RESUMO
Addressing current challenges in solid tumor research requires advanced in vitro three-dimensional (3D) cellular models that replicate the inherently 3D architecture and microenvironment of tumor tissue, including the extracellular matrix (ECM). However, tumor cells exert mechanical forces that can disrupt the physical integrity of the matrix in long-term 3D culture. Therefore, it is necessary to find the optimal balance between cellular forces and the preservation of matrix integrity. This work proposes using polydopamine (PDA) coating for 3D microfluidic cultures of pancreatic cancer cells to overcome matrix adhesion challenges to sustain representative tumor 3D cultures. Using PDA's distinctive adhesion and biocompatibility, our model uses type I collagen hydrogels seeded with different pancreatic cancer cell lines, prompting distinct levels of matrix deformation and contraction. Optimizing the PDA coating enhances the adhesion and stability of collagen hydrogels within microfluidic devices, achieving a balance between the disruptive forces of tumor cells on matrix integrity and the maintenance of long-term 3D cultures. The findings reveal how this tension appears to be a critical determinant in spheroid morphology and growth dynamics. Stable and prolonged 3D culture platforms are crucial for understanding solid tumor cell behavior, dynamics, and responses within a controlled microenvironment. This advancement ultimately offers a powerful tool for drug screening, personalized medicine, and wider cancer therapeutics strategies.
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Carcinoma Ductal Pancreático , Hidrogéis , Indóis , Dispositivos Lab-On-A-Chip , Neoplasias Pancreáticas , Polímeros , Humanos , Indóis/química , Indóis/farmacologia , Polímeros/química , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Hidrogéis/química , Hidrogéis/farmacologia , Linhagem Celular Tumoral , Técnicas de Cultura de Células em Três Dimensões/métodos , Matriz Extracelular/química , Microambiente Tumoral/efeitos dos fármacosRESUMO
The extracellular matrix (ECM) plays an important regulatory role in the development and progression of tumoral tissue. Its functions and properties are crucial in determining tumor cell behavior such as invasion, migration, and malignancy development. Our study explores the role of collagen type I in cancer development and spread using engineered tumor models like multicellular spheroids grown in collagen-based hydrogels to simulate early tumor formation. We employ microfluidic techniques to test the hypothesis that (i) adding Laponite nanoclay to collagen hydrogels modifies mechanical and rheological properties and (ii) changing the stiffness of the collagen microenvironment affects tumor spheroid growth. Our findings support our theories and suggest the use of ECM components and engineered tumor models in cancer research, offering a biocompatible and biomimetic method to tailor the mechanical properties of conventional collagen hydrogels.
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Colágeno , Hidrogéis , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Linhagem Celular Tumoral , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Esferoides Celulares/metabolismo , Microambiente TumoralRESUMO
BACKGROUND: Outdoor air pollution may disturb immune system development. We investigated whether gestational exposure to traffic-related air pollutants (TRAP) is associated with unstimulated cytokine profiles in newborns. METHODS: Data come from 235 newborns of the NELA cohort. Innate response-related cytokines (IL-6, IFN-α, IL1-ß, and TNF-α), Th1-related (IFN-γ and IL-2), Th2-related (IL-4, IL-5, and IL-13), Th17-related (IL-17 and IL-23), and immunomodulatory cytokine IL-10 were quantified in the supernatant of unstimulated whole umbilical cord blood cells after 7 days of culture using the Luminex technology. Dispersion/chemical transport modeling was used to estimate long-term (whole pregnancy and trimesters) and short-term (15 days before delivery) residential exposures to traffic-related nitrogen dioxide (NO2 ), particulate matter (PM2.5 and PM10 ), and ozone (O3 ). We fitted multivariable logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression models. RESULTS: NO2 during the whole pregnancy increased the odds of detection of IL-1ß (OR per 10 µg/m3 increase = 1.37; 95% CI, 1.02, 1.85) and IL-6 (OR per 10 µg/m3 increase = 1.32; 95% CI 1.00, 1.75). Increased odds of detected concentrations of IL-10 was found in newborns exposed during whole pregnancy to higher levels of NO2 (OR per 10 µg/m3 increase = 1.30; 95% CI 0.99, 1.69), PM10 (OR per 10 µg/m3 increase = 1.49; 95% CI 0.95, 2.33), and PM2.5 (OR per 5 µg/m3 increase = 1.56; 95% CI 0.97, 2.51). Exposure to O3 during the whole pregnancy increased the odds of detected IL-13 (OR per 10 µg/m3 increase = 1.22; 95% CI 1.01, 1.49). WQS model revealed first and third trimesters of gestation as windows of higher susceptibility. CONCLUSIONS: Gestational exposure to TRAP may increase detection of pro-inflammatory, Th2-related, and T regulatory cytokines in newborns. These changes might influence immune system responses later in life.
