Photobiomodulation effects on periodontal ligament stem cells: A systematic review of in-vitro studies.

BACKGROUND: Stem cell therapy has been considered to play a paramount role in the treatment modalities available for regenerative dentistry. The established beneficial effects of photobiomodulation (PBM) at the cellular level have led to the combined use of these two factors (PBM and stem cells). The main goal of this study was firstly to critically appraise the effects of PBM on periodontal ligament stem cells (PDLSCs), and secondly to explore the most effective PBM protocols applied. METHODS: Pubmed, Cochrane, Scopus, Science Direct, and Google Scholar search engines were used to identify experimental in vitro studies in which PBM was applied to cultured PDLSCs. After applying specific keywords, additional filters, and inclusion/exclusion criteria, a preliminary number of 245 articles was narrowed down to 11 in which lasers and LEDs were used within the 630 - 1064 nm wavelength range. Selected articles were further assessed by three independent reviewers for strict compliance with PRISMA guidelines, and a modified Cochrane Risk of Bias to determine eligibility. STATISTICAL ANALYSIS: The dataset analysed was extracted from the studies with sufficient and clearly presented PBM protocols. Simple univariate regression analysis was performed to explore the significance of contributions of potential quantitative predictor variables towards study outcomes, and a one-way ANOVA model was employed for testing differences between the laser or LED sources of the treatments. The significance level for testing was set at α = 0.05. RESULTS: The proliferation rate, osteogenic differentiation, and expression of different indicative genes for osteogenesis and inflammation suppression were found to be positively affected by the application of various types of lasers and LEDs. With regard to the PBM protocol, only the wavelength variable appeared to affect the treatment outcome; indeed, the 940 nm wavelength parameter was found not to exert a favourable effect. CONCLUSIONS: Photobiomodulation can enhance the stemness and differentiation capacities of periodontal ligament stem cells. Therefore, for PBM protocols, there remains no consensus amongst the scientific community. Statistical analyses performed here indicated that the employment of a near-infrared (NIR) wavelength of 940 nm may not yield a significant favourable outcome, although those within the 630 - 830 nm range did so. Concerning the fluence, it should not exceed 8 J/cm2 when therapy is applied by LED devices, and 4 J/cm2 when applied by lasers respectively.

The influence of delivery power losses and full operating parametry on the effectiveness of diode visible-near infra-red (445-1064 nm) laser therapy in dentistry-a multi-centre investigation.

The development of protocols for laser-assisted therapy demands strict compliance with comprehensive operating parametry. The purpose of this investigation was to examine the accuracy of correlation between laser control panel and fibre emission power values in a selection of diode dental lasers. Through retrospective analysis using successive systematic review and meta-analysis, it is clear that there is inconsistency in the details, and possible inaccuracies in laser power applied and associated computed data. Through a multi-centre investigation, 38 semi-conductor ("diode") dental laser units were chosen, with emission wavelengths ranging from 445 to 1064 nm. Each unit had been recently serviced according to manufacturer's recommendations, and delivery fibre assembly checked for patency and correct alignment with the parent laser unit. Subject to the output capacity of each laser, four average power values were chosen using the laser control panel-100 mW, 500 mW, 1.0 W, and 2.0 W. Using a calibrated power meter, the post-fibre emission power value was measured, and a percentage power loss calculated. For each emission, a series of six measurements were made and analysed to investigate sources of power losses along the delivery fibre, and to evaluate the precision of power loss determinations. Statistical analysis of a dataset comprising % deviations from power setting levels was performed using a factorial ANOVA model, and this demonstrated very highly significant differences between devices tested and emission power levels applied (p < 10-142 and < 10-52 respectively). The devices × emission power interaction effect was also markedly significant (p < 10-66), and this confirmed that differences observed in these deviations for each prior power setting parameter were dependent on the device employed for delivery. Power losses were found to be negatively related to power settings applied. Significant differences have emerged to recommend the need to standardize a minimum set of parameters that should form the basis of comparative research into laser-tissue interactions, both in vitro and in vivo.

Effect of different types of adhesive systems on the bond strength and marginal integrity of composite restorations in cavities prepared with the erbium laser-a systematic review.

