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Introduction: This study aimed to compare the extent of buccal bone defects (dehiscences and fenestrations) and transversal tooth movement of mandibular lateral segments in patients after orthodontic treatment with and without piezocision in cone-beam computed tomography and digital dental models., Methods: The study sample of this study consisted of cone-beam computed tomography scans and digital dental models taken before (T0) and after (T1) orthodontic treatment of 36 patients with moderate mandibular anterior crowding. The experimental group consisted of 17 patients that had piezocision performed at the beginning of treatment with the goal of accelerating tooth movement, which was compared with 19 patients who did not receive piezocision. The measurement of bone defects, buccolingual inclination, and transversal distances of the tooth in the mandibular lateral segments (mandibular canines, premolars, and first molars) were evaluated at baseline and at the end of the orthodontic treatment., Results: Overall, an increase in dehiscences, buccal inclination, and arch width from T0 to T1 was observed in both groups, but no statistically significant difference was found between groups. A significant increase in fenestrations from T0 to T1 was observed only for the canines in the experimental group. No statistically significant association was found between the increase of dehiscences and the amount of buccolingual inclination or transversal width changes. However, the changes in transversal width were statistically significantly associated with the increase in buccal inclination at the canines, first and second premolars., Conclusions: No significant differences were found in buccal dehiscences and transversal tooth movement (buccolingual inclination and arch width) of mandibular lateral segments between patients after orthodontic treatment with and without piezocision. Dehiscences, buccal inclination, and arch width significantly increased from T0 to T1 in both groups., (Copyright © 2020. Published by Elsevier Inc.)

Background: Application of cone-beam computed tomography (CBCT) has grown exponentially across dentistry with a clear impact in implant dentistry. This review aims at providing the scientific context to understand if CBCT imaging should become the standard of care for patients requiring dental implants., Methods: A literature search for CBCT applications in implant dentistry was performed using the PubMed database that included studies published between January 1, 2000, and June 24, 2017., Results: Of 559 citations identified and manually screened, 161 were selected as suitable for the purpose of the review. The selected studies belonged to three distinct categories: 1) diagnosis and treatment outcome assessment, 2) implant treatment planning, and 3) anatomic characterization., Conclusions: The current available literature reflects an increased optimization of emerging CBCT imaging protocols and further highlights its diverse applications for dental implant therapy. This technology continues to be considered an advanced point-of-care imaging modality and should be used selectively as an adjunct to two-dimensional dental radiography. As with other ionizing radiation imaging modalities, CBCT imaging should be used only when the potential benefits to the patient outweigh the risks. Dental health care professionals should consider CBCT imaging only when they expect the diagnostic information yielded will lead to better patient care, enhanced patient safety, and ultimately facilitate a more predictable, optimal treatment outcome.

Background: The American Academy of Periodontology (AAP) recently embarked on a Best Evidence Consensus (BEC) model of scientific inquiry to address questions of clinical importance in periodontology for which there is insufficient evidence to arrive at a definitive conclusion. This review addresses oral indications for use of cone-beam computed tomography (CBCT)., Methods: To develop the BEC, the AAP convened a panel of experts with knowledge of CBCT and substantial experience in applying CBCT to a broad range of clinical scenarios that involve critical structures in the oral cavity. The panel examined a clinical scenario or treatment decision that would likely benefit from additional evidence and interpretation of evidence, performed a systematic review on the individual, debated the merits of published data and experiential information, developed a consensus report, and provided a clinical bottom line based on the best evidence available., Results: This BEC addressed the potential value and limitations of CBCT relative to specific applications in the management of patients requiring or being considered for the following clinical therapies: 1) placement of dental implants; 2) interdisciplinary dentofacial therapy involving orthodontic tooth movement in the management of malocclusion with associated risk on the supporting periodontal tissues (namely, dentoalveolar bone); and 3) management of periodontitis., Conclusion: For each specific question addressed, there is a critical mass of evidence, but insufficient evidence to support broad conclusions or definitive clinical practice guidelines.

Objective: Shared epitope (SE)-coding DRB1 alleles are associated with bone erosion in several diseases, including rheumatoid arthritis (RA) and periodontal disease (PD), but the underlying mechanism is unknown. We have recently identified the SE as an osteoclast-activating ligand. To better understand the biological effects of the SE in vivo, here we sought to determine whether it can facilitate spontaneous bone damage in naïve mice., Methods: 3-month old naïve transgenic mice that carry the human SE-coding allele DRB1*04:01 , or a SE-negative allele DRB1*04:02 were studied . Bone tissues were analysed by micro-CT, and the tooth-supporting tissues were studied by histology, immunohistochemistry and immunofluorescence. Serum biomarkers were determined by ELISA., Results: Transgenic mice expressing the SE-coding DRB1*04: 01 allele, but not mice carrying the SE-negative allele DRB1*04:02 , showed spontaneous PD associated with interleukin (IL)-17 overabundance and periostin disruption. Mandibular bone volumetric and mineralisation parameters were significantly lower in SE-positive mice, and alveolar bone resorption was significantly increased in these mice. SE-positive mice also had more slender tibiae, and their marrow, cortical and total areas were lower than those of SE-negative mice. Additionally, significantly increased serum IL-17, tumour necrosis factor-α and osteoprotegrin levels were found in SE-positive mice, while their receptor activator of nuclear factor κ-B ligand levels were significantly lower., Conclusions: A human SE-coding allele increases the propensity to spontaneous bone-destructive periodontal inflammation and skeletal bone damage in transgenic mice. These findings provide new insights into the previously documented but poorly understood association of the SE with accelerated bone erosion in RA and several other human diseases., Competing Interests: Conflicts of Interest: None declared.