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Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Teorema de Bayes , Citocinas , Exposição Ambiental/efeitos adversos , Feminino , Sangue Fetal , Humanos , Recém-Nascido , Dióxido de Nitrogênio/efeitos adversos , Dióxido de Nitrogênio/análise , Material Particulado/efeitos adversos , GravidezRESUMO
BACKGROUND: Primary prevention strategies for asthma are lacking. Its inception probably starts in utero and/or during the early postnatal period as the developmental origins of health and disease (DOHaD) paradigm suggests. OBJECTIVES: The main objective of Nutrition in Early Life and Asthma (NELA) cohort study is to unravel whether the following factors contribute causally to the developmental origins of asthma: (1) maternal obesity/adiposity and foetal growth; (2) maternal and child nutrition; (3) outdoor air pollution; (4) endocrine disruptors; and (5) maternal psychological stress. Maternal and offspring biological samples are used to assess changes in offspring microbiome, immune system, epigenome and volatilome as potential mechanisms influencing disease susceptibility. POPULATION: Randomly selected pregnant women from three health areas of Murcia, a south-eastern Mediterranean region of Spain, who fulfilled the inclusion criteria were invited to participate at the time of the follow-up visit for routine foetal anatomy scan at 19-22 weeks of gestation, at the Maternal-Fetal Medicine Unit of the "Virgen de la Arrixaca" University Clinical Hospital over a 36-month period, from March 2015 to April 2018. DESIGN: Prospective, population-based, maternal-child, birth cohort study. METHODS: Questionnaires on exposures and outcome variables were administered to mothers at 20-24 gestation week; 32-36 gestation week; and delivery. Children were surveyed at birth, 3 and 18 months of age and currently at 5 years. Furthermore, physical examinations were performed; and different measurements and biological samples were obtained at these time points. PRELIMINARY RESULTS: Among the 1350 women invited to participate, 738 (54%) were finally enrolled in the study and 720 of their children were eligible at birth. The adherence was high with 612 children (83%) attending the 3 months' visit and 532 children (72%) attending the 18 months' visit. CONCLUSION: The NELA cohort will add original and unique knowledge to the developmental origins of asthma.
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Asma , Coorte de Nascimento , Asma/epidemiologia , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Estado Nutricional , Gravidez , Estudos ProspectivosRESUMO
The scientific literature is scarce when referring to the influence of atmospheric pollutants on neurodegenerative diseases for present and future climate change scenarios. In this sense, this contribution evaluates the incidence of dementia (Alzheimer's disease, AD, and dementia from unspecified cause, DU) occurring in Europe associated with the exposure to air pollution (essentially NO2 and PM2.5) for the present climatic period (1991-2010) and for a future climate change scenario (RCP8.5, 2031-2050). The GEMM methodology has been applied to air pollution simulations using the chemistry/climate regional model WRF-Chem. Present population data were obtained from NASA's Center for Socioeconomic Data and Applications (SEDAC); while future population projections for the year 2050 were derived from the United Nations (UN) Department of Economic and Social Affairs-Population Dynamics. Overall, the estimated incidence rate (cases per year) of AD and DU associated with exposure to air pollution over Europe is 498,000 [95% confidence interval (95% CI) 348,600-647,400] and 314,000 (95% CI 257,500-401,900), respectively. An important increase in the future incidence rate is projected (around 72% for both types of dementia) when considering the effect of climate change together with the foreseen changes in the future population, because of the expected aging of European population. The climate penalty (impacts of future climate change alone on air quality) has a limited effect on the total changes of dementia (approx. 0.5%), because the large increase in the incidence rate over southern Europe is offset by its decrease over more northern countries, favored by an improvement of air pollution caused by the projected enhancement of rainfall.
