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1.
Artigo em Inglês | MEDLINE | ID: mdl-31302701

RESUMO

OBJECTIVES: Reports ranged from mixed to marginal tubing wear and spallation effects as a complication of roller pumps in cardiopulmonary bypass (CPB). Because the rollers constantly compress part of the tubing, we sought to determine whether circuit materials behave differently under a 3-h simulation of CPB. METHODS: Two different tubing materials (silicone and Tygon) were tested with a customized experimental circuit, designed to allow in vitro simulation of CPB with priming volumes, pressures, revolutions per minute and temperatures equivalent to the clinical scenario. Samples were analysed with optical and field-emission scanning electron microscopy. We collected 200-ml fluid samples at 4 different times: before starting the CPB (T0), when the predicted revolutions per minute corresponded to about 2 min of CPB (T1), at 90 min (T2) and at 180 min (T3). At the end of CPB, we harvested 2 samples of tubing. Lastly, optical investigations and field-emission scanning electron microscopy observations were used for qualitative and quantitative analysis of circulating fragments. RESULTS: T2 and T3 fluid samples showed more particles than T1 samples. Significant differences in terms of particle numbers were detected: silicone tubing released more fragments per millilitre than Tygon tubing, with both materials releasing particles from 5 to 500 µm. Silicone tubing was associated with a time-dependent increase in small particles released (P = 0.04), whereas this did not apply to large particles or to Tygon tubing. Yet, bootstrap estimates suggested that silicone tubing was associated with the release of more small particles whereas Tygon tubing released more large particles (both P < 0.01). Unlike silicone, Tygon samples taken from the portion of the circuit not subjected to the action of the roller pump did not show any erosion on their surfaces. Samples of both materials taken from the portion subjected to the compression of the roller pump showed signs of significant deterioration. CONCLUSIONS: Silicone showed a worse spallation performance than Tygon, thus appearing less safe for more complex surgery of prolonged duration or for patients with a prior cerebral ischaemic event. Additional risk and cost-effectiveness comparisons to determine the potential benefits of one type of tubing material over the other are warranted to further expand our findings.

2.
Carbohydr Polym ; 222: 114991, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31320060

RESUMO

Nowadays, natural polysaccharides have given promising results as drug carriers. Among them, the hydrogels, thanks to their versatile properties, have been produced and engineered at the nano-scale in order to develop nanovectors for diagnostic and therapeutic purposes. Here, we investigate the contribution that a natural biopolymer, hyaluronic acid (HA), can give to the field of Magnetic Resonance Imaging (MRI). In addition, we study the relaxometric properties of crosslinked and non-crosslinked hydrogel networks and outline the impact of both HA concentration and crosslinker, Divinyl Sulfone (DVS), on the relaxivity of aqueous polymer solutions, even in the absence of Contrast Agents (CAs). Results show that proper HA concentration and the presence of the crosslinking agent can enhance the longitudinal relaxation time of the surrounding water, even in the absence of CAs. These findings could inspire the design of novel nanostructured hydrogels with enhanced relaxometric properties for MRI applications and not only.

3.
J R Soc Interface ; 16(154): 20190030, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31138093

RESUMO

In this paper, the effect of coupled thermal dilation and stress on interstitial fluid transport in tumour tissues is evaluated. The tumour is modelled as a spherical deformable poroelastic medium embedded with interstitial fluid, while the transvascular fluid flow is modelled as a uniform distribution of fluid sink and source points. A hyperbolic-decay radial function is used to model the heat source generation along with a rapid decay of tumour blood flow. Governing equations for displacement, fluid flow and temperature are first scaled and then solved with a finite-element scheme. Results are compared with analytical solutions from the literature, while results are presented for different scaling parameters to analyse the various physical phenomena. Results show that temperature affects pressure and velocity fields through the deformable medium. Finally, simulations are performed by assuming that the heat source is periodic, in order to assess the extent to which this condition affects the velocity field. It is reported that in some cases, especially for periodic heating, the combination of thermoelastic and poroelastic deformation led to no monotonic pressure distribution, which can be interesting for applications such as macromolecule drug delivery, in which the advective contribution is very important owing to the low diffusivity.