There are inconclusive results regarding etching and bonding protocol to achieve optimal bond strength and marginal integrity of adhesive composite resin restorations in erbium laser prepared cavities. This systematic review aimed to consider which adhesive system protocol may be optimal in achieving the bond strength and marginal integrity in erbium laser-prepared cavities, comparable to that obtained with conventional method of cavity preparation. This review was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement with literature search based on all publications during the period January1, 2000-October 10, 2020, in three databases: MEDLINE, Google Scholar and ScienceDirect. The necessary information was extracted by two independent authors. The search resulted in 139 articles from all databases, and a total of thirty-one articles met the inclusion criteria. The results indicated that the selection of adhesives depending on their pH and composition and the laser pulse duration and pulse energy used plays an important role in predicting the adhesion and marginal integrity. The 10-MDP containing moderate self-etch adhesives has demonstrated predictable outcomes. Longer pulse durations used for cavity preparations may indicate the use of etch-and-rinse (EnR) or moderate self-etch adhesives (SEA) to allow better resin infiltration in deep craters formed due to laser irradiation. However, further studies with more standardizations in relation to adhesives and laser parameters are needed.

A Spectrophotometric Study on Light Attenuation Properties of Dental Bleaching Gels: Potential Relevance to Irradiation Parameters.

BACKGROUND: During in-office bleaching, appropriate light sources are applied in order to enhance the activity of the bleaching gels applied onto teeth. For this method to be effective, a high absorption of light within the gel is necessary. Variation in the light attenuation capability of the gel, the duration of application and light activation can contribute towards safety hazards associated with this procedure. METHODS: In this study, seven different gels and hydrogen peroxide have been evaluated for their optical properties by means of spectrophotometry (440-1000 nm). The transmitted light spectrum was used to estimate the intensity loss for each gel. The mean intensity decreases observed were statistically analysed using an analysis of variance (ANOVA). RESULTS: The five more-pigmented gels tested indicated a very similar intensity loss of around 80%, whereas the remaining two gels showed significantly less attenuation (predominantly, p < 10-6). CONCLUSIONS: Throughout the spectrum of wavelengths examined, and according to the underlying studies evaluated, five of the gels assessed demonstrated an attenuation high enough to possibly avoid overheating of the underlying enamel dentine and pulp. An evaluation of appropriate irradiation parameters is proposed.

Laser Analgesia Associated with Restorative Dental Care: A Systematic Review of the Rationale, Techniques, and Energy Dose Considerations.

It is a common experience amongst laser dentists and patients that mid-IR wavelength application in cavity preparation may be achieved without causing any associated pain. The erbium family of lasers (Er,Cr:YSGG 2780 nm and Er:YAG 2940 nm) are frequently used without employing injectable local anesthesia as an adjunct: the phenomenon arising from the application of these devices is known as laser analgesia. This review seeks to apply a systematic approach to the examination of appropriate published studies but also to highlight the need for much more structured clinical investigations that consolidate photonic dose and methodology. A search of published data using PRISMA criteria was carried out to examine clinical trials into laser analgesia in conjunction with restorative dentistry, applying inclusion and exclusion criteria. From this, 10 published articles were selected for analysis. Suitability assessment was carried out, using a modified Cochrane risk of bias methodology. In 8/10 of the included studies, laser-induced analgesia is claimed to be better and effective, while in 2/10 of the studies, no difference was exhibited compared to the control group. Statistical analysis of three split mouth studies concluded that only one of these investigations reviewed demonstrated a significant analgesic effect for laser treatment while the other two did not support this observation. From this data, it is inconclusive to assess the predictability of laser analgesia in cavity preparation. A possible rationale and laser operating parametry has been discussed. Successful implementation of this treatment modality remains technique sensitive and subject to further investigation.

