Mesenchymal Stem Cell and Immune Cell Modulation by Nano-Scale Surface Topography of Dental Implants

Immunomodulatory function during osseointegration is today known to involve multiple immune cells including macrophages. The macrophage plays both pro-inflammatory and regenerative roles that include the production of osteoinductive factors that can influence bone formation at the implant/bone interface. While descriptive studies have examined the influence of surface topography on macrophage and osteoprogenitor/mesenchymal stem cell function in the process of osseointegration, many questions remain. The goal of this project was to further characterize the adherent macrophage and mesenchymal stem cell phenotypes as a function of different implant topographies. We hypothesized that compared to a micro/nano hybrid topography, a nanoscale topography would promote anti-inflammatory phenotype of adherent macrophages and maintain the osteoinductive phenotype of adherent mesenchymal stem cells. In the present study, we have examined the effect of a nanoscale topography versus hybrid micron/nanoscale topography on adherent macrophage and mesenchymal stem cell function both in cell culture and in vivo. Our data implicates a dynamic process that may be influenced by nano topography at multiple stages of osseointegration including initial immunomodulation, recruitment of MSCs and later osteoblastic differentiation leading to bone matrix production and mineralization. Our results suggest that a nanoscale topography favorably modulates adherent macrophage polarization toward anti-inflammatory and regenerative phenotypes and promotes the osteoinductive phenotype of adherent mesenchymal stem cells. These studies support the continued investigation of purely nanoscale implant topography to improve clinical dental implant therapy. In this thesis, we have provided a summary of the most recent advances in the understanding of immunomodulation in osseointegration and the role of titanium surface topographies for directing progenitor and immune cell fate and function to improve implant osseointegration and prevent bone loss. In the past decade, descriptions of immune cell activities at the implant/tissue interface have illuminated the potential impact of immunomodulation in osseointegration. However, detailed mechanistic studies are lacking. Further, these studies have clearly revealed the impact of implant surface topography on the reported phenotypes of adherent immune cells. Still, gaps remain in our understanding of topography-related immunomodulatory events at the implant/tissue interface. The interaction of immune cells with MSC/osteoblastic cells and how surface related events influence surrounding bone tissue physiology remain under explored.