4.
Theranostics ; 9(6): 1809-1824, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037140

RESUMO

Recently, rational design of a new class of contrast agents (CAs), based on biopolymers (hydrogels), have received considerable attention in Magnetic Resonance Imaging (MRI) diagnostic field. Several strategies have been adopted to improve relaxivity without chemical modification of the commercial CAs, however, understanding the MRI enhancement mechanism remains a challenge. Methods: A multidisciplinary approach is used to highlight the basic principles ruling biopolymer-CA interactions in the perspective of their influence on the relaxometric properties of the CA. Changes in polymer conformation and thermodynamic interactions of CAs and polymers in aqueous solutions are detected by isothermal titration calorimetric (ITC) measurements and later, these interactions are investigated at the molecular level using NMR to better understand the involved phenomena. Water molecular dynamics of these systems is also studied using Differential Scanning Calorimetry (DSC). To observe relaxometric properties variations, we have monitored the MRI enhancement of the examined structures over all the experiments. The study of polymer-CA solutions reveals that thermodynamic interactions between biopolymers and CAs could be used to improve MRI Gd-based CA efficiency. High-Pressure Homogenization is used to obtain nanoparticles. Results: The effect of the hydration of the hydrogel structure on the relaxometric properties, called Hydrodenticity and its application to the nanomedicine field, is exploited. The explanation of this concept takes place through several key aspects underlying biopolymer-CA's interactions mediated by the water. In addition, Hydrodenticity is applied to develop Gadolinium-based polymer nanovectors with size around 200 nm with improved MRI relaxation time (10-times). Conclusions: The experimental results indicate that the entrapment of metal chelates in hydrogel nanostructures offers a versatile platform for developing different high performing CAs for disease diagnosis.

5.
Biochim Biophys Acta Proteins Proteom ; 1867(6): 637-644, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30710643

RESUMO

Acute myeloid leukemia (AML) is a clinically and a molecularly heterogeneous disease characterized by the accumulation of undifferentiated and uncontrolled proliferation of hematopoietic progenitor cells. The sub-group named "AML with gene mutations" includes mutations in nucleophosmin (NPM1) assumed as a distinct leukemic entity. NPM1 is an abundant multifunctional protein belonging to the nucleoplasmin family of nuclear chaperones. AML mutated protein is translocated into the cytoplasm (NPM1c+) retaining all functional domains except the loss of a unique NoLs (nucleolar localization signal) at the C-term domain (CTD) and the subsequent disruption of a three helix bundle as tertiary structure. The oligomeric state of NPM1 is of outmost importance for its biological roles and our previous studies linked an aggregation propensity of distinct regions of CTD to leukomogenic potentials of AML mutations. Here we investigated a polypeptide spanning the third and second helices of the bundle of type A mutated CTD. By a combination of several techniques, we ascertained the amyloid character of the aggregates and of fibrils resulting from a self-recognition mechanism. Further amyloid assemblies resulted cytoxic in MTT assay strengthening a new idea of a therapeutic strategy in AML consisting in the self-degradation of mutated NPM1.

6.
Analyst ; 144(4): 1369-1378, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30566146

RESUMO

Human cytomegalovirus (hCMV) infection is the leading cause of birth defects in newborns and death in immunosuppressed people. Traditional techniques require time-consuming and costly analyses, and sometimes result in false positive results; thus, a rapid and accurate detection for hCMV infection is necessary. Recently, hcmv-miR-US4-5p was selected as the biomarker for cytomegalovirus diagnosis and follow-up. Herein, we propose a bioassay based on microgels endowed with optical fluorescent oligonucleotide probes for the detection of circulating endogenous hcmv-microRNAs. In particular, a double strand probe, based on the fluorescence recovery after target capture, was conjugated on microgels and the probe density was opportunely optimised. Then, the microgels were directly mixed with the sample. The fluorescence read-out was measured as a function of target concentration at a fixed number of microgels per tube. As a bead-based assay, the performances of optical detection in terms of dynamic working range and limit of detection could be finely tuned by tuning the number of microgels per tube. The limit of detection of the assay could be tuned in the range from 39.1 fM to 156 aM by changing the microgel concentration from 50 µg mL-1 to 0.5 µg mL-1, respectively. The assay results specific for the selected target were stable over a one-year time span and they were not affected by the presence of human serum. Therefore, this bioassay based on microgels might represent a flexible platform that should be able to predict, identify and follow-up several diseases by monitoring freely circulating oligonucleotides in body fluids.


