Assessing the Viability of Laser-Activated Dental Bleaching Compared to Conventional In-Office Bleaching Methods: A Systematic Review of Clinical and In Vitro Studies

Abstract

Laser-activated tooth bleaching is discussed as a means to optimize results, while minimizing adverse side effects, but it lacks consensus in the scientific literature. Therefore, this systematic review aims to evaluate the protocols and outcomes of laser-activated vs. non-activated bleaching methods for safe and effective approaches. The PubMed, Cochrane, Scopus, ScienceDirect, and Google Scholar search engines, with the following MeSH terms and keywords: (bleaching OR whitening) AND laser AND (tooth OR dental OR enamel OR dentine), were used to identify human clinical trials and in vitro studies regarding laser-activated dental bleaching. After applying the keywords and additional filters, and inclusion and exclusion criteria, the final number of included articles was 19 clinical and 20 in vitro studies. Laser activation yielded no significant color improvement, but reduced gel contact time (10 min). Laser-activated bleaching required 24% less hydrogen peroxide (HP) concentration to achieve similar results. Additionally, there were no significant differences in terms of sensitivity and hard tissue alterations between the laser-activated and conventional groups. The benefits associated with laser-activated bleaching render it a compelling option. Nevertheless, a comprehensive evaluation of bleaching gels and activation protocols is imperative. Ultimately, this analysis provides clinical guidance pertaining to the facilitatory employment of laser irradiation.

1. Introduction

In recent years, a high demand for an attractive appearance and brighter smiles has led to an improvement in oral health, with marked increases in consultations at the dental office [1].

Amongst methods available for improvement, dental bleaching is a minimally invasive procedure to enhance the shade of the teeth, which can be performed at home following instruction by dental professionals, or as an in-office procedure [1,2]. In-office bleaching offers the benefit of providing immediate results, while requiring less effort on the part of the patient [3].

The mechanism of action can be described as follows: Bleaching agents such as hydrogen peroxide (HP—H₂O₂) or carbamide peroxide (CP—a 1:1 addition complex of urea with H₂O₂), of varying concentrations are applied to the tooth surface [4]. In view of its low molecular mass, HP is capable of permeating via diffusion through the interprismatic spaces in the enamel and the dentinal tubules in the dentin [5]. As HP penetrates the tooth structure, it has the ability to generate reactive oxygen species (ROS). Such ROS may directly engage with organic stain molecules or induce a chemical reaction that modifies the molecular structures of tooth pigments located inside the dentinal tubules, resulting in the formation of chemical species with altered optical characteristics [4,6,7,8,9]. In addition, the oxidation of the organic enamel matrix can contribute to the treated teeth acquiring a more “opaque” appearance [10].

The whitening effects outlined above may be accelerated through the implementation of various methods, including the use of higher concentrations of HP, an extended bleaching duration, the application of heat, and activation through light or laser systems [11]. By employing these techniques, it becomes possible to achieve higher levels of HP penetration into the dental tissue, a process consequently leading to an improved bleaching outcome [11]. In particular, the application of light or lasers during bleaching episodes has been described in the literature as a means to decrease patients’ chair time, and, more importantly, to minimize the contact time of these potentially toxic agents with dental tissues [1]. The main distinction between broad-band light and laser applications lies in the fact that ordinary light sources emit a broad spectrum, multi-wavelength photonic energy, compared to the monochromatic light characteristic of lasers [4,12]. However, this difference may constitute a higher risk of potential thermal damage with ordinary light sources [12].

In view of the transparency of HP to visible and near-infrared laser light commonly used in clinical practices, coloring agents are incorporated as absorbers within the bleaching gel to induce specific photothermal effects, resulting in increased ROS generation and improved color outcome [4]. This approach also mitigates heat-related risks to dental pulp [4,11,13]. Notably, a 10 °C temperature increase within the bleaching agent approximately doubles the rate of chemical reactions, leading to faster ROS reactions, and hence more rapid interaction with pigmented molecules within the teeth [1,4,6].

Furthermore, in terms of the photochemical effects (photodissociation), an activation of HP through direct excitation is exclusively achievable through irradiation with high-energy photons, since its dissociation energy is determined to be 2.02 eV [4,14]. Photonic energy and emission wavelength are inversely related, and therefore laser systems in wavelength ranges below 614 nm are capable of inducing this reaction [4,14,15].

Additionally, a physicochemical action may take place when specific absorbers, such as titanium dioxide (TiO₂) or carotenes (a range of photosynthetic pigments), are incorporated within the bleaching gel [14]. When exposed to light irradiation, they have the capacity to undergo modifications, resulting in changes in their electrical charges [16]. Consequently, this can lead to the destabilization of peroxides, or disruption of the pH balance of the whitening gel and hence to the generation of more reactive ROS, such as hydroxyl radical (^●OH) and/or mono-deprotonated peroxide (HO₂⁻), the latter only formed at significantly elevated pH values [14,16,17].

Evidently, laser-activated bleaching primarily relies on a photothermal reaction [1,15]. While optimizing the reaction rate and minimizing the risk of sensitivity reactions, it is crucial to exercise control over the heat transmitted to the dental pulp [15]. In consequence of the above, laser-activated bleaching may be considered a safe and effective option for achieving enhanced results [1,4,12,15].

However, it is important to emphasize that laser-activated bleaching may have the potential to alleviate the adverse effects commonly associated with this procedure [18,19].

The elements investigated in bleaching studies refer mainly to the color outcome and the sensitivity appearing coincident to, or following, the bleaching treatment [20]. The color outcome is a measure of the effectiveness of the procedure, and it remains the most critical factor for the applied treatment’s success, because of the growing aesthetic expectations of patients and dental practitioners [21]. The change in shade (ΔΕ) as defined by the Commission lnternationale de I’Eclairage (CIE) L*a*b* color system is commonly used to evaluate shade changes objectively. The shade change value ΔΕ is calculated using the equation:

ΔE = ([ΔL*]² + [Δa*]² + [Δb*]²)^½

(1)

where L* represents lightness, a* corresponds to the red–green, and b* corresponds to the yellow–blue axes [22,23]. In this regard, a mean color change value (ΔΕ) exceeding 3.3 is regarded as clinically significant. This threshold underscores the importance of achieving substantial color improvements to meet the demands of modern dental care [22,23]. The evaluation by instruments such as spectrophotometers, in addition to subjective visual assessments, is supported by the scientific literature since they offer a reliable and repeatable method for measurement [24].

Tooth sensitivity is a main concern, however, and may arise through selected pathways: (1) as a direct activation of neuronal receptors, or (2) through fluid shifts within the odontoblasts caused by desiccation or penetration of free radicals [25]. The exposure of pulp tissue to HP remains a subject of consideration. This occurs by inward diffusion through the odontoblasts [26]. The presence of HP and, further, more reactive ROS, may induce oxidative stress in the dental pulp tissue [25,26]. Oxidative stress is associated with various cellular alterations, which have the potential to induce apoptosis, and can result in cell death [27]. Fortunately, defense mechanisms such as enzymes within the pulp and the positive pulp pressure may reduce these phenomena [25]. The quantity of HP identified in the pulp chamber typically shows a tendency to rise proportionately with both the duration of exposure, and the concentration of HP in the bleaching gel [25,26,27].

Additionally, direct overheating of the pulp tissue may play a crucial role in the occurrence of bleaching sensitivity [25,28,29]. The critical threshold for a temperature increase is 5 °C for a duration of one minute, after which pulp vitality may be jeopardized [30]. The extended application of heat, even at temperatures of around 40 °C (as experienced during lamp-activated bleaching), has the potential to impact the health of the dental pulp [29,31]. During laser-activated bleaching, however, the temperature increase is brief, typically lasting around 30 s [31,32,33]. This allows sufficient time for the pulp tissue to relax, and when the irradiation parameters are appropriately combined with suitable absorbers in the bleaching gels, it is unlikely to give rise to any adverse events [15,34].

Furthermore, direct contact between the bleaching products and oral soft tissues can cause irritation. The “caustic” nature of the bleaching agents can result in soft tissue irritation, including gingival ulcers, erosions, and changes in the periodontal tissue [35]. By implementing a gingival barrier, and carefully isolating the soft tissues, this risk can be significantly reduced, ensuring a safer and more comfortable bleaching procedure for the patient [25,36]. Application of antioxidant gels (i.e., those containing Vitamin E) or neutralizing agents (sodium bicarbonate) has been proposed for an immediate alleviation of these symptoms [36].

Further concerns arise regarding potential side effects on dental hard tissue. The main alterations observed in enamel during the bleaching process include modifications in morphology, surface porosity, and roughness, alterations in organic content, and a decrease in microhardness [37]. These adverse effects are dependent on the composition of the bleaching gels, the concentration of peroxide, pH value, bleaching technique protocols, and the length of application. Scientific evidence is controversial, typically reporting mild-to-moderate changes where the majority of the studies are conducted in vitro [38,39], The presence of saliva and fluoride in the oral cavity plays a significant role on remineralization [40]. Thus, in situ studies reveal minimal enamel alterations in view of saliva’s beneficial role in the remineralization process [41,42]. Implementing shorter contact times and less acidic gels in bleaching protocols can effectively reduce potential side effects on tooth structure [43].

Moreover, there is a concern regarding the possibility of systemic exposure to HP and its by-products [25]. Inherent defense mechanisms at the cellular and tissue levels offer protection against potential damage caused by HP during oxidative reactions, and also facilitate the repair of any resulting damage [28]. These defense mechanisms rely on the action of enzymes such as catalase, superoxide dismutase (SOD), and peroxidase, which are naturally present in saliva, tissues, and organs [25,28]. By promoting the conversion of HP into water and oxygen, these enzymes help maintain a balance of ROS within the human body [25]. This balance is essential for cellular and tissue health, since excessive levels of ROS may lead to oxidative stress, and cell and tissue damage arising therefrom [25]. Nevertheless, a systemic exposure during in-office bleaching with reduced contact times and proper isolation techniques is rather insignificant [25].