Photobiomodulation Dose Parameters in Dentistry: A Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis of published randomized controlled trials examines a possible relationship between optical spot size at surface tissue, irradiance, radiant exposure, total energy delivered, operator technique and reported clinical outcomes. BACKGROUND: Clinical photobiomodulation (PBM) therapy has achieved a high level of evidence-based acceptance in the mitigation of oral mucositis associated with cancer radiotherapy and chemotherapy, and supportive clinical research in relation to orthodontic tooth movement, oral medical conditions, including burning mouth syndrome, xerostomia and lichen planus. Inconsistent outcomes have been reported not withstanding a substantial body of primary supportive research from clinical, in vitro and animal studies. MATERIALS AND METHODS: PubMed, Cochrane Database of Reviews and Google Scholar search engines were applied to identify human clinical trials of PBM therapy in clinical dentistry. A total of 766 articles between February 2009 and June 2020 were identified and following a full text evaluation, 38 papers with sufficient data to permit analyses are included in this investigation. RESULTS: Following a detailed assessment of potential factors that may have an influence in clinical outcome, a clear trend is apparent associating optical spot size to a positive or negative effect. Furthermore, there is a clear difference in the reported results in relation to total energy applied, delivery techniques and optical parameters, which merits further investigation. Factorial statistical analyses identified an association between smaller optical surface applications and an overall lower level of reported clinical success in treating superficial and deeper targets, and correspondingly sub-surface larger target tissues were found to be more responsive to therapy by use of a larger optical surface spot size. Moreover, use of multiple small diameter probe applications was found to provide inconsistent results. CONCLUSIONS: Many factors can confound clinical success including variations in anatomy, site location, clinical condition and subject individuality. To achieve higher levels of predictable outcome, a mature appreciation of these factors, plus an expanded understanding of laser parametry, tissue volume and target depth to deliver an adequate dose within current recommended guidelines, is essential.

Systematic Review of Post-Surgical Laser-Assisted Oral Soft Tissue Outcomes Using Surgical Wavelengths Outside the 650-1350 nm Optical Window.

Objective: To explore via systematic review the validation of uneventful post-surgical healing, associated with shorter and longer laser wavelength applications in minor oral surgery procedures. Methods: From April 28 to May 11, 2020, PubMed, Cochrane Database of Systemic Reviews, and Google Scholar search engines were applied to identify human clinical trials of photobiomodulation (PBM) therapy in clinical dentistry. The searches were carried out with reference to (1) dental laser wavelengths shorter than 650 nm; (2) wavelengths localized within the 2780-2940 nm; and (3) the 9300-10,600 nm range. Selected articles were further assessed by three independent reviewers for strict compliance with PRISMA guidelines and modified Cochrane Risk of Bias to determine eligibility. Results: Using selection filters of randomized clinical trials, moderate/low risk of bias, and the applied period, and following PRISMA guidelines, 25 articles were selected and examined. A risk of bias was completed, where 11 out of 25 publications were classified as low risk of bias, and 14 out of 25 were classified as medium risk status. In total, 6 out of 13 (46% of) studies comparing the examined laser wavelengths with scalpel-based treatment showed positive results, whereas 6 out of 13 (46%) showed no difference, and only 1 out of 13 (7.7%) presented a negative outcome. In addition, 5 out of 6 (83% of) studies comparing the examined laser wavelengths with other diodes (808-980 nm) showed positive results, whereas 1 out of 6 (17%) had negative outcomes. Conclusions: A detailed and blinded examination of published studies has been undertaken, applying strict criteria to demonstrate research outcome data, which suggests positive or at worst neutral comparatives when a given laser wavelength system is used against an alternative control therapy. As such, substantiated evidence for laser surgery in delivering uneventful healing and analgesic effects, as an expression of a PBM-like (quasi-PBM) influence, has been shown.

Laser-Assisted aPDT Protocols in Randomized Controlled Clinical Trials in Dentistry: A Systematic Review.

BACKGROUND: Antimicrobial photodynamic therapy (aPDT) has been proposed as an effective alternative method for the adjunctive treatment of all classes of oral infections. The multifactorial nature of its mechanism of action correlates with various influencing factors, involving parameters concerning both the photosensitizer and the light delivery system. This study aims to critically evaluate the recorded parameters of aPDT applications that use lasers as the light source in randomized clinical trials in dentistry. METHODS: PubMed and Cochrane search engines were used to identify human clinical trials of aPDT therapy in dentistry. After applying specific keywords, additional filters, inclusion and exclusion criteria, the initial number of 7744 articles was reduced to 38. RESULTS: Almost one-half of the articles presented incomplete parameters, whilst the others had different protocols, even with the same photosensitizer and for the same field of application. CONCLUSIONS: No safe recommendation for aPDT protocols can be extrapolated for clinical use. Further research investigations should be performed with clear protocols, so that standardization for their potential dental applications can be achieved.

