Abstract
Heterotopic ossification is the formation of lamellar bone in soft tissues and is a common complication of high-energy combat injury. This disabling condition can cause pain, joint ankylosis, and skin ulceration in the residua of amputees. This project is aimed at developing a novel treatment to dissolve hydroxyapatite in heterotopic ossification and prevent the crystallisation of this this mineral at sites of ectopic bone formation. Previously reported results demonstrated that hexametaphosphate could dissolve hydroxyapatite at physiological pH. Further work has been undertaken to investigate the mechanism of this dissolution and establish a means of temporal control of action. In addition, physicochemical analyses of samples of human heterotopic ossification have yielded important insights into the nature of this pathological tissue. Techniques include mapped micro X-ray fluorescence, mapped Raman spectroscopy, scanning electron microscopy, and micro computed tomography. Formulation engineering work has begun in order to develop an appropriate delivery vehicle for this agent. This includes rheological testing and hexametaphosphate elution profiles. Finally, micro CT analysis has shown that hexametaphosphate is able to dissolve human heterotopic ossification tissue. In summary, this work has moved us closer towards our goal of a novel injectable agent for the treatment and prevention of heterotopic ossification.
