Thesis (Ph.D.)--University of California, San Francisco, 2004. / Bibliography: leaves 108-116. Also available online.

Dissertation (PhD)--University of Stellenbosch, 2007. / Bibliography. Also available via the Internet.

Dissertation (Ph.D.).--University of Texas Graduate School of Biomedical Sciences at San Antonio, 2005. / Vita. Includes bibliographical references.

Use of load-bearing materials whose functionality arises from architectured microstructures, so called architectured materials, has been hindered by the challenge of connecting them. A solution in nature is found at the tendon enthesis, a tissue that connects tendon and bone, two vastly different natural architectured materials. The tendon enthesis provides stability and allows for mobility of a joint though effective transfer of muscle forces from tendon to bone, while exhibiting toughness across a wide range of loadings. Unfortunately, many painful and physically debilitating conditions occur at or near this interface when the enthesis architecture is compromised due to injury or degeneration. Surgical and natural repairs do not reconstitute the natural toughening mechanisms of the enthesis and often fail. Hence, understanding the architectural mechanisms by which healthy and pathologic tendon entheses achieve strength and toughness would inform the development of both biological and engineered attachments.Integrating biomechanical analyses, failure characterizations, numerical simulations, and novel imaging, this thesis presents architectural mechanisms of enthesis toughening in a mouse model. Imaging uncovered fibrous architecture within the enthesis, which controlled trade-offs between strength and toughness. Ex vivo enthesis failure modes exhibited nanoscale differences in damage, milliscale differences in fiber load-sharing, and macroscale differences in energy absorption that depended on structure, composition, and the nature of loading. The elastic and failure responses of the tendon enthesis also varied with the direction of loading. This variation was due to the fibrous nature of the tendon enthesis, with a clear role for bony anatomy and fiber recruitment in enthesis toughening behavior. In vivo, , the loss of toughening mechanisms at the enthesis due to pathologic loading was evaluated by either increased (i.e., overuse) loading via downhill treadmill running or decreased (i.e., underuse) loading via botulinum toxin A induced paralysis. These loading environments led to changes in the mineralization and architecture at the tendon enthesis. These micro-architectural adaptations compromised the trade-offs between strength and toughness; overuse loading prompted active reinforcement and stiffening of the underlying trabeculae, leading a maintenance of strength and a compromise in overall toughness, whereas underloading prompted active resorption of the underlying trabecular architecture, leading to a compromise in both strength and toughness. The mouse models of the tendon enthesis failure revealed a correlation between tendon enthesis architecture and injury prevention (i.e., toughening) mechanisms. To test this concept in a clinical setting, an injury classification system was developed for patellar tendinopathy and partial patellar tendon tears. This classification system identified the stages of tear progression and prognosis by tracking changes to patellar tendon architecture. Results revealed a relationship between patellar tendon thickness and likelihood of improvement with nonoperative treatment. Taken together, this dissertation revealed how fibrous architecture can be tailored to toughen attachments between vastly different materials. This understanding can have prognostic value: tracking changes to enthesis architecture can be used as a tool for identifying candidates for various treatment options, as we showed for the patellar tendon clinical example. Furthermore, the toughening mechanisms identified here provide guidance for enhancing enthesis surgical repair and designing enthesis tissue engineered scaffolds, as well as motivating biomimetic approaches for attachment of architectured engineering material systems.

