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Antonella Rocca,1,2 Attilio Marino,1,2 Veronica Rocca,3 Stefania Moscato,4 Giuseppe de Vito,5,6 Vincenzo Piazza,5 Barbara Mazzolai,1 Virgilio Mattoli,1 Thu Jennifer Ngo-Anh,7 Gianni Ciofani1 1Istituto Italiano di Tecnologia, Center for Micro-BioRobotics @SSSA, Pontedera, Italy, 2Scuola Superiore Sant’Anna, The BioRobotics Institute, Pontedera, Italy, 3Università di Pisa, Dipartimento di Ingegneria dell’Informazione, Pisa, Italy, 4Università di Pisa, Dipartimento di Medicina Clinica e Sperimentale, Pisa, Italy, 5Istituto Italiano di Tecnologia, Center for Nanotechnology Innovation @NEST, Pisa, Italy, 6Scuola Normale Superiore, NEST, Pisa, Italy, 7Directorate of Human Spaceflight and Operations, European Space Agency, Noordwijk, the Netherlands Background: Enhancement of the osteogenic potential of mesenchymal stem cells (MSCs) is highly desirable in the field of bone regeneration. This paper proposes a new approach for the improvement of osteogenesis combining hypergravity with osteoinductive nanoparticles (NPs).Materials and methods: In this study, we aimed to investigate the combined effects of hypergravity and barium titanate NPs (BTNPs) on the osteogenic differentiation of rat MSCs, and the hypergravity effects on NP internalization. To obtain the hypergravity condition, we used a large-diameter centrifuge in the presence of a BTNP-doped culture medium. We analyzed cell morphology and NP internalization with immunofluorescent staining and coherent anti-Stokes Raman scattering, respectively. Moreover, cell differentiation was evaluated both at the gene level with quantitative real-time reverse-transcription polymerase chain reaction and at the protein level with Western blotting.Results: Following a 20 g treatment, we found alterations in cytoskeleton conformation, cellular shape and morphology, as well as a significant increment of expression of osteoblastic markers both at the gene and protein levels, jointly pointing to a substantial increment of NP uptake. Taken together, our findings suggest a synergistic effect of hypergravity and BTNPs in the enhancement of the osteogenic differentiation of MSCs.Conclusion: The obtained results could become useful in the design of new approaches in bone-tissue engineering, as well as for in vitro drug-delivery strategies where an increment of nanocarrier internalization could result in a higher drug uptake by cell and/or tissue constructs. Keywords: mesenchymal stem cells, hypergravity, barium titanate nanoparticles, osteogenesis

Elmira FarrokhTakin,1,2 Gianni Ciofani,1 Gian Luigi Puleo,1 Giuseppe de Vito,3,4 Carlo Filippeschi,1 Barbara Mazzolai,1 Vincenzo Piazza,3 Virgilio Mattoli1 1Center for Micro-BioRobotics @SSSA, Fondazione Istituto Italiano di Tecnologia, Pontedera, Pisa, Italy; 2The Biorobotics Institute, Scuola Superiore Sant'Anna, Pontedera, Pisa, Italy; 3Center for Nanotechnology Innovation @NEST, Fondazione Istituto Italiano di Tecnologia, Pisa, Italy; 4NEST, Scuola Normale Superiore, Pisa, Italy Abstract: The development of new tools and devices to aid in treating cancer is a hot topic in biomedical research. The practice of using heat (hyperthermia) to treat cancerous lesions has a long history dating back to ancient Greece. With deeper knowledge of the factors that cause cancer and the transmissive window of cells and tissues in the near-infrared region of the electromagnetic spectrum, hyperthermia applications have been able to incorporate the use of lasers. Photothermal therapy has been introduced as a selective and noninvasive treatment for cancer, in which exogenous photothermal agents are exploited to achieve the selective destruction of cancer cells. In this manuscript, we propose applications of barium titanate core–gold shell nanoparticles for hyperthermia treatment against cancer cells. We explored the effect of increasing concentrations of these nanoshells (0–100 µg/mL) on human neuroblastoma SH-SY5Y cells, testing the internalization and intrinsic toxicity and validating the hyperthermic functionality of the particles through near infrared (NIR) laser-induced thermoablation experiments. No significant changes were observed in cell viability up to nanoparticle concentrations of 50 µg/mL. Experiments upon stimulation with an NIR laser revealed the ability of the nanoshells to destroy human neuroblastoma cells. On the basis of these findings, barium titanate core–gold shell nanoparticles resulted in being suitable for hyperthermia treatment, and our results represent a promising first step for subsequent investigations on their applicability in clinical practice. Keywords: barium titanate nanoparticles, gold nanoshells, NIR stimulation, human neuroblastoma

Gianni Ciofani1, Serena Danti2, Giada Graziana Genchi1,3, Delfo D'Alessandro2, Jean-Luc Pellequer4, Michaël Odorico4, Virgilio Mattoli1, Mario Giorgi51Italian Institute of Technology, Center of MicroBioRobotics co Scuola Superiore Sant'Anna, 2Department of Neuroscience, University of Pisa, 3The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy; 4Commissariat à l'Energie Atomique, Institut de Biologie Environnementale et Biotechnologie, Department of Biochemistry and Nuclear Toxicology, Bagnols-sur-Cèze, France; 5Division of Pharmacology and Toxicology, Veterinary Clinics Department, University of Pisa, Pisa, ItalyAbstract: Boron nitride nanotubes (BNNTs) have attracted huge attention in many different research fields thanks to their outstanding chemical and physical properties. During recent years, our group has pioneered the use of BNNTs for biomedical applications, first of all assessing their in vitro cytocompatibility on many different cell lines. At this point, in vivo investigations are necessary before proceeding toward realistic developments of the proposed applications. In this communication, we report a pilot toxicological study of BNNTs in rabbits. Animals were injected with a 1 mg/kg BNNT solution and blood tests were performed up to 72 hours after injection. The analyses aimed at evaluating any acute alteration of hematic parameters that could represent evidence of functional impairment in blood, liver, and kidneys. Even if preliminary, the data are highly promising, as they showed no adverse effects on all the evaluated parameters, and therefore suggest the possibility of the realistic application of BNNTs in the biomedical field.Keywords: boron nitride nanotubes, in vivo testing, toxicology

Thin and compliant conductive materials and electronic devices that are able to stand as free-standing membranes or to conform to surfaces are relevant for the development of human-device interfaces and unperceivable skin-contact personal health monitoring systems. In this work, a roll-to-roll (R2R) process for the preparation of conductive polymer nanosheets on large areas has been developed in view to move such technology towards real-world applications. R2R conductive nanosheets are obtained as free-standing structures through release from a temporary substrate and then transferred in conformal contact with any target surface with arbitrary shape, curvature and surface topography (including biological tissue such as skin). A specific high-conductivity formulation of PEDOT:PSS has been optimized for skin-contact applications, by making use of butylene glycol (BG) as a dopant: a dermatologically approved ingredient. The R2R nanosheets were tested as unperceivable surface electromyography electrodes able to record muscle-electrical activity. The present R2R process has advantageous properties such as continuous, high throughput printing on large area rolls, cost-effectiveness, speed of execution and use of industry-ready/mass-scale manufacturing technology. [ABSTRACT FROM AUTHOR]