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Periodontitis is an inflammatory disease induced by complex interactions between host immune system and plaque microorganism. Alveolar bone resorption caused by periodontitis is ...considered to be one of the main reasons for tooth loss in adults. To terminate the alveolar bone resorption, simultaneous anti-inflammation and periodontium regeneration is required, which has not appeared in the existing methods. In this study, chitosan (CS), β-sodium glycerophosphate (β-GP), and gelatin were used to prepare an injectable and thermosensitive hydrogel, which could continuously release aspirin and erythropoietin (EPO) to exert pharmacological effects of anti-inflammation and tissue regeneration, respectively. The releasing profile showed that aspirin and EPO could be continuously released from the hydrogels, which exhibited no toxicity both in vitro and in vivo, for at least 21 days. Immunohistochemistry staining and micro-CT analyses indicated that administration of CS/β-GP/gelatin hydrogels loaded with aspirin/EPO could terminate the inflammation and recover the height of the alveolar bone, which is further confirmed by histological observations. Our results suggested that CS/β-GP/gelatin hydrogels are easily prepared as drug-loading vectors with excellent biocompatibility, and the CS/β-GP/gelatin hydrogels loaded with aspirin/EPO are quite effective in anti-inflammation and periodontium regeneration, which provides a great potential candidate for periodontitis treatment in the dental clinic.
Statement of Significance
To terminate the alveolar bone resorption caused by periodontitis, simultaneous anti-inflammation and periodontium regeneration is required, which has not appeared in the existing methods. Here, (1) the chitosan (CS)/β-sodium glycerophosphate/gelatin hydrogels loaded with aspirin/erythropoietin (EPO) can form at body temperature in 5 min with excellent biocompatibility in vitro and in vivo; (2) The faster release of aspirin than EPO in the early stage is beneficial for anti-inflammation and provides a microenvironment for ensuring the regeneration function of EPO in the following step. In vivo experiments revealed that the hydrogels are effective in the control of inflammation and regeneration of the periodontium. These results indicate that our synthesized hydrogels have a great potential in the future clinical application.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Periodontitis, or gum disease, affects millions of people each year. Although it is associated with a defined microbial composition found on the surface of the tooth and tooth root, the contribution ...of bacteria to disease progression is poorly understood. Commensal bacteria probably induce a protective response that prevents the host from developing disease. However, several bacterial species found in plaque (the 'red-complex' bacteria: Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola) use various mechanisms to interfere with host defence mechanisms. Furthermore, disease may result from 'community-based' attack on the host. Here, I describe the interaction of the host immune system with the oral bacteria in healthy states and in diseased states.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Periodontal health is defined by absence of clinically detectable inflammation. There is a biological level of immune surveillance that is consistent with clinical gingival health and homeostasis. ...Clinical gingival health may be found in a periodontium that is intact, i.e. without clinical attachment loss or bone loss, and on a reduced periodontium in either a non‐periodontitis patient (e.g. in patients with some form of gingival recession or following crown lengthening surgery) or in a patient with a history of periodontitis who is currently periodontally stable. Clinical gingival health can be restored following treatment of gingivitis and periodontitis. However, the treated and stable periodontitis patient with current gingival health remains at increased risk of recurrent periodontitis, and accordingly, must be closely monitored.
Two broad categories of gingival diseases include non‐dental plaque biofilm–induced gingival diseases and dental plaque‐induced gingivitis. Non‐dental plaque biofilm‐induced gingival diseases include a variety of conditions that are not caused by plaque and usually do not resolve following plaque removal. Such lesions may be manifestations of a systemic condition or may be localized to the oral cavity. Dental plaque‐induced gingivitis has a variety of clinical signs and symptoms, and both local predisposing factors and systemic modifying factors can affect its extent, severity, and progression. Dental plaque‐induced gingivitis may arise on an intact periodontium or on a reduced periodontium in either a non‐periodontitis patient or in a currently stable “periodontitis patient” i.e. successfully treated, in whom clinical inflammation has been eliminated (or substantially reduced). A periodontitis patient with gingival inflammation remains a periodontitis patient (Figure 1), and comprehensive risk assessment and management are imperative to ensure early prevention and/or treatment of recurrent/progressive periodontitis.
