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.

In-situ optical assessment of rat epicardial kinematic parameters reveals frequency-dependent mechanic heterogeneity related to gender.

BACKGROUND: Gender-related cardiac mechanics following the electrical activity has been investigated from basic to clinical research, but results are still controversial. The aim of this work is to study the gender related cardiac mechanics and to focus on its heart rate dependency. METHODS: We employed 12 Sprague Dawley rats (5 males and 7 females) of the same age and, through a novel high resolution artificial vision contactless approach, we evaluated in-situ cardiac kinematic. The hearts were paced on the right atria appendage via cathodal stimuli at rising frequency. RESULTS: Kinematic data obtained at rising pacing rates are different between male and female rat hearts: male tended to maintain the same level of cardiac force, energy and contractility, while female responded with an increment of such parameters at increasing heart rate. Female hearts preserved their pattern of contraction and epicardial torsion (vorticity) at rising pacing rates compared to male. Furthermore, we observed a difference in the mechanical restitution: systolic time vs. diastolic time, as an index of cardiac performance, reached higher value in male compared to female hearts. CONCLUSION: Our innovative technology was capable to evaluate in-situ rat epicardial kinematic at high stimulation frequency, revealing that male preserved kinematic parameters but varying the pattern of contraction/relaxation. On the contrary, female preserved the pattern of contraction/relaxation increasing kinematic parameters.