1,720,963 research outputs found

    Poly-L-Lactic Acid (PLLA)-Based Biomaterials for Regenerative Medicine: A Review on Processing and Applications

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    Synthetic biopolymers are effective cues to replace damaged tissue in the tissue engineering(TE) field, both for in vitro and in vivo application. Among them, poly-L-lactic acid (PLLA) has beenhighlighted as a biomaterial with tunable mechanical properties and biodegradability that allowsfor the fabrication of porous scaffolds with different micro/nanostructures via various approaches.In this review, we discuss the structure of PLLA, its main properties, and the most recent advancesin overcoming its hydrophobic, synthetic nature, which limits biological signaling and proteinabsorption. With this aim, PLLA-based scaffolds can be exposed to surface modification or combinedwith other biomaterials, such as natural or synthetic polymers and bioceramics. Further, variousfabrication technologies, such as phase separation, electrospinning, and 3D printing, of PLLA-basedscaffolds are scrutinized along with the in vitro and in vivo applications employed in various tissuerepair strategies. Overall, this review focuses on the properties and applications of PLLA in theTE field, finally affording an insight into future directions and challenges to address an effectiveimprovement of scaffold properties

    Polylactic Acid/Bamboo Leaf Extract Electrospun Mats with Antioxidant Activity for Food Packaging Applications

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    This study focuses on developing an active and biodegradable packaging using electrospinning, with polylactic acid (PLA) as the matrix and bamboo leaf extract (BLE) as the antioxidant compound. The research systematically evaluates the relationship among process parameters, material properties, and structure. The electrospun membranes were produced using different BLE contents (10 wt%, 20 wt%, 30 wt%, and 40 wt%) and characterized by their morphology, mechanical properties, wettability, and antioxidant activity. Scanning electron microscopy (SEM) revealed BLE’s influence on fiber morphology, with a slight increase in diameter in PLA/BLE at 10% and 20%, attributed to higher viscosity. Conversely, PLA/BLE 30% and 40% showed a mild reduction in fiber diameter likely due to polyphenols’ capacity to enhance PLA chain mobility. Mechanical tests indicated proportional reductions in modulus, maximum stress, and strain at break, upon increasing the BLE concentration, although these parameters are still suitable for packaging applications. The decrease in modulus is attributed to polyphenol capacity to increase PLA chain mobility, while increased fragility results from embedded particles acting as local defects. Wettability tests demonstrated increased hydrophilicity with higher BLE content. Total polyphenol content, estimated through FOLIN assay, increased proportionally with incorporated BLE, impacting antioxidant properties assessed via FRAP assay

    Computational modeling and experimental characterization of fluid dynamics in micro-CT scanned scaffolds within a multiple-sample airlift perfusion bioreactor

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    The perfusion of flow during cell culture induces cell proliferation and enhances cellular activity. Perfusion bioreactors offer a controlled dynamic environment for reliable in vitro applications in the tissue engineering field. In this work, to evaluate the effects of the operating parameters of a custom-made bioreactor, numerical simulations were performed to solve the fluid velocity profile inside the bioreactor containing multi-grid support that allows allocating of multiple seeded scaffolds at the same time. The perfusion system exhibited a uniform distribution of liquid velocities within the regions, suitable for cell growth on seeded scaffolds. The effects of the porous microstructure of scaffolds on the extracellular matrix deposition also play a crucial role during perfusion cultures. In the present study, a numerical simulation was implemented at the pore level of the scaffold for fluid flow through porous media during perfused culture. Micro-computed tomography was used to obtain the digital 3D image of the complex geometry of a PLLA scaffold, offering a detailed analysis from a volume-based methodology without simplifications of the results as for pore or Darcy's law-models. Predictions about the uniformity of the flow field through the scaffolds-bioreactor system have been assessed by quantifying the cell viability of a perfusion culture while using pre-osteoblastic cells seeded on 24 PLLA scaffolds for up to 6 days

    Three-dimensional (3D) polylactic acid gradient scaffold to study the behavior of osteosarcoma cells under dynamic conditions

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    This study adopts an in vitro method to recapitulate the behavior of Saos-2 cells, using a system composed of a perfusion bioreactor and poly-L-lactic acid (PLLA) scaffold fabricated using the low-cost thermally-induced phase separation (TIPS) technique. Four distinct scaffold morphologies with different pore sizes were fabricated, characterized by Scanning electron microscopy and micro-CT analysis and tested with osteosarcoma cells under static and dynamic environments to identify the best morphology for cellular growth. In order to accomplish this purpose, cell growth and matrix deposition of the Saos-2 osteosarcoma cell line were assessed using Picogreen and OsteoImage assays. The obtained data allowed us to identify the morphology that better promotes Saos-2 cellular activity in static and dynamic conditions. These findings provided valuable insights into scaffold design and fabrication strategies, emphasizing the importance of the dynamic culture to recreate an appropriate 3D osteosarcoma model. Remarkably, the gradient scaffold exhibits promise for osteosarcoma applications, offering the potential for targeted tissue engineering approaches