Um dos maiores desafios da ortopedia moderna é recuperar o tecido ósseo que tenha sido perdido por motivo de doença ou acidente. Na busca de substitutos para os enxertos, tem-se utilizado comumente biomateriais para recuperação desse tecido. Um dos vários tipos de biomateriais usados são os preparados à base de colágeno. Além de desempenhar papel importante na estrutura dos tecidos, o colágeno é capaz de orientar a formação de tecidos em desenvolvimento fato altamente favorável na sua utilização como biomaterial. Uma nova vertente de pesquisa do processo de mineralização de matrizes colagênicas que vem sendo desenvolvida é a analise de como a organização do tecido interfere no modo como ocorre esse processo de deposição. O uso do tendão vem sido pesquisado devido ao fato de ser um tecido extremamente organizado, com as fibras colagênicas alinhadas por toda a sua extensão. Este trabalho teve como objetivo a preparação e caracterização de matrizes de colágeno tipo I, oriundas de tendão bovino (TB) e avestruz (TA) após a hidrólise alcalina e mineralização. Os tendões foram colocados em solução alcalina contendo sais de K+, Na+ e Ca2+ por 72, 96 e 120 h a 25°C e depois equilibrados em solução de sais, lavados em H3BO3, EDTA e água. As matrizes resultantes foram então mineralizadas em soluções de CaCl2 0,2 mol L-1, pH = 7,4 e de Na2HPO4 0,12 mol L-1 pH = 9,0 durante 6 h, ocorrendo a troca de soluções a cada 30 min. As matrizes antes e após mineralização foram congeladas, liofilizadas e submetidas à análise termogravimétrica (TG), calorimetria exploratória diferencial (DSC), microscopia eletrônica de varredura (MEV), espectroscopia no infra-vermelho (FT-IR) e dispersão de energia por raios-X (EDX). DSC mostrou que não houve desnaturação do colágeno durante o processo de tratamento alcalino e mineralização. A análise termogravimétrica mostrou que houve deposição de fosfato de cálcio, com o valor dependendo do número de ciclos de mineralização. MEV mostrou que essa mineralização não é uniforme, ocorrendo a formação de aglomerados. FT-IR e EDX mostrou que o fosfato de cálcio depositado provavelmente seja hidroxiapatita, mas não em sua estrutura estequiométrica. / One of greatest challenges of modern orthopedics is to restore bone tissue that has been lost due to sickness or accident. Searching for substitutes for grafts, biomaterials have been commonly used for recovery of bone tissue. Between different types of biomaterials, several are based on collagen. In addition to have important role in tissue structure, collagen is able to guide the formation of tissues, a highly favorable fact in its use as biomaterial. A possible research in collagen scaffolds mineralization is the analysis of how tissue organization interferes in deposition process. The tendon has been used because it is a highly organized tissue, with collagen fibers lined on its structure. This research aims the preparation and characterization of type I collagen scaffolds, prepared from bovine tendon (TB) and ostrich tendon (TA) after alkaline hydrolysis and mineralization. Tendons were maintained in alkaline solution containing K+, Na+ and Ca2+ ions for 72, 96 and 120 hours at 25°C and then equilibrated in salt solution, washed with H3BO3, EDTA and water. The resulting matrices were then mineralized in 0.2 mol L-1, pH = 7.4 CaCl2 solution and 0.12 mol L-1 Na2HPO4 pH = 9.0 for 6 h, changing solutions after 30 minutes. The matrices before and after mineralization were frozen, lyophilized and subjected to thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), infrared spectroscopy (FT-IR) and energy dispersive X-ray spectroscopy (EDS). DSC showed that the collagen was not denaturated by alkaline treatment process and mineralization. TG analysis showed deposition of calcium phosphate on the scaffolds, with values depending on the number of mineralization cycles. SEM showed that the mineralization is not uniform, forming clusters of phosphate crystals. FT-IR and EDS showed that the deposited calcium phosphate is probably hydroxyapatite, but not in its stoichiometric structure.

