Mechanobiology of Blast on Muscle Cell Homeostasis: Enhancing Muscle survival from Explosive Blast.

During the conflict in Afghanistan, 2,792 British casualties sustained a total of 14,252 injuries. Blast as a mechanism of injury accounted for ~70% of these, with a total of 5313 IED detonations recorded(7-10). Two hundred and ninety-one servicemen and women required some form of amputation as a result of their injuries.

Comparatively, civilian landmine casualties stood at 6,461 in 2015; a 75% increase on the previous year(11). Hence the burden of this traumatic process is both significant and widespread, producing a considerable socioeconomic burden globally.

Despite this injury burden, little work exists that investigates the mechanobiology of wounds exposed to blast trauma, particularly the effect on their cellular phenotype. Comprehensively understanding the relationship between extracellular mechanical stimulation and the extent to which this results in phenotypic preconditioning is critical(12, 13). It has been observed that blast wounds evolve following removal of the initial blast insult, with late tissue death. Muscle cells that are potentially preconditioned into a 'stressed', pro-apoptotic state by blast, may be at a greater risk of death during subsequent wound management with closed circuit negative pressure dressings. The investigation of mechanobiological preconditioning specific to blast trauma and the role on cellular homeostasis through physical wound therapies is a directly-relevant, novel, exciting, and potentially directly-translatable avenue for military research that, amongst other treatments, could allow development and tailoring of physical wound therapies to change our very early clinical management of traumatic wounds to the benefit of our injured.

We hypothesis that the energy from blast shock wave, disrupts mechanical cell decision enough to initiate a multitude of different cell states that ultimately lead to the loss of bulk muscle.

In surgical reconstruction, predicting injury patterns, understanding the surgical requirements and preventing unnecessary tissue loss are crucial. Grasping the cellular basis of disease is critical. It will facilitate a change in knowledge as well as the outlook for designing future therapies.

To understand the current cellular response to blast it is necessary gain a broad snapshot of the cells immediate response. This can be achieved by looking at the comprehensive genome activity using an RNA Sequence analysis. This will be undertaken in collaboration between the Defense Science and Technology Laboratories (DSTL) of Dr Abigail Spear, at Porton Down, and the Centre for Genomics, University of Oxford.

Utilizing this dataset we will then be able to identify possible mechanical targets that are lynchpins to muscle homeostasis following blast injury. At Professor Mark Thompson's labs at the Institute of Biomedical Engineering (IBME), University of Oxford, we will develop a validated reliable model for investigating blast on cell culture. With collaborative help from Dr Abigail Spear at DSTL we will construct a system capable of diverse analysis of muscle cells from a blast stimulus, to understand the detailed cellular response. This will utilize facilities both at DSTL and the University of Oxford to conduct analysis allowing live visualization of cellular responses, through live microscopy, to techniques to quantify the degree of response and expression, such as qPCR or Flow Cytometry.

The overall aim of this research theme is to understand and unlock the mechanisms by which blast shock wave alters cellular function. This knowledge will not only allow us to design novel therapeutics to mitigate against this dysfunction, but directly broaden clinicians knowledge to improve patient care.


This work will also interest and benefit neurobiologists, neuroscientists and clinicians involved in the research of blast neurotrauma.