Orthodontic Tooth Movement Research Articles

Comparison of various modes of acceleration of orthodontic tooth movement- A clinical study

The objective of the present study is to evaluate the effects of Micro-osteoperforations (MOPs), Corticision, Low Level Laser Therapy (LLLT) and Platelet Rich Plasma (PRP) on the rate of orthodontic tooth movement. Randomly10 patients were selected in each study group. All the studies had a split-mouth study design. All the patients were bonded with MBT 0.022 X 0.028 inch brackets and maxillary canine retraction was performed on 0.019 X 0.025 stainless steel wires with different methods of accelerating tooth movement. Data was collected from the orthodontic study models prepared from alginate impression taken at each appointment interval. The results of the study revealed that the amount of maxillary canine retraction was rapid in all the groups as compared to conventional method of orthodontic tooth movement and the results conclude thatmicro-osteoperfortaions showed better rate of accelerated orthodontic tooth movement as compared to other methods.

Efficacy of low-level laser therapy enhances the rate of canine retraction by increasing β glucoronidase and pentraxin – 3 in gingival crevicular fluid: A clinical study

The aim of the study was to evaluate the efficacy of low-level laser therapy in enhancing the rate of orthodontic tooth movement using β glucoronidase and pentraxin-3 (TNF) biomarkers in gingival crevicular fluid.A split-mouth design was used in 16 subjects (8 experimental and 8 controlled) aged 14 to 25 years, who’s maxillary first premolars were extracted. A gallium-aluminium-arsenide semiconductor diode laser (wavelength, 810 nm; energy density, 10 J/cm2; power output, 100 mW) delivered low-level laser therapy to the experimental canine undergoing distalization at 10 points. The control canine was distalized without low-level laser therapy. The experimental and control canines were distalized using a force of 150 g provided by nickel-titanium closed coil springs. Gingival crevicular fluid was collected at 5 time points from the control and experimental sides, and the levels of β glucoronidase and pentraxin-3 were analysed by enzyme-linked immuno-sorbent assay (ELISA). The rate of canine retraction was calculated by using ortho analyser software.Increased levels of β glucoronidase and pentraxin-3 were observed in the experimental canines compared with the control canines (P <0.001). Cumulative tooth movements over an 8-week experimental period were greater for the experimental canines compared with the control canines. A positive correlation existed between the β glucoronidase and pentraxin-3 levels and the amounts of tooth movement across all time intervals.Low level laser therapy in adjunct with continuous and light forces leads to increase in β glucoronidase and pentraxin-3 leading to accelerated orthodontic tooth movement.: Low-level laser therapy fastens the rate of canine retraction thus accelerating the orthodontic tooth movement. The levels of β glucoronidase and Pentraxin 5 are increased significantly after laser irradiation which aids in accelerating orthodontic tooth movement.

Effects of isotretinoin on tooth movement, orthodontically induced and non-orthodontic root resorption: A micro-CT study.

This study aims to investigate whether cumulative dose-dependent isotretinoin (Roaccutane®) could affect orthodontic tooth movement (OTM) and root resorption. Ninety male Wistar Albino rats were divided into 4 groups. While, the control (SALINE), solvent (SOYBEAN) and orthodontic drug (ISOTM) groups underwent orthodontic force, the non-orthodontic drug group (ISO) did not. The rats were administrated saline, soybean oil (SBO) and isotretinoin diluted in SBO (ISOTM, ISO) for 30 days, respectively. Six rats were euthanized in each orthodontic group. Fifty grams of orthodontic force was applied to the remaining rats' first molars using the incisors as anchorage. Six more rats in each group were euthanized on the 7th, 14th and 21st days of the force application. In the ISO group, six rats were euthanized on the 37th, 44th and 51st days of administration. Six rats that were euthanized for ISOTM on the 30th day were also used for ISO to reduce the number of rats used. Micro-computed tomography (micro-CT) and histological analysis were performed. Independent of orthodontic force, isotretinoin caused root resorption in the apical region. However, there was no statistically significant influence of isotretinoin on OTM and orthodontically induced root resorption (OIRR). Despite the lack of strong evidence supporting the orthodontically induced resorptive effect of isotretinoin, this study provided findings regarding the resorptive effects of isotretinoin on non-orthodontic root resorption. Therefore, the present results underscore the importance of close monitoring during orthodontic treatment to mitigate potential root resorption in patients who use isotretinoin because of acne complaints.