Objectives: The aim of this study was to explore the development of soft tissue expanders, their different types and their potential applications prior to bone augmentation and implant placement., Material and Methods: A review of pertinent literature was performed using PubMed to comprehend the dynamics of soft tissue expanders and determine the current position of their pre-augmentation applications., Results: There is promising, albeit preliminary information regarding the benefits of pre-augmentation soft tissue expansion. Findings cannot be generalised due to relatively small sample size., Conclusions: Further clinical trials with larger sample sizes and long-term follow-up are needed before soft tissue expanders can be confidently applied in everyday clinical practice., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Tissue repair and regeneration is assisted by the efficient coordination of cell and extracellular matrix interactions mediated by matricellular molecules such as periostin. Given its high expression around the teeth, the periodontal organ represents an ideal system to capture the protein dynamics during wound healing., Methods: An observational prospective case-control study was designed to characterize periostin changes over time after periodontal surgery in tissue, oral fluids and serum by histological, protein and mRNA analyses., Results: Histological analysis showed lower periostin with a diffuse local distribution pattern in disease patients. Levels of periostin in gingival crevicular fluid (GCF) increased over time for both groups, more noticeably in the periodontitis subjects. A transient and subtle change in circulating periostin levels was also noticed. The mRNA periostin levels contrasted with the protein levels and may indicate the underlying post-transcriptional regulatory process during chronic inflammation. Levels of known periodontal disease biomarkers such as IL-β, IL1-α, TNF-α, MIP-1α and CRP served as tissue stability markers and complemented the clinical parameters recorded., Conclusion: The transient local increase in GCF periostin after eliminating the local etiology in periodontally affected sites suggests its importance in the maturation and stability of the connective tissue. The decreasing levels observed as the tissue healed highlight its spatial/temporal significance., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The regeneration of the original structure and function of bone-ligament interfaces remains a major challenge in biomedical research. A preclinical model that maintains physiologic mechanical loads and controls for other external factors, such as microbial influence, is of great value for testing novel regenerative materials, provided that studies are performed by highly trained researchers with proper regard for animal welfare. The tooth root fenestration preclinical model is an ideal tool for hard tissue evaluation by micro-computed tomography, histological techniques and RNA analyses. The procedure starts with an extraoral incision lateral to the mandible and reflection of the masseter muscle. Superficial lateral mandibular bone is removed with standardized dimensions to expose the roots of the teeth and to eliminate periodontal ligament and cementum to expose the tooth dentin. The testing material can subsequently be applied to the defect and the flap can be repositioned and secured back in place. At specific time points, samples are collected and processed according to the subsequent analyses to be performed, which can include descriptive histology, histomorphometry, immunostaining, 3D bone imaging, electron microscopy, gene expression analyses and safety assessments.

