Дисертації з теми "Biomaterials platform"
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Müller, Eike, Weijia Wang, Wenlian Qiao, Martin Bornhäuser, Peter W. Zandstra, Carsten Werner, and Tilo Pompe. "Distinguishing autocrine and paracrine signals in hematopoietic stem cell culture using a biofunctional microcavity platform." Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-208979.
Повний текст джерелаAduba, Donald C. Jr. "Multi-platform arabinoxylan scaffolds as potential wound dressing materials." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/3955.
Повний текст джерелаKelly, Jennifer Yvonne DeSimone Joseph M. "Novel fluoroelastomers composed of tetrafluoroethylene and vinylidene fluoride oligomers synthesized in carbon dioxide for use in soft lithography to enable a platform for the fabrication of shape- and size-specific, monodisperse biomaterials." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2008. http://dc.lib.unc.edu/u?/etd,1934.
Повний текст джерелаTitle from electronic title page (viewed Dec. 11, 2008). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Chemistry." Discipline: Chemistry; Department/School: Chemistry.
Govindarajan, Sudhanva Raj. "THE DESIGN OF A MULTIFUNCTIONAL INITIATOR-FREE SOFT POLYESTER PLATFORM FOR ROOM-TEMPERATURE EXTRUSION-BASED 3D PRINTING, AND ANALYSIS OF PRINTABILITY." University of Akron / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=akron1466778249.
Повний текст джерелаMelo, Priscila Cristina Soares. "Electromechanical Poly(L-lactic acid) PLLA platforms for regenerative medicine." Master's thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/15135.
Повний текст джерелаThe discovery of piezoelectricity in bone by Fukada brought to light the idea of using piezoelectrics to enhance bone growth. Piezoelectric polymers like poly (L-lactic) acid (PLLA), a synthetic semi-crystalline polyester combining adjustable biodegradability and physical properties, stands out and therefore can be used as scaffolds for bone regeneration. In addition, some PLLA products have been approved for implantation in human body by the Food and Drug Administration (FDA). In the present work PLLA films with different crystallinities and thicknesses were produced in order to improve the dielectric properties and cellular adhesion. The maximum crystalline degree obtained was 35%. A complete characterization of PLLA films with different thicknesses and crystallinities was performed. The dielectric analysis included permittivity, dielectric loss and polarization. The highest relative permittivity value was 52.58 for amorphous samples at 120 ºC and 153 kHz. Dielectric loss reached its maximum at 27 ºC for a frequency of 1 MHz, being the value 1.64 on crystalline films. Polarization was studied by the technique Thermal Stimulated Depolarization Currents (TSDC), a method that measures polarization through thermal stimulus. In terms of polarization, the values increase proportionally with crystallinity, being the highest values 180 μC/cm2 on crystalline samples polarized during half an hour. In addition to cell-based assays, exists the metabolomics studies, a powerful tool since it can provide detailed information on the specific metabolic pathways responding and adapting to each of the selected material formulations. The work carried out in this project is the first stage of a wider program including in vitro biological characterization. It is presented the first metabolomics study using human osteoblasts in contact with piezoelectric PLLA, on PLLA standard films with 3% crystallinity, negatively poled.
