Osteoimmunology drives dental implant osseointegration: A new paradigm for implant dentistry

Abstract

There is a complex interaction between titanium dental implants, bone, and the immune system. Among them, specific immune cells, macrophages play a crucial role in the osseointegration dynamics. Infiltrating macrophages and resident macrophages (osteomacs) contribute to achieving an early pro-regenerative peri-implant environment. Also, multinucleated giant cells (MNGCs) in the bone-implant interface and their polarization ability, maintain a peri-implant immunological balance to preserve osseointegration integrity. However, dental implants can display cumulative levels of antigens (ions, nano and microparticles and bacterial antigens) at the implant-tissue interface activating an immune-inflammatory response. If the inflammation is not resolved or reactivated due to the stress signals and the immunogenicity of elements present, this could lead implants to aseptic loosening, infections, and subsequent bone loss. Therefore, to maintain osseointegration and prevent bone loss of implants, a better understanding of the osteoimmunology of the peri-implant environment would lead to the development of new therapeutic approaches. In this line, depicting osteoimmunological mechanisms, we discuss immunomodulatory strategies to improve and preserve a long-term functional integration between dental implants and the human body. Scientific field of dental science: implant dentistry.

Keywords: Bone loss; Dental implant; Immunomodulation; Osseointegration; Osteoimmunology.

Fig. 1

Hypothetical scenario: Functional dental implant and eventual accumulation of antigens (ions, nano and microparticles and bacterial antigens) with the presence of activated immunological sentinels (DCs and macrophages) throughout the implant-tissue interface. If the inflammation is not resolved or reactive due to the stress signals and the immunogenicity of the elements present, there is a risk that initially relatively harmless peri-implant bone loss progresses to a more damaging and vicious stage, due to the polarization capacity of the MNGC. Ag = antigen; DC = dendritic cell; F = fibroblast; HBMMSC = human mesenchymal stem cells derived from bone marrow; L = lymphocyte; M1 = macrophage; MNGCs = multinucleated giant cells; Ob = osteoblast; Oc = osteoclast; Ost = osteocyte.

Fig. 2

Immunomodulation strategies to improve, maintain and eventually recover osseointegration: A) Modification of implant surfaces properties may improve osseointegration, probably by switching the phenotype of peri-implant macrophages from the pro-inflammatory (M1) subset to a pro-regenerative one (M2). B) Osseointegration needs to be maintained, this could be possible by reducing an eventual secretion of pro-inflammatory cytokines through ionic-treated implant surfaces with LiCl or Mg. C) Another approach is centered on the modulation of macrophage phenotype using polarizing cytokines such IL-4. D) Recently, it has been proposed that an external mechanical stimulus directed to the peri-implant tissue could promote the innate immunomodulatory capacities of BMMSCs, influencing CDs and macrophages, this through mechano-signal transduction and the release of exosomes (ex). Ag = antigen; Ex = exosome; HBMMSC = human mesenchymal stem cells derived from bone marrow; M2 = macrophage; MNGCs = multinucleated giant cells; Ob = osteoblast; Oc = osteoclast; Ost = osteocyte; Tol-DC = tolerogenic dendritic cell.