Assuntos
Bioensaio/métodos , Citomegalovirus/isolamento & purificação , Corantes Fluorescentes/química , MicroRNAs/análise , Sondas de Oligonucleotídeos/química , RNA Viral/análise , Sequência de Bases , Infecções por Citomegalovirus/virologia , Géis , Humanos , Limite de Detecção , Espectrometria de Fluorescência
7.
Biomed Opt Express ; 9(11): 5194-5204, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30460122

RESUMO

We implemented a completely label-free biophysical (morphometric and optical) property characterization of living monocytes in flow, using measurements obtained from two coherent imaging techniques: a pure light scattering approach to obtain an optical signature (OS) of cells, and a digital holography (DH) approach to achieve optical cell reconstructions in flow. A precise 3D cell alignment platform, taking advantage of viscoelastic fluid properties and microfluidic channel geometry, was used to investigate the OS of cells to achieve their refractive index, ratio of the nucleus over cytoplasm, and overall cell dimension. Further quantitative phase-contrast reconstructions by DH were employed to calculate surface area, dry mass, and biovolume of monocytes by using the OS outcomes as input parameters. The results show significantly different biophysical cell properties, confirming the possibility to differentiate monocytes from other cell classes in flow, thus avoiding chemical cell staining or labeling, which are nowadays used.

8.
Nutrients ; 10(9)2018 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-30223482

RESUMO

Doxorubicin is a highly active antineoplastic agent, but its clinical use is limited because of its cardiotoxicity. Although nutraceuticals endowed with anti-inflammatory properties exert cardioprotective activity, their bioavailability and stability are inconsistent. In an attempt to address this issue, we evaluated whether bioavailable nanoemulsions loaded with nutraceuticals (curcumin and fresh and dry tomato extracts rich in lycopene) protect cardiomyoblasts (H9C2 cells) from doxorubicin-induced toxicity. Nanoemulsions were produced with a high-pressure homogenizer. H9C2 cells were incubated with nanoemulsions loaded with different nutraceuticals alone or in combination with doxorubicin. Cell viability was evaluated with a modified MTT method. The levels of the lipid peroxidation products malondialdehyde (MDA) and 4-hydroxy-2-butanone (4-HNA), and of the cardiotoxic-related interleukins IL-6, IL-8, IL-1ß and IL-10, tumor necrosis factor-alpha (TNF-α), and nitric oxide were analyzed in cardiomyoblasts. The hydrodynamic size of nanoemulsions was around 100 nm. Cell viability enhancement was 35⁻40% higher in cardiomyoblasts treated with nanoemulsion + doxorubicin than in cardiomyoblasts treated with doxorubicin alone. Nanoemulsions also protected against oxidative stress as witnessed by a reduction of MDA and 4-HNA. Notably, nanoemulsions inhibited the release of IL-6, IL-8, IL-1ß, TNF-α and nitric oxide by around 35⁻40% and increased IL-10 production by 25⁻27% versus cells not treated with emulsions. Of the nutraceuticals evaluated, lycopene-rich nanoemulsions had the best cardioprotective profile. In conclusion, nanoemulsions loaded with the nutraceuticals described herein protect against cardiotoxicity, by reducing inflammation and lipid oxidative stress. These results set the stage for studies in preclinical models.

