Diffusion induced anisotropic cancer invasion: A novel experimental method based on tumor spheroids

Tumour invasion is strongly influenced by microenvironment and, among other parameters, chemical stimuli play an important role. An innovative methodology for the quantitative investigation of chemotaxis in vitro by live imaging of morphology of cell spheroids, in 3D collagen gel, is presented here. The assay was performed by using a chemotactic chamber to impose a controlled gradients of nutrients (glucose) on spheroids, mimicking the chemotactic stimuli naturally occurring in the proximity of blood vessels. Different tumoral cell lines (PANC-1 and HT-1080) are compared to non-tumoral ones (NIH/3T3). Morphology response is observed by means a Time-lapse workstation equipped with an incubating system and quantified by image analysis techniques. Description of invasion phenomena was based on an engineering approach, based on transport phenomena concepts. As expected, NIH/3T3 spheroids are characterized by a limited tendency of cells to invade the surrounding tissue, unlike PANC-1 and HT-1080 that show relatively stronger response to gradients.Comment: 14 pages, 9 figure

Compressional stress stiffening & softening of soft hydrogels - how to avoid artefacts in their rheological characterisation

Hydrogels have been successfully employed as analogues of the extracellular matrix to study biological processes such as cells' migration, growth, adhesion and differentiation. These are governed by many factors, including the mechanical properties of hydrogels; yet, a one-to-one correlation between the viscoelastic properties of gels and cell fate is still missing from literature. In this work we provide experimental evidence supporting a possible explanation for the persistence of this knowledge gap. In particular, we have employed common tissues' surrogates such as polyacrylamide and agarose gels to elucidate a potential pitfall occurring when performing rheological characterisations of soft-materials. The issue is related to (i) the normal force applied to the samples \textit{prior} to performing the rheological measurements, which may easily drive the outcomes of the investigation outside the materials' linear viscoelastic regime, especially when tests are performed with (ii) geometrical tools having unbefitting dimensions (i.e., too small). We corroborate that biomimetic hydrogels can show either compressional stress softening or stiffening, and we provide a simple solution to quench these undesired phenomena, which would likely lead to potentially misleading conclusions if they were not mitigated by a good practice in performing rheological measurements, as elucidated in this work

i-Rheo-optical assay: Measuring the viscoelastic properties of multicellular spheroids

This study introduces a novel mechanobiology assay, named “i-Rheo-optical assay”, that integrates rheology with optical microscopy for analysing the viscoelastic properties of multicellular spheroids. These spheroids serve as three-dimensional models resembling tissue structures. The innovative technique enables real-time observation and quantification of morphological responses to applied stress using a cost-effective microscope coverslip for constant compression force application. By bridging a knowledge gap in biophysical research, which has predominantly focused on the elastic properties while only minimally exploring the viscoelastic nature in multicellular systems, the i-Rheo-optical assay emerges as an effective tool. It facilitates the measurement of broadband viscoelastic compressional moduli in spheroids, here derived from cancer (PANC-1) and non-tumoral (NIH/3T3) cell lines during compression tests. This approach plays a crucial role in elucidating the mechanical properties of spheroids and holds potential for identifying biomarkers to discriminate between healthy tissues and their pathological counterparts. Offering comprehensive insights into the biomechanical behaviour of biological systems, i-Rheo-optical assay marks a significant advancement in tissue engineering, cancer research, and therapeutic development

Sensible heat thermal energy storage performance of mono and blended nanofluids in a free convective-radiation inclined system

The photothermal conversion performance (PCP) of a nanofluid-based solar energy system is investigated numerically and experimentally. The impacts of particle size, volume concentration, nanoparticle type, base fluid type and collector inclination angle on the PCP are investigated. It is observed that using nanoparticles improves the ability to absorb solar energy. Temperature gain is 2.2, 3.2, 3.8, 4.2, and 9 times better than pure water for water-based Al, Al2O3, Au, Cu, and Graphite mono nanofluids, respectively. Interestingly, blended nanofluids containing the same nanoparticles significantly argument the optical properties, with useful heat enhancement ranging from 62.8 (mono) to 194 kJ/kg (hybrid). However, the collector's inclination angle, which ranges from 0 to 60°, has a negative impact on the PCP by reducing the solar radiation absorption of the nanofluids due to a decrease in the radiation penetrating the collector. Furthermore, as nanoparticle size increases, so does the thermal performance of the nanofluid. An experimental investigation is carried out for pure water and nanofluid at various wind speeds and solar irradiation levels ranging from 1 to 4 m/s and 200–1000 W/m2, respectively, to validate the numerical results

Alveolar bone changes after rapid maxillary expansion with tooth-born appliances: a systematic review

