Differential surgical and immunological control in a long-term pig polytrauma model

• Applicants: Professor Dr. Frank Hildebrand; Professor Dr. Markus Huber-Lang
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2020 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 429837092

Multiple trauma induces a complex molecular and cellular danger response. Despite the use of modern treatment strategies, this response can regularly results in severe posttraumatic complications (sepsis, multiple organ dysfunction syndrome, death) over the clinical course. Particularly Toll-like receptors (TLR) and the complement system are involved in the recognition and elimination of pathogens and damaged tissue. While the pathophysiology and immunologic consequences in the early phase after multiple trauma (<24 h) have been investigated in several clinical and experimental studies, there is no long-term large animal model, in which morphological and functional consequences as well as the molecular danger response can be investigated in a clinically relevant setting. Long-term large animal models also seem to be indispensable for the evaluation of new therapeutic strategies. Therefore, we aim to investigate the influence of different surgical strategies (intramedullary femur nail & surgical control of liver rupture vs external fixator & liverpacking) as well as immune control with a parallel blockade of C5 and CD14 in an established porcine multiple trauma model with standardized tissue damage and hemorrhagic shock and guideline directed intensive care therapy. In addition, local and systemic expression patterns of microvesicles concerning origin and content including miRNAs will be elucidated. Target genes for miRNA will be also investigated. As a future perspective, new diagnostic and therapeutic approaches for the treatment of the multiple trauma patient with improvements of cellular and organ function and a consecutively higher survival might be developed.

• DFG Programme: Research Grants
• Co-Investigators: Privatdozent Dr. Klemens Horst; Professor Dr. Ingo Marzi