gms | German Medical Science

Objectives: Intramedullary nailing (IMN) after trauma activates the immune system. Overactivation of the immune system may form the basis for inflammatory (pulmonary) complications. As an adjunct to IMN, different reaming techniques have been developed and implemented into fracture care. The impact of these different reaming techniques on biomolecular homeostasis is unclear. At the biomolecular level, microRNAs (miRNAs) are believed to play an important role in the development of post-traumatic inflammatory complications, as they are key regulators of gene expression. The aim of this study was to determine the role of the applied reaming technique prior to IMN on the expression of circulating miRNAs in a porcine trauma model. In this model, three different reamer types were used in two different trauma severities.

Methods: 36 Swiss Landrace pigs were randomized into two study groups: monotrauma (MT; n=18; unilateral femur fracture) and polytrauma (PT; n=18; femur fracture, liver laceration, blunt chest trauma, and haemorrhagic shock). Animals were operatively stabilized after a 60-min shock phase and, based on the reaming technique, allocated to one of the following subgroups: 1) SynReam, 2) RIA-1, and 3) RIA-2 (all three: DePuy Synthes, Raynham, MA, USA). Serum was collected at the end of the shock phase, and 2 and 6 h after trauma. MiRNAs were isolated, transcribed and pooled for qPCR array analyses per reamer subgroup from each trauma severity. Subsequently, in silico mRNA target prediction and bioinformatic analyses were performed.

Results and conclusion: Compared to MT, the circulating miRNA-signature of PT at the end of the shock phase (and before reaming) was more pro-inflammatory in nature, including deregulations of miRNAs linked to shock and tissue damage (miRNAs 93, 99a, and 107). Apart from several overlapping miRNA deregulations among the different reamer subgroups of both MT and PT at the 2 and 6h timepoints, distinct differences were observed. RIA 1 and 2 significantly decreased the expression of pro-inflammatory and pro-fibrotic miRNAs compared to SynReam. This effect was most prominent in the PT group as compared to the MT group. Overall, in both the MT and PT groups, the RIA 1 and 2 systems exhibited a more regenerative miRNA profile compared to SynReam.

This study is the first to describe a specific circulating miRNA signature, which were associated to trauma severity and the applied reaming technique. More specifically, our findings imply that the application of SynReam boosts systemic inflammation as compared to RIA 1 and 2. The irrigation and aspiration function of the RIA system, combined with the additional cooling of the intramedullary canal during reaming, thereby reducing osteoinflammation/osteonecrosis, may underlie these observations. These results warrant further research into the potential application of miRNAs as diagnostic/prognostic immunological markers after trauma.