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dc.contributor.authorFeniyanos, Emile
dc.date.accessioned2019-08-29T14:44:18Z
dc.date.available2019-08-29T14:44:18Z
dc.identifier.urihttp://hdl.handle.net/10222/76348
dc.descriptionIn an age where men and women are remaining physically active into the geriatric years, age-related changes in soft tissue injuries and healing are becoming more important to clinical care. Differences in structure and function of human tendons with aging, sex, and diabetes are poorly understood, despite reported differences in the frequencies of specific tendon injuries. Furthermore, in using bovine models, due to overload, a serial kinking mechanism occuring in collagen fibrils coined discrete plasticity has been found in low load tendons. The objectives of this thesis were to investigate whether variations occur in (i) molecular-level structure, (ii) multi-fascicle level mechanics and (iii) ultrastructural failure mechanisms in the human sartorius tendon that are determined by tissue bank donor age (16-60 years), sex and diabetic status (in male donors). It was thought that thermal stability would change with age due to an increase in crosslinking, independent of donor sex, and that the thermal stability would increase with diabetes (increase in AGE crosslinking). It was found that the thermal stability actually decreased with age within each donor sex, and that the thermal stability remained largely unchanged with diabetes in male donors. It was hypothesized that tendon mechanics and mechanical properties would not change with age and donor sex while becoming more brittle with diabetes. Age was found not to determined sartorius tendon mechanics whereas tendon samples from female non-diabetic donors had lowered strength, toughness and extensibility when compared to tendons from male non-diabetic donors. In male donors, evidence of a brittle tissue was found with lowered toughness and extensibility with diabetes. Damage motifs (found independent of age, sex and diabetes) evaluated at the nanoscale via scanning electron microscopy revealed evidence of elastic recoil (knotting, balling and twisting), hairpin turns, local failure and complete breakage of isolated and neighboring fibrils, and lastly a plastic damage – that differed from discrete plasticity – that occurred only in younger male non-diabetic donors. Lastly, histology and immunohistochemistry experiments revealed that the combination of diabetes and aging in male donors contributed to qualitative increases in collagen crimp wavelength, decreases in cell nuclei numbers and increases in the pentosidine epitope concentration in the human sartorius tendon. Altogether, the human sartorius tendon is a highly crosslinked structure that remains relatively unchanged with age, sex and diabetes, sacrificing the toughness mechanism discrete plasticity for molecular stability and elastic mechanical strength. This stability of structure with age is belied by the surprisingly high cellular density which is partially retained into early geriatric life. This study has contributed to advancing modern knowledge of tendon structure-function relations, with potential future applications in treatment of soft tissue injuries and engineering of tendon or ligament replacements.en_US
dc.description.abstractIn an age where men and women are remaining physically active into the geriatric years, age-related changes in soft tissue injuries and healing are becoming more important to clinical care. Differences in structure and function of human tendons with aging, sex, and diabetes are poorly understood, despite reported differences in the frequencies of specific tendon injuries. The objectives of this thesis were to investigate whether variations occur in (i) molecular-level structure, (ii) multi-fascicle level mechanics and (iii) ultrastructural failure mechanisms in the human sartorius tendon that are determined by tissue bank donor age, sex and diabetic status. Human sartorius tendons were collected from the NSHA Regional Tissue Bank (Halifax, N.S) from donors ranging in age from 16–56 (female, non-diabetic only) and 24–60 (male, non-diabetic or diabetic). Blinded donor information included height, weight and diabetic status. To assess molecular-level changes in structure, hydrothermal isometric tension (HIT) analysis and differential scanning calorimetry (DSC) were used. The mechanics of the sartorius tendon multi-fascicle subsamples were assessed using uniaxial tensile overload testing to rupture. After rupture, tendon collagen ultrastructure was examined using SEM and compared with undamaged samples. Histology and immunohistochemistry were performed on fixed tendon samples (from predominantly male diabetic and non-diabetic donors) to identify changes in (i) collagen crimp, (ii) cell nuclei content and (iii) pentosidine epitope concentration with aging and diabetes. Results demonstrated that the sartorius tendon collagen is highly crosslinked, from early adulthood through early geriatric life. Under overload to rupture, this crosslinking results in high energy, sequential elastic rupture of individual tendon fascicles. Ultrastructural studies with SEM revealed fibril-level failure mechanisms consistent with elastic recoil (twisting, balling and knotting), hairpin turns, and local failure and complete breakage of isolated and neighboring fibrils – but with an absence of serial discrete plasticity kinking observed in other species. Fascicle mechanical properties were largely maintained with age. Thermal stability and heterogeneity of collagen decreased modestly with age under HIT and DSC. In the non-diabetic donors, tendon samples from female donors were 25% weaker, 38% less tough and 16% less extensible than those from non-diabetic male donors. In males, diabetic tendon samples were 37% less tough and 20% less extensible than normal tendons, yet modulus and strength remained unchanged. A slight increase in collagen denaturation temperature was observed with diabetes, likely due in part to accumulation of advanced glycation product crosslinks. The combination of aging and diabetes qualitatively increased collagen crimp length, decreased cell nuclei numbers and increased pentosidine epitope concentration. The human sartorius tendon is a highly crosslinked structure that remains relatively unchanged with age, sex and diabetes, sacrificing the toughness mechanism discrete plasticity for molecular stability and elastic mechanical strength. This stability of structure with age is belied by the surprisingly high cellular density which is partially retained into early geriatric life. This study has contributed to advancing modern knowledge of tendon structure-function relations, with potential future applications in treatment of soft tissue injuries and engineering of tendon or ligament replacements.en_US
dc.language.isoen_USen_US
dc.subjectSartorius Tendonen_US
dc.subjectTendon Mechanicsen_US
dc.subjectDiabetesen_US
dc.subjectSexen_US
dc.subjectHuman Tendonen_US
dc.subjectHydrothermal Isometric Tension Testingen_US
dc.subjectDifferential Scanning Calorimetryen_US
dc.subjectAging Tendonsen_US
dc.subjectMechanical Testingen_US
dc.subjectPentosidineen_US
dc.subjectScanning Electron Microscopyen_US
dc.subjectDiscrete Plasticityen_US
dc.subjectThermal Stabilityen_US
dc.subjectHistologyen_US
dc.subjectCollagenen_US
dc.titleAge-, Sex-, and Diabetes-Determined Changes in the Structure and Mechanics of Human Sartorius Tendon Collagenen_US
dc.date.defence2019-08-22
dc.contributor.departmentDepartment of Biomedical Engineeringen_US
dc.contributor.degreeMaster of Applied Scienceen_US
dc.contributor.external-examinerDr. Derek Rutherforden_US
dc.contributor.graduate-coordinatorDr. Jeremy Brownen_US
dc.contributor.thesis-readerDr. Samuel Veresen_US
dc.contributor.thesis-supervisorDr. J. Michael Leeen_US
dc.contributor.thesis-supervisorDr. Sarah Wellsen_US
dc.contributor.ethics-approvalReceiveden_US
dc.contributor.manuscriptsNoen_US
dc.contributor.copyright-releaseNot Applicableen_US
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