Manipulating neural stem cell (NSC) fate is of great importance for improving the therapeutic efficacy of NSCs to treat neurodegenerative disorders. Biophysical cues, in addition to biochemical factors, regulate NSC phenotype and function. In this study, we assessed the extent to which surface nanotopography of culture substrates modulates human NSC (hNSC) differentiation. Fibronectin-coated polymer substrates with diverse nanoscale shapes (groove and pillar) and dimensions (ranging from 300 to 1500 nm groove width and pillar gap) were used to investigate the effects of topographical cues on hNSC morphology, alignment, focal adhesion, and differentiation. The majority of nanopatterned substrates induced substantial changes in cellular morphology and alignment along the patterned shapes, leading to alterations in focal adhesion and F-actin reorganization. Certain types of nanopatterned substrates, in particular the ones with small nanostructures (e.g., 300-300 nm groove ridges and 300-300 nm pillar diameter gaps), were found to effectively enhance focal adhesion complex development. Consequently, these substrates enhanced hNSC differentiation toward neurons and astrocytes. Nanotopographical-induced formation of focal adhesions in hNSCs activates integrin-mediated mechanotransduction and intracellular signaling pathways such as MEK-ERK, which may ultimately promote gene expression related to NSC differentiation. This strategy of manipulating matrix surface topography could be applied to develop culture substrates and tissue engineered scaffolds that improve the efficacy of NSC therapeutics.

Both self-healable conductors and stretchable conductors have been previously reported. However, it is still difficult to simultaneously achieve high stretchability, high conductivity, and self-healability. Here, we observed an intriguing phenomenon, termed “electrical self-boosting”, which enables reconstructing of electrically percolative pathways in an ultrastretchable and self-healable nanocomposite conductor (over 1700% strain). The autonomously reconstructed percolative pathways were directly verified by using microcomputed tomography and in situ scanning electron microscopy. The encapsulated nanocomposite conductor shows exceptional conductivity (average value: 2578 S cm–1; highest value: 3086 S cm–1) at 3500% tensile strain by virtue of efficient strain energy dissipation of the self-healing polymer and self-alignment and rearrangement of silver flakes surrounded by spontaneously formed silver nanoparticles and their self-assembly in the strained self-healing polymer matrix. In addition, the conductor maintains high conductivity and stretchability even after recovered from a complete cut. Besides, a design of double-layered conductor enabled by the self-bonding assembly allowed a conducting interface to be located on the neutral mechanical plane, showing extremely durable operations in a cyclic stretching test. Finally, we successfully demonstrated that electromyogram signals can be monitored by our self-healable interconnects. Such information was transmitted to a prosthetic robot to control various hand motions for robust interactive human-robot interfaces.

We present a microfabricated hybrid biopolymer microcantilever, in which the contractile force of self-organized cardiomyocytes can be measured and studied, as a prototype for the development of cell-driven actuators. The microcantilever is made of a flexible, transparent, biocompatible poly(dimethylsiloxane) substrate, using a simple microfabrication technique. Seeding and culturing cardiomyocytes on the specific cantilever allows us to perform highly sensitive, quantitative, and noninvasive measurement of the contractile force of the self-organized cells in real time. The motions of the microcantilever showed good agreement with an analytical solution based on Stoney's equation and finite element modeling (FEM) of the hybrid system. Immunostaining of the cells on the hybrid system showed continuous high-order coalignment of actin filaments and parallel sarcomeric organization in the direction of the longitudinal axis of the microcantilever without structural constraints, such as microgrooves or lines, and proved our FEM and the synchronous contraction of cardiomyocytes. The presented device should facilitate measurement of the contractile force of self-organized cardiomyocytes on a specific area, which may help the understanding of heart failure and the design of optimal hybrid biopolymer actuators, as well as assist development of a microscale cell-driven motor system.

In this paper, we describe an approach to generate microporous cell-laden hydrogels for fabricating biomimetic tissue engineered constructs. Micropores at different length scales were fabricated in cell-laden hydrogels by micromolding fluidic channels and leaching sucrose crystals. Microengineered channels were created within cell-laden hydrogel precursors that contained agarose solution mixed with sucrose crystals. The rapid cooling of the agarose solution was used to gel the solution and form micropores in place of the sucrose crystals. The sucrose leaching process generated micropores that were homogeneously distributed within the gels, while enabling the direct immobilization of cells within the gels. We also characterized the physical, mechanical, and biological properties (i.e. microporosity, diffusivity, and cell viability) of cell-laden agarose gels as a function of engineered porosity. The microporosity was controlled from 0% to 40% and the diffusivity of molecules in the porous agarose gels increased as compared to controls. Furthermore, the viability of human hepatocyte cells that were cultured in microporous agarose gels corresponded to the diffusion profile generated away from the microchannels. Based on their enhanced diffusive properties, microporous cell-laden hydrogels containing a microengineered fluidic channel could be a useful tool for generating tissue structures for regenerative medicine and drug discovery applications.