1. A review of the literature on cartilage canals is given. 2. The formation of cartilage canals commences when the cartilage mass exceeds the maximum thickness which can be nourished by diffusion of fluid from the surface. This maximum thickness or the critical size at which canalization would occur, has been worked out in the distal femoral epiphysis at various developmental stages. It varies with the age of the foetus 0.25 mm. at the fourth month and gradually increasing to about 0.6 mm. at full-term. 3. Because of the restricted area of origin of the cartilaginous epiphysis of long bones, the canals seldom found, to be arranged in a radial fashion to the whole epiphysis, but they arranged so as to distribute the blood evenly through the whole mass. 4. (i) The clear, well-formed communicating canals have been seen in the epiphysis of human long bone as early as the fourth month of foetal life. (ii) As development proceeds, some of the communicating canals appear to become obliterated in, the region of proliferating cartilage adjacent to the metaphysis: this obliteration of canals occurs more rapidly after the onset of epiphyseal ossification so that by the time ossification of the epiphysis is complete, no communications between the diaphysis and the epiphysis remain. (iii) It is suggested that probably the primary cause of the formation of the communicating canal is the chemio-taxio influence in the zone of actively growing cartilage in the region adjacent to metaphysis, which directs the ends of the canals arising from the perichondrium near the end of the shaft to bend towards the diaphyseal end. (iii) The probable function of the communicating canals is that they assist in the supply of nutrition to and in the removal of waste products from the cells in the active juxta-metaphyseal cartilage. The almost invariable absence of osteogenic elements in these canals given no support to the hypothesis that they take part in the formation of the centre of epiphyseal ossification. (v) The vascular connective tissue buds which are identical with the communicating canals in the epiphysis of long bone, have boon observed in the cartilaginous sternal end of the clavicle of a human foetus. 5. It is suggested that the cartilage canals grow by a combination of three methods that is by surface accretion, stretching due to interstitial growth and active invasion of the cartilage by the tip of the canal. 6. The cartilage canal connective tissue contents are of perichondrial origin, and are not formed by back differentiation of the cartilage to an embryonic type of connective tissue. 7. In the long bone of the human, the cartilage canals are probably responsible for the formation of the epiphyseal ossification centre.

Low back pain is one of the major health concerns in the US. It affects up to 80% of the population at some time during their lives. It not only causes discomfort to patients and affects their physical ability but also has a huge economic impact on society. Although the cause of low back pain is still poorly understood, it is implicated that degeneration of the intervertebral disc is the primary factor. Currently, researchers are trying to use tissue engineering approaches to develop new treatments capable of removing the degenerated disk and replacing it with a biological substitute. However, to create such a biological substitute, we need to first understand the structure-function relationship of the tissue. Only when we understand the function of the tissue, can we begin creating biological substitutes. While culturing a biological substitute, we also need methods to determine how the substitute responds to its environment. At present, there are many different types of bioreactors developed for cartilaginous tissues. However, there is a lack of a system that can detect the chemical, electrical and mechanical response noninvasively with control feedback in real-time. It is hard to provide the optimal culture environment to the substitute without knowing its response in real-time. The objective of this dissertation is to develop new methods to investigate the transport property, oxygen consumption rate and mechano-electrochemical and mechanical properties of the tissue. Because cells are responsible for the tissue health, it is necessary to understand how they can obtain nutrients under different environments, e.g. under different loading condition. In addition, with the use of a bioreactor with the capability of detecting the real-time response combined with a feedback control system, we can provide the most favorable conditions for tissue or biological substitutes to grow. The new measurement methods developed in this dissertation can contribute to further understanding the function of the tissue. The methods outlined in this dissertation can also provide new tools for future tissue engineering applications. Moreover, the findings in this dissertation can provide information for developing a more comprehensive theoretical model to elucidate the etiology of disc degeneration.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19891号 / 医博第4140号 / 新制||医||1016(附属図書館) / 32968 / 京都大学大学院医学研究科医学専攻 / (主査)教授 妻木 範行, 教授 山田 泰広, 教授 開 祐司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

