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京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19550号 / 医博第4057号 / 新制||医||1012(附属図書館) / 32586 / 京都大学大学院医学研究科医学専攻 / (主査)教授 坂井 義治, 教授 三嶋 理晃, 教授 開 祐司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Coronary stent placement is a routine treatment of coronary artery disease, the leading cause of death worldwide. Intravascular Optical Coherence Tomography (IVOCT) is a superior imaging assessment technique in coronary stenting. To characterize IVOCT artifacts, phantom blood vessels were constructed and metallic and bioabsorable coronary stents were deployed with and without phantom neointima. High resolution Micro-CT images of the stent strut were recorded as a gold standard and utilized to create a three-dimensional representation of a strut that was imported into computer optical simulations. Simulated IVOCT images were computed that include the IVOCT catheter, light reflection from stent struts with varying neointimal thickness and scattering in the vessel lumen. The simulation results along with IVOCT images of the phantom vessels were utilized to elucidate the mechanisms underlying the “sunflower effect”, bending of stent struts toward the imaging catheter and “merry-go-round” effect, variable apparent strut size of metallic stents. Atomic force microscopy was used to examine surface properties of metallic and bioabsorbale stents, revealing sources of the distinctive appearance of bioabsorable stents in IVOCT images. The model formed a basis to develop a correction algorithm to remove stent artifacts in clinical IVOCT images. / text

Introdução: O uso de molas metálicas para o tratamento das craniossinostoses têm ganho cada vez mais espaço no arsenal terapêutico do cirurgião Crânio-Maxilo-Facial, na intenção de minimizar procedimentos extensos e mórbidos. Apesar da simplificação cirúrgica promovida pela mesma ainda persiste a necessidade de sua remoção. Objetivos: Realizar expansão craniana cirúrgica em modelo animal, utilizando-se de um implante (mola) totalmente integrado, confeccionado em blenda polimérica bioabsorvível. Testar sua eficácia e realizar análise histológica. Material e Métodos: Estudo experimental, aberto e prospectivo, utilizando doze coelhos fêmeas da raça New Zealand (Oryctolagus cuniculus) com seis semanas de vida. Os animais foram randomizados em dois grupos: controle (G1) aonde foi realizada craniectomia linear, e estudo (G2) aonde além da craniectomia foi inserida uma mola confeccionada a partir de uma blenda de POLI ÁCIDO LÁCTICO-CO-GLICÓLICO/POLI ISOPRENO, com o objetivo de realizar expansão craniana no sentido transversal à ostectomia. A movimentação craniana foi mensurada radiologicamente nas 12 semanas seguintes, através de marcadores e ao final foi realizada análise histológica para avaliação de reação inflamatória. Resultados: As molas confeccionadas apresentaram uma força média de 4,2N. A expansão craniana no grupo estudo no nível do marcador frontal foi de 9,6mm a 11,67mm e foi significante em relação a grupo controle. A análise histológica demonstrou pequena reação inflamatória. Conclusão: É possível a realização de expansão craniana em modelo animal utilizando-se uma mola bioabsorvível através de craniectomia linear, com boa tolerabilidade dos tecidos circunjacentes ao implante. / Introduction: The use of metal springs for the treatment of craniosynostosis have gaining more and more posicion in the therapeutic armory of the Craniofacial surgeon in the intention to minimize morbid and extensive procedures. Objectives: Perform cranial expansion surgery in an animal model, using an implant elastic (spring) fully integrated, made of bio-absorbable polymeric material. Test its efficacy and histological analysis Methods: An experimental study, open, prospective, using twelve New Zealand female rabbits (Oryctolagus cuniculus) with six weeks. The animals were randomized into two groups: control (G1) where linear craniectomy was performed and study (G2) where besides the craniectomy a spring made from a blend of POLY LACTIC ACID-CO-GLYCOLIC / POLI ISOPRENE, in order to perform cranial expansion in the transverse osteotomy. The cranial movement was assessed radiographically at 12 weeks following the surgical procedure and the final histological analysis was performed to evaluate the inflammatory reaction. Results: The springs made showed a medium force of 4,2N. The cranial expansion in the study group in the level of the frontal marker was of 9,6mm to 11,67 and was significant in relation to the control group. The histological analysis showed a small inflammatory reaction. Conclusion: It is possible to perform cranial expansion in an animal model using a bio-absorbable spring through the linear craniectomy. There was good tolerability of the surrounding tissues to the implant.

