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The COVID-19 pandemic has amplified mental health problems and highlighted inequitable gaps in care worldwide. In response there has been an explosion of digital interventions such as smartphone applications ("apps") to extend care. The objective of this trial is to evaluate the effectiveness and cost-effectiveness of a digital depression intervention (VMood), delivered via a smartphone app. VMood is adapted from an in-person intervention that was delivered by non-specialist providers and shown to be effective in the Vietnamese context in our previous trial (2016-2019). A stepped-wedge, randomized controlled trial will be conducted across eight provinces in Vietnam. Adults aged 18 years and over will be recruited through community-based primary care centres and screened for depression using the embedded Patient Health Questionnaire-9 (primary outcome measure). Participants scoring 10-19, indicating depression caseness, will be randomly allocated to the intervention or control group until the target of 336 is reached. Secondary outcome measures will examine the effect of the intervention on commonly co-occuring anxiety, quality of life and work productivity, along with use of alcohol and tobacco products. Assessments will be administered through an online survey platform (REDCap) at baseline, and at every 3 months until 3 months post-intervention. Intervention-group participants will receive VMood for a 3-month period, with online support provided by social workers. Control-group participants will receive a limited version of the app until they cross into the intervention group. Generalized Linear Mixed-effect Models for clustered measures will be used for all outcomes data. We will conduct a cost-effectiveness analysis alongside the trial to capture VMood's costs and benefits. This trial will provide evidence on the effectiveness and cost-effectiveness of a digital mental health intervention adapted from an in-person intervention. This trial will also contribute important information to the growing and promising field of digital mental health. Trail regulation. Registered at ClinicalTrials.gov, identifier [NCT05783531]., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

There is a growing interest in tissue engineering, in which biomaterials play a pivotal role in promoting bone regeneration. Furthermore, smart functionalization can provide biomaterials with the additional role of preventing orthopedic infections. Due to the growing microbial resistance to antimicrobials used to treat those infections, metal ions, such as silver, thanks to their known wide range of bactericidal properties, are believed to be promising additives in developing antibacterial biomaterials. In this work, novel poly(ε-caprolactone) (PCL)-based 3D scaffolds have been designed and developed, where the polymer matrix was modified with both silver (Ag), to supply antibacterial behavior, and calcium phosphates (biphasic calcium phosphate, BCP) particles to impart bioactive/bioresorbable properties. The microstructural analysis showed that constructs were characterized by square-shaped macropores, in line with the morphology and size of the templating salts used as pore formers. Degradation tests demonstrated the important role of calcium phosphates in improving PCL hydrophilicity, leading to a higher degradation degree for BCP/PCL composites compared to the neat polymer after 18 days of soaking. The appearance of an inhibition halo around the silver-functionalized PCL scaffolds for assayed microorganisms and a significant ( p < 0.05) decrease in both adherent and planktonic bacteria demonstrate the Ag+ release from the 3D constructs. Furthermore, the PCL scaffolds enriched with the lowest silver percentages did not hamper the viability and proliferation of Saos-2 cells. A synergic combination of antimicrobial, osteoproliferative and biodegradable features provided to 3D scaffolds the required potential for bone tissue engineering, beside anti-microbial properties for reduction in prosthetic joints infections.

In bone tissue engineering research, bioreactors designed for replicating the main features of the complex native environment represent powerful investigation tools. Moreover, when equipped with automation, their use allows reducing user intervention and dependence, increasing reproducibility and the overall quality of the culture process. In this study, an automated uni-/bi-directional perfusion bioreactor combinable with pulsed electromagnetic field (PEMF) stimulation for culturing 3D bone tissue models is proposed. A user-friendly control unit automates the perfusion, minimizing the user dependency. Computational fluid dynamics simulations supported the culture chamber design and allowed the estimation of the shear stress values within the construct. Electromagnetic field simulations demonstrated that, in case of combination with a PEMF stimulator, the construct can be exposed to uniform magnetic fields. Preliminary biological tests on 3D bone tissue models showed that perfusion promotes the release of the early differentiation marker alkaline phosphatase. The histological analysis confirmed that perfusion favors cells to deposit more extracellular matrix (ECM) with respect to the static culture and revealed that bi-directional perfusion better promotes ECM deposition across the construct with respect to uni-directional perfusion. Lastly, the Real-time PCR results of 3D bone tissue models cultured under bi-directional perfusion without and with PEMF stimulation revealed that the only perfusion induced a ~ 40-fold up-regulation of the expression of the osteogenic gene collagen type I with respect to the static control, while a ~ 80-fold up-regulation was measured when perfusion was combined with PEMF stimulation, indicating a positive synergic pro-osteogenic effect of combined physical stimulations., (© 2022. The Author(s).)