Background and Objective: Dental pulp repair is a common process triggered by microbial and mechanical challenges. Matricellular modulators, such as periostin, are key for extracellular matrix stability and tissue healing. In the scope of the dental pulp, periostin expression has been reported during development and active dentinogenesis. However, the specific dental pulp cell population capable of expressing periostin in response to known regulators has not been clearly defined. Among the different relevant cell populations (i.e., stem cells, fibroblasts and pre-odontoblasts) potentially responsible for periostin expression in the dental pulp, this study aimed to determine which is the primary responder to periostin regulators., Methods: Human dental pulp stem cells (DPSCs), human dental pulp fibroblasts (DPFs), and rat odontoblast-like cells (MDPC-23) were treated with different concentrations of TGF-β1 or different regimens of biomechanical stimulation to evaluate periostin expression by qRT-PCR, Western blot and ELISA. Statistical analyses were performed by Student's t-test and ANOVA with Fisher's LSD post hoc tests (p ≤ 0.05)., Results: DPSC and MDPC-23 showed a statistically significant increase in periostin mRNA expression after exposure to TGF-β1 for 48 h. TGF-β1 also up-regulated periostin protein levels in DPSC. However, periostin significantly down-regulated protein expression in DPF. Different regimens of biomechanical stimulation showed different patterns in protein and mRNA periostin expression., Conclusions: Expression of periostin was identified in each of the analysed dental pulp cell lines, which can be regulated by TGF-β1 and biomechanical stimulation. Overall, DPSCs are the most responsive cells to stimulation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Historically, periodontal regeneration has focused predominantly on bone substitutes and/or barrier membrane application to provide for defect fill and/or selected cell repopulation of the lesion. More recently, a number of technologies have evolved that can be viewed as emerging therapeutic approaches for periodontal regeneration, and these technologies were considered in the review paper and by the consensus group. The goal of this consensus report on emerging regenerative approaches for periodontal hard and soft tissue reconstruction was to develop a consensus document based on the accompanying review paper and on additional materials submitted before and at the consensus group session., Methods: The review paper was sent to all the consensus group participants in advance of the consensus conference. In addition and also before the conference, individual consensus group members submitted additional material for consideration by the group. At the conference, each consensus group participant introduced themselves and provided disclosure of any potential conflicts of interest. The review paper was briefly presented by two of the authors and discussed by the consensus group. A discussion of each of the following topics then occurred based on the content of the review: a general summary of the topic, implications for patient-reported outcomes, and suggested research priorities for the future. As each topic was discussed based on the review article, supplemental information was then added that the consensus group agreed on. Last, an updated reference list was created., Results: The application of protein and peptide therapy, cell-based therapy, genetic therapy, application of scaffolds, bone anabolics, and lasers were found to be emerging technologies for periodontal regeneration. Other approaches included the following: 1) therapies directed at the resolution of inflammation; 2) therapies that took into account the influence of the microbiome; 3) therapies involving the local regulation of phosphate and pyrophosphate metabolism; and 4) approaches directed at harnessing current therapies used for other purposes. The results indicate that, with most emerging technologies, the specific mechanisms of action are not well understood nor are the specific target cells identified. Patient-related outcomes were typically not addressed in the literature. Numerous recommendations can be made for future research priorities for both basic science and clinical application of emerging therapies. The need to emphasize the importance of regeneration of a functional periodontal organ system was noted. The predictability and efficacy of outcomes, as well as safety concerns and the cost-to-benefit ratio were also identified as key factors for emerging technologies., Conclusions: A number of technologies appear viable as emerging regenerative approaches for periodontal hard and soft tissue regeneration and are expanding the potential of reconstructing the entire periodontal organ system. The cost-to-benefit ratio and safety issues are important considerations for any new emerging therapies. Clinical Recommendation: At this time, there is insufficient evidence on emerging periodontal regenerative technologies to warrant definitive clinical recommendations.

Focused Clinical Question: Can emerging technologies for periodontal regeneration become clinical reality? Summary: Emerging technologies are presenting options to hopefully improve the outcomes of regeneration in challenging clinical scenarios. Cellular allografts represent a current technology in which cells and scaffolds are being delivered directly to the periodontal lesion. Recombinant human fibroblast growth factor 2 and teriparatide (parathyroid 1-34) have each been tested in controlled prospective human randomized clinical trials, and both have been shown to have potential for periodontal regeneration. These examples, as well as other emerging technologies, show promise for continued advancement in the field of periodontal regenerative therapy. Conclusions: At present, there are indications that emerging technologies can be used successfully for periodontal regeneration. Case reports and clinical trials are being conducted with a variety of emerging technologies. However, many are yet to be approved by a regulatory agency, or there is a lack of evidence-based literature to validate their expanded use., (© 2015 American Academy of Periodontology.)

More than 30 years have passed since the first successful application of regenerative therapy for treatment of periodontal diseases. Despite being feasible, periodontal regeneration still faces numerous challenges, and complete restoration of structure and function of the diseased periodontium is often considered an unpredictable task. This review highlights developing basic science and technologies for potential application to achieve reconstruction of the periodontium. A comprehensive search of the electronic bibliographic database PubMed was conducted to identify different emerging therapeutic approaches reported to influence either biologic pathways and/or tissues involved in periodontal regeneration. Each citation was assessed based on its abstract, and the full text of potentially eligible reports was retrieved. Based on the review of the full papers, their suitability for inclusion in this report was determined. In principle, only reports from scientifically well-designed studies that presented preclinical in vivo (animal studies) or clinical (human studies) evidence for successful periodontal regeneration were included. Hence, in vitro studies, namely those conducted in laboratories without any live animals, were excluded. In case of especially recent and relevant reviews with a narrow focus on specific regenerative approaches, they were identified as such, and thereby the option of referring to them to summarize the status of a specific approach, in addition to or instead of listing each separately, was preserved. Admittedly, the presence of subjectivity in the selection of studies to include in this overview cannot be excluded. However, it is believed that the contemporary approaches described in this review collectively represent the current efforts that have reported preclinical or clinical methods to successfully enhance regeneration of the periodontium. Today's challenges facing periodontal regenerative therapy continue to stimulate important research and clinical development, which, in turn, shapes the current concept of periodontal tissue engineering. Emerging technologies--such as stem cell therapy, bone anabolic agents, genetic approaches, and nanomaterials--also offer unique opportunities to enhance the predictability of current regenerative surgical approaches and inspire development of novel treatment strategies.