Background. Operative stabilisation of paediatric supracondylar elbow fractures is most commonly achieved through the use of percutaneous Kirschner wires. These implants are inert, cheap and simple to use. However, the requirement for removal and the possibility of pin site infection provides opportunity for the development of new techniques that eliminate these drawbacks. Bioabsorbable pins that remain in situ and allow definitive closure of skin at the time of surgery could provide such advantages. However, their ability to maintain fracture reduction and their effect on the growth plate has not been adequately evaluated. Hypotheses. The Acumed® Biotrak Helical Nail (a bioabsorbable fixation implant) has comparable strength to Kirschner wires and does not result in significant disruption of the growth plate or subsequent growth. Studies. Three complementary studies were performed. (1) A retrospective cohort analysis was performed to establish the prevalence of complications related to Kirschner wire fixation of paediatric supracondylar elbow fractures. (2) A saw-bone model was designed to compare the mechanical performance of the Helical Nail and Kirschner wires. (3) An ovine model was designed to assess the in vivo effects of the Helical Nail on limb growth and physeal morphology. The surgical practicalities of the device and its potential for use in the paediatric setting were evaluated. The primary outcome was femoral length six months after Helical Nail insertion. Micro-CT evaluation of growth plate thickness, percentage disruption and bony infiltration was undertaken – the first time this technique has been used in a large animal study. Traditional histopathological techniques complimented the Micro-CT analysis and offered comment on the microscopic appearance of the growth plate immediately adjacent to the bioabsorbable nails. Results. The infection rate within a large tertiary referral centre was 9.6%, which was marginally higher than previous cohort studies. Mechanical testing demonstrated that the Helical Nail had comparable strength in rotation, but inferior resistance to posterior translation, when compared to Kirschner wires. In the ovine model, the Helical Nail disrupted 3.4% of the physis. The nails had no effect on femoral growth during the six month study period. Micro-CT analysis of both the helical nail and Kirschner wire groups demonstrated multiple bony bridges, with two cases of physeal tethering in the Helical Nail group. There was no difference in physeal thickness or bony infiltration of the physis. Histopathology did not reveal any significant inflammatory or foreign body reaction adjacent to the nails. Conclusion. The Helical Nail demonstrated a number of encouraging attributes which indicate its potential. However, in its current state the device is not suitable for use in the stabilisation of paediatric supracondylar elbow fractures.

Introdução: O uso de molas metálicas para o tratamento das craniossinostoses têm ganho cada vez mais espaço no arsenal terapêutico do cirurgião Crânio-Maxilo-Facial, na intenção de minimizar procedimentos extensos e mórbidos. Apesar da simplificação cirúrgica promovida pela mesma ainda persiste a necessidade de sua remoção. Objetivos: Realizar expansão craniana cirúrgica em modelo animal, utilizando-se de um implante (mola) totalmente integrado, confeccionado em blenda polimérica bioabsorvível. Testar sua eficácia e realizar análise histológica. Material e Métodos: Estudo experimental, aberto e prospectivo, utilizando doze coelhos fêmeas da raça New Zealand (Oryctolagus cuniculus) com seis semanas de vida. Os animais foram randomizados em dois grupos: controle (G1) aonde foi realizada craniectomia linear, e estudo (G2) aonde além da craniectomia foi inserida uma mola confeccionada a partir de uma blenda de POLI ÁCIDO LÁCTICO-CO-GLICÓLICO/POLI ISOPRENO, com o objetivo de realizar expansão craniana no sentido transversal à ostectomia. A movimentação craniana foi mensurada radiologicamente nas 12 semanas seguintes, através de marcadores e ao final foi realizada análise histológica para avaliação de reação inflamatória. Resultados: As molas confeccionadas apresentaram uma força média de 4,2N. A expansão craniana no grupo estudo no nível do marcador frontal foi de 9,6mm a 11,67mm e foi significante em relação a grupo controle. A análise histológica demonstrou pequena reação inflamatória. Conclusão: É possível a realização de expansão craniana em modelo animal utilizando-se uma mola bioabsorvível através de craniectomia linear, com boa tolerabilidade dos tecidos circunjacentes ao implante. / Introduction: The use of metal springs for the treatment of craniosynostosis have gaining more and more posicion in the therapeutic armory of the Craniofacial surgeon in the intention to minimize morbid and extensive procedures. Objectives: Perform cranial expansion surgery in an animal model, using an implant elastic (spring) fully integrated, made of bio-absorbable polymeric material. Test its efficacy and histological analysis Methods: An experimental study, open, prospective, using twelve New Zealand female rabbits (Oryctolagus cuniculus) with six weeks. The animals were randomized into two groups: control (G1) where linear craniectomy was performed and study (G2) where besides the craniectomy a spring made from a blend of POLY LACTIC ACID-CO-GLYCOLIC / POLI ISOPRENE, in order to perform cranial expansion in the transverse osteotomy. The cranial movement was assessed radiographically at 12 weeks following the surgical procedure and the final histological analysis was performed to evaluate the inflammatory reaction. Results: The springs made showed a medium force of 4,2N. The cranial expansion in the study group in the level of the frontal marker was of 9,6mm to 11,67 and was significant in relation to the control group. The histological analysis showed a small inflammatory reaction. Conclusion: It is possible to perform cranial expansion in an animal model using a bio-absorbable spring through the linear craniectomy. There was good tolerability of the surrounding tissues to the implant.