A descoberta da piezoeletricidade no osso por Fukada levou à ideia de usar materiais piezoeléctricos para melhorar o crescimento ósseo. Polímeros piezoeléctricos como o poli (L-ácido láctico) (PLLA), um poliéster semicristalino sintético que combina biodegradabilidade e propriedades físicas ajustáveis, destacam-se pois podem ser utilizados como estruturas temporárias para a regeneração óssea. Para além disso, alguns produtos feitos à base de PLLA estão já aprovados para implantação no corpo humano pela Food and Drug Administration (FDA).Neste trabalho foram produzidos filmes de PLLA com diferentes cristalinidades e espessuras com o intuito de melhorar as propriedades dielétricas do material e a adesão celular. O grau de cristalinidade máximo obtido foi de aproximadamente 35%. Efectuou-se uma caracterização completa dos filmes com diferentes cristalinidades e espessuras. As medidas dielétricas realizadas abrangeram permitividade relativa, perda dielétrica e polarização. O valor mais alto de permitividade relativa medido foi de 52,58 para o filme amorfo, a 120 ºC e 153 kHz. A perda dielétrica atingiu o seu máximo nos filmes cristalinos aos 27 ºC para uma frequência de 1 MHz, com o valor de 1,64. A polarização foi estudada segundo a técnica TSDC (Thermal Stimulation Depolarization Current), um método que mede a polarização do material através do estímulo térmico. Em termos de polarização os valores aumentaram proporcionalmente com a cristalinidade, sendo o mais elevado 180 μC/cm2 para as amostras cristalinas polarizadas durante meia hora. Para além dos ensaios celulares, existe a metabolómica, hoje em dia uma ferramenta poderosa pois pode fornecer informações detalhadas sobre as vias metabólicas específicas que respondem e permitem a adaptação celular a cada uma das formulações de materiais selecionados. O trabalho realizado neste projecto constitui a primeira etapa de um programa mais amplo de caracterização biológica in vitro. É apresentado o primeiro estudo de metabolómica, utilizando osteoblastos humanos, em contato com o piezoelétrico PLLA, utilizando filmes de PLLA standard, 3% de cristalinidade, polarizados negativamente.
Paradis, Mathieu. "Development and characterization of Poly(L-lactic acid) (PLLA) platforms for bone tissue engineering." Master's thesis, Universidade de Aveiro, 2015. http://hdl.handle.net/10773/15771.
Повний текст джерелаThe development of scaffolds based on biomaterials is a promising strategy for Tissue Engineering and cellular regeneration. This work focuses on Bone Tissue Engineering, the aim is to develop electrically tailored biomaterials with different crystalline and electric features, and study their impacts onto cell biological behavior, so as to predict the materials output in the enhancement of bone tissue regeneration. It is accepted that bone exhibits piezoelectricity, a property that has been proved to be involved in bone growth/repair mechanism regulation. In addition electrical stimulations have been proved to influence bone growth and repair. Piezoelectric materials are therefore widely investigated for a potential use in bone tissue engineering. The main goal is the development of novel strategies to produce and employ piezoelectric biomaterials, with detailed knowledge of mechanisms involved in cell-material interaction. In the current work, poly (L-lactic) acid (PLLA), a synthetic semi-crystalline polymer, exhibiting biodegradibility, biocompatibility and piezoelectricity is studied and proposed as a promoter of enhanced tissue regeneration. PLLA has already been approved for implantation in human body by the Food and Drug Administration (FDA), and at the moment it is being used in several clinical strategies. The present study consists of first preparing films with different degrees of crystallinity and characterizing these PLLA films, in terms of surface and structural properties, and subsequently assessing the behavior of cells in terms of viability, proliferation, morphology and mineralization for each PLLA configuration. PLLA films were prepared using the solvent cast technique and submitted to different thermal treatments in order to obtain different degrees of crystallinity. Those platforms were then electrically poled, positively and negatively, by corona discharge in order to tailor their electrical properties. The cellular assays were conducted by using two different osteoblast cell lines grown directly onto the PLLA films:Human osteoblast Hob, a primary cell culture and Human osteosarcoma MG-63 cell line. This thesis gives also a comprehensive introduction to the area of Bone Tissue Engineering and provides a review of the work done in this field in the past until today, in that same field, including the one related with bone’s piezoelectricity. Then the experimental part deals with the effects of the crystallinity degrees and of the polarization in terms of surface properties and cellular bio assays. Three different degrees of crystallinity, and three different polarization conditions were prepared; which results in 9 different configurations under investigation.
