Autologous Platelet Concentrates in Treatment of Furcation Defects-A Systematic Review and Meta-Analysis.

BACKGROUND: The aim of this review was to evaluate the adjunctive effect of autologous platelet concentrates (APCs) for the treatment of furcation defects, in terms of scientific quality of the clinical trials and regeneration parameters assessment. METHODS: A systematic search was carried out in the electronic databases MEDLINE, SCOPUS, CENTRAL (Cochrane Central Register of Controlled Trials), and EMBASE, together with hand searching of relevant journals. Two independent reviewers screened the articles yielded in the initial search and retrieved the full-text version of potentially eligible studies. Relevant data and outcomes were extracted from the included studies. Risk of bias assessment was also carried out. The outcome variables, relative to baseline and post-operative defect characteristics (probing pocket depth (PPD), horizontal and vertical clinical attachment loss (HCAL, VCAL), horizontal and vertical furcation depth (HFD, VFD) were considered for meta-analysis. RESULTS: Ten randomized trials were included in this review. Only one study was judged at high risk of bias, while seven had a low risk, testifying to the good level of the evidence of this review. The meta-analysis showed a favorable effect regarding all outcome variables, for APCs used in adjunct to open flap debridement (p < 0.001). Regarding APCs in adjunct to bone grafting, a significant advantage was found only for HCAL (p < 0.001, mean difference 0.74, 95% CI 0.54, 0.94). The sub-group analysis showed that both platelet-rich fibrin and platelet-rich plasma in adjunct with open flap debridement, yielded significantly favorable results. No meta-analysis was performed for APCs in combination with guided tissue regeneration (GTR) as only one study was found. CONCLUSION: For the treatment of furcation defects APCs may be beneficial as an adjunct to open flap debridement alone and bone grafting, while limited evidence of an effect of APCs when used in combination with GTR was found.

Regeneration of the cementum and periodontal ligament using local BDNF delivery in class II furcation defects.

Periodontal furcation defects are usually addressed by the placement of a physical barrier which may limit the regenerative potential of periodontal wounds. This study morphometrically quantified the regenerative effect of brain-derived neurotrophic factor (BDNF) in furcation defects in a non-human primate model. Grade II furcation defects (with and without induced inflammation prior to surgery) were created on the first and second molars of eight non-human primates. Defects were treated with open flap debridement and subsequently filled with either: Group A; BDNF (500 µg mL-1 ) in high-molecular weight-hyaluronic acid (HMW-HA), Group B; BDNF (50 µg mL-1 ) in HMW-HA, Group C; HMW-HA acid only, Group D; unfilled defect, or Group E; BDNF (500 µg mL-1 ) in saline. Periodontal wound healing was observed every 2 weeks by computed-tomography. At 11 weeks all animals were sacrificed and maxillary and mandibular block biopsies were referred for nondecalcified histology. Linear measurements of new cementum (cellular and acellular) and periodontal ligament (PDL) formation were performed. Computerized-tomography reconstruction and software quantification demonstrated successful bone fill for all groups. However, histometric assessment demonstrated significantly higher level of total periodontal regeneration for the 500 µg mL-1 BDNF HMW-HA relative to all other groups. No significant differences in cementogenesis were observed among groups. Significantly higher acellular cementum formation was observed for sites where inflammation was not induced prior to surgical procedures. While all groups experienced similar bone fill and cementogenesis, the 500 µg mL-1 BDNF HMW-HA appeared to most effectively repair PDL (minimum increase of ∼22% relative to all groups; over 200% relative to unfilled defects). © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1611-1617, 2018.

The sphingosine-1-phosphate receptor 1 binding molecule FTY720 inhibits osteoclast formation in rats with ligature-induced periodontitis.

