The host response toward biomaterial component of tissue-engineered devices has been extensively investigated. The objective of this research was to understand the response of dendritic cells (DCs) to different biomaterials upon contact and identify biomaterials suitable for use in tissue engineering constructs for rheumatoid arthritis (RA) applications. Differential levels of functional DC maturation were observed depending on the type of biomaterial in 2-dimensional films or 3-dimensional scaffolds used to treat immature DCs; Poly(lactic-co-glycolic acid) (PLGA) or chitosan supported higher levels of DC maturation, as compared to immature DCs. Alginate supported moderate levels of DC maturation. Agarose did not support DC maturation whereas hyaluronic acid inhibited DC maturation. Further, these DCs treated with different biomaterials induced differential phenotype and polarization of autologous T cells upon co-culture of DCs and T cells; DCs treated with PLGA induced T helper type I with immunogenic response while DCs treated with agarose did T helper type II with tolerogenic response. Effect of different biomaterials (PLGA and agarose) was assessed in vivo upon implantation of them into the knee joint of RA-induced rabbit. Total leukocyte concentrations in the peripheral blood or in the joint lavage of the left knees (untreated control) were observed in differential levels depending on the biomaterial implant, possibly due to the systemic circulation of the peripheral blood. Furthermore, cartilage and bone healing progression was differentially observed in the osteochondral defect of the knee joint of RA-induced rabbit, depending on type of biomaterial scaffold implanted into the defect. Collectively, these results demonstrate the multifunctional impacts of inherently different biomaterials on in vitro immunomodulation of phenotype and polarization of DCs and autologous T cells. Furthermore, taken together with these immunomodulatory impacts of biomaterials, in vivo effects of different biomaterial scaffolds on RA environment shown in this study can suggest the criteria of selection and design of biomaterials for orthopedic tissue engineering, which may ultimately be best integrated into the diseased cartilage and bone.

Biomimetic materials that recapitulate the complex mechanical and biochemical cues in load-bearing tissues are of significant interest in regenerative medicine and tissue engineering applications. Several investigators have endeavored to not only emulate the mechanical properties of the vasculature, but to also mimic the biologic responsiveness of the blood vessel in creating vascular substitutes. Previous studies in our lab generated the elastin-like protein polymer LysB10, which was designed with the capability of physical and chemical crosslinks, and was shown to display a range of elastomeric properties that more closely matched those of the native artery. While extensive validation of the mechanical properties of elastin-mimetic polymers has demonstrated their functionality in a number of tissue engineering applications, limited cell growth on the surfaces of the polymers has motivated further optimization for biological interaction. Recent biologically-inspired surface strategies have focused on functionalizing material surfaces with extracellular matrix molecules and bioactive motifs in order to encourage integrin-mediated cellular responses that trigger precise intracellular signaling processes, while limiting nonspecific biomaterial interactions. Consequently, this dissertation addresses three approaches to modulating cellular behavior on elastin-mimetic analogs with the goal of promoting vascular wall healing and tissue regeneration: genetic engineering of elastin-like protein polymers (ELPs) with cell-binding domains, biofunctionalization of elastin-like protein polymers via chemoselective ligation of bioactive ligands, and incorporation of matrix protein fibronectin for engineering of cell-seeded multilamellar collagen-reinforced elastin-like constructs. The synthesis of recombinant elastin-like protein polymers that integrate biologic functions of the extracellular matrix provides a novel design strategy for generating clinically durable vascular substitutes. Ultimately, the synthesis of model protein networks provides new insights into the relationship between molecular architecture, biomimetic ligand presentation, and associated cellular responses at the cell-material interface. Understanding how each of these design parameters affects cell response will contribute significantly to the rational engineering of bioactive materials. Potential applications for polymer blends with enhanced mechanical and biological properties include surface coatings on vascular grafts and stents, as well as composite materials for tissue engineered scaffolds and vascular substitutes.

Cardiovascular diseases are the leading cause of death throughout the world and various estimates predict that heart disease will remain the number one killer in the world. Pharmacotherapies have not shown significant long term survival benefits to the patients, therefore alternate therapeutic strategies such as bioactive agent delivery and cell therapy based approaches are being investigated. One of the major causes of heart failure is the disease progression after an ischemic event and any successful therapy will be needed over the course of several days/weeks. Oxidative stress is greatly increased in the myocardium following infarction. This plays a significant role in cardiac disease progression and it has also been implicated in the failure of implanted cell therapy. Therefore, reducing oxidative stress in damaged tissue using antioxidants may have broad clinical implications for both the treatment of cardiac dysfunction and for cardiac regeneration applications. This dissertation work examines the effect of sustained delivery of endogenous antioxidant superoxide dismutase (SOD) to the rat myocardium following ischemia/reperfusion (IR) using polyketal polymers as drug carriers. The second major objective of this dissertation is to examine the effects of oxidative stress on cardiac progenitor cells - a promising endogenous adult stem cell in cardiac cell therapy applications