O desenvolvimento de scaffolds baseados em biomateriais é uma estratégia promissora para a engenharia de tecidos e entrega de fármacos. Este trabalho centra-se na engenharia de tecido ósseo, o objectivo é desenvolver biomateriais electricamente modificados, com diferentes valores de cristalinidade e propriedades eléctricas, e estudar o seu impacto no comportamento biológico da célula de modo a prever o efeito desses materiais na regeneração do tecido. É já amplamente conhecido o fato de o osso possuir características piezoeléctricas, e reconhecido que estas contribuem para os mecanismos de regulação do crescimento e reparação do tecido ósseo. Além disso é um facto aceite que a estimulação eléctrica também influencia o crescimento e reparação do osso. Os materiais piezoeléctricos apresentam assim vantagens quanto à sua utilização em engenharia de tecido ósseo, e têm vindo a ser estudados para esse efeito. No presente trabalho foram desenvolvidos filmes de ácido poli-L-láctico (PLLA), um polímero sintético semi-cristalino que é biocompatível, biodegradável, e piezoeléctrico, que se apresenta como promotor da regeneração óssea. O PLLA é um material aceite para implantes em humanos pela “Food and Drug Administration” (FDA), e está já a ser utilizado em várias estratégias e produtos para uso clínico. O presente estudo consiste numa primeira fase de preparação e caracterização de filmes de PLLA em termos de propriedades estruturais e de superfície, e numa segunda fase de avaliação do comportamento celular em termos de viabilidade, proliferação, morfologia e mineralização, para cada uma das configurações de PLLA obtidas. Os filmes foram preparados pelo método de evaporação do solvente com molde, e submetidos a diferentes tratamentos térmicos de forma a obter diferentes valores de cristalinidade. Estas plataformas foram depois electricamente polarizadas, positiva e negativamente, por meio de descarga de corona para modular as suas propriedades eléctricas. Os ensaios celulares foram realizados utilizando duas linhas celulares osteoblásticas, em contacto direto com as superfícies de PLLA: Osteoblastos Humanos - Hob, cultura primária de células, e linha de Osteosarcoma Humano - MG-63. Este trabalho também inclui uma introdução teórica para área da Engenharia de Tecido Ósseo, e resume o trabalho de investigação realizado nesta área até hoje incluindo aquele relacionado com a piezoelectricidade do tecido ósseo. A parte experimental dedica-se aos efeitos do grau de cristalinidade e da polarização nas propriedades de superfície do material e nos ensaios biológicos. Foram estudadas nove configurações, originadas por três valores de cristalinidade: 0, 7 e 35%, e três tipos de polarização: positiva, negativa e neutra (apenas com o tratamento térmico análogo).
Recha, Sancho Lourdes Georgina. "Development of biomaterial self-assembling based platforms to obtain human cartilage tissue in vitro." Doctoral thesis, Universitat Ramon Llull, 2016. http://hdl.handle.net/10803/394009.
Повний текст джерелаEl cartílago articular tiene una capacidad limitada de crecimiento y regeneración y, los tratamientos para restaurar la función del tejido, después de una lesión, son limitados y poco entendidos por la comunidad médica. Existe, por tanto, un gran interés en encontrar una solución práctica y agradable para el paciente que consiga la reparación del cartílago. La ingeniería de tejidos surgió para restaurar tejidos dañados usando nuevas plataformas terapéuticas basadas en células y/o biomateriales. Estas nuevas terapias pretenden crear estructuras similares al cartílago que imiten las propiedades mecánicas y biológicas que se dan in vivo. En este sentido, el uso de matrices biomiméticas que reproduzcan estructural y funcionalmente el microambiente nativo ha generado gran interés en este campo. Los péptidos auto-ensamblantes representan candidatos ideales para crear nichos celulares dado que, sus nanofibras y propiedades biomecánicas son similares a las de la matriz extracelular. En esta tesis, se han desarrollado nuevos biomateriales sintéticos con gran potencial para la reparación de cartílago. Éstos, están basados en el péptido auto-ensamblante RAD16-I decorado con motivos bioactivos, tratando de reproducir la matriz del cartílago. Dada la versatilidad del hidrogel RAD16-I, las nuevas matrices se formaron por simple mezcla del péptido RAD16-I con moléculas de heparina, condroitin sulfato y decorina. Estas matrices bi-compuestas presentan buena estabilidad química y estructural a pH fisiológico y son capaces de unir y liberar, gradualmente, factores de crecimiento. La evaluación de estas matrices se llevó a cabo mediante dos estrategias in vitro diferentes: la rediferenciación de condrocitos articulares humanos y, la inducción del linaje condrogénico en células madre derivadas de tejido adiposo. Ambos tipos celulares son considerados una buena fuente de células para obtener constructos que reparen defectos en el cartílago. Los resultados presentados en este