Regenerative benefits of using growth factors in treatment of periodontal defects: A systematic review and meta-analysis with Trial Sequential Analysis on preclinical studies.

The ultimate goal in periodontal treatments is to achieve a functional and anatomical regeneration of the lost tissues. Numerous studies have in some way illustrated the beneficial effects of biologic modifiers in this process, yet they are subject to a rather large degree of diversity in their results. Thanks to the promising outcomes of bioengineering techniques in the field of periodontal regeneration, this systematic review aims to evaluate the effect of various biologic modifiers used in periodontal defects of animal models. Electronic databases (Medline, Scopus, Embase, Web of Science, and Google Scholar) were searched (March 2010-December 2020) for every study that used biomolecules for regeneration of periodontal osseous defects in animal models. Regenerated bone height or area, new cementum, new connective tissues, new regenerated periodontal ligament and the dimensions of epithelial attachment (either in mm/mm2 or percentage) were the investigated outcomes. The risk of bias of the included studies was assessed using the SYRCLE tool. In closing, there was a meta-analysis carried out on the outcomes of interest. Trial Sequential Analysis was also carried out to figure out the power of meta-analytic outcomes. From 1995 studies which were found in the initial search, 34 studies were included in this review, and 20 of them were selected for the meta-analysis. The eligible studies were categorized according to the morphology of the experimental periodontal defects as one-, two-, and three-wall intrabony defects; furcation defects, and recession-type defects. The most studied biomolecules were rhFGF-2, rhGDF-5, platelet-derived growth factor, bone morphogenetic protein-2, and enamel matrix derivative (EMD). Based on the meta-analysis findings, combined application of biomolecules with regenerative treatments could improve new bone and cementum formation near 1 mm when compared to the control groups in one, two and three-wall intrabony defect models (p < 0.001). In furcation grade II defect, the addition of biomolecules was observed to enhance bone area gain and cementum height regeneration up to almost 2 mm (p < 0.001). Trial Sequential Analysis results confirmed the significant effect in the aforementioned meta-analyses. In cases of the buccal recession model, the application of rhFGF-2 and rhGDF-5 decreased the dimension of epithelial attachments besides regenerative advantages on bone and cementum formation, but EMD deposition exerted no inhibitory effect on epithelial down-growth. Application of biologic modifiers especially FGF-2 and GDF-5, could positively improve the regeneration of periodontal tissues, particularly cementum and bone in animal models. Trial Sequential Analysis confirmed the results but the power of the evidences was high just in some subgroup meta-analyses, like bone and cementum regeneration in furcation grade II model and cementum regeneration in one-wall intrabony defects. The outcomes of this study can potentially endow clinicians with guidelines for the appropriate application of growth factors in periodontal regenerative therapies.

Survival and complication analyses of avulsed and replanted permanent teeth.

This retrospective clinical study investigated the survival probability of avulsed and replanted permanent teeth in relation to functional healing, replacement and inflammatory resorption. The explorative data analysis included data from 36 patients and 49 replanted permanent teeth with a minimum observation time of 60 days; the patients were generally treated according to the current guidelines of the International Association of Dental Traumatology at the university hospital in Munich, Germany, between 2004 and 2017. The mean observation period was 3.5 years. Functional healing was observed in 26.5% (N = 13/49) of the included avulsion cases. In comparison, replacement resorption affected 51.0% (N = 25/49) of the replanted teeth, of which 24.0% (N = 6/25) were lost over the course of years (mean, 6.1 years). In contrast, inflammatory resorption resulted in the early loss of all replanted teeth (mean, 1.7 years) and affected 22.5% (N = 11/49) of all the monitored teeth. Therefore, it can be concluded that tooth avulsion remains a severe dental injury with an unpredictable prognosis. This topic demands further fundamental research aiming to maintain and/or regenerate the periodontal ligament after tooth avulsion, particularly in association with non-physiological tooth rescue.

The Effects of Continual Intermittent Parathyroid Hormone Treatment on Human Periodontal Ligament Fibroblasts in an In Vitro Wound Repopulation Model.