KAT6A/YAP/TEAD4 pathway modulates osteoclastogenesis by regulating the RANKL/OPG ratio on the compression side during orthodontic tooth movement

BackgroundOrthodontic tooth movement (OTM) is a dynamic equilibrium of bone remodeling, involving the osteogenesis of new bone and the osteoclastogenesis of old bone, which is mediated by mechanical force. Periodontal ligament stem cells (PDLCSs) in the periodontal ligament (PDL) space can transmit mechanical signals and regulate osteoclastogenesis during OTM. KAT6A is a histone acetyltransferase that plays a part in the differentiation of stem cells. However, whether KAT6A is involved in the regulation of osteoclastogenesis by PDLSCs remains unclear.ResultsIn this study, we used the force-induced OTM model and observed that KAT6A was increased on the compression side of PDL during OTM, and also increased in PDLSCs under compression force in vitro. Repression of KAT6A by WM1119, a KAT6A inhibitor, markedly decreased the distance of OTM. Knockdown of KAT6A in PDLSCs decreased the RANKL/OPG ratio and osteoclastogenesis of THP-1. Mechanistically, KAT6A promoted osteoclastogenesis by binding and acetylating YAP, simultaneously regulating the YAP/TEAD axis and increasing the RANKL/OPG ratio in PDLSCs. TED-347, a YAP-TEAD4 interaction inhibitor, partly attenuated the elevation of the RANKL/OPG ratio induced by mechanical force.ConclusionOur study showed that the PDLSCs modulated osteoclastogenesis and increased the RANKL/OPG ratio under mechanical force through the KAT6A/YAP/TEAD4 pathway. KAT6A might be a novel target to accelerate OTM.

Biomodulation effects induced by ultrasound stimulation in periodontal cells implicated in orthodontic tooth movement: A systematic review.

Accelerating orthodontic tooth movement (OTM) is increasingly important for shorter treatment times, which reduces periodontal risks, root resorption and dental caries. Techniques to accelerate OTM focus on stimulating bone remodelling by enhancing osteoclast and osteoblast activity and include both surgical and non-surgical methods. The therapeutic potential of ultrasounds is highly recognized among many medical areas and has shown promising results in modulating bone remodelling and inflammation phenomena. This systematic review aims to collect and analyse the current scientific invitro and exvivo evidence on ultrasound stimulation (US) bioeffects in cells implicated in tooth movement. This review was conducted according to PRISMA 2020 guidelines. A bibliographic search was carried out in the PubMed, Scopus and Web of Science databases. Sixteen articles were selected and included in this review. The revised studies suggest that US of 1.0 and 1.5 MHz, delivered at 30 mW/cm2, 10 to 30 min daily over three to 14 days seems to be effective in promoting osteoclastogenic activity, while US of 1.5 MHz, 30 to 90 mW/cm2, in 5- to 20-min sessions delivered daily for 5 to 14 days exhibits the potential to stimulate osteogenic activity and differentiation. Previous research yielded varied evidence of the effectiveness of US in orthodontics. Future animal studies should employ the recommended US parameters and investigate how distinct protocols can differentially impact tissue remodelling pathways. The knowledge arising from this review will ultimately potentiate the application of US to accelerate OTM in the clinical setting.

Influence of a Proposed Micro-Osteoperforation Approach on the Root Resorption During Orthodontic Tooth Movement: An Immuno-Histochemical Study in a Rabbit Model

Influence of a Proposed Micro-Osteoperforation Approach on the Root Resorption During Orthodontic Tooth Movement: An Immuno-Histochemical Study in a Rabbit Model

Clinical and preclinical evidence on the bioeffects and movement-related implications of photobiomodulation in the orthodontic tooth movement: A systematic review.