The development of small diameter tissue engineered blood vessels (TEBVs) with low thrombogenicity, low immunogenicity, suitable mechanical properties, and a capacity to remodel to their environment could significantly advance the treatment of coronary and peripheral artery disease. Despite significant advances in the field of tissue engineering, autologous vessels are still primarily utilized as grafts during bypass surgeries. However, undamaged autologous tissue may not always be available due to disease or prior surgery. TEBVs lack long-term efficacy due to a variety of types of failures including aneurysmal dilations, thrombosis, and rupture; the mechanisms of these failures are not well understood. In vitro mechanical testing may help the understanding of these failure mechanisms. The typical mechanical tests lack standardized methodologies; thus, results vary widely. The overall goal of this study is to develop novel experimental and mathematical models to study the mechanical properties and failure mechanisms of TEBVs. Our results suggest that burst pressure tests, the current standard, are not sufficient to assess a TEBVs’ suitability as a coronary substitute; creep and/or cyclic loading tests are also required. Results from this model can help identify the most insightful experiments and quantities to be measured – ultimately reducing the overall number of experimental iterations. Improving the testing and characterization of TEBVs is critically important in decreasing the time necessary to validate the mechanical and functional responses of TEBVs over time, thus quickly moving TEBVs from the benchtop to the patient.

This thesis begins with a brief overview of supramolecular chemistry and selfassembly and simple examples derived from Nature that provide the motivation for the work presented here. The concept of a synthetic noncovalent toolbox is then introduced. The discussion then focuses more explicitly on side-chain and main-chain functionalized motifs and the methodologies employed in supramolecular polymer functionalization. The primary hypothesis of the thesis is that the combination of supramolecular strategies, ring-opening metathesis polymerization, and a well-understood toolbox of functionalities capable of noncovalent interactions, comprises a method for generating bioinspired materials. This hypothesis was tested by synthesizing unique functionalized supramolecular polymers that allowed for a detailed understanding of the orthogonality of noncovalent interactions and how such interactions can begin to mimic the complexity of functional biomaterials. The strategies and methods discussed in the synthesis of these bioinspired materials are divided into three chapters: (1) an exploration of the self-sorting phenomena between two non-complementary pairs of hydrogen bonds along polymer side-chains, (2) the extension of the self-sorting concept to include a metal coordination moiety, and (3) the side-chain functionalization strategies of chapters 2 and 3 in combination with the main-chain ROMP methodologies discussed in chapter 1 to form orthogonally self-assembled multifunctional block copolymers. The main results of this thesis include the results that multifunctional block copolymers can be fashioned via ROMP, functionalized in both the main- and side-chains, and self-assembled in an orthogonal fashion. In addition, these studies have found that self-sorting between pairs of non-complementary hydrogen bonding motifs can occur in supramolecular synthetic systems, that the interactions are extremely solvent dependent and that these interactions can result in unexpected phenomena. These results demonstrate the importance of a fully understood toolbox for the rapid development of supramolecular materials. The knowledge derived from this toolbox and presented in chapters 2, 3, and 4, allows for the careful selection of compounds for cleverly designed self-assembly materials inspired by Nature. Finally, conclusions are drawn to the success of the synthetic toolbox and the various strategies presented herein, and potential future directions are discussed.

Modification of the surface chemistry of materials used as implants in biomedical applications affords the ability to control cell adhesion, prevent inflammation and enhance integration with the host. Titanium and its alloys are strong and lightweight thereby making them desirable for applications such as hip and knee replacements, dental implants, and cardiac pacemaker implants. However, the lifetime of these implants is often limited by poor incorporation into the surrounding bone which results in loosening and wear. In order to overcome these limitations we have studied the modification of titanium substrates with a self-assembled monolayer that can be used to perform surface-initiated atom transfer radical polymerization (SI-ATRP) of a monomer to afford polymer brushes that effectively prevent the adhesion of cells. In addition, the polymer brushes afford the ability to tether a peptide sequence. Specific peptides containing adhesion sequences have been tethered to the polymer brushes. The resulting surfaces promote cell adhesion and osteoblast differentiation, thereby increasing bone tissue formation around the implant resulting in better incorporation of the implant.

This work examines the chemical and physical effects of a material treatment process on the biopolymers PEEK, POM-h, POM-c, PTFE and UHMWPE. The polymers are analyzed physically and chemically using atomic force microscopy, profilometry, scanning electron microscopy, optical microscopy, contact angle measurement, FT infra-red spectroscopy and energy dispersive X-ray spectrometry. PEEK is found to be the most suitable polymer and FT Infra-red spectroscopy an informative analytic tool.