BACKGROUND AND OBJECTIVE: Osteoclast precursors (OPs) re-migrate from the bone surface into blood vessels through sphingosine-1-phosphate receptor 1 (S1PR1) expression. T cells also express S1PR1, mediating their migration from the lymph nodes into blood vessels. OP and T-cell migration are one of the sequential steps related to osteoclast formation. To characterize the role of S1PR1 in osteoclast formation induced by periodontitis, we investigated the effect of S1PR1-binding molecule FTY720 (FTY) on the number of OPs and T cells in periodontal tissue and peripheral blood of rats with ligature-induced periodontitis. MATERIAL AND METHODS: Rats were divided into four groups; control (Con), FTY, periodontitis (Peri), and periodontitis+FTY (Peri+FTY) groups. Ligatures were placed around the first molars in the left and right mandibles. The rats were intraperitoneally injected with vehicle or 3 mg/kg FTY daily until they were killed. The number of osteoclasts and cluster of differentiation (CD)11b, CD3 and receptor activator of NF-κB ligand (RANKL)-positive cells in first molar furcation were counted by tartrate-resistant acid phosphatase or immunohistochemistry staining. The number of CD11b- and CD3-positive cells in peripheral blood was estimated by flow cytometry. RESULTS: The number of osteoclasts in the Peri group was higher than Con, Peri+FTY and FTY groups (p < 0.05) and CD11b, CD3 and RANKL-positive cells were also higher in the Peri group than other groups in furcation (p < 0.05). While CD11b-positive cells in furcation of the Peri+FTY group were lower than the Peri group (p < 0.05), they were higher in peripheral blood (p < 0.05). Dissimilar to CD11b-positive cells, CD3-positive cells in the Peri+FTY group were lower in peripheral blood as well as furcation than the Peri group (p < 0.05). RANKL-positive cells in furcation of the Peri+FTY group were also lower than Peri group (p < 0.05). CONCLUSION: These results indicate that FTY may facilitate re-migration of OPs from the alveolar bone surface into blood vessels, blocking T-cell migration from the lymph nodes into blood vessels and subsequently reducing osteoclast formation induced by periodontitis. This suggests that S1PR1-S1P binding may play a role in osteoclast formation of periodontitis by modulating OP and T-cell migration.

Localization of RANK, RANKL and osteoprotegerin during healing of surgically created periodontal defects in sheep.

BACKGROUND AND OBJECTIVE: Modeling of periodontal bone regeneration in a large animal enables better examination of the spatial and temporal regulation of osteogenesis and the remodeling of the healing defect. RANK, RANKL and osteoprotegerin (OPG) are known to be important regulators of bone healing. The aim of this study was to create periodontal defects surgically in a large animal model and to examine bone regeneration and the expression of RANK, RANKL and OPG proteins in the defect site during bone regeneration. MATERIAL AND METHODS: Periodontal defects were made in the furcation of the second mandibular premolar of sheep. Wound healing was examined 6 h, and 1, 4 and 6 wk after surgery and in control tissue. The teeth and defect region were decalcified and paraffin embedded. Immunohistochemistry for RANK, RANKL and OPG was conducted. Osteoclasts were identified using TRAP staining. RESULTS: The defects were examined at different time points after surgery and by 6 wk the defect region had fully regenerated with new bone, albeit less dense than that in the unwounded controls. RANK-positive osteoclasts were present at the edge of the wound from week 1 and were found within the defect at week 6, corresponding to osteoclast activation and bone remodeling. RANKL staining increased from week 1 compared with unwounded tissue, and peaked at 4 and 6 wk, as the osteoblast numbers increased. At the same time, OPG immunostaining was high in controls and at week 6, suggesting that it may act to block RANKL and control the bone remodeling within the defect. CONCLUSION: Distinctive temporal and spatial expression patterns for RANK, RANKL and OPG proteins were observed during healing of surgically created periodontal wounds in a sheep model. The research identifies possible therapeutic approaches to periodontal bone repair via modulation of these members of the tumor necrosis factor family.

Comparison of clinical and cone beam computed tomography measurements to diagnose furcation involvement.

AIM: This study aimed to determine the degree of discrepancy between clinical measurement of furcation involvement (FI) and cone beam computed tomography image analysis of multirooted teeth. METHODS: FI measurements obtained from clinical records were compared to CBCT images of the same teeth to determine the degree of discrepancy between CBCT FI grading and clinical FI grading. RESULTS: Of the hundred and fifty-four sites analysed, 22% of FI measurements from probing and CBCT were in agreement. Fifty-eight percent of clinical FI recordings were overestimated, and 20% were underestimated when compared to CBCT analysis. CONCLUSION: Clinical recording of FI is both over and underestimated compared to CBCT analysis. This was highest for probing recording grade I furcation involvement where it was highly overestimated. The occurrence of over and under estimation of FI will affect the assignment of prognosis to multirooted teeth, which can influence treatment planning for periodontal therapy and may result in inappropriate treatment.

Extracellular matrix expression and periodontal wound-healing dynamics following guided tissue regeneration therapy in canine furcation defects.