Photobiomodulation (PBM) has been demonstrated as a non-invasive and painless technique with great potential to accelerate orthodontic tooth movement (OTM). However, there is a great inconsistency among PBM protocols and reported outcomes, probably due to the poor translatability of preclinical knowledge into early clinical practice. Hence, this review aims to fill this gap by establishing the state-of-the-art on both preclinical and clinical applications of PBM, and by comprehensively discussing the most suitable stimulation protocols described in the literature. This review was conducted according to PRISMA guidelines. A bibliographic search was carried out in the PubMed, Scopus and Cochrane databases using a combination of keywords. Only studies written in English were eligible and no time limit was applied. A total of 69 studies were selected for this review. The revised literature describes that PBM can effectively reduce orthodontic treatment time and produce analgesic and anti-inflammatory effects. We found that PBM of 640 ± 25, 830 ± 20 and 960 ± 20 nm, delivered at a minimum energy density per irradiation point of 5 J/cm2 daily or every other day sessions is robustly associated with increased tooth movement rate. Pain relief seems to be achieved with lower irradiation doses compared to those required for OTM acceleration. For the first time, the bioeffects induced by PBM for the acceleration of OTM are comprehensively discussed from a translational point of view. Collectively, the evidence from preclinical and clinical trials supports the use of PBM as a coadjuvant in orthodontics for enhancing tooth movement and managing treatment-associated discomfort. Overall, the revised studies indicate that optimal PBM parameters to stimulate tissue remodelling are wavelengths of 830 ± 20 nm and energy densities of 5-70 J/cm2 applied daily or every other day can maximize the OTM rate, while lower doses (up to 16 J/cm2 per session) delivered in non-consecutive days seem to be optimal for inducing analgesic effects. Future research should focus on optimizing laser parameters and treatment protocols customized for tooth and movement type. By fine-tuning laser parameters, clinicians can potentially reduce treatment times, improve patient comfort and achieve more predictable outcomes, making orthodontic care more efficient and patient-friendly, thus consolidating PBM usage in orthodontics.

Validation of reliable reference genes for qPCR of CD4+ Tcells exposed to compressive strain.

For accurate interpretation of quantitative real-time PCR (qPCR) data, stable reference genes are essential for normalization of target genes. To date, there is no information on reliable housekeeping genes in CD4+ Tcells in athree-dimensional (3D) matrix under pressure stimulation. This in vitro study describes for the first time amethod for pressure stimulation of CD4+ Tcells in a3D matrix in the context of orthodontic tooth movement (OTM) and identifies aset of reliable reference genes. CD4+ Tcells were isolated from murine spleen and activated with anti-CD3/-CD28 Dynabeads (Thermo Fisher, Langenselbold, Germany) on standard cell culture plates or in 3D scaffolds with or without compressive strain. Expression stability of nine potential reference genes was examined using four mathematical algorithms. Gene expression of Il2 was normalized to all potential reference genes to highlight the importance of correct normalization. Cell proliferation and the expression of the surface markers CD25 and CD69 were also determined. The 3D matrix did not inhibit proliferation after immunological activation of Tcells and embedded the cells sufficiently to expose them to pressure load. Expression of ubiquitin C (Ubc) and hypoxanthine phosphoribosyltransferase (Hprt) was the most stable under all conditions tested. Acombination of these two genes was suitable for normalization of qPCR data. Normalization of Il2 gene expression showed highly variable results depending on the reference gene used. Pressure reduced cell proliferation and the number of CD69-positive Tcells. This study provides abasis for performing valid and reliable qPCR experiments with CD4+ Tcells cultured in 3D scaffolds and exposed to compressive forces simulating OTM.

Studying Orthodontic Tooth Movement in Mice.

Orthodontic tooth movement (OTM) represents a dynamic process in which the alveolar bone undergoes resorption at compression sites and deposition at tension sites, orchestrated by osteoclasts and osteoblasts, respectively. This mechanism serves as a valuable model for studying various aspects of bone adaptation, including root resorption and the cellular response to mechanical force stimuli. The protocol outlined here offers a straightforward approach to investigate OTM, establishing 0.35 N as the optimal force in a mouse model employing a nickel-titanium (NiTi) coil spring. Utilizing micro-computed tomography analysis, we quantified OTM by assessing the discrepancy in the linear distance at the cement-enamel junction. The evaluation also included an analysis of orthodontic-induced inflammatory root resorption, assessing parameters such as root mineral density and the percentage of root volume per total volume. This comprehensive protocol contributes to advancing our understanding of bone remodeling processes and enhancing the ability to develop effective orthodontic treatment strategies.

