Bioprinting stem cells: building physiological tissues one cell at a time.

Bioprinting aims to direct the spatial arrangement in three dimensions of cells, biomaterials, and growth factors. The biofabrication of clinically relevant constructs for the repair or modeling of either diseased or damaged tissues is rapidly advancing, resulting in the ability to three-dimensional (3D) print biomimetic platforms which imitate a large number of tissues in the human body. Primary tissue-specific cells are typically isolated from patients and used for the fabrication of 3D models for drug screening or tissue repair purposes. However, the lack of resilience of these platforms, due to the difficulties in harnessing, processing, and implanting patient-specific cells can limit regeneration ability. The printing of stem cells obviates these hurdles, producing functional in vitro models or implantable constructs. Advancements in biomaterial science are helping the development of inks suitable for the encapsulation and the printing of stem cells, promoting their functional growth and differentiation. This review specifically aims to investigate the most recent studies exploring innovative and functional approaches for the printing of 3D constructs to model disease or repair damaged tissues. Key concepts in tissue physiology are highlighted, reporting stem cell applications in biofabrication. Bioprinting technologies and biomaterial inks are listed and analyzed, including recent advancements in biomaterial design for bioprinting applications, commenting on the influence of biomaterial inks on the encapsulated stem cells. Ultimately, most recent successful efforts and clinical potentials for the manufacturing of functional physiological tissue substitutes are reported here, with a major focus on specific tissues, such as vasculature, heart, lung and airways, liver, bone and muscle.

Pt(II) versus Pt(IV) in Carbene Glycoconjugate Antitumor Agents: Minimal Structural Variations and Great Performance Changes.

Octahedral Pt(IV) complexes (2Pt-R) containing a glycoconjugate carbene ligand were prepared and fully characterized. These complexes are structural analogues to the trigonal bipyramidal Pt(II) species (1Pt-R) recently described. Thus, an unprecedented direct comparison between the biological properties of Pt compounds with different oxidation states and almost indistinguishable structural features was performed. The stability profile of the novel Pt(IV) compounds in reference solvents was determined and compared to that of the analogous Pt(II) complexes. The uptake and antiproliferative activities of 2Pt-R and 1Pt-R were evaluated on the same panel of cell lines. DNA and protein binding properties were assessed using human serum albumin, the model protein hen egg white lysozyme, and double stranded DNA model systems by a variety of experimental techniques, including UV-vis absorption spectroscopy, fluorescence, circular dichroism, and electrospray ionization mass spectrometry. Although the compounds present similar structures, their in-solution stability, cellular uptake, and DNA binding properties are diverse. These differences may represent the basis of their different cytotoxicity and biological activity.

Reversible Cavitation-Induced Junctional Opening in an Artificial Endothelial Layer.

Targeting pharmaceuticals through the endothelial barrier is crucial for drug delivery. In this context, cavitation-assisted permeation shows promise for effective and reversible opening of intercellular junctions. A vessel-on-a-chip is exploited to investigate and quantify the effect of ultrasound-excited microbubbles-stable cavitation-on endothelial integrity. In the vessel-on-a-chip, the endothelial cells form a complete lumen under physiological shear stress, resulting in intercellular junctions that exhibit barrier functionality. Immunofluorescence microscopy is exploited to monitor vascular integrity following vascular endothelial cadherin staining. It is shown that microbubbles amplify the ultrasound effect, leading to the formation of interendothelial gaps that cause barrier permeabilization. The total gap area significantly increases with pressure amplitude compared to the control. Gap opening is fully reversible with gap area distribution returning to the control levels 45 min after insonication. The proposed integrated platform allows for precise and repeatable in vitro measurements of cavitation-enhanced endothelium permeability and shows potential for validating irradiation protocols for in vivo applications.

The detailed acoustic signature of a micro-confined cavitation bubble.