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Design of perfusion bioreactors and PLLA-based scaffolds for in vitro tissue engineering

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    L'ingegneria tissutale rappresenta un nuovo approccio che integra cellule e matrici ingegnerizzate per la formazione di nuovi tessuti. In questa strategia, tre componenti essenziali costituiscono la cosiddetta triade della Tissue Engineering: segnali regolatori, cellule e scaffold tridimensionali (3D) biodegradabili e porosi. Tali elementi sono combinati per sviluppare un tessuto funzionale organizzato e 3D che simula la matrice extracellulare (ECM) del tessuto da rigenerare. Le funzioni specifiche dei tessuti nativi sono correlate agli ambienti complessi che, all'esterno del corpo, possono essere imitati usando degli strumenti chiamati bioreattori. Questi sistemi forniscono un ambiente in cui i parametri specifici possono essere controllati per raggiungere le condizioni biologiche desiderate. In questa tesi, tutti questi componenti sono stati impiegati per lo sviluppo di modelli in vitro in diverse applicazioni dell'ingegneria tissutale. In particolare, sono stati analizzati e discussi i temi relativi a: scaffold a base di poli-(acido L-lattico) (PLLA), fabbricazione di scaffold tramite separazione di fase, colture cellulari statiche e colture cellulari dinamiche utilizzando bioreattori di perfusione. Due sezioni principali compongono questa tesi: diverse configurazioni sperimentali che utilizzano scaffold a base di PLLA per vari sistemi in vitro; e la progettazione e la modellazione di un bioreattore di perfusione utilizzando fluidodinamica computazionale (CFD) ed equazioni matematiche. In primis, un rigoroso quadro teorico è stato investigato per studiare le proprietà del biomateriale PLLA, l'uso di bioreattori a perfusione per la medicina rigenerativa e i modelli sviluppati per studiare la crescita delle cellule su matrici 3D coltivate all'interno di un sistema dinamico. Negli esperimenti, la morfologia di diversi scaffold in PLLA prodotti attraverso vari protocolli della tecnica di separazione di fase indotta termicamente (TIPS) è stata analizzata in base alle proprietà desiderate per scaffold adatti agli scopi dell’ingegneria tissutale, in termini di porosità, interconnessione dei pori e dimensione dei pori. Le colture cellulari sono state eseguite in questi costrutti per creare un ambiente 3D in modo che le cellule seminate potessero crescere sia in coltura statica 3D che nel bioreattore a perfusione. La proliferazione e l'adesione delle cellule sono state osservate fino a 7 giorni di coltura in vitro, dimostrando che la morfologia degli scaffold può indurre la crescita delle cellule sia in condizioni statiche che dinamiche. Per la seconda parte, si è seguito un approccio combinato di modellazione e sperimentazione. Il sistema di perfusione usato è un bioreattore airlift (precedentemente progettato dal mio gruppo di ricerca) che fornisce un ambiente a basso sforzo di taglio e una buona miscelazione, risolvendo i limiti del trasporto di massa e fornendo stimoli fisici Sommario v vantaggiosi per la proliferazione e la differenziazione delle cellule. L'idrodinamica (gas holdup, velocità superficiale del liquido e sforzo di taglio) e il trasferimento di massa (in termini di coefficiente di trasferimento di massa) sono stati modellati e determinati da analisi CFD per esaminare l'influenza di questi parametri sulla crescita delle cellule e dei tessuti. I risultati della simulazione hanno indicato che l'idrodinamica, i dati matematici e la validazione sperimentale erano in linea tra di loro. In seguito, cellule osteoblastiche sono state coltivate su scaffold posti su un supporto all’interno del bioreattore perfuso con terreno di coltura a 10ml/ min per un massimo di 6 giorni. Combinando i risultati della proliferazione e l'analisi statistica, è stata quantificata e analizzata la crescita cellulare in funzione dello spazio all'interno del sistema bioreattore. Data la natura gerarchica del sistema bioreattore-scaffold, tale sistema è stato considerato dalla scala della matrice extracellulare alla scala del bioreattore. Le proprietà dipendenti dal flusso di una matrice ingegnerizzata e coltivata all'interno di un bioreattore a perfusione sono state studiate teoricamente e valutate sperimentalmente, sottolineando l'influenza delle dipendenze inter-scala. I bioreattori a perfusione sono sistemi in vitro utili per testare famaci poiché imitano l'ambiente in vivo. A questo scopo, è stato modellato e validato sperimentalmente un sistema ottimizzato del bioreattore airlift in grado di indurre un doppio flusso su uno scaffold fabbricato con un canale al suo interno. In particolare, il sistema è stato testato per la diffusione di carriers e per simulare un sistema aria-liquido-interfaccia (ALI) tale da riprodurre l'ambiente della mucosa nasale. Il razionale di tale sistema è il potenziale legato alla combinazione di un flusso interno ed uno esterno di fluidi indipendenti al fine di diffondere i carriers in tutta la matrice ingegnerizzata per pre-screening di farmaci o reindirizzare il mezzo di coltura nel canale