trabajo muestran diferencias a nivel de comportamiento celular, patrones de expresión y propiedades mecánicas entre los dos tipos celulares y las diferentes condiciones de cultivo (matrices y medios). Cabe destacar que, ambos tipos celulares se diferencian a un linaje condrogénico en medio de inducción y que los constructos presentan propiedades mecánicas compatibles con un sistema condrogénico. Además, se ha determinado que la presencia de moléculas de heparina en la matriz promueve la supervivencia de las células madre derivadas de tejido adiposo. En conjunto, las nuevas matrices bi-compuestas representan un material fácil de preparar y prometedor para promover la diferenciación condrogénica. Por último, parte de esta tesis se ha centrado en el desarrollo de una nueva matriz compuesta mediante la infiltración del péptido RAD16-I con células en microfibras de policaprolactona (PCL). Se ha demostrado que esta nueva combinación ofrece una estructura funcional y biomimética, dado que, proporciona soporte mecánico por las fibras PCL y a su vez, facilita la adhesión y el crecimiento celular debido al hidrogel RAD16-I. El cultivo in vitro de condrocitos humanos desdiferenciados demuestra que la nueva matriz compuesta promueve la supervivencia celular y el restablecimiento del linaje condrogénico. En general, las propiedades sinérgicas de la nueva matriz compuesta proporcionan una plataforma terapéutica ideal para ayudar a la reparación del cartílago.
Adult articular cartilage has a limited capacity for growth and regeneration and, after injury, treatments to restore tissue function remain poorly understood by the medical community. Therefore, there is currently great interest in finding practical and patient-friendly strategies for cartilage repair. Tissue engineering has emerged to restore damaged tissue by using new cellular or biomaterial-based therapeutic platforms. These approaches aim to produce cartilage-like structures that reproduce the complex mechanical and biological properties found in vivo. To this end, the use of biomimetic scaffolds that recreate structurally and functionally the native cell microenvironment has become of increasing interest in the field. Self-assembling peptides are attractive candidates to create artificial cellular niches, because their nanoscale network and biomechanical properties are similar to those of the natural extracellular matrix (ECM). In the present thesis, new composite synthetic biomaterials were developed for cartilage tissue engineering (CTE). They were based on the non-instructive self-assembling peptide RAD16-I and decorated with bioactive motifs, aiming to emulate the native cartilage ECM. We employed a simple mixture of the self-assembling peptide RAD16-I with either heparin, chondroitin sulfate or decorin molecules, taking advantage of the versatility of RAD16-I. The bi-component scaffolds presented good structural and chemical stability at a physiological pH and the capacity to bind and gradually release growth factors. Then, these composite scaffolds were characterized using two different in vitro assessments: re-differentiation of human articular chondrocytes (ACs) and induction of human adipose derived stem cells (ADSCs) to a chondrogenic commitment. Both native chondrocytes and adult mesenchymal stem cells (MSCs), either bone marrow or adipose-tissue derived, are considered good cell sources for CTE applications. The results presented in this work revealed differences in cellular behavior, expression patterns and mechanical properties between cell types and culture conditions (scaffolds and media). Remarkably, both cell types underwent into chondrogenic commitment under inductive media conditions and 3D constructs presented mechanical properties compatible to a system undergoing chondrogenesis. Interestingly, as a consequence of the presence of heparin moieties in the scaffold cell survival of ADSCs was enhanced. Altogether, the new bi-component scaffolds represent a promising "easy to prepare" material for promoting chondrogenic differentiation. Finally, part of this thesis was focus on developing a composite scaffold by infiltrating a three-dimensional (3D) woven microfiber poly (ε-caprolactone) (PCL) scaffold with the RAD16-I self-assembling peptide and cells. This new combination resulted into a multi-scale functional and biomimetic tissue-engineered structure providing mechanical support by PCL scaffold and facilitating cell attachment and growth by RAD16-I hydrogel. The in vitro 3D culture of dedifferentiated human ACs evidenced that the new composite supports cell survival and promotes the reestablishment of the chondrogenic lineage commitment. Overall, the synergistic properties of the novel composite scaffold may provide an ideal therapeutic platform to assist cartilage repair.
Puigmal, Domínguez Núria. "Skin-targeting platforms based on poly (β-amino ester)s for local immunotherapy". Doctoral thesis, Universitat Ramon Llull, 2021. http://hdl.handle.net/10803/672238.
