Despite the effort to optimize soft contact lens performance, almost half of the 140 million contact lens wearers worldwide experience symptoms of ocular dryness and discomfort, especially towards the end of the day. These symptoms are attributed to reduced compatibility between the contact lens and the ocular surface and are the main reason for contact lens discontinuation. As the interactions of the contact lens-eye interface are dynamic, the surface properties play a key role in improving ocular compatibility, comfort and overall performance of contact lenses. One promising method to reduce adverse interfacial interactions between the contact lens and the ocular surface is to modify the contact lens surface with a biomimetic layer inspired by the ocular surface and the tear film. Hyaluronic acid (HA) is a non-sulfated glycosaminoglycan naturally found in the ocular environment providing ocular hydration and lubrication. Proteoglycan 4 (PRG4), a mucin-like glycoprotein naturally produced at the ocular surface contributes to natural lubrication during blinking and to tear film stability. Surface modification with HA or PRG4 has been shown to result in improved wetting, lubricating and antifouling properties. Moreover, HA and PRG4 have been previously found to interact and synergistically reduce friction further. In the current work, novel HA and PRG4-grafted soft contact lens surfaces were prepared, and the impact of the surface tethered layer on important contact lens properties was assessed. Furthermore, the potential synergistic effect between HA and rhPRG4 on the examined properties was evaluated. Surface immobilization of HA on model conventional (pHEMA) and silicone (pHEMA-co-TRIS) hydrogel contact lenses was achieved by thiol-ene “click” chemistry, while full-length recombinant human PRG4 (rhPRG4) was surface grafted via carbonyldiimidazole (CDI) linking chemistry respectively. The chemical structure after each modification step was determined by attenuated total reflectance FTIR (FTIR-ATR) and X-ray photoelectron spectroscopy (XPS) analyses. HA-grafted model soft contact lenses were characterized by improved surface wettability, antifouling and water retentive properties, while a decreasing trend in boundary friction was observed but only for the HA-grafted pHEMA-co-TRIS materials. Surface-tethering of rhPRG4 was found to effectively enhance the surface wettability and boundary lubricating properties of pHEMA-co-TRIS hydrogels only, whereas both rhPRG4-grafted pHEMA and pHEMA-co-TRIS materials exhibited lower protein sorption and dehydration rate. Overall, the surface immobilization processes followed herein did not alter the optical transparency of the model soft contact lenses or their in vitro compatibility with human corneal epithelial cells. Finally, there was evidence that HA and rhPRG4 synergistically interacted, further improving the contact lens properties. However, the degree of HA/rhPRG4 synergy was found to be dependent on the configuration of the formed HA/rhPRG4 complex as well as the composition of the substrate hydrogel material, with the noted improvement being more significant for the model silicone hydrogels. This is the first study to examine surface grafted full-length rhPRG4 and the effect of this modification on contact lens properties. Moreover, the study is the first to investigate the interactions between covalently tethered rhPRG4 and solutions containing HA. The results of this thesis demonstrate that HA and rhPRG4 are good candidates for the development of novel biomimetic surfaces, especially for silicone hydrogel contact lenses. The potential for using these compounds in synergy was also demonstrated, with wetting solutions of HA showing promise for modifying rhPRG4 modified materials to improve symptoms of discomfort. These naturally occurring ocular agents have the potential to improve the management of ocular dryness and discomfort, thus optimizing the overall soft contact lens performance. / Thesis / Doctor of Philosophy (PhD)