<p>An accurate understanding of the respiratory fluid dynamics is instrumental for medical applications, such as drug delivery system and treatment of diseases. Substantial research has been done to study such flow. However, a great number of these studies have the prevailing assumption of having a smooth wall, in despite the human trachea and bronchi is sustain by a series of cartilaginous rings, which creates height differences near the wall. To study the effect of including cartilaginous rings in the respiratory flow we developed two experiments, presenting a comparison between a smooth model and a model with cartilaginous rings. First, we present an experimental observation of a simplified Weibel-based model of the human trachea and bronchi with cartilaginous rings. The experiments were carried out with a flow rate comparable with a resting state (trachea-based Reynolds number of Re_D = 2650). In the second experiment, we developed a similar experiment but in a model with a tracheal stenosis (70% in the middle of the model) and no bronchi. In this case we increase the Reynolds number to Re_D= 3350, still a resting breathing state condition.</p> <p>For both experiments, we used transparent models and refractive index-matching methods were used to observe the flow, particularly near the wall. The flow was seeded with tracers to perform particle image velocimetry and particle tracking velocimetry to quantify the effect the rings have on the flow near the trachea and bronchi walls. From the results, we present a previously unknown phenomenon in the cavities between the cartilaginous rings: a small recirculation is observed in the upstream side of the cavities throughout the trachea. This recirculation is due to the adverse pressure gradient created by the expansion, which traps particles within the ring cavity. In addition, we found that the cartilaginous rings induce velocity fluctuations into the flow, which enhances the near-wall momentum of the flow reducing the separation after the stenosis. Size of the recirculation is reduced by 11% and the maximum upstream velocity is reduced by 38%, resulting in a much weaker recirculation because of the rings. Also noticed a delay in the separation from the trachea to bronchi bifurcation. </p> <p>The detection of recirculation zones in the cartilage ring cavities and the perturbation sheds light on the particle deposition mechanism and helps explain results from previous studies that have observed an enhancement of particle deposition in models with cartilage rings. The results highlight the importance to include the cartilaginous rings in respiratory flow studies. Finally, we compared the results from the stenotic case with Reynolds-averaged Navier-Stokes (RANS) models (k – ε, k – ε RNG, k – ω, k – ω SST, k – ω SST LRN and 4-equation Transition SST). In the results, indicate significant discrepancies between the experimental measurements and the simulations, mainly in the area with flow separation after the contraction. Therefore, RANS algorithms should not be considered reliable for research purposes in respiratory fluid dynamics without experimental validation. </p>

Submitted by Onia Arantes Albuquerque (onia.ufg@gmail.com) on 2018-10-30T13:45:30Z No. of bitstreams: 2 Dissertação - Lorena Damasio Cardoso - 2018.pdf: 3279572 bytes, checksum: 019cc5a3b996db0774fcbab0c3c38770 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2018-10-30T15:16:02Z (GMT) No. of bitstreams: 2 Dissertação - Lorena Damasio Cardoso - 2018.pdf: 3279572 bytes, checksum: 019cc5a3b996db0774fcbab0c3c38770 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-10-30T15:16:02Z (GMT). No. of bitstreams: 2 Dissertação - Lorena Damasio Cardoso - 2018.pdf: 3279572 bytes, checksum: 019cc5a3b996db0774fcbab0c3c38770 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-10-01 / The loss of tissue because of congenital defects, pathological processes or traumas stimulated the development of tissue engineering, with the aim of repairing or replacing damaged tissues or organs. Due to its elastic properties, cartilaginous tissue has been widely used in reconstructive procedures. The use of this tissue as biomaterial mainly aims at maintaining the three-dimensional properties of the matrix, prioritizing structural, mechanical and biological support for the cells and allowing adequate remodeling. The ideal is to obtain a biomaterial with characteristics of biocompatibility, biofunctionality and mechanical resistance. In this sense, treatments were developed in order to minimize possible inflammatory processes and rejection of the biomembrane at the receptor. The aim of this study was to compare the histological changes in elastic cartilages of the external ear of bovines, submitted to different treatments of conservation with chemical treatment by alkaline solution. The samples were cleaned, standardized and divided into control group and treatment groups. The conservation methods were evaluated with supersaturated salt solution, supersaturated sugar solution, glycerine, formalin and alkaline solution. The samples were maintained in storage media for 60 days and in alkaline solution for 72 hours. After, they underwent preparation, analysis and interpretation on histological slides. In each treatment were evaluated microstructureal parameters, as the maintenance of elastic fibers, fundamental amorphous substance and decellularization. When comparing to the other groups, we verified that the cartilages treated in alkaline solution had better decellularization rate, fundamental amorphous substance removal and mantainance of elastic fibers tridimensional structure. For this reason, this group was considered the most effective method in this study. / A perda de tecidos devido a defeitos congênitos, processos patológicos ou traumas estimulou o desenvolvimento da engenharia tecidual com objetivo de reparo ou substituição de tecidos ou órgãos danificados. Devido às suas propriedades elásticas, o tecido cartilaginoso tem sido bastante utilizado em procedimentos reconstrutivos. A utilização deste tecido como biomaterial se dá principalmente pela manutenção das propriedades tridimensionais da matriz, priorizando sustentação estrutural, mecânica e biológica para as células e permitindo remodelamento adequado. O ideal é que se obtenha um biomaterial com características de biocompatibilidade, biofuncionalidade e resistência mecânica. Neste sentido, foram desenvolvidos tratamentos a fim de minimizar possíveis processos inflamatórios e rejeição da biomembrana no receptor. Objetivou-se comparar as alterações histológicas em cartilagens elásticas de orelha externa de bovinos submetidas a diferentes métodos de conservação com tratamento químico por solução alcalina. As amostras passaram por um processo de dissecação e higienização, sendo posteriormente divididas em grupo controle e grupos de tratamentos. Foram avaliados os métodos de conservação com solução supersaturada de sal, solução supersaturada de açúcar, glicerina, formalina e solução alcalina. As amostras foram mantidas em meios de conservação durante 60 dias e em solução alcalina durante 72 horas. Posteriormente passaram por preparação, análise e interpretação em lâminas histológicas. Em cada tratamento foram avaliados parâmetros microestruturais tais como a manutenção de fibras elásticas, substância fundamental amorfa e descelularização. Em comparação aos demais grupos, foi observado que o grupo do tratamento alcalino apresentou maior descelularização, remoção da substância fundamental amorfa e manutenção da estrutura tridimensional das fibras elásticas. Por isso, este grupo foi considerado o método mais efetivo neste estudo.