Filmes finos nanométricos de nitreto de zircônio (ZrN) foram depositados sobre diferentes substratos, objetivando-se estudar a microestrutura da superfície e investigar o comportamento eletroquímico para obter a melhor composição que minimize reações de corrosão. Os filmes finos foram produzidos por deposição física de vapor (PVD). Foi estudada a influência da pressão parcial do gás nitrogênio, do tempo e da temperatura de deposição nas propriedades da superfície. Os filmes de ZrN foram caracterizados por espectrometria de retroespalhamento Rutherford (RBS), espectroscopia de fotoelétrons gerados por raios X (XPS), difração de raios X (DRX), nanodureza, microscopia eletrônica de varredura (MEV) e ensaios de corrosão. As propriedades dos filmes finos de ZrN variam com os parâmetros de deposição. Quanto maior a temperatura usada na deposição dos filmes maior a resistência contra corrosão. Quando depositado sobre o Titânio e sobre uma liga de NiTi, os ensaios de corrosão mostram que o revestimento de ZrN depositado por PVD pode efetivamente melhorar a resistência contra a corrosão. / Submitted by Marcelo Teixeira (mvteixeira@ucs.br) on 2014-06-04T16:16:38Z No. of bitstreams: 1 Dissertacao Daiane Roman.pdf: 1913372 bytes, checksum: 3fc49a90d63debc4754aeb458d421795 (MD5) / Made available in DSpace on 2014-06-04T16:16:38Z (GMT). No. of bitstreams: 1 Dissertacao Daiane Roman.pdf: 1913372 bytes, checksum: 3fc49a90d63debc4754aeb458d421795 (MD5) / Zirconium nitride (ZrN) nanometric films were deposited onto different substrates, in order to study the surface microstructure and also to investigate the electrochemical behavior to obtain a better composition that minimizes corrosion reactions. The thin films were produced by physical vapor deposition (PVD). The influence of the nitrogen partial pressure, deposition time and temperature over the surface properties was studied. Rutherford backscattering spectrometry (RBS), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), nanohardness, scanning electron microscopy (SEM) and corrosion experiments were performed to characterize the ZrN thin films. The thin films properties and microstructure changes according to the deposition parameters. The corrosion against resistance increases with temperature used in the films deposition. Corrosion tests show that ZrN thin films deposited by PVD onto titanium and onto alloy nitinol substrate effectively improve the corrosion resistance.

A contaminação por biofilmes bacterianos tem um forte impacto negativo, especialmente quando aderidos na superfície de próteses, implantes, pinos e outros dispositivos médico-cirúrgicos. Neste trabalho foram produzidas amostras metálicas de titânio e AISI 304 com íons Ag+ implantados por IPD a diferentes energias: 2 e 4 keV; e com diferentes tempos de implantação: 30, 45, 60 e 90 min visando a obtenção de superfícies com propriedades bactericidas. A profundidade e o perfil de distribuição dos íons implantados foram estimados por simulação de Monte Carlo utilizando o software SRIM 2008, juntamente com a determinação da concentração de prata incorporada nas amostras por técnicas espectroscópicas. A atividade bactericida das amostras de titânio com diferentes concentrações de prata foi avaliada por meio do tratamento de um efluente industrial líquido, que foi submetido à contagem de Escherichia coli antes e depois do contato do efluente com as amostras. O ângulo de contato foi medido para avaliação da molhabilidade das amostras de titânio que apresentaram as maiores concentrações de prata, fator determinante na adesão de bactérias e células humanas. A citotoxidade foi avaliada através de teste de viabilidade celular e análise morfológica. Obteve-se uma redução de 27% de E.coli no efluente industrial tratado com a amostra implantada a 4 keV por 45 min, com concentração inicial de 3,35 × 1015 átomos cm-2.Não foi detectado efeito tóxico da prata para células humanas MG63, mesmo considerando as maiores concentrações prata, uma vez que não houve redução na adesão e proliferação celular em relação ao titânio não tratado. Para as amostras de AISI 304, os ensaios de adesão microbiana foram realizados para as bactérias Listeria monocytogenes e Salmonella Enteritidis, resultando em uma redução de 65,9 e 69,8%, respectivamente. Por fim, os resultados mostraram que o tratamento estudado para obtenção de materiais metálicos com ação bactericida é promissor para aplicações na área médica, no entanto é necessário uma avaliação em longo prazo para garantir a segurança de sua utilização. / Submitted by Ana Guimarães Pereira (agpereir@ucs.br) on 2017-07-05T14:10:05Z No. of bitstreams: 1 Tese Tatiana Pacheco Soares Zamboni.pdf: 2896094 bytes, checksum: a93cbf9d375f0634bd1237b20bc12d83 (MD5) / Made available in DSpace on 2017-07-05T14:10:05Z (GMT). No. of bitstreams: 1 Tese Tatiana Pacheco Soares Zamboni.pdf: 2896094 bytes, checksum: a93cbf9d375f0634bd1237b20bc12d83 (MD5) Previous issue date: 2017-07-05 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES. / Contamination by bacterial biofilms has a strong negative impact, especially when given on the surface of prostheses, implants, pins and other medical-surgical devices. In this study metal samples of Titanium cp and AISI 304 were produced with Ag+ ions implanted by IPD at different energies: 2 and 4 keV and different implantation times: 30, 45, 60 and 90 min to obtain surfaces with bactericidal properties. The depth and the distribution profile of the implanted ions were estimated by Monte Carlo simulation using the SRIM 2008 software. The Ag+ ions concentration incorporated in the samples was determinate by spectroscopic techniques. Bactericidal activity of the titanium samples with different concentration of Ag+ ions was evaluated by the treatment of a liquid industrial waste. It was submitted to Escherichia coli counting before and after the contact of the waste with the samples. The contact angle was measured to evaluate the wettability of the titanium samples that presented the highest silver concentration. Wettability is a determinant factor in the adhesion of bacteria and human cells. Cytotoxicity was evaluated by cell viability test and morphological analysis. A 27% reduction of E. coli in the industrial waste treated with the sample implanted at 4 keV was achieved for 45 min with an initial concentration of 3.35 × 1015 atoms cm2. No toxic effect of silver was detected on human MG63 cells, even considering the higher concentration of silver, since there was no reduction in cell adhesion and proliferation c to untreated titanium. For the AISI 304 samples, the microbial adhesion assays were performed for the bacteria Listeria monocytogenes and Salmonella Enteritidis, resulting in a reduction of 65.9 and 69.8%, respectively. Finally, the results showed that the treatment studied to obtain metallic materials with bactericidal action is promising for applications in the medical field, however a long term evaluation is necessary to guarantee the safety of its use.

