Isabelle Rennekampff (Aachen / DE), Rald Victor Maria Groven (Aachen / DE), Nils Becker (Aachen / DE), Qun Zhao (Aachen / DE), Changlin Qi (Aachen / DE), Nan Zhou (Aachen / DE), Frank Hildebrand (Aachen / DE), Klemens Horst (Aachen / DE), Martijn van Griensven (Maastricht / NL), Elizabeth Rosado Balmayor (Aachen / DE)
Introduction Early Total Care (ETC) and Damage Control Orthopedics (DCO) influence local and systemic immunological processes and tissue regeneration, with which deregulation of miRNAs may be associated. However, the impact on miRNA expression of conversion from temporary to definitive fracture fixation as exerted by DCO is hardly investigated. Therefore, this study aimed to investigate the effect of DCO vs. ETC fracture fixation in the context of polytrauma on the expression of local and systemic miRNAs over time.
Methods The rat polytrauma model consisted of blunt chest trauma, hemorrhagic shock, and a unilateral femur fracture (fx). Three groups were defined: sham, n=9; ETC, n=18; DCO, n=18. In the ETC group, the fx was treated with intramedullary nailing (IMN). In the DCO group, an external fixator (EF) was initially used. At day 6 post-trauma, a conversion of the EF to IMN was performed. Serum samples were analyzed at 6 hours (h), 72 h, 7 days (d), and 21d. Lung, heart, liver, and kidney were analyzed at 7d and 21d. MiRNAs were isolated, transcribed, and pooled for qPCR array analysis, followed by bioinformatic analyses.
Results qPCR array data exhibited distinct systemic upregulation of inflammatory miRNAs after trauma in both groups. More regenerative miRNAs were found systemically in the DCO group at an early stage (6h), notably with elevated levels of members of the miR-200 family. Despite conversion to IMN, and the associated increased expression of inflammatory miRNAs in the circulation, the DCO group enabled more organ regenerative responses on day 7 after trauma in the lung, heart, liver, and kidney.
Conclusion This study showed that DCO led to a reduction in systemically expressed pro-inflammatory miRNAs after polytrauma, but that conversion to IMN significantly reactivated the systemic miRNA inflammatory response. These data warrant further research into the expression of miRNAs over time in relation to definitive fracture fixation after trauma.
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