Osteoimmune regulation underlies oral implant osseointegration and its perturbation

Abstract

In the field of biomaterials, an endosseous implant is now recognized as an osteoimmunomodulatory but not bioinert biomaterial. Scientific advances in bone cell biology and in immunology have revealed a close relationship between the bone and immune systems resulting in a field of science called osteoimmunology. These discoveries have allowed for a novel interpretation of osseointegration as representing an osteoimmune reaction rather than a classic bone healing response, in which the activation state of macrophages ((M1–M2 polarization) appears to play a critical role. Through this viewpoint, the immune system is responsible for isolating the implant biomaterial foreign body by forming bone around the oral implant effectively shielding off the implant from the host bone system, i.e. osseointegration becomes a continuous and dynamic host defense reaction. At the same time, this has led to the proposal of a new model of osseointegration, the foreign body equilibrium (FBE). In addition, as an oral wound, the soft tissues are involved with all their innate immune characteristics. When implant integration is viewed as an osteoimmune reaction, this has implications for how marginal bone is regulated. For example, while bacteria are constitutive components of the soft tissue sulcus, if the inflammatory front and immune reaction is at some distance from the marginal bone, an equilibrium is established. If however, this inflammation approaches the marginal bone, an immune osteoclastic reaction occurs and marginal bone is removed. A number of clinical scenarios can be envisioned whereby the osteoimmune equilibrium is disturbed and marginal bone loss occurs, such as complications of aseptic nature and the synergistic activation of pro-inflammatory pathways (implant/wear debris, DAMPs, and PAMPs). Understanding that an implant is a foreign body and that the host reacts osteoimmunologically to shield off the implant allows for a distinction to be drawn between osteoimmunological conditions and peri-implant bone loss. This review will examine dental implant placement as an osteoimmune reaction and its implications for marginal bone loss.

Osseointegration and osteoimmunology in implantology: assessment of the immune sustainability of dental implants using advanced sonographic diagnostics: research and case reports

“…There are likely further complex mechanisms in dental implantology that have not yet been fully appreciated, given that osseointegration involves a continuous and dynamic host defense reaction. 62 The results of our combined diagnostic (Ti-Stim and CTU) and pathogenetic (CCL5) findings support the consistent use of Cer-Impl. Additional clinical and multicenter studies, particularly with respect to the stability of the assessed implants, are necessary to further validate the methods and statements presented in our study.…”

Biomaterials science and surface engineering strategies for dental peri-implantitis management

“…lipopolysaccharides) activate innate immune cells (dendritic cells, macrophages, and neutrophils), which are recruited and migrate into the lesion, leading to both innate and acquired immune responses aimed at combating bacterial infections [ 65 ]. During this process, macrophages are in an M1 polarization state, resulting in high levels of pro-inflammatory cytokines, especially interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), leading to augmented tissue destruction surrounding the implant [ 66 – 68 ]. Enhancing osteogenic function can not only reduce the adverse impact of inflammatory-immune responses induced by bacterial contamination but also accelerate the healing process and facilitate bone-implant integration.…”

Harnessing osteoimmunity to treat peri-implant inflammatory osteolysis

“…Instead, they should be classified as osteoimmunomodulatory and co-participate in the process of alveolar bone remodeling. 3 If bacterial plaque microorganisms cause hyperimmune rejection, the implant will transition from being osteoimmunomodulatory to being targeted by the immune system. This may lead to inflammation and osteolysis around the implant.…”