9.
Acta Biomater ; 73: 236-249, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29679778

RESUMO

Tumor and microenvironmental heterogeneity hinders the study of breast cancer biology and the assessment of therapeutic strategies, being associated with high variability and drug resistance. In this context, it is mandatory to develop three-dimensional breast tumor models able to reproduce this heterogeneity and the dynamic interaction occurring between tumor cells and microenvironment. Here we show a new breast cancer microtissue model (T-µTP) uniquely able to present intra-tumor morphological heterogeneity in a dynamic and responsive endogenous matrix. T-µTP consists of adenocarcinoma cells, endothelial cells and stromal fibroblasts. These three kinds of cells are totally embedded into an endogenous matrix which is rich in collagen and hyaluronic acid and it is directly produced by human fibroblasts. In this highly physiologically relevant environment, tumor cells evolve in different cluster morphologies recapitulating tumor spatiotemporal heterogeneity. Moreover they activate the desmoplastic and vascular reaction with affected collagen content, assembly and organization and the presence of aberrant capillary-like structures (CLS). Thus, T-µTP allows to outline main crucial events involved in breast cancer progression into a single model overcoming the limit of artificial extra cellular matrix surrogates. We strongly believe that T-µTP is a suitable model for the study of breast cancer and for drug screening assays following key parameters of clinical interest. STATEMENT OF SIGNIFICANCE: Tumor and microenvironmental heterogeneity makes very hurdle to find a way to study and treat breast cancer. Here we develop an innovative 3D tumor microtissue model recapitulating in vitro tumor heterogeneity. Tumor microtissues are characterized by the activation of the stromal and vascular reaction too. We underline the importance to mimic different microenvironmental tumor features in the same time and in a single tissue in order to obtain a model of spatiotemporal tumor genesis and progression, suitable for the study of tumor treatment and resistance.

10.
Neurosci Lett ; 672: 108-112, 2018 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-29486288

RESUMO

24-hydroxycholesterol (24OH-C) is synthesized almost exclusively in neurons. This oxysterol is mostly present as ester form in both cerebrospinal fluid and plasma. The enzyme lecithin-cholesterol acyltransferase esterifies 24OH-C in the brain, and the level of 24OH-C esters in cerebrospinal fluid was found to be correlated with the level of 24OH-C esters in plasma. Decreased levels of 24OH-C esters levels were previously found in Alzheimer's disease and Amyotrophic Lateral Sclerosis. This finding was attributed to the inhibitory effect of oxidative stress on lecithin-cholesterol acyltransferase activity in neurodegenerative conditions. Data reported here show that the plasma level of 24OH-C esters is decreased also in Parkinson's disease. ROC analysis identified 69.0% of 24OH-C esterification as the threshold (AUC = 0.98) discriminating patients (N = 19) from healthy subjects (N = 19) with 100% specificity vs controls, 89.5% sensitivity, 94.7% accuracy, and 100% precision. The level of 24OH-C esters was not correlated with UPDRS I or UPDRS III when evaluated at the time of blood sampling. By contrast, it was negatively correlated with UPDRS I (r = -0.4984, p = 0.0299) after one year of follow up. Therefore, this level might represent a novel biomarker of neurodegeneration in Parkinson's disease. The biomarker level is here proposed as a measure to evaluate the severity of disease, as well as to monitor the progression of this pathology.

11.
Nanomedicine ; 14(2): 483-491, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29175599

RESUMO

Nanoparticles (NPs) are a promising tool for in vivo multimodality imaging and theranostic applications. Hyaluronic acid (HA)-based NPs have numerous active groups that make them ideal as tumor-targeted carriers. The B-lymphoma neoplastic cells express on their surfaces a clone-specific immunoglobulin receptor (Ig-BCR). The peptide A20-36 (pA20-36) selectively binds to the Ig-BCR of A20 lymphoma cells. In this work, we demonstrated the ability of core-shell chitosan-HA-NPs decorated with pA20-36 to specifically target A20 cells and reduce the tumor burden in a murine xenograft model. We monitored tumor growth using high-frequency ultrasonography and demonstrated targeting specificity and kinetics of the NPs via in vivo fluorescent reflectance imaging. This result was also confirmed by ex vivo magnetic resonance imaging and confocal microscopy. In conclusion, we demonstrated the ability of NPs loaded with fluorescent and paramagnetic tracers to act as multimodal imaging contrast agents and hence as a non-toxic, highly specific theranostic system.

