FOR 5417:  Translational Polytrauma Research to Provide Diagnostic and Therapeutic Tools for Improving Outcomes

• Subject Area: Medicine
• Term: from 2022 to 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 465409392

Trauma remains a leading cause of morbidity and mortality worldwide. Pathophysiology of trauma has been better understood the recent years through experimental models and clinical data from registries such as the German Trauma Registry (TR)-DGU®. Still, predicting individual outcomes remains a major challenge. The DFG Research Group 5417 has successfully investigated complex post-traumatic responses, identifying novel mechanisms, biomarkers, and treatment strategies. Its reported achievements to date lay the foundation for the next phase of polytrauma (PT) research. The upcoming funding period will shift focus from local to systemic mechanisms, emphasizing cross-organ communication at cellular, subcellular, and humoral levels. Building on our current expertise in extracellular vesicle (EV) research, the next step is in vivo development of EV-based therapies. This will be pursued through multiple experimental approaches, using shared platforms. The Central Project (CP) will continue to manage the NTF (Network Trauma Research DGU) serum and NTF-EV Biobanks and the Serum Database and will introduce a traumatic brain injury (TBI) module into the TR-DGU®, recently developed under the group’s leadership. CP will also provide clinical data and biospecimens to subprojects. Several subprojects will examine organ crosstalk in PT, focusing on systemic and paracrine EVs. Project FA-1 will study post-traumatic cardiac dysfunction; F-2 will investigate systemic and brain-derived EVs in neuroinflammation post-PT with or without TBI. A-1 will examine lung–bone axis crosstalk and regeneration; U-1 will address intestinal mucosal immunity and remote pancreatic injury. UA-3 will focus on the kidney–bone axis and EV-mediated mechanisms of delayed fracture healing. In parallel, subprojects will initiate therapeutic in vivo studies. A-1 will test nebulized EVs from pneumocytes and bone marrow-derived mesenchymal stromal cells (BM-MSCs); A-2 will assess M2 macrophage-derived EVs; F-3 will evaluate hyperthermia-primed BM-MSC-EVs for anti-inflammatory potential. U-2 will explore targeting A20 to support individualized care in alcohol-intoxicated trauma patients. AU-3 will test Ribonuclease 1 to prevent T cell-mediated complications. While subprojects explore specific organ axes, CP will take a systems-level approach, analyzing global molecular profiles and the complex, dynamic interactions from molecular to organ system levels. Comprehensive omics and bioinformatics analyses, conducted with domain experts, will support identification of mechanisms linked to inflammation, multiple organ dysfunction, and adverse outcomes. Together with data from the NTF Biobank and Databank, this will offer an integrative view of trauma pathophysiology. By linking mechanisms with observed therapeutic effects, the project aims to deepen understanding and advance personalized treatment strategies tailored to individual physiological responses and clinical trajectories.

• DFG Programme: Research Units
• International Connection: Netherlands

Projects

• Anti-inflammatory potential of extracellular vesicles (EVs) from hyperthermia-primed murine mesenchymal stem cells (MSCs) as a therapeutic approach in polytrauma mouse model (Applicants Leppik, Ph.D., Liudmila ;  Störmann, Philipp )
• Coordination Funds (Applicant Marzi, Ingo )
• Dysfunction of intestinal mucosal immunity after polytrauma - impact of remote pancreatic injury (Applicant Huber-Lang, Markus )
• Establishment of a nationwide NTF-EV-Biobank from polytraumatized patients: dependency of EV-characteristics in response to the injury pattern (Applicants Marzi, Ingo ;  Weber, Birte )
• Heparanase and macrophage migration inhibitory factor as diagnostic/therapeutic targets in trauma and haemorrhagic shock-associated multiple organ failure (Applicant Martin, Lukas )
• Impact of aging on combined traumatic brain injury and hemorrhage: role of the H2S system (Applicant Radermacher, Peter Leonhard )
• Influence and Role of Extracellular Vesicles and their Cargo in Neuroinflammatory Processes following Polytrauma with Traumatic Brain Injury (Applicants Henrich, Ph.D., Dirk ;  Schindler, Cora Rebecca )
• Nebulized regenerative extracellular vesicles: a novel therapeutic approach after multiple trauma in a pre-clinical large animal model (Applicants Horst, Klemens ;  Rosado Balmayor, Ph.D., Elizabeth )
• Role of Extracellular Vesicles (EVs) in post-traumatic cardiac dysfunction – Systemic and paracrine Effects of EVs on Cardiomyocytes (CM) (Applicants Marx, Gernot ;  Weber, Birte )
• The Kidney’s Role in Bone Repair: Extracellular Vesicle-Mediated Mechanisms in Poly-trauma-Induced Delayed Fracture Healing (Applicants Halbgebauer, Rebecca ;  Rosado Balmayor, Ph.D., Elizabeth )
• The lung-bone axis after major trauma: insights into organ crosstalk and tissue regeneration (Applicants Groven, Ph.D., Rald Victor Maria ;  Hildebrand, Frank )
• Therapeutic targeting A20 for individualized therapy to improve the long-term outcome in alcohol-intoxicated trauma (Applicant Relja, Borna )
• Therapeutic use of Ribonuclease 1 to prevent T-cell dependent complications in polytrauma (Applicants Bergmann, Christian ;  Zechendorf, Elisabeth )

• Spokesperson: Professor Dr. Ingo Marzi