Orientadora: Prof.ª Dr.ª Juliana Kelmy Macário Barboza Daguano / Dissertação (mestrado) - Universidade Federal do ABC. Programa de Pós-Graduação em Engenharia Biomédica, 2017. / A busca por materiais funcionais que possam desempenhar reparo e/ou regeneracao de tecidos biologicos de maneira satisfatoria tem crescido cada vez mais. Para tal aplicacao, uma classe que vem sendo bem aceita e a de materiais compositos, capazes de aliar propriedades de materiais diferentes. Dentre os polimeros biorreabsorviveis, encontra-se o poli(¿Ã-caprolactona), que vem se mostrando bastante adequado para usos em implantes, devido a caracteristicas biocompativeis e uso ja bastante difundido. O BiosilicatoR, vitroceramica altamente bioativa, tambem tem se mostrado uma excelente alternativa para reparo osseo, alem de outras possiveis aplicacoes. Nesse contexto, o objetivo desse estudo e o desenvolvimento e caracterizacao de filmes bioativos de composito a base de poli(¿Ã-caprolactona) e o BiosilicatoR, inicialmente, para regeneracao de tecido osseo. Este estudo consistiu de duas etapas, onde a primeira foi um estudo piloto, para definicao das condicoes de processamento, e na segunda foi analisado o desempenho dos materiais desenvolvidos. Com a associacao desses dois materiais, foram desenvolvidos compositos (PCL/BS) a partir de duas rotas diferentes. A Rota 1 consiste da tecnica de evaporacao de solvente e a Rota 2 consta da precipitacao de fases seguida por evaporacao de solvente. A caracterizacao foi realizada utilizando as tecnicas de MO, MEV, DRX e DSC. Quanto ao desempenho, foram avaliadas a bioatividade e a degradacao in vitro e propriedades mecanicas por ensaio de tracao. As duas rotas produziram filmes com diferentes morfologias, apresentando graus de cristalinidade distintos (de 30 a 67%), sendo maior a cristalinidade para a rota 2, alem da obtencao de filmes densos e porosos, respectivamente para as Rotas 1 e 2. Os testes em SBF indicaram que a adicao de BS possibilitou a formacao da fase HCA nos compositos apos 7 dias de imersao, atestando a bioatividade dos mesmos, mas nao contribuiu de forma significativa para a degradacao da fase polimerica, ao menos para o tempo de 21 dias. A caracterizacao mecanica mostrou que a Rota 1 originou amostras consideravelmente mais resistentes que a Rota 2, devido a alta porosidade associada a estas, e que a adicao de BS permitiu um aumento do Modulo de Young em torno de 46%, apesar de diminuir a tensao maxima e a tensao de escoamento do material composito. Entretanto, os valores de propriedade mecanica dos materiais desenvolvidos sao compativeis aos dos tecidos biologicos. Por fim, e possivel concluir que parametros de processamento para a obtencao de compositos poli(¿Ã-caprolactona)-BiosilicatoR (PCL/BS) foram bem estabelecidos, possibilitando o desenvolvimento de materiais com caracteristicas distintas, em funcao da rota utilizada, mas independentemente, de interesse a aplicacoes biomedicas. / The search for functional materials thatrepair and/or regenerate of biological tissues in a satisfactory manner has continually risen in the past few years. For such applications, composite materials are each time being more well accepted, capable of merge properties from different materials. Between all the bio-resorbable, one can find the Poly(å-caprolactone), which shows to be suitable to be used as implants, due to its biocompatibility and widespread use. The Biosilicate® is a glass-ceramic highly bioactive that has also shown to be an excellent alternative to bone healing, among others applications. In this context, the purpose of this study is the development and characterization of bioactive composite films based on Poly(å-caprolactone) and Biosilicate®, originally for bone tissue regeneration. Associating these to materials a composite was developed (PCL/BS) from two different routes. This study has two main stages, the first was a pilot study, to define the processing conditions, and the second one analyzedthe materials performance. Route 1 uses the solvent casting technique, and route 2 consists in phase precipitation followed by solvent casting. The characterization was made using OM, SEM, XRD and DSC. For performance evaluation, in vitro bioactivity and degradation and mechanical properties had been analyzed. The two routes produced films with different morphology, showing individual degree of crystallinity (from 30 to 67%).The route 2presented higher crystallinity and porosity, and the route 1 produced denser films. The SBF tests show that the BS addition allowed the formation of HCA phase in the composite, after seven days immersion, proving their bioactivity, but, at the same time, it doesn¿t improve significantly the degradation of the polymeric phase, at least for 21 days tests. The mechanical tests show that route 1 presents samples more resistant than route 2, probably due to it high porosity levels. The addition of BSyielded an increase in the Young¿s modulus of around 46%, although the maximum stress and yield strength were reduced. Nevertheless, the mechanical properties of the developed materials are compatible with the biological tissues. Therefore, it is possible to conclude that the processing parameters to obtain PCL-BS composites were well-established, allowing the development of materials with different characteristics, according to the used route, and with biomedical applications interest.

Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2014-12-16T19:58:48Z No. of bitstreams: 2 Dissertação - Percília de Andrade Lucena - 2014.pdf: 1506404 bytes, checksum: c895c029b3a1ac62acf42cd19fad7214 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2014-12-22T10:32:36Z (GMT) No. of bitstreams: 2 Dissertação - Percília de Andrade Lucena - 2014.pdf: 1506404 bytes, checksum: c895c029b3a1ac62acf42cd19fad7214 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-12-22T10:32:36Z (GMT). No. of bitstreams: 2 Dissertação - Percília de Andrade Lucena - 2014.pdf: 1506404 bytes, checksum: c895c029b3a1ac62acf42cd19fad7214 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-03-19 / Polymeric nanoparticles have been used as carriers of drugs that are able to increase the efficacy of many active ingredients. Among the nanocarriers include nanocapsules (NCs), which are vesicular structures containing oil inside surrounded by a polymer wall and nanospheres (NSs) that are impregnated with polymer matrices drug throughout its surface. These structures have many applications such as optimizing drug delivery and reducing the toxic potential of drugs. Itraconazole family of a drug Azole has a broad spectrum of action against fungi and has appropriate pharmacokinetic characteristics for a drug. Thus, this study aims to develope and characterize nanostructured systems containing Itraconazole. Polymeric nanoparticles were obtained by the nanoprecipitation technique, lyophilized, characterized, and evaluated physical-chemically incorporated into mucoadhesive topical formulation. Nanocapsules containing Itraconazole showed encapsulation efficiency rate of 99 ± 6.9%, a mean diameter of 190 ± 10.1 nm, PDI 0.1 ± 0:06 and zeta potential -15 ± 2.5 mV. The nanospheres exhibited rate of encapsulation efficiency of 97 ± 2.8%, mean diameter 120 ± 0.8 nm, 0.1 ± 0.01 PDI and zeta potential -10 ± 3.5 mV. Lyophilization was carried out with 10% trehalose + 10% sucrose, achieving satisfactory results. The drug release after 30 days at 37 °C was 99% for the NCs and 92% for the NEs. The mucoadhesive topical formulation has in its composition 60% Poloxamer 188, 20% polyethylene glycol 400 and 5mg nanostructured itraconazole were incorporated homogeneously. The results indicate that the formulation of Itraconazole in polymeric nanoparticles has potential for in vivo use in the topical treatment of fungal infections. / Nanopartículas poliméricas têm sido utilizadas como carreadores de fármacos capazes de aumentar a eficácia de muitos insumos ativos. Dentre os nanocarreadores, destacam-se: nanocápsulas (NCs), que são estruturas vesiculares, contendo óleo no interior, circundadas por uma parede polimérica e nanoesferas (NEs) que são matrizes poliméricas impregnadas com fármaco por toda sua superfície. Essas estruturas possuem diversas aplicações como otimizar a entrega de fármacos e reduzir o potencial tóxico. O Itraconazol um fármaco da família dos azóis possui um amplo espectro de ação contra fungos e apresenta características farmacocinéticas apropriadas para um fármaco. Sendo assim, o presente trabalho tem como objetivo desenvolver e caracterizar sistemas nanoestruturados contendo Itraconazol. As nanopartículas poliméricas foram obtidas através da técnica da nanoprecipitação, liofilizadas, caracterizadas, avaliadas físicoquimicamente e incorporadas em formulação tópica mucoadesiva. As nanocápsulas contendo Itraconazol apresentaram taxa de eficiência de encapsulação de 99±6.9%, diâmetro médio de 190±10.1 nm, PDI 0.1±0.06 e potencial zeta -15±2.5 mV. As nanoesferas exibiram taxa de eficiência de encapsulação de 97±2.8%, diâmetro médio de 120±0.8 nm, PDI 0.1±0.01 e potencial zeta -10±3.5 mV. A liofilização foi realizada com 10% de trealose + 10% de sacarose, alcançando resultados satisfatórios. A liberação do fármaco após 30 dias a 37°C foi de 99% para as NCs e 92% para as NEs. A formulação tópica mucoadesiva possui em sua composição 60% Poloxamer 188 e 20% de Polietilenoglicol 400 e 5mg de itraconazol nanoestruturado foram incorporados homogeneamente. Os resultados indicam que a formulação de itraconazol em nanopartículas poliméricas apresenta potencial para utilização in vivo no tratamento tópico de infecções fúngicas.