During normal activity, tendons are subjected to dynamic tensile strains of approximately 1-10%, whilst mechanical overload can lead to damage and degradation and the development of tendinopathy. The tenocytes within tendon respond to this mechanical environment although the mechanisms are poorly understood. Primary cilia consist of a slender axoneme composed of acetylated α-tubulin and are known to regulate a variety of signalling pathways including mechanosignalling. In various cell types, mechanical loading also influences primary cilia length. However relatively little is known about tendon primary cilia structure and function. This thesis set out to examine the structure and organisation of primary cilia in tendon cells and the effect of mechanical loading, both in situ and in isolated cells cultured in monolayer. Studies analysed cilia expression using confocal immunofluorescence microscopy in tendon fascicles from rat tail and isolated human tenocytes. Results demonstrated that the prevalence and orientation of primary cilia was different in the fascicular matrix (FM) and interfascicular matrix (IFM) regions of the tendon. Stress deprivation caused differential cilia elongation between the FM and IFM, associated with disruption of the surrounding extracellular matrix and alterations in tissue biomechanics. In isolated tenocytes, primary cilia were significantly longer with a greater prevalence than in situ. Cyclic tensile loading applied using the Flexcell system resulted in cilia disassembly within 8 hours with a dramatic reduction in prevalence and length. This effect was completely reversible on removal of strain. A similar response was observed in situ within both FM and IFM regions of the tendon. This mechanically-induced cilia disassembly was shown to be mediated, at least in part, by the release of TGFβ and activation of HDAC6 which causes tubulin deacetylation. These results in this thesis suggest a novel feedback mechanism through which physiological and pathological mechanical loading may regulate primary cilia signalling.

