Three-Dimensional Bioprinting of Organoid-Based Scaffolds (OBST) for Long-Term Nanoparticle Toxicology Investigation.

The toxicity of nanoparticles absorbed through contact or inhalation is one of the major concerns for public health. It is mandatory to continually evaluate the toxicity of nanomaterials. In vitro nanotoxicological studies are conventionally limited by the two dimensions. Although 3D bioprinting has been recently adopted for three-dimensional culture in the context of drug release and tissue regeneration, little is known regarding its use for nanotoxicology investigation. Therefore, aiming to simulate the exposure of lung cells to nanoparticles, we developed organoid-based scaffolds for long-term studies in immortalized cell lines. We printed the viscous cell-laden material via a customized 3D bioprinter and subsequently exposed the scaffold to either 40 nm latex-fluorescent or 11-14 nm silver nanoparticles. The number of cells significantly increased on the 14th day in the 3D environment, from 5 × 105 to 1.27 × 106, showing a 91% lipid peroxidation reduction over time and minimal cell death observed throughout 21 days. Administered fluorescent nanoparticles can diffuse throughout the 3D-printed scaffolds while this was not the case for the unprinted ones. A significant increment in cell viability from 3D vs. 2D cultures exposed to silver nanoparticles has been demonstrated. This shows toxicology responses that recapitulate in vivo experiments, such as inhaled silver nanoparticles. The results open a new perspective in 3D protocols for nanotoxicology investigation supporting 3Rs.

Bionic for Training: Smart Framework Design for Multisensor Mechatronic Platform Validation.

Home monitoring supports the continuous improvement of the therapy by sharing data with healthcare professionals. It is required when life-threatening events can still occur after hospital discharge such as neonatal apnea. However, multiple sources of external noise could affect data quality and/or increase the misdetection rate. In this study, we developed a mechatronic platform for sensor characterizations and a framework to manage data in the context of neonatal apnea. The platform can simulate the movement of the abdomen in different plausible newborn positions by merging data acquired simultaneously from three-axis accelerometers and infrared sensors. We simulated nine apnea conditions combining three different linear displacements and body postures in the presence of self-generated external noise, showing how it is possible to reduce errors near to zero in phenomena detection. Finally, the development of a smart 8Ws-based software and a customizable mobile application were proposed to facilitate data management and interpretation, classifying the alerts to guarantee the correct information sharing without specialized skills.

Author Correction: In-vivo vascular application via ultra-fast bioprinting for future 5D personalised nanomedicine.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

In-vivo vascular application via ultra-fast bioprinting for future 5D personalised nanomedicine.

The design of 3D complex structures enables new correlation studies between the engineering parameters and the biological activity. Moreover, additive manufacturing technology could revolutionise the personalised medical pre-operative management due to its possibility to interplay with computer tomography. Here we present a method based on rapid freeze prototyping (RFP) 3D printer, reconstruction cutting, nano dry formulation, fast freeze gelation, disinfection and partial processes for the 5D digital models functionalisation. We elaborated the high-resolution computer tomography scan derived from a complex human peripheral artery and we reconstructed the 3D model of the vessel in order to obtain and verify the additive manufacturing processes. Then, based on the drug-eluting balloon selected for the percutaneous intervention, we reconstructed the biocompatible eluting-freeform coating containing 40 nm fluorescent nanoparticles (NPs) by means of RFP printer and we tested the in-vivo feasibility. We introduced the NPs-loaded 5D device in a rat's vena cava. The coating dissolved in a few minutes releasing NPs which were rapidly absorbed in vascular smooth muscle cell (VSMC) and human umbilical vein endothelial cell (HUVEC) in-vitro. We developed 5D high-resolution self-dissolving devices incorporating NPs with the perspective to apply this method to the personalised medicine.

Modeling, Fabrication and Testing of a Customizable Micromachined Hotplate for Sensor Applications.

In the sensors field the active sensing material frequently needs a controlled temperature in order to work properly. In microsystems technology, micro-machined hotplates represent a platform consisting of a thin suspended membrane where the sensing material can be deposited, usually integrating electrical stimuli and temperature readout. The micro-hotplate ensures a series of advantages such as miniaturized size, fast response, high sensitivity, low power consumption and selectivity for chemical sensing. This work compares the coplanar and the buried approach for the micro-hotplate heaters design with the aim to optimize the fabrication process and to propose a guideline for the choice of the suitable design with respect to the applications. In particular, robust Finite Element Method (FEM) models are set up in order to predict the electrical and thermal behavior of the micro-hotplates. The multiphysics approach used for the simulation allows to match as close as possible the actual device to the predictive model: geometries, materials, physics have been carefully linked to the fabricated devices to obtain the best possible accuracy. The materials involved in the fabrication process are accurately selected in order to improve the yield of the process and the performance of the devices. The fabricated micro-hotplates are able to warm the active region up to 400 °C (with a corresponding power consumption equal to 250 mW @ 400 °C) with a uniform temperature distribution in the buried micro-hotplate and a controlled temperature gradient in the coplanar one. A response time of about 70 ms was obtained on the virtual model, which perfectly agrees with the one measured on the fabricated device. Besides morphological, electrical and thermal characterizations, this work includes reliability tests in static and dynamic modes.