Orientadores: Cecília Amélia de Carvalho Zavaglia, Antonio Celso Fonseca de Arruda / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecânica / Made available in DSpace on 2018-08-22T11:48:56Z (GMT). No. of bitstreams: 1 Cardoso_GuineaBrasilCamargo_D.pdf: 9557754 bytes, checksum: 02a2fe1340ad1877992a3e0b603d0ad0 (MD5) Previous issue date: 2013 / Resumo: A variedade de sítios anatômicos e diferentes propriedades mecânicas são essenciais para o êxito em cirurgias de reconstrução óssea, com isso tratamentos envolvendo fraturas complexas, perda óssea e próteses são beneficiadas com o uso dos biomateriais. Com o presente estudo, buscou-se uma proposta original no uso de um biomaterial compósito para implantes na região da mandíbula, a singularidade deste dispositivo é a estrutura física do material, que é composto por um núcleo denso em uma matriz porosa. As influências das estruturas e dos materiais utilizados foram analisadas por caracterizações físicas, químicas e as atividades celulares em ensaios in vitro, analisando o comportamento dessas em condições similares ao ambiente de implantação o que permitiu qualificar este biomaterial. Para tanto, foram sintetizados reagentes primários para a síntese de fosfato tricálcico (?-TCP), que ao ser hidrolisado resultou em whiskers de hidroxiapatita. As cerâmicas foram caracterizadas pelas análises de difração de raios X (DRX), fluorescência de raios X (FRX), microscopia eletrônica de varredura (MEV) e ensaio de citotoxicidade. As diversas composições poliméricas e compósitas foram analisadas utilizando os resultados obtidos pelos ensaios de ângulo de contato, calorimetria exploratória diferencial (DSC), microscópio de força atômica (MFA), microscopia óptica com luz polarizada (MO), ensaio mecânico de tração e ensaios in vitro com células U20S. Os suportes tridimensionais passaram por análises como de: ensaio mecânico de compressão e ensaios in vitro com células tronco mesenquimais. Os estudos foram realizados para a verificação do potencial de aplicação clínica desse material na engenharia tecidual óssea. As amostras que se apresentaram mais promissoras foram as de composições poli (?-caprolactona) / ácido oléico/ hidroxiapatita e poli caprolactona/ ácido oléico. Resistência mecânica, hidrofilicidade, rugosidade, cristalinidade, espraiamento celular e osteoindução foram os critérios utilizados neste trabalho. Os resultados obtidos demostraram-se promissores e irão incentivar pesquisas futuras envolvendo estes materiais / Abstract: The variety of anatomical sites and different mechanical properties are essential to the success of surgery bone reconstruction. Treatments involving this complex fractures, bone loss and prosthetics are benefited with the use of biomaterials. In the present study, we sought to an original use of a composite biomaterial for implants in the jaw area; the uniqueness of this device is the physical structure of the material, which is composed of a dense core in a porous matrix. The influences of structures and materials were analyzed by characterizing the physical, chemical and cellular activities in in vitro assays, analyzing the behavior of those in similar conditions to the deployment environment which would allow qualifying this biomaterial. Therefore, primers were synthesized reagents for the synthesis of tricalcium phosphate (?