INTRODUCTION: Periodontal ligament fibroblasts (PDLFs) play a vital role in periodontal regeneration. Parathyroid hormone (PTH) is important in catabolic regulation on osteoclasts; it also has anabolic effects on hard tissue formation. Using an in vitro wound repopulation model, this study investigated the effect of continual intermittent administration of PTH on PDLFs wound repopulation. Methods and Materials: PDLFs were grown in 12-well plates and divided into 0 (control), 5, 10, 20, 40, and 80 nM of PTH treatments. A 3-mm wound was created on confluent and synchronized cells. Six PTH treatments were initiated using serum-free medium with supplements. Cell repopulation was measured at four time points: 5, 10, 15, and 20 days. RESULTS: A 5% increase wound repopulation showed an enhancement on day 10 for all treatment groups as compared to control groups. On days 15 and 20, treatment groups showed a decrease in proliferation and migration compared to controls with significant decreases at concentrations of 40 and 80 nM. CONCLUSION: Continual intermittent treatment with PTH has the potential to enhance proliferation and migration of PDLFs for wound repopulation at early time points. A dose-dependent correlation was seen with a positive trend on day 10 while a significant decrease on day 20.

In silico study of cuspid' periodontal ligament damage under parafunctional and traumatic conditions of whole-mouth occlusions. A patient-specific evaluation.

BACKGROUND AND OBJECTIVE: Although traumatic loading has been associated with periodontal ligament (PDL) damage and therefore with several oral disorders, the damage phenomena and the traumatic loads involved are still unclear. The complex composition and extremely thin size of the PDL make experimentation difficult, requiring computational studies that consider the macroscopic loading conditions, the microscopic composition and fine detailed geometry of the tissue. In this study, a new methodology to analyse the damage phenomena in the collagen network and the extracellular matrix of the PDL caused by parafunctional and traumatic occlusal forces was proposed. METHODS: The entire human mandible and a portion thereof containing a full cuspid tooth were separately modelled using finite element analysis based on computed tomography and micro-computed tomography images, respectively. The first model was experimentally validated by occlusion analysis and subjected to the muscle loads produced during hard and soft chewing, traumatic cuspid occlusion, grinding, clenching, and simultaneous grinding and clenching. The occlusal forces computed by the first model were subsequently applied to the single tooth model to evaluate damage to the collagen network and the extracellular matrix of the PDL. RESULTS: Early occlusal contact on the left cuspid tooth guided the mandible to the more occluded side (16.5% greater in the right side) and absorbed most of the lateral load. The intrusive occlusal loads on the posterior teeth were 0.77-13.3% greater than those on the cuspid. According to our findings, damage to the collagen network and the extracellular matrix of the PDL could occur in traumatic and grinding conditions, mainly due to fibre overstretching (>60%) and interstitial fluid overpressure (>4.7 kPa), respectively. CONCLUSIONS: Our findings provide important biomechanical insights into the determination of damage mechanisms which are caused by mechanical loading and the key role of the porous-fibrous behaviour of the PDL in parafunctional and traumatic loading scenarios. Besides, the 3D loading conditions computed from occlusal contacts will help future studies in the design of new orthodontics appliances and encourage the application of computing methods in medical practice.

Identification of Aberrantly Expressed lncRNAs Involved in Orthodontic Force Using a Subpathway Strategy.

BACKGROUND: The aim of the study was to identify key long noncoding RNAs (lncRNA) and related subpathways in the periodontal ligament tissue following orthodontic force. METHODS: We adopt a novelty subpathway strategy to identify lncRNAs competitively regulated functions and the key competitive lncRNAs in periodontal ligament disorders after undergoing orthodontic force. To begin with, patients with orthodontics in our hospital were enrolled in our research. The relationship of lncRNA-mRNA was established through shared predicted miRNA by using the hypergeometric test, Jaccard coefficient standardization, and the Pearson coefficient to determine the valid interaction relationship. After embedding screened lncRNA interactions to pathways, the significant subpathways were recognized by lenient distance and Wallenius approximation methods to calculate the false discovery rate value of each subpathway. RESULTS: The lncRNA-mRNA intersections including 263 lncRNAs, 1,599 mRNAs, and 3,762 interacting pairs were obtained. The enriched mRNAs were further enriched into various candidate pathways such as the PI3K-Akt signaling pathway. Several subpathways were screened, including the PI3K-Akt signaling pathway, 04510_1 focal adhesion, and p53 signaling pathway, respectively. The network of pathway-lncRNA-mRNA was constructed. Several key lncRNAs including DNAJC3-AS1, WDFY3-AS2, LINC00482, and DLEU2 were screened. CONCLUSIONS: DNAJC3-AS1, WDFY3-AS2, LINC00482, and DLEU2 as aberrantly expressed lncRNAs involved in orthodontic force might play crucial roles in periodontal ligament disease pathogenesis.

