No abstract

Since hydrogel therapies have been introduced into clinic treatment procedures, the biomedical industry has to face the technology transfer and the scale-up of the processes. This will be key in the roadmap of the new technology implementation. Transfer technology and scale-up are already known for some applications but other applications, such as 3D printing, are still challenging. Decellularized tissues offer a lot of advantages when compared to other natural gels, for example they display enhanced biological properties, due to their ability to preserve natural molecules. For this reason, even though their use as a source for bioinks represents a challenge for the scale-up process, it is very important to consider the advantages that originate with overcoming this challenge. Therefore, many aspects that influence the scaling of the industrial process should be considered, like the addition of drugs or cells to the hydrogel, also, the gelling process is important to determine the chemical and physical parameters that must be controlled in order to guarantee a successful process. Legal aspects are also crucial when carrying out the scale-up of the process since they determine the industrial implementation success from the regulatory point of view. In this context, the new law Regulation (EU) 2017/745 on biomedical devices will be considered. This review summarizes the different aspects, including the legal ones, that should be considered when scaling up hydrogels of natural origin, in order to balance these different aspects and to optimize the costs in terms of raw materials and engine.

Aims. The aim of the project is to identify wide common proper motion companions to a sample of spectroscopically confirmed M and L metal-poor dwarfs (also known as subdwarfs) to investigate the impact of metallicity on the binary fraction of low-mass metal-poor binaries and to improve the determination of their metallicity from the higher-mass binary. Methods. We made use of Virtual Observatory tools and large-scale public surveys to look in Gaia for common proper motion companions to a well-defined sample of ultracool subdwarfs with spectral types later than M5 and metallicities below or equal to −0.5 dex. We collected low-resolution optical spectroscopy for our best system, which is a binary composed of one sdM1.5 subdwarf and one sdM5.5 subdwarf located at ∼1360 au, and for another two likely systems separated by more than 115 000 au. Results. We confirm one wide companion to an M subdwarf, and infer a multiplicity for M subdwarfs (sdMs) of 1.0−1.0+2.0% for projected physical separations of up to 743 000 au. We also find four M–L systems, three of which are new detections. No colder companion was identified in any of the 219 M and L subdwarfs of the sample, mainly because of limitations on the detection of faint sources with Gaia. We infer a frequency of wide systems for sdM5–9.5 of 0.60−0.60+1.17% for projected physical separations larger than 1 360 au (up to 142 400 au). This study shows a multiplicity rate of 1.0−1.0+2.0% in sdMs, and 1.9−1.9+3.7% in extreme M subdwarfs. We did not find any companion for the ultra M subdwarfs of our sample, establishing an upper limit of 5.3% on binarity for these objects.

Aims. With the latest Gaia DR3 data, we analyse the widest pairs in the Washington Double Star (WDS) catalogue with angular separations, ρ, greater than 1000 arcsec. Methods. We confirmed the pairs' membership to stellar systems based on common proper motions, parallaxes, and (when available) radial velocities, together with the locii of the individual components in colour-magnitude diagrams. We also looked for additional closer companions to the ultrawide pairs, either reported by WDS or found by us with a new Gaia astrometric search. In addition, we determined masses for each star (and white dwarf) and, with the projected physical separation, computed the gravitational potential energy, |U * g |, of the systems. Results. Of the 155 159 pairs currently catalogued by WDS, there are 504 with ρ > 1000 arcsec. Of these, only 2 ultrawide pairs have not been identified, 10 do not have any available astrometry, 339 have not passed a conservative filtering in proper motion or parallax, 59 are members of young stellar kinematic groups, associations or open clusters, and only 94 remain as bona fide ultrawide pairs in the galactic field. Accounting for the additional members at shorter separations identified in a complementary astrometric and bibliographic search, we found 79 new stars (39 reported, plus 40 not reported by WDS) in 94 ultrawide stellar systems. This sample is expanded when including new close binary candidates with large Gaia DR3 RUWE, σ Vr , or a proper motion anomaly. Furthermore, the large fraction of subsystems and the non-hierarchical configurations of many wide systems with three or more stars is remarkable. In particular, we found 14 quadruple, 2 quintuple, 3 sextuple, and 2 septuple systems. The minimum computed binding energies, |U * g | ∼ 10 33 J, are in line with theoretical predictions of tidal destruction by the Galactic gravitational potential. The most fragile and massive systems have huge projected physical separations of well over 1 pc. Therefore, they are either in the process of disruption or they are part of unidentified juvenile stellar kinematic groups.