-TCP), which when hydrolyzed resulted in hydroxyapatite whiskers. The ceramics were characterized by analysis of X-ray diffraction (XRD), X-ray fluorescence (XRF), scanning electron microscopy (SEM) and cytotoxicity assay. The various compositions were analyzed using the results obtained by contact angle tests, differential scanning calorimetry (DSC), atomic force microscope (AFM); optical microscopy with polarized light (OM), mechanical tests and in vitro assays with cells U20S. The scaffolds have undergone analyzes as: mechanical compression test and in vitro assays with mesenchymal stem cells. Studies were conducted to verify the potential clinical application of this material in bone tissue engineering. Because the analysis of the results of the characterizations, the samples which were the most promising compositions of poly (?-caprolactone) / oleic acid and poly(?- caprolactone)/ oleic acid/ hydroxyapatite. Mechanical strength, hydrophilicity, roughness, crystallinity, cell spreading and osteoinduction were the criteria used in this work. The results showed to be promising and will encourage future research involving these materials / Doutorado / Materiais e Processos de Fabricação / Doutora em Engenharia Mecânica

Orientador: Cecília Amélia de Carvalho Zavaglia / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecânica / Made available in DSpace on 2018-08-23T08:49:24Z (GMT). No. of bitstreams: 1 Brito_TalitaAlmeidaVidade_M.pdf: 2327615 bytes, checksum: 1370c441c447a5a8dae05303883562b5 (MD5) Previous issue date: 2013 / Resumo: Este trabalho apresenta a preparação e caracterização de nanofibras da blenda poli (L-ácido láctico) (PLLA)/poli (?-caprolactona) (PCL) através dos processos de eletrofiação e rotofiação destinada à produção de fibras visando futuras aplicações como suporte para a engenharia tecidual. As blendas foram preparadas através da dissolução do polímero em clorofórmio e clorofórmio mais acetona, resultando em uma solução de 6%. A eletrofiação é um processo relativamente simples e de baixo custo, que consiste na aceleração de uma solução polimérica, inicialmente contida em um capilar metálico, pela presença de um campo elétrico externo, para produzir fibras com diâmetro médio reduzido. Apesar da popularidade e da versatilidade, o processo de eletrofiação apresenta algumas desvantagens, tais como o uso de fonte de alta tensão, baixa taxa e longo tempo de produção das fibras. Com a necessidade de encontrar um método de produção de fibras para sanar eventuais obstáculos encontrados na eletrofiação, foi realizado um estudo com um novo processo: a rotofiação. O processo de rotofiação é um processo simples que forma fibras durante o jateamento da solução polimérica através de um orifício central utilizando alta velocidade de rotação e não utiliza campo elétrico de alta voltagem, como na eletrofiação. As fibras obtidas por meio dos dois processos foram analisadas e caracterizadas pelos seguintes métodos: microscopia eletrônica de varredura (MEV), análise termogravimétrica (TGA), calorimetria exploratória diferencial (DSC), e espectroscopia na região do infravermelho por transformada de fourier (FTIR). A análise das fibras por microscopia eletrônica de varredura (MEV) mostrou que é possível a formação de nanofibras da blenda PLLA/PCL através dos dois processos. Verificou-se que ocorreram diferenças significativas no diâmetro médio dos fios entre os processos, onde na rotofiação, os diâmetros foram maiores, os dois processos estudados permitiram a obtenção de fibras porosas, uma característica importante requerida na engenharia tecidual. Os resultados das análises térmicas indicaram o comportamento imiscível das blendas PLLA/PCL. Através da análise de FTIR foi possível demonstrar eliminação completa dos solventes durante o processamento e também a imiscibilidade dos polímeros / Abstract: This work presents the preparation and characterization of nanofibers of poly (L-lactic acid) (PLLA) / poly (?