Project Details
Projekt
The Kidney’s Role in Bone Repair: Extracellular Vesicle-Mediated Mechanisms in Poly-trauma-Induced Delayed Fracture Healing
Subject Area
Orthopaedics, Traumatology, Reconstructive Surgery
Term
since 2026
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 465409392
Polytrauma not only causes severe local injuries but can also lead to multi-organ dysfunction, significantly complicating patient outcomes. Among these systemic effects, acute kidney injury (AKI) is one of the most common and serious complications, contributing to high morbidity and mortality. However, the impact of AKI on fracture healing in polytrauma patients has yet to be thoroughly explored. Emerging evidence suggests that kidney dysfunction following trauma may impair fracture healing by disrupting the intricate crosstalk between distant organ systems, par-ticularly through extracellular vesicle (EV)-mediated signaling. Our previous data shows that > 5% of patients with femur fracture developed a trauma-related AKI, facing an over 3-times higher 180 day-mortality rate. This study investigates the kidney's involvement in delayed fracture healing through three key hypotheses: (i) bone fractures in polytrauma induce AKI in rats, independent of age or gender; (ii) kidney-derived EVs are central to the interplay between renal and bone cells, influencing fracture healing outcomes; and (iii) targeted interventions, such as the administration of therapeutic exosomes, can enhance bone regeneration in the context of multiple trauma. To test these hypotheses, we employ a rat model of polytrauma, integrating advanced analyses of serum biomarkers, kidney functional and morphological changes, and EV profiles. Particular emphasis is placed on the characterization of kidney-derived EVs, including their cargo of pro-teins, lipids, and RNA, and their functional impact on cellular and molecular pathways critical to bone repair. By correlating systemic kidney responses with fracture site dynamics, this project seeks to unravel the mechanisms through which kidney-derived EVs modulate healing trajecto-ries. Our findings have the potential to inform novel therapeutic strategies that enhance bone repair and recovery in patients with multiple trauma.
DFG Programme
Research Units
