There has been considerable interest in characterizing the polymer layer that is effectively irreversibly bound to nanoparticles (NPs) because it is thought to underpin the unusual thermomechanical properties of polymer nanocomposites (PNC). We study PNCs formed by mixing silica nanoparticles (NPs) with poly-2-vinylpyridine (P2VP) and compare the bound layer thickness δ determined by three different methods. We show that the thickness obtained by thermogravimetric analysis (TGA) and assuming that the bound layer has a density corresponding to a dense melt clearly underestimates the real bound layer thickness. A more realistic extent of the bound layer is obtained by in situ measurements of the interaction pair potential between NPs in PNCs via analysis of TEM micrographs; we verify these estimates using Dynamic Light Scattering (DLS) in θ solvent. Our results confirm the existence of long-ranged interactions between NPs corresponding roughly in size to the radius of gyration of the bound chains.
Physical loading is a potent stimulus required to maintain bone homeostasis, partly through the renewal and osteogenic differentiation of mesenchymal stem cells (MSCs). However, the mechanism by which MSCs sense a biophysical force and translate that into a biochemical bone forming response (mechanotransduction) remains poorly understood. The primary cilium is a single sensory cellular extension, which has recently been shown to demonstrate a role in cellular mechanotransduction and MSC lineage commitment. In this study, we present evidence that short periods of mechanical stimulation in the form of oscillatory fluid flow (OFF) is sufficient to enhance osteogenic gene expression and proliferation of human MSCs (hMSCs). Furthermore, we demonstrate that the cilium mediates fluid flow mechanotransduction in hMSCs by maintaining OFF-induced increases in osteogenic gene expression and, surprisingly, to limit OFF-induced increases in proliferation. These data therefore demonstrate a pro-osteogenic mechanosensory role for the primary cilium, establishing a novel mechanotransduction mechanism in hMSCs. Based on these findings, the application of OFF may be a beneficial component of bioreactor-based strategies to form bone-like tissues suitable for regenerative medicine and also highlights the cilium as a potential therapeutic target for efforts to mimic loading with the aim of preventing bone loss during diseases such as osteoporosis. Furthermore, this study demonstrates a role for the cilium in controlling mechanically mediated increases in the proliferation of hMSCs, which parallels proposed models of polycystic kidney disease. Unraveling the mechanisms leading to rapid proliferation of mechanically stimulated MSCs with defective cilia could provide significant insights regarding ciliopathies and cystic diseases. Stem Cells2012;30:2561–2570
The advent of adaptive manufacturing techniques supports the vision of cell-instructive materials that mimic biological tissues. 3D jet writing, a modified electrospinning process reported herein, yields 3D structures with unprecedented precision and resolution offering customizable pore geometries and scalability to over tens of centimeters. These scaffolds support the 3D expansion and differentiation of human mesenchymal stem cells in vitro. Implantation of these constructs leads to the healing of critical bone defects in vivo without exogenous growth factors. When applied as a metastatic target site in mice, circulating cancer cells home in to the osteogenic environment simulated on 3D jet writing scaffolds, despite implantation in an anatomically abnormal site. Through 3D jet writing, the formation of tessellated microtissues is demonstrated, which serve as a versatile 3D cell culture platform in a range of biomedical applications including regenerative medicine, cancer biology, and stem cell biotechnology.
Back Cover: 3D ordered macroporous films can be fabricated using ordered arrays of the monodispersed droplets as templates of the macropores, which are self-assembled in the space between two parallel flat glass plates. In the case with two or more layers, the lattice structure of the macroporous films also changes due to the confinement effects. Further details can be found in the article by Y. Iwai, Y. Uchida,* H. Yabu, and N. Nishiyama on page 1600502. Front Cover: 2D and 3D light-triggered modulation of hydrogel stiffness is described. UV lithography and 3D two-photon direct laser writing technology afford to alter hydrogel crosslinking degree in two and three dimensions, exploiting a specific chemistry design. Spatially controlled changes in hydrogel mechanical properties induce a biological response: elongated cells and higher proliferation are evident on 2D stiff patterns compared to the less cross-linked soft regions. 3D ordered macroporous films with a pore diameter of more than 100 μm can be fabricated using ordered arrays of monodispersed droplets self-assembling in the space between two flat glass plates as templates. As the gap between the glass plates changes, the number of the layer and the lattice structure of the macro-porous films change due to the confinement effects. A novel needleless electrohydrodynamic cojetting technique allows for the preparation of particles and fibers with two distinct compartments. Application of a high electric field results in the spontaneous formation of several distinct Taylor cones along a fluid interface, resulting in the deposition of bicompartmental fibers and particles. Production rates of fibers are more than 30 times higher than needle-based cojetting methods. Nanoparticles made by polymerization-induced self-assembly can show reversible stimulus-triggered polymorphism ("shape-shifting") that differs from the phase behaviour known for unimeric smart polymers. This review explains the background of this promising behaviour and summarises the current state-of-the-art. A hydrogel material with tailorable 2D and 3D cross-linking degree by conventional UV lithography and 3D two-photon direct laser writing technology is presented. Mechanical properties (e.g., stiffness) can be modulated to induce different cell behaviors: elongated cells and higher proliferation are evident on 2D stiff patterns compared to the less cross-linked soft regions. Communications
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