-caprolactone) (PCL) through electrospinning and rotary jet spinning processes for the production of fibers aiming future applications as scaffolds for tissue engineering. The blends were prepared using the two polymers cited above in chloroform and chloroform plus acetone, resulting in a solution of 6%. Electrospinning is relatively simple and low cost process, which consists in the acceleration of a polymer solution initially contained in a capillary, the presence of an external electric field to produce fibers with reduced average diameter reduced. Despite the popularity and versatility, the electrospinning process has some disadvantages such as the use of high voltage supply, low spinning rates and takes time for long fiber production. With the need to find a method of producing fibers to remedy any obstacles encountered in electrospinning, a study was conducted with a new process: rotary jet spinning. The process of rotary jet spinning is a simple process that forms fibers during the blasting of the polymer solution through a central hole using high-speed rotation and does not use high intensity electric fields, as in electrospinning. The fibers obtained by the two processes were analyzed and characterized by the following methods: scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and infrared spectroscopy fourier transform (FTIR). The fiber analysis by scanning electron microscopy (SEM) showed that it is possible to form nanofibers of PLLA / PCL through two processes. It was found that there were significant differences in the average diameter of the fibers between the processes, where higher diameters were observed in rotary jet spinning, the two processes studied allowed to obtain porous fibers, an important feature required in tissue engineering. The results of thermal analysis indicated that it was formed immiscible blends of PLLA / PCL. By FTIR analysis it was demonstrated complete elimination of the solvents during processing and also the immiscibility of the polymers / Mestrado / Materiais e Processos de Fabricação / Mestra em Engenharia Mecânica

Tissue engineering is receiving tremendous attention due to the necessity to overcome the limitations related to injured or diseased tissues or organs. It is the perfect combination of cells and biomimetic-engineered materials. With the appropriate biochemical factors, it is possible to develop new effective bio-devices that are capable to improve or replace biological functions. Latest developments in microfabrication methods, employing mostly synthetic biomaterials, allow the production of three-dimensional (3D) scaffolds that are able to direct cell-to-cell interactions and specific cellular functions in order to drive tissue regeneration or cell transplantation. The presented work offers a rapid and efficient method of 3D scaffolds fabrication by using optical lithography and micro-molding techniques. Bioresorbable polymer poly-ε-caprolactone (PCL) was the material used thanks to its high biocompatibility and ability to naturally degrade in tissues. 3D PCL substrates show a particular combination in the designed length scale: cylindrical shaped pillars with 10μm diameter, 10μm height, arranged in a hexagonal lattice with spacing of 20μm were obtained. The sidewalls of the pillars were nanostructured by attributing a 3D architecture to the scaffold. The suitability of these devices as cell culture technology supports was evaluated by plating NIH/3T3 mouse embryonic fibroblasts and human Neural Stem Cells (hNSC) on them. Scanning Electron Microscopy (SEM) analysis was carried out in order to examine the micro- and nano-patterns on the surface of the supports. In addition, after seeding of cells, SEM and immunofluorescence characterization of the fabricated systems were performed to check adhesion, growth and proliferation. It was observed that cells grow and develop healthy on the bio-polymeric devices by giving rise to well-interconnected networks. 3D PCL nano-patterned pillared scaffold therefore may have considerable potential as effective tool for applications in tissue engineering.