Numerous scenarios exist for a cavitation bubble growing in a liquid. We focus here on cavitation phenomena within water under static tension in a confined environment. Drawing inspiration from the natural materials in plants, we design a novel experimental setup where a micrometric volume of water is confined by a hydrogel-based material. We show that, submerging the sample in a hypertonic solution, the water within the cavity is placed under tension and the acoustic emission produced by the resulting bubble nucleation is precisely detected. This new experimental procedure is able to strongly reduce the acoustic reflections occurring at the hydrogel/air interface with more classical techniques. We also propose a mathematical model to characterise the pressure wave emitted in order to correctly take into account the dissipation effect induced by the visco-elastic behaviour of the confining hydrogel. Both bubble resonant frequency and damping are captured by the model and quantitatively match the values found in the experiments.

A scoping review on innovative methods for personality observation.

Background: Personality's investigation has always been characterized as a central area of research for psychology, such that it was established in the 1920s as an autonomous scientific-disciplinary field. Identifying and observing the people's typical ways of "being in the world" has made possible to define the predictability of a pattern of behavioral responses related both to the possession of distinct characteristics of the agent subject and to specific environmental situations. In the actual scientific landscape, there is a strand of research that makes a description of personality through methodologies and indicators not usually used by psychology, but scientifically validated through standardized procedures. Such studies seem to be significantly increasing and reflect the emerging need to have to consider the human being in his or her complexity, whose existential and personal dimensions can no longer be traced to classification systems that are divorced from the epochal reference. Objective: In this review, attention is focused on highlighting publications in the literature that have included the use of unconventional methods in the study of nonpathological personality, based on the Big Five theoretical reference model. To better understand human nature, an alternative based on evolutionary and interpersonal theory is presented. Design: Online databases were used to identify papers published 2011-2022, from which we selected 18 publications from different resources, selected according to criteria established in advance and described in the text. A flow chart and a summary table of the articles consulted have been created. Results: The selected studies were grouped according to the particular method of investigation or description of personality used. Four broad thematic categories were identified: bodily and behavioral element; semantic analysis of the self-descriptions provided; integrated-type theoretical background; and use of machine learning methods. All articles refer to trait theory as the prevailing epistemological background. Conclusion: This review is presented as an initial attempt to survey the production in the literature with respect to the topic and its main purpose was to highlight how the use of observational models based on aspects previously considered as scientifically uninformative (body, linguistic expression, environment) with respect to personality analysis proves to be a valuable resource for drawing up more complete personality profiles that are able to capture more of the complexity of the person. What has emerged is a rapidly expanding field of study.

Modelling skeletal pain harnessing tissue engineering.

Bone pain typically occurs immediately following skeletal damage with mechanical distortion or rupture of nociceptive fibres. The pain mechanism is also associated with chronic pain conditions where the healing process is impaired. Any load impacting on the area of the fractured bone will stimulate the nociceptive response, necessitating rapid clinical intervention to relieve pain associated with the bone damage and appropriate mitigation of any processes involved with the loss of bone mass, muscle, and mobility and to prevent death. The following review has examined the mechanisms of pain associated with trauma or cancer-related skeletal damage focusing on new approaches for the development of innovative therapeutic interventions. In particular, the review highlights tissue engineering approaches that offer considerable promise in the application of functional biomimetic fabrication of bone and nerve tissues. The strategic combination of bone and nerve tissue engineered models provides significant potential to develop a new class of in vitro platforms, capable of replacing in vivo models and testing the safety and efficacy of novel drug treatments aimed at the resolution of bone-associated pain. To date, the field of bone pain research has centred on animal models, with a paucity of data correlating to the human physiological response. This review explores the evident gap in pain drug development research and suggests a step change in approach to harness tissue engineering technologies to recapitulate the complex pathophysiological environment of the damaged bone tissue enabling evaluation of the associated pain-mimicking mechanism with significant therapeutic potential therein for improved patient quality of life. Graphical abstract: Rationale underlying novel drug testing platform development. Pain detected by the central nervous system and following bone fracture cannot be treated or exclusively alleviated using standardised methods. The pain mechanism and specificity/efficacy of pain reduction drugs remain poorly understood. In vivo and ex vivo models are not yet able to recapitulate the various pain events associated with skeletal damage. In vitro models are currently limited by their inability to fully mimic the complex physiological mechanisms at play between nervous and skeletal tissue and any disruption in pathological states. Robust innovative tissue engineering models are needed to better understand pain events and to investigate therapeutic regimes.

A Microfluidic Platform for Cavitation-Enhanced Drug Delivery.

