Guidelines for Manufacturing and Application of Organoids: Lung.

The objective of standard guideline for utilization of human lung organoids is to provide the basic guidelines required for the manufacture, culture, and quality control of the lung organoids for use in non-clinical efficacy and inhalation toxicity assessments of the respiratory system. As a first step towards the utilization of human lung organoids, the current guideline provides basic, minimal standards that can promote development of alternative testing methods, and can be referenced not only for research, clinical, or commercial uses, but also by experts and researchers at regulatory institutions when assessing safety and efficacy.

Three-dimensional assembly of nanoparticles from charged aerosols.

The capability of assembling nanoparticles into a desired ordered pattern is a key to realize novel devices which are based not only on the unique properties of nanoparticles but also on the arrangements of nanoparticles. While two-dimensional arrays of nanoparticles have been successfully demonstrated by various techniques, a controlled way of building ordered arrays of three-dimensional (3D) nanoparticle structures remains challenging. We report that a variety of 3D nanoparticle structures can be formed in a controlled way based on the ion-induced focusing, electrical scaffold, and antenna effects from charged aerosols. Particle trajectory calculations successfully predict the whole process of 3D assembly. New surface enhanced Raman scattering substrates based on our 3D assembly were constructed as an example showing the viability of the present approach. This report extends the current capability of positioning nanoparticles on surface to another spatial dimension, which can serve as the foundation of future optical, magnetic, and electronic devices taking the advantage of multidimensions.

Toxicity and clearance of intratracheally administered multiwalled carbon nanotubes from murine lung.

Carbon nanotubes (CNT) are known to have widespread industrial applications; however, several reports indicated that these compounds may be associated with adverse effects in humans. In this study, multiwalled carbon nanotubes were administered to murine lungs intratracheally to determine whether acute and chronic pulmonary toxicity occurred. In particular, pristine multiwalled carbon nanotubes (PMWCNT) and acid-treated multiwalled carbon nanotubes (TMWCNT) were used in this study. In broncheoalveolar lavage fluid (BALF) cell analysis, PMWCNT induced more severe acute inflammatory cell recruitment than TMWCNT. Histopathologically, both PMWCNT and TMWCNT induced multifocal inflammatory granulomas in a dose-dependent manner. The observed granulomas were reversible, with TMWCNT-induced granulomas diminishing faster than PMWCNT-induced granulomas. Although the area of granuloma reduced with time, hyperplasia and dysplastic characteristics such as mitotic figures, anisokaryosis, and anisocytosis were still observed. These findings demonstrate that MWCNT induces granulomatous inflammation, and the duration and pattern of inflammation seem to vary depending upon the types of MWCNT to which mice are exposed. Therefore, toxicity studies on various types of CNT are needed as the responsiveness to these compounds differs.

High-resolution, parallel patterning of nanoparticles via an ion-induced focusing mask.

An ion-induced focusing mask under the simultaneous injection of ions and charged aerosols generates invisible electrostatic lenses around each opening, through which charged nanoparticles are convergently guided without depositing on the mask surface. The sizes of the created features become significantly smaller than those of the mask openings due to the focusing capability. It is not only demonstrated that material-independent nanoparticles including proteins can be patterned as an ordered array on any surface regardless of the conductive, nonconductive, or flexible nature of the substrate, but also that the array density can be increased. Highly sensitive gas sensors based on these focused nanoparticle patterns are fabricated via the concept.