Browsing by Subject "Angiogenese"

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Zelluläre Mechanismen beim Neuro Tissue-Engineering
(2007) Dreesmann, Lars; Schloßhauer, Burkhard
To date, numerous tissue engineering approaches aim to develop artificial nerve guide implants for the treatment of lesioned nerves. However, the gold standard in this therapeutical application is still the autologous nerve transplantation. By allocation of a native structure, comprising Schwann cells as well as endothelial cells, an optimal supply of regenerating axons is warranted. Because this surgical procedure retrieves several risks, intensive research is done worldwide to develop alternatives. In this context, Schwann cells play an important role. By migration along the lesion site, they built up guidance rails, so called bands of Büngner. These bands offer an ideal substratum for regrowing axons. However, antagonistic fibroblasts may hamper these events. Hence, the interaction between the two cell types was analyzed in detail, setting a focus on migration. Results indicated that fibroblasts foster Schwann cell migration. Neuregulin was identified as molecular mediator causing this effect. Further experiments revealed that neuregulin promotes Schwann cell migration via erB-receptor and the RhoA pathway. With respect to the concept of a nerve guide implant this means, that the inner membrane should allow diffusion of growth factors, but exclude regeneration inhibiting fibroblasts from the inside. For this purpose, gelatin membranes were characterized regarding their physical and chemical properties. Cell biological testing with gelatin tubes shed light on permissivness for Schwann cells, semipermeability for nutrients and exclusion of fibroblasts. Because a better supply with nutrients promises an additional acceleration of regeneration, the formation of blood vessels next to the implant should be promoted by a gelatin sponge. The immigration of blood vessel forming endothelial cells was analyzed using immunocytochemistry and microscopy. Neovascularisation, biocompatibility and inflammation were investigated on the chorioallantoic membrane of the chicken egg, as well as with subcutaneous implantation into mice. Implantation of gelatin nerve guide tubes in lesioned rat sciatic nerves showed an increased angiogenesis and hardly any inflammation. Within the scope of this work, the application of several molecular and cell biological assays, in combination with three different animal models, made a contribution to the detailed comprehension of mechanisms during nerve regeneration, together with an interdisciplinary bridging between material science and biology in development of innovative therapeutical approaches.