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Complications during fracture healing in form of healing disorders or non-union still occur (Haas, 2000). In this project, a defect osteotomy on a sheep model was performed to obtain a fracture hematoma. The fracture was provided with a rigid external fixator. For comparison purposes, a muscle damage has been done to cause a soft tissue hematoma. The aim of the project was to determine the cellular composition of both hematoma and the expression of various cytokines, growth factors, transcription factors, transmembrane transport- and extracellular matrix proteins. Especially at the inflammatory processes, there are significant differences in fracture healing compared to soft tissue injuries.
In osteotomy hematoma are less inflammatory cells available than in soft tissue hematoma. In return, proinflammatory factors show a much greater intensity than in the soft tissue hematoma. Antiinflammatory factors are significantly stronger upregulated in the osteotomy hematoma as well as antiinflammatory T helper cells are found in larger numbers.
It is therefore likely that the reason for the scarless healing of a fracture is a result of the regulation of the inflammatory response. This gets more evident as early upregulation of angiogenic factors, which begins simultaneously with the upregulation of antiinflammatory factors, suggesting a rapid revascularization. The restoration of blood supply, the influx of migrating cells, which are involved in healing of the newly established vessels, the removal of cellular waste and degradation products are essential for successful healing.
The classification of fracture healing in four overlapping phases (see fig. 1.1.) is well known and accepted. Using this experimental project, the processes of the initial phase has been substantiated. Immediately after the emergence of a fracture there is an increase of proinflammatory factors. At the same time, the damage to the tissue, especially of the vessels is clearly visible on the increase of the hypoxic marker. After 1 to 4 hours in the osteotomy hematoma the hypoxia is very pronounced. Both the inflammation and the hypoxia in the soft tissue injury are not as strongly developed as after a bone injury. The studies show that after a fracture the regulation of inflammation and hypoxia starts very quickly.
This is done on the one hand on the molecular and on the other hand at the cellular level. It should be emphasized that the increase of antiinflammatory and angiogenic factors starts simultaneously. Osteogenic factors already appear after 24 hours. It can be assumed that the foundation of a solid bridging of the osteotomy gap is set very early. The results of this work show that the initial healing phase, the inflammatory phase, gives the direction for the healing outcome. A more differentiated understanding of the immunological processes at the beginning of bone healing is the first step towards the development of promising new therapeutic approaches. The influence of the inflammatory response both at the molecular and the cellular level is conceivable. Recent studies show an association between CD8+ T cells, means negatively influencing immune cell populations, and delayed bone healing (Reinke et al., 2013). The elimination of such cells could provide the positive influence of regeneration. It is also conceivable to add factors, allowing the modeling of the early phase of fracture healing. BMPs have been successfully used in practice. The use of antiinflammatory factors such as TGF β and IL-10 to stem inflammation should be further investigated. Also the influence of mesenchymal stem cells by TGF β and regulatory T-cells, and as a result a reduction of the inflammatory response is another starting point for further developments. The restoration of the vascular system is also essential for successful fracture healing. The use of angiogenic factors such as PDGF, VEGF and OPN during fracture healing is another approach to promote new developments.