Photobiomodulation and Oral Mucositis: A Systematic Review.

Oral mucositis (OM) is a debilitating complication of chemotherapy, and head and neck radiotherapy. In an effort to offer the best possible advice within the limitations of published research, a systematic review with an extended discussion and commentary on dosimetry and dose delivery is presented. Using keywords as listed, Pubmed, Google Scholar and Cochrane databases were searched during a period extending from 1995 to 2019. A total of 782 abstracts were identified. A total of 50 papers were analysed, and of these, 29 satisfied criteria required for systematic review in accordance with an optimized PRISMA statement. Clinical outcome as reported was subject to analysis with respect to time of intervention, incidence and severity of oral mucositis, and pain amelioration, and a comprehensive combined univariate and multivariate statistical analysis of the methods employed was performed. Recommendations are made with respect to the timing of the intervention. Moreover, there is an extended discussion available on the treatment care rationale of photobiomodulation (PBM), and its adjunctive association with OM. In conclusion, early prophylactic application offers clear advantages in clinical management. The many studies and associated variables and covariables assessed here revealed a choice of delivery techniques, associated wavelengths and many further indices to consider with regard to the accomplishment of optical parameters. It is therefore our recommendation that clinicians use PBM as a therapy with a full and proper understanding and training in order to optimise the clinical effects achievable.

Do Lasers Have an Adjunctive Role in Initial Non-Surgical Periodontal Therapy? A Systematic Review.

(1) Background: dental lasers have numerous applications for periodontal therapy which include surgical procedures of soft tissue and osseous structures, and non-surgical treatments such as pathogen reduction, removal of surface accretions, and photobiomodulation. The aim of this review was to evaluate the scientific literature to ascertain whether lasers have a beneficial role when used adjunctively in initial non-surgical periodontal therapy. (2) Methods: A PubMed search was performed specifically for randomized clinical trials where a dental laser was used adjunctively for initial periodontal therapy on human patients published from January 2010-April 2020. The first search identified 1294 eligible studies. After additional criteria and filters were applied, 20 manuscripts were included in this review. (3) Results: The chosen manuscripts reported on investigations into initial therapy for patients diagnosed with chronic periodontitis. After periodontal charting, conventional instrumentation such as hand and ultrasonic scaling was performed on all patients in the studies, and then a test group or groups of patients were treated adjunctively with a laser. That adjunctive laser group's periodontal findings showed various degrees of improved health compared to the group treated with only conventional methods. (4) Conclusion: This systematic review found that 70% of the included studies reported significantly better outcomes in certain clinical parameters, but no improvement in others. The remaining 30% of the manuscripts reported no significant difference in any of the measurements. With consideration to correct parametry, lasers have an adjunctive role in initial non-surgical periodontal therapy.

Potential Advantages of Peroxoborates and Their Ester Adducts Over Hydrogen Peroxide as Therapeutic Agents in Oral Healthcare Products: Chemical/Biochemical Reactivity Considerations In Vitro, Ex Vivo And In Vivo.