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Poluentes Atmosféricos , Poluição do Ar , Demência , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Mudança Climática , Demência/induzido quimicamente , Demência/epidemiologia , Europa (Continente)/epidemiologia , Humanos , Material Particulado/análiseRESUMO
Metastasis, a hallmark of cancer development, is also the leading reason for most cancer-related deaths. Furthermore, cancer cells are highly adaptable to micro-environments and can migrate along pre-existing channel-like tracks of anatomical structures. However, more representative three-dimensional models are required to reproduce the heterogeneity of metastatic cell migration in vivo to further understand the metastasis mechanism and develop novel therapeutic strategies against it. Here, we designed and fabricated different microfluidic-based devices that recreate confined migration and diverse environments with asymmetric hydraulic resistances. Our results show different migratory potential between metastatic and nonmetastatic cancer cells in confined environments. Moreover, although nonmetastatic cells have not been tested against barotaxis due to their low migration capacity, metastatic cells present an enhanced preference to migrate through the lowest resistance path, being sensitive to barotaxis. This device, approaching the study of metastasis capability based on confined cell migration and barotactic cell decisions, may pave the way for the implementation of such technology to determine and screen the metastatic potential of certain cancer cells.
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Dispositivos Lab-On-A-Chip , Neoplasias , Linhagem Celular Tumoral , Movimento Celular , Humanos , Microambiente TumoralRESUMO
BACKGROUND: Hazards of traffic-related air pollution (TRAP) on the developing immune system are poorly understood. We sought to investigate the effects of prenatal exposure to TRAP on cord blood immune cell distributions; and to identify gestational windows of susceptibility. METHODS: In-depth immunophenotyping of cord blood leukocyte and lymphocyte subsets was performed by flow cytometry in 190 newborns embedded in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015-2018). Long-term (whole pregnancy and trimesters) and short-term (15-days before delivery) residential exposures to traffic-related nitrogen dioxide (NO2), particulate matter (PM2.5 and PM10), and ozone (O3) were estimated using dispersion/chemical transport modelling. Associations between TRAP concentrations and cord blood immune cell counts were assessed using multivariate Poisson regression models. RESULTS: Mean number of natural killer (NK) cells decreased 15% in relation to higher NO2 concentrations (≥36.4 µg/m3) during whole pregnancy (incidence relative risk (IRR), 0.85; 95% CI, 0.72, 0.99), with stronger associations in the first trimester. Higher PM2.5 concentrations (≥13.3 µg/m3) during whole pregnancy associated with a reduced mean number of cytotoxic T cells (IRR, 0.88; 95% CI, 0.78, 0.99). Newborns exposed to higher PM10 (≥23.6 µg/m3) and PM2.5 concentrations during the first and third trimester showed greater mean number of helper T type 1 (Th1) cells (P < 0.05). Decreased number of regulatory T (Treg) cells was associated with greater short-term NO2 (IRR, 0.90; 95% CI, 0.80, 1.01) and PM10 (IRR, 0.88; 95% CI, 0.77, 0.99) concentrations. CONCLUSIONS: Prenatal exposure to TRAP, particularly in early and late gestation, impairs fetal immune system development through disturbances in cord blood leukocyte and lymphocyte distributions.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Asma , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , Poluição do Ar/estatística & dados numéricos , Feminino , Sangue Fetal/química , Humanos , Recém-Nascido , Dióxido de Nitrogênio/análise , Dióxido de Nitrogênio/toxicidade , Material Particulado/análise , Material Particulado/toxicidade , GravidezRESUMO
Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal tumor types, with extremely low survival rates due to late diagnosis and resistance to standard therapies. A more comprehensive understanding of the complexity of PDA pathobiology, and especially of the role of the tumor microenvironment in disease progression, should pave the way for therapies to improve patient response rates. In this study, we identify galectin-1 (Gal1), a glycan-binding protein that is highly overexpressed in PDA stroma, as a major driver of pancreatic cancer progression. Genetic deletion of Gal1 in a Kras-driven mouse model of PDA (Ela-KrasG12Vp53-/- ) results in a significant increase in survival through mechanisms involving decreased stroma activation, attenuated vascularization, and enhanced T cell infiltration leading to diminished metastasis rates. In a human setting, human pancreatic stellate cells (HPSCs) promote cancer proliferation, migration, and invasion via Gal1-driven pathways. Moreover, in vivo orthotopic coinjection of pancreatic tumor cells with Gal1-depleted HPSCs leads to impaired tumor formation and metastasis in mice. Gene-expression analyses of pancreatic tumor cells exposed to Gal1 reveal modulation of multiple regulatory pathways involved in tumor progression. Thus, Gal1 hierarchically regulates different events implicated in PDA biology including tumor cell proliferation, invasion, angiogenesis, inflammation, and metastasis, highlighting the broad therapeutic potential of Gal1-specific inhibitors, either alone or in combination with other therapeutic modalities.