The potential advantages of laser activation of bleaching materials have not been widely embraced by the scientific community, even though numerous studies have been performed over many years [11,12,44,45,46]. Acceleration of the bleaching procedure, shortening of the gel–tissue interaction time, and a more efficient and targeted production of ROS, along with reductions in side effects, are some of the possible benefits declared [1,47]. There is inconsistency of study findings which can be attributed to the diverse study designs, variations in whitening materials utilized, and the usage of differential activating lights [40]. With regard to laser-activated bleaching, it should be noted that, even with the use of similar devices, there can be discrepancies in parameter selection and power output, which further contribute to the inconsistencies observed [48]. In order to develop suitable protocols, it is essential to have a thorough understanding of laser–tissue interaction fundamentals, knowledge of laser safety, and comprehensive clinical training. These prerequisites may ensure the proper application of lasers in dental procedures [49].

Consequently, the aim of this systematic review is to critically scrutinize the protocols applied in laser-activated, compared with non-laser-activated, bleaching methods, and to evaluate their outcomes. This involved the exploration of several key factors, including the comparison of laser application with non-activated methods, evaluating the influence of photonic fluence on outcomes and potential sensitivity issues, defining a safe fluence range, assessing the impact of specific handpieces, studying the differences between “high-power” and “low-power” groups in terms of color and sensitivity, investigating the effect of irradiation wavelength applied, understanding the relationship between higher concentrations of active ingredients (HP) and outcome, and considerations of the significance of HP interaction times. These elements are crucial for the pursuit of an optimized dental bleaching protocol.

2. Materials and Methods

2.1. Protocol and Registration

The protocol of the present study was registered with the International Prospective Register of Systematic Reviews (PROSPERO—CRD42022306443) and followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement for reports [50].

The Review questions are:

• Is laser-activated dental bleaching a favorable alternative compared to conventional in-office bleaching?
• Which laser wavelengths, parameters, and gel concentrations are applied during these applications? An evaluation of both clinical and in vitro studies will be performed to explore this.

2.1.1. PICOS Questions for Clinical Studies [51]

• Participant (P): adult patients who underwent vital tooth bleaching treatment.
• Intervention (I): laser-activated in-office bleaching procedures.
• Control (C): conventional in-office bleaching and/or at-home bleaching or different active substance concentrations.
• Outcome (O): color change or intensity of sensitivity after dental bleaching.
• Study Type (S): clinical studies.

2.1.2. PICOS Questions for In Vitro Studies

• Participant (P): extracted human teeth.
• Intervention (I): laser-activated bleaching procedures.
• Control (C): conventional bleaching or different active substance concentrations.
• Outcome (O): color change, morphology, tooth demineralization or micro-hardness changes, pulp/gel temperature changes.
• Study Type (S): in vitro studies.

2.2. Search Strategy

An electronic search was performed relating to the effects of laser-activated dental bleaching. Databases used were PubMed, Cochrane, Scopus, ScienceDirect, and Google Scholar with the following MeSH terms and keywords: (bleaching OR whitening) AND laser AND (tooth OR dental OR enamel OR dentine) published after 2010. The last search for possible recently published papers was performed in July 2023.

The initial articles retrieved numbered 1001 and were allocated per database as follows:

• Pubmed n = 259.
• Cochrane n = 85.
• Scopus n = 238.
• Science Direct n = 204.
• Google Scholar n = 215.

After removing 764 duplicate reports and ineligible clinical trial registrations, 237 studies remained.

Subsequently, following the exclusion of 114 irrelevant studies, titles and abstracts of the articles were independently screened by two reviewers (E.A. and V.M.) via application of the inclusion and exclusion criteria listed below. In the case of any disagreements arising, these were resolved by discussions between the researchers involved.

Inclusion criteria:

• Articles in English language.
• Laser activation by wavelengths in the range of 445–980 nm.
• Clinical studies on vital teeth of adult patients.
• In vitro studies using human teeth.
• Control group; conventional non-activated in-office bleaching.
• At least 10 patients/samples per group.
• Sufficient protocol description.

Exclusion criteria:

• Review papers or systematic reviews.
• Conference papers.
• Book chapters.
• Editorials.
• Short notes.
• Articles in press.
• Language other than English.
• Experimental studies not focused on teeth.
• No conventional bleaching control group.
• No laser applied as activation medium.
• Laser applied out of wavelength range 445–980 nm.
• Non-vital teeth/internal bleaching.
• Animal studies.
• Incomplete parameters described.
• Case series/pilot studies/less than 10 samples.
• Use of bovine teeth.
• Studies not retrievable.

After implementation of these criteria, the remaining 123 articles were further reduced to 38.

Additionally, one study was included via manual citation searching from the above articles.

Eventually, 39 studies were included in this systematic review.

Regarding the nature of the articles, these studies could be further sub-divided as shown:

• Clinical studies: 19.
• In vitro studies: 20.

In accordance with the PRISMA 2020 statement [50], details of the selection criteria are presented in Figure 1.

2.3. Data Extraction

After having reached a consensus on included studies, the full paper files were transferred into the reference manager software Mendeley desktop version 1.19.8 (https://www.mendeley.com/ accessed on 28 August 2023). Data were independently extracted by the same two reviewers (E.A. and V.M.) based on the following factors:

Clinical studies:

• Origin.
• Number of patients in test/control groups.
• Randomization/blinding.
• Aim of study/examination method.
• Gel parameters: H₂O₂ concentration/gel layer thickness/gel contact time.
• Laser wavelength applied.
• Laser application parameters.
• Fluence (originally noted or calculated).
• Outcome (Statistical significance).

In vitro studies:

• Origin.
• Number of samples in test/control groups.
• Randomization.
• Aim of study/examination method.
• Gel parameters: H₂O₂ concentration/gel layer thickness/gel contact time.
• Laser wavelength applied.
• Laser application parameters.
• Fluence (originally noted or calculated).
• Temperature increase (ΔΤ).
• Outcome (statistical significance).

In the case of missing data, the principal investigators/authors of the study reports concerned were contacted for clarification or additional details.

The extracted data were inserted into two tables (clinical and in vitro) for further evaluation, and in case of any disagreements, these were resolved by discussions between the researchers involved.

2.4. Quality Assessment

Risk of bias assessment of all included articles was performed following data extraction by the same two reviewers (E.A. and V.M.) independently. The Cochrane risk of bias tool [52] was modified according to the requirements of this systematic review. Two tables of risk of bias were created concerning the nature of the studies (clinical and in vitro). In both cases, the risk of bias was determined according to the number of “yes” or “no” responses to the questions provided below, which were allocated to each study.

Regarding the clinical studies the variables evaluated were:

• Randomization.
• Sample size calculation and required sample number included.
• Control group treated with conventional non-activated bleaching method available.
• Blinding.
• Parameters of bleaching gels appropriately described.
• Parameters of laser use appropriately described, and associated calculations correct.
• Power meter for calibration of the laser used.
• Numerical results available (statistics).
• Outcome data complete.
• Correct interpretation of data acquired.

Regarding the in vitro studies, the respective variables evaluated were:

• Randomization.
• Sample size calculation and required sample number included.
• Control group treated with conventional non-activated bleaching method available.
• Standardization of the samples.
• Parameters of bleaching gels appropriately described.
• Parameters of laser use appropriately described, and associated calculations correct.
• Power meter for calibration of the laser used.
• Numerical results available (statistics).
• Outcome data complete.
• Correct interpretation of data acquired.

In both cases, the classification was performed according to the total number of “yes” answers to the above questions. The degree of bias was computed according to the score limits provided below:

• High risk: 0–4.
• Moderate risk: 5–7.
• Low risk: 8–10.

In case of any disagreements arising, these were resolved by discussions between the researchers involved.

2.5. Strategy for Data Analysis

Qualitative and quantitative statistical analyses were performed for both study categories, as explained below.

(a) Regarding the clinical studies:

• Analysis of aims of studies and respective evaluation methods.
• Outcome assessment.
• Evaluation of gel and laser application protocols from the studies showing a positive outcome.

(b) Regarding the in vitro studies:

• Analysis of aims of studies and respective evaluation methods.
• Outcome assessment.
• Evaluation of gel and laser application protocols from the studies showing a positive outcome.

2.6. Statistical Analysis

The objective was to employ suitable statistical analysis models to determine the significance and magnitude of variable contributions towards differences observed between standard (control) and laser-enhanced tooth-whitening processes for the aims of tooth-whitening efficacy and tooth sensitivity in the clinical, and tooth-whitening efficacy and enamel/dentine morphology alterations, in the in vitro studies. For both categories, data originating from the included studies were inserted into a Microsoft Excel software module spreadsheet, version 16.71 for a Mac (Microsoft Corporation, Redmond, Washington, DC, USA), and further evaluated by statistical analysis using XLSTAT2020 software version 22.4 (Addinsoft, New York, NY, USA; www.xlstat.com, accessed on 28 August 2023).

For both clinical and in vitro studies, the data processing and transformations were the following:

Dependent (Output) Variables:

• +1 (Test Group More Effective than Control Group for Study).
• 0 (No Difference Observed Between Test and Control Groups for Study).
• −1 (Control Group More Effective than Test Group for Study).

