Silvia Scaglione | National Research Centre (original) (raw)

Papers by Silvia Scaglione

ABSTRACT A wide range of software has been moving to Cloud platforms, except for 3D applications,... more ABSTRACT A wide range of software has been moving to Cloud platforms, except for 3D applications, which require hardware (access to high-end GPU1) and software (use of libraries for 3D graphics like OpenGL or DirectX) not yet supported. Therefore, we here present an innovative technology, enabling “3D Clouds”, i.e. Clouds able to host 3D applications and provide them “as a service”. Achieving this goal can be very useful in Biomedicine and Life Sciences, where 3D visualization and image analysis play a key role. End users are immediately empowered by taking full advantage of high-end graphics cards, fast I/O performance and large memory nodes hosted in "Public or Private 3D Cloud", rather than waiting for the next upgrade of the graphics workstations. Even if the technology supports a wide range of 3D applications, we here present a case study in molecular modeling field, considering crucial aspects of security and data management.

River Publishers eBooks, Sep 1, 2022

This book chapter presents the main key innovations being devised, implemented and validated in t... more This book chapter presents the main key innovations being devised, implemented and validated in the scope of Anastacia H2020 EU research project, to meet the cybersecurity challenge of protecting dynamically heterogenous IoT scenarios, endowed with SDN/NFV capabilities, which face evolving kind of cyber-attacks. The key innovations encompasses, among others, policy-based security management in IoT networks, trusted and dynamic security orchestration of virtual networks security functions using SDN/NFV technologies, security monitoring and cognitive reaction to countering cyber-treats, behavioural analysis, anomaly detection and automated testing for the detection of known and unknown vulnerabilities in both physical and virtual environments as well as secured and authenticated dynamic seal system as a service.

Alternatives to animal experimentation, 2022

Bioelectromagnetics, 2003

Spontaneous processes in an aqueous solution of body simulated fluid (SBF) were monitored in clos... more Spontaneous processes in an aqueous solution of body simulated fluid (SBF) were monitored in closed vessel for a period of 1 month at 310 K, at atm pressure, and initial pH of 7.2, both with and without exposure to a square pulsed extremely low frequency electromagnetic fields (EM-ELF) of 250 microT, repeated at 75 Hz. The most important findings are that the SBF surface tension (gamma), evaluated under the EM-ELF field, is lower than the corresponding value measured without EM-ELF at any time. Furthermore, the pH of the exposed SBF is always more basic than that of the unexposed solution. As a consequence, when the EM-ELF is applied, calcium phosphate salts do not precipitate from the SBF solution for a period as long as 30 days. Behind all these experimental evidences there is only one mechanism: the vaporisation from the SBF-air interface of the CO(2)(aq) dissolved into the aqueous electrolyte solution. Thermodynamic analysis of these results establish that, at any given time, the difference, Delta, between the measured surface tensions with and without EM-ELF applied, gives the work of the electromagnetic forces to change the extent at which the CO(2)(aq) adsorbs at the liquid-air interface. It has been demonstrated that the work supply per second and per unit of area by the electromagnetic forces, 3.73 x 10(-10) mJ/s cm(2), is very near to the experimental slope in the plot Delta vs. t 1.7 x 10(-10) mJ/s cm(2). This leads to the conclusion that the EM-ELF fields have an interfacial effect on the concentration value of the CO(2) (aq) at the SBF-air interface. Because of that, the EM-ELF field is enhancing the CO(2) vaporisation rate; thus any other steps, which are a consequence of this mechanism, are changing. These results allow explanation of previous experiments concerning the precipitation of calcium carbonate from flowing hydrogen carbonate aqueous solution in the temperature range 353-373 K at a pressure of 0.1 MPa under the effect of static magnetic fields.