Effect of variable periodontal ligament thickness and its non-linear material properties on the location of a tooth's centre of resistance.

In orthodontics, the 3D translational and rotational movement of a tooth is determined by the force-moment system applied and the location of the tooth's centre of resistance (CR). Because of the practical constraints of in-vivo experiments, the finite element (FE) method is commonly used to determine the CR. The objective of this study was to investigate the geometric model details required for accurate CR determination, and the effect of material non-linearity of the periodontal ligament (PDL). A FE model of a human lower canine derived from a high-resolution µCT scan (voxel size: 50 µm) was investigated by applying four different modelling approaches to the PDL. These comprised linear and non-linear material models, each with uniform and realistic PDL thickness. The CR locations determined for the four model configurations were in the range 37.2-45.3% (alveolar margin: 0%; root apex: 100%). We observed that a non-linear material model introduces load-dependent results that are dominated by the PDL regions under tension. Load variation within the range used in clinical orthodontic practice resulted in CR variations below 0.3%. Furthermore, the individualized realistic PDL geometry shifted the CR towards the alveolar margin by 2.3% and 2.8% on average for the linear and non-linear material models, respectively. We concluded that for conventional clinical therapy and the generation of representative reference data, the least sophisticated modelling approach with linear material behaviour and uniform PDL thickness appears sufficiently accurate. Research applications that require more precise treatment monitoring and planning may, however, benefit from the more accurate results obtained from the non-linear constitutive law and individualized realistic PDL geometry.

In vivo effects of different orthodontic loading on root resorption and correlation with mechanobiological stimulus in periodontal ligament.

Orthodontic root resorption is a common side effect of orthodontic therapy. It has been shown that high hydrostatic pressure in the periodontal ligament (PDL) generated by orthodontic forces will trigger recruitment of odontoclasts, leaving resorption craters on root surfaces. The patterns of resorption craters are the traces of odontoclast activity. This study aimed to investigate resorptive patterns by: (i) quantifying spatial root resorption under two different levels of in vivo orthodontic loadings using microCT imaging techniques and (ii) correlating the spatial distribution pattern of resorption craters with the induced mechanobiological stimulus field in PDL through nonlinear finite-element analysis (FEA) in silico. Results indicated that the heavy force led to a larger total resorption volume than the light force, mainly by presenting greater individual crater volumes ( p < 0.001) than increasing crater numbers, suggesting that increased mechano-stimulus predominantly boosted cellular resorption activity rather than recruiting more odontoclasts. Furthermore, buccal-cervical and lingual-apical regions in both groups were found to have significantly larger resorption volumes than other regions ( p < 0.005). These clinical observations are complemented by the FEA results, suggesting that root resorption was more likely to occur when the volume average compressive hydrostatic pressure exceeded the capillary blood pressure (4.7 kPa).

Can interfaces at bracket-wire and between teeth in multi-teeth finite element model be simplified?

OBJECTIVE: Finite element (FE) method's correctness depends heavily on modeling method. This study aimed at determining whether the interfaces at bracket-wire and between teeth can be simplified for multi-teeth FE analysis. METHOD: A three-dimensional FE model of a mandible was created from cone-beam computed tomography scan. Due to symmetry, only a half of the mandible was modeled, which consisted of five teeth (first premolar extraction and only first molar), brackets and archwire, periodontal ligament (PDL), cortical bone, and cancellous bone. All the bone, teeth, and PDL were considered to be isotropic and linear. The En-masse retraction case was simulated. A detailed model, which has contact elements between the bracket and archwire and between teeth, was developed to allow relative motion at the interfaces. A model with simplified interfacial conditions, which does not allow the relative motion, was also created. The stresses and displacements as results of the treatment on these two models were calculated and compared. RESULTS: The stress and displacement distributions from the detailed model were more close to reality based on the expected displacement pattern of the clinical case than from the simplified model. The maximum stresses from the two methods were also different. The highest stress from the detailed model is twice as high as from the simplified model. CONCLUSIONS: The detailed model provides much more reasonable results than the simplified model. Thus, the simplified model should not be used to replace the detailed model if the stress magnitude and highest stress location are the expected outcomes.

Effect of loaded orthodontic miniscrew implant on compressive stresses in adjacent periodontal ligament.