Periodontal Ligament Cell Apoptosis Activates Lepr+ Osteoprogenitors in Orthodontics

Alveolar bone (AB) remodeling, including formation and absorption, is the foundation of orthodontic tooth movement (OTM). However, the sources and mechanisms underlying new bone formation remain unclear. Therefore, we aimed to understand the potential mechanism of bone formation during OTM, focusing on the leptin receptor+ (Lepr+) osteogenitors and periodontal ligament cells (PDLCs). We demonstrated that Lepr+ cells activated by force-induced PDLC apoptosis served as distinct osteoprogenitors during orthodontic bone regeneration. We investigated bone formation both in vivo and in vitro. Single-cell RNA sequencing analysis and lineage tracing demonstrated that Lepr represents a subcluster of stem cells that are activated and differentiate into osteoblasts during OTM. Targeted ablation of Lepr+ cells in a mouse model disrupted orthodontic force–guided bone regeneration. Furthermore, apoptosis and sequential fluorescent labeling assays revealed that the apoptosis of PDLCs preceded new bone deposition. We found that PDL stem cell–derived apoptotic vesicles activated Lepr+ cells in vitro. Following apoptosis inhibition, orthodontic force–activated osteoprogenitors and osteogenesis were significantly downregulated. Notably, we found that bone formation occurred on the compression side during OTM; this has been first reported here. To conclude, we found a potential mechanism of bone formation during OTM that may provide new insights into AB regeneration.

Strontium ranelate modulates circular RNA BACH1/microRNA-155-5p to ameliorate root resorption and tooth anchoring during orthodontic tooth movement.

The tooth movement is a fundamental requirement during any orthodontic treatment. This study aimed to investigate the action and mechanism of strontium ranelate (SR) in orthodontic tooth movement (OTM). Rats were given SR by gavage daily, along with lentiviral vectors interfering with circBACH1 or miR-155-5p. Three weeks later, an OTM rat model was established. RANKL and osteoprotegerin (OpG) in serum were measured. The gap between the first and second molar and root resorption were examined. Osteoclast test was used; and root condition was examined. Detection of miR-155-5p, circBACH1, CLC7 and cathepsin K was performed. The binding of circBACH1 to miR-155-5p was verified. In OTM rats, circBACH1 was elevated (p<0.05) and miR-155-5p was silenced (p<0.05). SR reduced osteoclast activity (p<0.05) and improved root resorption (p<0.05) in OTM rats, which was enhanced by silenced circBACH1 (p<0.05) or elevated miR-155-5p (p<0.05). circBACH1 inhibited miR-155-5p expression (p<0.05). Silenced miR-155-5p reversed the ameliorative effect of circBACH1 on tooth root resorption in OTM rats (all p<0.05). SR modulates circBACH1/miR-155-5p to ameliorate root resorption and tooth fixation during OTM.

THE IMPACT OF LEUKOCYTE-PLATELET-RICH FIBRIN (L-PRF) ON THE ACCELERATION OF ORTHODONTIC TOOTH MOVEMENT

Objective. To determine the efficacy of leukocyte-platelet-rich fibrin (L-PRF) in orthodontics in achieving accelerated orthodontic tooth movement (OTM). Materials and methods. The search of records was carried out based on PRISMA methodological guidelines. Articles were identified using four electronic databases: PubMed, ScienceDirect, Web of Science, and Wiley Online Library. The search in selected databases was performed using combinations of the following keywords: (orthodontic tooth movement) AND (L-PRF) OR (leukocyte platelet-rich fibrin). The JBI critical appraisal tool was utilized to assess the quality of selected studies. Results. A total of 780 articles were identified. After eliminating duplicates and applying eligibility criteria, five studies were included in the review. The trials included 74 patients. Four studies showed a statistically significant increase in canine distalization with L-PRF on the experimental intervention sides compared to the control sides. However, one study indicated that L-PRF decreased the rate of OTM. The results of four studies show that L-PRF had the greatest effect on the distalization rate during the first 8 weeks; after 8 weeks, the rate of OTM decreased.