Assuntos
Carcinoma Ductal Pancreático/terapia , Galectina 1/fisiologia , Galectinas/fisiologia , Terapia de Alvo Molecular , Neoplasias Pancreáticas/terapia , Animais , Carcinoma Ductal Pancreático/irrigação sanguínea , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/imunologia , Divisão Celular/genética , Movimento Celular/genética , Meios de Cultivo Condicionados , Galectinas/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Ontologia Genética , Xenoenxertos , Humanos , Linfócitos do Interstício Tumoral/imunologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Metástase Neoplásica , Neovascularização Patológica , Neoplasias Pancreáticas/irrigação sanguínea , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/imunologia , Células Estreladas do Pâncreas/metabolismo , Células Estreladas do Pâncreas/transplante , Comunicação Parácrina , RNA Interferente Pequeno/genética , Células Estromais/metabolismo , Microambiente TumoralRESUMO
The vision impairments suffered by millions of people worldwide and the shortage of corneal donors show the need of substitutes that mimic native tissue to promote cell growth and subsequent tissue regeneration. The current study focused on the in vitro assessment of protein-based biomaterials that could be a potential source for corneal scaffolds. Collagen, soy protein isolate (SPI), and gelatin films cross-linked with lactose or citric acid were prepared and physicochemical, transmittance, and degradation measurements were carried out. In vitro cytotoxicity, cell adhesion, and migration studies were performed with human corneal epithelial (HCE) cells and 3T3 fibroblasts for the films' cytocompatibility assessment. Transmittance values met the cornea's needs, and the degradation profile revealed a progressive biomaterials' decomposition in enzymatic and hydrolytic assays. Cell viability at 72 h was above 70% when exposed to SPI and gelatin films. Live/dead assays and scanning electron microscopy (SEM) analysis demonstrated the adhesion of both cell types to the films, with a similar arrangement to that observed in controls. Besides, both cell lines were able to proliferate and migrate over the films. Without ruling out any material, the appropriate optical and biological properties shown by lactose-crosslinked gelatin film highlight its potential for corneal bioengineering.
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Materiais Biocompatíveis/química , Córnea/metabolismo , Engenharia Tecidual/métodos , Células 3T3 , Animais , Linhagem Celular , Ácido Cítrico/química , Colágeno/química , Colágeno/metabolismo , Reagentes de Ligações Cruzadas/química , Epitélio Corneano/efeitos dos fármacos , Gelatina/química , Humanos , Lactose/química , Camundongos , Proteínas de Soja/química , Proteínas de Soja/metabolismo , Suínos , Alicerces Teciduais/químicaRESUMO
Two Alteromonas sp. strains isolated from deep seawater were grown to promote the production of exopolysaccharides (EPS, E611 and E805), which were incorporated into chitosan solutions to develop films. The combination of the major marine polysaccharides (chitosan and the isolated bacterial EPS) resulted in the formation of homogenous, transparent, colorless films, suggesting good compatibility between the two components of the film-forming formulation. With regards to optical properties, the films showed low values of gloss, in the range of 5-10 GU, indicating the formation of non-glossy and rough surfaces. In addition to the film surface, both showed hydrophobic character, with water contact angles higher than 100 º, regardless of EPS addition. Among the two EPS under analysis, chitosan films with E805 showed better mechanical performance, leading to resistant, flexible, easy to handle films.