Physiologic bioengineering of the oral, dental, and craniofacial complex requires optimized geometric organizations of fibrous connective tissues. A computer-designed, fiber-guiding scaffold has been developed to promote tooth-supporting periodontal tissue regeneration and functional restoration despite limited printing resolution for the manufacture of submicron-scaled features. Here, we demonstrate the use of directional freeze-casting techniques to control pore directional angulations and create mimicked topographies to alveolar crest, horizontal, oblique, and apical fibers of natural periodontal ligaments. For the differing anatomic positions, the gelatin displayed varying patterns of ice growth, determined via internal pore architectures. Regardless of the freezing coordinates, the longitudinal pore arrangements resulted in submicron-scaled diameters (~50 µm), along with corresponding high biomaterial porosity (~90%). Furthermore, the horizontal + coronal ([Formula: see text]) freezing orientation facilitated the creation of similar structures to major fibers in the periodontal ligament interface. This periodontal tissue-mimicking microenvironment is a potential tissue platform for the generation of naturally oriented ligamentous tissues consistent with periodontal ligament neogenesis., (© International & American Associations for Dental Research.)

Although some risk factors of peri-implant disease are well defined, the lack of efficient and predictable approaches to treat peri-implantitis has created difficulty in the management of those complications. The aim of this review was to evaluate the reliability of the diagnosis methods and to provide a set of guidelines to treat peri-implant diseases. A search of PubMed and a hand search of articles related to peri-implant diseases were conducted up to August 2013. A summary of the current methods for the diagnosis of peri-implantitis, its potential risk factors, and a flow chart to guide the clinical management of these conditions are presented.

In the oral and craniofacial complex, tooth loss is the most commonly acquired disfiguring injury. Among the most formidable challenges of reconstructing tooth-supporting osseous defects in the oral cavity is the regeneration of functional multi-tissue complexes involving bone, ligament, and tooth cementum. Furthermore, periodontal multi-tissue engineering with spatiotemporal orientation of the periodontal ligament (PDL) remains the most challenging obstacle for restoration of physiological loading and homeostasis. We report on the ability of a hybrid computer-designed scaffold--developed utilizing computed tomography--to predictably facilitate the regeneration and integration of dental supporting tissues. Here, we provide the protocol for rapid prototyping, manufacture, surgical implantation, and evaluation of dual-architecture scaffolds for controlling fiber orientation and facilitating morphogenesis of bone-ligament complexes. In contrast to conventional single-system methods of fibrous tissue formation, our protocol supports rigorous control of multi-compartmental scaffold architecture using computational scaffold design and manufacturing by 3D printing, as well as the evaluation of newly regenerated tissue physiology for clinical implementation.

Background: In the chronic established periodontal lesion, the proliferation and migration potential of periodontal ligament (PDL) cells are significantly compromised. Thus, the progressive loss of tissue integrity is favored and normal healing and regeneration compromised. Periostin, a known PDL marker, modulates cell-matrix interactions, cell behavior, as well as the matrix biomechanics and PDL homeostasis., Objective: To evaluate whether periostin restores the regenerative potential of PDL cells in terms of proliferation, migration, and activation of survival signaling pathways after being challenged by Porphyromonas gingivalis lipopolysaccharides and tumor necrosis factor alpha α., Methods: Human PDL (hPDL) cells were cultured under different conditions: control, periostin (50 or 100 ng/mL), and fibroblast growth factor 2 (10 ng/mL) to evaluate cell proliferation (by Ki67), cell migration (by scratch assays) and PI3K/AKT/mTOR pathway activation (by western blot analyses of total AKT, phospho-AKT and PS6). A different set of cultures was challenged by adding tumor necrosis factor alpha α (10 ng/mL) and P. gingivalis lipopolysaccharides (200 ng/mL) to evaluate the effects of periostin as described above., Results: Periostin significantly increased cell proliferation (twofold), migration (especially at earlier time points and low dose) and activation of survival signaling pathway (higher phosphorylation of AKT and PS6). Furthermore, periostin promoted similar cellular effects even after being challenged with proinflammatory cytokines and bacterial virulence factors., Conclusion: Periostin acts as an important modulator of hPDL cell-matrix dynamics. It modulates hPDL proliferation, migration and PI3K/AKT/mTOR pathway. It also helps in overcoming the altered biological phenotype that chronic exposure to periodontal pathogens and proinflammatory cytokines produce in hPDL cells., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Current knowledge about Periostin biology has expanded from its recognized functions in embryogenesis and bone metabolism to its roles in tissue repair and remodeling and its clinical implications in cancer. Emerging evidence suggests that Periostin plays a critical role in the mechanism of wound healing; however, the paracrine effect of Periostin in epithelial cell biology is still poorly understood. We found that epithelial cells are capable of producing endogenous Periostin that, unlike mesenchymal cell, cannot be secreted. Epithelial cells responded to Periostin paracrine stimuli by enhancing cellular migration and proliferation and by activating the mTOR signaling pathway. Interestingly, biomechanical stimulation of epithelial cells, which simulates tension forces that occur during initial steps of tissue healing, induced Periostin production and mTOR activation. The molecular association of Periostin and mTOR signaling was further dissected by administering rapamycin, a selective pharmacological inhibitor of mTOR, and by disruption of Raptor and Rictor scaffold proteins implicated in the regulation of mTORC1 and mTORC2 complex assembly. Both strategies resulted in ablation of Periostin-induced mitogenic and migratory activity. These results indicate that Periostin-induced epithelial migration and proliferation requires mTOR signaling. Collectively, our findings identify Periostin as a mechanical stress responsive molecule that is primarily secreted by fibroblasts during wound healing and expressed endogenously in epithelial cells resulting in the control of cellular physiology through a mechanism mediated by the mTOR signaling cascade.

