京都大学 / 新制・課程博士 / 博士(医学) / 甲第24992号 / 医博第5026号 / 新制||医||1069(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 後藤 慎平, 教授 安達 泰治, 教授 平井 豊博 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 161-178).

Thesis (Ph.D. in Pharmaceutical Sciences) -- University of Colorado, 2006. / Typescript. Includes bibliographical references (leaves 144-161). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;

The goal of this research was to develop a system of individualized medicine that could be applied to dermal wounds serving as a wound dressing and synthetic extracellular matrix while delivering stem cells to the wound bed. First, fabrication parameters for electrospinning polymer fibers were determined. This involved evaluating fiber morphology with respect to polymer selection and solution concentration. Next, construct fabrication was examined to produce an integrated void space, or cargo area, suitable to maintain stem cells. In vitro studies to ensure stem cell viability and phenotype were conducted, and results supported the notion that cells could be administered to the wound site through construct pre-seeding. Lastly, in vivostudies were conducted to evaluate the construct as an applied biomaterial and as a cellular delivery device. Wound closure and quality were assessed, and neo-vascularization quantified. This project will provide insight into the tissue engineering field regarding cell-based therapies and dermal wound healing.

Made available in DSpace on 2014-06-11T19:31:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-08-19Bitstream added on 2014-06-13T21:02:12Z : No. of bitstreams: 1 zanetti_lss_dr_araca.pdf: 1415676 bytes, checksum: 6158721af6f6a1ee60c101f886650479 (MD5) / Este estudo avaliou o uso do c opolímero de ácido poliláctico e poliglicólico (PLA/PGA) associado ao osso autógeno raspado, no reparo ósseo ocorrido ao redor de implantes inseridos em leitos sobrefresados, em tíbias de coelhos. (2) Material e métodos: Foram incluídos no estudo 20 coelhos e inseridos 40 implantes, divididos em dois grupos: Controle (C) e PLA/PGA adicionado a osso autógeno (G). Após fresagem controlada para simular a perda da estabilidade primária, cada implante foi inserido no leito preparado, tendo sido adicionado a sua superfície o copolímero PLA/PGA associado a osso autógeno raspado obtido manualmente. O grupo controle consistiu do implante com o espaço do leito preenchido por coágulo sangüíneo. Os animais foram sacrificados nos períodos de 15, 40 e 60 dias pós-operatórios, e foram realizadas as análises biomecânica e Imunoistoquímica. As tíbias onde estavam inseridos os implantes foram removidas, desc alcificadas, crioprotegidas e obtidos cortes que foram submetidos à reação imunoistoquímica mediante a utilização de anticorpos primários para RANKL, OPG e OC. No período de 60 dias pós-operatórios a analise biomecânica de torque-reverso foi realizada antes da descalcificação. (3) Resultados: Os resultados obtidos demonstraram que o copolímero PLA/PGA misturado ao osso autógeno apresentou-se biocompatível, bioabsorvivel e permitiu a neoformação óssea em contato com o implante, revelada pela análise da expressão das proteínas que regulam o ganho e a perda de massa óssea. E, houve predominância significante de deposição óssea e estabilidade revelada pela análise de torque-reverso (a= 0,05). (4) Conclusões: O copolímero de PLA/PGA pode ser utilizado no preenchimento de defeitos sobrefresados ao redor... / This study evaluated the polylactic and polyglycolic acid copolymer (PLA/PGA) with sc raped bone harvest in the bone repair occurrence of implants placed in large stream beds, in rabbit tibia. (2) Materials and Methods: Twenty rabbits had been enclosed in the study and 40 implants, in two groups: Control (C), PLA/PGA with the autologous bone scraped (G). After controlled drilled to simulate the loss of the primary stability, each implant was placed in the prepared stream bed, having been added to its surface the PLA/PGA copolymer with autologous bone scraped manually (G). The control group consisted of the implant placed in the space filled by blood. The animals had been sacrificed in the periods 15, 40 and 60 postoperative days, where the analyses had been carried through biomechanics and imunohistochemistry. The tibias where the implants were inserted had been removed, decalcified, frozen and getting cuts that had been submitted the imunoistochemistry reaction by means of the use of primary antibodies for RANK L, OPG and OC. In the 60 days period postoperative the against-torque biomechanics was carried through before the decalcified. (3) Results: The gotten results had disclosed that the copolymer PLA/PGA with bone graft showed biocompatibility, bioabsorption and allowed bone growing in contact with the implant, disclosed by expression of the proteins that regulate the profit and mass bone loss. And, had significant predominance of bone deposition and stability disclosed by against-torque ( = 0,05). (4) Conclusions: The PLA/PGA copolymer can be used filling defects drilled around implants in tibia of rabbits, when added bone harvest sc raped, therefore it presents characteristic s like biocompatibility and biodegradation, being totally resorpted and substituted by bone, allowing the bone formation with quality in the interface bone/implant.