Analysis of Three-Dimensional Tooth Movement: A Comparative Study Between Digital Dental Models and Craniofacial Models.

This study aims to validate the efficacy of using a digital dental model (DM) with reference to the palatal region of interest (PROI) for assessing orthodontic tooth movement (TM)by comparing it with the analysis of a computed tomography (CT) model with reference to the cranial region of interest (CROI). Thirty-four patients (mean age: 21 years and 11 months) with jaw deformities underwent DM and CT scans before and after presurgical orthognathic treatment. Linear and angular measurements during TM were conducted in three dimensions using both DM and CT to assess reliability. DM analysis with PROI registration exhibited high levels of reproducibility, with minimal standard errors in X, Y, and Z displacements (<0.15 mm) and 0.43 degrees in angular change. CT analysis with CROI registration demonstrates similarly high reproducibility, with standard errors inferior to DM analysis (<0.20 mm). Bland-Altman analysis indicated agreement in linear changes of each X, Y, and Z displacement between DM and CT measurements, with limits of agreement (LOA) below 0.91 mm. The results of this study suggest that the PROI, focusing on the third palatal rugae and the horizontal part of the palatal vault, serves as a reliable reference region for evaluating three-dimensional (3D) tooth movement. Digital dental models offer distinct advantages including the absence of X-ray exposure, no metal artifacts, and the ability to generate high-resolution 3D models. The methodology demonstrated high precision and reproducibility, supporting its potential clinical utility in orthodontic treatment planning and assessment.

Expression patterns of interleukin-6 and microRNA-146A during orthodontic relapse in a rat model.

In this study, we established an experimental rat model to simulate orthodontic tooth movement relapse and a human periodontal ligament stem cell (PDLScs) model. Our aim was to explore the relationship between microRNA-146a (miR-146a) expression in periodontal tissue, the inflammatory factor interleukin-6 (IL-6), and orthodontic relapse subsequent to mechanical intervention. In the animal experiment, a total of 30 healthy male Wistar rats were randomly allocated to either the control group (n=6) or the model group (n=24). In the model group, the orthodontic appliance was removed 14 days after force application. Gingival crevicular fluid (GcF) and periodontal tissue samples were collected at intervals of days 0, 7, 14, and 21 following removal of the orthodontic appliance to assess alterations in miR-146a and IL-6 expressions. In the in vitro cell culture study, human premolar tooth tissue was isolated 24 hours following the addition of the transfection reagent to harvest PDLScs. Reverse transcription quantitative polymerase chain reaction was employed to evaluate the expression levels of the miRNA-146a gene, while Western blot analysis was utilized to assess the production of the IL-6 protein. As a result in comparison to the control group, the protein expression of IL-6 notably escalated to its peak value in the model-day 7 group (p<0.05). Subsequently, although experiencing a slight decline, the IL-6 expression in the model-day 14 group remained significantly elevated compared to control group (p<0.05). In the model-day 21 group, the protein expression of IL-6 approached that of the control group, with no significant difference observed (p>0.05). conversely, in relation to the control group, the gene expression of miR-146a drastically decreased to its lowest point in the model-day 7 group (p<0.05). While exhibiting a slight increase, the miR-146a expression in the model-day 14 group remained significantly diminished compared to control group (p<0.05). Following the identification of human periodontal ligament cells (hPDLcs) through immunofluorescence in the in vitro study, a subsequent experiment was conducted to specifically inhibit miR-146a expression. In comparison to the control group, the protein expression of IL-6 demonstrated a significant increase in the anti-miRNA oligodeoxyribonucleotide (AMO) group, where miR-146a expression was effectively suppressed (p<0.05). Throughout the process of orthodontic tooth movement relapse in rats, there was a notable reduction in the gene expression of miR-146a, accompanied by a significant increase in the expression of IL-6.

