Effects of titanium substratum and grooved surface topography on metalloproteinase-2 expression in human fibroblasts.

The chemical and topographic effects of com- mercially pure titanium on cell morphology and the regula- tion of matrix metalloproteinase-2 (MMP-2) gene expres- sion, synthesis, and activity were investigated in early passage human gingival fibroblasts. Scanning electron mi- croscopy showed that on smooth titanium (Ti), fibroblasts remained well spread and randomly oriented throughout the culture period. In contrast, cells on V-shaped grooved titanium (VTi) were oriented along the grooves by 16 h and proliferated in this organization throughout the culture pe- riod. The effects of substratum surface chemistry on MMP-2 expression were found to be distinct from those of topogra- phy. Northern hybridization analysis of fibroblasts cultured on Ti revealed an MMP-2 mRNA time-course expression pattern parallel to that observed on the tissue culture plastic (TCP) dishes, but at significantly lower levels at each time- point. The Ti mRNA levels were decreased by 34% at 16 h, 55% at 40 h, and 45% at 90 h relative to TCP. In contrast, MMP-2 mRNA expression on VTi showed both an altered time-course expression pattern and altered levels compared to Ti and TCP. Relative to TCP, VTi MMP-2 mRNA levels were ~80% less at 16 h and ~50% less at 40 h, but not sig- nificantly different at 90 h. Relative to Ti, VTi MMP-2 mRNA levels were ~75% less at 16 h, but ~40% greater at 40 h and ~70% greater at 90 h. These differences may be explained in part by the observed changes in MMP-2 mRNA half-life which decreased by ~40% on Ti but increased by over four- fold on VTi relative to TCP. The smooth Ti also showed an approximate twofold increase of MMP-2 secretion in the late cultures over TCP controls. These results indicate that substratum surface chemistry and topography-induced changes in cell shape can alter MMP-2 expression in normal fibroblasts. The molecular approach to investigating the ma- jor molecules involved in tissue degradation may provide sensitive indicators of tissue remodeling at the tissue-bio- material interface. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 437-445, 1998.