Orientador: Idelmo Rangel Garcia Júnior / Banca: Paulo Sérgio Perri de Carvalho / Banca: Eduardo Hochuli Vieira / Banca: Márcio de Moraes / Banca: André Alberto Camara Puppin / Resumo: (1) Proposiç ão: Este estudo avaliou o uso do c opolímero de ácido poliláctico e poliglicólico (PLA/PGA) associado ao osso autógeno raspado, no reparo ósseo ocorrido ao redor de implantes inseridos em leitos sobrefresados, em tíbias de coelhos. (2) Material e métodos: Foram incluídos no estudo 20 coelhos e inseridos 40 implantes, divididos em dois grupos: Controle (C) e PLA/PGA adicionado a osso autógeno (G). Após fresagem controlada para simular a perda da estabilidade primária, cada implante foi inserido no leito preparado, tendo sido adicionado a sua superfície o copolímero PLA/PGA associado a osso autógeno raspado obtido manualmente. O grupo controle consistiu do implante com o espaço do leito preenchido por coágulo sangüíneo. Os animais foram sacrificados nos períodos de 15, 40 e 60 dias pós-operatórios, e foram realizadas as análises biomecânica e Imunoistoquímica. As tíbias onde estavam inseridos os implantes foram removidas, desc alcificadas, crioprotegidas e obtidos cortes que foram submetidos à reação imunoistoquímica mediante a utilização de anticorpos primários para RANKL, OPG e OC. No período de 60 dias pós-operatórios a analise biomecânica de torque-reverso foi realizada antes da descalcificação. (3) Resultados: Os resultados obtidos demonstraram que o copolímero PLA/PGA misturado ao osso autógeno apresentou-se biocompatível, bioabsorvivel e permitiu a neoformação óssea em contato com o implante, revelada pela análise da expressão das proteínas que regulam o ganho e a perda de massa óssea. E, houve predominância significante de deposição óssea e estabilidade revelada pela análise de torque-reverso (a= 0,05). (4) Conclusões: O copolímero de PLA/PGA pode ser utilizado no preenchimento de defeitos sobrefresados ao redor... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: (1) Purpose: This study evaluated the polylactic and polyglycolic acid copolymer (PLA/PGA) with sc raped bone harvest in the bone repair occurrence of implants placed in large stream beds, in rabbit tibia. (2) Materials and Methods: Twenty rabbits had been enclosed in the study and 40 implants, in two groups: Control (C), PLA/PGA with the autologous bone scraped (G). After controlled drilled to simulate the loss of the primary stability, each implant was placed in the prepared stream bed, having been added to its surface the PLA/PGA copolymer with autologous bone scraped manually (G). The control group consisted of the implant placed in the space filled by blood. The animals had been sacrificed in the periods 15, 40 and 60 postoperative days, where the analyses had been carried through biomechanics and imunohistochemistry. The tibias where the implants were inserted had been removed, decalcified, frozen and getting cuts that had been submitted the imunoistochemistry reaction by means of the use of primary antibodies for RANK L, OPG and OC. In the 60 days period postoperative the against-torque biomechanics was carried through before the decalcified. (3) Results: The gotten results had disclosed that the copolymer PLA/PGA with bone graft showed biocompatibility, bioabsorption and allowed bone growing in contact with the implant, disclosed by expression of the proteins that regulate the profit and mass bone loss. And, had significant predominance of bone deposition and stability disclosed by against-torque ( = 0,05). (4) Conclusions: The PLA/PGA copolymer can be used filling defects drilled around implants in tibia of rabbits, when added bone harvest sc raped, therefore it presents characteristic s like biocompatibility and biodegradation, being totally resorpted and substituted by bone, allowing the bone formation with quality in the interface bone/implant. / Doutor