No description available.

The structural evolution of micromolded poly(ε-caprolactone) (PCL) and its miscible blends with noncrystallizable poly(vinyl methyl ether) (PVME) at the nanoscale was investigated as a function of deformation ratio and blend composition using in situ synchrotron smallangle X-ray scattering (SAXS) and scanning SAXS techniques. It was found that the deformation mechanism of the oriented samples shows a general scheme for the process of tensile deformation: crystal block slips within the lamellae occur at small deformations followed by a stressinduced fragmentation and recrystallization process along the drawing direction at a critical strain where the average thickness of the crystalline lamellae remains essentially constant during stretching. The value of the critical strain depends on the amount of the amorphous component incorporated in the blends, which could be traced back to the lower modulus of the entangled amorphous phase and, therefore, the reduced network stress acting on the crystallites upon addition of PVME. When stretching beyond the critical strain the slippage of the fibrils (stacks of newly formed lamellae) past each other takes place resulting in a relaxation of stretched interlamellar amorphous chains. Because of deformation-induced introduction of the amorphous PVME into the interfibrillar regions in the highly oriented blends, the interactions between fibrils becomes stronger upon further deformation and thus impeding sliding of the fibrils to some extent leading finally to less contraction of the interlamellar amorphous layers compared to the pure PCL / National Natural Science Foundation of China (21204088 and 21134006). This work is within the framework of the RCUK/EPSRC Science Bridges China project of UK−China Advanced Materials Research Institute (AMRI).

Two-dimensional (2D) nanoscale confinement effects on poly(ε-caprolactone) (PCL) crystallization were probed through crystallization studies of PCL-b-poly(tert-butyl acrylate) (PCL-b-PtBA) copolymers, PCL with bulky tri-tert-butyl ester endgroups (PCL triesters), PCL with triacid end groups (PCL triacids), and magnetic nanoparticles stabilized by PCL triacid (PCL MNPs) at the air/water (A/W) interface. Thermodynamic analyses of surface pressure-area per monomer (Π−A)) isotherms for the Langmuir films at the A/W interface showed that PCL-b-PtBA copolymers, PCL triheads and PCL MNPs all formed homogenous monolayers below the dynamic collapse pressure of PCL, Π_C ~11 mN•m⁻¹. For compression past the collapse point, the PCL monolayers underwent a phase transition to three-dimensional (3D) crystals and the nanoscale confinements impacted the PCL crystalline morphologies. Studies of PCL-b-PtBA copolymers revealed that the morphologies of the LB-films became smaller and transitioned to dendrites with defects, stripes and finally nano-scale cylindrical features as the block length of PtBA increased. For the case of PCL triester, irregularly shaped crystals formed at the A/W interface and this was attributed to the accumulation of bulky tert-butyl ester groups around the crystal growth fronts. In contrast, regular, nearly round-shaped lamellar crystals were obtained for PCL triacids. These morphological differences between PCL triacids and PCL triesters were molar mass dependent and attributed to differences in dipole density and the submersion of carboxylic acid groups in the subphase. Nonetheless, enhanced uniformity for PCL triacid crystals was not retained once the polymers were tethered to the spherical surface of a PCL MNP. Instead, the PCL MNPs exhibited small irregularly shaped crystals. This nano-scale confinement effect on the surface morphology at the A/W interface was also molar mass dependent. For the small molar mass PCL MNPs, two layers of collapsed nanoparticles were observed. In a later chapter, studies of polyethylene glycol (PEG) surfactant adsorption onto phospholipid bilayers through quartz crystal microbalance with dissipation monitoring (QCM-D) measurements revealed a strong dependence of the adsorption and desorption kinetics on hydrophobic tail group structure. PEG surfactants with a single linear alkyl tail inserted and saturated the bilayer surface quickly and the surfactants had relatively fast desorption rates. In contrast, PEG lipids, including dioleoyl PEG lipids and cholesterol PEGs, demonstrated slower adsorption and desorption kinetics. The interactions of Pluronics and Nonoxynol surfactants with phospholipid bilayers were also studied. Pluronics showed no apparent affinity for the phospholipid bilayer, while the Nonoxynol surfactants damaged the lipid bilayers as PEG chain length decreased. / Ph. D.

