Micro and Nanofabrication methods to control cell-substrate interactions and cell behavior: A review from the tissue engineering perspective

Abstract

Cell-substrate interactions play a crucial role in the design of better biomaterials and integration of implants with the tissues. Adhesion is the binding process of the cells to the substrate through interactions between the surface molecules of the cell membrane and the substrate. There are several factors that affect cell adhesion including substrate surface chemistry, topography, and stiffness. These factors physically and chemically guide and influence the adhesion strength, spreading, shape and fate of the cell. Recently, technological advances enabled us to precisely engineer the geometry and chemistry of substrate surfaces enabling the control of the interaction cells with the substrate. Some of the most commonly used surface engineering methods for eliciting the desired cellular responses on biomaterials are photolithography, electron beam lithography, microcontact printing, and microfluidics. These methods allow production of nano- and micron level substrate features that can control cell adhesion, migration, differentiation, shape of the cells and the nuclei as well as measurement of the forces involved in such activities. This review aims to summarize the current techniques and associate these techniques with cellular responses in order to emphasize the effect of chemistry, dimensions, density and design of surface patterns on cell-substrate interactions. We conclude with future projections in the field of cell-substrate interactions in the hope of providing an outlook for the future studies.

Cell alignment by smectic liquid crystal elastomer coatings with nanogrooves

“…The simplest and often the most effective is topography of linear grooves. Numerous reports, reviewed in Chen, Yan, and Zheng (), Di Cio and Gautrot (), Ermis, Antmen, and Hasirci (), Heath and Cooper (), Martínez, Engel, Planell, and Samitier (), and Ruprecht et al () demonstrate that linear groves can align biological cells of practically any type. Cells such as rat dermal fibroblasts could sense nanogrooves that are as shallow as 35 nm and of width 100 nm and more (Loesberg et al, ).…”

Laser‐Assisted Strain Engineering of Thin Elastomer Films to Form Variable Wavy Substrates for Cell Culture

“…During the past decades, living cell sensitivity to physical properties of their environment, such as nano‐ and microtopography, has been well established . However, simple technologies that allow recapitulating in vitro the geometrical and highly dynamic properties of such multiscale structured environment are still lacking.…”

Electron beam lithography fabrication of SU-8 polymer structures for cell studies

“…Fabrication approaches such as mask-based photolithography 22 and mask-less photolithography 23,24 are frequently applied, but structure resolution are for both techniques limited by the optical diffraction limit. Other approaches such as dip pen lithography, 25 nano-sphere lithography, 26 block-copolymer lithography 27 and other similar approaches 28 are able to perform structuring with sub-100 nm resolution, but have a limited throughput.…”