Cell behavior is influenced to a large extent by the surrounding microenvironment. Therefore, in the body, the cellular microenvironment is highly controlled with cells growing within well-defined tissue architectures. However, traditional culture techniques allow only for the random placement of cells onto culture dishes and biomaterials. Cell micropatterning strategies aim to control the spatial localization of cells on their underlying material and in relation to other cells. Developing such strategies provides us with tools necessary to eventually fabricate the highly-controlled microenvironments found in multicellular organisms. Employing natural extracellular matrix (ECM) materials in patterning techniques can increase biocompatibility. In the future, with such technologies, we can hope to conduct novel studies in cell biology or optimize cell behavior and function towards the development of new cell-based devices and tissue engineering constructs. Herein, a novel cell patterning platform was developed on a hydrogel base of crosslinked hyaluronic acid (HA). Hydrogels are often employed in tissue engineering due to their ability to mimic the physicochemical properties of natural tissues. HA is a polymer present in all connective tissues. Cell-adhesive regions on the hydrogel were created using the RGDS peptide sequence, found within the cell-adhesive ECM protein, fibronectin. The peptide was bound to a 2-nitrobenzyl “caging group” via a photolabile bond to render the peptide light-responsive. Finally, this “caged” peptide was covalently bound to the hydrogel to form a novel HA hydrogel with a cell non-adhesive surface which could be activated with near-UV light to become adhesive. In this way, we successfully formed chemically patterned cell-adhesive regions on a HA hydrogel using light as a stimulus to form controlled cell patterns. While the majority of cell patterning strategies to date are limited to patterning one cell population and cannot be changed with time, our strategy was novel in using small, adhesive, caged peptides combined with multiple, aligned light exposure steps to allow for dynamic chemical cell patterning on a hydrogel. Multiple cell populations, even held apart from one another, were successfully patterned on the same hydrogel. Furthermore, cell patterns were deliberately modified with time to direct cell growth and/or migration on the hydrogel base.

Orientador: Marcos Akira d'Ávila / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecânica / Made available in DSpace on 2018-08-22T03:44:39Z (GMT). No. of bitstreams: 1 Salles_TaisHelenaCosta_M.pdf: 2536678 bytes, checksum: 358cfaf694adc91a715f58aabead529d (MD5) Previous issue date: 2013 / Resumo: A eletrofiação é reconhecida como uma técnica eficiente para a fabricação de microfibras e nanofibras de polímero, devido à sua versatilidade e potencial para aplicações em diversos campos. As aplicações notáveis incluem engenharia tecidual, biossensores, filtração, curativos, liberação controlada de fármacos e imobilização de enzimas. As nanofibras são geradas através da aplicação de um campo elétrico em uma solução polimérica. As fibras fiadas por este processo oferecem várias vantagens, como elevada área de superfície em relação ao volume, alta porosidade e a capacidade de manipular a composição de nanofibras, a fim de obter as propriedades e funções desejadas. Neste trabalho, a eletrofiação de blendas de gelatina com polivinilpirrolidona (PVP) para a fabricação de nanofibras foi investigada. Os polímeros foram fiados a partir de soluções contendo diversas concentrações de água e ácido acético. As soluções foram fiadas a uma tensão positiva de 29,0-29,2 kV, uma distância da ponta da agulha ao coletor de 10 cm, e uma vazão de 1 mL / h. Todas as soluções foram avaliadas quanto ao pH, condutividade elétrica, tensão superficial e viscosidade. Foram investigados os efeitos da concentração de ácido acético nas propriedades das soluções que por sua vez, influenciaram no processo de obtenção de fibras por eletrofiação. Foi observado que há uma correlação entre a concentração de ácido acético e a formação de fibras desse sistema, assim como a influência no diâmetro final das fibras. No presente estudo, uma matriz de nanofibras uniformes com diâmetro aproximado de 519, 355 e 154 nm foram produzidas via eletrofiação. A morfologia das membranas foi avaliada por Microscopia Eletrônica de Varredura (MEV). Foi realizada a análise térmica termogravimétrica (TGA) e avaliação de citotoxicidade, visando futuras aplicações em engenharia tecidual / Abstract: The electrospinning is recognized as an efficient technique for the fabrication of polymeric microfibers and nanofibers due to its versatility and potential for applications in many