Les travaux de recherche réalisés, dans le cadre de la préparation de cette thèse ont pour objectif l’élaboration de nouveaux réseaux thermoréversibles biodégradables à base de polyglycolide (PGA) et d’hydrogels à base de polylactide (PLA) modifiés chimiquement au moyen du noyau furanique et du cycle maléimide. La réticulation du PGA, en suivant deux stratégies, en vue d’élaborer des réseaux thermoréversibles et biodégradables via la réaction de Diels-Alder a fait l’objet de la première partie de ce travail. Le but était entre autres de valoriser le PGA en conduisant à des structures réticulées avec des propriétés mécaniques requises tout en améliorant ses propriétés de stabilité. Des réseaux hybrides de PLA/PEG et PLA/PHEMA ont été ensuite synthétisés en phase fondu en adoptant la réaction de Diels-Alder comme mécanisme de réticulation. Une fois obtenus, leur mise au contact de l’eau conduit à la formation d’hydrogels. Les analyses structurales menées par RMN ont permis de confirmer la formation des structures attendues. La thermoréversibilité des réseaux obtenus a été montrée par des analyses rhéologiques. La morphologie des gels avant et après gonflement a été analysée par Microscopie Electronique à balayage. La dégradabilité des réseaux préparés a été examinée selon deux modes : hydrolytique et par les microorganismes en milieu aérobie. / The research conducted for the preparation of this thesis aims to develop new thermoreversible and biodegradable polyglycolic-acid (PGA) based networks and polylactic-acid (PLA) based hydrogels, from polymers chemically modified by means of furanic, and maleimide cycle. The cross-linking of PGA to develop thermoreversible and biodegradable networks via the Diels-Alder reaction has been done by following two strategies and was the first part of this work. The aim was, among other things, to enhance the PGA by leading to reticulated structures with required mechanical properties while improving its stability properties. Hybrid networks of PLA / PEG and PLA / PHEMA were then synthesized in the melt by adopting the Diels-Alder reaction as a crosslinking mechanism. Once obtained, their contact with water leads to the formation of hydrogels. NMR structural analyzes confirmed the formation of expected structures. The thermoreversibility of the obtained networks has been shown by rheological analyzes. The morphology of the gels before and after swelling was analyzed by Scanning Electron Microscopy. The degradability of prepared networks was examined in two modes: hydrolytic and aerobic by microorganisms.

In einer prospektiv-randomisierten klinischen Studie zur Leistenhernienreparation wurde die konventionelle Shouldice Operation mit den spannungsfreien Verfahren durch Netzimplantation in endoskopischer (transabdominelle praeperitoneale Netzplastik, TAPP) und offener Technik (Plug und Patch Reparation; PP) verglichen. Bezogen auf das Hauptzielkriterium postoperative Schmerzen ergaben beide spannungsfreie Verfahren (TAPP, PP) signifikant guenstigere Ergebnisse als die Shouldice Operation. Bei vergleichbarer Komplikationsrate war die Dauer postoperativer Einschraenkungen bei den spannungsfreien Verfahren ebenfalls signifikant kuerzer als nach Shouldice Operation. Zur Verbesserung der fuer die spannungsfreie Reparation erforderlichen Netzimplantate wurde in einer Tierstudie versucht, die bislang durch Resorption ungenuegende mechanische Stabilitaet eines resorbierbaren Polyglycolsaeure-Netzes durch Zugabe von Fibrinkleber bzw. humanen thrombozytaeren Wachstumsfaktoren zu verbessern. Hierdurch gelang ein signifikanter Anstieg der mechanischen Stabilitaet, so daß in dem verwendeten Tiermodell keine Herniationen auftraten. / In a prospective-randomized study conventional Shouldice operation was compared with tension-free procedures using mesh implantation in endoscopic (transabdominal preperitoneal mesh repair, TAPP) and open technique (Plug and patch repair; PP) for inguinal hernia repair. Regarding the mean end point postoperative pain both tension-free procedures (TAPP, PP) revealed significantly better results than Shouldice operation. Complications were comparable between the groups but duration of postoperative restrictions was significantly shorter after both tension-free procedures. To improve mesh quality for tension-free hernia repair an animal experiment was performed using a resorbable polyglycolic acid mesh. Despite good incorporation this mesh shows insufficient tensile strength due to absorption. Application of fibrin glue or platelet releasates significantly improve the mechanical stability of the repair protecting against herniation in this animal model.