Background: During rapid maxillary expansion (RME), heavy forces are transmitted to the maxilla by the anchored teeth causing buccal inclination and buccal bone loss of posterior teeth. Objective: To systematically review the literature in order to investigate whether RME causes periodontal sequelae, assessed by cone-beam computed tomography (CBCT). Search methods: Fifteen electronic databases and reference lists of studies were searched up to March 2017. Selection criteria: To be included in the systematic review, articles must be human studies on growing subjects, with transversal maxillary deficiency treated with RME and with assessment of buccal bone loss by CBCT images. Only randomized and non-randomized trials were included. Data collection and analysis: Two authors independently performed study selection, data extraction, and risk of bias assessment. Study characteristics (study design, sample size, age, sex, skeletal maturity, type of appliance, daily activation, evaluated linear measurements, observation period, CBCT settings), and study outcomes (loss of buccal bone thickness and marginal bone) were reported according to the PRISMA statement. Results: On the basis of the applied inclusion criteria, only six articles, three randomized clinical trials and three controlled clinical trials were included. An individual analysis of the selected articles was undertaken. The risks of bias of the six trials were scored as medium to low. Limitations: The results of the present systematic review are based on a limited number of studies and only one study included a control group. Conclusions and implications: In all considered studies, significant loss of buccal bone thickness and marginal bone level were observed in anchored teeth, following RME. Further prospective studies correlating the radiological data of bone loss to the periodontal soft tissues reaction after RME are required. A preliminary evaluation of the patient-related risk factors for RR may be advisable when considering to administering RME

Designing Advanced Drug Delivery Systems: Core-Shell Alginate Particles through Electro-Fluid Dynamic Atomization

Innovations in drug delivery systems are crucial for enhancing therapeutic efficiency. Our research presents a novel approach based on using electro-fluid dynamic atomization (EFDA) to fabricate core-shell monophasic particles (CSMp) from sodium alginate blends of varying molecular weights. This study explores the morphological characteristics of these particles in relation to material properties and process conditions, highlighting their potential in drug delivery applications. A key aspect of our work is the development of a mathematical model that simulates the release kinetics of small molecules, specifically sodium diclofenac. By assessing the diffusion properties of different molecules and gel formulations through transport and rheological models, we have created a predictive tool for evaluating the efficiency of these particles in drug delivery. Our findings underscore two critical, independent parameters for optimizing drug release: the external shell thickness and the diffusivity ratios within the dual layers. This allows for precise control over the timing and intensity of the release profile. This study advances our understanding of EFDA in the fabrication of CSMp and offers promising avenues for enhancing drug delivery systems by tailoring release profiles through particle characteristic manipulation

Hybrid Cellular Automata Modeling Reveals the Effects of Glucose Gradients on Tumour Spheroid Growth

Purpose: In recent years, mathematical models have become instrumental in cancer research, offering insights into tumor growth dynamics, and guiding the development of pharmacological strategies. These models, encompassing diverse biological and physical processes, are increasingly used in clinical settings, showing remarkable predictive precision for individual patient outcomes and therapeutic responses. Methods: Motivated by these advancements, our study introduces an innovative in silico model for simulating tumor growth and invasiveness. The automated hybrid cell emulates critical tumor cell characteristics, including rapid proliferation, heightened motility, reduced cell adhesion, and increased responsiveness to chemotactic signals. This model explores the potential evolution of 3D tumor spheroids by manipulating biological parameters and microenvironment factors, focusing on nutrient availability. Results: Our comprehensive global and local sensitivity analysis reveals that tumor growth primarily depends on cell duplication speed and cell-to-cell adhesion, rather than external chemical gradients. Conversely, tumor invasiveness is predominantly driven by chemotaxis. These insights illuminate tumor development mechanisms, providing vital guidance for effective strategies against tumor progression. Our proposed model is a valuable tool for advancing cancer biology research and exploring potential therapeutic interventions

ANNURCA APPLE POLYPHENOL EXTRACT DECREASES THE IN VITRO MIGRATORY AND INVASIVE POTENTIAL OF TRIPLE NEGATIVE BREAST CANCER CELLS

Breast cancer is the most common invasive cancer among women in the world. Over the past two decades, although the treatment for breast cancer has substantially improved, its metastasis is still a major cause of mortality and poor prognosis. Cancer cell migration is essential for the early steps of metastasis, during which cancer cells move through the primary tumor and reach the blood vessels. Thus, suppression of cancer cell migration and invasion represents an important therapeutic target and the development of new therapeutic agents to prevent cancer cell migration and invasion is highly desirable. Triple-negative breast cancer (TNBC) is a highly invasive subgroup of breast carcinomas that lacks expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2. Proven active targeted therapy is presently unavailable for patients with TNBC and currently, chemotherapy represents the standard of care for patients with early advanced TNBC. Dietary polyphenols are among the naturally-occurring substances that have shown promising anti-cancer properties and low toxicity in comparison to standard chemotherapeutic agents. Previous works from our group led us to select polyphenol extract from Annurca apple (APE) as a potential candidate for drug development against breast cancer. We have indeed reported that APE displays a potent prooxidant cytotoxic effect in MCF-7 human breast carcinoma cells and, more recently, we demonstrated that APE is able to selectively kill MDA-MB-231 TNBC cells through ROS generation, sustained JNK activation and cell growth and survival inhibition while exerting a protective antioxidant effect in normal cells. The wound healing assay is widely used to investigate cell migrationin vitro and video-time lapse microscopy allows to monitor in real time the migration process. Several experimental factors, such as uneven cell density among different samples can affect the reproducibility and reliability of this assay. In this study the dose-dependent inhibitory effect exerted by APE on migration of MDAMB- 231 TNBC cells has been highlighted by means of a novel methodological approach to quantify wound healing process that is based on the analysis of the wound closure as a diffusion reaction process, and the potential underlying molecular mechanisms have been explored