Introdução: O uso de molas metálicas para o tratamento das craniossinostoses têm ganho cada vez mais espaço no arsenal terapêutico do cirurgião Crânio-Maxilo-Facial, na intenção de minimizar procedimentos extensos e mórbidos. Apesar da simplificação cirúrgica promovida pela mesma ainda persiste a necessidade de sua remoção. Objetivos: Realizar expansão craniana cirúrgica em modelo animal, utilizando-se de um implante (mola) totalmente integrado, confeccionado em blenda polimérica bioabsorvível. Testar sua eficácia e realizar análise histológica. Material e Métodos: Estudo experimental, aberto e prospectivo, utilizando doze coelhos fêmeas da raça New Zealand (Oryctolagus cuniculus) com seis semanas de vida. Os animais foram randomizados em dois grupos: controle (G1) aonde foi realizada craniectomia linear, e estudo (G2) aonde além da craniectomia foi inserida uma mola confeccionada a partir de uma blenda de POLI ÁCIDO LÁCTICO-CO-GLICÓLICO/POLI ISOPRENO, com o objetivo de realizar expansão craniana no sentido transversal à ostectomia. A movimentação craniana foi mensurada radiologicamente nas 12 semanas seguintes, através de marcadores e ao final foi realizada análise histológica para avaliação de reação inflamatória. Resultados: As molas confeccionadas apresentaram uma força média de 4,2N. A expansão craniana no grupo estudo no nível do marcador frontal foi de 9,6mm a 11,67mm e foi significante em relação a grupo controle. A análise histológica demonstrou pequena reação inflamatória. Conclusão: É possível a realização de expansão craniana em modelo animal utilizando-se uma mola bioabsorvível através de craniectomia linear, com boa tolerabilidade dos tecidos circunjacentes ao implante. / Introduction: The use of metal springs for the treatment of craniosynostosis have gaining more and more posicion in the therapeutic armory of the Craniofacial surgeon in the intention to minimize morbid and extensive procedures. Objectives: Perform cranial expansion surgery in an animal model, using an implant elastic (spring) fully integrated, made of bio-absorbable polymeric material. Test its efficacy and histological analysis Methods: An experimental study, open, prospective, using twelve New Zealand female rabbits (Oryctolagus cuniculus) with six weeks. The animals were randomized into two groups: control (G1) where linear craniectomy was performed and study (G2) where besides the craniectomy a spring made from a blend of POLY LACTIC ACID-CO-GLYCOLIC / POLI ISOPRENE, in order to perform cranial expansion in the transverse osteotomy. The cranial movement was assessed radiographically at 12 weeks following the surgical procedure and the final histological analysis was performed to evaluate the inflammatory reaction. Results: The springs made showed a medium force of 4,2N. The cranial expansion in the study group in the level of the frontal marker was of 9,6mm to 11,67 and was significant in relation to the control group. The histological analysis showed a small inflammatory reaction. Conclusion: It is possible to perform cranial expansion in an animal model using a bio-absorbable spring through the linear craniectomy. There was good tolerability of the surrounding tissues to the implant.

