Gingipains protect Porphyromonas gingivalis from macrophage-mediated phagocytic clearance.

Porphyromonas gingivalis (Pg) is a keystone pathogen in periodontitis, a highly prevalent disease manifested by chronic inflammation of the periodontium, alveolar bone resorption and tooth loss. During periodontitis pathobionts such as Pg can enter the bloodstream and growing evidence correlates periodontitis with increased risk of cardiovascular and neurodegenerative diseases. However, the mechanism by which immune cells respond to Pg challenge in vivo remains elusive.

An advanced in silico model of the oral mucosa reveals the impact of extracellular spaces on chemical permeation.

Accurately predicting the permeation of chemicals through human epithelial tissues is crucial for pharmaceutical therapeutic design and toxicology. Current mathematical models of multi-layered stratified squamous epithelium such as those in the oral cavity use simplistic 'bricks and mortar' geometries that do not fully account for the complex cellular architecture that may affect chemical permeation in these tissues. Here we aimed to develop a new, advanced mechanistic mathematical model of the human epithelium that more accurately represents chemical tissue permeation.

Controlled dual drug release from adhesive electrospun patches for prevention and treatment of alveolar osteitis.

Approximately one in five individuals experience alveolar osteitis (AO) following wisdom tooth extraction. AO is characterised by loss of the blood clot from the tooth extraction socket leading to infection and pain, resulting in repeated hospital visits that impose a substantial burden on healthcare systems. Current treatments are sub-optimal; to address this we developed a novel drug-loaded mucoadhesive patch composed of dual electrospun polyvinyl pyrrolidone/Eudragit RS100 (PVP/RS100) and poly(N-isopropylacrylamide) (PNIPAM) fibres protected by a poly(ε-caprolactone) (PCL) backing layer.

Restriction of arginine induces antibiotic tolerance in Staphylococcus aureus.

Staphylococcus aureus is responsible for a substantial number of invasive infections globally each year. These infections are problematic because they are frequently recalcitrant to antibiotic treatment. Antibiotic tolerance, the ability of bacteria to persist despite normally lethal doses of antibiotics, contributes to antibiotic treatment failure in S.

Understanding and supporting young people exposed to online misinformation about eczema.

The traditional patient-clinician relationship is changing as young people and their families often now turn to the internet and social media for health information, treatment advice and support. Much of that content, however, is unregulated, unverified and inaccurate, which leads to the dissemination of health misinformation. Healthcare professionals working with young people with eczema and their families need to understand why young people turn to social media for health information, identify trends in online misinformation about eczema, and provide alternative, trustworthy sources of information.

Limiting extracellular matrix expansion in diet-induced obese mice reduces cardiac insulin resistance and prevents myocardial remodelling.

Objective: Obesity increases deposition of extracellular matrix (ECM) components of cardiac tissue. Since obesity aggregates with insulin resistance and heart disease, it is imperative to determine whether the increased ECM deposition contributes to this disease cluster. The hypotheses tested in this study were that in cardiac tissue of obese mice i) increased deposition of ECM components (collagens and hyaluronan) contributes to cardiac insulin resistance and that a reduction in these components improves cardiac insulin action and ii) reducing excess collagens and hyaluronan mitigates obesity-associated cardiac dysfunction.

Bioactive Protein and Peptide Release from a Mucoadhesive Electrospun Membrane.

Protein-based biologics constitute a rapidly expanding category of therapeutic agents with high target specificity. Their clinical use has dramatically increased in recent years, but administration is largely via injection. Drug delivery across the oral mucosa is a promising alternative to injections, in order to avoid the gastrointestinal tract and first-pass metabolism.

Uncovering the relationship between macrophages and polypropylene surgical mesh.

Currently, in vitro testing examines the cytotoxicity of biomaterials but fails to consider how materials respond to mechanical forces and the immune response to them; both are crucial for successful long-term implantation. A notable example of this failure is polypropylene mid-urethral mesh used in the treatment of stress urinary incontinence (SUI). The mesh was largely successful in abdominal hernia repair but produced significant complications when repurposed to treat SUI.

laser speckle contrast imaging of microvascular blood perfusion using a chip-on-tip camera.

Laser speckle contrast imaging (LSCI) is an important non-invasive capability for real-time imaging for tissue-perfusion assessment. Yet, the size and weight of current clinical standard LSCI instrumentation restricts usage to mainly peripheral skin perfusion. Miniaturization of LSCI could enable hand-held instrumentation to image internal organ/tissue to produce accurate speckle-perfusion maps.

Protocol for a placenta-on-a-chip model using trophoblasts differentiated from human induced pluripotent stem cells.

Organ-on-a-chip technology incorporating stem cell techniques represents a promising strategy to improve modeling of human organs. Here, we present a protocol for generating a standardized 3D placenta-on-a-chip model using trophoblast derived from human induced pluripotent stem cells (hiPSCs). We describe steps for seeding hiPSCs into multi-chip OrganoPlate devices and on-chip differentiation into trophoblasts against an extracellular matrix under perfused conditions.

Electrospinning polymersomes into bead-on-string polyethylene oxide fibres for the delivery of biopharmaceuticals to mucosal epithelia.

Fibrous mucoadhesive polymer membranes prepared using electrospinning demonstrate many advantages for mucosal drug delivery compared to other formulations. Previous electrospun membrane formulations have been developed mainly for the delivery of small molecule drugs. There remains great potential to further develop the technology for the delivery of vesicular vectors that allow administration of advanced therapeutic agents.

Extracellular Matrix Abnormalities Contribute to Cardiac Insulin Resistance and Associated Dysfunction in Diet-induced Obese Mice.