Повний текст джерелаEl potencial curativo de las inmunoterapias para estimular o suprimir el sistema inmune ha revolucionado el paradigma bajo el que enfermedades como el cáncer o trastornos autoinmunes son tratados; no obstante, la implementación de dichas terapias se ha visto restringida por su toxicidad. Dada la capacidad de los nanomateriales para redirigir fármacos inmunomoduladores a tejidos dianas, las plataformas de liberación basadas en biomateriales podrían solventar las mayores necesidades del ámbito incluyendo, liberación específica a células diana, localizada —en vez de sistémica— y acumulación en tejidos diana para así aumentar su potencia y seguridad. Usando los poly(β-amino ester)s (PBAEs) como piedra angular, esta tesis propone desarrollar vectores dirigidos hacía la piel con el fin de modular el sistema inmune a nivel local en ámbitos tales como vacunación con ácidos nucleicos, inmunoterapia contra cáncer y terapia celular adoptiva. Se ha presentado una nueva librería de PBAEs modificados con oligopéptidos y manosa que poseen especificidad celular hacia células dendríticas, las principales instigadoras en la presentación de antígenos en la piel. El efecto sinérgico entre oligopéptidos y ligando ha permitido mejorar sustancialmente estos vehículos de transporte para vacunación. Además, los PBAEs se han podido formular como vectores alternativos a las nanopartículas y que no precisan solventes, así como integrarlos en dispositivos médicos como microagujas, ya sea en forma de partículas o de films, para transferir genes de manera no invasiva. Como terapia contra el cáncer, se han diseñado microagujas de hidrogel que permiten la liberación de un fármaco inmunoestimulante además de colectar líquido intersticial para monitorear la respuesta a la terapia in situ. Las microagujas cargadas con PBAEs pudieron reducir el tamaño de los tumores y modular el microambiente tumoral, la composición del cual correlaciona con la del líquido intersticial colectado con dicha plataforma. Finalmente, las microagujas fueron usadas para restablecer el equilibrio inmunológico en trasplantes de piel. Las microagujas pudieron reclutar células T reguladoras hacia el trasplante mediante la liberación de citoquinas quimioatrayentes además de informar sobre su proceso de migración hacia el trasplante. En conclusión, esta tesis demuestra el potencial de las plataformas transdérmicas basadas en PBAEs para inducir inmunomodulación local. Priorizando plataformas sin solventes, locales, y poco invasivas, se han desarrollado sistemas basados en PBAEs e integrados con microagujas para inmunoterapia.
The curative potential of immunotherapies to augment or suppress immune responses has shifted the paradigm for managing various diseases including cancer and autoimmune disorders, yet broad implementation has been curtailed by detrimental off-target toxicities. Given the ability of nanomaterials to direct immunomodulators to target tissues, nanomedicine-based delivery platforms formulated in carrier biomaterials could surmount the most pressing needs in the field being cell-specific targeting, local —rather than systemic— administration, and tissue accumulation to ultimately enhance the safety and potency of these therapeutic products. Using poly(β-amino ester)s (PBAEs) as foundational nanocarriers, this thesis proposes to engineer PBAE-based delivery platforms to target the immunologically rich milieu of the skin for local immunomodulation in the contexts of nucleic acid vaccination, cancer immunotherapy and adoptive T cell therapy. First, a novel library of oligopeptide- and mannose-modified PBAEs is presented for refined targeting of dendritic cells (DCs) as primary orchestrators of antigen presentation in the skin. The synergistic potential of oligopeptide and ligand decoration to target dermal DC subsets has been demonstrated as a powerful tool to upgrade delivery vectors for gene vaccination. Nanoparticle- and solvent-free delivery of nucleic acids using PBAEs formulated as polyelectrolyte films (PEMs) has also been confirmed. PBAEs can be successfully integrated in transdermal devices such as microneedles, either as PEMs or as polyplexes, to mediate minimally-invasive gene transfer. Moving to cancer immunotherapy, a hydrogel-based MN platform is presented for delivery of an immunostimulatory drug and retrieval of interstitial skin fluid (ISF) for in situ immune surveillance of the response to therapy. It has been proven that PBAE-loaded MNs suppress tumor growth and modulate the immune signature of the tumor microenvironment, which appears to correlate with that from MN-sampled ISF. Finally, hydrogel MNs are proposed for restoring immune homeostasis in transplanted skin allografts. Recruitment of adoptively-transferred regulatory T cells into the allografts has been achieved by delivering chemoattractant chemokines with the MNs while also monitoring the Treg homing process via ISF sampling, confirming the potential of MNs as a mode of tissue surveillance. In conclusion, this thesis demonstrates the potential of transdermal platforms derived from PBAEs for local immunomodulation. Shifting from hypodermic administration to solvent-free, local, and minimally-invasive approaches, PBAE-based systems have been engineered with microneedles for immunotherapy delivery.
