Giant cells around bone biomaterials: Osteoclasts or multi-nucleated giant cells?

Miron, Richard J.; Zohdi, Hamoon; Fujioka‐Kobayashi, Masako; Bosshardt, Dieter D.

doi:10.1016/j.actbio.2016.09.029

Cited by 99 publications

(76 citation statements)

References 155 publications

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“…However, Miron et al indicated that macrophages might have a beneficial effect on bone wound healing/remodeling. Furthermore, a recently published review argued that MNGCs on the surface of implant and bone substitute material, as their precursor macrophages, may roughly classified into two categories with different markers and cytokine expression profile: pro‐inflammatory M1‐MNGCs (previously referred to as FBGCs) and wound‐healing M2‐MNGCs . MNGCs were hypothesized to shift from M1 pro‐inflammatory toward M2 wound‐healing phenotype and vice versa in light of the properties of the local and systemic cytokine environment .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a recently published review argued that MNGCs on the surface of implant and bone substitute material, as their precursor macrophages, may roughly classified into two categories with different markers and cytokine expression profile: pro‐inflammatory M1‐MNGCs (previously referred to as FBGCs) and wound‐healing M2‐MNGCs . MNGCs were hypothesized to shift from M1 pro‐inflammatory toward M2 wound‐healing phenotype and vice versa in light of the properties of the local and systemic cytokine environment . The role of macrophage and MNGCs around the implant in bone homeostasis is not fully understood and requires further investigation at present.…”

Section: Discussionmentioning

confidence: 99%

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Macrophage polarization in aseptic bone resorption around dental implants induced by Ti particles in a murine model

Wang

Liu

Feng

et al. 2019

J of Periodontal Research

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Background and Objectives Titanium particles/ions detected in peri‐implant tissues have been considered as a potential etiologic factor for crestal bone loss around oral implants. However, the definite impact of titanium wear particles on the health of surrounding structures remains undetermined. The purpose of this study was to investigate the effects of titanium particles‐induced foreign body reaction on peri‐implant bone level and the related mechanism by using clodronate liposomes to deplete macrophages. Material and Methods Sprague Dawley rats with custom‐made titanium screw implanted in bilateral maxillary first molar area for 4 weeks to obtain osseointegration were randomly divided into four groups. Twenty microgram titanium particles were introduced into the peri‐implant tissue to induce aseptic foreign body reaction, and macrophages were depleted by the local injection of 100 μL clodronate liposome immediately and re‐injection every 3 days until the sacrifice of the rats (Ti + LipClod group). Titanium‐injected rats also treated with phosphate buffer solution (Ti + PBS) or empty liposome (Ti + Lip) as well as rats injected with PBS alone (Control) were included as controls. Eight weeks later, animals were sacrificed and samples containing implants were collected. Half of the samples were analyzed radiologically to measure bone level change, and macrophage markers (CD68, CCR7, CD163) was also characterized by immunofluorescence to evaluate macrophage number, density, and phenotype distribution (CCR7+M1/CD163+M2). The rest of the samples were used to determine the relative mRNA expression levels of TNF‐α, IL‐1β, IL‐6, and RANKL with real‐time PCR analysis. Results No obvious bacterial contamination was found in all titanium‐injected areas, and the implant survival rate was 100% with no implant loss. Compared with Ti + PBS and Ti + Lip group, macrophage density (1.64 ± 0.86%) infiltrated into peri‐implant tissue and bone loss (0.17 ± 0.03 mm) around implant decreased significantly in the Ti + LipClod group. Immunofluorescence analysis showed that more macrophage infiltrated into peri‐implant tissue in the Ti + PBS and Ti + Lip groups, predominantly with M1 phenotype. In contrast, the macrophage density was lower and M2 phenotype was dominant in the Control group, while macrophages density was significantly reduced and the M1 type macrophages were slightly more than M2 type in the Ti + LipClod group. Accordingly, TNF‐α, IL‐1β, IL6, and RANKL mRNA expression increased significantly in the Ti + PBS and Ti + Lip groups compared with Control and Ti + LipClod groups. Conclusions Titanium particles had a negative effect on peri‐implant tissue by activating macrophages which induced an M1 macrophage phenotype promoting local secretion of inflammatory cytokines. It was found that clodronate liposome treatment attenuated the severity of inflammation and bone loss by depletion of macrophages. Therefore, the present study revealed the marked impact of macrophage polarization with respect to peri‐implant bone loss caused...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Macrophage polarization in aseptic bone resorption around dental implants induced by Ti particles in a murine model

