Charakterisierung und Modulation der Wundheilung durch Epoxyeicosatriensäuren an der Defektwunde am Ohr der Maus: normale Wunde vs. Ischämie/Diabetes mellitus

• Applicant: Dr. Anna Lena Sander
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2010 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 188702338

The immune system represents a vulnerable gateway through which trauma and sepsis exert their deleterious effect on the wound healing process resulting in increased morbidity and mortality for the surgical patient. Though previous studies have suggested that wound healing is impaired in a septic host, the mechanism by which systemic infection alters the inflammatory and reparative response at remote sites of injury (skin) is not fully understood. Ultimately, such mechanistic information may contribute to the development of therapeutic treatments to counteract this disordered inflammatory response in wound healing. The decreased chemotaxis is probably multifactorial and may involve either changes in surface receptor expression and ligand engagement or alterations in intracellular signaling. We postulate that a finite number of polymorphonuclear neutrophils (PMN), macrophages and hematopoietic stem cells (HSC) are available for delivery to one or more sites of injury and that the cells are concentrated in the site of the predominant injury due to an increased chemotactic gradient. Based on this background, the aim of the present study is the characterization of the cell distribution between the site of the predominant and secondary injury by combining the murine cecal ligation and puncture (CLP)-induced sepsis model with full-thickness wounds on the back of mice. Due to the fact that stromal cell-derived factor (SDF) 1-alpha contributes to homing of PMNs and survival in sepsis as well as HSC cell proliferation/mobilization and induction of angiogenesis in wound healing, the activation of SDF1-alpha by autocrine or paracrine mechanisms may constitute a negative feedback pathway to control the systemic inflammatory response and compensate the dysregulation of wound healing in sepsis. In the second part of the present study, we examine the hypothesis that the local application of SDF1-alpha can ameliorate the inhibitory effects of sepsis on cutaneous wound healing to provide a strong foundation for the development of prospective multifunctional angiogenic therapeutics.

• DFG Programme: Research Grants