Differenzierte Chirurgische und Immunologische Kontrolle nach Polytrauma im Langzeit Großtiermodell
Zusammenfassung der Projektergebnisse
The main goals of the collaborative DFG project between the University Hospital Aachen and the University Hospital Ulm were to investigate the effects of different surgical techniques on the local and systemic posttraumatic inflammation, to analyze the systemic EVs composition and their influence on the fracture healing and to perform the immune monitoring-guided immunomodulation in a 72-h model of porcine polytrauma and hemorrhagic shock. The successful cooperation resulted in different publications (several in submission). The authors reported on the effect of DCO and ETC of the local posttraumatic immunologic response and organ injury in regard to the applied surgical strategies. Furthermore, the miRNA and EV data have been presented in international conferences, that is TERMIS (Tissue Engineering and Regenerative Medicine International Society), ORS-ISFR (orthopaedic research society-International society of fracture repair), and ESTROT (European Society of Tissue Regeneration in Orthopaedics and Traumatology). Of note, three awards were won at these international conferences, indicating the novel and interesting value of the research. In Frontiers of Immunology the group reported on the beneficial effects of immune modulation (C5/CD14 inhibition) on the systemic inflammation and its role in preventing the traumarelated coagulopathy and multiple organ dysfunction. Furthermore, this project reflects the first study of an immune monitoring-guided immunomodulation with protection on multiple organ levels after polytrauma. In conclusion, this project offers new insights regarding the effect of commonly used surgical strategies in traumatized patients on posttraumatic immunologic reactions and organ damage, as well as the modulatorty pathways via EVs including their miRNA cargos. This highlights the beneficial effects of immunomodulation. The gained information impresses by its high level translational significance and might be the foundation for further research on development and prevention of trauma-related complications. Moreover, the group demonstrated that synergistic efforts of interuniversity collaborations and partnerships are necessary to successfully perform such a staff- and time-consuming long-term model of combined trauma. In this collaborative study, we demonstrated that: 1. both surgical strategies (DCO and ETC) commonly used in polytraumatized organisms are applicable in regard to their impact on the systemic and local systemic posttraumatic reaction and their impact on organ function. 2. EVs are important modulators and their miRNA cargo has an influence on important transcriptional factors for angiogenesis, osteogenesis, and inflammation. 3. The early (within the first posttraumatic „golden-hour”) administration of the combined inhibition therapy of C5 and CD14, accompanied by a meticulous immune monitoring can: • Improve the hemodynamic performance and reduce the catecholamine requirements • Reduce the systemic inflammation without compromising the normal immune response • Reduce the risk of developing of posttraumatic coagulopathy • Reduce the organ damage, thus preventing the trauma-induced multiple organ dysfunction. An interuniversity collaborative research effort appears mandatory for performing a clinically relevant long-term polytrauma ICU model.
Projektbezogene Publikationen (Auswahl)
-
Dexamethasone-stimulated osteoblast-EVs markedly enhance osteogenesis in vitro (Vortragsnummer AB19-514) „Deutscher Kongress für Orthopädie und Unfallchirurgie" (DKOU22), Berlin
Nan Zhou, Q. Zhao, X. Zhang, Ümit Mert, Klemens Horst, Martijn van Griensven, Markus Huber-Lang, Tom Eirik Mollnes, Johannes Greven, Frank Hildebrand
-
Effect of Combined inhibition of C5 and CD14 on alveolar macrophages in a porcine polytrauma model with acute lung injury (Vortragsnummer AV46-2888). „Deutscher Kongress für Orthopädie und Unfallchirurgie" (DKOU22), Berlin
Ümit Mert, Johannes Greven, Kang Qin, Ludmila Lupu, Rald VM Groven, Martijn van Griensven, Markus Huber-Lang, Tom Eirik Mollnes, Klemens Horst, Frank Hildebrand
-
Extracellular vesicles contain microRNAs and differ depending on fracture treatment in a multiple trauma setting. ORS ISFR 17th Internation Biennial Meeting, 2022, Edinburgh, Scotland
Rald VM Groven, Johannes Greven, Ümit Mert, Sam Majoor, Martijn Poeze, Taco Blokhuis, Markus Huber-Lang, Frank Hildebrand, Martijn van Griensven
-
MicroRNAs and their role in fracture healing: comparing different surgical treatment strategies. ORS ISFR 17th Internation Biennial Meeting, 2022, Edinburgh, Scotland
Rald VM Groven, Ümit Mert, Johannes Greven, Martijn Poeze, Taco Blokhuis, Markus Huber-Lang, Frank Hildebrand, Martijn van Griensven
-
MicroRNAs and their role in polytrauma: profiling local and systemic expression levels. Tissue Engineering and Regenerative Medicine International Society (TERMIS) European Chapter Conference, 2022, Krakow, Poland
Rald VM Groven, Ümit Mert, Johannes Greven, Martijn Poeze, Taco Blokhuis, Markus Huber-Lang, Frank Hildebrand, Martijn van Griensven
-
Multiple trauma treatment influences extracellular vesicles’ microRNA cargo: a multiple trauma animal model. ESTROT 2022, Maastricht, the Netherlands
Rald VM Groven, Johannes Greven, Ümit Mert, Sam Majoor, Martijn Poeze, Taco Blokhuis, Markus Huber-Lang, Frank Hildebrand, Martijn van Griensven
-
Simultaneous C5 and CD14 inhibition limits inflammation and organ dysfunction in pig polytrauma. Frontiers in Immunology, 13 (2022, 8, 18).
Lupu, Ludmila; Horst, Klemens; Greven, Johannes; Mert, Ümit; Ludviksen, Judith A.K.; Pettersen, Kristin; Lau, Corinna; Li, Yang; Palmer, Annette; Qin, Kang; Zhang, Xing; Mayer, Benjamin; van Griensven, Martijn; Huber-Lang, Markus; Hildebrand, Frank & Mollnes, Tom Eirik