Independent (Explanatory) Variables:

• Test Group minus Control Group difference in median H₂O₂ doses or levels.
• Test Group minus Control Group difference in gel contact times.
• Fluence.

The median H₂O₂ dose levels were classified as follows: 1 = 5–9%, 2 = 10–19%, 3 = 20–29%, 4 = 30–39%.

2.6.1. Clinical Studies

For the analysis performed on the potential quantitative “predictor” variables, primarily one-way (completely randomized design) analysis-of-variance (ANOVA) was performed in a univariate context in order to test the significance of outcome-mediated differences between the three “predictor” variables, specifically: (1) the above (test group—control group) difference in median H₂O₂ dose levels (w/v%), (2) the (test group—control group) difference in gel contact times (minutes), and (3) the fluence (J/cm²) applied, with a total of three separate ANOVA models applied for each of these predictor variables. This approach was applied for both Aims 1 and 2 (tooth-whitening efficacy and tooth sensitivity respectively for the clinical studies).

However, for the qualitative “predictor” variables evaluated, the above model was adapted for use as its non-parametric version, i.e., the Kruskal–Wallis test, again with the above dependent variable representing outputs of +1, 0, and −1. These qualitative variables were wavelength and handpiece size, and were only relevant to the laser treatment groups.

All study variables were weighted according to the total sample size of the study conducted.

2.6.2. In Vitro Studies

Data processing and transformations, together with statistical analyses of these datasets, were performed as described for the clinical studies above. However, the outcomes evaluated were tooth-whitening efficacy and enamel/dentine morphology alterations, where morphology alterations include or are indicated by changes in microhardness, roughness, permeability, adhesion, chemical stability, and caries susceptibility. As for the sensitivity parameter, the exploration of this outcome is not applicable, in view of the in vitro nature of the studies considered here.

3. Results

3.1. Primary Outcomes

The primary goals of this systematic review were:

(a) to evaluate the efficacies of laser-activated dental bleaching compared to those of conventional in-office bleaching procedures, both clinically and in vitro, and (b) to critically appraise the laser bleaching protocols.

3.2. Data Presentation

The extrapolated data appraised for the clinical and in vitro studies are presented in

Table 1. Extrapolated data for the clinical studies.

