Identifying the Irreversible Mechanical Behaviour of Individual Mineralised Collagen Fibril Assemblies

Osteoporosis and osteoarthritis affect millions of patients around the world and are eventually characterised by a reduction of bone strength that results in increased rates of fractures. Life expectancy continues to rise but patient specific treatment solutions to optimally manage those patients are sill not available. Such solutions could consist of tailored medication strategies and, at a later stage, tailored implant solutions which require a thorough understanding of the mechancial competence of structural tissue. While the mechanical behaviour of bone is currently well characterised at the upper level of tissue organisation, the underlying nonlinear mechanical properties of mineralised collagen fibre assemblies, however, remain obscured by structural features such as cellular porosity, lamellar organisation, cement lines, cracks and other interfaces. Starting from preliminary pilot experiments, this proposal aims at performing simultaneous uniaxial micropillar strength tests and structural measurements using small-angle X-ray scattering and wide-angle X-ray diffraction on micron-sized volumes of the extra-cellular matrix (ECM) and, thus, on mineralised collagen fibre assemblies only. This project will result in a versatile and powerful experimental framework that will be used to understand the structure-mechanics relation of ECM with an unprecedented spatial resolution of the mechanical experiment. The results of this project will inform the engineering of patient-specific material solutions in silico through all relevant length scales starting from the ECM level. This, in turn, will foster the development and realisation of production technologies for manufacturing patient-specific "implants on demand" which could be offered as a service or embedded in a hospital. The novel experimental techniques may be useful for testing and developing functional thin films such as implant coatings, investigating the impact of pathological changes on the ECM, or even to reduce, refine, and replace animal experiments.

Society: As an ageing society UK is highly affected since over 11 million (approximately 17 %) inhabitants suffer from osteoporosis or osteoarthritis. Osteoporosis itself is associated with a dramatic increase in mortality and it causes women beyond menopause to spend more days in hospital than due to diabetes, heart attack or breast cancer. The diseases would be highly manageable if diagnostics, treatments, and compliance could be improved. A corner stone could be the development of patient specific diagnoses and treatment strategies. Those strategies necessarily rely on a thorough understanding of structure-mechanics relationships of the affected tissues at the extra-cellular matrix level. The present project makes a major contribution to this end.

Science: Simultaneous uniaxial strength tests and X-ray diffraction measurements on micron-sized volumes of the extra-cellular matrix are a breakthrough to understand biological hard tissues. The proposed experiments are a new technical challenge that could be extended to a much broader class of biological, biomimetic and non-biological composites and nanostructured materials. It will lead directly to novel questions and challenges on different tissue types both healthy and subject to pathological changes.

Specifically targeting bone in such a challenging project will help to understand the mechanical behaviour of the fundamental building blocks of bone and the scale transition of bone mechanical properties beyond the elastic loading regime in general. This is a prerequisite to develop optimal strategies for diagnosis, treatment, and the management of patients with musculoskeletal diseases. The results will have a direct and substantial impact in my field of research and will inform a broad audience of researchers ranging from theoretical and experimental biomechanics, through tissue engineering and synthetic biology, to pre-clinical and clinical orthopaedics.

Technology: The versatile and powerful experimental framework developed at the core of this project will be of use for a wide range of researchers crossing disciplines from geoscience, to biomedical and energy engineering, materials science, to functional coatings and optical materials. This will be realised through the collaborations within this project and then by making the novel experimental framework available for new scientific and industrial collaborations.