OBJECTIVES: To describe the relationship between the proximity of miniscrew implants (MSIs) to the periodontal ligament (PDL) and stress in the PDL under different load magnitudes and different bone properties. MATERIALS AND METHODS: Sixteen subject-specific finite element models of the region of the maxillary first molar and second premolar were developed using computed tomography images of four patients. For each patient, an MSI surface model derived from micro-computed tomography was placed at four different distances from the premolar PDL. Finite element analysis was conducted with mesial load on the MSI, increasing from 1 N to 4 N. Peak absolute compression stress (CS) was calculated at each 1 N step. Stepwise multiple regression modeling was conducted to explain compressive stress by proximity, load magnitude, and bone properties. RESULTS: The multiple regression model explained 83.47% of the variation of CS and included all three factors: proximity, load magnitude, and bone properties. The model expected significant interaction between the bone properties and load magnitude, implying that strong bone properties could be associated with significant increases in CS at small increases in load. CONCLUSIONS: To ensure the safety of adjacent roots, MSIs should be placed at least 1 mm from the roots. Assessment of alveolar bone properties is recommended when the use of MSI is intended, as some patients may present with strong bone properties and thereby a high risk of MSI-induced root resorption.

Non-invasive evaluation of periodontal ligament stiffness during orthodontic tooth movement.

OBJECTIVES: To evaluate the longitudinal changes in periodontal ligament (PDL) stiffness during orthodontic tooth movement using the Advanced System for Implant Stability Testing (ASIST). MATERIALS AND METHODS: ASIST measurements of maxillary canines that were actively retracted into an extraction space were collected approximately once per month for 12 adolescent female patients. The ASIST Stability Coefficient (ASC) values, which are directly related to PDL stiffness, were determined for each visit to examine longitudinal changes for individual canines as they were exposed to different forces (approximately 80 and 150 g) during retraction. RESULTS: The pattern of longitudinal changes in ASC was similar for both canines (regardless of the two force levels applied) in individual patients and across patients. All patients showed some decrease in ASC, with an average maximum reduction in stiffness of 73.4 ± 7.7%. Some recovery was observed for most patients; however, none of the patients had the PDL stiffness return to the pre-treatment value at the final measurement appointment which was some time close after space closure was completed. On average, the ASC value at the final measured visit was 48.1 ± 12.2% of the initial value. No measurements are available after removal of orthodontic appliances and during retention. CONCLUSIONS: The ASIST was able to detect changes in PDL stiffness during orthodontic treatment, providing some insight into the mechanical changes that occur at the tooth root interface.

Characterization and evaluation of graphene oxide scaffold for periodontal wound healing of class II furcation defects in dog.

INTRODUCTION: The 3-dimensional scaffold plays a key role in volume and quality of repair tissue in periodontal tissue engineering therapy. We fabricated a novel 3D collagen scaffold containing carbon-based 2-dimensional layered material, named graphene oxide (GO). The aim of this study was to characterize and assess GO scaffold for periodontal tissue healing of class II furcation defects in dog. MATERIALS AND METHODS: GO scaffolds were prepared by coating the surface of a 3D collagen sponge scaffold with GO dispersion. Scaffolds were characterized using cytotoxicity and tissue reactivity tests. In addition, GO scaffold was implanted into dog class II furcation defects and periodontal healing was investigated at 4 weeks postsurgery. RESULTS: GO scaffold exhibited low cytotoxicity and enhanced cellular ingrowth behavior and rat bone forming ability. In addition, GO scaffold stimulated healing of dog class II furcation defects. Periodontal attachment formation, including alveolar bone, periodontal ligament-like tissue, and cementum-like tissue, was significantly increased by GO scaffold implantation, compared with untreated scaffold. CONCLUSION: The results suggest that GO scaffold is biocompatible and possesses excellent bone and periodontal tissue formation ability. Therefore, GO scaffold would be beneficial for periodontal tissue engineering therapy.

Reduced Orthodontic Tooth Movement in Enpp1 Mutant Mice with Hypercementosis.

