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    Cell-to-cell communication--periodontal regeneration. Bosshardt Dieter D,Stadlinger Bernd,Terheyden Hendrik Clinical oral implants research BACKGROUND:Although regenerative treatment options are available, periodontal regeneration is still regarded as insufficient and unpredictable. AIM:This review article provides scientific background information on the animated 3D film Cell-to-Cell Communication - Periodontal Regeneration. RESULTS:Periodontal regeneration is understood as a recapitulation of embryonic mechanisms. Therefore, a thorough understanding of cellular and molecular mechanisms regulating normal tooth root development is imperative to improve existing and develop new periodontal regenerative therapies. However, compared to tooth crown and earlier stages of tooth development, much less is known about the development of the tooth root. The formation of root cementum is considered the critical element in periodontal regeneration. Therefore, much research in recent years has focused on the origin and differentiation of cementoblasts. Evidence is accumulating that the Hertwig's epithelial root sheath (HERS) has a pivotal role in root formation and cementogenesis. Traditionally, ectomesenchymal cells in the dental follicle were thought to differentiate into cementoblasts. According to an alternative theory, however, cementoblasts originate from the HERS. What happens when the periodontal attachment system is traumatically compromised? Minor mechanical insults to the periodontium may spontaneously heal, and the tissues can structurally and functionally be restored. But what happens to the periodontium in case of periodontitis, an infectious disease, after periodontal treatment? A non-regenerative treatment of periodontitis normally results in periodontal repair (i.e., the formation of a long junctional epithelium) rather than regeneration. Thus, a regenerative treatment is indicated to restore the original architecture and function of the periodontium. Guided tissue regeneration or enamel matrix proteins are such regenerative therapies, but further improvement is required. As remnants of HERS persist as epithelial cell rests of Malassez in the periodontal ligament, these epithelial cells are regarded as a stem cell niche that can give rise to new cementoblasts. Enamel matrix proteins and members of the transforming growth factor beta (TGF-ß) superfamily have been implicated in cementoblast differentiation. CONCLUSION:A better knowledge of cell-to-cell communication leading to cementoblast differentiation may be used to develop improved regenerative therapies to reconstitute periodontal tissues that were lost due to periodontitis. 10.1111/clr.12543
    Cellular and Molecular Pathways Leading to External Root Resorption. Iglesias-Linares A,Hartsfield J K Journal of dental research External apical root resorption during orthodontic treatment implicates specific molecular pathways that orchestrate nonphysiologic cellular activation. To date, a substantial number of in vitro and in vivo molecular, genomic, and proteomic studies have supplied data that provide new insights into root resorption. Recent mechanisms and developments reviewed here include the role of the cellular component-specifically, the balance of CD68, iNOS M1- and CD68, CD163 M2-like macrophages associated with root resorption and root surface repair processes linked to the expression of the M1-associated proinflammatory cytokine tumor necrosis factor, inducible nitric oxide synthase, the M1 activator interferon γ, the M2 activator interleukin 4, and M2-associated anti-inflammatory interleukin 10 and arginase I. Insights into the role of mesenchymal dental pulp cells in attenuating dentin resorption in homeostasis are also reviewed. Data on recently deciphered molecular pathways are reviewed at the level of (1) clastic cell adhesion in the external apical root resorption process and the specific role of α/β integrins, osteopontin, and related extracellular matrix proteins; (2) clastic cell fusion and activation by the RANKL/RANK/OPG and ATP-P2RX7-IL1 pathways; and (3) regulatory mechanisms of root resorption repair by cementum at the proteomic and transcriptomic levels. 10.1177/0022034516677539
    Intentional Replantation Techniques: A Critical Review. Becker Bradley D Journal of endodontics INTRODUCTION:Techniques and armamentarium for intentional replantation have varied throughout the years with no universally accepted clinical treatment guidelines. A wide range of success rates has been reported, and accordingly, this treatment method has often been regarded as a treatment of last resort. However, recent studies have shown more consistent success rates as high as 88% to 95%. In light of these new studies, intentional replantation may now be considered a more commonly accepted treatment modality. The purpose of this review was to critically examine reported techniques for intentional replantation. METHODS:A search of the literature on intentional replantation techniques was performed using electronic databases including PubMed, Medline, and Scopus. A total of 3183 articles were generated and screened for relevance based on defined inclusion and exclusion criteria. Subsequently, 27 studies were included for critical review of technique. RESULTS:There has been an evolution in technique for intentional replantation over the decades. CONCLUSIONS:Numerous aspects of the procedure exhibit variations, whereas other aspects exhibit considerable consistency. Few studies reported techniques consistent with modern endodontic surgical principles. 10.1016/j.joen.2017.08.002