fields. Notable applications include tissue engineering, biosensors, filtration, wound dressings, controlled drug release and enzyme immobilization. The nanofibers are generated by applying an electric field in a polymer solution. The fibers spun by this process offers several advantages such as high surface area relative to volume, high porosity and the ability to manipulate the composition of nanofibers in order to obtain the desired properties and functions desired. In this work, the electrospinning blends of gelatin with polyvinylpyrrolidone (PVP) to fabrication nanofibers were investigated. The polymers were electrospun from solutions containing various concentrations of water and acetic acid. The solutions were electrospun at a positive voltage of 29.0 to 29.2 kV, a distance from the needle tip to the collector of 10 cm and a flow rate of 1 mL / h. All solutions were analyzed as your pH, electrical conductivity, surface tension and viscosity. We investigated the effects of acetic acid concentration on the properties of the solutions, on the other hand, influenced the process of obtaining fibers by electrospinning. It was observed that there was a correlation between the concentration of acetic acid and formation of fibers of that system, as well the influence on the final diameter of the fibers. In the present study, a matrix of nanofibers uniform with diameters of approximately 519, 355 and 154 nm had been produced by electrospinning. The morphology of the membranes was evaluated by Scanning Electron Microscopy (SEM). We made thermal analysis (TGA) and assessment of cytotoxicity, aiming future applications in tissue engineering / Mestrado / Materiais e Processos de Fabricação / Mestra em Engenharia Mecânica

Orientador: Cecília Amélia de Carvalho Zavaglia / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecânica / Made available in DSpace on 2018-08-22T11:32:15Z (GMT). No. of bitstreams: 1 Rigon_GuaciradosReis_M.pdf: 2217729 bytes, checksum: 84fa9de78a4fef6ee35a155f229d49bf (MD5) Previous issue date: 2013 / Resumo: Nos últimos anos, os polímeros biorreabsorvíveis ganharam importância na área médica e odontológica, sendo utilizados em um amplo número de aplicações no corpo humano, entre elas matrizes porosas tridimensionais como suporte no crescimento de células na área da engenharia tecidual. Com o objetivo de aperfeiçoar o processo de formação de matrizes como suporte na engenharia tecidual, estudou-se a utilização do compósito formado pelo copolímero PLDLA e um tipo de nanohidroxiapatita (HA) desenvolvida no laboratório de biomateriais da FEM/UNICAMP, na formação de matrizes através do processo de rotofiação. Os compósitos foram preparados utilizando-se 5% e 10% de HA em relação ao copolímero disperso em solvente clorofórmio na presença do surfactante ácido oléico. O processo de rotofiação é um processo simples, que forma uma matriz utilizando alta velocidade de rotação durante o jateamento da solução polimérica através de um orifício central sendo desnecessária, neste caso, a utilização de campo elétrico de alta voltagem, como ocorre para o processo de eletrofiação. As matrizes foram caracterizadas pelas técnicas de microscopia eletrônica de varredura (MEV), análise termogravimétrica (TGA), calorimetria diferencial de varredura (DSC), e espectroscopia de infravermelho com transformada de Fourier (FTIR). Os resultados obtidos pela microscopia eletrônica de varredura (MEV) mostraram que houve formação de uma matriz porosa e, portanto, o compósito pode ter uma aplicação promissora como suporte para cultura de células / Abstract: In the last years, bioresorbable polymers have been receiving more importance in the medical and dentistry areas, and they have been used in a large number of applications on the human body, such as tissue engineering scaffolds. This work studies the use of a composite of poly (L-co-DL-lactic acid) (PLDLA) and nanoparticles of hydroxyapatite developed at FEM/ UNICAMP to produce membranes by Rotary Jet Spinning process. Composites were prepared with 5% and 10% of HA in a clorophormium polymer solution. Rotary Jet spinning is a simple process to produce 3D structures that does not require a high-voltage electric field, like electrospinning. The results were characterized by the following methods: scanning electron microscopy (SEM), thermogravimetry analysis (TGA), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). The results from SEM showed that a porous membrane was obtained which could be used as scaffold in tissue engineering / Mestrado / Materiais e Processos de Fabricação / Mestra em Engenharia Mecânica