Previous studies revealed that cementum formation is tightly regulated by inorganic pyrophosphate (PPi), a mineralization inhibitor. Local PPi concentrations are determined by regulators, including ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which increases PPi concentrations by adenosine triphosphate hydrolysis. Orthodontic forces stimulate alveolar bone remodelling, leading to orthodontic tooth movement (OTM). To better understand how disturbed mineral metabolism and the resulting altered periodontal structures affect OTM, we employed Enpp1 mutant mice that feature reduced PPi and increased cervical cementum in a model of OTM induced by a stretched closed-coil spring ligated between the maxillary left first molar and maxillary incisors. We analyzed tooth movement, osteoclast/odontoclast response, and tooth root resorption by micro-computed tomography, histology, histomorphometry, and immunohistochemistry. Preoperatively, we noted an altered periodontium in Enpp1 mutant mice, with significantly increased periodontal ligament (PDL) volume and thickness, as well as increased PDL-bone/tooth root surface area, compared to wild-type (WT) controls. After 11 d of orthodontic treatment, Enpp1 mutant mice displayed 38% reduced tooth movement versus WT mice. Molar roots in Enpp1 mutant mice exhibited less change in PDL width in compression and tension zones compared to WT mice. Root resorption was noted in both groups with no difference in average depths, but resorption lacunae in Enpp1 mutant mice were almost entirely limited to cementum, with 150% increased cementum resorption and 92% decreased dentin resorption. Osteoclast/odontoclast cells were reduced by 64% in Enpp1 mutant mice, with a predominance of tartrate-resistant acid phosphatase (TRAP)-positive cells on root surfaces, compared to WT mice. Increased numbers of TRAP-positive cells on root surfaces were associated with robust immunolocalization of osteopontin (OPN) and receptor-activator of NF-κB ligand (RANKL). Collectively, reduced response to orthodontic forces, decreased tooth movement, and altered osteoclast/odontoclast distribution suggests Enpp1 loss of function has direct effects on clastic function/recruitment and/or indirect effects on periodontal remodeling via altered periodontal structure or tissue mineralization.

The biological basis of treating jaw discrepancies: An interplay of mechanical forces and skeletal configuration.

Jaw discrepancies and malrelations affect a large proportion of the general population and their treatment is of utmost significance for individuals' health and quality of life. The aim of their therapy is the modification of aberrant jaw development mainly by targeting the growth potential of the mandibular condyle through its cartilage, and the architectural shape of alveolar bone through a suture type of structure, the periodontal ligament. This targeted treatment is achieved via external mechanical force application by using a wide variety of intraoral and extraoral appliances. Condylar cartilage and sutures exhibit a remarkable plasticity due to the mechano-responsiveness of the chondrocytes and the multipotent mesenchymal cells of the sutures. The tissues respond biologically and adapt to mechanical force application by a variety of signaling pathways and a final interplay between the proliferative activity and the differentiation status of the cells involved. These targeted therapeutic functional alterations within temporo-mandibular joint ultimately result in the enhancement or restriction of mandibular growth, while within the periodontal ligament lead to bone remodeling and change of its architectural structure. Depending on the form of the malrelation presented, the above treatment approaches, in conjunction or separately, lead to the total correction of jaw discrepancies and the achievement of facial harmony and function. Overall, the treatment of craniofacial and jaw anomalies can be seen as an interplay of mechanical forces and adaptations occurring within temporo-mandibular joint and alveolar bone. The aim of the present review is to present up-to-date knowledge on the mechano-biology behind jaw growth modification and alveolar bone remodeling. Furthermore, future molecular targeted therapeutic strategies are discussed aiming at the improvement of mechanically-driven chondrogenesis and osteogenesis.

A cross-sectional, clinical study to evaluate mobility of teeth during pregnancy using periotest.

BACKGROUND AND OBJECTIVE: Over a century, an increased prevalence of gingival diseases associated with increasing plasma sex steroid hormone levels has been reported. These situations present unique challenges to the oral health-care professional. It is believed that hormonal fluctuations such as those associated with pregnancy, menstruation, and use of hormonal contraceptives lead to an increase in tooth mobility. However, this effect of female sex hormones on periodontal ligament and tooth-supporting alveolar bone has rarely been investigated. Hence, this study was conducted to understand the effect of hormonal changes during pregnancy on tooth mobility. MATERIALS AND METHODS: Mobility of index teeth 16, 13, 21, 23, 24, 36, 33, 41, 43, and 44 was measured with periotest for fifty pregnant females at first trimester (12th week), second trimester (24th week), and third trimester (35th week). Simplified oral hygiene index, plaque index, Gingival index (GI), and probing depth were also evaluated during the three trimesters of pregnancy for each subject participating in the study. STATISTICAL ANALYSIS: The results of the study were subjected to statistical analysis. Data analysis was done by applying Z-test for comparing difference between two sample means. RESULTS: A small but statistically significant influence on the periotest value was seen during the three trimesters of pregnancy. GI scores significantly increased throughout pregnancy despite no significant change in plaque levels. CONCLUSION: Pregnancy had a significant influence on tooth mobility. Highest value of tooth mobility was seen in the last month of pregnancy. The maximum severity of gingivitis was also seen during the third trimester of pregnancy.