Background: Periostin is a matricellular protein essential for tissue integrity and maturation and is believed to have a key function as a modulator of periodontal ligament (PDL) homeostasis. The aim of this study is to evaluate whether periodontal disease-associated pathogen-related virulence factors (endotoxins/lipopolysaccharides [LPS]) and proinflammatory cytokines alter the expression of periostin in PDL cells., Methods: Human PDL cultures were exposed to inflammatory mediators (tumor necrosis factor-α [TNF-α]), bacterial virulence factors (Porphyromonas gingivalis LPS) or a combination in a biomechanically challenged environment. Culture conditions were applied for 24 hours, 4 days, and 7 days. Periostin and TGF-β inducible gene clone H3 (βIGH3) mRNA expression from cell lysates were analyzed. Periostin and βIGH3 proteins were also detected and semiquantified in both cell lysates and cell culture supernatants by Western blot. In addition, periostin localization by immunofluorescence was performed. Analysis of variance and Fisher tests were used to define the statistical differences among groups (P <0.05)., Results: In a mechanically challenged environment, periostin protein was more efficiently incorporated into the matrix compared to the non-loaded controls (higher levels of periostin in the supernatant in the non-loaded group). Interestingly, chronic exposure to proinflammatory cytokines and/or microbial virulence factors significantly decreased periostin protein levels in the loaded cultures. There was greater variability on βIGH3 levels, and no particular pattern was clearly evident., Conclusions: Inflammatory mediators (TNF-α) and bacterial virulence factors (P. gingivalis LPS) decrease periostin expression in human PDL fibroblasts. These results support a potential mechanism by which periostin alterations could act as a contributing factor during periodontal disease progression.

Gene transfer of key regulators of osteogenesis for mesenchymal stem cells represents a promising strategy to regenerate bone. It has been reported that LMP3, a transcription variant of LIM domain mineralization protein (LMP) lacking LIM domains, can induce osteogenesis in vitro and in vivo. As little is known about the effects of LMP3 gene therapy on periodontal ligament (PDL) cell osteogenic differentiation, this study sought to explore whether gene delivery of LMP3 can promote PDL cell mineralization and bone formation. Our results showed that adenoviral mediated gene transfer of LMP3 (AdLMP3) significantly upregulated ALP (Alkaline Phosphatase), BSP (Bone Sialoprotein) and BMP2 gene expression and increased in vitro matrix mineralization in human PDL. Although AdLMP3 gene delivery to PDL cells did not induce ectopic bone formation in vivo, we found that AdLMP3 augments new bone formation, which co-delivered with AdBMP7 gene transfer. Our study provides the evidence that there is a synergistic effect between LMP3 and BMP-7 in vivo, suggesting that LMP3 delivery may be used to augment BMP-mediated osteogenesis. LMP3 and BMP-7 combinatory gene therapy may also have specific applications for oral and periodontal regenerative medicine.

Periostin, a matricellular adapter protein highly expressed by periodontal ligament fibroblasts, is implicated in the maintenance of periodontal integrity, which is compromised during periodontal diseases. The aim of this study was to explore the influence of chronic periodontal inflammation on tissue periostin levels. Periodontal breakdown was induced in a pre-clinical ligature periodontal inflammatory disease model. Periodontal tissue specimens were harvested at baseline, 2 weeks, and 4 weeks and prepared for histologic, immunofluorescence, and micro-CT examination. Statistical analyses were conducted by Kruskal-Wallis, Mann-Whitney, and Spearman's tests. Periostin detection levels were reduced over time in response to the inflammatory process (1 ± 0.05; 0.67 ± 0.03; 0.31 ± 0.02; p < 0.001; baseline, 2, and 4 weeks, respectively). Simultaneously, alveolar bone loss increased from baseline to the 2- and 4-week time-points (0.40 ± 0.02 mm; 1.39 ± 0.08 mm; 1.33 ± 0.15 mm; p < 0.001), which was inversely correlated with the levels of periostin (ρ = -0.545; p < 0.001). In conclusion, periostin PDL tissue levels significantly decrease under chronic inflammatory response and correlate with the detrimental changes to the periodontium over time.