Citation [Ref.]	Type of Study/nr of Patients Test/Control	Aim	Gel/Layer Thickness/Contact Time	Laser Wavelength (nm)/Manufacturer	Parameters	Fluence (J/cm2)	Outcome
Gurgan, S. [53]	40 patients 4 groups (n = 10) (a) Conventional OpB (non-activated) (b) LW10 + 810 (c) RemeWhite + PAC (d) By-White + LED	Evaluation of the efficiency of in-office bleaching systems with different light sources for color change, tooth sensitivity, and gingival irritations	(a) 38% HP Opalescence Boost (45 min) (b) 37% HP Laserwhite10 (16 min) (c) RemeWhite 35% HP (60 min) (d) By-White 38% HP (40 min) All 1 mm layer	810 (Biolase Lasersmile)	10 W 15 s 2.8 cm2 (quadrant handpiece)	46	Laser group: statistically higher ΔE values and significantly lower tooth and gingival sensitivity scores
Polydorou, O. [54]	60 patients 3 groups (n = 20) (a) 38% HP conventional (non-activated) (b) 38% HP + halogen (c) 38% HP + 980	Evaluation of color stability of vital bleaching using a halogen unit, laser, or only chemical activation up to three months after treatment	38% HP Opalescence Boost (Ultradent) Thickness not mentioned 4 × 15 min (including 4 × 30 s activation for laser group and 4 × 8 min for halogen group)	980 (Kavo Gentleray)	6 W 30 s kavo 5 mm diameter handpiece 0.33 cm2 spot Single-tooth handpiece	180	Immediate result: laser-group sign less than other groups, while halogen sign better After 3 months: no difference between groups 4/20 patients from the laser group had to discontinue due to sensitivity and were evaluated at the point they stopped
Ahrari, F. [55]	60 patients 4 groups (n = 15) (a) 20% CP home bleaching 14 days (b) 34% HP + 810 (c) 34% HP + PAC (d) 34% HP conventional in-office (non-activated)	Evaluation of the efficacy and complications of bleaching methods in patients with discolored teeth after orthodontic treatment	34% HP Laserwhite10 (Biolase) (20 min) 34% HP Everbrite (40 min) 38% HP Opalescence Boost (40 min) All 1 mm layer 20% CP home bleaching (4 h × 14 days)	810 (Gigaa)	3 W 30 s per tooth 400 μm fiber 1 mm distance scanning movements of approximately 5 mm/s Single-tooth bare-fiber	88	Tooth color ΔΕ: no difference 1 w after Tooth sensitivity: significantly higher in conventional compared to laser group. In other groups no difference Satisfaction scores: no significant difference
Surmelioglu, D. [56]	45 patients 3 groups (n = 15) (a) 38% HP conventional (OpB) (non-activated) (b) 35% HP + 980 (c) 35% HP + Er,Cr:YSGG	To compare the effectiveness, color stability, and postoperative sensitivity after conventional, diode-activated, or Er,Cr:YSGG-laser-activated bleaching	35% HP WhitenessHP Blue (980—2 × 15 min) (Erbium 20 min) 38% HP Opalescence Boost (2 × 20 min) All 2 mm layer	980 (Gigaa Cheese)	7 W 12 s 5.85 cm2 spot 5 mm distance (quadrant handpiece)	14.3	ΔΕ: no significant intergroup differences Sensitivity: diode 980 nm sign higher at 24 h and 1 week
Sürmelioğlu, D. [57]	48 patients 3 groups (n = 16) (a) Ozone bleaching (b) 38% HP conventional (c) 38% HP + 980	To determine the oxidative DNA damage biomarker levels in serum, saliva, and gingival crevicular fluid (GCF) by measuring 8-hydroxy-20-deoxyguanosine (8-OHdG) after different bleaching methods	38% HP Opalescence Boost (Ultradent) 1 mm thickness Conventional (45 min) Laser-activated (30 min) Ozone (60 min)	980 (Gigaa Cheese)	7 W 12 s 5.85 cm2 spot 5 mm distance (quadrant handpiece)	14.3	Biomarkers in blood and serum: no difference Biomarkers in GCF: sign higher in order Conventional > laser > ozone Color outcome: no difference
Oz, O.P. [58]	80 patients 4 groups (n = 20) (a) Nd:YAG + 38% HP (b) 810 + 38% HP (c) LED + 38% HP (d) Conventional 38% HP	To investigate the effectiveness of different light activation methods on color change duration and tooth sensitivity	38% HP Opalescence Boost (Ultradent) 1 mm thickness All groups 3 × 15 min contact time	810 (Gigaa Cheese)	4 W 18 s 5.85 cm2 spot 1 cm distance (quadrant handpiece)	12.5	Tooth color: no difference (except 6 months after where conventional sign less rebound) Sensitivity: no difference
de Freitas, P.M. [59]	22 patients 1 group split-mouth (n = 22) Hemiarches: 35% HP conventional vs. 35% HP + 810-470 hybrid	Influences of hybrid light source (LED/laser) on temperature of enamel surfaces during 35% (HP) bleaching, Effectiveness, and tooth sensitivity	35% HP Lase Peroxide Sensy (DMC) Conventional (3 × 15 min) Hybrid (3 × 8 min) All 1–2 mm layer	810-470 (Hybrid light, Whitening Lase II, DMC)	810 nm diode 60 s × 300 mW/cm2 simultaneously 470 nm 60 s × 300 mW/cm2 (Full-arch applicator)	18 18	Effectiveness or sensitivity: no difference Temperature on gel/enamel: sign higher for LED/laser (approx 4 °C)
Kossatz, S. [60]	30 patients 2 groups (n = 15) (a) 35% HP + 810-470 hybrid (b) 35% HP conventional	Evaluation of bleaching effectiveness (BE) and tooth sensitivity (TS) during in-office bleaching with LED/laser activation vs. conventional non-activated in-office bleaching	35% HP Whiteness HP Maxx (FGM Dental) 1 mm layer 3 × 15 min both groups	810-470 (Whitening Lase Light Plus, DMC)	810 nm diode 60 s × 200 mW/cm2 simultaneously 470 nm 60 s × 350 mW/cm2 (Full-arch applicator)	12 21	Color change: sign faster for LED/laser group after first session, no difference after the second Sensitivity: no difference immediately after, but persisting sign longer for the LED/laser group
Mena-Serrano, A.P. [61]	76 patients 4 groups (n = 19) (a) 35% HP conventional (b) 35% HP + 810-470 hybrid (c) 20% HP conventional (d) 20% HP + 810-470 hybrid	Comparison of bleaching efficacy and tooth sensitivity of two hydrogen peroxide concentrations (20% and 35%) used for in-office bleaching associated or not with light activation	35% HP Whiteness HP Maxx (FGM Dental) 20% HP Whiteness HP (FGM Dental) All 1 mm layer 3 × 15 min for all groups	810-470 (Whitening Lase Light Plus, DMC)	810 nm diode 60 s × 200 mW/cm2 simultaneously 470 nm 60 s × 350 mW/cm2 (Full-arch applicator)	12 21	Color change and sensitivity: no difference
Mondelli, R.F. [62]	48 patients 5 groups (n = 16) split-mouth design (a) 35% HP + 810-470 hybrid (b) 35% HP conventional (c) 38% HP + 810-470 hybrid (d) 38% HP conventional (e) 15% CP home-bleaching	Evaluation of tooth sensitivity, ΔE and bleaching maintenance after 2 years, and comparison of effectiveness of at-home and in-office bleaching techniques, with and without activation with hybrid LED/laser light	35% HP Lase Peroxide Sensy (DMC) 38% HP Opalescence Boost (Ultradent) Hybrid (3 × 11 min) Conventional (3 × 15 min) All 1 mm layer	810-470 (Hybrid light, Whitening Lase II, DMC)	810 nm diode 180 s × 200 mW/cm2 simultaneously 470 nm 180 s × 350 mW/cm2 (Full-arch applicator)	36 63	ΔΕ: no differences between LED/laser and conventional groups. Home-bleaching group sign better Sensitivity: no differences
Mondelli, R.F.L. [63]	20 patients 4 groups (n = 10) split-mouth (a) 35% HP conventional (b) 35% HP + 810-470 hybrid (c) 25% HP conventional (d) 25% HP + 810-470 hybrid	Evaluation of effectiveness of a hybrid light (HL) source on the color change, stability, and tooth sensitivity in patients submitted to different in-office bleaching (25 and 35%)	35% H2O2 Lase Peroxide Sensy (DMC) 25% HP Lase Peroxide Sensy II or Whiteness (DMC) Conventional (3 × 15 min) Hybrid (3 × 7.5 min) All 1–2 mm layer	810-470 (Hybrid light, Whitening Lase II, DMC)	810 nm diode 120 s × 200 mW/cm2 simultaneously 470 nm 120 s × 350 mW/cm2 (Full-arch applicator)	24 42	ΔΕ: no differences Sensitivity: sign lower in LED/laser groups
Moncada, G. [64]	87 patients 3 groups (a) 15% HP with TiO_N + 810-470 hybrid (n = 25) (b) 35% HP (LPS) + 810-470 hybrid (n = 27) (c) 35% HP (WGO) conventional (n = 35)	To determine the relationship among tooth sensitivity, light activation, and agent concentration and to correlate dental sensitivity with tooth thickness in the application of three different bleaching systems	35% HP Lase Peroxide Sensy (DMC) (30 min) 15% HP with TiO_N (45 min) 35% HP White Gold Office (Dentsply) (45 min) All 1–2 mm layer	810-470 (Hybrid light, Whitening Lase II, DMC)	810 nm diode 60 s × 450 mW/cm2 simultaneously 470 nm 60 s × 300 mW/cm2 (Full-arch applicator)	27 18	Sensitivity: no difference and no effect of tooth thickness
Bortolatto, J.F. [65]	40 patients 2 groups (a) 15% HP with TiO_N + 810-470 hybrid (n = 12) (b) 35% HP Conventional (n = 13)	Compare the efficacy and tooth sensitivity of LED/laser activated 15% H2O2 gel with TiO_N (HP15) vs. conventional 35% H2O2 (HP35)	15% HP with TiO_N Lase Peroxide Light (DMC) 3 × 16 min 35% HP Lase Peroxide Sensy DMC) 3 × 15 min All 1–2 mm layer	810-470 (Hybrid light, Whitening Lase II, DMC)	810 nm diode 60 s × 300 mW/cm2 simultaneously 470 nm 60 s × 300 mW/cm2 (Full-arch applicator)	18 18	Color ΔΕ: LED/laser group sign better Sensitivity: LED/laser group sign less
Karaarslan, E.S. [66]	10 patients 4 groups (n = 10 premolars) Split mouth (a) 38% HP + 940 (b) 35%HP + halogen (c) 35% HP conventional (d) negative control	To compare the potential effects of the three different bleaching methods on proteolytic activities (cathepsin B, MMPs) and ROS designation responses of the human premolar dentin–pulp complex	38% HP Laserwhite20 (Biolase) Thickness n/a (2 × 9 min) 35% HP Whiteness HP Maxx (FGM Dental) Thickness n/a Halogen: (4 × 30 s, interval 3 min between activations) Total 15 min Conventional: Total 15 min	940 (Biolase EzLase)	7 W 30 s 2.8 cm2 (Quadrant)	70	Cathepsin B and MMP: no differences in dentin, pulp, and between dentin and pulp ROS in dentin: sign higher in laser and halogen group ROS in pulp: no differences Total ROS in dentin sign higher than in pulp
De Almeida, L.C.A.G. [67]	40 patients 4 groups (n = 10) (a) 10% CP home-bleaching (b) 35% HP conventional (c) 35%HP + halogen (d) 35% HP + 810-470 hybrid	Comparison of the effect of CP (at-home) and HP (in-office) bleaching gels, with or without halogen light or LED/laser irradiation on the occurrence, duration, intensity, and location of tooth sensitivity	35% HP (Whiteness HP, FGM, Brazil) Thickness n/a 3 × 10 min (three sessions-once per week) 10% CP (Whiteness Perfect, FGM, Brazil 4 h per day/21 days	810-470 (Hybrid light, Whitening Lase II, DMC)	810 nm diode 180 s × 200 mW/cm2 simultaneously 470 nm 180 s × 120 mW/cm2 (Full-arch applicator)	36 21	Duration of sensitivity and pain intensity: sign lower in home bleaching. No differences in other groups.
De Almeida, L.C.A.G. [68]	40 patients 4 groups (n = 10) (a) 10% CP home-bleaching (b) 35% HP conventional (c) 35%HP + halogen (d) 35% HP + 810-470 hybrid	To compare the effectiveness and color stability of at-home and in-office bleaching techniques and to evaluate whether the use of light sources can alter bleaching results	35% HP (Whiteness HP, FGM, Brazil) Thickness n/a 3 × 10 min (three sessions-once per week) 10% CP (Whiteness Perfect, FGM, Brazil) 4 h per day/21 days	810-470 (Hybrid light, Whitening Lase II, DMC)	810 nm diode 180 s × 200 mW/cm2 simultaneously 470 nm 180 s × 120 mW/cm2 (Full-arch applicator)	36 21	Color change: no differences Color stability: no differences after 6 months For clinically sign color changes: >1 week home bleaching or 30 min session of in-office bleaching with 35% HP
Mondelli, R.F.L. [69]	34 patients 4 groups (n = 17) Split mouth (a) Acid-etched 35% HP + 810-470 hybrid (b) non-etched 35% HP + 810-470 hybrid (c) Acid-etched 35% HP conventional (d) Non-etched 35% HP conventional	Evaluation of the efficiency of a HL, with and without prior enamel acid etching, assessing the gel application time, degree of color change, sensitivity, and treatment stability up to 12 months	35% HP (Lase Peroxide Sensy, DMC, Brazil) Layer 1 mm LED/laser 3 × 8 min Conventional 3 × 15 min	810-470 (Hybrid light, Whitening Lase II, DMC)	810 nm diode 180 s × 200 mW/cm2 simultaneously 470 nm 180 s × 350 mW/cm2 (Full-arch applicator)	36 63	Contact time: sign less with the order: acid-etched LED/laser <non-etched LED/laser < conventional groups. ΔΕ and sensitivity: no differences
Bortolatto, J.F. [70]	40 patients 2 groups (n = 20) (a) 35% HP conventional (b) 35% HP + 810-470 hybrid	Evaluation of LED/laser irradiation on the efficiency and tooth sensitivity of in-office bleaching treatment	35% HP (Lase Peroxide Sensy, DMC, Brazil) Thickness n/a LED/laser 4 × 8 min Conventional 3 × 15 min Three sessions-once per week	810-470 (Hybrid light, Whitening Lase II, DMC)	810 nm diode 60 × 300 mW/cm2 simultaneously 470 nm 60 s × 300 mW/cm2 (Full-arch applicator)	18 18	Luminosity (ΔL) and color change (ΔΕ): no differences Sensitivity: sign lower for LED/laser
Bersezio, C. [71]	31 patients 2 groups (n = 31) Split-mouth (a) 6% HP with TiO_N + 810-470 hybrid (b) 35% HP conventional	Evaluation of the longevity and effects on QoL of hybrid-light activated 6% hydrogen peroxide with titanium dioxide nanoparticles compared with non-activated 35% H2O2	6% HP with TiO_N (Lase Peroxide Light, DMC, Brazil) Thickness n/a 2 × 12 min 35% HP (Lase Peroxide, DMC, Brazil) Thickness n/a 2 × 12 min Three sessions-once per week	810-470 (Hybrid light, Whitening Lase Plus, DMC)	810 nm diode 60 s × 300 mW/cm2 simultaneously 470 nm 60 s × 300 mW/cm2 (Full-arch applicator)	18 18	Color outcome and longevity: no differences up to 24 months

and

Table 2. Extrapolated data for the in vitro studies.