Orientador: Eliana Aparecida de Rezende Duek / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecânica / Made available in DSpace on 2018-08-18T15:18:31Z (GMT). No. of bitstreams: 1 Mas_BrunaAntunes_M.pdf: 4024365 bytes, checksum: 4922b258d265a9070576f02830e45d40 (MD5) Previous issue date: 2011 / Resumo: Polímeros biorreabsorvíveis são amplamente empregados como arcabouços na engenharia tecidual. No entanto, devido à natureza hidrofóbica, técnicas de modificação de superfície embasadas na enxertia de grupos químicos funcionais e imobilização de moléculas bioativas são desenvolvidas no intuito de promover a biofuncionalização da superfície desses polímeros, ocasionando uma melhora significativa da interação célula /polímero. Este estudo teve por objetivo desenvolver e caracterizar uma superfície biomimética em arcabouços do copolímero poli (L-co-D,L ácido lático)- PLDLA, através da enxertia de grupos (-COOH) e imobilização de colágeno tipo I. Os arcabouços de PLDLA 70/30 foram obtidos pela técnica de lixiviação de porógenos e submetidos ao método de fotopolimerização oxidativa da superfície do material, seguido da copolimerização enxertiva do ácido acrílico (PLDLA-AAc) e imobilização do colágeno tipo I (PLDLA-Col). A superfície das amostras foi caracterizada por Microscopia Eletrônica de Varredura (MEV), Microscopia de Força Atômica (MFA), Espectroscopia de Reflectância Total Atenuada (FTIR-ATR), Espectroscopia de Fotoelétrons Excitados por raios-X (XPS) e ângulo de contato. As imagens da MFA e fotomicrografias da MEV demonstraram a formação de poros e rugosidade na superfície dos arcabouços de PLDLA-AAc e, deposição do colágeno com formação de uma estrutura fibrilar em pontos inespecíficos da superfície dos arcabouços do PLDLA-Col, resultando no aumento da rugosidade superficial de 149.5nm (PLDLA puro) para 295nm (PLDLA-Col). Os espectros de FTIR-ATR do PLDLA, PLDLA-AAc e PLDLA-Col confirmaram a presença dos mesmos picos de absorção para todos os tratamentos e, a presença dos picos em 1662 e 1559cm-1, típicos de amida I e II nas amostras de PLDLA-Col. A citocompatibilidade dos arcabouços foi avaliada através do cultivo de células osteoblásticas primárias submetidas aos ensaios de citotoxicidade e adesão celular inicial, síntese de colágeno e observação da morfologia celular, obtidas pela MEV. Os resultados obtidos mostraram que a superfície biomimética dos arcabouços de PLDLA-Col melhora, significantemente, a taxa de adesão e proliferação celular bem como estimula a síntese de colágeno (p<0,01). Estes resultados são indicativos de que o método de modificação de superfície utilizado no presente estudo pode ser usado no desenvolvimento de arcabouços bioativos e biomiméticos com potencial aplicação na engenharia tecidual / Abstract: Bioreabsorbable polymers are widely used as scaffolds in tissue engineering. However, due to their hydrophobic nature, modification techniques based on graft of chemical functional groups and immobilization of bioactive molecules have been developed, in order to promote biofuncionalization of material surface, causing better interaction between cell / polymer. This study aimed at developing and characterizing a biomimetic surface on scaffolds of the copolymer poly (L-co-D, L lactic acid) (PLDLA 70/30), by grafting of chemical functional groups and immobilized with collagen type I. The scaffolds were obtained by porogen leaching, and submitted to photo-oxidation method of the material surface followed by grafting polymer polymerization of the acrylic acid solution (PLDLA-Acc) and immobilization of the type I collagen (PLDLA-Col). The sample surfaces were characterized by Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM) , Attenuated Total Reflectance Infrared Spectroscopy (ATR-FTIR), X-ray Photoelectron Spectroscopy (XPS) and contact angle. AFM images and SEM electromicrographs exhibited porous formation and roughness on the PLDLA-AAc surfaces and collagen deposition with net-like fibrillar structure in non-specific areas of the PLDLA-Col scaffolds, resulting an increase in surface roughness from 149.5 nm (PLDLA pure) to 295nm (PLDLA-Col). ATR-FTIR spectra of PLDLA, PLDLA-AAc and PLDLA-Col exhibited the same absorption peaks for all samples, as well as peaks of 1662 and 1559cm-1 , typical of amide I and II in PLDLA-Col samples. Scaffolds cytocompatibilty was evaluated by osteoblastic-like cell culture, submitted to cytotoxicity and initial cell adhesion assays, collagen synthesis and observation of cell morphology obtained by SEM. The result showed that biomimetic surface of PLDLA-Col scaffolds significantly improves adhesion and cell proliferation rates, as well as stimulates collagen synthesis (p<0,01). These results indicate that the surface modification method in the present study can be used in the development of bioactive and biomimetic scaffold with potential application in tissue engineering / Mestrado / Materiais e Processos de Fabricação / Mestre em Engenharia Mecânica