Weisman, Jeffery A. "Nanotechnology and additive manufacturing platforms for clinical medicine| An investigation of 3D printing bioactive constructs and halloysite nanotubes for drug delivery and biomaterials." Thesis, Louisiana Tech University, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=3662483.
Повний текст джерелаPersonalized medicine requires the development of new technologies for controlled or targeted drug delivery. Three-dimensional (3D) printing and additive manufacturing techniques can be used to generate customized constructs for bioactive compound delivery. Nanotechnology in the form of nanoparticles, used as a stand-alone construct or for material enhancements, can significantly improve established biomaterials such as PMMA based bone cements or enable new technology to have enhanced capabilities. Combinations of the technologies can be used in such applications as infectious disease treatments, chemotherapeutic targeted drug delivery or targeted delivery of nearly any bioactive compound.
Chemotherapeutic or antibiotic enhanced 3D printing filaments were invented and designed to allow for the fabrication of antibiotic beads, drug eluting catheters, drains, stents, screws or any bioactive construct. Halloysite nanotubes (HNTs) were investigated as a modular platform and solely or in combinations were coated in metals including: iron for magnetic targeted delivery including hyperthermia, gold for laser targeted hyperthermia or barium as a contrast agent for visualization. The particles were test loaded with antibiotics or chemotherapeutics as well as coated in biocompatible coatings containing lipids or layered polyelectrolytes. Nanoparticles were added to 3D printing filaments or bone cements to test increases in strength, contrast or pore size.
3D print filaments and bioactive constructs that eluted gentamicin sulfate were tested using clinical microbiology lab standards and were shown to inhibit bacterial growth. 3D print filaments that eluted methotrexate were shown to inhibit proliferation of osteosarcoma cells and also provided a means for sustained drug release. Halloysite was successfully shown as a modular platform that could be highly customized for patient specific uses. Single coatings or combinations of magnetically susceptible iron coatings, gold coatings, drug loading of multiple bioactive compounds and biocompatible coatings were also developed. Bone cements with barium-coated particles were shown to have enhanced contrast.
The first ever ability to create and use bioactive 3D printing filaments on consumer printers was realized and HNTs were developed as proof of principle for multifunctional and real time customizable nanoparticle platforms. Nanoparticles as additives showed ways to modify established biomaterials or 3D printing filaments with enhanced features and properties.
Wilson, David Scott. "Rational design and synthesis of drug delivery platforms for treating diseases associated with intestinal inflammation." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/45803.
Повний текст джерелаAleksanian, Samuel. "Study of stimuli-responsive degradation using a disulfide platform in different polymeric biomaterials." Thesis, 2014. http://spectrum.library.concordia.ca/978343/1/Aleksanian_MSc_S2014.pdf.
Повний текст джерелаChiang, Min-Yu, and 江敏瑜. "Cross-scale Manipulation of Biomaterials and Bioparticles via an Electro-Microfluidic Platform for Tissue Engineering and Drug Delivery System." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/44fvhr.
Повний текст джерела(6863093), Li-Kai Lin. "Pollutant and Inflammation marker detection using low-cost and portable microfluidic platform, and flexible microelectronic platform." Thesis, 2019.
Знайти повний текст джерелаOliveira, Mariana B. "High-throughput combinatorial analysis of three-dimensional biomaterials behavior using superhydrophobic patterned platforms." Doctoral thesis, 2014. http://hdl.handle.net/1822/35423.