Bioengineering

In oncology, the poor success rate of clinical trials is becoming increasingly evident due to the... more In oncology, the poor success rate of clinical trials is becoming increasingly evident due to the weak predictability of preclinical assays, which either do not recapitulate the complexity of human tissues (i.e., in vitro tests) or reveal species-specific outcomes (i.e., animal testing). Therefore, the development of novel approaches is fundamental for better evaluating novel anti-cancer treatments. Here, a multicompartmental organ-on-chip (OOC) platform was adopted to fluidically connect 3D ovarian cancer tissues to hepatic cellular models and resemble the systemic cisplatin administration for contemporarily investigating drug efficacy and hepatotoxic effects in a physiological context. Computational fluid dynamics was performed to impose capillary-like blood flows and predict cisplatin diffusion. After a cisplatin concentration screening using 2D/3D tissue models, cytotoxicity assays were conducted in the multicompartmental OOC and compared with static co-cultures and dynamic sing...

Cancers

In recent years, immunotherapy has emerged as a promising novel therapeutic strategy for cancer t... more In recent years, immunotherapy has emerged as a promising novel therapeutic strategy for cancer treatment. In a relevant percentage of patients, however, clinical benefits are lower than expected, pushing researchers to deeply analyze the immune responses against tumors and find more reliable and efficient tools to predict the individual response to therapy. Novel tissue engineering strategies can be adopted to realize in vitro fully humanized matrix-based models, as a compromise between standard two-dimensional (2D) cell cultures and animal tests, which are costly and hardly usable in personalized medicine. In this review, we describe the main mechanisms allowing cancer cells to escape the immune surveillance, which may play a significant role in the failure of immunotherapies. In particular, we discuss the role of the tumor microenvironment (TME) in the establishment of a milieu that greatly favors cancer malignant progression and impact on the interactions with immune cells. Then...

SLAS Technology, 2022

In vitro diffusive models are an important tool to screen the penetration ability of active ingre... more In vitro diffusive models are an important tool to screen the penetration ability of active ingredients in various formulations. A reliable assessment of skin penetration enhancing properties, mechanism of action of carrier systems, and an estimation of a bioavailability are essential for transdermal delivery. Given the importance of testing the penetration kinetics of different compounds across the skin barrier, several in vitro models have been developedThe aim of this study was to compare the Franz Diffusion Cell (FDC) with a novel fluid-dynamic platform (MIVO) by evaluating penetration ability of caffeine, a widely used reference substance, and LIP1, a testing molecule having the same molecular weight but a different lipophilicity in the two diffusion chamber systems. A 0.7% caffeine or LIP1 formulation in either water or propylene glycol (PG) containing oleic acid (OA) was topically applied on the Strat-M® membrane or pig ear skin, according to the infinite-dose experimental condition (780 ul/cm 2). The profile of the penetration kinetics was determined by quantify the amount of molecule absorbed at different time-points (1, 2, 4, 6, 8 hours), by means of HPLC analysis. Both diffusive systems show a similar trend for caffeine and LIP1 penetration kinetics. The Strat-M® skin model shows a lower barrier function than the pig skin biopsies, whereby the PGOA vehicle exhibits a higher penetration, enhancing the effect for both diffusive chambers and skin surrogates. Most interestingly, MIVO diffusive system better predicts the lipophilic molecules (i.e. LIP1) permeation through highly physiological fluid flows resembled below the skin models.

Frontiers in Bioengineering and Biotechnology

The success of immunotherapeutic approaches strictly depends on the immune cells interaction with... more The success of immunotherapeutic approaches strictly depends on the immune cells interaction with cancer cells. While conventional in vitro cell cultures under-represent the complexity and dynamic crosstalk of the tumor microenvironment, animal models do not allow deciphering the anti-tumor activity of the human immune system. Therefore, the development of reliable and predictive preclinical models has become crucial for the screening of immune-therapeutic approaches. We here present an organ-on-chip organ on chips (OOC)-based approach for recapitulating the immune cell Natural Killer (NK) migration under physiological fluid flow, infiltration within a 3D tumor matrix, and activation against neuroblastoma cancer cells in a humanized, fluid-dynamic environment. Circulating NK cells actively initiate a spontaneous “extravasation” process toward the physically separated tumor niche, retaining their ability to interact with matrix-embedded tumor cells, and to display a cytotoxic effect ...

