Age-, Sex-, and Diabetes-Determined Changes in the Structure and Mechanics of Human Sartorius Tendon Collagen
MetadataShow full item record
In 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.
Showing items related by title, author, creator and subject.
Sparavalo, SaraInjuries to soft tissues such as tendons affect millions of people annually. Injuries produced by in vitro mechanical overload result in damage to constituent collagen. Using bovine models, it has been found that damage ...
Establishment and validation of a rat Achilles tendon overuse exercise model with characterization of histology, biochemistry, biomechanics and collagen crosslinking. Glazebrook, Mark. (Dalhousie University, 2006)