by Chong Wai Sing, Wilson. / Thesis submitted in: August 2002. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 116-126). / Abstracts in English and Chinese. / ACKNOWLEDGEMENT --- p.i / ABBREVIATION --- p.ii / ABSTRACT (Chinese & English) --- p.iii / TABLE OF CONTENT --- p.vii / INDEX FOR FIGURES --- p.x / INDEX FOR TABLES --- p.xiii / Chapter 1. --- Introduction --- p.1 / Chapter 1.1 --- "Bone-tendon junction - types, structures and functions" --- p.2 / Chapter 1.1.1 --- Indirect insertion --- p.3 / Chapter 1.1.2 --- Direct insertion --- p.3 / Chapter 1.1.3 --- Functional adaptations of insertions --- p.4 / Chapter 1.2 --- Incidence and type of injuries near insertion site --- p.5 / Chapter 1.3 --- Treatment protocol for injuries near insertion site --- p.5 / Chapter 1.3.1 --- Non-operative versus operative approach --- p.5 / Chapter 1.3.2 --- Previous studies on validations of outcomes of difference repair methods --- p.6 / Chapter 1.4 --- Modes of healing underlying different repair approach --- p.7 / Chapter 1.4.1 --- Fracture healing --- p.7 / Chapter 1.4.2 --- Tendon healing --- p.8 / Chapter 1.4.3 --- Bone-tendon healing --- p.9 / Chapter 1.5 --- Objectives --- p.9 / Chapter 2. --- Materials and Methods --- p.12 / Chapter 2.1 --- Animal model --- p.13 / Chapter 2.2 --- Experimental design --- p.13 / Chapter 2.3 --- Surgery --- p.13 / Chapter 2.3.1 --- Bone-to-bone repair --- p.14 / Chapter 2.3.2 --- Bone-to-tendon repair --- p.14 / Chapter 2.3.3 --- Tendon-to-tendon repair --- p.15 / Chapter 2.4 --- Post-operative follow-up --- p.15 / Chapter 2.4.1 --- Radiographic examination --- p.15 / Chapter 2.4.2 --- Polychrome sequential labeling --- p.16 / Chapter 2.4.2.1 --- Reagents --- p.16 / Chapter 2.4.2.2 --- Route of administration --- p.16 / Chapter 2.5 --- Sampling --- p.17 / Chapter 2.6 --- Histology --- p.17 / Chapter 2.6.1 --- Decalcification --- p.17 / Chapter 2.6.1.1 --- Tissue decalcification --- p.17 / Chapter 2.6.1.2 --- Tissue processing --- p.17 / Chapter 2.6.1.3 --- Immunohistochemistry of collagen type II and III --- p.18 / Chapter 2.6.1.3.1 --- Reagents and solution preparation --- p.18 / Chapter 2.6.1.3.2 --- Experimental procedures --- p.20 / Chapter 2.6.2 --- Undecalcification --- p.22 / Chapter 2.6.2.1 --- Specimen preparations --- p.22 / Chapter 2.6.2.2 --- Toluidine blue staining --- p.22 / Chapter 2.7 --- Mechanical test --- p.23 / Chapter 2.7.1 --- Sample preparation --- p.23 / Chapter 2.7.2 --- Embedding procedures --- p.23 / Chapter 2.7.3 --- Measurement of cross-sectional area of healing interface --- p.23 / Chapter 2.7.3.1 --- CSA for BB --- p.23 / Chapter 2.7.3.2 --- CSA for BT and TT --- p.24 / Chapter 2.7.4 --- Tensile test --- p.24 / Chapter 2.7.4.1 --- Testing procedures --- p.24 / Chapter 2.7.4.2 --- Interpretation of testing results --- p.25 / Chapter 2.7.5 --- Statistical analysis --- p.26 / Chapter 3. --- Results --- p.42 / Chapter 3.1 --- Surgical outcome --- p.43 / Chapter 3.1.1 --- Radiographic examination --- p.43 / Chapter 3.1.1.1 --- Bone-to-bone healing --- p.43 / Chapter 3.1.1.2 --- Bone-to-tendon healing --- p.44 / Chapter 3.1.2 --- Fluorochrome injection --- p.44 / Chapter 3.2 --- Histology --- p.45 / Chapter 3.2.1 --- Bone-to-bone healing --- p.45 / Chapter 3.2.1.1 --- Gross anatomy --- p.45 / Chapter 3.2.1.2 --- Microscopic examination --- p.45 / Chapter 3.2.1.3 --- Polarised light microscopy --- p.46 / Chapter 3.2.1.4 --- Fluorochrome microscopy --- p.46 / Chapter 3.2.2 --- Bone-to-tendon healing --- p.47 / Chapter 3.2.2.1 --- Gross anatomy --- p.47 / Chapter 3.2.2.2 --- Microscopic examination --- p.47 / Chapter 3.2.2.3 --- Polarised light microscopy --- p.48 / Chapter 3.2.2.4 --- Fluorochrome microscopy --- p.49 / Chapter 3.2.3 --- Tendon-to-tendon healing --- p.49 / Chapter 3.2.3.1 --- Gross anatomy --- p.49 / Chapter 3.2.3.2 --- Microscopic examination --- p.49 / Chapter 3.2.3.3 --- Polarised light microscopy --- p.50 / Chapter 3.3 --- Mechanical testing --- p.50 / Chapter 3.3.1 --- Bone-to-bone healing --- p.50 / Chapter 3.3.1.1 --- Change of cross sectional area --- p.50 / Chapter 3.3.1.2 --- Load at failure --- p.50 / Chapter 3.3.1.3 --- Strength --- p.51 / Chapter 3.3.1.4 --- Energy --- p.51 / Chapter 3.3.2 --- Bone-to-tendon healing --- p.51 / Chapter 3.3.2.1 --- Change of cross sectional area --- p.51 / Chapter 3.3.2.2 --- Load at failure --- p.52 / Chapter 3.3.2.3 --- Strength --- p.52 / Chapter 3.3.2.4 --- Energy --- p.52 / Chapter 3.3.3 --- Tendon-to-tendon healing --- p.52 / Chapter 3.3.3.1 --- Change of cross sectional area --- p.53 / Chapter 3.3.3.2 --- Load at failure --- p.53 / Chapter 3.3.3.3 --- Strength --- p.53 / Chapter 3.3.3.4 --- Energy --- p.53 / Chapter 3.3.4 --- "Comparison of healing quality among BB, BT, and TT repair" --- p.54 / Chapter 3.3.4.1 --- Change of cross sectional area --- p.54 / Chapter 3.3.4.2 --- Load at failure --- p.54 / Chapter 3.3.4.3 --- Strength --- p.54 / Chapter 3.3.4.4 --- Failure mode --- p.55 / Chapter 4. --- Discussion --- p.102 / Chapter 4.1 --- Use of goat calcaneus-Achilles junction as a bone-tendon reseach model --- p.103 / Chapter 4.2 --- "Bone-to-bone, bone-to-tendon, and tendon-to-tendon fixation" --- p.104 / Chapter 4.3 --- Histological characterization of different healing tissues --- p.105 / Chapter 4.3.1 --- Bone-to-bone healing (Fracture healing) --- p.105 / Chapter 4.3.2 --- Bone-to-tendon healing --- p.106 / Chapter 4.3.3 --- Tendon-to-tendon healing --- p.106 / Chapter 4.3.4 --- Regeneration versus repair --- p.107 / Chapter 4.4 --- Spatial and temporal expression of different type of collagen in different form of healing --- p.108 / Chapter 4.5 --- Mechanical properties of healing interface under different form of fixation --- p.108 / Chapter 4.5.1 --- Failure mode --- p.110 / Chapter 4.6 --- Limitations --- p.111 / Chapter 4.6.1 --- Goat animal model --- p.111 / Chapter 4.6.2 --- Immunohistochemistry --- p.111 / Chapter 4.7 --- Future study --- p.112 / Chapter 5. --- Conclusion --- p.113 / Chapter 6. --- References --- p.116