Orientador: Cecília Amélia de Carvalho Zavaglia / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecânica / Made available in DSpace on 2018-08-26T18:15:17Z (GMT). No. of bitstreams: 1 Pinto_StellaAparecidadeAndrade_M.pdf: 4585027 bytes, checksum: 9494a15673ef4d78415628bf5329a159 (MD5) Previous issue date: 2015 / Resumo: A engenharia de tecidos é um conceito no tratamento de doenças e ferimentos. Tal área engloba o uso de tecnologias da biologia molecular e celular, combinando as vantagens da ciência dos materiais e processamento com a finalidade de produzir a regeneração de tecidos em situações onde a evolução tenha determinado que as células não tenham a capacidade regenerativa ao longo do tempo. A essência da engenharia de tecidos é que todas as células sejam viáveis e a capacidade de iniciação, sustentação e processo de regeneração estão diretamente ligados através de fatores de crescimento ou genes de modo que elas produzam um novo tecido de variedade requerida. Isto pode ser alcançado com a ajuda de um scaffold (matriz de forma geométrica guiada) ou uma arquitetura de um novo tecido, permitindo personalizar um lugar básico sobre um ferimento em um paciente isolado ou em escala industrial maior, nos quais o tecido resultante pode ser reimplantado sobre o paciente. Este trabalho de pesquisa científica teve como objetivo desenvolver malhas poliméricas de PCL com 'beta'-TCP obtidas através do processo de rotofiação. Para tal foram desenvolvidas 3 amostras para estudo: AMOSTRA 1 - malha rotofiada de PCL (controle), AMOSTRA 2 - malha rotofiada de PCL com 'beta'-TCP 5% e AMOSTRA 3 - malha rotofiada de PCL com 'beta'-TCP 10%, sendo que as referidas amostras foram também imersas em solução de Kokubo (fluído corpóreo simulado). As características físico-químicas e estruturais da cerâmica 'beta'-TCP foram avaliadas através de ensaios de difração de RX (DRX), granulometria e microscopia eletrônica de varredura (MEV), enquanto as malhas compósitas obtidas neste estudo foram caracterizadas por microscopia óptica (MO) e MEV. Como resultados tivemos a obtenção de malhas poliméricas com biocerâmica 'beta'-TCP que caracterizam-se como materiais promissores para enxertia visando ao reparo ósseo, visto que demonstraram sua bioatividade pela precipitação de apatita em sua superfície após imersão em fluído corpóreo simulado, servindo de base científica para estudos futuros que viabilizem a reconstrução de defeitos ósseos em seres humanos / Abstract: Tissue engineering is a concept in injuries and diseases treatment. It uses biomolecular and celular technologies, combining the materials sciences advantages aiming tissue regeneration in situations that the human evolution had determinated that the cells can't regenerate over time. The essence of tissue engineering is that all cells are viable and it's ability of initiation, sustenance and regeneration process are directly linked through growth factors or genes to produce new tissue of the required variety. This can be achieved with an scaffold or matrix geometrically guided or an architecture of a new personalized tissue in a pacient or a bioreactor in industrial scale, that the new tissue can be reimplanted in the patient. The aim of this study was the development of polymer based scaffolds of PCL with 'beta'-TCP obtained by jet-spinning. Three samples were developed: SAMPLE 1 - scaffold of PCL (control), SAMPLE 2 - scaffold of PCL with 'beta'-TCP 5% and SAMPLE 3 - scaffold of PCL with 'beta'-TCP 10%, wherein the all of them were immersed in Kokubo's solution (simulated body fluid). The physico-chemical and structural characteristics of the ceramic 'beta'-TCP were evaluated by testing x-ray diffraction (DRX), granulometry and scanning electron microscopy (MEV) and the scaffolds of this study were characterized by optical microscopy (MO) and MEV. The results includes polymer based scaffolds with bioceramic 'beta'-TCP that can be considered promising biomaterials to be used as grafting materials focusing in bone healing and have demonstrated their bioactivity by the apatite precipitation in their surface after immersion in simulated body fluid, acting as scientific basis for future studies in reconstruction of osseous defects in humans / Mestrado / Materiais e Processos de Fabricação / Mestra em Engenharia Mecânica

