Identifying the origins of collagen connective tissue growth
and expansion with reference to inguinal herniation.
Doctoral thesis, UCL (University College London).
The aim of this project was to understand the key mechanisms which control and initiate the process(es) by which collagen connective tissues extend, remodel and grow under the influence of external tensile loads. Inguinal herniation was used as a model of natural cell mediated bio-creep to investigate the mechanisms behind such a process since the transversalis fascia (TF); a thin collagen connective tissue undergoes dramatic extension during herniation. It was hypothesized that the TF expands due to a process of growth and remodelling rather than stretch or injury and repair. The relationship between functional tissue mechanical properties, cell responses to mechanical forces and the architecture of the ECM were investigated. TEM imaging of TF collagen fibril ultrastructure demonstrated no differences between normal and hernia specimens and therefore no evidence of microdamage/ repair. An important finding was that hernia TF was not mechanically weaker or thinner than normal TF tissue, indicating it retains its normal material properties and thickness despite dramatic extension during herniation. In addition, the TF was identified to have anisotropic mechanical properties with greater strength and stiffness in the transverse anatomical plane, a finding which has not previously been reported for the TF. The ability of normal and hernia TF fibroblasts to contract and remodel a collagen matrix were almost identical, suggesting that hernia cells retain ‘normal’ cell behaviour in terms of their cytoskeletal and cell-motor functions. Analysis of TF fibroblast creep responses using an in vitro 3D bio-creep model demonstrated, to our knowledge, the first direct functional (mechanical) defect in hernia cell behaviour, since hernia cells did not demonstrate any capacity to mediate any measurable bio-creep. Our investigations of TF mechanics, structure and cellular behaviour suggest that TF expansion in inguinal herniation occurs due to growth/remodelling rather than stretch or micro-rupture and repair but the exact mechanisms remain inconclusive until further studies are carried out.
|Title:||Identifying the origins of collagen connective tissue growth and expansion with reference to inguinal herniation|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of) > Institute of Orthopaedics and Musculoskeletal Science|
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