Peroxides present in oral healthcare products generally exert favourable protective activities against the development and progression of tooth decay, plaque, gingivitis, and halitosis, etc. However, despite the high level of research focus on hydrogen and carbamide peroxides as therapeutically active (and tooth-whitening) agents, to date the use of alternative chemical forms of peroxides such as peroxoborates for these purposes has received only scant attention. Intriguingly, peroxoborate and its esters with polyols, such as glycerol, have a very diverse chemistry/biochemistry in aqueous solution, for which there is an increasing amount of evidence that it remains distinctive from that of hydrogen peroxide; such properties include self-associative and hydrolytic equilibria, and their abilities to participate in electrophile- or nucleophile-scavenging, metal ion-complexing, redox and free radical reactions, for example. Therefore, the purpose of this detailed commentary is to evaluate both differences and similarities between the molecular/biomolecular reactivities of peroxoborate species and hydrogen peroxide in vitro, ex-vivo and in vivo. It encompasses brief sectional accounts regarding the molecular heterogeneity of peroxoborates, the release of bioactive agents therefrom, and their oxidative attack on oral cavity biomolecules (the nucleophilic or electrophilic character of these oxidations are discussed). Further areas explored are the abilities of borates and peroxoborates to enhance the solubility of iron ions in aqueous solution, their involvements in free radical biochemistry (particularly the complexation of oxygen radical-promoting transition metal ions by, and antioxidant properties of, peroxoborate-polyol ester adducts), and the specific inhibition of protease enzymes. Further aspects focus on the tooth-whitening, oral malodor neutralizing, and potential mutagenic and genotoxic properties of peroxoborates, along with possible mechanisms for these processes. The abilities of peroxoborates, and peroxides in general, to modulate the activities of inflammatory mediators and vitamins, antioxidant or otherwise, are also explored.

Systematic Review on the Role of Lasers in Endodontic Therapy: Valuable Adjunct Treatment?

(1) Background: Adjunctive instruments, such as lasers have been investigated to address the risk of failure of endodontic therapy due to the complexity of the root canal system. Lasers have been used therapeutically, in direct irradiation of the root canals or adjunct to irrigants placed into the canals, in combination with a photosensitizer (antimicrobial photodynamic therapy) and in pain management (photobiomodulation). The purpose of this systematic review was to evaluate the evidence in clinical use within these three areas of therapy. (2) Methods: PubMed, Cochrane and Scopus search engines were used to identify human clinical trials regarding the use of lasers in endodontic therapy. (3) Results: After applying the keywords and additional filters, inclusion and exclusion criteria, the initial number of 1486 articles was reduced to 17. It was revealed that almost all studies (14/17) presented a statistically significant improved outcome in laser-assisted endodontic therapy, with the remaining three not showing any adverse effects. (4) Conclusions: The use of laser photonic energy of appropriate delivered parameters can be proposed as useful adjunctive when considering optimal treatment modalities in orthograde endodontics. Additionally, a tendency of research towards pain modulation in this field is developing.

Current Concepts of Laser-Oral Tissue Interaction.

Abstract: Fundamental to the adjunctive use of laser photonic energy for delivering therapy and tissue management, is the ability of the incident energy to be absorbed by target tissues. The aim of this review is to examine the differential performance of the separate components of oral hard and soft tissues when exposed to laser photonic irradiance of variable wavelengths and power values. Through an examination of peer-reviewed published data and materials, the interaction of laser photonic energy and target tissues are explored in detail. Varying laser wavelength emissions relative to anatomical structures explores the ability to optimise laser-tissue interactions, and also identifies possible risk scenarios as they apply to adjacent non-target structures. The concepts and practical aspects of laser photonic energy interactions with target oral tissues are clearly demonstrated. Emphasis was placed on optimising the minimum level of laser power delivery in order to achieve a desired tissue effect, whilst minimising the risk or outcome of collateral tissue damage.

Adjunctive Use of Lasers in Peri-Implant Mucositis and Peri-Implantitis Treatment: A Systematic Review.

BACKGROUND: The aim of this systematic review is to compare the effectiveness of lasers in the treatment of implant mucositis and peri-implantitis compared to conventional treatment (non-surgical or surgical: resective or regenerative). METHODS: Sources of PubMed, Cochrane and Google Scholar search engines were used on articles published from 1997 to 2020 in English, with selected keyword criteria applied. Nine randomized controlled trials (RCTs) were selected. RESULTS: All included studies were considered of "high quality" according to the quality assessment scale. The comparative assessment of the RCTs was done twice for each RCT based on the type of treatment and according to wavelength. There is strong scientific evidence that, regarding non-surgical treatment, adjunct laser application can provide better results only in the short term (three months). Regarding the surgical approach, the method of decontamination plays a subordinate role. All wavelengths/applications presented similar results. CONCLUSION: Within the limitations of this study, the adjunctive use of lasers in the treatment of peri-implant inflammation is effective for up to three months; there is no strong evidence regarding the long term benefit compared to conventional treatment.

