Abstract
Biophysical factors such as anisotropic topography composed of micro/nanosized structures are important for directing the fate of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and have been applied to neuronal differentiation. Via high-throughput screening (HTS) methods based on topography gradients, the optimum topography is determined and translated toward a hierarchical architecture designed to mimic the nerve nano/microstructure. The polydimethylsiloxane (PDMS)-based topography gradient with amplitudes (A) from 541 to 3073 nm and wavelengths (W) between 4 and 30 µm is developed and the fate commitment of MSC toward neuron lineage is investigated. The hierarchical structures, combining nano- and microtopography (W0.3/W26 parallel/perpendicular) are fabricated to explore the combined topography effects on neuron differentiation. From the immunofluorescent staining results (Tuj1 and MAP2), the substrate characterized by W: 26 µm; A: 2.9 µm shows highest potential for promoting neurogenesis. Furthermore, the hierarchical features (W0.3/W26 parallel) significantly enhance neural differentiation. The hBM-MSCs on the hierarchical substrates exhibit a significantly lower percentage of nuclear Yes-associated protein (YAP)/TAZ and weaker cell contractility indicating that the promoted neurogenesis is mediated by the cell tension and YAP/TAZ pathway. This research provides new insight into designing biomaterials for applications in neural tissue engineering and contributes to the understanding of topography-mediated neuronal differentiation.
Highlights
Stem cells are Biophysical factors such as anisotropic topography composed of micro/nano- undifferentiated cells with self-renewal sized structures are important for directing the fate of human bone marrowderived mesenchymal stem cells and have been applied to neuronal differentiation
A fresh mixture of elastomer base/crosslinker was applied on top of the molds. This imprinting approach led to a PDMS wrinkle gradient with different topographies but exhibiting the same surface chemistry and mechanical properties
There was no significant difference between the two hierarchical substrates. These results demonstrate that the promoted neurogenesis of hBM-MSCs on W0.3∥26 is mediated by cell tension and Yes-associated protein (YAP)–TAZ pathway
Summary
The hierarchical structures, combining nano- and microtopography (W0.3/W26 parallel/perpendicular) are fabricated to explore is critical for the development of therapeutic approaches.[12] Previous research has shown that, in natural stem cell niche, the biophysical properties of extracellular matrix, e.g., topography,[13,14,15,16,17,18] stiffness,[19,20,21,22]. The hBM-MSCs on the hierarchical substrates sophisticated influence on the behavior of stem cells, including their adhesion, self-renewal, migration, and differentiation.[27,28] The surface topography significantly affects cell morphology, spreading, exhibit a significantly lower percentage of nuclear Yes-associated protein and orientation through a phenomenon (YAP)/TAZ and weaker cell contractility indicating that the promoted neuroknown as contact guidance.[29] Cells sense genesis is mediated by the cell tension and YAP/TAZ pathway. Yim and co-workers[32,33,34] have developed a multiarchitecture chip (MARC) array consisting
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