dello scaffold per alimentare le cellule seminate. In conclusione, questo progetto di tesi si è concentrato sui principali aspetti dell'ingegneria tissutale e della medicina rigenerativa, spaziando da test in vitro per la crescita delle cellule su scaffold, a modelli per studiare sia le caratteristiche multi-scala di un sistema atto a replicare un tessuto sia l'efficacia della fluidodinamica di un sistema nuovo destinato a validare test farmacologici o mimare al meglio la fisiologia di un tessuto.Tissue engineering (TE) represents a novel approach that uses cells integrated with matrices to achieve the formation of new tissues. In this strategy, three essential components constitute the so-called triad of Tissue Engineering: regulatory signals, cells, and three-dimensional (3D) biodegradable porous scaffolds. They are combined to develop an organized 3D functional tissue that mimics the extracellular matrix (ECM) of tissue to be regenerated. The tissue-specific functions of native tissues are linked to complex environments that can be replicated outside the body by using special devices called bioreactors. These systems provide an environment where specific parameters can be controlled to match desired biological conditions. In this thesis, all these components are accounted for developing in vitro models for various applications in the field of Tissue Engineering. Specifically, poly-(L-lactic acid) (PLLA)-based scaffold, scaffold fabrication via phase separation, static cell cultures, and dynamic cell cultures using perfusion bioreactors are analyzed and discussed. Two main sections compose this thesis: several experimental setups using PLLA-based scaffolds for various in vitro systems; and the design and modeling of a custom perfusion bioreactor using computational fluid dynamics (CFD) and mathematical equations. A rigorous theoretical framework is developed to study the properties of PLLA biomaterial, the use of perfusion bioreactor for regenerative medicine, and models developed for investigating cells growth on 3D matrices cultured within a dynamic system. In the experiments, the morphology of different PLLA scaffolds produced through different protocols of the thermally induced phase separation technique (TIPS) is analyzed according to the targeted properties of TE scaffolds, i.e., porosity, pore interconnectivity, and pore size. Cell cultures are performed in these constructs to create a 3D environment so that seeded cells can grow both in static 3D culture and the perfusion bioreactor. Cell proliferation and adhesion are observed up to 7 days of in vitro culture, demonstrating that scaffold morphology can induce cell growth under both static and dynamic conditions. For the second part, a combined modeling and experimental approach is followed. The custom-made perfusion apparatus is an existing airlift bioreactor that provides a low-shear environment with good mixing, resolving mass transport limitations and providing physical stimuli beneficial for overall cells proliferation and differentiation. The hydrodynamics (gas holdup, superficial liquid velocity, and shear rate) and mass transfer (kLa and the volumetric mass transfer coefficient) are modeled and determined by CFD to examine the influence of Abstract iii these features on cell and tissue growth. The simulation results indicate that the hydrodynamics matched the mathematical data and experimental validation. Then, osteoblast cells are cultured on a support in the bioreactor perfused with culture medium at 10mL/min for up to 6 days. An evaluation combining proliferation results and statistical analysis allows the quantification of cell growth as a function of the space inside the system. Given the hierarchical nature of the bioreactor-scaffold system, its multi-scale nature will be considered, ranging from the extracellular matrix scale to the bioreactor scale. The flow-dependent properties of an engineered matrix cultured within a perfusion bioreactor are studied theoretically and evaluated experimentally, emphasizing the influence of inter-scale dependencies. Perfusion bioreactors are in vitro systems beneficial for drug screening because they mimic the in vivo environment. For this purpose, an optimized design of the airlift bioreactor that can induce a double-flow on a hollow scaffold is theoretically and experimentally validated. Specifically, the system is tested for carriers diffusion and air-liquid-interface (ALI) model to reproduce the nasal mucosa environment. The rationale is to combine an internal and an external flow of independent fluids for either diffusing the carriers throughout the engineered matrix for drug prescreening or redirecting the culture medium to feed the cells seeded into the channel of the hollow scaffold. In conclusion, this thesis project focuses on the major aspects of tissue engineering and regenerative medicine, varying from in vitro tests for growing cells on scaffolds toward models to study the multi-scale nature of a tissue-like system or recreate the physiology of a native tissue

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods
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