Lokale Inflammation und ossäre Zell-Kommunikation nach Trauma : Untersuchungen im Klein-und Großtiermodell [thesis]

Johannes Greven, Frank Hildebrand, Frank Müller, Gabriele Pradel
2020
Based on the results of studies to date, it remains unclear whether concomitant injuries or fracture treatment techniques (osteosynthesis) have a significant effect on local inflammation after a severe trauma and thus cause complications of fracture healing in the form of pseudathroses. Therefore, this dissertation should investigate the specific influence of injuries and osteosynthesis techniques on the local inflammatory response in a clinically relevant polytrauma large animal model. In a
more » ... imal model. In a second study, the effects of extracellular vesicles (EV) on fracture healing osteoblasts were investigated in a translational rat model, since EVs play a relevant role in the intercellular transport of inflammatory mediators and can thus influence their activity profile. Material and methods:The investigations in the large animal model included three groups: group monotrauma (isolated femur fracture), group polytrauma (femur fracture, thoracic trauma, liver laceration, hemorrhagic shock) and sham group (no trauma, only anesthesia/ventilation and catheterization). Depending on the group, the femur fracture was stabilized with an intramedullary nail or an external fixator. The total test duration was 72 h. Muscle and blood samples were taken at four time points (2, 24, 48 and 72 h post trauma) and cytokine concentration and expression as well as immune cell status were analyzed. Methods used were multiplex ELISAs, qRT-PCR and histological sections.In the rat model, a Krischner wire was first inserted intramedullary into the femur and then a femur fracture was induced by means of a blunt guillotine. Blood samples were collected after 3, 7 and 14 days and extracellular vesicles (EV) were isolated. Subsequently, primary osteoblasts were incubated with them and examined for viability and proliferation. In all approaches, EV-free plasma and plasma as a control were included. The analyses were performed by nanoparticle tracking analysis (NTA), immunohistological staining, newborn counts and a proliferation assay (MTT).R [...]
doi:10.18154/rwth-2020-11066 fatcat:ynhhpzu2hrci5mtesld5h5xauu