Mechanical Properties of Materials for Stem Cell Differentiation

Abstract

Traditionally, understanding differentiation pathway has been achieved by studying biochemical signal pathways controlled by various growth factors and cytokines. However, since various physical factors including tissue stiffness and topology can also determine the differentiation pathway of stem cells, mechanobiological pathway for controlling differentiation has been emphasized. Moreover, newly identified mechanobiological pathways have encouraged efforts to interpret stem cell differentiation in terms of cell-material interaction and provided clues to accurately design microenvironment of stem cells to control the direction of differentiation. Cells continuously recognize topographical and mechanical properties of the surrounding microenvironment and modulate their functional phenotypes through appropriate physiological responses to maintain homeostasis. Cell-cell and cell-extracellular matrix (ECM) interactions determine physical connections between the outside and the inside of individual cells to regulate various cellular functions, including adhesion, migration, proliferation, and cell differentiation. [3] Integrin, a transmembrane protein, is actively involved in outside-in and inside-out signaling mediated by polymerization and contraction of the cytoskeleton known to control cellular mechanotransduction pathways. [4] Therefore, a changed physical microenvironment can be detected by integrin-ECM interaction which has been traditionally considered as a primary target for controlling cell behavior through the material properties. Recent studies have shown that nuclear mechanosensation is a key process in response to physical stimuli. Nuclear membrane is tightly connected to integrin-based focal adhesion through cytoskeletal fibers that can transmit external force or cytoskeletal tension to the nuclear membrane, causing structural deformation of the nucleus. [5] Applied force not only changes nuclear shape, but also determines the conformation of many proteins located in nuclear membrane associated with various biochemical signals. [6] Since transcriptional regulatory mechanisms, such as histone modification and transcription factor activity, are controlled by force-mediated nuclear deformation, signal pathways for nuclear mechanosensation have been focused to interpret cellular adaptation mechanism including stem cell differentiation. [7] Various methods have been used to determine cell functions by changing cell adhesion through the corresponding changes in external substrates using micropatterned cell confinement, micro-/nanosized topographic substrates, and substrate stiffness. Micropatterning of ECM proteins is a well-established method to Recent findings about cell fate change induced by physical stimuli have expedited the discovery of underlying regulatory mechanisms that determine stem cell differentiation. Progress with regards to micro-/nanofabrication technology have led to the development of advanced materials that can mimic biophysical features of in vivo related circumstances of the human body...

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Fabrication of Biodegradable Polyurethane Foam Scaffolds with Customized Shapes and Controlled Mechanical Properties by Gas Foaming Technique

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Nanomaterials modulating stem cell behavior towards cardiovascular cell lineage

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