Effect of Experimental Periodontal Ligament Pain on Gingival Somatosensory Sensitivity.

AIMS: To use a randomized, blinded, crossover design to evaluate the possible heterotopic effects of experimental periodontal ligament pain on adjacent gingival somatosensory sensitivity. METHODS: A total of 12 healthy volunteers (8 female, 4 male; mean age ± standard error in means (SEM): 28 ± 1 years) participated in two randomized experimental quantitative sensory testing (QST) sessions, one in which capsaicin (experimental) was injected into the periodontal ligament and one in which isotonic saline (control) was injected. A total of 13 standardized QST measures were obtained on the buccal attached gingiva of a maxillary central incisor before, immediately after, and 30 minutes after injection of 30 µL of 5% capsaicin or isotonic saline into the periodontal ligament of the same incisor. The injection-evoked pain was evaluated on a 0-10 numeric rating scale (NRS). QST data were analyzed with two-way repeated measurement analysis of variance. RESULTS: Capsaicin injected into the periodontal ligament evoked moderate levels of pain (mean peak NRS ± SEM: capsaicin: 5.5 ± .7; control: 0.6 ± 0.5 [P < .001]). Capsaicin injected into the periodontal ligament significantly modulated gingival somatosensory sensitivity: increased sensitivity to warmth and painful heat stimuli occurred immediately and 30 minutes after the injection (P < .025), whereas decreased sensitivity to both tactile and painful mechanical stimuli (P < .011) occurred immediately after the injection and to painful mechanical stimuli only after 30 minutes (P = .016). No somatosensory changes were detected following the injection of isotonic saline (P > .050). CONCLUSION: Capsaicin injected into the periodontal ligament caused gain of heterotopic somatosensory sensitivity toward warmth and painful heat stimuli as well as reduction in mechanical sensitivity of the gingiva adjacent to the injected tooth. These findings may have implications for interpretation of somatosensory functions in patients with chronic intraoral pain, where gingival somatosensory profiles similar to those detected after capsaicin injection in the present study may be interpreted as signs of nerve damage.

Torque differences according to tooth morphology and bracket placement: a finite element study.

INTRODUCTION: Torque of the maxillary incisors is essential in esthetics and proper occlusion, while torque expression is influenced by many factors. The aim of this finite element study was to assess the relative effect of tooth morphology, bracket prescription, and bracket positioning on tooth displacement and developed stresses/strains after torque application. METHODS: A three-dimensional upper right central incisor with its periodontal ligament (PDL) and alveolus was modelled. The tooth varied in the crown-root angle (CRA) between 156°, 170°, and 184°. An 0.018-inch slot discovery® (Dentaurum, Ispringen, Germany) bracket with a rectangular 0.018 × 0.025-inch ß-titanium wire was modelled. Bracket torque prescription varied between 0°, 12°, and 22°, with bracket placement at the centre of the middle, gingival or incisal third of the crown. A total of 27 models were generated and a buccal root torque of 30° was applied. Afterwards, crown and apex displacement, strains in the PDL, and stresses in the bracket were calculated and analysed statistically. RESULTS: The palatal crown displacement was significantly affected by bracket positioning (up to 94 per cent), while the buccal apex displacement was significantly affected by bracket prescription (up to 42 per cent) and bracket positioning (up to 23 per cent). Strains in the PDL were affected mainly by CRA (up to 54 per cent), followed by bracket positioning (up to 45 per cent). Finally, bracket prescription considerably affected the stresses in the bracket (up to 144 per cent). LIMITATIONS: These in silico results need to be validated in vivo before they can be clinically extrapolated. CONCLUSION: Tooth anatomy and the characteristics of the orthodontic appliance should be considered during torque application.

The Root Membrane Technique: Human Histologic Evidence after Five Years of Function.

