Induced Experimental Peri-Implantitis and Periodontitis: What Are the Differences in the Inflammatory Response?
This preliminary study investigates the differences between experimental periodontitis and peri-implantitis in a dog model, with a focus on the histopathology, inflammatory responses, and specific immunoregulatory activities driven by Th1/Th2-positive cells. Twelve dental implants were inserted into the edentulated posterior mandibles of 6 beagle dogs and were given 12 weeks for osseointegration. Experimental peri-implantitis and periodontitis (first mandible molar) were then induced using cotton-floss ligatures. Twelve weeks later, alveolar bones were quantitated by cone beam-computer tomography. Histopathologic analysis of the inflamed gingiva and periodontal tissues was performed by light microscopy, and the Th1/Th2 cell populations were investigated by flow cytometry. Peri-implantitis and periodontitis were both found to be associated with pronounced bone resorption effects, both to a similar degree vertically, but with a differential bone resorption pattern mesio-distally, and with a significantly higher and consistent bone resorption result in peri-implantitis, although with a higher variance of bone resorption in periodontitis. The histologic appearances of the inflammatory tissues were identical. The percentages of Th1/Th2 cells in the inflamed gingival tissues of both experimental peri-implantitis and periodontitis were also found to be similar. Experimental periodontitis and peri-implantitis in the dog model show essentially the same cellular pathology of inflammation. However, bone resorption was found to be significantly higher in peri-implantitis; the histopathologic changes in the periodontal tissues were similar in both groups but showed a higher interindividual variation in periodontitis and appeared more uniform in peri-implantitis. This preliminary study indicates that more focused experimental in vivo inflammation models need to be developed to better simulate the human pathology in the 2 different diseases and to have a valuable tool to investigate more specifically how novel treatments/prevention approaches may heal the differential adverse effects on bone tissue and on periodontium in periodontitis and in periimplantitis.
Figure 1. Time course of experimental interventions. Scheme illustrating experimental interventions and measurements performed during the course of time; time points for cone-beam computed tomography imaging are indicated (▴). Figure 2. Gap-width measurement between implant and bone. Explanation of the measurements of the width of the gap space between the implant surface (in black) and the surrounding bone tissue (in red): equally spaced parallel lines were placed vertically to the implant surface and the gap widths (green arrows) measured along each line. The random starting point distance for placing the parallel vertical lines is indicated by a blue double arrow.
Figure 3. Illustration of the cotton-ligature method for induction of inflammation. Photographs of cotton ligature-induced periodontitis (POIS) (o) and peri-implantitis (PIIS) (i). (a) At time of ligature placement. (b) Three months after ligature placement. (c) X-ray of an osseointegrated implant 3 months after implantation at the time point of ligature placement. (d) X-ray of a POIS and PIIS case, 3 months after ligature placement. Figure 4. Depth of vertical and horizontal bone resorption. (a) Depth (vertical extension) of bone resorption of ligature-induced PIIS and POIS 3 months after ligature placement. Differences in vertical resorption of bone were not significant; POIS shows a larger variation (CE = 8.8 % [POIS] vs a CE of 5.3% [in PIIS]). (b) Horizontal width of bone resorption of ligature-induced PIIS and POIS. PIIS shows a significantly wider horizontal bone resorption effect than POIS (P = .005) 3 months after ligature placement. Moreover, the CE value of the PIIS group (CE = 6.3%) is markedly higher than the one of the POIS group (CE = 1.6%). **P < .01.
Figure 5. Histology of peri-implantitis (PIIS) and periodontitis (POIS). Histologic illustrations of PIIS (a) and POIS (d) 3 months after ligature placement. (a) Cotton ligature induced PIIS (bar = 1000 μm). (b and c; insert frame in b) Lower- (bar = 100 μm) and higher- (bar = 50 μm) magnification areas of resorbed bone that are replaced by connective tissue and that are rich in lymphocytes and macrophages. The degree of vascularity in the connective tissue is low. Osteoclast-induced bone resorption activity is clearly identifiable in c (higher magnification of the insert frame in b). (d) Cotton ligature induced POIS (bar = 1000μm). (e [bar = 100 μm] and f [bar = 50 μm]): the replacement tissue in the resorbed bone area is very rich in newly formed blood vessels and contains large numbers of lymphocytes and macrophages (to a similar degree as in b and c), and contains, to a small and irregular degree, neutrophils that only sporadically occur. Figure 6. High-magnification histology of PIIS and POIS. High-magnification light micrograph of PIIS illustrating (a) the inflamed and swollen peri-implant connective tissue spaces and (b) the inflammatory response extending into the surrounding bony tissue area and its association with bone resorption activities. In a, the high degree of vascularity and the extensive infiltration of the connective tissue extracellular matrix space by mainly lymphocytes is illustrated in these inflamed tissue spaces. b illustrates a fragment (debris) of bone tissue with multiple osteoclasts associated with the mineralized bony material and exhibiting resorption activity by the well-visible resorption pits along the mineralized bony surface. There are no signs present of bone forming activities or of the presence of osteoblasts. Also, this tissue area is highly infiltrated with predominantely lymphocytes, indicating the chronic stage attained of the inflammatory response, 3 months after ligature setting.
Figure 7. Comparative flow cytometry data. Flow cytometry analysis. The cells used were derived from peripheral blood. (a) Comparison of Th1 cells (within the CD4 subset) of a normal control with those of peri-implantitis (PIIS) cases. (b) Comparison of Th2 cells (within a CD4 subset) of normal controls with those of PIIS cases. (c) Comparison of Th2 cells (within a CD4 subset) of normal controls with periodontitis-derived cells (POIS). No significant differences are detected between any groups. Figure 8. Relative activity changes (in %) comparing cell activities (Th1, Th2) before and after induction of POIS and PIIS (peripheral blood cells). Flow cytometry analysis: illustration of the relative changes (in %) of Th1 and of Th2 cells (both from peripheral blood) over the experimental time period in PIIS and POIS. The variations are relatively large (see the extensive size of the vertical standard deviation bars); only in the case of the Th2 changes in POIS, this variation was smaller (coefficient of error: 120%). No significant differences are present between the groups (n = 4; bars indicate SD values). Figure 9. Relative proportions (in %) of Th1 and Th2 cells in the CD4 cell pool in the normal vs the PIIS gingiva. Flow cytometry analysis: the percentages of Th1 positive cells in the CD4 subsets are illustrated: (a) Th1 cells in normal gingiva vs Th1 in periimplantitis; (b) Th2 cells in normal gingiva vs Th-2 in PIIS.
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