    Interventions for treating traumatised permanent front teeth: avulsed (knocked out) and replanted. Day Peter F,Duggal Monty,Nazzal Hani The Cochrane database of systematic reviews BACKGROUND:Traumatic dental injuries are common. One of the most severe injuries is when a permanent tooth is knocked completely out of the mouth (avulsed). In most circumstances the tooth should be replanted as quickly as possible. There is uncertainty on which interventions will maximise the survival and repair of the replanted tooth. This is an update of a Cochrane Review first published in 2010. OBJECTIVES:To compare the effects of a range of interventions for managing traumatised permanent front teeth with avulsion injuries. SEARCH METHODS:Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 8 March 2018), Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 2) in the Cochrane Library (searched 8 March 2018), MEDLINE Ovid (1946 to 8 March 2018), and Embase Ovid (1980 to 8 March 2018). The US National Institutes of Health Ongoing Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA:We considered randomised and quasi-randomised controlled trials that included a minimum follow-up period of 12 months, for interventions for avulsed and replanted permanent front teeth. DATA COLLECTION AND ANALYSIS:Two review authors independently selected studies, extracted data and assessed the risk of bias. Authors were contacted where further information about their study was required. MAIN RESULTS:Four studies, involving a total of 183 participants and 257 teeth were identified. Each of the interventions aimed to reduce infection or alter the inflammatory response or both at the time of or shortly after the tooth or teeth were replanted. Each study assessed a different intervention and therefore it was not appropriate or possible to numerically synthesise the data. All evidence was rated as being of very low quality due to problems with risk of bias and imprecision of results. This means that we are very uncertain about all of the results presented in this review.One study at high risk of bias with 69 participants (138 teeth) compared a 20-minute soak with gentamycin sulphate for both groups prior to replantation with the experimental group receiving daily hyperbaric oxygen for 80 minutes for the first 10 days. There was some evidence of a benefit for the hyperbaric oxygen group in respect of periodontal healing, tooth survival, and pulpal healing.One study at unclear risk of bias with 22 participants (27 teeth) compared the use of two root canal medicaments, Ledermix and Ultracal. There was insufficient evidence of a difference for periodontal healing or tooth survival. This was the only study to formally report adverse events with none identified. Study authors reported that Ledermix caused a greater level of patient dissatisfaction with the colour of avulsed and replanted teeth.A third study at high risk of bias with 19 participants compared extra- or intra-oral endodontics for avulsed teeth which were stored dry for longer than 60 minutes before replantation. There was insufficient evidence of a difference in periodontal healing.The fourth study at high risk of bias with 73 participants compared a 10-minute soak in either thymosin alpha 1 or saline before replantation followed by daily gingival injections with these same medicaments for the first 7 days. There was some evidence of a benefit for thymosin alpha 1 with respect to periodontal healing and tooth survival. AUTHORS' CONCLUSIONS:Based on the results of the included studies, there is insufficient evidence to support or refute the effectiveness of different interventions for avulsed and replanted permanent front teeth. The overall quality of existing evidence was very low, and therefore great caution should be exercised when generalising the results of the included trials. There is urgent need for further well-designed randomised controlled trials. 10.1002/14651858.CD006542.pub3
    Cellular therapy in periodontal regeneration. Nuñez Javier,Vignoletti Fabio,Caffesse Raul G,Sanz Mariano Periodontology 2000 Periodontitis is a chronic inflammatory condition leading to destruction of the tooth supporting tissues, which if left untreated may cause tooth loss. The treatment of periodontitis mainly aims to arrest the inflammatory process by infection control measures, although in some specific lesions a limited periodontal regeneration can also be attained. Current regenerative approaches are aimed to guide the cells with regenerative capacity to repopulate the lesion and promote new cementum and new connective tissue attachment. The first phase in periodontal tissue regeneration involves the differentiation of mesenchymal cells into cementoblasts to promote new cementum, thus facilitating the attachment of new periodontal ligament fibers to the root and the alveolar bone. Current regenerative approaches limit themselves to the confines of the lesion by promoting the self-regenerative potential of periodontal tissues. With the advent of bioengineered therapies, several studies have investigated the potential use of cell therapies, mainly the use of undifferentiated mesenchymal cells combined with different scaffolds. The understanding of the origin and differentiation patterns of these cells is, therefore, important to elucidate their potential therapeutic use and their comparative efficacy with current technologies. This paper aims to review the in vitro and experimental studies using cell therapies based on application of cementoblasts and mesenchymal stem cells isolated from oral tissues when combined with different scaffolds. 10.1111/prd.12250