Precision dental medicine defines a patient‐centered approach to care, and therefore, creates differences in the way in which a “case” of gingival health or gingivitis is defined for clinical practice as opposed to epidemiologically in population prevalence surveys. Thus, case definitions of gingival health and gingivitis are presented for both purposes. While gingival health and gingivitis have many clinical features, case definitions are primarily predicated on presence or absence of bleeding on probing. Here we classify gingival health and gingival diseases/conditions, along with a summary table of diagnostic features for defining health and gingivitis in various clinical situations.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The aim of this review is to discuss the clinical utility of stem cells in periodontal regeneration by reviewing relevant literature that assesses the periodontal‐regenerative potential of stem ...cells. We consider and describe the main stem cell populations that have been utilized with regard to periodontal regeneration, including bone marrow‐derived mesenchymal stem cells and the main dental‐derived mesenchymal stem cell populations: periodontal ligament stem cells, dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla and dental follicle precursor cells. Research into the use of stem cells for tissue regeneration has the potential to significantly influence periodontal treatment strategies in the future.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract Periodontitis, an inflammatory disease, is the most common cause of tooth loss in adults. Attempts to regenerate the complex system of tooth-supporting apparatus (i.e., the periodontal ...ligament, alveolar bone and root cementum) after loss/damage due to periodontitis have made some progress recently and provide a useful experimental model for the evaluation of future regenerative therapies. Concentrated efforts have now moved from the use of guided tissue/bone regeneration technology, a variety of growth factors and various bone grafts/substitutes toward the design and practice of endogenous regenerative technology by recruitment of host cells (cell homing) or stem cell-based therapeutics by transplantation of outside cells to enhance periodontal tissue regeneration and its biomechanical integration. This shift is driven by the general inability of conventional therapies to deliver satisfactory outcomes, particularly in cases where the disease has caused large tissue defects in the periodontium. Cell homing and cell transplantation are both scientifically meritorious approaches that show promise to completely and reliably reconstitute all tissue and connections damaged through periodontal disease, and hence research into both directions should continue. In view of periodontal regeneration by paradigms that unlock the body's innate regenerative potential has been reviewed elsewhere, this paper specifically explores and analyses the stem cell types and cell delivery strategies that have been or have the potential to be used as therapeutics in periodontal regenerative medicine, with particular emphasis placed on the efficacy and safety concerns of current stem cell-based periodontal therapies that may eventually enter into the clinic.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We wished to evaluate whether epigenetic modifiers have a beneficial effect on treating experimental periodontitis and mechanisms for regulating the cell fate of mesenchymal stem cells (MSCs) in ...inflammatory microenvironments. We isolated MSCs from healthy and inflamed gingival tissues to investigate whether trichostatin A (TSA) could improve osteogenic differentiation and resolve inflammation in vitro. The tissue regenerative potentials were evaluated when treated with a temperature‐dependent, chitosan‐scaffold‐encapsulated TSA, in a rat model of periodontitis. After induction with the conditioned medium, TSA treatment increased the osteogenic differentiation potential of inflamed MSCs and healthy MSCs. In addition, interleukin‐6 and interleukin‐8 levels in supernatants were significantly decreased after TSA treatment. Moreover, TSA promoted osteogenic differentiation by inhibiting nuclear factor‐κB (p65) DNA binding in MSCs. In rats with experimental periodontitis, 7 weeks after local injections of chitosan‐scaffold‐encapsulated TSA, histology and microcomputed tomography showed a significant increase in alveolar bone volume and less inflammatory infiltration compared with vehicle‐treated rats. The concentrations of interferon‐γ and interleukin‐6 were significantly decreased in the gingival crevicular fluid after TSA treatment. This study demonstrated that TSA had anti‐inflammatory properties and could promote periodontal tissue repair, which indicated that epigenetic modifiers hold promise as a potential therapeutic option for periodontal tissue repair.
This study showed that trichostatin A (TSA) could rescue impaired osteogenic differentiation of gingiva‐derived mesenchymal stem cell (GMSCs) from inflammatory conditions, reduce inflammation, and promote periodontal tissue repair in vivo by inhibiting nuclear factor‐κB (NF‐κB) signaling. These results indicated that epigenetic modifiers might be a promising therapeutic approach in clinical treatments of periodontitis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract Periodontal regeneration has been challenged with chemical reagents and/or biological approaches, however, there is still no sufficient technique that can regenerate complete periodontium, ...including alveolar bone, cementum, and well-oriented collagen fibers. The purpose of this study was to examine multi-layered sheets of periodontal ligament (PDL)-derived cells for periodontal regeneration. Canine PDL cells were isolated enzymatically and expanded in vitro . The cell population contained cells capable of making single cell-derived colonies at an approximately 20% frequency. Expression of mRNA of periodontal marker genes, S100 calcium binding protein A4 and periostin, was observed. Alkaline phosphatase activity and gene expression of both osteoblastic/cementoblastic and periodontal markers were upregulated by osteoinductive medium. Then, three-layered PDL cell sheets supported with woven polyglycolic acid were transplanted to dental root surfaces having three-wall periodontal defects in an autologous manner, and bone defects were filled with porous β-tricalcium phosphate. Cell sheet transplantation regenerated both new bone and cementum connecting with well-oriented collagen fibers, while only limited bone regeneration was observed in control group where cell sheet transplantation was eliminated. These results suggest that PDL cells have multiple differentiation properties to regenerate periodontal tissues comprising hard and soft tissues. PDL cell sheet transplantation should prove useful for periodontal regeneration in clinical settings.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK