Abstract
Trauma arising from landmines and improvised explosive devices promotes heterotopic ossification, the formation of extra-skeletal bone in non-osseous tissue. To date, experimental platforms that can replicate the loading parameter space relevant to improvised explosive device and landmine blast wave exposure have not been available to study the effects of such non-physiological mechanical loading on cells. Here, we present the design and calibration of three distinct in vitro experimental loading platforms that allow us to replicate the spectrum of loading conditions recorded in near-field blast wave exposure. We subjected cells in suspension or in a three-dimensional hydrogel to strain rates up to 6000 s−1 and pressure levels up to 45 MPa. Our results highlight that cellular activation is regulated in a non-linear fashion—not by a single mechanical parameter, it is the combined action of the applied mechanical pressure, rate of loading and loading impulse, along with the extracellular environment used to convey the pressure waves. Finally, our research indicates that PO MSCs are finely tuned to respond to mechanical stimuli that fall within defined ranges of loading.
Highlights
It is generally accepted that the world’s landmine and improvised explosive device (IED) threat is reaching crisis level
The in vitro platforms consisted of the integration of a modified drop-weight rig (DW), and a split-Hopkinson pressure bar (SHPB) as these cover the ranges of strain rates associated with dynamic and traumatic events
Twenty-four hours post-loading, we found that only the dynamic loading conditions (SHPB and DW) upregulated Runx2 mRNA in the PO mesenchymal stromal cell (MSC) (SHPB low = 3.12 ± 1.00; SHPB high = 6.76 ± 2.03; DW low = 3.76 ± 1.26; DW high = 4.65 ± 1.14)
Summary
It is generally accepted that the world’s landmine and improvised explosive device (IED) threat is reaching crisis level. In the recent operational theaters of Iraq and Afghanistan, injury to limbs accounted for more than 8 of every 10 combat wounds due to explosive devices [3, 4]. In 64% of amputees that have lost limbs through IEDs and landmines, heterotopic ossification (HO) is reported [5,6,7,8]. Blast-mediated HO is the formation of ectopic bone due to inappropriate mesenchymal stromal cell (MSC) osteogenesis in non-skeletal tissues. Recent data have indicated that HO initiates from the local biochemical and biomechanical effects at the injury site [7]. The etiology of blast-mediated HO in IED/landmine trauma remains the subject of much research
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