Key words: End zone, prestress transfer, wire tendon, transmission length, pull-in, plain wire, indented wire, concrete strength, size of wire, gradual release, sudden release, shock release, time dependent effects.An empirical investigation into the transfer of prestress force from wire tendons to concrete in the end zones of pretensioned prestressed concrete beams was accomplished in this project. The experimental tests featured 56 small scale prestressed concrete beams.Some of the factors influencing prestress transfer which were considered in the current tests are as follows:(a) type of release - gradual, sudden or shock(b) surface condition of the wire - plain or indented(c) size of the wire(d) concrete compressive strength at the time of transfer(e) time dependent effectsMost of the tests involved gradual release of steel tendons with the prestressing force transferred in approximately ten equal increments. Sudden release in a single step was achieved by allowing the supporting abutments to retract rapidly. Shock release was implemented in some beams by angle grinding the wires. The type of release which gave the best quality of prestress transfer was gradual release. This was followed by sudden and shock releases respectively.There were four types of wires used in the laboratory tests: namely the 5 mm dia. Plain, 5 mm dia. Chevron indented, 7 mm dia. Plain and 7 mm dia. Belgian indented wires. Transmission lengths were determined from strain distributions for these wires. Pull-ins of the wire tendons at the ends of the beams were also measured.There was significant scatter in the experimental data. Different ranges of transmission lengths and pull-ins were obtained for the various types of wires used.Three equations were derived for the 5 mm dia. Plain, 5 mm dia. Chevron and 7 mm dia. Plain wires, which linearly correlated pull-ins to the transmission lengths. ++ / These relationships provide a qualitative and quantitative method of indirectly monitoring for the transmission lengths through the measurements of pull-in.Statistical inference tests proved that indented wires were superior in performance compared to plain wires, but the differences were more apparent for the pull-ins than for the transmission lengths.Comparisons on the influence of tendon size substantiated that greater pull-ins occurred for larger wires but the differences were not significant for the transmission lengths.For concrete strength at the time of transfer of less than 32 MPa, the transmission lengths and pull-ins were significantly larger than those for higher strengths. It is recommended that concrete strength at transfer be at least 32 MPa for pretensioned prestressed concrete.Apart from the maturity and strength of concrete, the quality of a mix also influenced the transmission length and there was limited data to suggest that a better grade mix despite having lower strength at a more tender age could outperform a lower grade mix with greater strength released after a longer curing period.Formulae for plain and indented wires were found by dimensional analysis which correlated the transmission length to the diameter of wire tendon and the stress/strength ratio of the prestressed beams.Pull-ins increased significantly over 6 months but the changes in the transmission lengths were small. Normalised longitudinal strain distributions did not indicate that transmission lengths would remain unchanged over time.

Thesis (M. Phil.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

Reproduction de : Thèse de doctorat : Pathologie, Toxicologie, Génétique et Nutrition : Toulouse, INPT : 2007. / Titre provenant de l'écran-titre. Bibliogr. 256 réf.