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

  • Yulan Wang
  • Yufeng ZhangEmail author
  • Anton Sculean
  • Dieter D Bosshardt
  • Richard J MironEmail author
Original Article



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.


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.


SLA ZLA Hydrophilic surfaces Titanium Zirconia Dental implants 



This work was funded by the International Team for Implantology (ITI) Foundation grant 1154_2016.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

No ethical approval was required for this study, as human samples were not identified.

Informed consent

For this type of study, informed consent to conduct the experiments outlined in this study was provided prior to blood draw.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of EducationWuhan UniversityWuhanPeople’s Republic of China
  2. 2.Department of Oral ImplantologyWuhan UniversityWuhanChina
  3. 3.Department of PeriodontologyUniversity of BernBernSwitzerland

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