Staging of Orthodontic Tooth Movement in Clear Aligner Treatment: Macro-Staging and Micro-Staging—A Narrative Review

Abstract: Aims: This review aims to analyze the multiple factors affecting the staging of the orthodontic tooth movement during clear aligner treatment and to provide an efficient work methodology in this regard during digital treatment planning. Materials and Methods: A literature search was conducted on electronic databases (Pubmed, Scopus, Google Scholar and CNKI). The results of the present study have been divided into several sections: (1) definition and concept of staging, (2) basic principles of clear aligners, (3) macro-staging, (4) micro-staging, and (5) limitations. Results: The terminology of macro-staging and micro-staging proposed in this paper aims to be a first step towards a more detailed analysis of staging. The macro-staging constitutes the general biomechanics of movements that need to be prioritized to meet the objectives of the treatment plan. It provides a comprehensive view of the movements occurring in each dental arch. The micro-staging constitutes the biomechanics of movements for each individual tooth. This involves studying the movements in the different planes of space in which each tooth is programmed, deciding if they are compatible, and having strategies to create space to avoid lack of expression. Conclusions: Further studies should focus on exploring different staging approaches to address similar malocclusions to determine which are the most effective and applicable to clinical practice.

How does orthodontic tooth movement influence the dental pulp? RNA-sequencing on human premolars.

The objective of this study is to analyse the gene expression profile of the dental pulp (DP) of human premolars subjected to 7 and 28 days of orthodontic force (OF) in vivo by using RNA sequencing. The maxillary and mandibular DP were additionally compared. Healthy patients requiring orthodontic premolar extractions were randomly assigned to one of the three groups: control (CG) where no OF was applied, 7 and 28 days, where premolars were extracted either 7 or 28 days after the application of a 50-100 g OF. Total RNA was extracted from the DP and analysed via RNA-seq. Differentially expressed genes (DEGs) were identified using a false discovery rate and fold change threshold of <0.05 and ≥1.5, respectively. Functional analysis was performed. After 7 days of OF, pulp reaction indicates immune response, hypoxia, DNA damage and epigenetic regulation. After 28 days, cell adhesion, migration, organization and tissue repair are evident. The maxillary and mandibular pulp tissues react differently to OF. The maxilla exhibits minimal alterations, mostly related to immune response at 7 days and tissue repair at 28 days, whereas the mandible shows mostly DNA damage and epigenetic regulation at 7 days and return to the original state at 28 days. This study demonstrates that the early reaction of the DP to OF is marked by immune response, hypoxia and DNA damage. In contrast, after 28 days, cell adhesion, migration, organization, tissue repair and dentine formation are observed. Maxillary and mandibular premolars react differently to OF: although the maxilla exhibits minimal alterations at both time points, the mandible mostly shows DNA damage, epigenetic regulation, and immune response at 7 days. These disparities could stem from different blood supplies or the lower maxillary bone density, potentially triggering faster biological changes. Our findings provide insights into the gene regulatory networks modulating DP response to OF.

Effects of Vibration on Accelerating Orthodontic Tooth Movement in Clinical and In Vivo Studies: A Systematic Review.

This systematic review aims to assess the impact of high (>30 Hz) and low (≤30 Hz) frequency vibrations on orthodontic tooth movement (OTM). Several articles were collected through a systematic search in the databases MEDLINE and SCOPUS, following PRISMA methodology and using a PICO question. Relevant information on selected articles was extracted, and the quality of each study was assessed by the quality assessment tools EPHPP, ROBINS-1 and STAIR. Out of 350 articles, 30 were chosen. Low-frequency vibrations did not seem to accelerate OTM with aligners or fixed appliances, despite some positive outcomes in certain studies. Conversely, high-frequency vibrations were linked to increased aligner change, tooth movement, and space closure with fixed appliances. In vivo studies reported favourable results with high-frequency vibrations (60 Hz to 120 Hz), which stimulate bone biomarkers, facilitating alveolar bone remodelling. The results suggest that high-frequency vibration effectively speeds up orthodontic tooth movement, showing promise in both in vivo and clinical studies. Larger-scale research is needed to strengthen its potential in orthodontics.

