Nanotopographic Regulation of Human Mesenchymal Stem Cell Osteogenesis

Abstract

Mesenchymal stem cell (MSC) differentiation can be manipulated by nanotopographic interface providing a unique strategy to engineering stem cell therapy and circumventing complex cellular reprogramming. However, our understanding of the nanotopographic-mechanosensitive properties of MSCs and the underlying biophysical linkage of the nanotopography-engineered stem cell to directed commitment remains elusive. Here, we show that osteogenic differentiation of human MSCs (hMSCs) can be largely promoted using our nanoengineered topographic glass substrates in the absence of dexamethasone, a key exogenous factor for osteogenesis induction. We demonstrate that hMSCs sense and respond to surface nanotopography, through modulation of adhesion, cytoskeleton tension, and nuclear activation of TAZ (transcriptional coactivator with PDZ-binding motif), a transcriptional modulator of hMSCs. Our findings demonstrate the potential of nanotopographic surfaces as noninvasive tools to advance cell-based therapies for bone engineering and highlight the origin of biophysical response of hMSC to nanotopography.

Dynamic Mechanics‐Modulated Hydrogels to Regulate the Differentiation of Stem‐Cell Spheroids in Soft Microniches and Modeling of the Nonlinear Behavior

“…The shape and the size of the cell during the cycle are not only dependent on its growth but also on cell–cell and cell–matrix forces . Thus, we used fractal analysis to quantify cytoskeletal density changes under the dynamic culture condition . The cytoskeleton arrangement was assigned a fractal dimension ( D f ), as shown in Figure A.…”

<p>Functionalized Graphene Nanoparticles Induce Human Mesenchymal Stem Cells to Express Distinct Extracellular Matrix Proteins Mediating Osteogenesis</p>

“…Besides biochemical stimuli, physical properties of scaffolds including, surface patterns, elasticity and nano-topography have been shown to affect osteogenic differentiation of MSCs. [52][53][54] It is possible that the areas of cell clustering observed on LOG nanoparticles overlap with areas of increased surface roughness, and provide an ideal niche for anchoring, proliferation, and potentially osteogenic differentiation and mineralization. Published research supports that rough surfaces allow cells to attach more easily due to the multiple sites for cell-surface interaction and increasing cytoskeletal stresses result in the recruitment of more adhesive molecules.…”

Probing Single-Cell Mechanical Allostasis Using Ultrasound Tweezers

“…Cells actively modulate cellular sensing and signaling transduction components, such as cell CSK structures and intra-and inter-cellular mechanosensitive molecules to adapt to mechanical cues,. 37,50,57,60,72 Yet it remains unclear how the transformation or deterioration of a cell's CSK properties featured in disease progression contributes to a cell's dynamics response to mechanical stress in allostasis. As a cell makes up the foundation of larger-scale behaviors, exploring single-cell allostasis at a subcellular domain may help us better understand the etiology of various diseases and progression of aging.…”