Rald VM Groven (Maastricht / NL), Ümit Mert (Aachen / DE), Johannes Greven (Aachen / DE), Martijn Poeze (Maastricht / NL), Taco Blokhuis (Maastricht / NL), Markus Huber-Lang (Ulm / DE), Frank Hildebrand (Aachen / DE), Martijn van Griensven (Maastricht / NL)
Abstract text (incl. references and figure legends)
Objectives Cellular signalling and communication, both at the site of injury and over distance, are key in tissue regeneration after multiple trauma. Among others, surgical treatment strategies, such as early-total-care (ETC) and damage-control-orthopedics (DCO), influence tissue regeneration. To examine this, we investigated miRNA (miR) expression systemically and at the fracture site in a porcine multiple trauma model. Methods The model consisted of blunt chest trauma, liver laceration, bilateral femur fracture, and controlled haemorrhagic shock. Animals were monitored under ICU-standards for 72 hours. Three treatment groups were defined: sham (n=6), ETC (n=7), and DCO (n=8) (fig.1). Fracture hematoma, fractured bone, bone from an unfractured long bone, and Extracellular Vesicles (EVs) from blood plasma were sampled. MiRs were isolated, transcribed and pooled for qPCR array analysis followed by in silico mRNA target analysis. Results Array data revealed miR expression levels specific to the multiple trauma treatment method and sample type. Locally, in bone and fracture hematoma tissue, anti-inflammatory miR were upregulated in the ETC group compared to the DCO group. Systemically, upregulation of anti-inflammatory miR, packaged in EVs, was observed in the DCO group. Furthermore, a clear EV-derived miR signature showed expression of injury specific miR in the systemic circulation. A total of 177 mRNA targets were identified to interact with most deregulated miRs. Conclusion This study revealed multiple trauma specific, as well as treatment specific miR expression profiles at the site of injury, linked to key processes in inflammation, tissue regeneration, and fracture healing. Distinct patterns of acute phase miR expression were identified in plasma-derived EVs. This study showed that miRs are important in regulating tissue regeneration after trauma, that EVs are involved in miR transport over distance, and that their expression might be of prognostic value.
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