A structural characterisation of human heterotopic bone
File(s)
Author(s)
Wiles, Crispin Charles Raymond
Type
Thesis
Abstract
Heterotopic ossification (HO) is the formation of new extra-skeletal osseous tissue. It is a common outcome following trauma, affecting up to 91% of blast-related amputees. However, the pathogenesis of HO remains poorly understood and there has been little investigation of the heterotopic bone which develops. The main objective of this thesis was to perform a multiscale characterisation of the structure of human heterotopic bone formed following trauma, for systematic and quantitative comparison with orthotopic bone. This was achieved using several analytical techniques. At microscale, µCT imaging was employed for 3-D visualisation and to perform digital histomorphometry and topological analysis on trabecular structure and osteocyte lacunae. At nanoscale, scanning wide- and small-angle X-ray scattering techniques using a synchrotron source were used to measure and map variations in the structural organisation of collagen fibrils and mineral crystals, supplemented by microscopic methods permitting direct visualisation of the collagen fibrillar organisation and mineral crystals. The data collected reveal that at microscale, heterotopic bone broadly resembles orthotopic bone tissue. At nanoscale, it undergoes a maturation process similar to that of fracture callus; and by around 50 – 100 weeks after injury it structurally resembles adult orthotopic bone. These similarities extend from the size and organisation of the nanoscale components including mineral crystals and collagen fibrils, to a common topological organisation of the trabecular bone, and the presence of a cortical shell. However, greater nanostructural heterogeneity was also observed. These observations provide support for the interpretation that heterotopic bone is essentially normal osseous tissue, where the structural abnormalities observed relate to the abnormal tissue environment rather than intrinsic structural differences relative to orthotopic bone. These findings extend prior understanding of heterotopic bone structure and have a range of implications which include providing indirect support for attempts to model HO in silico.
Version
Open Access
Date Issued
2019-07
Date Awarded
2019-11
Copyright Statement
Creative Commons Attribution NonCommercial Licence
Advisor
McGregor, Alison
Bull, Anthony
Abel, Richard
Sponsor
Imperial College London
Publisher Department
Department of Surgery & Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)