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Alteromonas/metabolismo , Quitosana/química , Polissacarídeos Bacterianos/química , Cor , Composição de Medicamentos , Interações Hidrofóbicas e Hidrofílicas , Polissacarídeos Bacterianos/isolamento & purificação , Água do Mar/microbiologia , Propriedades de Superfície , Resistência à Tração , Microbiologia da ÁguaRESUMO
Aberrant sialylation is frequently found in pancreatic ductal adenocarcinoma (PDA). α2,3-Sialyltransferases (α2,3-STs) ST3GAL3 and ST3GAL4 are overexpressed in PDA tissues and are responsible for increased biosynthesis of sialyl-Lewis (sLe) antigens, which play an important role in metastasis. This study addresses the effect of α2,3-STs knockdown on the migratory and invasive phenotype of PDA cells, and on E-selectin-dependent adhesion. Characterization of the cell sialome, the α2,3-STs and fucosyltransferases involved in the biosynthesis of sLe antigens, using a panel of human PDA cells showed differences in the levels of sialylated determinants and α2,3-STs expression, reflecting their phenotypic heterogeneity. Knockdown of ST3GAL3 and ST3GAL4 in BxPC-3 and Capan-1 cells, which expressed moderate to high levels of sLe antigens and α2,3-STs, led to a significant reduction in sLex and in most cases in sLea, with slight increases in the α2,6-sialic acid content. Moreover, ST3GAL3 and ST3GAL4 downregulation resulted in a significant decrease in cell migration and invasion. Binding and rolling to E-selectin, which represent key steps in metastasis, were also markedly impaired in the α2,3-STs knockdown cells. Our results indicate that inhibition of ST3GAL3 and ST3GAL4 may be a novel strategy to block PDA metastasis, which is one of the reasons for its dismal prognosis.
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Selectina E/metabolismo , Neoplasias Pancreáticas/metabolismo , RNA Interferente Pequeno/farmacologia , Sialiltransferases/genética , Linhagem Celular Tumoral , Movimento Celular , Fucosiltransferases/genética , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Antígenos do Grupo Sanguíneo de Lewis/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Sialiltransferases/antagonistas & inibidoresRESUMO
OBJECTIVE: To compare surgical outcomes in women who underwent vaginal hysterectomy with enlarged (> 12 weeks size) and non-prolapsed uterus utilizing different morcellation techniques with or without concomitant Deschamps needle use to vaginal hysterectomy for prolapsed uterus. MATERIAL AND METHODS: Retrospective cohort study in women who underwent vaginal hysterectomy performed between January 2009 and June 2014 in the National Institute of Perinatology. The study group comprised 48 women who had vaginal hysterectomy with enlarged and non-prolapsed uterus in which were utilized different morcellation techniques with or without concomitant Deschamps needle use and 50 women who had vaginal hysterectomy for prolapsed uterus served as control. RESULTS: The groups had statistical difference in age, number of cesarean sections, body mass index (BMI), grade of prolapse (Point Cx and D with POPQ quantification system) and surgical prediagnosis (p < 0.001); mean uterus weight was 182.5 g and 106 g, respectively (p < 0.001), as well as for transverse and antero-posterior dimensions and realization of morcellation with or without use of Deschamps needle. Both groups had no statistical difference in preoperative hemoglobin, concomitant surgeries for incontinence and prolapsed, estimated blood loss, operation time, length of stay and complications. CONCLUSION: Vaginal hysterectomy utilizing different morcellation techniques with or without concomitant Deschamps needle use in women with enlarged and non-prolapsed uterus is safe, effective, and with similar complications to vaginal hysterectomies in prolapse uterus.
