Development of a Novel Orthogonal Double Gradient for High‐Throughput Screening of Mesenchymal Stem Cells–Materials Interaction

Abstract

Surface gradients provide a powerful platform to accelerate multiscale design by efficiently studying of material–cell interactions to ultimately enhance function of synthetic clinical biomaterials. Herein, a novel orthogonal double gradient is reported in which surface stiffness and wettability vary independently and continuously in perpendicular directions, providing unique combinations of stiffness and wettability over a broad range (stiffness: 6–89 MPa; water contact angle: 29°–90°). It is found that mesenchymal stem cell behavior is nonlinearly regulated by surface stiffness and wettability. These combined stiffness and wettability properties of a material significantly affect stem cell adhesion, spreading, nucleus size, and vinculin expression. This high‐throughput screening system enables elucidation of the relationships between biointerface properties and biological behavior, and thereby serves a potential tool for accelerating the development of high‐performance biomaterials.

The stiffness of living tissues and its implications for tissue engineering

“…If in the beginning the mechanical properties of a bulk material were only seen as a requirement for scaffold integration and integrity 2 , emerging discoveries and the rise of mechanobiology 113 have placed mechanical properties at the same level as long-known biochemical cues. Changing the elastic moduli of the cellular environment, either approaching or moving away from those of native tissues, can lead to tremendous differences in cellular responses from simple adhesion 173,174 and morphology [175][176][177] to the more complex differentiation [178][179][180] . In fact, this variation can be of such magnitude that high-throughput technologies are now being applied to derive the best-fit conditions in terms of surface stiffness for distinct cell types 174,181 , and approaches to do the same in 3D environments are both needed and expected.…”

Topography induced stiffness alteration of stem cells influences osteogenic differentiation

“…39 Wave-like topographies were produced as a result of varying the elastomer base/cross-linker ratio, stretching deformation, plasma pressure, and oxidation time. Plasma oxidation alters both chemical composition and the stiffness 41,42 and therefore an altered preparation approach was needed to exclude all effects other than topography. To exclude variations in chemical composition and mechanical properties that might arise due to the different preparation procedures, PDMS with different topographies were applied as molds on which we applied a fresh mixture of elastomer base/ cross-linker.…”

Biomaterial screening of protein coatings and peptide additives: towards a simple synthetic mimic of a complex natural coating for a bio-artificial kidney

“…34 Other groups have evaluated biomaterial libraries based on protein coatings, 32,33 peptide functionalizations, 6,31 topography, 35 and hydrophobicity. 36 Protein and peptide functionalizations are seldom directly compared for a desired cell response, even though peptides are often selected to mimic proteins. 37 In this study, a natural ECM protein coating library and a synthetic supramolecular additive library were investigated for their capacity to induce REC monolayers.…”