Bioactive glasses are often designed as porous implantable templates in which newly-formed bone can grow in three dimensions (3D). This research work aims to investigate the bone regenerative capability of silicate bioactive glass scaffolds produced by robocasting in comparison with powder and granule-like materials (oxide system: 47.5SiO 2 -10Na 2 O-10K 2 O-10MgO-20CaO-2.5P 2 O 5 , mol.%). Morphological and compositional analyses performed by scanning electron microscopy (SEM), combined with energy dispersive spectroscopy (EDS) after the bioactivity studies in a simulated body fluid (SBF) confirmed the apatite-forming ability of the scaffolds, which is key to allowing bone-bonding in vivo. The scaffolds exhibited a clear osteogenic effect upon implantation in rabbit femur and underwent gradual resorption followed by ossification. Full resorption in favor of new bone growth was achieved within 6 months. Osseous defect healing was accompanied by the formation of mature bone with abundant osteocytes and bone marrow cells. These in vivo results support the scaffold's suitability for application in bone tissue engineering and show promise for potential translation to clinical assessment.

In vitro and in vivo studies are fundamental steps in the characterization of new implantable materials to preliminarily assess their biological response. The present study reports the in vitro and in vivo characterizations of a novel experimental silicate bioactive glass (BG) (47.5B, 47.5SiO 2 -10Na 2 O-10K 2 O-10MgO-20CaO-2.5P 2 O 5 mol.%). Cytocompatibility tests were performed using human mature osteoblasts (U2OS), human mesenchymal stem cells (hMSCs) and human endothelial cells (EA.hy926). The release of the early osteogenic alkaline phosphatase (ALP) marker suggested strong pro-osteogenic properties, as the amount was comparable between hMSCs cultivated onto BG surface and cells cultivated onto polystyrene control. Similarly, real-time PCR revealed that the osteogenic collagen I gene was overexpressed in cells cultivated onto BG surface without biochemical induction. Acute toxicity tests for the determination of the median lethal dose (LD 50 ) allowed classifying the analyzed material as a slightly toxic substance with LD 50 = 4522 ± 248 mg/kg. A statistically significant difference in bone formation was observed in vivo through comparing the control (untreated) group and the experimental one, proving a clear osteogenic effect induced by the implantation at the defect site. Complete resorption of 47.5B powder was observed after only 3 months in favor of newly formed tissue, thus confirming the high osteostimulatory potential of 47.5B glass.

Since 2006, the foam replica method has been commonly recognized as a valuable technology for the production of highly porous bioactive glass scaffolds showing three-dimensional, open-cell structures closely mimicking that of natural trabecular bone. Despite this, there are important drawbacks making the usage of foam-replicated glass scaffolds a difficult achievement in clinical practice; among these, certainly the high operator-dependency of the overall manufacturing process is one of the most crucial, limiting the scalability to industrial production and, thus, the spread of foam-replicated synthetic bone substitutes for effective use in routine management of bone defect. The present review opens a window on the versatile world of the foam replica technique, focusing the dissertation on scaffold properties analyzed in relation to various processing parameters, in order to better understand which are the real issues behind the bottleneck that still puts this technology on the Olympus of the most used techniques in laboratory practice, without moving, unfortunately, to a more concrete application. Specifically, scaffold morphology, mechanical and mass transport properties will be reviewed in detail, considering the various templates proposed till now by several research groups all over the world. In the end, a comprehensive overview of in vivo studies on bioactive glass foams will be provided, in order to put an emphasis on scaffold performances in a complex three-dimensional environment.