Transcriptomic profiling of peripheral blood cells during mandibular fracture healing: the iBeam study

The immune response is essential in shaping bone healing outcomes and is of particular interest in mandible fractures, as opposed to other fractures, because of the presence of teeth that are colonised by a multitude of microbes that can cause infection or complicate healing. This study investigated the peripheral blood cell transcriptome during mandibular fracture healing phases with particular focus on immune-related indicators. Blood samples from mandibular fracture patients who had normal healing were collected at the time of injury, then 2 weeks and 6 weeks following the injury, corresponding to the inflammation, repair, and remodelling phases of bone healing, respectively. RNA sequencing was performed for blood cells and analysed using the Ingenuity Pathway Analysis (IPA) software. Data validation was conducted using ELISA for soluble serum factors and blood cell counting using Sysmex. The results indicated distinctive systemic changes between the three healing phases. A significant increase in activity and counts of blood neutrophils and monocytes was noted during the inflammatory and repair phases compared to the remodelling phase. In contrast, a prominent activity and increased quantity of blood lymphocytes were detected in the remodelling phase. Furthermore, increased serum levels and activated signalling of interleukin 10 (IL10) were detected, mainly during the inflammation and repair phases. Interestingly, blood cells were found to express high levels of osteogenesis-related markers during the repair phase, with significantly increased serum levels of Insulin-like growth factor 2 (IGF2). In conclusion, systemic blood cell transcriptomic profiling showed a shift from predominantly innate toward adaptive immune response during mandible healing, with serum IL10 and IGF2 levels indicating the resolution of inflammation and the start of osteogenic repair. Therefore, peripheral blood cells and serum factors could be a promising source of non-invasive biomarkers for monitoring healing trajectories of mandible injuries.