28 research outputs found

    Surfactant-assisted distal pulmonary distribution of Budesonide revealed by mass spectrometry imaging

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    13openInternationalBothDirect lung administration of budesonide in combination with surfactant reduces the incidence of bronchopulmonary dysplasia. Although the therapy is currently undergoing clinical development, the lung distribution of budesonide throughout the premature neonatal lung has not yet been investigated. Here, we applied mass spectrometry imaging (MSI) to investigate the surfactant-assisted distal lung distribution of budesonide. Unlabeled budesonide was either delivered using saline as a vehicle (n = 5) or in combination with a standard dose of the porcine surfactant Poractant alfa (n = 5). These lambs were ventilated for one minute, and then the lungs were extracted for MSI analysis. Another group of lambs (n = 5) received the combination of budesonide and Poractant alfa, followed by two hours of mechanical ventilation. MSI enabled the label-free detection and visualization of both budesonide and the essential constituent of Poractant alfa, the porcine surfactant protein C (SP-C). 2D ion intensity images revealed a non-uniform distribution of budesonide with saline, which appeared clustered in clumps. In contrast, the combination therapy showed a more homogeneous distribution of budesonide throughout the sample, with more budesonide distributed towards the lung periphery. We found similar distribution patterns for the SP-C and budesonide in consecutive lung tissue sections, indicating that budesonide was transported across the lungs associated with the exogenous surfactant. After two hours of mechanical ventilation, the budesonide intensity signal in the 2D ion intensity maps dropped dramatically, suggesting a rapid lung clearance and highlighting the relevance of achieving a uniform surfactant-assisted lung distribution of budesonide early after delivery to maximize the anti-inflammatory and maturational effects throughout the lungopenZecchi, Riccardo; Franceschi, Pietro; Tigli, Laura; Pioselli, Barbara; Mileo, Valentina; Murgia, Xabier; Salomone, Fabrizio; Pieraccini, Giuseppe; Usada, Haruo; Schmidt, Augusto F; Hillman, Noah H.; Kemp, Matthew W.; Jobe, Alan H.Zecchi, R.; Franceschi, P.; Tigli, L.; Pioselli, B.; Mileo, V.; Murgia, X.; Salomone, F.; Pieraccini, G.; Usada, H.; Schmidt, A.F.; Hillman, N.H.; Kemp, M.W.; Jobe, A.H

    Integra® dermal matrix bioengineered with platelet rich plasma (PRP) and mesenchymal stromal cells to serve as niche for skin regeneration

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    Regenerative medicine strategies represent one of the main challenges to improve tissue healing and repair after damage or chronic pathologies. In this perspective, the setting of bioengineered scaffolds, namely synthetic matrices enriched with growth factors and stem cells, is considered a hot issue by numerous research groups. In a previous “in vitro” study we have demonstrated that rat bone marrow-derived mesenchymal stem cells (MSCs) seeded on an artificial dermal matrix Integra®, enriched with platelet-rich plasma (PRP) displayed enhanced proliferative attitude as compared with those cultured in the presence of PRP or on the scaffold alone. To this purpose, in this study we wanted to extend the experimentation by evaluating the efficacy of the bioengineered Integra® in an in vivo model of skin damage in rats. In particular, we used MSC derived from genetically modified rats overexpressing green fluorescent protein (GFP). Rats were divided into different groups: those receiving Integra® or PRP alone, Integra® plus PRP, Integra® plus PRP and MSC, and injured and untreated rats. Skin biopsies, obtained at different times from the injury and the implant, were examined to evaluate the regeneration process and neovascularization pattern of the substrate at light an confocal immunofluorescence microscopy. In parallel experiments we evaluated the ability of MSC to release growth factors, namely VEGF and FGF, and immunomodulatory cytokines, to underscore the paracrine effects of these cells on the surrounding host tissue

    Técnicas regenerativas para os aumentos ósseos verticais e horizontais Em atrofias mandibulares nos setores posteriores

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    Objetivo: o objetivo desta revisão sistemática integrativa é analisar e comparar as diferentes técnicas regenerativas mais utilizadas e documentadas na literatura, a fim de identificar aquelas que podem ser aplicadas nas atrofias mandibulares com maior previsibilidade e eficácia em longo prazo. Para isso, diferentes parâmetros foram avaliados:ISR (taxa de sobrevivência implantar), SSR (taxa de sucesso implantar), quantidade de aumento ósseo vertical e horizontal ao longo do tempo, quantidade de reabsorção ossea perimplantar e do enxerto. Materiais e métodos: Pesquisa Bibliográfica realizada principalmente na base de dados Pubmed, resultado um total de 375 artigos. Após a leitura dos títulos e do “abstract”, foram selecionados 100, sendo 15 duplicados. Dos 85 restantes, apenas 22 corresponderam aos critérios de inclusão e exclusão definidos. Resultados: em relação ao índice de sobrevivência e sucesso do implante "ISR; SSR", todas as técnicas analisadas apresentaram valores acima de 85% com seguimento de 5 a 74 meses. A quantidade de aumento ósseo previsível a longo prazo foi em torno de 5 mm para o aumento vertical e 4 mm para o aumento horizontal, sem diferenças estatisticamente significativas entre as técnicas analisadas. A quantidade de reabsorção óssea vertical e horizontal variou muito dependendo do posicionamento do enxerto, da técnica utilizada e das variáveis individuais. Conclusões: Os procedimentos de aumento ósseo vertical e horizontal geralmente apresentam uma taxa significativa de complicações; diferenciar quais técnicas têm maior previsibilidade é complicado e o sucesso do procedimento depende muito da habilidade do operador
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