Macrophage behavior and interplay with gingival fibroblasts cultured on six commercially available titanium, zirconium, and titanium-zirconium dental implants

Objectives: The host-material interface has been a crucial relationship dictating the successful integration of biomaterials, including dental implants. The aim of the present study was to first investigate how macrophages behaved on various dental implant surfaces and thereafter to investigate their effect on soft tissue cells.

Materials and methods: Macrophage adhesion, proliferation, and polarization towards either an M1 or M2 phenotype were investigated on six implant surfaces fabricated from pure titanium (Ti), pure zirconium (ZLA), and a titanium-zirconium (Ti-Zi) alloy of various surface topographies/chemistries. Thereafter, conditioned media (CM) collected from macrophages seeded on these various implant surfaces was cultured with murine gingival fibroblasts and investigated for their ability to promote collagen synthesis.

Results: Macrophages attached and proliferated in similar levels on all implant surfaces; however, the modSLA hydrophilic surfaces tended to decrease the pro-inflammatory response by lowering the gene expression of TNF-alpha, IL-1, and IL-6 and promoting tissue resolution through the expression of an M2-macrophage cytokine IL-10. Thereafter, CM from macrophages were seeded with gingival fibroblasts on each implant surface. In general, CM from macrophages significantly promoted gingival fibroblast cell attachment on all implant surfaces at either 4 or 8 h and, most notably, significantly promoted fibronectin and TGF-beta gene expression on both Ti and Ti-Zi hydrophilic surfaces.

Conclusions and clinical relevance: The present study found that implant surface topography and chemistry substantially impacted macrophage behavior. Most notably, modifications via hydrophilicity to both the pure Ti and Ti-Zi were shown to favor the secretion of macrophage pro-resolution markers and favored subsequent gingival fibroblast cell behavior when cultured with CM, whereas surface composition (Ti vs ZLA vs Ti-Zi) had little effect on macrophage polarization or gingival fibroblast behavior. This finding suggests that surface hydrophilicity would improve the soft tissue integration of dental implants, irrespective of material composition.