Increased deposition of extracellular matrix (ECM) components such as collagens and hyaluronan contributes to the pathogenesis of obesity-associated insulin resistance in muscle, liver, and adipose tissue. Despite the significance of the heart in cardiovascular and metabolic diseases, maladaptive ECM remodelling in obesity-associated cardiac insulin resistance and cardiac dysfunction has not been studied. Using genetic and pharmacological approaches in mice fed a high fat (HF) diet, we demonstrated a tight association between increased ECM deposition with cardiac insulin resistance.

Angiogenic markers and maternal echocardiographic indices in women with hypertensive disorders of pregnancy.

Objective: The maternal cardiovascular system of women with hypertensive disorders of pregnancy (HDP) can be impaired, with higher rates of left ventricular (LV) remodeling and diastolic dysfunction compared to those with normotensive pregnancy. The primary objective of this prospective study was to correlate cardiac indices obtained by transthoracic echocardiography (TTE) and circulating angiogenic markers, such as soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF).

Methods: In this study, 95 women with a pregnancy complicated by HDP and a group of 25 with an uncomplicated pregnancy at term underwent TTE and blood tests to measure sFlt-1 and PlGF during the peripartum period (before delivery or within a week of giving birth).

Healthy and diseased placental barrier on-a-chip models suitable for standardized studies.

Pathologies associated with uteroplacental hypoxia, such as preeclampsia are among the leading causes of maternal and perinatal morbidity in the world. Its fundamental mechanisms are yet poorly understood due to a lack of good experimental models. Here we report an in vitro model of the placental barrier, based on co-culture of trophoblasts and endothelial cells against a collagen extracellular matrix in a microfluidic platform.

Pan-Genomic Regulation of Gene Expression in Normal and Pathological Human Placentas.

In this study, we attempted to find genetic variants affecting gene expression (eQTL = expression Quantitative Trait Loci) in the human placenta in normal and pathological situations. The analysis of gene expression in placental diseases (Pre-eclampsia and Intra-Uterine Growth Restriction) is hindered by the fact that diseased placental tissue samples are generally taken at earlier gestations compared to control samples. The difference in gestational age is considered a major confounding factor in the transcriptome regulation of the placenta.

A versatile multiplexed assay to quantify intracellular ROS and cell viability in 3D on-a-chip models.

Reactive oxygen species (ROS) have different properties and biological functions. They contribute to cell signaling and, in excessive amounts, to oxidative stress (OS). Although ROS is pivotal in a wide number of physiological systems and pathophysiological processes, direct quantification in vivo is quite challenging and mainly limited to in vitro studies.

Electrospun patch delivery of anti-TNFα F(ab) for the treatment of inflammatory oral mucosal disease.

Chronic ulcerative oral mucosal inflammatory diseases, including oral lichen planus and recurrent aphthous stomatitis, are painful and highly prevalent, yet lack effective clinical management. In recent years, systemic biologic therapies, including monoclonal antibodies that block the activity of cytokines, have been increasingly used to treat a range of immune-mediated inflammatory conditions such as rheumatoid arthritis and psoriasis. The ability to deliver similar therapeutic agents locally to the oral epithelium could radically alter treatment options for oral mucosal inflammatory diseases, where pro-inflammatory cytokines, in particular tumour-necrosis factor-α (TNFα), are major drivers of pathogenesis.

The relationship between meniscal pathologies, cartilage loss, joint replacement and pain in knee osteoarthritis: a systematic review.

Objective: We conducted a systematic review in order to understand the relationship between imaging-visualised meniscus pathologies, hyaline cartilage, joint replacement and pain in knee osteoarthritis (OA).

Design: A search of the Medline, Excerpta Medica database (EMBASE) and Cochrane library databases was performed for original publications reporting association between imaging-detected meniscal pathology (extrusion or tear/damage) and longitudinal and cross-sectional assessments of hyaline articular cartilage loss [assessed on magnetic resonance imaging (MRI)], incident joint replacement and pain (longitudinal and cross-sectional) in knee OA. Each association was qualitatively characterised by a synthesis of data from each analysis, based upon study design and quality scoring (including risk of bias assessment and adequacy of covariate adjustment using Cochrane recommended methodology).

Computational Modelling for Electrical Impedance Spectroscopy-Based Diagnosis of Oral Potential Malignant Disorders (OPMD).

A multiscale modelling approach has been applied to the simulation of the electrical properties of oral tissue, for the purpose of informing an electrical impedance-based method of oral potential malignant disorder (OPMD) diagnosis. Finite element models of individual cell types, with geometry informed by histological analysis of human oral tissue (normal, hyperplastic and dysplastic), were generated and simulated to obtain electrical parameters. These were then used in a histology-informed tissue scale model, including the electrode geometry of the ZedScan tetrapolar impedance-measurement device.

Determinants of Dental Pulp Stem Cell Heterogeneity.

Introduction: The aim of this review is to provide a narrative review on the determinants of dental pulp stem cell (DPSC) heterogeneity that may affect the regenerative properties of these cells.

Methods: PubMed, Scopus, and MEDLINE (Ovid) literature searches were done on human dental pulp stem cell heterogeneity. The focus was on human dental pulp stem cells with a primary focus on DPSC heterogeneity.

Fusobacterium nucleatum mediates endothelial damage and increased permeability following single species and polymicrobial infection.

Background: Numerous lines of evidence link periodontal pathobionts and their virulence factors with endothelial damage. Most research has been conducted using single species infections at the exclusion of other periodontal microorganisms that have been identified in vascular tissue. Here, we assessed endothelial infection with either single or mixed periodontal species infection and examined their effect on endothelial damage and permeability.