Hydrolysestabile Bioaktivierung medizinischer Hochleistungskeramik durch Quervernetzung von RGD-Peptiden, BMP-2- und HGF-Proteinen an Silan-Monoschichten
The aim of the present work was the development and characterization of a hydrolytically stable biological activation of the high performance ceramics Al2O3, Y-TZP, ZTA, and ATZ via crosslinking of c(RGDyK), BMP-2 and HGF. The Hypothesis was the significant promotion of adhesion and osteogenic differentiation of hMSC by the biological activation. For this, hydrolytically stable adhesion promoting SiOx-films were deposited by the comparison of two methods, PVD and PE-CVD. The adhesive strength of the films was proven via tensile and shear strength tests. Functional groups were introduced by the silanization with APDS, MPTES and THPS as shown by XPS. These served as binding points for the crosslinking with BS3 and SMCC. Successful crosslinking of c(RGDyK) was possible by labeling the Peptide with I125 beforehand. A significant increase in hMSC adhesion was afterwards measured in centrifugation tests up to 50 g. Both HGF and BMP-2 were homogeneously immobilized on the surface, the latter with 323 ng/cm2 and 70 % retention over 21 days after an initial burst release. HGF was additionally genetically modified to express a tPA cleavage site and a Cystein-Linker and successfully coupled to the surface. Cultivation of hMSC on BMP-2 modified surfaces showed their osteogenic differentiation towards osteoblasts. The developed method may enable the tissue integration of a new class of biomaterials in vivo via recruitment and differentiation of endogenous stem cells