12.
Redox Biol ; 14: 557-565, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29132127

RESUMO

The human DKC1 gene encodes dyskerin, an evolutionarily conserved nuclear protein whose overexpression represents a common trait of many types of aggressive sporadic cancers. As a crucial component of the nuclear H/ACA snoRNP complexes, dyskerin is involved in a variety of essential processes, including telomere maintenance, splicing efficiency, ribosome biogenesis, snoRNAs stabilization and stress response. Although multiple minor dyskerin splicing isoforms have been identified, their functions remain to be defined. Considering that low-abundance splice variants could contribute to the wide functional repertoire attributed to dyskerin, possibly having more specialized tasks or playing significant roles in changing cell status, we investigated in more detail the biological roles of a truncated dyskerin isoform that lacks the C-terminal nuclear localization signal and shows a prevalent cytoplasmic localization. Here we show that this dyskerin variant can boost energy metabolism and improve respiration, ultimately conferring a ROS adaptive response and a growth advantage to cells. These results reveal an unexpected involvement of DKC1 in energy metabolism, highlighting a previously underscored role in the regulation of metabolic cell homeostasis.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Metabolismo Energético , Proteínas Nucleares/metabolismo , Células HeLa , Humanos , Mitocôndrias/metabolismo , Isoformas de Proteínas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Superóxidos/metabolismo
13.
Nanomedicine (Lond) ; 12(18): 2199-2210, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28816102

RESUMO

AIM: The efficacy of gadolinium (Gd) chelates as contrast agents for magnetic resonance imaging remains limited owing to poor relaxivity and toxic effects. Here, the effect of the hydration of the hydrogel structure on the relaxometric properties of Gd-DTPA is explained for the first time and called Hydrodenticity. RESULTS: The ability to tune the hydrogel structure is proved through a microfluidic flow-focusing approach able to produce crosslinked hyaluronic acid nanoparticles, analyzed regarding the crosslink density and mesh size, and connected to the characteristic correlation times of the Gd-DTPA. CONCLUSION: Hydrodenticity explains the boosting (12-times) of the Gd-DTPA relaxivity by tuning hydrogel structural parameters, potentially enabling the reduction of the administration dosage as approved for clinical use. [Formula: see text].


Assuntos
Gadolínio DTPA/química , Ácido Hialurônico/química , Hidrogéis/química , Nanopartículas/química , Quelantes/química , Meios de Contraste/química , Reagentes para Ligações Cruzadas/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Dispositivos Lab-On-A-Chip , Estrutura Molecular , Relação Estrutura-Atividade
14.
Nanomedicine (Lond) ; 12(18): 2223-2231, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28814136

RESUMO

AIM: Although there has been an improvement in the hardware and software of the PET/MRI system, the development of the nanoprobes exploiting the simultaneous acquisition of the bimodal data is still under investigation. Moreover, few studies on biocompatible and clinically relevant probes are available. This work presents a core-shell polymeric nanocarrier with improved relaxometric properties for simultaneous PET/MRI acquisitions. MATERIALS & METHODS: Core-shell nanoparticles entrapping the Gd-DTPA and 18F-FDG are obtained by a complex coacervation. RESULTS & DISCUSSION: The boosting of r1 of the entrapped Gd-DTPA up to five-times compared with 'free Gd-DTPA', is confirmed by the PET/MRI scan. The sorption of 18F-FDG into the nanoparticles is studied and designed to be integrated downstream for the production of the tracer.


Assuntos
Fluordesoxiglucose F18/química , Gadolínio DTPA/química , Imagem por Ressonância Magnética/métodos , Nanoconchas/química , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/química , Quitosana/química , Meios de Contraste/química , Humanos , Ácido Hialurônico/química , Tamanho da Partícula , Propriedades de Superfície
15.
Nanomedicine (Lond) ; 12(18): 2211-2222, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28814137