BACKGROUND: The "root membrane" (RM) is a technique that has become popular among implantologists for placement of immediate implants in the anterior maxilla. PURPOSE: To present histologic evidence of an immediate implant placed in the human anterior maxilla, according to the RM technique, and retrieved after five years. METHODS: A fixture, along with the surrounding tissues, was retrieved from the anterior maxilla of a 68-year-old patient, who had been treated five years earlier with immediate implant placement and RM technique. The specimen was processed for histologic/histomorphometric evaluation. RESULTS: The buccal bone plate was maintained without any resorption; a healthy periodontal ligament was evidenced. The implant showed osseointegration, with a high percentage of bone-to-implant contact (BIC = 76.2%). With regard to the space between the RM and the implant, the apical and medial thirds were filled with compact, mature bone; the coronal third was colonized by noninfiltrated connective tissue. CONCLUSIONS: The RM technique appears to be effective in preventing bone resorption of the buccal bone plate of the human anterior maxilla, five years after the placement of an immediate implant.

RUNX2 mutation impairs bone remodelling of dental follicle cells and periodontal ligament cells in patients with cleidocranial dysplasia.

RUNX2 is an important osteo-specific factor with crucial functions in bone formation and remodelling as well as resorption of teeth. Heterozygous mutation of RUNX2 can cause cleidocranial dysplasia (CCD), a systemic disease with extensive skeletal dysplasia and abnormality of tooth growth. In our study, dental follicle cells (DFCs) and periodontal ligament cells (PDLCs) were isolated, cultured and identified from one patient with CCD and compared with normal controls. This CCD patient was confirmed to have a heterozygous frameshift mutation of RUNX2 (c.514delT, p.Ser172fs) in the previous study. The results showed that the proliferation abilities of DFCs and PDLCs were both disturbed by the RUNX2 mutation in the CCD patient compared with the normal control. A co-culture system of these cells with human peripheral blood mononuclear cells was then used to investigate the effect of RUNX2 mutation on osteoclastogenesis. We found that the RUNX2 mutation in CCD reduced the expression of osteoclast-related genes, such as RUNX2, CTR, CTSK, RANKL and OPG The ability of osteoclastogenesis in DFCs and PDLCs detected by tartrate-resistant acid phosphatase staining in the co-culture system was also reduced by the RUNX2 mutation compared with the normal control. These outcomes indicate that the RUNX2 mutation disturbs the modulatory effects of DFCs and PDLCs on the differentiation of osteoclasts and osteoblasts, thereby interfering with bone remodelling. These effects may contribute in part to the pathological manifestations of retention of primary teeth and delayed eruption of permanent teeth in patients with CCD.

Deleterious effect of chronic continuous hypoxia on oral health.

OBJECTIVE: To evaluate the effect of chronic continuous hypoxia (CCH) in alveolar bone and its correlation with the inflammatory markers which play a key role in the development of periodontitis. MATERIAL AND METHODS: Wistar rats were exposed to CCH (600mbar, 3 months). Macroscopic and histological analyses of alveolar bone were performed, together with measurement of oxidative stress and inflammatory parameters in gums and submandibular glands (SMG). RESULTS: HCC induced cortical alveolar bone loss, decreased interradicular bone volume and increased the periodontal ligament height compared to control rats (p<0.05). CCH enhanced iNOS activity in gums (from 2735,04±662,96 nmol/min/mg proteins to 4289,58±915,63 p<0.05) and in SMG (from 56,71±12,05 nmol/min/mg proteins to 90,15±21,78 p<0.05). PGE2 did not change in gums or in SMG by means of CCH, while TNFα decreased in gums (p<0.05). Regarding oxidative stress, thiobarbituric acid reactive species concentration in CCH animals was higher both in gums as in SMG, and catalase activity was decreased in SMG. CONCLUSION: Higher iNOS activity both in gums and SMG under CCH could be associated with the alveolar bone loss observed. The increase in oxidative stress occurring in SMG and gums, together with a lower antioxidant capacity might indicate a deleterious effect of HX in oral health.

Cryogenically salvaged teeth as a potential source for grafting dentoalveolar, periodontal or maxillofacial defects.

Bone grafting uses a wide range of materials derived mainly from exogenous sources. Autogenous teeth are often used fresh or fixed with alcohol for later use. Proposed here is a method of using cryogenically preserved autogenous extracted teeth, which could be macerated after thawing. This method avoids the possibility of tissue being denatured by alcohol and preserves intact all calcified structures for optimal bone grafting success.