Background: Migration of dental implants into the maxillary sinus is an uncommon, but increasingly reported complication. Implant migration may result from initial lack of primary stability, intrasinusal and nasal pressure changes, autoimmune reaction to the implant or incorrect distribution of occlusal forces. This retrospective study aims at analyzing the factors that may influence implant migration into the maxillary sinus cavity., Material and Methods: Fourteen patients presenting a total 15 implants that migrated into the maxillary sinus were recruited. Diagnosis of this complication was based on imaging techniques, such as cone beam computerized tomography scan and panoramic radiography. Clinical data were recorded in all cases and processed for statistical analysis., Results: ABH was below 6 mm in the majority of cases. However, almost 50% of the patients did not receive any site preparation treatment prior to implant insertion. Five patients (33.3%) were treated by osteotome techniques, but only one of them had bone grafting. Therefore, 73.3% of sites did not receive any biomaterial to increase available bone height. The most common complication-associated factors found on this study were related to implant design (cylindrical), implant dimension (diameter), implant restoration/rehabilitation method (partial removable denture), site-specific anatomy (initial residual bone height between 5 and 6.9 mm), demographics (age), and biomaterials., Conclusion: Patient selection and proper treatment planning, as well as the application of the appropriate sinus augmentation technique, are critical aspects that should be controlled to minimize the risk of implant migration into the maxillary sinus cavity., (© 2011 John Wiley & Sons A/S.)

Purpose: The International Congress of Oral Implantologists has supported the development of this consensus report involving the use of Cone Beam Computed Tomography (CBCT) in implant dentistry with the intent of providing scientifically based guidance to clinicians regarding its use as an adjunct to traditional imaging modalities., Materials and Methods: The literature regarding CBCT and implant dentistry was systematically reviewed. A PubMed search that included studies published between January 1, 2000, and July 31, 2011, was conducted. Oral presentations, in conjunction with these studies, were given by Dr. Erika Benavides, Dr. Scott Ganz, Dr. James Mah, Dr. Myung-Jin Kim, and Dr. David Hatcher at a meeting of the International Congress of Oral Implantologists in Seoul, Korea, on October 6-8, 2011., Results: The studies published could be divided into four main groups: diagnostics, implant planning, surgical guidance, and postimplant evaluation., Conclusions: The literature supports the use of CBCT in dental implant treatment planning particularly in regards to linear measurements, three-dimensional evaluation of alveolar ridge topography, proximity to vital anatomical structures, and fabrication of surgical guides. Areas such as CBCT-derived bone density measurements, CBCT-aided surgical navigation, and postimplant CBCT artifacts need further research. ICOI RECOMMENDATIONS: All CBCT examinations, as all other radiographic examinations, must be justified on an individualized needs basis. The benefits to the patient for each CBCT scan must outweigh the potential risks. CBCT scans should not be taken without initially obtaining thorough medical and dental histories and performing a comprehensive clinical examination. CBCT should be considered as an imaging alternative in cases where the projected implant receptor or bone augmentation site(s) are suspect, and conventional radiography may not be able to assess the true regional three-dimensional anatomical presentation. The smallest possible field of view should be used, and the entire image volume should be interpreted.

In humans, microbially induced inflammatory periodontal diseases are the primary initiators that disrupt the functional and structural integrity of the periodontium (i.e., the alveolar bone, the periodontal ligament, and the cementum). The reestablishment of its original structure, properties, and function constitutes a significant challenge in the development of new therapies to regenerate tooth-supporting defects. Preclinical models represent an important in vivo tool to critically evaluate and analyze the key aspects of novel regenerative therapies, including (1) safety, (2) effectiveness, (3) practicality, and (4) functional and structural stability over time. Therefore, these models provide foundational data that supports the clinical validation and the development of novel innovative regenerative periodontal technologies. Steps are provided on the use of the root fenestration animal model for the proper evaluation of periodontal outcome measures using the following parameters: descriptive histology, histomorphometry, immunostaining techniques, three-dimensional imaging, electron microscopy, gene expression analyses, and safety assessments. These methods will prepare investigators and assist them in identifying the key end points that can then be adapted to later stage human clinical trials.

Regeneration of bone-ligament complexes destroyed due to disease or injury is a clinical challenge due to complex topologies and tissue integration required for functional restoration. Attempts to reconstruct soft-hard tissue interfaces have met with limited clinical success. In this investigation, we manufactured biomimetic fiber-guiding scaffolds using solid free-form fabrication methods that custom fit complex anatomical defects to guide functionally-oriented ligamentous fibers in vivo. Compared to traditional, amorphous or random-porous polymeric scaffolds, the use of perpendicularly oriented micro-channels provides better guidance for cellular processes anchoring ligaments between two distinct mineralized structures. These structures withstood biomechanical loading to restore large osseous defects. Cell transplantation using hybrid scaffolding constructs with guidance channels resulted in predictable oriented fiber architecture, greater control of tissue infiltration, and better organization of ligament interface than random scaffold architectures. These findings demonstrate that fiber-guiding scaffolds drive neogenesis of triphasic bone-ligament integration for a variety of clinical scenarios., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Inflammatory periodontal diseases are a leading cause of tooth loss and are linked to multiple systemic conditions, such as cardiovascular disease and stroke. Reconstruction of the support and function of affected tooth-supporting tissues represents an important therapeutic endpoint for periodontal regenerative medicine. An improved understanding of periodontal biology coupled with current advances in scaffolding matrices has introduced novel treatments that use cell and gene therapy to enhance periodontal tissue reconstruction and its biomechanical integration. Cell and gene delivery technologies have the potential to overcome limitations associated with existing periodontal therapies, and may provide a new direction in sustainable inflammation control and more predictable tissue regeneration of supporting alveolar bone, periodontal ligament, and cementum. This review provides clinicians with the current status of these early-stage and emerging cell- and gene-based therapeutics in periodontal regenerative medicine, and introduces their future application in clinical periodontal treatment. The paper concludes with prospects on the application of cell and gene tissue engineering technologies for reconstructive periodontology.