Assuntos
Histerectomia Vaginal/métodos , Doenças Uterinas/cirurgia , Prolapso Uterino/cirurgia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Histerectomia Vaginal/instrumentação , Tempo de Internação , Pessoa de Meia-Idade , Agulhas , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos RetrospectivosRESUMO
Coffee wastes are underused materials, largely available in coffee producing regions, which can be used to obtain pectins for the development of films for packaging. Coffee residual water (CRW) provided a phenolic and protein rich-pectic fraction (CRWP), which has 49 % uronic acid. This pectic fraction was used for the development of films with chitosan (Chit). Additionally, pectins extracted from coffee pulp with acid, Coffea arabica pectin (CAP), hot water-soluble pectic fraction (HWSP), and chelating agent-soluble pectic fraction (CSP), were used to develop pectin-chitosan films. Flow and viscoelastic properties of film forming solutions were assessed, showing better characteristics for the pectins from the pulp over those from the residual water. The different composition of the pectin fractions allowed to relate film properties with their structural features and Fourier transform infrared (FTIR) spectroscopy showed interactions between pectin and chitosan in the films. Results showed that CAP-Chit and CSP-Chit films were transparent, hydrophobic, and had the best mechanical properties. These results demonstrate that coffee residual wastes have the potential to provide pectins that can be used for the development of films.
RESUMO
Inks based on soybean protein isolate (SPI) were developed and their formulations were optimized as a function of the ink heat treatment and the content of other biopolymers to assess the effects of protein-polysaccharides and protein-protein interactions. First, the rheological behavior of the inks was analyzed in relation to the polyvinyl alcohol (PVA) concentration employed (20, 25, and 30 wt%) and, as a result of the analysis, the ink with 25 wt% PVA was selected. Additionally, sodium alginate (SA) and gelatin (GEL) were added to the formulations to improve the viscoelastic properties of the inks and the effect of the SA or GEL concentrations (1, 2, and 3 wt%) was studied. All inks showed shear thinning behavior and self-supporting abilities. Among all the 3D printed scaffolds, those with higher SA (3 wt%) or GEL (2 and 3 wt%) content showed higher shape fidelity and were selected for further characterization. Texture profile analysis demonstrated that the scaffolds prepared with previously heat-treated inks containing 3 wt% GEL showed the highest strength. Additionally, these scaffolds showed a higher water-uptake capacity profile.
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With the aim of replacing synthetic macromolecules by biological macromolecules for advanced applications, collagen films were produced with two different ionic liquids (ILs), choline dihydrogen phosphate ([Ch][DHP]) and choline serinate ([Ch][Seri]), added in order to modulate the electrical responses. The films were prepared by casting, varying IL content between 0 and 6 wt%. The morphology and thermal properties of the resulting films were found to be independent of both IL type and content. However, the highest direct curret (d.c.) electrical conductivity (1.4 × 10-8 S·cm-1) was achieved for collagen films containing 3 wt% [Ch][DHP]. Furthermore, it was demonstrated that IL/collagen films were non-cytotoxic, with cell activity values exceeding 70 %. These collagen films were proven to be suitable for force sensing applications, displaying excellent sensitivity and stability upon repeated testing.
Assuntos
Materiais Biocompatíveis , Líquidos Iônicos , Materiais Biocompatíveis/farmacologia , Colágeno , Colina , FosforilcolinaRESUMO
Taking into account that natural polymers are renewable and biodegradable, hybrid materials based on natural polymers are required for advanced technological applications with reduced environmental footprint. In this work, sustainable composites have been developed based on collagen as a polymeric matrix and different magnetic fillers, in order to tailor magnetic response. The composites were prepared by solution casting with 30 wt% of magnetite nanoparticles (Fe3O4 NPs), magnetite nanorods (Fe3O4 NRs) or cobalt ferrite nanoparticles (CoFe2O4 NPs). It is shown that the magnetic filler type has no bearing on the morphology, physical-chemical, or thermal characteristics of the composites, whereas the mechanical properties are determined by the magnetic filler, leading to a reduction in tensile strength, with values of 4.95 MPa for Fe3O4 NPs, 9.20 MPa for Fe3O4 NRs and 5.21 MPa for CoFe2O4 NPs containing samples. However, the highest magnetization saturation is obtained for Fe3O4 NPs (44 emu.g-1) and the higher coercive field for CoFe2O4 NPs (2062 Oe). In order to prove functionality of the developed composites, a self-sensing magnetic actuator device has been developed with the composite film with CoFe2O4 NPs, showing high stability over cycling.