RESUMO

AIM: A high versatile microfluidic platform is proposed to design, in a one-step strategy, PEGylated crosslinked hyaluronic acid nanoparticles (cHANPs) entrapping a magnetic resonance imaging contrast agent and a dye for multimodal imaging applications. MATERIALS & METHODS: Clinically relevant biomaterials were shaped in the form of spherical NPs through a microfluidic flow focusing approach. A comparison between post processing and simultaneous PEGylation is reported to evaluate the potentiality of the chemical decoration of the cHANPs in microfluidics. RESULTS: An accurate control of the NPs in terms of size, PEGylation and loading was obtained. Furthermore, in vitro cell viability is reported and their ability to boost the magnetic resonance imaging signal is also confirmed. CONCLUSION: The proposed microfluidic approach reveals its ability to overcome several limitations of the traditional processes and to become an easy-to-use platform for theranostic applications.


Assuntos
Reagentes para Ligações Cruzadas/química , Ácido Hialurônico/química , Técnicas Analíticas Microfluídicas/instrumentação , Nanopartículas/química , Polietilenoglicóis/química , Células A549 , Sobrevivência Celular , Meios de Contraste/química , Portadores de Fármacos , Estabilidade de Medicamentos , Corantes Fluorescentes/química , Humanos , Imagem por Ressonância Magnética , Nanomedicina , Imagem Óptica , Tamanho da Partícula , Propriedades de Superfície
16.
Mol Imaging ; 16: 1536012117706237, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28654388

RESUMO

Strategies to enhance the relaxometric properties of gadolinium (Gd)-based contrast agents (CAs) for magnetic resonance imaging (MRI), without the chemical modification of chelates, have recently had a strong impact on the diagnostic field. We have taken advantage of the interaction between Gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) and the hydrogel structure of hyaluronic acid to design cross-linked hyaluronic acid nanoparticles down to 35 nm for use in MRI applications. The proposed bioformulations enable the control of the relaxometric properties of CAs, thus boosting the relaxation rate of T1. Our results led us to identify this approach as an adjustable scenario to design intravascularly injectable hydrogel nanoparticles entrapping Gd-DTPA. This approach overcomes the general drawbacks of clinically approved CAs having poor relaxivity and toxic effects.


Assuntos
Ácido Hialurônico/química , Imagem por Ressonância Magnética/instrumentação , Microfluídica/métodos , Nanopartículas/química , Meios de Contraste/química , Gadolínio/química
17.
J Tissue Eng Regen Med ; 11(6): 1865-1875, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28586547

RESUMO

The evolution of microscaffolds and bone-bioactive surfaces is a pivotal point in modular bone tissue engineering. In this study, the design and fabrication of porous polycaprolactone (PCL) microscaffolds functionalized with hydroxyapatite (HA) nanoparticles by means of a bio-safe and versatile thermally-induced phase separation process is reported. The ability of the as-prepared nanocomposite microscaffolds to support the adhesion, growth and osteogenic differentiation of human mesenchymal stem cells (hMSCs) in standard and osteogenic media and using dynamic seeding/culture conditions was investigated. The obtained results demonstrated that the PCL-HA nanocomposite microparticles had an enhanced interaction with hMSCs and induced their osteogenic differentiation, even without the exogenous addition of osteogenic factors. In particular, calcium deposition, alizarin red assay, histological analysis, osteogenic gene expression and collagen I secretion were assessed. The results of these tests demonstrated the formation of bone microtissue precursors after 28 days of dynamic culture. These findings suggest that PCL-HA nanocomposite microparticles represent an excellent platform for in vitro modular bone tissue engineering. Copyright © 2015 John Wiley & Sons, Ltd.


Assuntos
Células da Medula Óssea/metabolismo , Osso e Ossos/metabolismo , Diferenciação Celular , Durapatita/química , Células-Tronco Mesenquimais/metabolismo , Osteogênese , Poliésteres/química , Tecidos Suporte/química , Células da Medula Óssea/citologia , Osso e Ossos/citologia , Humanos , Células-Tronco Mesenquimais/citologia
18.
Adv Healthc Mater ; 6(13)2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28407433