Submitted by Diogo Misoguti (diogo.misoguti@gmail.com) on 2016-06-24T19:52:09Z No. of bitstreams: 1 2015-12-doutorado-pedro-debieux-vargas-silva.pdf: 2344545 bytes, checksum: 1ecd3c6040fb5757f7f2df3ba6314152 (MD5) / Approved for entry into archive by Diogo Misoguti (diogo.misoguti@gmail.com) on 2016-06-24T19:52:38Z (GMT) No. of bitstreams: 1 2015-12-doutorado-pedro-debieux-vargas-silva.pdf: 2344545 bytes, checksum: 1ecd3c6040fb5757f7f2df3ba6314152 (MD5) / Made available in DSpace on 2016-06-24T19:52:38Z (GMT). No. of bitstreams: 1 2015-12-doutorado-pedro-debieux-vargas-silva.pdf: 2344545 bytes, checksum: 1ecd3c6040fb5757f7f2df3ba6314152 (MD5) Previous issue date: 2015 / Introdução: Esta revisão avalia se os parafusos de interferência bioabsorvíveis podem apresentar melhores resultados do que os parafusos de interferência metálicos quando utilizados para a fixação do enxerto na reconstrução do LCA. Objetivo: Comparar a efetividade dos parafusos de interferência bioabsorvíveis e metálicos para a fixação do enxerto na reconstrução do ligamento cruzado anterior, através de meta-análise. Métodos: Foram pesquisadas as bases de dados: Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, The Cochrane Library, MEDLINE, EMBASE, LILACS, Current Controlled Trials e the World Health Organization Clinical Trials Registry Platform. Ensaios clínicos randomizados e quasi-randomizado comparando parafusos de interferência bioabsorvíveis com metálicos foram incluídos na pesquisa. Os desfechos primários foram função, qualidade de vida, falhas de tratamento e nível de atividade. Ao menos dois autores selecionaram estudos elegíveis e avaliaram de forma independente o risco de viés. Os dados relevantes foram agrupados. Resultados: Onze ensaios envolvendo 981 participantes foram incluídos na revisão. Em relação à função (avaliada pelo Lysholm), quatro ensaios clínicos (220 participantes) não mostraram diferenças entre os dois métodos de fixação com 12 ou 24 meses de seguimento: MD -026, IC 95%, -1,63 a 1,11 e MD 1,10, IC 95% -1,44 a 1,64, respectivamente. Quando realizada a análise de subgrupos do Lysholm, entretanto, foi observada diferença estatística favorável ao parafuso metálico, quando o parafuso bioabsorvível era constituído por Ácido-L-Polilático (PLLA): RR -4,00, 95% CI -7,59 a -0,41. Três estudos com 24 meses (RR 1,00, 95% CI 0,81-1,24) e dois estudos com 12 meses de seguimento (RR 1,01, 95% CI 0,94-1,08) não mostraram diferenças no IKDC. Em relação ao nível de atividade (analisado pelo Tegner), dois estudos (117 participantes) com 12 meses, e três estudos com 24 meses de seguimento não evidenciaram diferenças entre o grupo bioabsorvível e o grupo que usou parafuso de metal: MD 0.08, 95% CI -0,39 a 0,55 e MD 0,41, IC 95% -0,23 a 1,05, respectivamente. Na análise de subgrupos, houve diferença estatística favorável ao parafuso de PLLA: RR 1,27, 95% CI 0,49 a 3,30. Apesar da diferença estatística, em nenhum dos desfechos supracitados observou-se relevância clínica. Em relação às falhas de tratamento, foi demonstrada uma diferença significativa entre os dois métodos de fixação, quando considerada a quebra de implante (RR 7,06, 95% CI 1,31-2,75) e quanto ao risco global de falha do tratamento (RR 1,89, 95% CI 1,31-2,75), tendo o parafuso bioabsorvível mais falhas nestes aspectos. Em oposição, não houve diferença significativa para estabilidade, testes funcionais, derrame articular, re-lesões, infecção, reação de corpo estranho, dor ou limitação de movimento. Conclusão: Não há evidência que demonstre diferença de efetividade entre parafusos de interferência metálicos com relação aos bioabsorvíveis para fixação do enxerto na reconstrução do ligamento cruzado anterior quanto a função, qualidade de vida e o nível de atividade; entretanto, há evidências de que parafusos bioabsorvíveis estão associados a mais falhas de tratamento global e quebra do implante. Os ensaios clínicos randomizados presentes na literatura fornecem evidências de moderada/baixa qualidade. / Introduction: This review assesses whether bioabsorbable interference screws may show better results than metal ones when used for fixing the graft in the reconstruction of the anterior cruciate ligament (ACL). Objective: To compare the effects of bioabsorbable and metal interference screws for fixing the graft in the reconstruction of the anterior cruciate ligament, by metaanalysis. Methods: The following databases were searched: Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, The Cochrane Library, MEDLINE, EMBASE, LILACS, Current Controlled Trials and the