Three-dimensional (3D) cell cultures represent fundamental tools for the comprehension of cellula... more Three-dimensional (3D) cell cultures represent fundamental tools for the comprehension of cellular phenomena both in normal and pathological conditions. In particular, mechanical stimuli not less than chemical ones have a relevant role on cell fate, cancer onset and malignant progression. Here, we realize mechanically tuned alginate hydrogels for studying the role of substrate elasticity on breast adenocarcinoma cells activity. Hydrogels Elastic Modulus (E) was measured via Atomic Force Microscopy and a remarkable range (20\u20134000 kPa) was obtained. A breast cancer cell line, MCF-7, was seeded within the 3D gels, on standard Petri and alginate-coated dishes (2D controls). Cells showed dramatic morphological differences when cultured in 3D vs. 2D, exhibiting a flat shape morphology in both 2D conditions, while they maintained within gels a circular, clusterorganized conformation similar to the in vivo one. In 3D culture, we observed a strict correlation between cells viability and...

<b>Copyright information:</b>Taken from "A Grid-based solution for management an... more <b>Copyright information:</b>Taken from "A Grid-based solution for management and analysis of microarrays in distributed experiments"http://www.biomedcentral.com/1471-2105/8/S1/S7BMC Bioinformatics 2007;8(Suppl 1):S7-S7.Published online 8 Mar 2007PMCID:PMC1885859.

The International Journal of Artificial Organs, 2010

Purpose The aim of this study was to design, develop and validate a simple, compact bioreactor sy... more Purpose The aim of this study was to design, develop and validate a simple, compact bioreactor system for tissue engineering. The resulting bioreactor was designed to achieve ease-of-use and low costs for automated cell-culturing procedures onto three-dimensional scaffolds under controlled torsion/traction regimes. Methods Highly porous poly-caprolactone-based scaffolds were used as substrates colonized by fibroblast cells (3T3 cell line). Constructs were placed within the cylindrical culture chamber, clumped at the ends and exposed to controlled sequences of torsional stimuli (forward/back-forward sequential cycles of 100° from neutral position at a rate of 600°/min) through a stepper-motor; working settings were defined via PC by an easy user-interface. Cell adhesion, morphology, cytoskeletal fiber orientation and gene expression of extracellular matrix proteins (collagen type I, tenascin C, collagen type III) were evaluated after three days of torsional stimulation in the bioreac...

ACS Applied Materials & Interfaces, 2018

Graphene-derived materials, such as graphene oxide (GO), have been widely explored for biomedical... more Graphene-derived materials, such as graphene oxide (GO), have been widely explored for biomedical and biological applications, including cancer research. Despite some recent works proving that GO inhibits the migration and invasion of different cancer cells, so far most of these in vitro studies have been conducted using GO sheets dispersed in solution or as a planar film. On the contrary, little is known about cellular activities, such as cell viability, adhesion, and spreading, when cancer cells interface with GO functionalized hydrogel-based surfaces, biomechanically and structurally more similar to the tumor environment. Here, we evaluate the interactions of human breast cancer cells (MDA-MB-231) with alginate (Alg)/GO hydrogel-based substrates, and compare them with a cancer cell line from human osteosarcoma (HOS) and healthy murine fibroblasts (3T3). We observed that GO addition selectively inhibits malignant breast cancer cell adhesion efficiency and spreading area, while promotes HOS and 3T3 adhesive processes. Furthermore, we did not observe the same results over Alg substrates with GO nanosheets dispersed in the medium, without embedment into the Alg. This suggests that cancer (MDA-MB-231 and HOS) and healthy (3T3) cell adhesion efficacy does not depend on the cellular tumoral nature and it is driven by the topographical cues provided by the GO-based substrates, whose physical-mechanical characteristics better mimic those of the cell native tissue. We envision that this study can provide a rational for future design and use of graphenebased nanomaterials for cancer research by deepening the knowledge of graphene−cancer cell specific interactions.