Orientador: Cecilia Amélia de Carvalho Zavaglia / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecânica / Made available in DSpace on 2018-08-26T21:01:51Z (GMT). No. of bitstreams: 1 Santana_Marcio_M.pdf: 2241450 bytes, checksum: 6a2d73eb696ed813c03446c21f1f74e3 (MD5) Previous issue date: 2015 / Resumo: Neste trabalho foram pesquisados as cerâmicas óxido de alumínio e óxido de zircônio na forma de compósito para aplicação em próteses odontológicas mais especificamente como pilar de fixação (Abutment). A alumina, em sua fase alfa, é uma cerâmica que apresenta excelentes propriedades mecânicas e é biocompatível, porém tem como restrição a sua baixa tenacidade à fratura o que a impede de ser utilizada com mais regularidade em aplicações estruturais. O óxido de zircônio também possui excelentes propriedades mecânicas, maior tenacidade à fratura das cerâmicas avançadas e é biocompatível, entretanto apresenta uma restrição à sua aplicação em meios fisiológicos abaixo de 300º C quando o material se degrada, inicia um processo de propagação de trinca e se rompe depois de um determinado período. O compósito alumina-zircônia apresenta melhores propriedades mecânicas e maior tenacidade à fratura para aplicação estrutural, portanto melhores condições de ser aplicado em uma prótese dentária. Foram estudadas e caracterizadas 3 composições (30, 40, 50% em vol. de zircônia na matriz de alumina) deste compósito sub-microestruturado. Foram realizados ensaios para avaliar as propriedades de cada composição e sua morfologia no intuito de analisar qual a composição é a mais adequada para a construção de um pilar de fixação. Os resultados apontados indicam uma melhora nas propriedades mecânicas do compósito com 30% de zircônia quando comparado à alumina e a zircônia puras. Os resultados para o compósito de 30% de zircônia de dureza foi de 14,73 GPa, de tenacidade a fratura foi 8,64 MPa.m1/2 e de compressão diametral foi de 252,41 MPa / Abstract: The present work was researched the alumina oxide and zirconia oxide ceramic in the form of composite for application in dental prostheses specifically abutment. Alumina in its Alpha stage is a ceramic that presents excellent mechanical properties and is biocompatible, however your low fracture toughness has the restriction which prevents it from being used more regularly in structural applications. The zirconia oxide also has excellent mechanical properties, is biocompatible and has higher fracture toughness than Alumina, although presents hidrothermal degradation in physiological environment below 300° C that causes cracks and breakage after a period of time. The alumina-zirconia composite have better mechanical properties and fracture toughness higher for structural application, so better able to apply in a dental prosthesis. Were studied and characterized three compositions (30, 40 50% vol. Zirconia Alumina in the matrix) of this sub-microstructured composite through tests to evaluate the properties, exam in SEM Microscopy of each composition and compare the final results to selected a best composition to construction of a dental abutment. The results presented so far indicates an improvement in the mechanical properties of the composite with 30% of zirconia when compared to other compositions and pure alumina and zirconia. The results for the 30% zirconia composite for micro-hardness was 14,73 GPa, fracture toughness was 8,64 MPa.m1/2 and testing for diametral compression for 252,41 MPa / Mestrado / Materiais e Processos de Fabricação / Mestre em Engenharia Mecânica

Metais são bastante usados como materiais implantáveis, principalmente para dispositivos feitos na área de ortopedia. Há uma constante relação dos processos de corrosão nesse biomateriais com a agressividade do meio fisiológico. Usando quatro tipo de metais e ligas metálicas – titânio puro, liga de titânio, aço inoxidável de baixo carbono e liga de cobalto – o processo de corrosão foi estudado. Além disso, o desempenho desses materiais revestidos com nitreto de titânio foi avaliado. Dois processos de revestimento por PVD – evaporação e magnetron sputtering – foram executados, verificando a eficiência desses materiais em meio fisiológico - O melhor comportamento se deu para o revestimento obtido por evaporação. O mecanismo de corrosão predominante para as amostras foi indicado. / Metals are very much used as implantable materials mainly for the construction of devices orthopaedic area. There is a constant concern about the corrosion process in those metallic biomaterials due to the aggressiveness of the physiological environment. By using four types of metals and metallic alloys – pure titanium, titanium alloy, low carbon stainless steel and cobalt-chromium alloy – the corrosion process in physiologic environment has been studied. Also, the performance of such materials coated with titanium nitrate was evaluated. Two PVD coating methods – evaporation and magnetron sputtering – were performed, and the efficiency of those materials in physiologic medium was verified. The best behaviour was found by the evaporation coating method. The predominant corrosion mechanism for coated samples was suggested.

