Injectable hyaluronic acid bionanocomposite hydrogels: from biomaterial development to biological performance outcomes

Introduction: Injectable hyaluronic acid (HA) hydrogels have been increasingly applied in tissue engineering (TE) envisioning minimal invasive approaches. However, traditional HA hydrogels lack structural integrity that makes them less competitive in strategies where good mechanical properties are required. Here we propose the use of cellulose nanocrystals (CNCs), the nature â carbon nanotubesâ , as nanofillers and crosslinkers in a fully biobased strategy for the production of reinforced HA nanocomposite hydrogels[1]. Due to their distinct mechanical properties, biocompatibility and excellent aqueous colloidal stability, CNCs are being increasingly considered in hydrogel development targeting biomedical applications[2]. We hypothesise that besides structural reinforcement, in TE strategies the CNCâ s surface SO3-groups may also potentially act as semisynthetic mimicry of ECM sulfated glycosaminoglycans, which are known to induce and control specific cell functions on the cellular microenvironment through interactions with soluble biomolecules, e.g. proteins, growth factors (GFs)[3]. Materials and Methods: In situ crosslinkable and injectable hydrogels were prepared based on hydrazone coupling of adipic acid dihydrazide-modified HA (ADH-HA) and aldehyde-modified HA (a-HA), reinforced with aldehyde-modified CNCs (a-CNCs) (Figure 1). The hydrogel precursors were fully characterized by several spectroscopic, chromatographic, and imaging techniques, and the hydrogels were characterized in terms of internal morphology, mechanical properties, swelling and degradation behaviour in the presence of hyaluronidase. The biological performance of the developed nanocomposites was assessed towards human adipose derived stem cells (hASCs). Results and Discussion: The incorporation of a-CNCs in the hydrogelâ s network had a remarkable impact over the physical and biological performance of the injectable biomaterial. Nanocomposite hydrogels showed improved microstructure and mechanical properties (increased Eâ  up to 2.7-fold compared to unfilled hydrogels), lower equilibrium swelling ratios and higher resistance to bulk hyaluronidase degradation. HA-CNCs exhibited preferential cell supportive properties in in vitro culture conditions, in both surface cell seeding and cell encapsulation tests. Particularly, hASCs encapsulated in HA-CNCs hydrogels demonstrated ability to spread within the volume of gels and exhibited pronounced proliferative activity. This impact over cellâ s behaviour is correlated with the higher structural integrity of the hydrogel matrix and potential interaction of soluble microenvironmental cues with the CNCâ s surface sulphate groups. Conclusions: The proposed strategy demonstrated to be a valuable approach for fine tuning the structural, biomechanical and biochemical properties of injectable HA hydrogels.  The combined effects of enhanced stability and mechanical properties with the incorporation of mimetic ECM biochemical cues in HA-CNCs hydrogels, proved to positively impact their biological performance for TE applications. Considering the promising outcomes, we are currently exploring the potential of the developed system when combined with discrete GFs or the GFs pool from platelet lysates in specific TE strategies

Intrinsic time resolution of 3D-trench silicon pixels for charged particle detection

In the last years, high-resolution time tagging has emerged as the tool to tackle the problem of high-track density in the detectors of the next generation of experiments at particle colliders. Time resolutions below 50ps and event average repetition rates of tens of MHz on sensor pixels having a pitch of 50$\mu$m are typical minimum requirements. This poses an important scientific and technological challenge on the development of particle sensors and processing electronics. The TIMESPOT initiative (which stands for TIME and SPace real-time Operating Tracker) aims at the development of a full prototype detection system suitable for the particle trackers of the next-to-come particle physics experiments. This paper describes the results obtained on the first batch of TIMESPOT silicon sensors, based on a novel 3D MEMS (micro electro-mechanical systems) design. Following this approach, the performance of other ongoing silicon sensor developments has been matched and overcome, while using a technology which is known to be robust against radiation degradation. A time resolution of the order of 20ps has been measured at room temperature suggesting also possible improvements after further optimisations of the front-end electronics processing stage.Comment: This version was accepted to be published on JINST on 21/07/202

The Effect of Message Framing on COVID-19 Vaccination Intentions among the Younger Age Population Groups: Results from an Experimental Study in the Italian Context