Made available in DSpace on 2014-06-11T19:32:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-01-27Bitstream added on 2014-06-13T19:03:28Z : No. of bitstreams: 1 oliveira_jag_dr_guara.pdf: 2054384 bytes, checksum: 2056494b4d46299584c8acf22e9f6838 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Os Biomateriais Metálicos são utilizados para reforçar ou para restaurar a forma e função de tecidos duros. Os implantes e próteses são utilizados para substituir ombros, joelhos, quadris e dentes perdidos entre outros. Nos últimos anos, varias ligas de titânio para aplicações biomédicas foram avaliadas. Neste trabalho, a influência do tratamento de superfície biomimético na osseointegração de implantes dentários da liga Ti-7,5Mo foi avaliada. Os lingotes foram obtidos a partir de titânio e molibdênio utilizando um forno a arco voltaico. Eles foram submetidos a tratamento térmico e conformados a frio em prensa rotativa. Posteriormente foram confeccionados implantes (2,0 mm de diâmetro e 2,5 mm de comprimento) sob medida os quais submetidos ao tratamento de superfície biomimético. Os implantes foram inseridos e analisados histológica realizada após 28 dias. A caracterização microestrutural e mecânica da liga Ti-7,5Mo também foi realizada. Aliga Ti-7,5Mo exibiu baixo modulo de elasticidade e elevada relação resistência/modulo. O uso do tratamento de superfície biomimético promoveu um aumento da osseointegração sobre a superfície dos implantes / Metallic biomaterials are used to reinforce or to restore form and function of hard tissues. Implants and prosthesis are used to replace shoulders, knees, hips and teeth. In the last years, several titanium alloys for biomedical applications have been studied. In the present work, influence of biomimetic surface treatment in osseointegration of Ti-7.5Mo dental implant was evaluated. Ingots were obtained from titanium and molybdenum by using an arc-melting furnace. They were submitted to heat treatment and cold worked by swaging. Then, screw-shaped implants (2.0 mm diameter by 2.5 mm length) were custom made and they were submitted biomimetic surface treatment. Implants were implanted in the rat’s femur and histological analysis was realized after 28 days. Also, microstructural and mechanical properties of Ti-7.5Mo alloy were evaluated. Ti-7.5Mo showed low elasticity modulus and higher ratio strength/modulus. Results obtained suggest that Ti-7.5Mo exhibited excellent bulk properties. The use of the biomimetic surface treatment was able to promote an increase of osseointegration on surface of dental implants

Orientador: Ana Paula Rosifini Alves Claro / Coorientador: Maria Cristina Rosifini Alves Rezende / Banca: Carlos Roberto Grandini / Banca: Estevão Tomomitsu Kimpara / Banca: Mônica Beatriz Mathor / Banca: Ana Christina Alves Rezende / Resumo: Os Biomateriais Metálicos são utilizados para reforçar ou para restaurar a forma e função de tecidos duros. Os implantes e próteses são utilizados para substituir ombros, joelhos, quadris e dentes perdidos entre outros. Nos últimos anos, varias ligas de titânio para aplicações biomédicas foram avaliadas. Neste trabalho, a influência do tratamento de superfície biomimético na osseointegração de implantes dentários da liga Ti-7,5Mo foi avaliada. Os lingotes foram obtidos a partir de titânio e molibdênio utilizando um forno a arco voltaico. Eles foram submetidos a tratamento térmico e conformados a frio em prensa rotativa. Posteriormente foram confeccionados implantes (2,0 mm de diâmetro e 2,5 mm de comprimento) sob medida os quais submetidos ao tratamento de superfície biomimético. Os implantes foram inseridos e analisados histológica realizada após 28 dias. A caracterização microestrutural e mecânica da liga Ti-7,5Mo também foi realizada. Aliga Ti-7,5Mo exibiu baixo modulo de elasticidade e elevada relação resistência/modulo. O uso do tratamento de superfície biomimético promoveu um aumento da osseointegração sobre a superfície dos implantes / Abstract: Metallic biomaterials are used to reinforce or to restore form and function of hard tissues. Implants and prosthesis are used to replace shoulders, knees, hips and teeth. In the last years, several titanium alloys for biomedical applications have been studied. In the present work, influence of biomimetic surface treatment in osseointegration of Ti-7.5Mo dental implant was evaluated. Ingots were obtained from titanium and molybdenum by using an arc-melting furnace. They were submitted to heat treatment and cold worked by swaging. Then, screw-shaped implants (2.0 mm diameter by 2.5 mm length) were custom made and they were submitted biomimetic surface treatment. Implants were implanted in the rat's femur and histological analysis was realized after 28 days. Also, microstructural and mechanical properties of Ti-7.5Mo alloy were evaluated. Ti-7.5Mo showed low elasticity modulus and higher ratio strength/modulus. Results obtained suggest that Ti-7.5Mo exhibited excellent bulk properties. The use of the biomimetic surface treatment was able to promote an increase of osseointegration on surface of dental implants / Doutor