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Immune modulatory approaches represent a novel therapeutic treatment stratagy in the context of fracture healing. Especially interferences in the early fracture healing phase could be done directly intra-operatively when a fracture is treated in the clinic, avoiding a stressful second surgery. For such an approach, a deeper characterisation of the patient and thus the identification of a potential impaired healer is indespensable
Investigation of detrimental immune cells
Examination of the number of CD8+ TEMRA cells over time revealed that the difference in CD8+ TEMRA cell number in patients with delayed healing reflects the individual's immune profile, rather than an acute fracture-related event. These cells specifically occur in the early fracture hematoma. Strikingly the depletion of CD8 + T cells improves bone regeneration, whereas adding CD8+ T cells impaires fracture healing. Hence, we focus on these CD8 + TEMRA cells as research target to serve as future marker for interventions in patients with delayed bone fracture healing.
Investigation of supportive immune cells
Regulatory T-cells (Tregs) are an anti-inflammatory cell type as they secrete factors, which suppress pro-inflammatory cells like the CD8+ T-cells. In our group we investigate the possibility to improve the fracture healing outcome by the application of Tregs. A deeper understanding of the mode of action of Tregs in the course of fracture healing could be used in the future in clinical applications to help patients with an impaired healing situation.
Pharmacological immune modulation
Application of Immunmodulatory Factors to support fracture healing is also a focus of our group. Such factors are among others protein-based Interleukins or Antibodies, which target specific cell types and can suppress them. They can also induce a polarization of Immune cells towards a beneficial anti-inflammatory type, like in Macrophages. Whereas antibodies can even deplete entire cell fractions, like the unwanted CD8+ T-Cells. Furthermore, we focus on small signalling molecules, which are already applied in the clinics, and which further revealed anti-inflammatory properties recently. They can suppress pro-inflammatory cells and/or stimulate anti-inflammatory cellular responses. For the application of immunemodulatory factors we investigate local releases from biomaterials besides intravenious injections.
PRIME Study - Mesenchymal Stroma Cells
In the clinics, mesenchymal stroma cells (MSC) are applied in patients with dealyed healing or non-union in form of autologous cancelous bone from the iliac crest or as RIA (reaming-irrigation-aspiration) material. MSCs are precurser cells that undergo osteogenic differentiation and therefore can improve healing. However, the efficacy of the cells varies greatly between the patients. We want to improve the micro millieu the cells encounter after implantation into the bone defect in order to enhance their bone forming properties.