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A sustained-release Trametinib bio-multifunction hydrogel inhibits orthodontically induced inflammatory root resorption.

ABSTRACT: Orthodontic tooth movement (OTM) is a bone reconstruction process. In most cases, OTM could induce root resorption as a common side effect, called orthodontically induced inflammatory root resorption (OIIRR). OIIRR affects tooth health and interferes with the stability of orthodontic treatment. Osteoclasts, which perform bone resorption in OTM, attack cementum, causing OIIRR. Many signaling pathways are involved in the maturation and differentiation of osteoclasts, among which the ERK1/2 is one of the important pathways. In this experiment, we added Trametinib (Tra), a specific inhibitor of ERK1/2, to catechol-modified chitosan (CHI-C) and oxidized dextran (ODex) to form a CCOD-Trametinib composite hydrogel (CCOD-Tra) to prevent OIIRR. CCOD-Tra exhibited good biocompatibility, injectability, strong adhesion, good hemostatic function and sustained release of Tra. We performed local injection of CCOD-Tra into the periodontal tissues of rats. CCOD-Tra firmly adhered to the periodontal tissues and then released Tra to establish a good biological environment and maintain a drug concentration at a high level around the roots for a long time. H&E, TRAP, immunochemistry staining and micro-CT indicated that CCOD-Tra had a good effect in terms of preventing OIIRR. Cell experiments showed that CCOD-Tra reduced the expression of TRAP, MMP-9 and C-FOS in osteoclast cells through the ERK1/2 signaling pathway to inhibit the differentiation and maturation of osteoclasts. Based on the above results, we concluded that CCOD-Tra had the ability to prevent OIIRR, the high adhesion and injectability of CCOD may provide better therapeutic ideas for clinical prevention of OIIRR.

SUBMITTER: Yu H

PROVIDER: S-EPMC9168831 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesTo develop a clinical practice guideline on orthodontically induced external apical root resorption (EARR), with evidence-based and, when needed, consensus-based recommendations concerning diagnosis, risk factors, management during treatment, and after-treatment care.Materials and methodsThe Appraisal of Guidelines for Research and Evaluation II instrument and the Dutch Method for Evidence-Based Guideline Development were used to develop the guideline. Based on a survey of all Dutch orthodontists, we formulated four clinical questions regarding EARR. To address these questions, we conducted systematic literature searches in MEDLINE and Embase, and we performed a systematic literature review. The quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. After discussing the evidence, a Task Force formulated considerations and recommendations. The drafted guideline was sent for comments to all relevant stakeholders.ResultsEight studies were included. The quality of evidence (GRADE) was rated as low or very low. Only the patient-related risk factors, 'gender' and 'age', showed a moderate quality of evidence. The Task Force formulated 13 final recommendations concerning the detection of EARR, risk factors, EARR management during treatment, and after-treatment care when EARR has occurred. Stakeholder consultation resulted in 51 comments on the drafted guideline. After processing the comments, the final guideline was authorized by the Dutch Association of Orthodontists. The entire process took 3 years.LimitationsThe quality of the available evidence was mainly low, and patient-reported outcome measures were lacking.Conclusions/implicationsThis clinical practice guideline allows clinicians to respond to EARR based on current knowledge, although the recommendations are weak due to low-quality evidence. It may reduce variation between practices and aid in providing patients appropriate information.

Project description:BackgroundThe application of orthodontic forces causes root resorption of variable severity with potentially severe clinical ramifications.ObjectiveTo systematically review reports on the pathophysiological mechanisms of orthodontically induced inflammatory root resorption (OIIRR) and the associated risk factors based on in vitro, experimental, and in vivo studies.Search methodsWe undertook an electronic search of four databases and a separate hand-search.Selection criteriaStudies reporting on the effect of orthodontic forces with/without the addition of potential risk factors on OIIRR, including (1) gene expression in in-vitro studies, the incidence root resorption in (2) animal studies, and (3) human studies.Data collection and analysisPotential hits underwent a two-step selection, data extraction, quality assessment, and systematic appraisal performed by duplicate examiners.ResultsOne hundred and eighteen articles met the eligibility criteria. Studies varied considerably in methodology, reporting of results, and variable risk of bias judgements.In summary, the variable evidence identified supports the notion that the application of orthodontic forces leads to (1) characteristic alterations of molecular expression profiles in vitro, (2) an increased rate of OIIRR in animal models, as well as (3) in human studies. Importantly, the additional presence of risk factors such as malocclusion, previous trauma, and medications like corticosteroids increased the severity of OIIRR, whilst other factors decreased its severity, including oral contraceptives, baicalin, and high caffeine.ConclusionsBased on the systematically reviewed evidence, OIIRR seems to be an inevitable consequence of the application of orthodontic forces-with different risk factors modifying its severity. Our review has identified several molecular mechanisms that can help explain this link between orthodontic forces and OIIRR. Nevertheless, it must be noted that the available eligible literature was in part significantly confounded by bias and was characterized by substantial methodological heterogeneity, suggesting that the results of this systematic review should be interpreted with caution.RegistrationPROSPERO (CRD42021243431).

Project description:BackgroundControversial results have been reported regarding the impact of photobiomodulation (PBM) on orthodontically induced inflammatory root resorption (OIIRR). The aim of this study was to evaluate the influence of two PBM protocols, one of them requiring a high application frequency (on days 0, 3, 7, 14, then every 2 weeks), while the second requires less frequent applications (every 3 weeks), on OIIRR accompanying orthodontic treatment.MethodsTwenty female patients were recruited for this randomized controlled trial, requiring the therapeutic extraction of maxillary first premolars, and they were randomly divided into 2 equal groups. In Group A, one side of the maxillary arch randomly received PBM on days 0, 3, 7, 14, and every 2 weeks thereafter, while in Group B, one side was randomly chosen to receive PBM every 3 weeks. The laser applied was a Diode laser with a wavelength of 980 nm, in a continuous mode. Canine retraction in both groups was carried out using closed-coil springs, delivering 150 g of force, and the force level was checked every 3 weeks, over a 12-week study period. Pre-retraction and post-retraction cone-beam computed tomography (CBCT) was done for the evaluation of OIIRR.ResultsNo significant differences in the amount of OIIRR have been reported between the laser and control sides in both groups A and B. Also, no significant differences have been reported between the laser sides in both groups.ConclusionsPhotobiomodulation does not affect OIIRR, whether by increasing or decreasing its occurrence, with both laser application protocols. Therefore, it can be stated that PBM does not result in root resorption less than the commonly observed range elicited with conventional orthodontic treatment, and that it has no effect on OIIRR. Trial registration Two Low-level Laser Irradiation Protocols on the Rate of Canine Retraction (NCT04926389), 15/06/2021-retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT04926389 .

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A sustained-release Trametinib bio-multifunction hydrogel inhibits orthodontically induced inflammatory root resorption.

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