Wang

Liu

Feng

et al. 2019

J of Periodontal Research

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“…The role of these MNGCs have recently been disputed for their association with bone formation . MNGCs have previously been characterized as foreign body giant cells and associated with biomaterial rejection, however more recently their phenotypes have been implicated with wound healing and tissue regeneration . Some studies clearly demonstrated very long‐term existence of MNGCs near biomaterials without displaying a necessary foreign body reaction .…”

Section: Discussionmentioning

confidence: 99%

Effect of recombinant human bone morphogenic protein 9 (rhBMP9) loaded onto bone grafts versus barrier membranes on new bone formation in a rabbit calvarial defect model

Fujioka‐Kobayashi

Kobayashi

Schaller

et al. 2017

J Biomedical Materials Res

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Recent research has demonstrated that recombinant human bone morphogenetic protein 9 (rhBMP9) has been considered the most osteoinductive growth factor of the BMP-family. In the present study, rhBMP9 was investigated for its influence in combination with two biomaterials for bone regenerative medicine. Either porcine-derived collagen membrane (CM) or deproteinized bovine bone mineral (DBM) combined with 20 µg of rhBMP9 were implanted in 6 mm rabbit calvarial defects. Bone augmentation was evaluated by microCT and histomorphometry at 8 weeks post-surgery. Both CM + rhBMP9 and DBM + rhBMP9 groups significantly promoted mineralized tissue volume (microCT) and area, new bone height and area (histomorphometric measurements) when compared to CM and DBM alone groups or control (empty). All specimens in the CM + rhBMP9 group but not all in the DBM + rhBMP9 group induced a complete horizontal bone defect closure. Multinucleated giant cells (MNGCs) were observed directly in contact with DBM surfaces irrespective of rhBMP9, whereas CM was generally not associated to the presence of MNGCs. When combined with rhBMP9, DBM augmented a larger volume of mineralized tissue (including the mineralized bone graft), whereas CM induced greater volume of native host bone. While DBM in combination with rhBMP9 induced higher mineralized tissue mostly associated with the bone grafting material, CM may have presented preferable results based on a higher horizontal defect closure with a faster regeneration of host new bone. The effect of including collagen within the carrier system of rhBMP9 on bone regeneration justifies further evaluation of this combination procedure in larger animal models. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2655-2661, 2017.

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“…Furthermore, as in the present study, where residual graft BCP particles accounted for 25.4% of the total tissue area, a selected class of bone substitutes (especially synthetic and BB substitutes) are routinely found to have significantly higher numbers of MNGCs . These findings further question the role of MNGCs in biomaterials because these cells were once thought to only contribute to the foreign body reaction and, as documented recently, their phenotypes are implicated in wound healing and tissue regeneration and have the potential to degrade biomaterials …”

Section: Discussionmentioning

confidence: 99%

“…[39][40][41] These findings further question the role of MNGCs in biomaterials because these cells were once thought to only contribute to the foreign body reaction and, as documented recently, their phenotypes are implicated in wound healing and tissue regeneration and have the potential to degrade biomaterials. 20,42 It has been shown that the presence of MNGCs within biomaterial implantation beds is not only related to the type of bone substitute material used but also to the granule size of the bone substitute material used. Smaller xenogeneic bone substitute granules have been associated with MNGCs, 43 whereas larger granules are integrated within the implantation bed by means of mononuclear cell-triggered granulation tissue.…”

Section: Discussionmentioning

confidence: 99%

Comparison between mineralized cancellous bone allograft and an alloplast material for sinus augmentation: A split mouth histomorphometric study

Kolerman

Nissan

Rahmanov

et al. 2017

Clin Implant Dent Rel Res

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Giant cells around bone biomaterials: Osteoclasts or multi-nucleated giant cells?

Cited by 99 publications

References 155 publications

Macrophage polarization in aseptic bone resorption around dental implants induced by Ti particles in a murine model

Macrophage polarization in aseptic bone resorption around dental implants induced by Ti particles in a murine model

Effect of recombinant human bone morphogenic protein 9 (rhBMP9) loaded onto bone grafts versus barrier membranes on new bone formation in a rabbit calvarial defect model

Comparison between mineralized cancellous bone allograft and an alloplast material for sinus augmentation: A split mouth histomorphometric study

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