In Canada, one in five people suffers from arthritis, of which the most common type is osteoarthritis (OA). OA is a group of joint diseases that cause pain and loss of range of motion and for which there is currently no cure. OA can be caused by numerous factors such as aging, genetics, environmental elements, and abnormal joint biomechanics (e.g., injury, obesity). These diseases are degenerative and lead to the progressive breakdown of joint cartilage, as well as changes in the underlying bone and other tissues of the joint over a period of years to decades. Articular cartilage incorporates a single type of resident cells, termed chondrocyte cells. These cells are entrapped within a dense extracellular matrix that limits their ability to proliferate and migrate to a site of injury, while the absence of blood vessels in the cartilage, amongst other factors, hinders the ability of progenitor cells to reach the site of injury, contributing to a limited capacity for intrinsic regeneration of the damaged tissue following an injury. As such, efforts to develop tissue engineering strategies that combine a biomaterial with bioactive signals to induce cells with the chondrogenic potential to regenerate tissue have been pursued actively. In this thesis, we investigate the potential of one such cartilage tissue engineering approach, whereby chondrocytes are encapsulated with alginate hydrogels incorporating inorganic polyphosphate (polyP), a promising chondrogenic signal. The driving hypothesis of the work was that polyanionic polyP would crosslink within the alginate hydrogel meshwork by ionic bonds with the multivalent cations used to form the hydrogel. Initial efforts focussed on optimizing the sterile chondrocyte encapsulation protocol for alginate beads, chondrocyte culture conditions to reduce proliferation – a response that is associated with dedifferentiation and a pathological state – and protocol for the incorporation of polyP in alginate bead when using calcium as a cationic crosslinker. We observed that polyP release from the calcium-alginate bead exhibited an important burst release to nearly 80% of the initial polyP loading within 24 hours of incubation in the culture medium. Increasing the alginate concentration led to approximately a 2.5-fold increase in polyP retention following the burst release. Subsequent incubation showed a more controlled release for at least 1 week. Efforts to reduce hydrogel swelling and increase its stability by substituting Ca2+ by Sr2+ as a crosslinker did not reduce the release rate during the burst release phase, nor did it increase the polyP retention following this initial stage. Other divalent cations including Mg2+ and Co2+, and pre-loading the polyP-alginate solution with a small concentration of Ca2+ did not impact the release profile either. Chondrocytes encapsulated in calcium- and strontium-alginate beads showed decreased DNA content and increased sulfated glycosaminoglycan accumulation at 1 week when polyP was incorporated in the beads compared to controls without polyP; however, this effect was lost at longer time points. These results suggest that this new material may find applications as a vehicle for the short-term delivery of polyP in joints and other tissues. Further efforts to improve the polyP release profile from alginate beads lead to promising results with the use of polyethylenimine (PEI) as a cationic tethering molecule between polyP and alginate. This thesis aims to generate novel biomaterials that can be used to stimulate cartilage tissue regeneration and to eventually develop a treatment strategy for OA. The work presented here will serve as a basis for continued efforts to ensure the prolonged retention of exogenous polyP into the joint.

