Heterotopic ossification: physicochemical analysis and development of a novel treatment strategy

Eisenstein, Neil Michael (2018). Heterotopic ossification: physicochemical analysis and development of a novel treatment strategy. University of Birmingham. Ph.D.

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Heterotopic ossification (HO) is the pathological formation of ectopic bone and can be a devastating complication of military injuries. It causes multiple problems, including prosthetic limb fitting difficulties and ankylosis, ultimately causing loss of mobility, independence, and dignity. There is no effective prophylaxis and the only treatment is surgery, which causes rehabilitation delays and risks of bleeding and nerve injury. This work aimed to develop a new therapy for HO. A review of mineralised tissue analytical methods was performed and used to guide the study of human HO samples using X-ray micro computed-tomography, X-ray fluorescence, synchrotron X-ray diffraction / nano-tomography, Raman spectroscopy, and scanning electron microscopy. Screening of therapies demonstrated that hexametaphosphate (HMP) could dissolve hydroxyapatite (the mineral component of bone) under physiological conditions. Formulation engineering principles were applied to control this effect temporally and anatomically. A murine HO model was developed and used for feasibility testing of injected HMP as an HO therapy, showing that it had no adverse effect on normal bone. In summary, this project revealed the physicochemical structure of HO in unprecedented detail, discovered and developed a novel therapy, set up an animal model of HO, and showed that injected HMP is feasible in this model.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
College/Faculty: Colleges (2008 onwards) > College of Engineering & Physical Sciences
School or Department: School of Chemical Engineering
Funders: Other
Other Funders: Diamond Light Source, The Drummond Foundation, European Synchrotron Research Facility, Orthopaedic Research UK, Royal Centre For Defence Medicine Patient Welfare Fund
Subjects: Q Science > QH Natural history > QH301 Biology
R Medicine > RM Therapeutics. Pharmacology
T Technology > TP Chemical technology
URI: http://etheses.bham.ac.uk/id/eprint/8289


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