Although collagen is commonly used as components of tissue-engineered nerve-guidance channels, little is known about the effect of the mechanical properties of commonly used gel concentrations on the extension of neurites. This study focused on neurite extension of dissociated chick dorsal root ganglia in vitro over a range of collagen concentrations (0.4-2.0 mg/ml). Neurite length increased in all gels between day 1 and day 4, except at the highest collagen concentration, where a 9% decrease was noted at day 4. Although maximum neurite extension was seen in lower concentration gels (0.6-0.8 mg/ml), mechanical stiffness of each gel significantly increased with increasing concentration, from 2.2 Pa at 0.4 mg/ml to 17.0 Pa at 2.0 mg/ml. A previous model of mechanical stiffness versus neurite outgrowth did not fit this data well, likely because of interactions between the growth cone and the collagen fibers. Overall, these results provided insight regarding factors that influence neurite elongation and may be utilized to further optimize tissue-engineered scaffolds.

Our nationwide network of BME women faculty collectively argue that racial funding disparity by the National Institutes of Health (NIH) remains the most insidious barrier to success of Black faculty in our profession. We thus refocus attention on this critical barrier and suggest solutions on how it can be dismantled.

Modular, bioactive, macroporous scaffolds were formed by crosslinking poly(ethylene glycol) (PEG) microspheres around living cells. Hydrogel microspheres were produced from reactive PEG derivatives in aqueous sodium sulfate solutions without the use of surfactants or copolymers. Microspheres were formed following thermally induced phase separation if the gel point was reached prior to extensive coarsening of the PEG-rich domains. Three types of PEG microspheres with different functionalities were used to form scaffolds. One type of PEG microsphere provided mechanical support, the second type provided controlled delivery of the angiogenesis-promoting molecule, sphingosine 1-phosphate (S1P), and the third type served as a slowly dissolving noncytotoxic porogen. Scaffolds were formed by centrifuging microspheres in the presence of HepG2 hepatoma cells, resulting in a homogenous distribution of cells. During overnight incubation at 37°C, the microspheres reacted with serum proteins in cell culture medium to stabilize the scaffolds. Within two days in culture, macropores formed due to the dissolution of the porogenic PEG microspheres, without affecting cell viability. Gradients in porosity were produced by varying the buoyancy of the porogenic microspheres. Conjugated RGD cell adhesion peptides and delivery of sphingosine 1-phosphate promoted endothelial cell infiltration through macropores in the scaffolds. The scaffolds presented here differ from previous hydrogel scaffolds in that: 1) cells are not encapsulated in hydrogel, 2) macropores form in the presence of cells, and 3) scaffold properties are controlled by the modular assembly of different microspheres that perform distinct functions.

Neurons and neural stem cells are sensitive to their mechanical and topographical environment, and cell-substrate binding contributes to this sensitivity to activate signaling pathways for basic cell functions. Many transmembrane proteins transmit signals into and out of the cell, including integrins, growth factor receptors, G-protein-coupled receptors, cadherins, cell adhesion molecules, and ion channels. Specifically, integrins are one of the main transmembrane proteins that transmit force across the cell membrane between a cell and its extracellular matrix, making them critical in the study of cell-material interactions. This review focuses on mechanotransduction, defined as the conversion of force a cell generates through cell-substrate bonds to a chemical signal, of neural cells. The chemical signals relay information via pathways through the cellular cytoplasm to the nucleus, where signaling events can affect gene expression. Pathways and the cellular response initiated by substrate binding are explored to better understand their effect on neural cells mechanotransduction. As the results of mechanotransduction affect cell adhesion, cell shape, and differentiation, knowledge regarding neural mechanotransduction is critical for most regenerative strategies in tissue engineering, where novel environments are developed to improve conduit design for central and peripheral nervous system repair in vivo.

This study aimed to reveal the influence of brief DC electric stimulation on neurite outgrowth and outgrowth rates after application. Chick embryo dorsal root ganglia neurite outgrowth, rates, and overall alignment to EF were measured before stimulation and at two time points after stimulation. The presence of a 25 V/m EF for 10 min increased overall neurite outgrowth over controls for up to 48 h after stimulation and all growth was symmetric. These results demonstrate that even 10 min of stimulation, which is approximately 80% shorter than previous studies, promotes enhanced nerve growth.