AI and Conventional Techniques used for Drugs and Orthodontic Tooth Movement

Artificial Intelligence (AI) is emerging as a transformative force in both drug development and orthodontics. This paper provides an overview of key AI techniques employed in these fields. In drug development, AI is accelerating discovery, development, and delivery through generative models, predictive modeling, image analysis, and natural language processing. Orthodontics benefits from AI through image analysis, treatment planning, and patient experience enhancement. Common AI techniques in both domains include machine learning, deep learning, natural language processing, and computer vision. By leveraging these technologies, researchers and clinicians can achieve significant advancements in drug discovery, treatment efficacy, and patient care.

Enhancement of Orthodontic Tooth Movement by Local Administration of Biofunctional Molecules: A Comprehensive Systematic Review.

Enhancement of orthodontic tooth movement (OTM) through local administration of biofunctional molecules has become increasingly significant, particularly for adult patients seeking esthetic and functional improvements. This comprehensive systematic review analyzes the efficacy of various biofunctional molecules in modulating OTM, focusing on the method of administration and its feasibility, especially considering the potential for topical application. A search across multiple databases yielded 36 original articles of experimental human and animal OTM models, which examined biofunctional molecules capable of interfering with the biochemical reactions that cause tooth movement during orthodontic therapy, accelerating the OTM rate through their influence on bone metabolism (Calcitriol, Prostaglandins, Recombinant human Relaxin, RANKL and RANKL expression plasmid, growth factors, PTH, osteocalcin, vitamin C and E, biocompatible reduced graphene oxide, exogenous thyroxine, sclerostin protein, a specific EP4 agonist (ONO-AE1-329), carrageenan, and herbal extracts). The results indicated a variable efficacy in accelerating OTM, with Calcitriol, Prostaglandins (PGE1 and PGE2), RANKL, growth factors, and PTH, among others, showing promising outcomes. PGE1, PGE2, and Calcitriol experiments had statistically significant outcomes in both human and animal studies and, while other molecules underwent only animal testing, they could be validated in the future for human use. Notably, only one of the animal studies explored topical administration, which also suggests a future research direction. This review concluded that while certain biofunctional molecules demonstrated potential for OTM enhancement, the evidence is not definitive. The development of suitable topical formulations for human use could offer a patient-friendly alternative to injections, emphasizing comfort and cost-effectiveness. Future research should focus on overcoming current methodological limitations and advancing translational research to confirm these biomolecules' efficacy and safety in clinical orthodontic practice.

Evaluating the long-term stability of a predefined palatal region for tooth movement analysis

ObjectivesWe conducted a three-dimensional (3D) analysis of orthodontic tooth movement (TM) using digital dental models (DMs), focusing on the palatal region of interest (PROI), aiming to evaluate the long-term stability of the PROI, validate the 3D TM analysis with PROI registration, and compare it with conventional lateral cephalometric analyses. MethodsTwenty adult patients treated with a multibracket appliance were evaluated at their first visit (T0) and at least 5 years later (T1) using DMs and lateral cephalograms (LCs). The long-term stability of PROI was assessed by calculating the point cloud distances between DM-T0 and DM-T1. TM analysis using DM with PROI registration for the maxillary central incisors was assessed through linear and angular measurements in the sagittal view and subsequently compared with the LCs. ResultsThe average point cloud distance of the PROI between DM-T0 and DM-T1 was 0.21 mm (standard deviation, 0.13 mm). TM analysis using DMs demonstrated excellent reproducibility for both linear and angular measurements (intra-rater correlation coefficient, > 0.99). The 95 % limits of agreement between the DM and LC measurements were < 5.14° for angular change, 3.53 mm for horizontal displacement, and 0.98 mm for vertical displacement. No significant differences were observed in the angular and linear measurements when the TM was compared using the DMs and LCs. ConclusionsThe PROI remained stable for over 5 years, supporting the reproducibility and accuracy of TM assessment using PROI registration in orthodontic clinical practice. Clinical significanceDM analysis lacks the risks associated with X-ray exposure and can be easily performed in daily clinical practice, indicating its potential for future clinical applications. These findings further support the use of DM with PROI registration for TM analysis in orthodontic clinical practice, emphasizing its long-term stability and reproducibility.