Background: Understanding the molecular features of bone repair and osseointegration may aid in the development of therapeutics to improve implant outcomes. The purpose of this investigation is to determine the gene expression dynamics during alveolar bone repair and implant osseointegration., Methods: An implant osseointegration preclinical animal model was used whereby maxillary defects were created at the time of oral implant placement, while a tooth extraction socket healing model was established on the contralateral side of each animal. The surrounding tissues in the zone of the healing defects were harvested during regeneration for temporal evaluation using histology, immunohistochemistry, laser capture microdissection, and quantitative reverse transcription-polymerase chain reaction for the identification of a panel of 17 putative genes associated with wound repair., Results: In both models, three distinct expression patterns were displayed: 1) genes that are slowly increased during the healing process, such as bone morphogenetic protein 4, runt-related transcription factor 2, and osteocalcin; 2) genes that are upregulated at the early stage of healing and then downregulated at later stages, such as interleukin and chemokine (C-X-C motif) ligands 2 and 5; and 3) genes that are constitutively expressed over time, such as scleraxis. Although some similarities between osseointegration and tooth extraction socket were seen, distinct features developed and triggered a characteristic coordinated expression and orchestration of transcription factors, growth factors, extracellular matrix molecules, and chemokines., Conclusions: Characterization of these events contributes to a better understanding of cooperative molecular dynamics in alveolar bone healing, and highlights potential pathways that could be further explored for the enhancement of osseous regenerative strategies.

Periostin plays multiple functions during development. Our previous work showed a critical role of this disulfide-linked cell adhesion protein in maintenance of periodontium integrity in response to occlusal load. In this study, we attempted to address whether this mechanical response molecule played a direct role in postnatal tooth development. Our key findings are 1) periostin is expressed in preodontoblasts, and odontoblasts; and the periostin-null incisor displayed a massive increase in dentin formation after mastication; 2) periostin is also expressed in the ameloblast cells, and an enamel defect is identified in both the adult-null incisor and molar; 3) deletion of periostin leads to changes in expression profiles of many non-collagenous protein such as DSPP, DMP1, BSP, and OPN in incisor dentin; 4) the removal of a biting force leads to reduction of mineralization, which is partially prevented in periostin-null mice; and 6) both in vitro and in vivo data revealed a direct regulation of periostin by TGF-β1 in dentin formation. In conclusion, periostin plays a novel direct role in controlling postnatal tooth formation, which is required for the integrity of both enamel and dentin.

A major clinical challenge in the reconstruction of large oral and craniofacial defects is the neogenesis of osseous and ligamentous interfacial structures. Currently, oral regenerative medicine strategies are unpredictable for repair of tooth-supporting tissues destroyed as a consequence of trauma, chronic infection or surgical resection. Here, we demonstrate multi-scale computational design and fabrication of composite hybrid polymeric scaffolds for targeted cell transplantation of genetically modified human cells for the formation of human tooth dentin-ligament-bone complexes in vivo. The newly-formed tissues demonstrate the interfacial generation of parallel- and obliquely-oriented fibers that grow and traverse within the polycaprolactone (PCL)-poly(glycolic acid) (PGA) designed constructs forming tooth cementum-like tissue, ligament, and bone structures. This approach offers potential for the clinical implementation of customized periodontal scaffolds that may enable regeneration of multi-tissue interfaces required for oral, dental and craniofacial engineering applications., (Copyright 2010 Elsevier Ltd. All rights reserved.)

A new spontaneous mouse mutant (ntl) with autosomal-recessive osteopetrosis was characterized. These mice formed tartrate-resistant acid phosphate (TRAP)-positive osteoclasts but their osteoclasts had no ruffled border and did not resorb bone. These mice displayed no tooth eruption or tooth root formation. Adult mutant mice developed odontoma-like proliferations near the proximal ends of the incisors. Intraperitoneal injection of progenitor cells from the liver of 16.5 days postcoitum wild-type embryos into newborn mutants rescued the osteopetrosis phenotype, indicating that the defects were intrinsic to the osteoclasts. Our findings not only provide further support for a critical role of osteoclasts in tooth eruption and tooth root development, but also suggest that the perturbation of the homeostasis of the odontogenic precursors of the incisors is primarily responsible for the development of the odontoma-like proliferations in this osteopetrosis mutant. Genetic mapping has narrowed down the location of the mutant allele to a genetic interval of 3.2 cM on mouse chromosome 17.