Systematic Review of Orthodontic Treatment Management with Photobiomodulation Therapy.

Objective: This systematic review of published research evaluates the parameters and reported outcomes in photobiomodulation therapies (PBMTs) used in management of pain and accelerated tooth movement during orthodontic treatment. Background: Consequent to positive in vitro and animal studies, there has been considerable interest in the potential applications of PBMT to ameliorate pain and to accelerate orthodontic tooth movement. Due to the lack of consistency of wavelengths and parameters applied, there is as yet no consensus in respect of guidance for clinical use. Within the limitations of the reported literature, a digest of key outcomes and parameters is presented here to assist researchers and interested clinicians. Materials and methods: Search engines, PubMed, Google Scholar, and Cochrane, were applied to identify clinical investigations into the potential benefits of PBMTs in orthodontic management. Keywords used were "low-level laser therapy," "low-level light therapy," "photobiomodulation," "orthodontics," "pain," "tooth movement," and "randomized clinical trial ≥5 years." A total of 35 articles were identified, covering the 5-year period January 2013 to December 2018. Only human clinical trials were considered. Seventeen articles were included in this investigation and the reported parameters and outcomes were assessed and presented for comparison. Results: Seven of nine studies supported the effectiveness of PBMT to reduce or prevent pain. There was no consensus on choice of wavelength and a range of parameters were found beneficial. Of the seven tooth movement studies included, four of the seven were positive, of which two used a home-use light-emitting diode (LED) device, as opposed to a clinician-applied laser. A variety of wavelengths and parameters were found to be effective in accelerating tooth movement in the range of 20-40% compared with control. Conclusions: Due to a lack of consistency in approach, further studies are required to achieve a high level of acceptance. The clinical logistics associated with frequent applications supports the concept of patient home delivery use of LED devices, although there are insufficient studies at present to make an evidence-based determination of this type of appliance. To gain more general professional acceptance of the use of PBMT in orthodontics, a continued effort to extend the number of quality human clinical trials is required. Based on the current evidence base, further positive onward progression can be regarded as inevitable.

Systematic Review of Delivery Parameters Used in Dental Photobiomodulation Therapy.

Objective: This systematic review of published data critically appraises the consistency in the reported delivery parameters used in photobiomodulation (PBM) therapies research within clinical dentistry and makes reporting recommendations for future clinical protocols. Background: Key to the standardization of randomized clinical trials and associated peer-reviewed articles is the disclosure of all laser and light-emitting diode operating parameters. The current status shows a lack of full parameters and significantly impacts on the ability to integrate published data with current and future investigation into clinical PBM therapy. Materials and methods: Search engines, PubMed, Google Scholar, and Cochrane, were scanned for investigation into the effects of PBM therapy research within clinical dentistry. Key words "Low-Level-Laser," "PBM," "Photobiomodulation," "Oral" and "Therapy" were used and a total of 754 articles identified, spanning a period of 9 years and 1 month between February 2009 and March 2018. Only human clinical trials were considered. Fifty-two articles were included in this investigation and the reported basic delivery parameters used in PBM therapies research were considered for each clinical trial. Results: The overall reported basic delivery parameters used in PBM therapies research were too inadequate to be able to be replicated in further studies. These included parameters related to the power meter, beam cross-sectional dynamics, fluence, and wider aspects of dosimetry. Conclusions: The delivery parameters used in PBM therapy research within clinical dentistry, investigated in this study, presented a wide variation in their recording or nonrecording of all significant elements needed to have scientific validity. A constant inconsistency in delivering valid, reliable, PBM therapy doses, to target tissues was also identified. The lack of consensus in delivering a sound protocol for PBM therapy, is partly due to the lack of adequate reported materials and methods, which are essential for replication of individual studies. One way to resolve this problem is for Journals to insist on all comprehensive parameter records, used in PBM therapies, to be part of author guidelines in submitting articles of studies on PBM therapy in clinical dentistry.