The goal of this project is to develop an in vitro system using endosteal cells to elucidate the early biochemical events which take place at the surface of am implant. The number of endosseous dental implants placed continues to rise each year. While oral rehabilitation with implants has enjoyed clinical success, knowledge of the exact biological processes involved in implant integration is lacking. Improvement in future implant designs demands that the biological process of osseointegration be defined at the cellular and molecular level. Research in previous implant studies has focused on in vivo histological and ultrastructural findings at the late stages of implant integration. Additionally, most in vitro implant studies have utilized neonatal periosteal bone cells. The fact that the majority of an implant surface is placed within endosteal bone, and that endosteal bone cells appear to exhibit different cellular characteristics than periosteal bone cells supports the use of an endosteal cell model to study the cellular responses to implants. This proposal will examine some of the biochemical events which takes place during the early exposure of endosteal cells to different types of implant materials. The principal investigator's group will examine the effects of different implant surfaces on early cell activation; particularly the up-regulation of phosphorylated signal transduction intermediates that are associated with cell adhesion. The effect of different extracellular matrix proteins on endosteal cell activation will also be addressed. Furthermore, the subpopulations of endosteal cells that are activated by the implant surface will be defined. Finally, the specific integrin receptors present on endosteal cells that are responsible for cellular adhesion to implant surfaces will be examined. Knowledge of the biochemical events that take place at the implant surface will allow a more rational approach to the future construction of the implant materials. Analysis of different matrix proteins to enhance cellular adhesion and activation will give insight into implant surface characteristics that will accelerate the implant integration and allow for a more rapid treatment regime.