Unlabelled: BACKGROUND OF PROBLEMS:: Sinus augmentation is a predictable procedure to increase bone height in the posterior maxilla to facilitate ideal implant placement. However, the effect of residual alveolar bone height upon overall implant success remains unclear., Aims: : Hence, the objective of this study was to review and evaluate the correlation between amount of remaining crest alveolar bone before sinus augmentation and implant survival rate in grafted areas., Materials: : Medline search was used to identify articles published through September 2006, with preset selection criteria., Results: : A total of 156 peer-reviewed publications were selected. Eighteen publications fulfilled the selection criteria. Despite the great heterogeneity found among the selected studies, we were able to group the selected articles in 2 distinct groups and show average implant survival rate in the following residual bone categories: (1) <5 mm: 96% (80%-100%); and (2) >4 mm 99% (97%-100%)., Conclusion: : The data reviewed from the literature suggests a higher implant survival predictability as available residual bone increases. However, prospective studies with adequate sample size and control of confounding factors are needed to validate this observation.

Background: The ability of the periodontal ligament (PDL) to absorb and distribute forces is necessary for periodontal homeostasis. This adaptive response may be determined, in part, by a key molecule, periostin, which maintains the integrity of the PDL during occlusal function and inflammation. Periostin is primarily expressed in the PDL and is highly homologous to betaig-H3 (transforming growth factor-beta [TGF-beta] inducible gene). Cementum, alveolar bone, and the PDL of periostin-null mice dramatically deteriorate following tooth eruption. The purpose of this study was to determine the role of periostin in maintaining the functional integrity of the periodontium., Methods: The periodontia from periostin-null mice were characterized followed by unloading the incisors. The effect of substrate stretching on periostin expression was evaluated using a murine PDL cell line. Real-time reverse transcription-polymerase chain reaction was used to quantify mRNA levels of periostin and TGF-beta. TGF-beta1 neutralizing antibodies were used to determine whether the effects of substrate stretching on periostin expression are mediated through TGF-beta., Results: Severe periodontal defects were observed in the periostin-null mice after tooth eruption. The removal of masticatory forces in periostin-null mice rescue the periodontal defects. Periostin expression was increased in strained PDL cells by 9.2-fold at 48 hours and was preceded by a transient increase in TGF-beta mRNA in vitro. Elevation of periostin in response to mechanical stress was blocked by the addition of 2.5 ng/ml neutralizing antibody to TGF-beta1, suggesting that mechanical strain activates TGF-beta to have potential autocrine effects and to increase periostin expression., Conclusion: Mechanical loading maintains sufficient periostin expression to ensure the integrity of the periodontium in response to occlusal load.

Unlabelled: The role of DMP1 in mineralization was analyzed by comparing bone mineral and matrix properties in dmp1-null female mice to heterozygous and wildtype controls by FTIR imaging spectroscopy. The observed decreased mineral content in dmp1 null mice indicates a key role for dmp1 in bone mineralization. Indirect effects of DMP1 on other systems also determine the KO phenotype., Introduction: Dentin matrix protein 1 (DMP1), an acidic phosphorylated extracellular matrix protein, is highly expressed in mineralized tissues. In vitro, DMP1 peptides can promote or inhibit mineralization depending on the extent of phosphorylation, the peptide size, and concentration. To clarify the biological function of DMP1 protein on in vivo mineralization, this study analyzed bone properties of dmp1 knockout (KO) mice compared with heterozygous (HET) and wildtype (WT) controls., Materials and Methods: Tibias from dmp1 KO and age-, sex-, and background-matched HET and WT mice at 4 and 16 weeks (N(total) = 60) were examined by Fourier transform infrared imaging (FTIRI), histology (n = 6 per genotype and age; N = 36), and geometry by muCT (n = 4 per genotype and age; N = 24). Serum ionic calcium and phosphate concentrations were also determined., Results: The mineral-to-matrix ratios (spectroscopic parameter of relative mineral content) were significantly lower in dmp1 KO mice tibias compared with WT and HET at 4 and 16 weeks. The mineral crystallinity (crystal size/perfection) was significantly increased in dmp1 KO and HET mice relative to WT. Collagen cross-link ratios (a spectroscopic parameter related to the relative amounts of nonreducible/reducible collagen cross-links) in dmp1 KO were not significantly different from WT and HET. Based on muCT, cortical bone cross-sectional areas at 16 but not 4 weeks were significantly reduced in the KO compared with controls. Maximum, minimum, and polar cross-sectional moments of inertia were significantly lower in dmp1 KO than in HET at 16 weeks but not at 4 weeks. Histological analysis and muCT 3-D images suggested that dmp1 KO mice had osteomalacia. Dmp1 KO mice had significantly lower ionic calcium and phosphate concentrations relative to WT, whereas in the HET, values for phosphate were equivalent, and calcium values were decreased relative to WT values., Conclusions: The findings of decreased mineral-to-matrix ratio and increased crystal size in bones of dmp1 KO mice suggest that DMP1 has multiple roles (both direct and indirect) in the regulation of postnatal mineralization. We suggest that direct effects on mineral formation, crystal growth, and indirect effects on regulation of Ca x P concentrations and matrix turnover all contribute to the dominant phenotype in the dmp1 KO mouse.