Citation [Ref.]	Number of Samples Test/Control	Aim	Gel/Layer Thickness/Contact Time	Laser Wavelength (nm)	Parameters	Fluence (J/cm2)	Temperature ΔΤ (°C)	Outcome
Suresh, S. [72]	40 human tooth slices Groups: (a) 5 samples negative control (b) 5 samples positive control (Acid etching) (c) 10 conventional (d) 10 LED-activated (e) 10 laser-activated	Effect on mineral content and surface topography by EDX and SEM	35% HP Laserwhite20 Layer n/a (17 min) 35% HP PolaOffice (24 min) 37.5% HP PolaOffice+ (24 min)	940	7 W 30 s 2.8 cm2 Quadrant handpiece	70	Not tested/not within the aim	SEM: mild surface alterations seen in group d (LED) and group e (laser). Group c (non-act) partial removal of aprismatic layer with shallow erosions. Mineral content: calcium significantly higher in laser group phosphorus similar
Cevval Ozkocak, B.B. [73]	180 human incisors 18 groups (n = 10 per group) Control (conventional) Laser-activated Each subgroup with three different adhesive procedures and two different waiting times (immediate/7d)	Effect on shear-bond strength of different adhesive systems to enamel and SEM examination of adhesive enamel interface microscope	35% HP Laserwhite20 Layer 2 mm (16 min) 38% HP Opalescence Boost (40 min)	940	7 W 30 s 2.8 cm2 Quadrant handpiece	70	Not tested/not within the aim	SEM: morphological surface changes more pronounced after chemical-activated bleaching. Immediate adhesion: Both bleaching groups with all three agents tested significantly less SBS than control (laser > chem). 7d adhesion: both bleaching groups with all three agents tested significantly better than immediate, but significantly less SBS than control (no significance between laser/chem)
Saeedi, R. [74]	40 human incisors 4 groups (n = 10) (a) 10 LW20/810 nm (b) 10 LW20/940 nm (c) 10 LW20/980 nm (d) 10 non-activated Opalescence boost (conventional control)	Efficacy of laser bleaching with three different wavelengths compared to conventional bleaching	35% HP Laserwhite20 Layer 1 mm Contact 10.5 min 38% HP Opalescence Boost (20 min)	810 940 980	1.5 W 30 s 1 cm2 Single-tooth handpiece	45	Not tested/not within the aim	No statistically significant difference of ΔΕ between groups
Saberi, S. [75]	65 human third molars 5 groups (n = 13) (a) OPB 915 nm 1.5 w (b) OPB 915 nm 2.5 w (c) OPB 445 nm 1 w (d) OPB 445 nm 1.5 w (e) OPB non-activated (control)	Effect of 445/915 nm and different parameters on enamel micro-hardness (Vickers) compared to non-activated bleaching	38% HP Opalescence Boost Layer n/a Contact time: laser groups 18.5 min non-activated control 20 min	445 915	445 nm: 1 W 30 s 8 mm tip 1 mm distance 445 nm and 915 nm 1.5 W 30 s 8 mm tip 1 mm distance 915 nm 2.5 W 30 s 8 mm tip 1 mm distance Single-tooth handpiece	55 84 139	Not tested/not within the aim	915 nm activation significantly reduces the micro-hardness of the enamel (p = 0.000) No significant difference between control and 445 nm groups
Gao, Y. [76]	30 human incisors + 30 premolars 6 groups (n = 10 (5 + 5)) (a) 10 BEyond (b) 10 OpBoost (c) 10 KTP + BE (d) 10 KTP + OPB (e) 10 Nd:YAG + BE (f) 10 Nd:YAG + OPB	Thermal elevation and bleaching efficacy of gel alone or gel irradiated by KTP/Nd:YAG laser	38% HP Opalescence boost 2 mm layer Contact time 15 min 35% HP Beyond 2 mm layer Contact time 15 min	532 1064	800 mW 5 mm tip 180 s 4.2 w/cm2 Single-tooth handpiece	84	5.13 KTP + OPB 3.71 KTP + BE	KTP + OPB temp sign higher than other All other groups similar Nd:YAG no sign diff to conventional KTP + OPB sign higher ΔΕ
Abbasi, M. [77]	50 human incisors 5 groups (n = 10) (a) 10 LW20/810 (b) 10 LW20/940 (c) 10 LW20/980 (d) 10 non-activated OPB (e) 10 untreated	Quantification of HP penetration into pulp chamber during laser vs. conventional bleaching	35% HP Laserwhite20 Layer 2 mm Contact time laser groups 8.5 min 38% HP Opalescence Boost Non-activated control 15 min	810 940 980	1.5 W 30 s 1 cm2 Single-tooth handpiece	45	Not tested/ not within the aim	No sign. difference of HP into pulp chamber between groups. 980-activated significantly higher HP penetration than 810 nm
Shahabi, S. [78]	70 human incisors 7 groups (n = 10) (a) 10 neg control (b) 10 conventional (c) 10 LED (d) 10 KTP (e) 10 Diode (810) (f) 10 Nd:YAG (g) 10 CO2	Colorimetric evaluation	38% HP Opalescence Boost 2 mm layer Control: 3 × 20 min Laser: 30 s × 4 1 min interval +3 min resting time after last irradiation = 8 min	810 KTP Nd:YAG CO2	1.5 W 30 s 1 cm2 Single-tooth handpiece	45	Not tested/not within the aim	KTP statistically significant difference Diode 810 and CO2 no sign. difference to conventional
Lopes, F.C. [79]	27 human maxillary canines’ dentine slabs (a) gel only (b) laser only (c) laser + gel	Morphology and chemical stability of intracoronal dentine	35% HP Heydent 1.5 mm layer Control: 4 min Laser only (without gel) 30 s irradiation Laser + gel: 30 s irradiation + 4 min resting	970	0.8 W average 200 μm fiber 2 cm distance 30 s Bare fiber	90	Not tested/not within the aim	Chemical stability: No difference Morphology: Laser + gel: sign increase of roughness compared to laser-only) HP-only: sign increased perimeter and area of tubules compared to Laser + HP Laser + HP improved dentin surface protection
Ashnagar, S. [80]	60 human third molars 4 groups (n = 15) (a) 15 conventional (b) 15 810 nm (c) 15 Nd:YAG (d) 15 neg control	Evaluation of bleaching methods on enamel susceptibility to caries development	38% HP Opalescence boost Layer 1.5 mm Control: 3 × 20 min Laser: 30 s × 3 1 min interval +3 min resting time after last irradiation (total contact time 6.5 min)	810 (1064 Nd:YAG)	1.5 W 30 s 1 cm2 Single-tooth handpiece	45	Not tested/not within the aim	Enamel microhardness: no difference Diagnodent value: significantly better in diode and conventional groups compared to neg control.
Kiomars, N. [81]	40 human premolars (a) 810 nm + JW (b) 980 + JW (c) 810 + LW20 (d) 980 + LW20 (e) conventional OPB	Effectiveness of diode laser during dental bleaching using different wavelengths	35% HP Heydent white TiO2Gel (JW) Layer 2 mm 35% HP Laserwhite 20 Layer 2 mm Control: Opalescence boost 38% 3 × 20 min Laser-groups 30 s × 3 1 min interval +5 min resting time after last irradiation total 8.5 min	810 980	1.5 W 30 s 1 cm2 Single-tooth handpiece	45	Not tested/not within the aim	Laser had no effect. All techniques resulted in significant tooth whitening (ΔE > 3.3) Conventional group significantly higher ΔΕ (7.58) explained by the 3 × 20 application time
Mirzaie, M. [82]	75 human incisors 5 groups (n = 15) (a) 15 810 nm + JW (b) 15 Nd:YAG + JW (c) 15 810 + LW20 (d) 15 Nd:YAG + LW20 (e) 15 conventional Kimia-Gel	Evaluation of enamel micro-roughness	35% HP Heydent White TiO2 gel (JW) 35% HP Laserwhite 20 35% Kimia-Gel Layer 1 mm 30 s + 1 min interval 30 s + 3 min resting time Total 5 min	810 (1064 Nd:YAG)	1.5 W 30 s 1 cm2 Single-tooth handpiece	45	Not tested/not within the aim	Both laser-activated groups significantly less microroughness than conventional control LW20 significantly lower microroughness than Heydent
Bhutani, N. [83]	30 human incisors 3 groups (n = 10) (a) 10 conventional PolaOfficePlus (b) 10 Light + PolaOfficePlus (c) 10 810 + PolaOfficePlus	Evaluation of the role of light and laser sources in the bleaching ability	35% HP PolaOffice 2 mm layer Contact time Conventional and light activated 3 × 8 = 24 min Laser activated (6 × 30 + resting time 4 min) × 4 = 28 min	810	7 w 30 s quadrant handpiece 2.8 cm2 area	72	Not tested/not within the aim	No significant difference between laser and conventional except at 2 weeks postbleaching
Al-Karadaghi, T.S. [84]	30 extracted human premolars 3 groups (n = 10) (a) 10 940 nm + LW20 (b) 10 980 nm + LW20 (c) 10 LW20 control	Whitening efficacy of 940 nm and 980 nm -activated bleaching by analyzing pulp chamber temperature and tooth color change	35% HP Laserwhite 20 2 mm layer Laser activated (4 × 30 + resting time 2.5 min) Total contact time 20 min	940 980	940 nm 7 W 30 s quadrant handpiece (2.9 cm2) 980 nm 7 W 30 s quadrant handpiece (4 cm2)	43 72	2.63 2.99	Pulp temp increase: No difference Laser-activated groups stat. significantly better than control in color change, but no difference between them
Nguyen, C. [85]	36 human incisors, canines and premolars 6 groups (n = 6) Additionally each tooth-half served as its own non-irradiated control (a) 35% HP vs. 35% HP + KTP (b) 35% HP vs. 35% HP + Er:YAG (c) 35% HP + KTP vs. 35% HP + Er:YAG (d) 6% HP vs. 6% HP + KTP (e) 6% HP vs. 6% HP + Er:YAG (f) 6% HP + KTP vs. 6% HP + Er:YAG	To compare gel temperature, color change and morphology, of 532 nm and 2940 nm with two different concentrations of HP (35% vs. 6%)	35% HP PolaOffice with dark-violet stain to absorb KTP Thickness n/a All 35% groups 15 min All PolaOffice 6% groups 60 min	532	1 W 30 s 8 mm spot Single-tooth handpiece	58	ΔΤ Gel KTP Er:YAG	ΔΕ 35% HP: Er: YAG vs. non-irradiated gel significant difference Other groups no difference ΔΕ 6%Gel: No significant difference between groups ΔΤ gel: Significantly higher for Er:YAG than KTP for both gels 6% and 35% ΔΤ-Gel KTP approximately 13.5 °C after 30 s irradiation for both gels
Bennett, Z.Y. [86]	160 human permanent tooth root slices 8 groups (n = 20) (a) control (b) 3LT light alone (c) Smartbleach gel alone (d) 3LT light and Smartbleach gel (e) KTP laser alone (f) KTP laser and Smartbleach gel (g) 3LT light and 3LT gel (h) 3LT gel alone	Effects of 532 KTP and 532 LED on tetracycline stains	6% HP Rhodamine3LT 30% HP Smartbleach Rhodamine Thickness n/a Contact time: KTP (3 × 10 min) LED (30 min)	532	1 W 30 s 6 mm spot 3 cycles Single-tooth handpiece	50	Not tested/not within the aim	Non-activated gels sign better than neg control KTP + Smartbleach significantly better than LED + SB KTP + Smartbleach significantly better than LED + 3LTgel
Parreiras, S.O. [87]	77 human premolars 3 groups (n = 17) (a) 17 conventional 35% HP (b) 17 35% HP + LED/laser (c) 17 negative control 10 conventional vs. 10 activated microhardness 6 samples conventional 6 LED/Laser activated 6 negative control SEM Edx Ca/P	Effect of bleaching on permeability, microhardness, and mineral content of enamel	35% HP Whiteness HP Maxx Thickness n/a For all groups (3 × 15 min) × 2	LED/laser 810 nm diode 470 nm LED	LED/laser 810 nm diode (60 s × 200 mW/cm2) simultaneously 470 nm (60 s × 350 mW/cm2)	12 + 21		No significant differences between groups in any of the evaluated effects
Anaraki, S.N. [88]	15 intact human molars divided into halves = 30 samples 2 groups (n = 15) (a) 15 Conventional 38% HP (OpB) (b) 15 810 + 35% HP (Heydent)	Evaluation of the effects of in-office versus laser bleaching on enamel surface roughness	35% HP Heydent Thickness 1 mm Contact time [(3 × 15 s) + 1 min interval] × 3 + 3 min resting total: 7:15 min 38% HP Opalescence Boost control Thickness 1 mm Contact time 2 × 10 min	810 nm	1.5 W 15 s 1 cm2 Single-tooth handpiece	22.5	Not tested/not within the aim	Laser group significantly less surface roughness
Hahn, P. [89]	80 human third molars 4 groups (n = 20) (a) Conventional control (b) Halogen + OpB (c) LED + OpB (d) 980 + OpB	Evaluation of color stability of bleaching activated by halogen, laser, LED or chemical activation up to 3 months after treatment	38% HP Opalescence Thickness n/a Contact time 4 × 15 min all groups Halogen (8 min activation + 7 min resting) × 4 LED (40 s activation + 14:20 min resting) × 4 Laser (30 s activation + 14:30 min resting) × 4	980 nm	6 W 30 s 8 mm single-tooth handpiece	180	Halogen 17.93 LED 2.31 laser 13.49	Color change: no difference between groups (halogen > LED > laser > control without significance) Pulp temperature: Halogen > laser > LED
Torres, C.R.G. [90]	90 human premolars (180 halves) 8 test groups (n = 20) (a) Halogen (b) 470/795 (c) 470 LED (d) 470/830 (e) 470 LED (f) 530/795 (g) Negative control (n = 10) (h) Positive control (n = 10)	Effectiveness of color change of hybrid light-emitting diode (LED) and low-intensity infrared diode laser devices for activating dental bleaching and to verify the occurrence of a color regression with time	35% HP Whiteness HP Maxx 2 mm layer 3 × 10 min	470 795 470 830 530 795	470 nm 9 J/cm2 795 nm 10 J/cm2 470 nm 27 J/cm2 830 nm 44 J/cm2 530 nm 5.7 J/cm2 795 nm 6.8 J/cm2	0 10 27 44		All light-activated groups, except green LED/laser (very low fluence, show significantly higher ΔE than the control group LED/laser and LED no difference
Ozyilmaz, O.Y. [91]	40 maxillary central incisors 4 groups (n = 10) (a) non-activated 35% HP control (b) LED + 35% HP (c) 980 + 35% HP (d) Nd:YAG + 35% HP	Evaluation of influence of light-activation by LED, Diode, Nd:YAG on the pulp temperature increases during bleaching with 35% HP.	35% HP Whiteness HP Maxx 1 mm layer Activation time 20 s, total contact time 10 min control (15 min)	LED Diode 980 Nd:YAG	980 nm 4 W 20 s 2 mm distance quadrant handpiece (5.85 cm2 spot size)	17.7	Control 0 ± 0 LED 3.2 ± 0.95 980 6.7 ± 1.18 Nd:YAG 10.7 ± 3.82	The three experimental groups differed significantly from each other (p < 0.05). Diode 980 significantly higher temp elevation than LED and control. Higher than safety threshold