Automatická segmentace biologických struktur v mikro-CT datech je stále výzvou, protože často objekt zájmu (v našem případě obličejová chrupavka) není charakterizovaný unikátním jasem či ostrými hranicemi. V posledních letech se konvoluční neuronové sítě (CNNs) staly mimořádně populárními v mnoha oblastech počítačového vidění. Konkrétně pro segmentaci biomedicínských obrazů je široce používaná architektura U-Net. Nicméně v případě mikro-CT dat vyvstává otázka, zda by nebylo výhodnější použít 3D CNN. Diplomová práce navrhla CNN architekturu založenou na síti V-Net včetně metodologie pro předzpracování a postprocessing dat. Základní architektura byla dále optimalizována pomocí pokročilých architektonických modifikací jako jsou pyramidální modul dilatovaných konvolucí (ASPP modul), škálovatelná exponenciálně-lineární jednotka (SELU aktivační funkce), víceúrovňová kontrola učení (multi-output supervision) či bloky s hustými propojeními (Dense blocks). Pro učení sítě byly použity moderní přístupy jako zahřívání kroku učení (learning rate warmup) či AdamW optimalizátor. I přes to, že 3D CNN v úloze segmentace obličejové chrupavky nepřekonala U-Net, optimalizace zvýšila medián Dice koeficientu z 69,74 % na 80,01 %. Používání těchto pokročilých architektonických modifikací v dalším výzkumu je proto vřele doporučováno, jelikož můžou být přidány do libovolné architektury typu U-Net a zároveň výrazně zlepšit výsledky.

Les maladies ostéoarticulaires représentent environ 10% de l’ensemble des pathologies identifiées en France chaque année. Ces maladies inflammatoires et dégénératives des articulations sont pour la plupart consécutives au vieillissement ou à un traumatisme et évoluent vers l’usure des cartilages, d’où un handicap sévère. Comme aucun traitement ne permet la réparation totale du tissu cartilagineux, la recherche médicale développe des techniques d’ingénierie tissulaire. Ces techniques utilisent des substrats polymériques et des cellules souches qui sont « contraints » de se développer pour former du tissu cartilagineux. Cependant, ces techniques ne peuvent pas encore être utilisées à l’échelle d’une articulation complète car il n’est pas possible de reproduire ex vivo à grande échelle la structure et les propriétés mécaniques et physicochimiques du cartilage articulaire. Dans ce contexte, les travaux de cette thèse ont permis de développer des matériaux polymères capables d’être implantés à l’échelle macroscopique dans les articulations pathologiques afin de combler l’usure des cartilages. Pour se faire, de nouveaux biomatériaux - hydrogels p(HEMA) - ont été obtenus en contrôlant le caractère hydrophile des hydrogels p(HEMA) au cours de leur synthèse chimique en présence de différents co-monomères (acide acrylique, acrylamide, acrylate d'éthylène et acrylate de butyle). Partant de là, les propriétés physicochimiques, mécaniques et tribologiques de ces nouveaux hydrogels ont été optimisées afin d’obtenir des propriétés similaires à celles du cartilage articulaire sain. Ensuite, la libération contrôlée de médicaments par ces hydrogels a été étudiée afin de minimiser les risques inflammatoires lors de leur utilisation en ingénierie tissulaire du cartilage articulaire. / Osteoarticular diseases re present approximately 10% of all diseases identified in France each year. These inflammatory and degenerative joint disease are mostly consecutive with age or injuries and the wear progress of cartilage, resulting in severe disability. Because no treatment will total repair the cartilage tissue, medical research is developing techniques based on tissue engineering. These techniques use polymer substrates and stem cells that are "forced" to develop into cartilage tissue. However, these techniques cannot be used across a run articulation because Il is not possible-to replicate ex vivo a large-scale structure and the physicochemical and mechanical properties of articular cartilage. In this context, the purpose of this thesis is to develop polymer materials that can be implanted at the macroscopic level in the joints disease that will fill the wear of the cartilage. To do so, new biomaterials - hydrogels p (HEMA)- were obtained by controlling the hydrophilic nature of hydrogels p (HEMA) during their chemical synthesis in the presence of various co-monomers (acrylic acid, acrylamide, acrylate ethylene and butyl acrylate). From there, physicochemical, mechanical and tribological properties of these novel hydrogels have been optimized to obtain similar properties to those of healthy articular cartilage. Then, the controlled release of drugs from these hydrogels was studied to minimize inflammatory when used in tissue engineering of articular cartilage.