human gingival and porcine epithelial cell response [8]. By 1997, we were in a position to fabricate substrates with feature (square) accuracy down to 14 nm (depth) to study Xenopus neurites outgrowth using electron-beam lithography [9,10]. To date, we have successfully imprinted various gratings and geometric shapes along different scales onto thermoplastic polymers to create biologically relevant topographical interfaces. Data obtained from these and other studies clearly illustrate that topographical features are powerful modulators of cell morphology and differential function [11–15]. Further, nanoand microscale arrays have been shown to be potent tools in maintaining the phenotype fidelity of permanently differentiated cells and in differentiating stem cells toward specific lineages [16,17]. Multiple topographic arrays have also been used as high-throughput systems to elucidate the cell–surface interactions and enable identification of improved surfaces for optimal/required cell response [18,19]. Specifically, topographical features have been shown to directly modulate cell–material interaction and to affect the composition, orientation and conformation of adsorbed extracellular matrix components [20,21]. Further, nanoimprinted materials have been shown to either 2D imprinted substrates and 3D electrospun scaffolds revolutionize biomedicine