La perte de l’organe dentaire entraine une perte de substance de l’os alvéolaire. Les techniques mises en place pour reconstruire l’os alvéolaire préalablement à la pose d’implant utilisent des membranes (seules ou associées à une greffe osseuse), faisant d’une part office de barrière vis-à-vis des tissus mous environnants, et permettant d’autre part le maintien d’un espace nécessaire à l’ostéogénèse. Ce travail de thèse pluridisciplinaire vise à développer des matrices innovantes destinées à la régénération osseuse. Inspirés par la nature hybride du tissu osseux, des revêtements à base de phosphates de calcium et de polymères organiques (chitosane et acide hyaluronique) ont été élaborés par pulvérisation simultanée de solutions d’espèces réactives. La construction de ces revêtements a permis la précipitation d’un composé à base d’apatite carbonatée et de brushite sur des lamelles de verre (preuve de concept), tandis qu’un composé hybride complexe (brushite, phosphate octocalcique et apatite nanocristalline) a été construit sur des membranes de collagène d’origine porcine, utilisées en régénération osseuse. Sur le verre, les revêtements semblent posséder les propriétés intrinsèques (rugosité, élasticité) en faveur d’une différenciation ostéoblastique, ce qui a été confirmé par une différenciation ostéoblastique précoce des cellules souches. Sur la membrane, le revêtement n’induit pas de différenciation mais stimule les propriétés ostéo-immunomodulatrices des cellules souches, nécessaires à la régénération osseuse. De plus, le revêtement a démontré dans les deux cas une activité antibactérienne, le rendant très attractif pour des applications en régénération osseuse. Enfin, le développement d’un dispositif médical de classe II à partir de la gelée de Wharton a été envisagé. Cette source allogénique semble prometteuse en médecine régénératrice osseuse. / Bone loss following tooth extraction requires pre-implantory surgery techniques to regenerate bone. These techniques use an occlusive membrane positioned over a bone graft material or not, providing space maintenance and enabling to seclude soft tissue infiltration to promote bone regeneration. This pluridisciplinary thesis work aims at developing innovative biomaterials for bone regeneration applications. Inspired by bone hybrid composition, coatings made of calcium phosphates and organic polymers (chitosan and hyaluronic acid) were developed using simultaneous spray coating of interacting species process. Coating build-up led to precipitation of a compound made of carbonated apatite and brushite on glass coverslip (proof of concept), whereas a complex hybrid compound (brushite, octacalcium phosphate and nanocrystalline apatite) was formed on collagen membrane. Coating on glass coverslip seems to possess required properties (roughness, elasticity) for osteoblastic differentiation, which was confirmed by stem cells early osteoblast commitment. However, coating on collagen membrane did not induce osteoblastic differentiation, but stimulated stem cells osteo-immunomodulatory properties, required for bone regeneration. Interestingly, coating demonstrated in both cases antibacterial activities, which makes it very attractive for bone regeneration applications. Finally, Wharton’s jelly from umbilical cord was suggested as an innovative source for new biomaterials, to replace xenogeneic membranes.

A novel antimicrobial dental composite system has been developed and evaluated.Both alumina and zirconia filler particles were covalently coated with an antibacterial resin and blended into a composite formulation, respectively. Surface hardness and bacterial viability were used to evaluate the coated alumina filler-modified composite.Compressive strength and bacterial viability were used to evaluate the coated zirconia filler-modified composite. Commercial composite Kerr was used as control. The specimens were conditioned in distilled water at 37°C for 24 h prior to testing. Four bacterial species Streptococcus mutans, Staphylococcus aureus, Pseudomon asaeruginosa and Escherichia coli were used to assess the bacterial viability. Effects of antibacterial moiety content, modified particle size and loading, and total filler content were investigated.<div><br><div>Chapter 2 describes how we studied and evaluated the composite modified with antibacterial resin-coated alumina fillers. The results showed that almost all the modified composites exhibited higher antibacterial activity along with improved surface hardness, as compared to unmodified one. Increasing antibacterial moiety content, particle size and loading, and total filler content generally increased surface hardness. Increasing antibacterial moiety, filler loading, and total filler content increased antibacterial activity. On the other hand, increasing particle size showed a negative impact on antibacterial activity. The leaching tests indicate that the modified experimental composite showed no leachable antibacterial component to bacteria.<br></div><div><br></div><div>Chapter 3 describes how we studied and evaluated the composite modified with antibacterial resin-coated zirconia fillers. The results showed that almost all the modified composites exhibited higher antibacterial activity along with decreased compressive strength, as compared to the unmodified control. It was found that with increasing antibacterial moiety content and modified filler loading, yield strength,modulus and compressive strength of the composite were decreased. In addition,the strengths of the composite were increased with increasing powder/liquid ratio.On the other hand, with increasing antibacterial moiety content, filler loading and powder/liquid ratio, antibacterial activity was enhanced.<br></div><div><br></div><div>In summary, we have developed a novel antibacterial dental composite system for improved dental restoratives. Both composites modified with the antibacterial resin-coated alumina and zirconia fillers have demonstrated significant antibacterial activities.The composite modified with the alumina fillers showed improved hardness values, but the composite modified with the zirconia fillers showed decreased compressive strength values. It appears that the developed system is a non-leaching antibacterial dental composite.<br></div></div>