RESUMO

Several skin equivalent models have been developed to investigate in vitro the re-epithelialization process occurring during wound healing. Although these models recapitulate closure dynamics of epithelial cells, they fail to capture how a wounded connective tissue rebuilds its 3D architecture until the evolution in a scar. Here, the in vitro tissue repair dynamics of a connective tissue is replicated by using a 3D human dermis equivalent (3D-HDE) model composed of fibroblasts embedded in their own extracellular matrix (ECM). After inducing a physical damage, 3D-HDE undergoes a series of cellular and extracellular events quite similar to those occurring in the native dermis. In particular, fibroblasts differentiation toward myofibroblasts phenotype and neosynthesis of hyaluronic acid, fibronectin, and collagen during the repair process are assessed. Moreover, tissue reorganization after physical damage is investigated by measuring the diameter of bundles and the orientation of fibers of the newly formed ECM network. Finally, the ultimate formation of a scar-like tissue as physiological consequence of the repair and closure process is demonstrated. Taking together, the results highlight that the presence of cell-assembled and responsive stromal components enables quantitative and qualitative in vitro evaluation of the processes involved in scarring during wound healing.


Assuntos
Derme/metabolismo , Matriz Extracelular/metabolismo , Modelos Biológicos , Miofibroblastos/metabolismo , Cicatrização , Derme/patologia , Matriz Extracelular/patologia , Feminino , Humanos , Masculino , Miofibroblastos/patologia
19.
Nanomedicine ; 13(1): 275-286, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27565688

RESUMO

Dual imaging dramatically improves detection and early diagnosis of cancer. In this work we present an oil in water (O/W) nano-emulsion stabilized with lecithin and loaded with cobalt ferrite oxide (Co0.5Fe2.5O4) nanocubes for photo-acoustic and magnetic resonance dual imaging. The nanocarrier is responsive in in vitro photo-acoustic and magnetic resonance imaging (MRI) tests. A clear and significant time-dependent accumulation in tumor tissue is shown in in vivo photo-acoustic studies on a murine melanoma xenograft model. The proposed O/W nano-emulsion exhibits also high values of r2/r1 (ranging from 45 to 85, depending on the magnetic field) suggesting a possible use as T2 weighted image contrast agents. In addition, viability and cellular uptake studies show no significant cytotoxicity on the fibroblast cell line. We also tested the O/W nano-emulsion loaded with curcumin against melanoma cancer cells demonstrating a significant cytotoxicity and thus showing possible therapeutic effects in addition to the in vivo imaging.


Assuntos
Cobalto/química , Meios de Contraste , Imagem por Ressonância Magnética , Melanoma/diagnóstico por imagem , Nanopartículas/química , Técnicas Fotoacústicas , Células 3T3 , Animais , Emulsões/química , Humanos , Masculino , Melanoma Experimental , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Óxidos/química
20.
J Biomed Nanotechnol ; 13(3): 337-48, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29381292

RESUMO

In this work, metal-ceramic nanocomposites were obtained through short (up to 2 h) thermal treatments at relatively moderate temperatures (750­800 °C) under a reducing atmosphere, using Fe-exchanged zeolite A as the precursor. The as-obtained materials were characterized by X-ray powder diffraction analysis, N2 adsorption at ­196 °C, and highresolution transmission electron microscopy. The results of these analyses showed that the nanocomposites consisted of a dispersion of metallic Fe nanoparticles within a porous ceramic matrix, mainly based on amorphous silica and alumina. These nanocomposites were magnetically characterized, and their magnetic response was studied. Finally, the obtained metal-ceramic nanocomposite materials were used in the separation of Escherichia coli DNA from a crude cell lysate. The results of the DNA separation experiments showed that the obtained materials could perform this type of separation.


Assuntos
DNA Bacteriano/isolamento & purificação , DNA Bacteriano/efeitos da radiação , Separação Imunomagnética/métodos , Nanocompostos/química , Nanocompostos/ultraestrutura , Ultrafiltração/métodos , Zeolitas/química , DNA Bacteriano/química , Campos Magnéticos , Teste de Materiais , Ligas Metalo-Cerâmicas/química , Nanocompostos/efeitos da radiação , Nanoporos/ultraestrutura , Tamanho da Partícula , Porosidade
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