Publikationsdatenbank

Mimicking the initial phase of fracture healing in vitro (2021)

Art

Hochschulschrift

Autor

Pfeiffenberger, Moritz (WE 11)

Quelle

Berlin: Mensch und Buch Verlag, 2021 — XII, 144 Seiten

Sprache

Englisch

Verweise

URL (Volltext): https://refubium.fu-berlin.de/handle/fub188/30971

Kontakt

Institut für Tierschutz, Tierverhalten und Versuchstierkunde

Königsweg 67
14163 Berlin
+49 30 838 61146
tierschutz@vetmed.fu-berlin.de

Abstract / Zusammenfassung

The initial phase after a fracture is particularly susceptible to fracture healing disorders. This is noticeable both in horses and humans. In order to better understand processes, especially during this phase, there are a number of different research approaches. While animal models, mostly conducted in small animals like mice and rats, were the only available option, possibilities to generate research results using 2D and 3D in vitro models have arisen more recently. These offer the possibility to transfer the obtained results into the human preclinical stage. The aim of this thesis was to develop an in vitro model that will help to develop new therapeutic strategies focused on fracture healing. First, an equine and a human fracture hematoma (FH model) were developed. The models show a clear overlap with ex vivo and in vivo experiments in animal and human models. Thus, essential processes (osteogenesis, inflammation, adaptation to hypoxia and angiogenesis) could be shown on the cell, RNA and protein level for the initial phase. In addition, three-dimensional scaffold-free bone constructs (bone model, SFBC) were developed, which are very similar to native initial bone in structure, cell composition and mineralization. In the final step, the immune component (FH model) was co-cultured with the bone component (SFBC) to simulate the fracture gap. This also shows significant overlap with ex vivo and in vivo experiments in animals and humans. The complete model makes it possible to mimic the initial phase of fracture healing. The later use of the model aims to provide a platform for the development of new therapeutic strategies for fracture healing and to enable drug testing, especially prior to animal testing, in order to evaluate a suitable candidate group prior to animal testing.