TRAP-Positive Multinucleated Giant Cells Are Foreign Body Giant Cells Rather Than Osteoclasts: Results From a Split-Mouth Study in Humans
This study compared the material-specific tissue response to the synthetic, hydroxyapatite-based bone substitute material NanoBone (NB) with that of the xenogeneic, bovine-based bone substitute material Bio-Oss (BO). The sinus cavities of 14 human patients were augmented with NB and BO in a split-mouth design. Six months after augmentation, bone biopsies were extracted for histological and histomorphometric investigation prior to dental implant insertion. The following were evaluated: the cellular inflammatory pattern, the induction of multinucleated giant cells, vascularization, the relative amounts of newly formed bone, connective tissue, and the remaining bone substitute material. NB granules were well integrated in the peri-implant tissue and were surrounded by newly formed bone tissue. Multinucleated giant cells were visible on the surfaces of the remaining granules. BO granules were integrated into the newly formed bone tissue, which originated from active osteoblasts on their surface. Histomorphometric analysis showed a significantly higher number of multinucleated giant cells and blood vessels in the NB group compared to the BO group. No statistical differences were observed in regard to connective tissue, remaining bone substitute, and newly formed bone. The results of this study highlight the different cellular reactions to synthetic and xenogeneic bone substitute materials. The significantly higher number of multinucleated giant cells within the NB implantation bed seems to have no effect on its biodegradation. Accordingly, the multinucleated giant cells observed within the NB implantation bed have characteristics more similar to those of foreign body giant cells than to those of osteoclasts.
Scans of the overall implantation area of the investigated biomaterials: (a) NanoBone (hematoxylin & eosin [H & E] staining). (b) Bio-Oss (azan staining).
Tissue reactions to the two investigated bone substitute materials. Within the Bio-Oss group, particles are integrated within a network of newly formed bone tissue and mildly vascularized connective tissue. (a1) Hematoxylin and eosin, original magnification ×100, scale bar 100 μm. (a2) Giemsa staining, original magnification ×200, scale bar 10 μm. (a3) Giemsa staining, original magnification ×400, scale bar 10 μm. In the NanoBone group, bone substitute materials were embedded in remaining connective tissue, supporting more new bone formation compared to the Bio-Oss group: (b1) Movat's pentachrome staining, original magnification ×100, scale bar 100 μm. (b2) azan staining, original magnification ×200, scale bar 10 μm. (b3) Movat's pentachrome, original magnification ×400, scale bar 10 μm. In both groups, mononuclear cells (black arrows) and multinuclear cells (red arrows) can be found in close proximity to the biomaterial granules, indicating that these cells induce degradation/breakdown of the material.
Histochemical staining of tartrate-resistant acid phosphatase. This enzyme is mainly expressed by multinucleated giant cells (red arrows). When analyzing the distribution of multinucleated giant cells within the two groups, the giant cells are more prominently expressed in the NanoBone (b1–2) group. Fewer multinucleated giant cells can be found in the Bio-Oss group (a1–2). (a1, b1) Immunohistochemical TRAP staining, original magnification ×200, scale bar 10 μm. (a2, b2). Immunohistochemical TRAP staining, original magnification ×400, scale bar 10 μm.
Figure 4. Histomorphometric analysis of the tissue distribution in the implantation beds of the analyzed bone substitute materials. Measurements of the amounts of connective tissue, new bone tissue, and remaining biomaterial were not significantly different. Figure 5. Histomorphometric analysis of the number of multinucleated giant cells. (a) Histomorphometric analysis of the total amount of multinucleated giant cells revealed a significantly greater amount in the NanoBone group (**). (b) Histomorphometric analysis of the total amount of TRAP(+) giant cells revealed significantly more cells in the NanoBone group compared to the Bio-Oss group (**). (c) Histomorphometric analysis of the total number of TRAP(-) giant cells in the Bio-Oss and NanoBone groups revealed a significantly higher number in the NanoBone group (*). Figure 6. Histomorphometric analysis of the vessel density (a) and vascularization (b). The vessel density and the percent vascularization were statistically significantly higher in the NanoBone group (a: ***, b: **).
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