Macrophage behavior and interplay with gingival fibroblasts cultured on six commercially available titanium, zirconium, and titanium-zirconium dental implants
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.
KeywordsSLA 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.
No ethical approval was required for this study, as human samples were not identified.
For this type of study, informed consent to conduct the experiments outlined in this study was provided prior to blood draw.
- 1.Miron RJ, Bosshardt DD (2016) OsteoMacs: key players around bone biomaterials. Biomaterials 82:1–19. https://doi.org/10.1016/j.biomaterials.2015.12.017 CrossRefPubMedGoogle Scholar
- 2.Romeo E, Lops D, Margutti E, Ghisolfi M, Chiapasco M, Vogel G (2003) Long-term survival and success of oral implants in the treatment of full and partial arches: a 7-year prospective study with the ITI dental implant system. Int J Oral Maxillofac Implants 19:247–259Google Scholar
- 3.Karoussis IK, Salvi GE, Heitz-Mayfield LJA, Brägger U, Hämmerle CHF, Lang NP (2003) Long-term implant prognosis in patients with and without a history of chronic periodontitis: a 10-year prospective cohort study of the ITI® dental implant system. Clin Oral Implants Res 14:329–339CrossRefGoogle Scholar
- 7.Cabrera-Dominguez J, Castellanos-Cosano L, Torres-Lagares D, Machuca-Portillo G (2017) A prospective case-control clinical study of titanium-zirconium alloy implants with a hydrophilic surface in patients with type 2 diabetes mellitus. Int J Oral Maxillofac Implants 32:1135–1144. https://doi.org/10.11607/jomi.5577 CrossRefPubMedGoogle Scholar
- 8.Herrmann J, Hentschel A, Glauche I, Vollmer A, Schlegel KA, Lutz R (2016) Implant survival and patient satisfaction of reduced diameter implants made from a titanium-zirconium alloy: a retrospective cohort study with 550 implants in 311 patients. J Craniomaxillofac Surg 44:1940–1944. https://doi.org/10.1016/j.jcms.2016.09.007 CrossRefPubMedGoogle Scholar
- 9.Schincaglia GP, Kim YK, Piva R, Sobue T, Torreggiani E, Kalajzic I (2017) Osteogenesis during early healing around titanium and Roxolid implants: evaluation of bone markers by immunohistochemistry and RT-PCR analysis in miniature pigs: a pilot study. Int J Oral Maxillofac Implants 32:42–51. https://doi.org/10.11607/jomi.4859 CrossRefPubMedGoogle Scholar
- 13.Trindade R, Albrektsson T, Galli S, Prgomet Z, Tengvall P, Wennerberg A (2017) Osseointegration and foreign body reaction: titanium implants activate the immune system and suppress bone resorption during the first 4 weeks after implantation. Clin Implant Dent Relat Res 20:82–91. https://doi.org/10.1111/cid.12578 CrossRefPubMedGoogle Scholar
- 16.Lee H-J, Lee J, Lee J-T, Hong J-S, Lim B-S, Park H-J, Kim Y-K, Kim T-I (2015) Microgrooves on titanium surface affect peri-implant cell adhesion and soft tissue sealing; anin vitroandin vivostudy. J Periodontal Implant Sci 45:120. https://doi.org/10.5051/jpis.2015.45.3.120 CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Lee HJ, Lee J, Lee JT, Hong JS, Lim BS, Park HJ, Kim YK, Kim TI (2015) Microgrooves on titanium surface affect peri-implant cell adhesion and soft tissue sealing; an in vitro and in vivo study. J Periodontal Implant Sci 45:120–126. https://doi.org/10.5051/jpis.2015.45.3.120 CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Tan KS, Qian L, Rosado R, Flood PM, Cooper LF (2006) The role of titanium surface topography on J774A.1 macrophage inflammatory cytokines and nitric oxide production. Biomaterials 27:5170–5177. https://doi.org/10.1016/j.biomaterials.2006.05.002 CrossRefPubMedGoogle Scholar
- 33.Wei L, Ke J, Prasadam I, Miron RJ, Lin S, Xiao Y, Chang J, Wu C, Zhang Y (2014) A comparative study of Sr-incorporated mesoporous bioactive glass scaffolds for regeneration of osteopenic bone defects. Osteoporos Int 25:2089–2096. https://doi.org/10.1007/s00198-014-2735-0 CrossRefPubMedGoogle Scholar
- 34.Anderson JM, Rodriguez A and Chang DT (2008) Foreign body reaction to biomaterials. Book title. ElsevierGoogle Scholar
- 38.Morra M, Cassinelli C, Bruzzone G, Carpi A, Santi GD, Giardino R and Fini M (2003) Surface chemistry effects of topographic modification of titanium dental implant surfaces: 1. Surface analysis. Int J Oral Maxillofac Implants 18:40–45Google Scholar
- 40.Hotchkiss KM, Clark NM, Olivares-Navarrete R (2018) Macrophage response to hydrophilic biomaterials regulates MSC recruitment and T-helper cell populations. Biomaterials 182:202–215. https://doi.org/10.1016/j.biomaterials.2018.08.029 CrossRefPubMedGoogle Scholar