The coronavirus pandemic has been recognized as a major threat to public health. Widespread acceptance of COVID-19 vaccines is crucial for achieving adequate immunization coverage to end the global pandemic. However, to date, there are still hesitant people, especially among the younger population groups. For this reason, it is essential to identify the psychological variables that may affect vaccination intention among these “at risk groups” and to select possible successful communication frames in order to increase vaccination rates. An online cross-sectional survey was carried out on 208 Italian citizens younger than 50 years old, to explore message framing effects on their intention to receive the vaccination and to understand the psychological factors influencing it. Results showed that depending on the goal (stimulate vaccination intention, vaccination trust, or vaccine attitude), not all the communication stimuli are equally effective on this target population. Furthermore, the study showed that sociodemographic variables do not help to explain the vaccination intention of the younger population groups, while the psychological variables have been found to have a stronger impact on such attitude. Trust and attitudes towards vaccines, concern about the pandemic and concern about infecting others have been found to be the most effective predictive variables of people vaccination intention. The study results underline the importance of understanding the psychological roots behind vaccine hesitancy to shape sensitization actions and vaccination campaigns targeting this population group

Design of a Mobile App for Nutrition Education (TreC-LifeStyle) and Formative Evaluation With Families of Overweight Children

Nutrition and diet apps represent today a popular area of mobile health (mHealth), offering the possibility of delivering behavior change (BC) interventions for healthy eating and weight management in a scalable and cost-effective way. However, if commercial apps for pediatric weight management fail to retain users because of a lack of theoretical background and evidence-based content, mHealth apps that are more evidence-based are found less engaging and popular among consumers. Approaching the apps development process from a multidisciplinary and user-centered design (UCD) perspective is likely to help overcome these limitations, raising the chances for an easier adoption and integration of nutrition education apps within primary care interventions

A novel GH-1 gene mutation (GH-P59L) causes partial GH deficiency type II combined with bioinactive GH syndrome

Despite the differences in the main characteristics between the autosomal dominant form of GH deficiency (IGHD II) and the bioinactive GH syndrome, a common feature of both is their impact on linear growth leading to short stature in all affected patients

XRCC1 and ERCC1 variants modify malignant mesothelioma risk: a case-control study.

Malignant pleural mesothelioma (MPM) is a rare aggressive tumor associated with asbestos exposure. The possible role of genetic factors has also been suggested and MPM has been associated with single nucleotide polymorphisms (SNPs) of xenobiotic and oxidative metabolism enzymes. We have identified an association of the DNA repair gene XRCC1 with MPM in the population of Casale Monferrato, a town exposed to high asbestos pollution. To extend this observation we examined 35 SNPs in 15 genes that could be involved in MPM carcinogenicity in 220 MPM patients and 296 controls from two case-control studies conducted in Casale (151 patients, 252 controls) and Turin (69 patients, 44 controls), respectively. Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Two DNA repair genes were associated with MPM, i.e. XRCC1 and ERCC1. Considering asbestos-exposed only, the risk increased with the increasing number of XRCC1-399Q alleles (Casale: OR=1.44, 95%CI 1.02-2.03; Casale+Turin: OR=1.34, 95%CI 0.98-1.84) or XRCC1 -77T alleles (Casale+Turin: OR=1.33, 95%CI 0.97-1.81). The XRCC1-TGGGGGAACAGA haplotype was significantly associated with MPM (Casale: OR=1.76, 95%CI 1.04-2.96). Patients heterozygotes for ERCC1 N118N showed an increased OR in all subjects (OR=1.66, 95%CI 1.06-2.60) and in asbestos-exposed only (OR=1.59, 95%CI 1.01-2.50). When the dominant model was considered (i.e. ERCC1 heterozygotes CT plus homozygotes CC versus homozygotes TT) the risk was statistically significant both in all subjects (OR=1.61, 95%CI 1.06-2.47) and in asbestos-exposed only (OR=1.56, 95%CI 1.02-2.40). The combination of ERCC1 N118N and XRCC1 R399Q was statistically significant (Casale: OR=2.02, 95%CI 1.01-4.05; Casale+Turin: OR=2.39, 95%CI 1.29-4.43). The association of MPM with DNA repair genes support the hypothesis that an increased susceptibility to DNA damage may favour asbestos carcinogenicity

Suicide prevention discussed at the WHO European Ministerial Conference on Mental Health. (Editorial).