World Health Organization International Clinical Trials Registry Platform. Randomized controlled trials and quasi-randomized trials comparing bioabsorbable with metal interference screws were included in the survey. Primary outcome measures were function, quality of life, treatment failures and activity level. At least two authors selected eligible studies and independently assessed the risk of bias. The relevant data were pooled. Results: Eleven trials involving 981 participants were included in the review. Regarding the function (assessed by Lysholm), four trials (220 participants) showed no differences between the two fixation methods with 12 or 24 months of follow-up: MD -026, CI 95% -1.63 - 1.11 and MD 1.10, CI 95% - 1.44 to 1.64, respectively. However, when subgroup analysis using Lysholm score was performed, statistical difference was observed favoring the metal screw when the bioabsorbable screw was comprised of L-polylactic acid (PLLA): RR -4.00, CI 95%, -7.59 - -0.41. Three studies at 24 months (RR 1.00, 95% CI 0.81 to 1.24) and two studies at 12 months follow-up (RR 1.01, 95% CI 0.94 to 1.08) showed no differences the in the IKDC. Regarding the level of activity (analyzed by Tegner activity level scale), two studies (117 participants) at 12 months and three studies at 24 months follow-up showed no differences between the bioabsorbable group and the group using metal screws: MD 0.08, 95 % CI -0.39 to 0.55 and MD 0.41, 95% CI -0,23-1,05 respectively. In the subgroup analysis, a statiscally favorable difference was found for the PLLA screw: RR 1.27, 95% CI 0.49 to 3.30. Despite the statistical differences, none of the above outcomes has presented clinical relevance. With regard to treatment failures, a significant difference was found between the two methods of attachment, when considering the implant breaks (RR 7.06, 95% CI 1.31 to 2.75) and the overall risk of failure (RR 1.89, CI 95% 1.31 to 2.75), with the bioabsorbable screw having more failures in these respects. In contrast, there was no significant difference in stability, functional testing, joint effusion, re-injury, infection, foreign body reaction, pain or limitation of movement. Conclusion: There is no evidence that demonstrates an effective difference between metal and bioabsorbable interference screws for graft fixation in the reconstruction of the anterior cruciate ligament when considering function, quality of life and level of activity. However, there is evidence that bioabsorbable screws are associatewith more failures in the global treatment as well as breaks of the implant. Clinical trials in the literature provide moderate / low quality evidence.

L’objectif de ce travail était d’élaborer un copolymère biodégradable dans le but de développer une endoprothèse biorésorbable. Ainsi, des copolymères de lactide et de glycolide ont été synthétisés par copolymérisation par ouverture de cycle, dans des conditions permettant le contrôle de leurs paramètres macromoléculaires. Après plastification et mise en forme des copolymères par extrusion, l’étude des propriétés mécaniques, à l’état sec et après immersion en milieu aqueux, a été réalisée. Les essais de traction ont permis de vérifier l’importance de la vitesse de sollicitation et d’accéder à certaines grandeurs caractéristiques du matériau. L’étude de la dégradation des copolymères, sous forme de jonc, a mis en évidence un mécanisme de dégradation hétérogène sur une durée en accord avec l’application visée. La plastification par des molécules acides a permis d’accélérer la vitesse d’hydrolyse des copolymères. En conclusion, les propriétés mécaniques et de dégradation des copolymères PDLGA synthétisés sont donc en adéquation avec le cahier des charges de l’application biomédicale. / This work describes the synthesis of biodegradable copolymer to design a bioabsorbable endoprosthesis. Lactide and glycolide-based copolymers were synthesized by ring opening polymerization. Experimental conditions were chosen to produce controlled structures. The study of mechanical properties was performed in dry and wet states. During the tensile experiments, the effect of strain rate was noticed and some characteristics parameters were determined. Hydrolytic degradation of materials was fast and revealed a heterogeneous mechanism. Addition of acidic molecules for plasticizing increased the degradation rate of the copolymers.Mechanical properties and degradation of the PDLGA copolymers are indeed in good agreement with the specifications of this biomedical application.

No description available.