, respectively.

3.3. Quality Assessment Presentation

The risk of bias (ROB) considered for the included studies is presented in

Table 3. Risk of bias assessment results—clinical studies.

Citation [Ref]	Randomization	Sample Size Calculation and Required Number Included	Conventional Control Group	Blinding	Parameters of Bleaching Gels Described Appropriately	Parameters of Laser Use Described Appropriately and Calculations Correct	Power Meter Used	Numerical Results Available (Statistics)	Outcome Data Complete	Correct Inter-pretation of Data	Total Score /10
Gurgan, S. [53]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Polydorou, O. [54]	yes	no	yes	no	yes	no	no	yes	yes	yes	6
Ahrari, F. [55]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Surmelioglu, D. [56]	yes	yes	yes	no	yes	yes	no	yes	yes	yes	8
Sürmelioğlu, D. [57]	no	yes	yes	yes	yes	yes	no	yes	yes	yes	8
Oz, O.P. [58]	yes	yes	yes	no	yes	yes	no	yes	yes	yes	8
de Freitas, P.M. [59]	yes	yes	yes	yes	yes	yes	no	yes	yes	yes	9
Kossatz, S. [60]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Mena-Serrano, A.P. [61]	yes	yes	yes	yes	yes	yes	no	yes	yes	yes	9
Mondelli, R.F. [62]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Mondelli, R.F.L. [63]	yes	yes	yes	yes	yes	yes	no	yes	yes	yes	9
Moncada, G. [64]	yes	yes	yes	yes	yes	yes	no	yes	yes	yes	9
Bortolatto, J.F. [65]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Karaarslan, E.S. [66]	no	no	yes	no	yes	yes	no	yes	yes	yes	6
De Almeida, L.C.A.G. [67]	yes	no	yes	no	yes	yes	no	yes	yes	yes	7
De Almeida, L.C.A.G. [68]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Mondelli, R.F.L.; [69]	yes	yes	yes	yes	yes	yes	no	yes	yes	yes	9
Bortolatto, J.F. [70]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Bersezio, C. [71]	yes	yes	yes	yes	yes	yes	no	yes	yes	yes	9

and

Table 4. Risk of bias assessment results—in vitro studies.

Citation [ref]	Randomization	Sample Size Calculation and Required Number Included	Conventional Control Group	Standardization of Samples	Parameters of Bleaching Gels Described Appropriately	Parameters of Laser Use Described Appropriately and Calculations Correct	Power meter Used	Numerical Results Available (Statistics)	Outcome Data Complete	Correct Inter-Pretation of Data	Total Score /10
Suresh, S. [72]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Cevval Ozkocak, B.B. [73]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Saeedi, R. [74]	yes	yes	yes	yes	yes	yes	no	yes	yes	yes	9
Saberi, S. [75]	yes	yes	yes	yes	yes	yes	no	yes	yes	yes	9
Gao, Y. [76]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Abbasi, M. [77]	no	yes	yes	yes	yes	yes	no	yes	yes	yes	8
Shahabi, S. [78]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Lopes, F.C. [79]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Ashnagar, S. [80]	no	no	yes	yes	yes	yes	no	yes	yes	yes	7
Kiomars, N. [81]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Mirzaie, M. [82]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Bhutani, N. [83]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Al-Karadaghi, T.S. [84]	yes	no	yes	yes	yes	yes	yes	yes	yes	no	8
Nguyen, C. [85]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Bennett, Z.Y. [86]	yes	yes	yes	yes	yes	yes	yes	yes	yes	yes	10
Parreiras, S.O. [87]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Anaraki, S.N. [88]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Hahn, P. [89]	yes	no	yes	yes	yes	no	no	yes	yes	yes	7
Torres, C.R.G. [90]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8
Ozyilmaz, O.Y.; [91]	yes	no	yes	yes	yes	yes	no	yes	yes	yes	8

.

3.3.1. Clinical Studies

The classification revealed the following results:

• Low risk of bias in 16/19 of the articles (84.2%):

  o

  six [59,61,63,64,69,71] scoring 9/10;

  o

  ten [53,55,56,57,58,60,62,65,68,70] scoring 8/10.

• Moderate risk of bias in 3/19 of the articles (15.8%):

  o

  one [67] scoring 7/10;

  o

  two [54,66] scoring 6/10.

None of the studies finally included exhibited a high risk of bias.

Overall, the mean ± standard error (SEM) Cochrane risk of bias score parameter was 8.05 ± 0.23 out of a perfect value of 10 (95% confidence intervals 7.56–8.56).

A power meter was not used in any of the studies to calibrate the laser devices before their application. The other most common negative answers found concerned (a) the sample size calculations of studies and their required number included; and (b) blinding of the researchers.

3.3.2. In Vitro Studies

The classification revealed the following results:

• Low risk of bias in 18/20 of the articles (90%):

  o

  one [86] scoring 10/10;

  o

  two [74,75] scoring 9/10;

  o

  fifteen [72,73,76,77,78,79,81,82,83,84,85,87,88,90,91] scoring 8/10.

