| Summary: | The reactions at tissue-implant interfaces are key elements in the study of dental implantology.
Most previous studies have been limited to assessment of the interface at the morphological and
histological levels. The mechanisms underlying the tissue-implant interface reaction are largely
unknown. In this thesis I hypothesized that the surface chemistry and microtopography of
biomaterials could serve as signals to the attached cells and effectively regulate the interface
reaction at the molecular level. I predicted that expression of genes coding for specific molecules
involved in cell attachment and matrix assembly could be altered in vitro by substratum surface
chemistry and topography. If the hypothesis and prediction were accurate, the results from this
thesis would support the development of biomaterial-controlled interface reactions by modifying
the signals of surface chemistry and topography.
The hypothesis and prediction were tested in this thesis by examining the mRNA level, mRNA
stability, gene product secretion and activity of two major extracellular proteins, fibronectin and 72
kDa gelatinase (MMP-2), in human gingival fibroblasts cultured on smooth or micromachined
grooved titanium substrata to determine the effects of surface topography. Tissue culture plastic
substrata were compared with smooth titanium substrata to determine the effects of surface
chemistry.
The study revealed that a grooved substratum surface significantly altered the shape and orientation
of normal fibroblasts. Fibronectin mRNA levels, mRNA stability, amounts of secreted proteins
and matrix-assembly activity were significantly increased in the cells on grooved titanium surfaces
in comparison to the cells on smooth titanium surfaces. Compared to cells on smooth tissue
culture plastic, the cells on smooth titanium surfaces showed altered levels of fibronectin mRNA,
secretion and matrix-assembly activity, as well as reduced mRNA stability. The substratum
surface topography and chemistry also altered the MMP-2 mRNA levels and stability. Cell proliferation and total secreted protein levels were essentially unchanged in the cells cultured on the
different types of surfaces studied. These results indicated that the effects of surface topography
and chemistry can sensitively and selectively regulate specific molecules at several levels. Thus,
the techniques of molecular biology provide a sensitive and specific approach to the assessment of
cell response to biomaterials.
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