The goal of this work is to examine the applicability of the Lauritzen-Hoflinan (LH) surface nucleation theory to the crystallization kinetics of poly(ε-caprolactone), PCL. This theory has successfully predicted a number of experimental observations such as the temperature dependence of spherulitic growth rates and the inverse relation between undercooling and the lamellar thickness. Claims have appeared in the literature that analysis of growth rate data using the LH theory does not yield physically meaningful parameters. This work will show that the lateral and fold interfacial free energy parameters, σ and σₑ, found by analysis with the LH theory are related to the chemical structure of the polymer chain in the case of PCL. The fold interfacial free energy is related to the chain stiffness, and a recent proposal relates σ to the characteristic ratio, C_∞. This work will examine the validity of the proposed relationship for the case of PCL. The effect of polymer chain architecture on the crystallization behavior was also investigated. The crystallization behavior of poly(ε-caprolactone) was compared and contrasted to that of a triblock copolymer containing (ε-caprolactone) blocks. / Ph. D.

Polymeric bone scaffolds are a promising tissue engineering approach for the repair of critical-size bone defects. Porous three-dimensional (3D) scaffolds play an essential role as templates to guide new tissue formation. However, there are critical challenges arising from the poor mechanical properties and low bioactivity of bioresorbable polymers, such as poly(epsilon-caprolactone) (PCL) in bone tissue engineering applications. This research investigates the potential use of cellulose nanocrystals (CNCs) as multi-functional additives that enhance the mechanical properties and increase the biomineralization rate of PCL. To this end, an in vitro biomineralization study of both sulfuric acid hydrolyzed-CNCs (SH-CNCs) and surface oxidized-CNCs (SO-CNCs) has been performed in simulated body fluid in order to evaluate the bioactivity of the surface functional groups, sulfate and carboxyl groups, respectively. PCL nanocomposites were prepared with different SO-CNC contents and the chemical/physical properties of the nanocomposites were analyzed. 3D porous scaffolds with fully interconnected pores and well-controlled pore sizes were fabricated from the PCL nanocomposites with a 3D printer. The mechanical stability of the scaffolds were studied using creep test under dry and submersion conditions. Lastly, the biocompatibility of CNCs and 3D printed porous scaffolds were assessed in vitro. The carboxyl groups on the surface of SO-CNCs provided a significantly improved calcium ion binding ability which could play an important role in the biomineralization (bioactivity) by induction of mineral formation for bone tissue engineering applications. In addition, the mechanical properties of porous PCL nanocomposite scaffolds were pronouncedly reinforced by incorporation of SO-CNCs. Both the compressive modulus and creep resistance of the PCL scaffolds were enhanced either in dry or in submersion conditions at 37 degrees Celsius. Lastly, the biocompatibility study demonstrated that both the CNCs and material fabrication processes (e.g., PCL nanocomposites and 3D printing) were not toxic to the preosteoblasts (MC3T3 cells). Also, the SO-CNCs showed a positive effect on biomineralization of PCL scaffolds (i.e., accelerated calcium or mineral deposits on the surface of the scaffolds) during in vitro study. Overall, the SO-CNCs could play a critical role in the development of scaffold materials as a potential candidate for reinforcing nanofillers in bone tissue engineering applications. / Ph. D.