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Cobalto , Colágeno , Nanopartículas de Magnetita , Nanocompostos , Nanocompostos/química , Colágeno/química , Cobalto/química , Nanopartículas de Magnetita/química , Compostos Férricos/química , Resistência à Tração , Fenômenos MagnéticosRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal malignancy that accounts for more than 90% of pancreatic cancer diagnoses. Our research is focused on the physico-chemical properties of the tumour microenvironment (TME), including its tumoural extracellular matrix (tECM), as they may have an important impact on the success of cancer therapies. PDAC xenografts and their decellularized tECM offer a great material source for research in terms of biomimicry with the original human tumour. Our aim was to evaluate and quantify the physico-chemical properties of the PDAC TME. Both cellularized (native TME) and decellularized (tECM) patient-derived PDAC xenografts were analyzed. A factorial design of experiments identified an optimal combination of factors for effective xenograft decellularization. Our results provide a complete advance in our understanding of the PDAC TME and its corresponding stroma, showing that it presents an interconnected porous architecture with very low permeability and small pores due to the contractility of the cellular components. This fact provides a potential therapeutic strategy based on the therapeutic agent size.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Microambiente Tumoral , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Animais , Camundongos , Matriz Extracelular/metabolismoRESUMO
The management of food waste and by-products has become a challenge for the agri-food sector and an example are whey by-products produced in dairy industries. Seeking other whey valorisation alternatives and applications, whey protein films for food packaging applications were developed in this study. Films containing different amounts (0, 5, 10, and 15 wt%) of ascorbic acid were manufactured via compression-moulding and their physicochemical, thermal, barrier, optical, and mechanical properties were analysed and related to the film structure. Additionally, the environmental assessment of the films was carried out to analyse the impact of film manufacture. Regarding physicochemical properties, both FTIR and water uptake analyses showed the presence of non-covalent interactions, such as hydrogen bonding, between whey protein and ascorbic acid as band shifts at the 1500-1700 cm-1 region as well as a water absorption decrease from 380% down to 240% were observed. The addition of ascorbic acid notably improved the UV-Vis light absorbance capacity of whey protein films up to 500 nm, a relevant enhancement for protecting foods susceptible to UV-Vis light-induced lipid oxidation. In relation to the environmental assessment, it was concluded that scaling up film manufacture could lead to a reduction in the environmental impacts, mainly electricity consumption.
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Cellulose-containing residue from agar production was incorporated as a filler into soy protein-based hydrogels and revalorized without further purification. Rheological assessment of these hydrogels was carried out in order to confirm their shear-thinning behavior and their suitability for 3D printing. It was observed that all hydrogels behaved as weak gels, which are suitable for 3D printing and have good printability and shape fidelity. The addition of cellulose did not cause chemical crosslinking but physical interactions, which led to morphological changes, thereby promoting hardness and shape recovery of the 3D-printed products. The hydrogel with the highest residue content (8 wt %) showed the highest value (78%) in shape recovery. Furthermore, the physicochemical characterization of these 3D-printed products revealed that although they have high swelling capacity, they preserve their integrity in wet conditions. These results suggested the potential of the 3D-printed products developed using residues without further purification to promote circular economy, increasing the efficiency in resources utilization.
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309Sterilization is a crucial step in the process of developing bioinks for tissue engineering applications. In this work, alginate/gelatin inks were subjected to three sterilization methods: ultraviolet (UV) radiation, filtration (FILT), and autoclaving (AUTO). In addition, to simulate the sterilization effect in a real environment, inks were formulated in two different media, specifically, Dulbecco's Modified Eagle's Medium (DMEM) and phosphate-buffered saline (PBS). First, rheological tests were performed to evaluate the flow properties of the inks, and we observed that UV samples showed shear thinning behavior, which was favorable for three-dimensional (3D) printing. Furthermore, the 3D-printed constructs developed with UV inks showed better shape and size fidelity than those obtained with FILT and AUTO. In order to relate this behavior to the material structure, Fourier transform infrared (FTIR) analysis was carried out and the predominant conformation in protein was determined by deconvolution of the amide I band, which confirmed that the prevalence of a-helix structure was greater for UV samples. This work highlights the relevance of sterilization processes, which are essential for biomedical applications, in the research field of bioinks.