Scientific reports, Jan 28, 2018

Purpose of this study was the development of a 3D material to be used as substrate for breast can... more Purpose of this study was the development of a 3D material to be used as substrate for breast cancer cell culture. We developed composite gels constituted by different concentrations of Alginate (A) and Matrigel (M) to obtain a structurally stable-in-time and biologically active substrate. Human aggressive breast cancer cells (i.e. MDA-MB-231) were cultured within the gels. Known the link between cell morphology and malignancy, cells were morphologically characterized and their invasiveness correlated through an innovative bioreactor-based invasion assay. A particular type of gel (i.e. 50% Alginate, 50% Matrigel) emerged thanks to a series of significant results: 1. cells exhibited peculiar cytoskeleton shapes and nuclear fragmentation characteristic of their malignancy; 2. cells expressed the formation of the so-called invadopodia, actin-based protrusion of the plasma membrane through which cells anchor to the extracellular matrix; 3. cells were able to migrate through the gels and...

Carbon, 2017

Abstract The development of novel 3D systems is crucial for engineering artificial tissues since ... more Abstract The development of novel 3D systems is crucial for engineering artificial tissues since the behavior of cells growth on 2D cell culture substrates does not accurately reflect that of the physiological microenvironment. In this regard, desirable 3D composites should offer tunable structural and functional properties to support appropriate cellular growth and biomechanical loads. In this work, we realized 3D alginate hydrogels functionalized with graphene oxide (GO) nanosheets for the creation of cell laden hybrid materials with proper mechanical properties for tissue engineering applications. We monitored the mechanical proprieties of 2 wt% GO/Alg hydrogels up to one month demonstrating a significant improvement of the compressive elastic modulus reaching values of 300 KPa (6 times higher stiffness), which are close to those of articular tissues. This finding has been correlated to increased intermolecular hydrogen bonds over time between GO and Alg, observed through FT-IR analysis. Interestingly, we show that 3D GO/Alg hydrogels trigger cellular activity in vitro, as demonstrated by the statistically significant improvement of the viability of fibroblasts encapsulated in GO/Alg hydrogels and by the absence of cytotoxicity of suspended GO flakes. All these findings indicate that GO/Alg hydrogel is a promising material for articular tissue engineering, where biomechanical requirements are crucial.

Materials Science and Engineering: C, 2016

The really nontrivial goal of tissue engineering is combining all scaffold micro-architectural fe... more The really nontrivial goal of tissue engineering is combining all scaffold micro-architectural features, affecting both fluid-dynamical and mechanical performance, to obtain a fully functional implant. In this work we identified an optimal geometrical pattern for bone tissue engineering applications, best balancing several graft needs which correspond to competing design goals. In particular, we investigated the occurred changes in graft behavior by varying pore size (300 μm, 600 μm, 900 μm), interpore distance (equal to pore size or 300 μm fixed) and pores interconnection (absent, 45°-oriented, 90°-oriented). Mathematical considerations and Computational Fluid Dynamics (CFD) tools, here combined in a complete theoretical model, were carried out to this aim. Poly-lactic acid (PLA) based samples were realized by 3D printing, basing on the modeled architectures. A collagen (COL) coating was also realized on grafts surface and the interaction between PLA and COL, besides the protein contribution to graft bioactivity, was evaluated. Scaffolds were extensively characterized; human articular cells were used to test their biocompatibility and to evaluate the theoretical model predictions. Grafts fulfilled both the chemical and physical requirements. Finally, a good agreement was found between the theoretical model predictions and the experimental data, making these prototypes good candidates for bone graft replacements.