AIM: Temporal and spatial expression pattern of extracellular matrix (ECM) components in furcation defects following guided tissue regeneration (GTR) compared with open-flap debridement (OFD). MATERIAL AND METHODS: In 21 dogs, mandibular second and fourth pre-molars were treated with one non-resorbable and three different resorbable membranes. Third pre-molars were treated by OFD. After 2, 4, 8 weeks and 3, 6, and 12 months, tissues were analysed by immunohistochemistry for collagen I (Col-I) and III (Col-III), fibronectin (FN), bone sialoprotein (BSP), and osteopontin (OPN). RESULTS: At 2 weeks, the defect was mainly occupied by FN+ granulation tissue (GT), which was sequentially replaced by new connective tissue expressing FN, Col-I, and increasingly Col-III. Following superficial resorptions by OPN+ osteoclasts and odontoclasts, cementum and bone formation ensued with strong expression of BSP and OPN along bone and tooth surfaces. Deposition of Col-I, FN, BSP and OPN+ cementoid and osteoid became evident after 4 weeks. Extrinsic fibres of cementum and bone stained intensely for Col-III. The newly formed periodontal ligament expressed FN, Col-I, and Col-III, but no BSP or OPN. CONCLUSIONS: The spatial ECM expression was similar for OFD and the different GTR methods, although the timing and quantity of ECM expression were influenced by wound stabilization and inflammatory reactions.

Glycosaminoglycans in gingival crevicular fluid of patients with periodontal class II furcation involvement before and after guided tissue regeneration. A pilot study.

BACKGROUND: The levels of glycosaminoglycans in gingival crevicular fluid (GCF) are good indicators of underlying tissue turnover. We hypothesize that connective tissue elements in GCF may be used as indicators of tissue maturation underneath barrier membranes. Therefore, we investigated the levels of sulfated glycosaminoglycans in GCF at sites before and after guided tissue regeneration (GTR). METHODS: Six patients were selected on the basis of having at least one Class II buccal furcation involvement on a molar tooth. Each molar furcation was treated with the standard GTR surgical protocol using a non-resorbable expanded polytetrafluoroethylene membrane. Gingival crevicular fluid samples were taken at baseline (immediately prior to insertion of the membrane) and at 1, 2, 3, 4, 5, and 6 weeks (immediately prior to removal of the membrane). Glycosaminoglycan levels were determined using an Alcian blue dye detection system. RESULTS: The mean levels of chondroitin sulfate and total sulfated glycosaminoglycans in GCF significantly decreased during the first 4 weeks after GTR surgery. By week 5, the levels began to rise, and by week 6 the levels had returned to baseline levels. CONCLUSIONS: Sulfated glycosaminoglycans can be monitored in GCF at healing GTR sites. It is proposed that this is a useful means of monitoring the status of the regenerating tissues. However, further longitudinal studies are required to assess if the sulfated glycosaminoglycans can be used as indicators of tissue maturation under guided tissue membranes used to treat periodontal defects.

Immunohistochemical expression of extracellular matrix components of normal and healing periodontal tissues in the beagle dog.

Periodontal regeneration requires formation of periodontal tissues lost due to periodontal disease. To better understand the formation of new periodontal tissues during periodontal repair and regeneration, immunohistochemical expression of extracellular matrix components of normal as well as healing periodontal tissues was evaluated and compared using the avidin-biotin complex immunohistochemical technique. For this purpose, horizontal furcation defects were created around mandibular P2 and P4 of 6 dogs after extraction of P1 and P3. The root surfaces were conditioned with citric acid and expanded polytetrafluoroethylene (ePTFE) membranes were placed and retained 0.5 mm above the cemento-enamel junction. The mucoperiosteal flaps were sutured in a coronal position. Two animals were sacrificed at 2, 4, and 8 weeks, and mesio-distal tissue slices containing normal or healing periodontal tissues were demineralized, dehydrated, and embedded in paraffin. Immunohistochemical localization of type I collagen (CI), fibronectin (FN), secreted protein, acidic and rich in cysteine (SPARC), vitronectin (VN), and bone sialoprotein (BSP) was performed on 6 microns thick sections. Morphological results demonstrated that at 2 weeks after defect creation, lesions were filled primarily with granulation tissue which was gradually replaced by newly-formed fibrous connective tissue, periodontal ligament (PDL), cementum, and bone between 4 and 8 weeks. The results of immunohistochemical study revealed that at 2 weeks the granulation tissue, especially in the intercellular spaces of inflammatory cells, was intensively stained for FN and VN. At 4 and 8 weeks, staining for CI, FN, and VN was found in fibrous connective tissue, the newly-formed PDL, cementum, and osteoid. Further the attachment zone of the PDL collagen fibers to cementum showed intense staining for FN. Immunostaining for SPARC was positive in the new PDL, cementum, and bone, while staining for BSP was restricted to the new cementum and bone. Interestingly, the PDL, especially in areas adjacent to active bone formation, demonstrated intense staining for BSP. However, fibrous connective tissue and PDL proper were unstained for BSP. These results indicate that FN and VN are involved in the early stages of periodontal repair, and periodontal regeneration is achieved through formation of periodontal tissues that are composed of different matrix components specific to different types of periodontal tissues.