Three-dimensionally two-photon lithography realized vascular grafts

Generation of artificial vascular grafts as blood vessel substitutes is a primary challenge in biomaterial and tissue-engineering research. Ideally, these grafts should be able to recapitulate physiological and mechanical properties of natural vessels and guide the assembly of an endothelial cell lining to ensure hemo-compatibility. In this paper, we advance on this challenging task by designing and fabricating 3D vessel analogues by two-photon laser lithography using a synthetic photoresist. These scaffolds guarantee human endothelial cell adhesion and proliferation, and proper elastic behavior to withstand the pressure exerted by blood flow

CARACTERIZAÇÃO TECNOLÓGICA EM AMOSTRAS MINERALIZADAS A ESTANHO DO ESTADO DE RONDÔNIA

A crescente demanda por estanho no cenário mundial vem promovendo maior interesse no estudo de mineralizações primárias e mais complexas. Nesse contexto, estudos de caracterização tecnológica foram efetuados em duas amostras (sulfetada e oxidada), provenientes do norte do Brasil, Estado de Rondônia, com o objetivo de verificar as características da cassiterita e dos sulfetos presentes e suas associações com a ganga. Os estudos envolveram análises granulométricas, separações minerais e estudos de mineralogia quantitativa por microscopia eletrônica de varredura (MEV/EDS) utilizando análise de imagens automatizada (Mineral Liberation Analyser - MLA), possibilitando a obtenção da composição mineral, as características de associação e de liberação dos minerais de interesse e a partição dos elementos químicos nos minerais portadores. Os resultados indicam que as amostras têm teores semelhantes de estanho e de zinco e a mesma assembleia mineralógica, variando apenas a proporção relativa entre os minerais presentes. O grau de liberação da cassiterita para o material cominuído abaixo de 3,36 mm é da ordem de 40 a 50%. Os estudos sugerem que o processamento da cassiterita poderia ser efetuado em duas etapas de cominuição conjugados com concentração gravítica; os mistos e rejeitos, a depender dos teores de Sn e Zn, poderiam ser remoídos para a recuperação da esfalerita por flotação, obtendo-se ainda um eventual concentrado acabado de estanho

Simple yet effective methods to probe hydrogel stiffness for mechanobiology

In spite of tremendous advances made in the comprehension of mechanotransduction, implementation of mechanobiology assays remains challenging for the broad community of cell biologists. Hydrogel substrates with tunable stiffness are essential tool in mechanobiology, allowing to investigate the effects of mechanical signals on cell behavior. A bottleneck that slows down the popularization of hydrogel formulations for mechanobiology is the assessment of their stiffness, typically requiring expensive and sophisticated methodologies in the domain of material science. Here we overcome such barriers offering the reader protocols to set-up and interpret two straightforward, low cost and high-throughput tools to measure hydrogel stiffness: static macroindentation and micropipette aspiration. We advanced on how to build up these tools and on the underlying theoretical modeling. Specifically, we validated our tools by comparing them with leading techniques used for measuring hydrogel stiffness (atomic force microscopy, uniaxial compression and rheometric analysis) with consistent results on PAA hydrogels or their modification. In so doing, we also took advantage of YAP/TAZ nuclear localization as biologically validated and sensitive readers of mechanosensing, all in all presenting a suite of biologically and theoretically proven protocols to be implemented in most biological laboratories to approach mechanobiology

Single-cell analyses reveal YAP/TAZ as regulators of stemness and cell plasticity in glioblastoma

Glioblastoma (GBM) is a devastating human malignancy. GBM stem-like cells (GSCs) drive tumor initiation and progression. Yet the molecular determinants defining GSCs in their native state in patients remain poorly understood. Here we used single-cell datasets and identified GSCs at the apex of the differentiation hierarchy of GBM. By reconstructing the GSCs’ regulatory network, we identified the YAP/TAZ coactivators as master regulators of this cell state, irrespectively of GBM subtypes. YAP/TAZ are required to install GSC properties in primary cells downstream of multiple oncogenic lesions and are required for tumor initiation and maintenance in vivo in different mouse and human GBM models. YAP/TAZ act as main roadblock of GSC differentiation, and their inhibition irreversibly locks differentiated GBM cells into a nontumorigenic state, preventing plasticity and regeneration of GSC-like cells. Thus, GSC identity is linked to a key molecular hub integrating genetics and microenvironmental inputs within the multifaceted biology of GBM

Sulfadiazine-based drug delivery systems prepared by an effective sol-gel process

In the present contribution a versatile and sustainable strategy for the formulation of a Drug Delivery System (DDS) for the controlled release of antibiotics for topical administration was developed. Silver sulfadiazine (AgSD), an antimicrobial agent for preventing infections on burn wounds, was selected as model drug. The DDS was formulated by an effective one-pot sol-gel approach by using chitosan and silica alkoxides as organic and inorganic precursor, respectively, in order to obtain a hybrid material. Different silica alkoxides, characterized by different functionalities of the organic chain, and a series of synthetic parameters (water/precursor ratio, excipients, drug amount) were evaluated. The composition of the hybrid gel was selected to achieve the optimal synergy between the physico-chemical features and the gel texture taking into great account the final application, i.e., a topical administration. Drug delivery tests were performed in vitro with a Franz vertical diffusion cell. The new DDS reaches the therapeutic concentration in the same time of a commercial sample and allows the complete release of even 2.5wt% AgSD. The drug delivery is totally controlled and gradual over 48 hours and the formulated is stable in time. Such innovative organic-inorganic hybrid material is therefore an efficient DDS for acute skin infections treatment by controlled delivery.In the present contribution a versatile and sustainable strategy for the formulation of a drug delivery system for the controlled release of antibiotics for topical administration was developed. Silver sulfadiazine (AgSD), an antimicrobial agent for preventing infections on burn wounds, was selected as model drug. The drug delivery system was formulated by an effective one-pot sol-gel approach by using chitosan and silica alkoxides as organic and inorganic precursor, respectively, in order to obtain a hybrid material. Different silica alkoxides, characterized by different functionalities of the organic chain, and a series of synthetic parameters (water/precursor ratio, excipients, and drug amount) were evaluated. The composition of the hybrid gel was selected to achieve the optimal synergy between the physico-chemical features and the gel texture taking into great account the final application, i.e., a topical administration. Drug delivery tests were performed in vitro with a Franz vertical diffusion cell. The new drug delivery system reaches the therapeutic concentration in the same time of a commercial sample and allows the complete release of even 2.5 wt% AgSD. The drug delivery is totally controlled and gradual over 48 h and the formulated is stable in time. Such innovative organic-inorganic hybrid material is therefore an efficient drug delivery system for acute skin infections treatment by controlled delivery.[GRAPHICS