• Moderate risk of bias in 2/20 of the articles (10%):

  o

  two [80,89] scoring 7/10.

Similarly, none of the studies exhibited a high risk of bias.

Overall, the mean ± standard error (SEM) Cochrane risk of bias score parameter was 8.10 ± 0.14 out of a perfect value of 10 (95% confidence intervals 7.81–8.39).

In this category, a power meter was used in only two of the studies [84,86] to calibrate the laser devices before their performance. The other most common negative answer concerned the sample size calculation and the required number of these required for inclusion.

There was no significant difference between the two mean values of the ROB score parameter for clinical and in vitro studies (two-sample t-test), and nor did the intra-sample variances differ between these two groups.

3.4. Data Analysis

3.4.1. Clinical Studies

(a) Analysis of aims of studies and respective evaluation methods

The various aims of the studies and respective evaluation methods are provided below:

• Color change: 13/16 studies used an objective (spectrophotometric) method.
• Sensitivity: 14/14 used a Visual Analogue rating Scale (VAS).
• Temperature on enamel: 1/1 used a thermocouple.
• DNA Damage Biomarkers: 1/1 applied a biochemical examination (GCF, saliva, serum).
• Proteolytic and ROS activities in dentin-pulp complex: 1/1 applied a spectrofluorometric evaluation.

(b) Outcome assessment.

Regarding the primary outcome (a), 30% of the studies presented a positive outcome, 62% showed no difference between test and control groups, while only 8% showed a negative outcome for the test group.

Specifically, for each examined aim, the number of studies and the respective outcome are exhibited in Figure 2:

(c) Evaluation of gel and laser application protocols for studies showing a positive outcome

Regarding the primary outcome (b), the different laser bleaching protocols that exerted a beneficial effect are displayed in

Table 5. The laser bleaching protocols that exerted a beneficial effect in the clinical studies conducted.

	Gel Thickness (mm)	Gel Contact Time (min)	Spot Size/Handpiece	Irradiation Time (s) per Cycle	Fluence (J/cm2) per Cycle	Irradiation Cycles
810 nm + (34–38)% H2O2 [53,55]	1 mm	16 min	2.8 cm2/quadrant	15	46	8
	1 mm	20 min	400 μm/single-tooth	30	88	2
Hybrid + (35–38)% H2O2 [59,60,63,69,70]	1–2 mm	24 min	Full arch	60/60	18/18	3
	1 mm	45 min	Full arch	60/60	12/21	3
	1–2 mm	22.5 min	Full arch	120/120	24/42	3
	1 mm	24 min	Full arch	180/180	36/63	3
	Unknown	32 min	Full arch	60/60	18/18	4
Hybrid + 25% H2O2 [63]	1–2 mm	22.5 min	Full arch	120/120	24/42	3
Hybrid + 15% H2O2 with TiO2_ [65]	1–2 mm	48 min	Full arch	60/60	18/18	3

.

In the majority of the studies mentioned above, a hybrid LED/laser device was used in conjunction with varying H₂O₂ concentrations, resulting in observed inhomogeneity. However, the common irradiation parameters were 18/18 and 24/42 J/cm², repeated 3–4 times, with a total gel contact time of 24 min. For the lower concentrated bleaching gel, the duration extended up to 48 min. As for the sole use of one wavelength, there are two studies where an 810 nm laser was applied. However, these two protocols were completely different with regard to the spot size, irradiation time, and fluence parameters employed.

3.4.2. In Vitro Studies

(a) Analysis of aims of studies and respective evaluation methods

Respective evaluation methods concerning the various aims of the studies are shown below:

• Color change: 7/10 studies used an objective (spectrophotometric) method.
• Mineral content: 2/2 applied energy dispersive X-ray spectrometry (EDX) and Scanning Electron Microscopy (SEM).
• Adhesion: 1/1 used SEM.
• Microhardness: 1/3 used Vickers and 2/3 Knoop hardness method.
• Chemical stability of dentin: 1/1 used confocal microscopy and Raman spectroscopy.
• Morphology of dentin: 1/2 used confocal microscopy and Raman spectroscopy, while 1/2 used SEM.
• Microroughness: 2/2 used a profilometer.
• Permeability: 1/1 used a staining technique.
• HP penetration: 1/1 used a spectrophotometer to monitor this.
• Pulp ΔΤ: 4/4 used a thermocouple connected to a digital thermometer and data logger.
• Gel ΔΤ: 1/1 used a thermocouple connected to a digital thermometer and data logger.

(b) Outcome assessment

Regarding the primary outcome (a), 43% of the studies presented a positive outcome, 10% were negative, while 47% showed no difference between the test and control groups. Specifically, for each examined aim, the number of studies and the respective outcome are shown in Figure 3, where the abovementioned categories: mineral content, adhesion, microhardness, chemical stability of dentin, morphology of dentin, microroughness, permeability are grouped together under the term “hard tissue alterations”.

(c) Evaluation of gel and laser application protocols for the studies showing a positive outcome.

Regarding the primary outcome (b), the different laser bleaching protocols that exerted a beneficial effect are displayed in

Table 6. The laser bleaching protocols that exerted a beneficial effect in the in vitro studies.

	Gel Thickness (mm)	Gel Contact Time (min)	Spot Size/Handpiece	Irradiation Time (s) per Cycle	Fluence (J/cm2) per Cycle	Irradiation Cycles
532 nm + (30–38)% [76,78,85,86]	2 mm	15 min	5 mm/single tooth	180 s	84	1
	2 mm	8 min	1 cm2/single tooth	30 s	45	3
	Unknown	15 min	8 mm/single tooth	30 s	58	3
	Unknown	30 min	6 mm/single tooth	30 s	50	3
810 nm + (35–38)% [82,88]	1 mm	5 min	1 cm2/single tooth	30 s	45	3
	1 mm	7.15 min	1 cm2/single tooth	15 s	22.5	9
940 nm + (35–38)% [72,84]	Unknown	17 min	2.8 cm2/quadrant	30 s	70	4
	2 mm	20 min	2.9 cm2/quadrant	30 s	43	4
970 nm + 35% [79]	1.5 mm	4.5 min	200 μm fiber	30 s	90	1
980 nm + (35–38)% [84]	2 mm	20 min	4 cm2/quadrant	30 s	72	4
LED/laser hybrid + 35% [90]	2 mm	30 min	Full arch	60 s	9/10 (470–795 nm)	3
					27/44 (470–830 nm)	3

.

It was also revealed that, besides the green light and blue hybrid LED/laser device, the activation sources most commonly used are the near infrared (NIR) wavelengths ranging from 810 to 980 nm.

Except from the LED/laser hybrid, which was used in only one of the aforementioned studies, the other parameters applied are listed below:

• H₂O₂ concentration, high (30–38% (w/v)) is preferably applied.
• Gel thickness 1 to 2 mm.
• Contact time: 4.5–30 min, mainly 15–20 min.
• Spot size/handpiece: 200 μm fiber up to 4 cm²/quadrant; large spot sizes/single-tooth or quadrant handpieces were preferably applied.
• Irradiation time per cycle: 15–180 s, predominantly 30 s.
• Fluence per cycle: 22.5–90 J/cm², mainly 45–70 J/cm².
• Irradiation cycles: mostly 3.

(d) Evaluation of pulp temperature

Four of the included in vitro studies investigated pulp temperature increases as shown in

Table 7. Studies examining pulp temperature changes, including information on wavelength, bleaching gel, laser fluence, irradiation time, and temperature.

Reference	Wavelength (nm)	Bleaching Gel (Product Name)	Fluence (J/cm2)	Irradiation Time (Sec)	Pulp Temperature Increase (°C)
Gao [76]	532	Opalescence Boost	84	20	5.13
	532	Beyond	84	20	3.71
Ozyilmaz [91]	980	Whiteness HP	17.7	20	6.7
Hahn [89]	980	Opalescence Xtra Boost	180	30	14.06
Al-Karadaghi [84]	980	Laserwhite 20	72	30	2.63
	940	Laserwhite 20	43	30	1.99

[76,84,89,91]. Six different combinations of wavelength and bleaching gel were explored, with various fluences. The resulting temperature increase ranged from 1.99 °C to 14.06 °C.

3.5. Statistical Analysis

The objective was to provide results arising from the application of statistical analysis models to determine the significance and magnitude of variable contributions towards differences observed between standard (control) and laser-enhanced tooth-whitening processes for the aims of tooth-whitening efficacy and tooth sensitivity in the clinical, and tooth-whitening efficacy and enamel/dentine morphology alterations, for the in vitro studies.

3.5.1. Clinical Studies

The results from the statistical analysis among the study groups showing significantly better, indifferent, or significantly worse color and sensitivity outcomes (groups +1, 0, and −1 respectively) are shown in

Table 8. The parameters examined and the respective p values found regarding the two treatment outcomes. Abbreviations: ns, not significant (threshold significance level α = 0.05).

Parameter Examined	Color Change	Sensitivity
Gel concentration (median H2O2 dose grade)	p = 0.007	ns
Gel thickness	ns	ns
Contact time (min)	p = 0.069	ns
Fluence	ns	ns
Wavelength (nm)	ns	ns
Handpiece type	ns	ns

.

(a) Color change

Regarding the color change, only the H₂O₂ gel concentration can significantly affect this outcome. Therefore, this factor was further analyzed as shown in Figure 4.

