Post injury inappropriate bone formation

This project started in October 2015, and was funded by a New Investigator Research Grant from the Medical Research Council for 36 months. Dr Niall Logan, a PDRA working on this project, focused on understand the mechanisms behind blast wave induced heterotopic ossification (HO). HO is the inappropriate formation of ectopic bone in non-osseous tissue such as the muscle. Incidence after traumatic and combat related injuries has been reported to be as high as 63%, with the blast mechanism of injury highlighted as one of the primary risk factors for ectopic bone [1]. Methods of prophylaxis are still largely ineffective and result in the need for surgical excision of symptomatic lesions. Identification of the mechanisms that trigger blast induced ectopic bone formation could potentially lead to alternative and more effective methods of treatment.

Using bespoke shock tube equipment to expose in vitro cultures to blast waves, Niall found a synergistic effect of the blast wave together with osteogenic stimuli, which enhanced osteogenic differentiation in shock wave exposed samples. He also identified specific epigenetic changes which occur prior to osteogenic differentiation, and therapeutically targeted these changes to inhibit osteogenic differentiation [2].

In 2019, Krysia Broda, a PhD student funded by the Centre for Blast Injury Studies started working on this project. Krysia is developing a Trauma Responsive Index, to fully characterise the effect of shockwaves on cells which leads to HO.

References

1. Potter, B.K., et al., Heterotopic Ossification Following Traumatic and Combat-Related Amputations. Prevalence, Risk Factors, and Preliminary Results of Excision, 2007. 89(3): p. 476-486.

2. Logan, N.J., et al Demethylation of ITGAV accelerates osteogenic differentiation in a blast-induced heterotopic ossification in vitro cell culture model, 2018. 117: p. 149-160.