FINEP; CAPES; CNPQ; Fundação Araucária; ANEEL / O presente trabalho apresenta uma aplicação de sensores à fibra ótica baseados em redes de Bragg encapsulados em compósito de resina polimérica com reforço de fibra de vidro no formato de tubo. O objetivo do trabalho foi projetar, fabricar e caracterizar o dispositivo sensor aplicado ao ciclo da marcha e a mudança do centro de gravidade em amputado transtibial, através da análise de de deformação e resistência do tubo conector da prótese transtibial. Para essa investigação foi produzido um tubo com o material compósito descrito anteriormente através do método de Moldagem por Transferência de Resina (RTM), com quatro sensores óticos. A prótese em que o tubo original foi substituído é classificada como endoesquelético, possui encaixe à vácuo, tem o tubo conector de alumínio e pé com amortecimento de fibra de carbono. O voluntário para os testes foi um homem de 41 anos, 1,65 metros de altura, 72 quilogramas e canhoto. Sua amputação ocorreu devido a trauma (secção cirúrgica nível medial feita abaixo do joelho do membro inferior esquerdo). Ele é usuário de prótese transtibial há dois anos e oito meses A caracterização dos sensores óticos e análise da deformação mecânica e resistência do tubo deu-se pelo ciclo da marcha e a variação do centro de gravidade do corpo através dos seguintes testes: levantar-se, apoiar na perna sem a prótese, apoiar na perna com a prótese, locomoção para frente e locomoção para trás. Os resultados mostram além da caracterização do ciclo da marcha em um amputado transtibial, também um elevado grau de integração das FBGs no compósito e uma alta resistência mecânica do material. / This work presents an application of optical fiber sensors based on Bragg gratings integrated to a transtibial prosthesis tube manufactured with a polymeric composite systrem of epoxy resin reinforced with glass fiber. The main objective of this study is to characterize the sensors applied to the gait cycle and changes in the gravity center of a transtibial amputee, trough the analysis of deformation and strengh of the transtibial prosthesis tube. For this investigation it is produced a tube of the composite material described above using the molding method of resin transfer (RTM) with four optical sensors. The prosthesis in which the original tube is replaced is classified as endoskeletal, has vacuum fitting, aluminium conector tube and carbon fiber foot cushioning. The volunteer for the tests was a man of 41 years old, 1.65 meters tall, 72 kilograms and left-handed. His amputation occurred due to trauma (surgical section is in the medial level, and was made below the left lower limb knee). He has been a transtibial prosthesis user for two years and eight months. The characterization of the optical sensors and analysis of mechanical deformation and tube resistance occurred through the gait cycle and the variation of the center of gravity of the body by the following tests: stand up, support leg without the prosthesis, support in the leg with the prosthesis, walk forward and walk backward. Besides the characterization of optical sensors during the gait cycle and the variation of the gravity center in a transtibial amputated, the results also showed a high degree of integration of the sensors in the composite and a high mechanical strength of the material.