Injectable hyaluronic acid (HA)-based hydrogels compose a promising class of materials for tissue engineering and regenerative medicine applications. However, their limited mechanical properties restrict the potential range of application. In this study, cellulose nanocrystals (CNCs) were employed as nanofillers in a fully biobased strategy for the production of reinforced HA nanocomposite hydrogels. Herein we report the development of a new class of injectable hydrogels composed of adipic acid dihydrazide-modified HA (ADH-HA) and aldehyde-modified HA (a-HA) reinforced with varying contents of aldehyde-modified CNCs (a-CNCs). The obtained hydrogels were characterized in terms of internal morphology, mechanical properties, swelling, and degradation behavior in the presence of hyaluronidase. Our findings suggest that the incorporation of a-CNCs in the hydrogel resulted in a more organized and compact network structure and led to stiffer hydrogels (maximum storage modulus, <i>E</i>′, of 152.4 kPa for 0.25 wt % a-CNCs content) with improvements of <i>E</i>′ up to 135% in comparison to unfilled hydrogels. In general, increased amounts of a-CNCs led to lower equilibrium swelling ratios and higher resistance to degradation. The biological performance of the developed nanocomposites was assessed toward human adipose derived stem cells (hASCs). HA-CNCs nanocomposite hydrogels exhibited preferential cell supportive properties in in vitro culture conditions due to higher structural integrity and potential interaction of microenvironmental cues with CNC’s sulfate groups. hASCs encapsulated in HA-CNCs hydrogels demonstrated the ability to spread within the volume of gels and exhibited pronounced proliferative activity. Together, these results demonstrate that the proposed strategy is a valuable toolbox for fine-tuning the structural, biomechanical, and biochemical properties of injectable HA hydrogels, expanding their potential range of application in the biomedical field

Optimization of the gain layer design of ultra-fast silicon detectors

none20noneSiviero, F.; Arcidiacono, R.; Borghi, G.; Boscardin, M.; Cartiglia, N.; Centis Vignali, M. ; Costa, M.; Dalla Betta, G.-F.; Ferrero, M.; Ficorella, F.; Gioachin, G.; Mandurrino, M.; Mazza, S.; Menzio, L.; Pancheri, L.; Paternoster, G.; Sadrozinski, H.-F.W.; Seiden, A.; Sola, V.; Tornago, M.Siviero, F.; Arcidiacono, R.; Borghi, G.; Boscardin, M.; Cartiglia, N.; Centis Vignali, M.; Costa, M.; Dalla Betta, G. -F.; Ferrero, M.; Ficorella, F.; Gioachin, G.; Mandurrino, M.; Mazza, S.; Menzio, L.; Pancheri, L.; Paternoster, G.; Sadrozinski, H. -F. W.; Seiden, A.; Sola, V.; Tornago, M

Implementation of tele visit healthcare services triggered by the COVID-19 emergency: the Trentino Province experience

Aim In response to the SARS-CoV-2 emergency, the Competence Centre on digital health ‘TrentinoSalute4.0’ has developed TreC_Televisita, a tele visit solution that meets the needs of the Trentino healthcare system and maintains high-quality patient–doctor interactions while respecting social distancing. This paper highlights how ‘TreC_Televisita’ was integrated into the Trentino healthcare system and its potential to become a structural and durable solution for the future local healthcare service provisioning. Subject and methods This paper presents the multifactorial context that TreC_Televisita has faced for its implementation and the strategies adopted for its structural integration into the healthcare system. The analysis focuses on the main issues faced for the integration of the tele visits (e.g. privacy, payments) and how the context of TrentinoSalute4.0 permitted responding quickly to its implementation during the pandemic. It also describes how TreC_Televisita fits into the healthcare continuum from the organisational and technological standpoint, the end-user perspective and the barriers that could hamper the solution scalability. Results TreC_Televisita has demonstrated to be a technological solution that can be contextualised for different clinical domains beyond SARS-CoV-2. Moreover, it has shown its potential to scale up the solution beyond the COVID-19 emergency to the whole healthcare provisioning system in the long term. Conclusion Being a positive experience in the first months of its implementation, the long-term goal is to transform TreC_Televisita into a structural pillar of the Trentino healthcare system, setting the bases for a sustainable, win–win situation for all the stakeholders involved in healthcare service provisioning