Повний текст джерелаOne of the still unaccomplished struggles in the maintenance of population life quality is related to the current need for effective biomaterials. The optimization of tissue engineering (TE) strategies by combining biomaterials, cells and soluble factors usually relies on time-consuming iterative processes. Rapid and low-cost high-throughput testing is needed to accelerate the discovery of ideal TE systems. The main hypothesis of this thesis was that superhydrophobic surfaces patterned with wettable spots were amenable to be used as platforms for high-throughput complete testing of 3D biomaterials. Indeed, such platforms allowed taking advantage of wettability contrast to pattern biomaterials with precise shape and pre-determined height, by controlling the volume dispensed in each spot. The superhydrophobic chips were first used to pattern ionic alginate-based cell-laden hydrogels in the wettable spots. The chemical composition of each biomaterial was evaluated by FTIR and the cellular response of fibroblast and osteoblast-like cell lines was assessed on-chip by image-based analysis. Image-based non-destructive assessment was validated by comparison with conventional biochemical colorimetric tests. Superhydrophobic chips were later used to produce and study miniaturized porous scaffolds. The size of the spots in the milimetric range allowed having porous biomaterial structures with significant pore size for cell migration and growth. Chitosan/alginate scaffolds were processed by polyelectrolyte complexation and freeze-drying, followed by fibronectin adsorption. Cell number and viability were assessed using two cell lines. DMA and μCT techniques were adapted to be used on-chip, in dry conditions, to characterize the scaffolds mechanically and morphologically. The on-chip DMA method was upgraded to be performed under physiological-like conditions using chitosan/bioactive glass nanoparticles hydrogels. The selective adhesion and proliferation of a pre-osteoblast cell line allowed hit-spotting favorable in vitro biomaterial formulations. After demonstrating their adequacy for in vitro cell-3D biomaterials interactions assessment, superhydrophobic chips containing 36 biomaterials were implanted in single Wistar rats, allowing the high-throughput in vivo study of inflammatory response caused by biomaterials. An important aspect in TE is the dependency of tissue regeneration on prolonged action of bioactive agents. Superhydrophobic chips were imprinted with ring-shaped spots with concentric superhydrophobic regions where polymeric protein-loaded spheres were deposited. The acquisition of sequential images of each spot over time using microscopy methods allowed monitoring protein release. Finally, cell suspension droplets were fixed in the wettable regions of the chips to produce cell spheroids/microtissues for drug screening by the hanging drop methodology in a robot-free automated manner. In conclusion, the superhydrophobic platforms patterned with wettable spots used in this thesis proved to be compatible with a complete study of 3D biomaterials-cells interactions, comprising a wide set of factors as biomaterials characterization, in vitro testing, innovative in vivo assessment and bioactive molecules-related tests.
Um dos desafios correntes para a manutenção da qualidade de vida das populações prende-se com a falta de biomateriais eficazes. A otimização de estratégias em engenharia de tecidos (ET) através da combinação de biomateriais, células e fatores solúveis requer, em geral, processos iterativos. Testes expeditos e de baixo custo são necessários para acelerar a descoberta de sistemas de ET ideiais. A hipótese desta tese consiste na possibilidade do uso de superfícies superhidrofóbicas padronizadas com regiões hidrofílicas como plataformas para a análise expedita e completa de biomateriais 3D. As plataformas permitiram usar o contraste de molhabilidade para depositar biomateriais com forma e altura precisas, controlando o volume colocado em cada região hidrofílica. As plataformas foram usadas para dispensar hidrogéis de alginato com células encapsuladas nas regiões molháveis. A composição química de cada biomaterial foi avaliada por FTIR, e a resposta celular foi testada através de análises de imagem, efetuadas no chip. As análises não destrutivas baseadas em imagem foram validadas por comparação com teses bioquímicos colorimétricos. As plataformas foram depois adaptadas para a produção e caracterização de estruturas porosas miniaturizadas. A