Tetragonal barium titanate nanoparticles (BTNPs) have been exploited as nanotransducers owing to their piezoelectric properties, in order to provide indirect electrical stimulation to SH-SY5Y neuron-like cells. Following application of ultrasounds to cells treated with BTNPs, fluorescence imaging of ion dynamics revealed that the synergic stimulation is able to elicit a significant cellular response in terms of calcium and sodium fluxes; moreover, tests with appropriate blockers demonstrated that voltage-gated membrane channels are activated. The hypothesis of piezoelectric stimulation of neuron-like cells was supported by lack of cellular response in the presence of cubic nonpiezoelectric BTNPs, and further corroborated by a simple electroelastic model of a BTNP subjected to ultrasounds, according to which the generated voltage is compatible with the values required for the activation of voltage-sensitive channels.

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Soft robots hold promise for well-matched interactions with delicate objects, humans and unstructured environments owing to their intrinsic material compliance. Movement and stiffness modulation, which is challenging yet needed for an effective demonstration, can be devised by drawing inspiration from plants. Plants use a coordinated and reversible modulation of intracellular turgor (pressure) to tune their stiffness and achieve macroscopic movements. Plant-inspired osmotic actuation was recently proposed, yet reversibility is still an open issue hampering its implementation, also in soft robotics. Here we show a reversible osmotic actuation strategy based on the electrosorption of ions on flexible porous carbon electrodes driven at low input voltages (1.3 V). We demonstrate reversible stiffening (~5-fold increase) and actuation (~500 deg rotation) of a tendril-like soft robot (diameter ~1 mm). Our approach highlights the potential of plant-inspired technologies for developing soft robots based on biocompatible materials and safe voltages making them appealing for prospective applications.

The investigation of the crossing of exogenous substances through the blood-brain barrier (BBB) is object of intensive research in biomedicine, and one of the main obstacles for reliable in vitro evaluations is represented by the difficulties at the base of developing realistic models of the barrier, which could resemble as most accurately as possible the in vivo environment. Here, for the first time, a 1:1 scale, biomimetic, and biohybrid BBB model is proposed. Microtubes inspired to the brain capillaries were fabricated through two-photon lithography and used as scaffolds for the co-culturing of endothelial-like bEnd.3 and U87 glioblastoma cells. The constructs show the maturation of tight junctions, good performances in terms of hindering dextran diffusion through the barrier, and a satisfactory trans-endothelial electrical resistance. Moreover, a mathematical model is developed, which assists in both the design of the 3D microfluidic chip and its characterization. Overall, these results show the effective formation of a bioinspired cellular barrier based on microtubes reproducing brain microcapillaries to scale. This system will be exploited as a realistic in vitro model for the investigation of BBB crossing of nanomaterials and drugs, envisaging therapeutic and diagnostic applications for several brain pathologies, including brain cancer.

Electrical stimulation of cells and tissues is an important approach of interaction with living matter, which has been traditionally exploited in the clinical practice for a wide range of pathological conditions, in particular, related to excitable tissues. Standard methods of stimulation are, however, often invasive, being based on electrodes and wires used to carry current to the intended site. The possibility to achieve an indirect electrical stimulation, by means of piezoelectric materials, is therefore of outstanding interest for all the biomedical research, and it emerged in the latest decade as a most promising tool in many bioapplications. In this paper, we summarize the most recent achievements obtained by our group and by others in the exploitation of piezoelectric nanoparticles and nanocomposites for cell stimulation, describing the important implications that these studies present in nanomedicine and tissue engineering. A particular attention will be also dedicated to the physical modeling, which can be extremely useful in the description of the complex mechanisms involved in the mechanical/electrical transduction, yet also to gain new insights at the base of the observed phenomena.

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Oxidative stress represents a common issue in most neurological diseases, causing severe impairments of neuronal cell physiological activity that ultimately lead to neuron loss of function and cellular death. In this work, lipid-coated polydopamine nanoparticles (L-PDNPs) are proposed both as antioxidant and neuroprotective agents, and as a photothermal conversion platform able to stimulate neuronal activity. L-PDNPs showed the ability to counteract reactive oxygen species (ROS) accumulation in differentiated SH-SY5Y, prevented mitochondrial ROS-induced dysfunctions and stimulated neurite outgrowth. Moreover, for the first time in the literature, the photothermal conversion capacity of L-PDNPs was used to increase the intracellular temperature of neuron-like cells through near-infrared (NIR) laser stimulation, and this phenomenon was thoroughly investigated using a fluorescent temperature-sensitive dye and modeled from a mathematical point of view. It was also demonstrated that the increment in temperature caused by the NIR stimulation of L-PDNPs was able to produce a Ca 2+ influx in differentiated SH-SY5Y, being, to the best of our knowledge, the first example of organic nanostructures used in such an approach. This work could pave the way to new and exciting applications of polydopamine-based and of other NIR-responsive antioxidant nanomaterials in neuronal research.

The tissue composition and microstructures of plants have dynamic morphologies that change according to their environments. Recently, multifunctional responsive materials and smart structures also took inspiration from these plants' features. Dionaea muscipula leaves provide a remarkable example of an optimized structure that, owing to the synergistic integration of bistability, material, and geometrical properties, permits to overcome the performance limits of purely diffusive processes. In this paper, a hygroscopic bistable structure (HBS) inspired by the Venus flytrap leaves is presented, obtained by bonding prestretched poly(dimethylsiloxane) (PDMS) layers prior to depositing electrospun polyethylene oxide (PEO) nanofibers. A hygroresponsive bilayer (HBL) is also obtained by electrospinning of PEO on an unstretched PDMS layer. The hygroscopic material (Young's modulus and hygroscopic expansion) is mechanically characterized so as to predict the response time of a bending HBL in response to a step humidity variation. The HBS response time (≈1 s) is sensibly lower than the one of purely diffusive HBL (≈10 s) thanks to bistability. An illustrative implementation is also presented, exploiting an HBS to trigger the curvature of a PDMS optical focusing system. The developed plant‐inspired soft bistable structure can also be used for sensing (e.g., humidity), energy harvesting, as well as advanced soft robotics applications.