Materials science & engineering. C, Materials for biological applications, 2014

The development of bioactive materials is in the premise of tissue engineering. For several years... more The development of bioactive materials is in the premise of tissue engineering. For several years, surface functionalization of scaffolds has been one of the most promising approaches to stimulate cellular activity and finally improve implant success. Herein, we describe the development of a bioactive composite scaffold composed of a biodegradable photopolymer scaffold and titanate nanotubes (TNTs). The biodegradable photopolymer scaffolds were fabricated by applying mask-projection excimer laser photocuring at 308 nm. TNTs were synthesized and then spin-coated on the porous scaffolds. Upon culturing fibroblast cells on scaffolds, we found that nanotubes coating affects cell viability and proliferation demonstrating that TNT coatings enhance cell growth on the scaffolds by further improving their surface topography.

Optical Methods for Inspection, Characterization, and Imaging of Biomaterials, 2013

ABSTRACT Vascular prostheses are widely used devices fundamental to avoid the effect of life-thre... more ABSTRACT Vascular prostheses are widely used devices fundamental to avoid the effect of life-threatening diseases and defects. Besides a long experience in the fabrication of biomaterials for vascular applications, many issues still remain unattended. In particular, obtaining a bio-resorbable and bio-active scaffold is a challenge of paramount importance. We present a novel application in which a promising biodegradable polymer, poly-propylene fumarate (PPF), is printed using three dimensional laser-induced cross-linking micromachining device. To enhance the biological role of the scaffold, a bio-inspired approach was taken, by coating the surface of the PPF with elastin, the main constituent of the innermost layer of natural veins and arteries

Methods in Molecular Biology, 2012

The design of new bioactive materials, provided with &amp;amp;amp;amp;amp;amp;amp;amp;amp... more The design of new bioactive materials, provided with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;instructive properties&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and able to regulate stem cell behavior, is the goal for several research groups involved in tissue engineering. This new function, commonly reserved for growth factors, can lead to the development of a new class of implantable scaffolds, useful for accelerating tissue regeneration in a controlled manner. In this scenario, the likely most versatile and effective tools for the realization of such scaffolds are based on nano- and microtechnology. Here, we show how exploiting the electrostatic spinning (ES) technique for producing a nanofibrillar composite structure, by mimicking topographically the extracellular matrix environment, can influence the fate of human bone marrow mesenchymal stem cells, inducing osteogenic differentiation in the absence of chemical treatments or cellular reprogramming. Basic cues on the choice of the materials and useful experimental instructions for realizing composite nanofibrous scaffolds will be given as well as fundamental tips.

Tissue Engineering Part A, 2010

In tissue-engineered applications bone marrow stromal cells (BMSCs) are combined with scaffolds t... more In tissue-engineered applications bone marrow stromal cells (BMSCs) are combined with scaffolds to target bone regeneration; animal models have been devised and the cells' long-term engraftment has been widely studied. However, in regenerated bone, the cell number is severely reduced with respect to the initially seeded BMSCs. This reflects the natural low cellularity of bone but underlines the selectivity of the differentiation processes. In this respect, we evaluated the short-term survival of BMSCs, transduced with the luciferase gene, after implantation of cell-seeded scaffolds in a nude mouse model. Cell proliferation=survival was assessed by bioluminescence imaging: light production was decreased by 30% on the first day, reaching a 50% loss within 48 h. Less than 5% of the initial signal remained after 2 months in vivo. Apoptotic BMSCs were detected within the first 2 days of implantation. Interestingly, the initial frequency of clonogenic progenitors matched the percentage of in vivo surviving cells. Cytokines and inflammation may contribute to the apoptotic onset at the implant milieu. However, preculturing cells with tumor necrosis factor alpha enhanced survival, allowing detection of 8.1% of the seeded BMSCs 2 months after implantation. Thus culturing conditions may reduce the apoptotic overload of seeded osteoprogenitors, strengthening the constructs' osteogenic potential.