Screening Platform for Cell Contact Guidance Based on Inorganic Biomaterial Micro/nanotopographical Gradients

Abstract

High-throughput screening (HTS) methods based on topography gradients or arrays have been extensively used to investigate cell–material interactions. However, it is a huge technological challenge to cost efficiently prepare topographical gradients of inorganic biomaterials due to their inherent material properties. Here, we developed a novel strategy translating PDMS-based wrinkled topography gradients with amplitudes from 49 to 2561 nm and wavelengths between 464 and 7121 nm to inorganic biomaterials (SiO2, Ti/TiO2, Cr/CrO3, and Al2O3) which are frequently used clinical materials. Optimal substratum conditions promoted human bone-marrow derived mesenchymal stem cell alignment, elongation, cytoskeleton arrangement, filopodia development as well as cell adhesion in vitro, which depended both on topography and interface material. This study displays a positive correlation between cell alignment and the orientation of cytoskeleton, filopodia, and focal adhesions. This platform vastly minimizes the experimental efforts both for inorganic material interface engineering and cell biological assessments in a facile and effective approach. The practical application of the HTS technology is expected to aid in the acceleration of developments of inorganic clinical biomaterials.

Strategy for achieving standardized bone models

“…However, 2D culture conditions do not reproduce the typical environment of bone cells as they are forced to grow in monolayers (Antoni, Burckel, Josset, & Noel, ). An artificial flat and rigid surface is a geometrical, mechanical environment that affects the cytoskeleton (e.g., actin patterns) of bone cells and more broadly, their fate (Dalby, Gadegaard, & Oreffo, ; Zhou et al, ). Consequently, in contrast to 3D setups, 2D configurations notoriously skew bone cell responses to mechanical stimuli (Juignet et al, ; McCoy & O'Brien, ).…”

“…Surface microtopography and micropores are surface structures on a micron scale that are often mistaken for each other. Surface roughness influences the morphology, attachment, proliferation and differentiation of bone cells in vitro (Anselme & Bigerelle, ; Sola‐Ruiz, Perez‐Martinez, Martin‐del‐Llano, Carda‐Batalla, & Labaig‐Rueda, ; Zhou et al, ). In vitro, microporosity results in a larger surface area that is believed to contribute to ion exchange as well as higher bone‐inducing protein adsorption (Gariboldi & Best, ; Hannink & Arts, ).…”

“…The fluid displacement caused by the loading in the periosteocytic space (1) of the canaliculi (2) However, 2D culture conditions do not reproduce the typical environment of bone cells as they are forced to grow in monolayers (Antoni, Burckel, Josset, & Noel, 2015). An artificial flat and rigid surface is a geometrical, mechanical environment that affects the cytoskeleton (e.g., actin patterns) of bone cells and more broadly, their fate (Dalby, Gadegaard, & Oreffo, 2014;Zhou et al, 2017).…”

“…Apart from the permeability, mainly controlled by the macroscopic porous network, the size and geometry of macropores and interconnections were also proved to influence cell colonization, tissue growth and osteogenesis, for example, concave surfaces being greater for tissue growth, osteogenesis and microcapillary-like structure self-assembly than convex surfaces (Bianchi et al, 2014;Gariboldi, Butler, Best, & Cameron, 2019;Juignet et al, 2017;Rumpler, Woesz, Dunlop, van Dongen, & Fratzl, 2008 Rueda, 2015;Zhou et al, 2017). In vitro, microporosity results in a larger surface area that is believed to contribute to ion exchange as well as higher bone-inducing protein adsorption (Gariboldi & Best, 2015;Hannink & Arts, 2011).…”

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

“…Recently, spontaneously wrinkled substrates became a convenient tool for controlling living cell spreading and cytoskeletal arrangement on a sub-cellular scale roughness. [14][15][16][17][18] These wavy features present rounded edges that are inspired by in vivo nano-and microtopographies, allowing to different cell type manipulations. For example, bacterial biofilm growth reduction has been obtained on dynamic wrinkles with submicron to 2 µm valleys [19] and stem cell alignment and efficient internal organization for contraction have been shown on nano-scale wrinkles for tissue engineering applications.…”