An endothelial-lined blood vessel model is obtained in a PDMS (Polydimethylsiloxane) microfluidic system, where vascular endothelial cells are grown under physiological shear stress, allowing -like maturation. This experimental model is employed for enhanced drug delivery studies, aimed at characterising the increase in endothelial permeability upon microbubble-enhanced ultrasound-induced (USMB) cavitation. We developed a multi-step protocol to couple the optical and the acoustic set-ups, thanks to a 3D-printed insonation chamber, provided with direct optical access and a support for the US transducer. Cavitation-induced interendothelial gap opening is then analysed using a customised code that quantifies gap area and the relative statistics. We show that exposure to US in presence of microbubbles significantly increases endothelial permeability and that tissue integrity completely recovers within 45 min upon insonation. This protocol, along with the versatility of the microfluidic platform, allows to quantitatively characterise cavitation-induced events for its potential employment in clinics.

What Does Personality Mean in the Context of Mental Health? A Topic Modeling Approach Based on Abstracts Published in Pubmed Over the Last 5 Years.

Personality disorders (PDs) are one of the major problems for the organization of public health systems. Deepening the link between personality traits and psychopathological drifts, it seems increasingly essential for the often dramatic repercussions that PDs have on social contexts. Some of these disorders, such as borderline PD, antisocial PD, in their most tragic expression, are the basis of problems related to crime, sexual violence, abuse, and mistreatment of minors. Many authors propose a dimensional classification of personality pathology, which has received empirical support from numerous studies over the last 20 years based on more robust theoretical principles than those applied to current nosography. The present study investigates the nature of the research carried out in the last years on the personality in the clinical field exploring the contents of current research on personality relapses, evaluating, on the one hand, the emerging areas of greatest interest and others, those that they stopped generating sufficient motivations in scholars. This study evaluates text patterns regarding how the terms "personality" and "mental health" are used in titles and abstracts published in PubMed in the last 5 years. We use a topic analysis: Latent Dirichlet Allocation that expresses every report as a probabilistic distribution of latent topics that are represented as a probabilistic distribution of words. A total of 7,572 abstracts (from 2012 to 2017) were retrieved from PubMed for the query on "mental health" and "personality." The study found 30 topics organized in eight hierarchical clusters that describe the type of current research carried out on personality and its clinical relapse. The hierarchical clusters latent themes were the following: social dimensions, clinical aspects, biological issues, clinical history of PD, internalization and externalization symptoms, impulsive behaviors, comorbidities, criminal behaviors. The results indicate that the concept of personality is associated with a wide range of conditions. The study of personality and mental health still proceeds, mainly, according to a practical-clinical approach; too little moves, however, according to an innovative research approach, but the work shows the common commitment of scholars to a new way of dealing with the study of personality.

Keep moving without hurting: The interaction between physical activity and pain in determining cognitive function at the population level.

BACKGROUND: A number of studies have evaluated the association between cognitive function, pain, and physical activity. To our knowledge, however, no previous studies have evaluated these factors at the population level. AIMS: To evaluate the association between cognitive function in the elderly with pain, physical activity, and the interaction between these variables. Estimates are generated for the United States population. METHODS: We made use of the NHANES database (1999-2002), making adjustments so that our results represent the United States population. Cognitive function was evaluated through the Digit Symbol Substitution Test. Our main predictors were (1) pain, defined as soreness of either the shoulder, neck, lower back and joint, or a severe headache (2) physical activity, measured as the performance while performing tasks at home, physical activity intensity, walking, bicycle riding, and muscle strengthening. RESULTS: Most individual pain sites were not significantly associated with cognitive function, while all physical activity factors were associated with an increase in cognitive function. When evaluating the sample subset of those with cognitive scores lower than the median, a combination of more pain and less physical activity was consistently associated with lower cognitive scores when compared to those performing more physical activity with or without pain. When evaluating individuals with cognitive scores above the median, a similar association pattern was perceived. CONCLUSIONS: Among the population of individuals above the age of 60, higher cognitive levels are associated with more physical activity and less with pain, although both factors might impact cognition. Public policy resources should be commensurate with these findings when targeting cognitive function among the aging population.