The limits of cooperation? A multiscale lens relating bone matrix quality and whole bone strength in humans and mice
File(s)
Author(s)
Stavri, Richard
Type
Thesis
Abstract
This thesis addresses the critical knowledge gap in our understanding of bone mechanics across hierarchical scales, focusing on how interactions between nanoscale components – collagen fibrils and mineral apatite – contribute to macroscale fracture resistance. Despite extensive characterisation of bone at tissue and microscales, less is understood about nanoscale mechanisms, particularly how collagen-mineral interfaces respond to ageing and contribute to fracture risk. Through innovative methodological approaches, a novel multimode synchrotron platform was developed that, for the first time, combines small- and wide-angle X-ray scattering (SAXS/WAXS) with digital image correlation (DIC) to simultaneously capture nanoscale deformation and local tissue strain. This breakthrough technique revealed that hip fracture vulnerability stems from compromised nanoscale strain capacity, where both mineral and collagen components fail to sustain adequate deformation, leading to premature structural disengagement. In ageing bone, the research discovered a previously unrecognised compensatory mechanism where collagen fibrils maintain or increase strain contribution to offset declining mineral performance. The work challenges conventional bone quality assessment paradigms by demonstrating that strength emerges from dynamic interactions between organic and inorganic phases rather than from mineral density alone. Most significantly, this research provides mechanistic insights into how nanoscale disruptions propagate across scales, offering new targets for diagnostics and therapeutics beyond current density-focused approaches. The methodological innovations established here provide a valuable framework for future investigations into hierarchical biomaterials and represent a significant advance in our ability to characterise multiscale mechanical behaviour in biological tissues.
Version
Open Access
Date Issued
2025-04-06
Date Awarded
2026-04-01
Copyright Statement
Attribution-NonCommercial 4.0 International Licence (CC BY-NC)
License URL
Advisor
Abel, Richard
Hansen, Ulrich
Wiles, Crispin
Cobb, Justin
Sponsor
The Royal Osteoporosis Society
The Michael Uren Foundation
The Dr Mortimer and Theresa Sackler Foundation
Imperial College London
Diamond Light Source (Firm)
Publisher Department
Department of Surgery & Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)