dimensão milimétrica das regiões molháveis permitiu processar estruturas com poros de tamanho representativo para migração e crescimento celulares. As estruturas porosas de quitosano/alginato foram preparadas por complexação de polielectrólitos/liofilização, seguidas de adsorção de fibronectina. O número e viabilidade celulares foram estudados. As técnicas de DMA e μCT foram adaptadas para uso nos chips, em condições secas, para caracterização mecânica e morfológica. O método de DMA realizado no chip foi melhorado de forma a permitir uma análise em condições semelhantes às fisiológicas, usando hidrogéis de quitosano/nanopartículas de vidro bioactivo. A adesão selectiva e proliferação de uma linha celular de pré-osteoblastos permitiu selecionar as formulações de biomateriais mais favoráveis. Após demonstrar a sua adequabilidade para testes in vitro, implantaram-se plataformas superhidrofóbicas contendo 36 biomateriais em ratos Wistar, mostrando a sua utilidade para testes expeditos executados in vivo,para estudo da resposta inflamatória causada por biomateriais. Outro aspeto importante em ET é a dependência da regeneração de tecidos na ação prolongada de agentes bioactivos. Regiões molháveis com uma região superhidrofóbica concêntrica foram usadas para depositar esferas poliméricas contendo proteína. A aquisição sequencial de imagens por microscopia permitiu monitorizar a libertação de proteína. Finalmente, fixaram-se gotas de suspensão celular nas regiões hidrofílicas para produzir esferóides celulares para a análise de fármacos pelo método da gota suspensa. Em conclusão, as superficies superhidrofóbicas padronizadas com regiões molháveis usadas nesta tese provaram ser compatíveis com um estudo completo de interações entre células e biomateriais 3D, compreendendo um vasto conjunto de fatores, como caracterização dos biomateriais, testes in vitro e in vivo, e testes relacionados com moléculas bioactivas.
Fundação para a Ciência e a Tecnologia (FCT) for the PhD grant SFRH/BD/71396/2010. FEDER through the Competitive Factors Operation Program – COMPETE and by National funds through FCT in the scope of the project PTDC/CTM-BIO/1814/2012.
Hu, Mufeng. "Biomaterial-based Cell Culture Platform for Podocyte Phenotype Study with Shape and Substrate Rigidity Control." Thesis, 2016. https://doi.org/10.7916/D8930TFM.
Повний текст джерелаPapera, Valente Karolina. "The applications of microfluidic platforms for cancer research: the tumor microenvironment and drug delivery systems." Thesis, 2020. http://hdl.handle.net/1828/12039.
Повний текст джерелаGraduate
2021-07-20
Amador, Gonçalo Alexandre Camões de Bastos. "Optimization of the synthesis and manufacturing process of platforms for 3D culture produced from blood plasma proteins." Master's thesis, 2021. http://hdl.handle.net/10773/33004.
Повний текст джерелаA Metatissue® é uma empresa spin-off em ascensão, dedicada ao desenvolvimento de biomateriais inovadores para cultura celular, à base de proteínas humanas, quimicamente modificadas. Atualmente, a cultura de células de mamífero é um aspeto fundamental na maioria da investigação biomédica e no processo de descoberta/desenvolvimento de fármacos. O formato padrão bidimensional de cultura, extensivamente utilizado para validar mecanismos de ação, está desatualizado, devido a ser incapaz de imitar precisamente o microambiente natural in vivo. Os avanços na biotecnologia e engenharia de materiais levaram ao desenvolvimento de inúmeros modelos tridimensionais (3D) de cultura de células, comprovados em simular melhor o microambiente dos tecidos naturais, ao imitar a matriz extracelular nativa na sua bio funcionalidade e propriedades estruturais. Hidrogéis compostos por materiais com diferentes origens são a plataforma que lidera o mercado em aplicações de cultura celular e engenharia de tecidos. Porém, ainda se está por descobrir uma solução perfeita para ser alternativa às plataformas padrão ideais atuais. O produto de lisado de plaquetas de origem humana da Metatissue® representa uma solução sem componentes de espécies estranhas, personalizável, versátil e multifuncional, com propriedades mecânicas adaptáveis, sendo fácil de usar e de favorável custo-benefício. O enquadramento legal é também considerado e um certificado ISO 9001 está a ser implementado, de forma a garantir a qualidade e consistência do produto. Com uma clara estratégia de negócio e proposta de valor, a Metatissue® pretende ser um líder no mercado da cultura de células 3D.
Mestrado em Biotecnologia