    Periodontal Ligament Stem Cells: Regenerative Potency in Periodontium. Tomokiyo Atsushi,Wada Naohisa,Maeda Hidefumi Stem cells and development Periodontium is consisted of root cementum, bone lining the tooth socket, gingiva facing the tooth, and periodontal ligament (PDL). Its primary functions are support of the tooth and protection of tooth, nerve, and blood vessels from injury by mechanical loading. Severe periodontitis induces the destruction of periodontium and results in a significant cause of tooth loss among adults. Unfortunately, conventional therapies such as scaling and root planning are often only palliative. Therefore, the ultimate goal of the treatment for periodontitis is to restore disrupted periodontium to its original shape and function. Tissue engineering refers to the process of combining cells, scaffolds, and signaling molecules for the production of functional tissues to restore, maintain, and improve damaged organs. The discovery of periodontal ligament stem cells (PDLSCs) highlighted the possibility for development of tissue engineering technology-based therapeutics for disrupted periodontium. PDLSCs are a kind of somatic stem cells that show potential to differentiate into multiple cell types and undergo robust clonal self-renewal. Therefore, PDLSCs are considered a highly promising stem cell population for regenerative therapy in periodontium; however, their rarity prevents the progression of basic and clinical researches. In this review, we summarize recent research advancement and accumulated information regarding the self-renewal capacity, multipotency, and immunomodulatory effect of PDLSCs, as well as their contribution to repair and regeneration of periodontium and other tissues. We also discuss the possibility of PDLSCs for clinical application of regenerative medicine and provide an outline of the genetic approaches to overcome the issue about the rarity of PDLSCs. 10.1089/scd.2019.0031
    Survival and complication analyses of avulsed and replanted permanent teeth. Müller Daniel David,Bissinger Ricarda,Reymus Marcel,Bücher Katharina,Hickel Reinhard,Kühnisch Jan Scientific reports 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. 10.1038/s41598-020-59843-1
    Is Intentional Replantation Appropriate for Treatment of Extensive Endodontic-periodontal Lesions Related to Palatogingival Groove? Han Bing,Liu Ying Yi,Liu Kai Ning,Gao Min,Wang Zu Hua,Wang Xiao Yan The Chinese journal of dental research : the official journal of the Scientific Section of the Chinese Stomatological Association (CSA) This report describes the cases of two patients with a maxillary lateral incisor with palatogingival groove and extensive endodontic-periodontal lesions. Although it is reported that acceptable periodontal status is of great importance in case selection in intentional replantation, it is suggested in this report that intentional replantation could be chosen instead of immediate extraction if extensive endodontic-periodontal lesions exist in a tooth with palatogingival groove. The gingival margin position and gingival papilla were well preserved and the bone defect was almost completely repaired. This was beneficial to the aesthetic prosthodontic treatment and implantation, although external root resorption was observed. 10.3290/j.cjdr.a45225
    European Society of Endodontology position statement: Surgical extrusion, intentional replantation and tooth autotransplantation: European Society of Endodontology developed by. Plotino G,Abella Sans F,Duggal M S,Grande N M,Krastl G,Nagendrababu V,Gambarini G International endodontic journal This European Society of Endodontology (ESE) position statement on surgical extrusion, intentional replantation and tooth autotransplantation represents the consensus of an expert committee, convened by the ESE. A narrative review in the International Endodontic Journal (Plotino et al. 2020, international Endodontic Journal, 53, 1636-52) formed the basis for the position statement. The review provided detailed information on the background, clinical procedures and the outcome of surgical extrusion, intentional replantation and tooth autotransplantation techniques. The aim of the current statement is to summarize the best available evidence on these clinical techniques to provide appropriate clinical guidance to undergraduate and postgraduate students, dental practitioners, clinical teachers and researchers. The current position statement will be updated by the ESE periodically to reflect new evidence as it becomes available to provide the most current treatment guidance for clinical practice. 10.1111/iej.13456
    Cell-Based Therapy for Tooth Replantation Following Avulsion: A Systematic Review. Chew Jacob Ren Jie,Tan Bing Liang,Lu Jacinta Xiaotong,Tong Huei Jinn,Duggal Mandeep Singh Tissue engineering. Part B, Reviews The management of avulsed teeth undergoing delayed replantation remains a clinical challenge as there are currently no effective interventions that can improve periodontal healing and prevent replacement root resorption. While several preclinical studies have reported varied success using cell-based tissue engineering to improve periodontal healing, a consensus is required before further clinical translation. Therefore, this systematic review seeks to evaluate the efficacy of cell-based therapy in promoting periodontal healing following delayed replantation in animal models. MEDLINE (PubMed) and Embase were searched on September 27, 2020. Ten studies involving rodent and dog models met the inclusion criteria. Cell sources included gingiva, periodontal ligament (PDL), bone marrow, and adipose tissues. Generally, cell-based therapy had increased the proportion of root surfaces displaying periodontal healing and concomitantly reduced the proportion presenting with replacement root resorption and ankylosis. The best outcomes were observed following treatment with PDL-derived cells of various potency. Future preclinical studies will benefit from adopting measures to minimize bias during the conduct of animal experiments and the standardization of the outcome measures reporting. This will facilitate future reviews with possible pooling of results in the form of meta-analyses, allowing a consensus to be obtained from the literature. In addition, further research will be required to shed light on the implications of using allogeneic cells as well as the optimization of cell delivery protocols. The findings of this systematic review demonstrated the therapeutic potential of certain cell-based therapies in promoting periodontal healing following delayed replantation, thus highlighting their prospective clinical benefits and translational value. 10.1089/ten.TEB.2021.0016