The difference in median dose levels applied was found to be significantly lower for the −1 group than it was for the 0 group (p = 0.0032), with a mean ± 95% confidence interval (CI) difference in (w/w)% dose of −24.15 ± 10.15% H₂O₂. From this, it can be concluded that the non-laser-treated control group required a H₂O₂ dose level which was, on average, 24.15% (w/w) higher in order to achieve a status which is equivalent to that of the laser-activated bleaching group.

Nevertheless, for the contact time, this did not show any significant difference in terms of the color outcome (p = 0.069). However, on examining the contact times of each group (test and control), the values were significantly different (p = 0.002). Hence, it can be stated that, for no difference in whitening effect to be observed (score 0), a mean contact time of only 31.92 min was required for the test group, whereas 41.00 min for the control group was necessary, and this led to a clinically significant difference.

The other examined parameters (gel thickness, fluence, wavelength, and handpiece type) did not exert a statistically significant effect on the color outcome (Table 7).

(b) Sensitivity

One-way ANOVA or its non-parametric equivalent (Kruskal–Wallis test) showed that no significant differences were detected in any of the weighted parameter values examined on the sensitivity outcome.

3.5.2. In Vitro Studies

(a) Color change

The results from the statistical analysis are shown in

Table 9. Parameters examined and the respective p values found regarding the color change outcome. Abbreviations: ns, not significant (threshold significance level α = 0.05).

Parameter Examined	Color Change
Gel thickness	ns
Contact time	ns
Wavelength	ns
Handpiece type	ns
Fluence	ns

.

As noted in Table 9, no significant differences between the −1, 0, and +1 groups were detected for any of the examined parameters. The difference in median dose level could not be tested since these values were exactly the same (30–39%) for all papers evaluated.

However, there was a very highly significant difference (p = 0.0004) between gel contact time for the test and control groups, with the mean test–control group difference being −10.59 min. Therefore, in order to achieve a 0 score value of no difference between these two sets of samples, we may suggest that a contact time difference of >10 min is required.

(b) Hard tissue alterations

The results from the statistical analysis are shown in

Table 10. Parameters examined and the respective p values found regarding the morphology outcome. Abbreviations: ns, not significant (threshold significance level α = 0.05).

Parameter Examined	Hard Tissue Alterations
Test group wavelength	ns
Handpiece type	ns
Gel thickness	ns
Fluence test group	ns
Difference in gel contact time	p = 0.088

.

The difference in median dose level could not be tested since these values were exactly the same (30–39%) for all papers evaluated.

The difference in gel contact time was close to statistical significance (p = 0.088), and indicated an increase in outcome score (−1, 0, or +1) with increasing time.

4. Discussion

The primary goals of this systematic review were (a) to evaluate the efficacy of laser-activated dental bleaching compared to conventional in-office bleaching methods, and (b) to critically appraise the laser bleaching protocols employed to date. This systematic literature review encompassed a total of 19 clinical and 20 in vitro studies, incorporating both qualitative and quantitative assessments. The results indicated that clinical studies predominantly focused on evaluating color outcome and sensitivity, while in vitro studies primarily emphasized color outcome and hard tissue morphology alterations. Within the pool of included studies, there were 39 investigations where the bleaching gel was activated by a laser device. Specifically, a “hybrid” LED and laser combination device (HL) was applied in 12 of the clinical and 2 of the in vitro studies. Additionally, 17 clinical and all the 20 in vitro studies assessed gels of high HP concentration (i.e., HP 30% (w/v) or higher), and only 2 of the included clinical studies examined low concentration gels (i.e., HP below 20% (w/v)).

In a recent systematic review (Maran 2018) investigating whitening efficacy and tooth sensitivity (TS) in office vital bleaching, with or without light application, the authors concluded that bleaching efficacy and TS are not influenced by light activation [8]. The authors pointed out that this was an overall comparison without considering variations of protocols or the type of light applied. Specifically, out of the 21 included studies, ten applied a LED/laser combination, and only four applied a laser device to activate the bleaching gel, while the remaining seven applied another source of light activation. In our analysis, the focus was instead based on laser-activated protocols, and only such studies with at least one laser or hybrid LED/laser-activated group serving as the test group were included. Amongst the included 19 clinical and 20 in vitro studies, only three [54,56,71] and three respectively [81,89,91] revealed significantly worse results for the test groups. In contrast, nine clinical [53,55,57,60,63,65,66,69,70] and ten in vitro studies [72,76,77,78,79,82,84,86,88,90] could, at least in principle, provide significantly improved results for the laser and hybrid LED–laser groups. Nevertheless, the statistical analysis performed did not show a significant difference between these.

In another systematic review (Maran 2019) exploring the differences in efficacy (color outcome) between light-activated protocols and light-free in-office bleaching protocols, no significant difference in color change was found regardless of the HP concentration [92]. Amongst the 28 studies incorporated in the above analysis, a laser activation source was utilized in only four of them, while a LED/laser device was employed in 13 of the studies. In our study, through statistical analysis, it was revealed that the conventional (non-irradiated) control group requires a H₂O₂ (HP) dose level which is, on average, 24.15% (w/w) higher in order to achieve a color status which is equivalent to that of the laser-activated bleaching group. This difference was highly significant (p = 0.0032).

A previous systematic review (He 2012) [93] concluded that light increases the risk of tooth sensitivity during in-office bleaching, and light may not improve the bleaching effect when high concentrations of HP (25–35% (w/v)) are employed, but with lower concentrations the effect is significantly favorable for the activated groups [93]. This review and meta-analysis included 11 studies, of which three applied a hybrid LED/laser system, and only one study used a laser as the activation source. All other studies applied LED or halogen lamps. As stated above, in our analysis the control group would require a 24.15% higher HP level to achieve results similar to the laser-activated group. Additionally, and in contrast to the review of He [93], there was no significant change in sensitivity arising from laser activation.

Again, Maran et al. in 2020 conducted another systematic review which compared high and low hydrogen peroxide (HP) concentration bleaching gels [94]. Notwithstanding, it was highlighted that various aspects of the bleaching procedure were not taken into account in the analysis. These aspects included: (1) the duration of gel contact with dental tissue, (2) the number and frequency of bleaching applications, (3) the duration of each whitening session, (4) the utilization of light activation, (5) the age of the study population, (6) the pH of the products, and (7) the inclusion of additional substances in the whitening gels [94]. Hence, in view of this high level of heterogeneity, results arising therefrom cannot be compared to the present study which also showed similar variations. Nevertheless, here the only two significant factors influencing the outcome significantly were HP concentration and the bleaching gel contact time.

A further meta-analysis by SoutoMaior including 21 articles (out of which 11 used a LED/laser combination, only two used a laser in the test groups, and 14 used LED or halogen lamps amongst the test groups) concluded that light activation did not increase the bleaching efficacy in immediate, short, or medium terms of application [95]. Unfortunately, the analysis did not provide any distinction between the types of light applied in the studies included. Once again, a high heterogeneity of data was recorded concerning activation sources and exposure time to the bleaching agent. Sensitivity incidence was not significantly different between light vs. non-light activated procedures. However, in terms of sensitivity intensity, light-activated methods demonstrated a significantly lower intensity of tooth sensitivity than that of the non-light systems. The authors attributed this finding to the use of the LED/laser HL (hybrid light), and by its potential analgesic and anti-inflammatory effects. Additionally, the reduced contact time was found to play a contributory role towards this favorable result. In our study, no significant differences in color outcome or sensitivity were found between irradiated vs. non-irradiated groups, but similarly to SoutoMaior [95], a significantly reduced contact time (of ca. 10 min) was revealed for the test groups.

• Limitations of the Study:

One limitation of the study conducted in the current paper is the overall small number of “qualifying” studies that could be subjected to statistical analysis, both parametric and non-parametric. Indeed, for the clinical and in vitro studies explored, only n = 16/19 and 10/20 of these could be included, respectively, in the final statistical analysis conducted for color outcome (a), whereas for option (b) (tooth sensitivity and morphological alterations for clinical and in vitro studies respectively), only 13/19 and 8/20 could be assessed, respectively. These restrictions were applied in view of the availability of variable parameters and criteria for these evaluations, a sizeable proportion of which were lacking, most especially for the in vitro investigations.

4.1. Diffusion of Hydrogen Peroxide

Previous research has assessed the diffusion of various concentrations of HP through dentin. These results have revealed that within a span of 15 min, HP was able to permeate a dentin width of 0.5 mm. This diffusion resulted in concentrations of HP that could potentially damage fibroblast cultures [18,96]. Moreover, Trindade et al. [97] affirmed that the degree of cytotoxicity is higher when increasing the concentration and application time of the bleaching agent. Our findings, however, indicated that the laser groups had notably shorter contact times compared to the non-irradiated groups. Typically, the contact time was divided into 3–4 irradiation cycles, involving the removal and rinsing of the gel, followed by its re-application.

4.2. Pulp Response to Dental Bleaching

The pulpal response to dental bleaching has undergone extensive investigation [18,19,98,99,100]. Indeed, in a systematic review conducted by Briso [13], the influence of different light sources on pulp tissue response during dental bleaching procedures was examined. The review findings suggested that the application of different light parameters during dental bleaching can yield distinct effects on pulp tissue. Remarkably, it was observed that PBM, when implemented with specific parameters (10 J/cm² on cells [19]), offers a promising potential for mitigating the detrimental impact on pulp tissue caused by bleaching. However, these authors noted that the establishment of a safe and effective protocol for the clinical application of PBM in dental practice remains an ongoing pursuit.

Clinically, pulp health can be examined through its sensitivity [53,55,56,58,59,60,61,62,63,64,65,67,69,70], but also through the analysis of DNA-damage biomarkers, or proteolytic and/or ROS activities within the dentin–pulp complex [57,66]. In the current study, the laser-activated groups did not demonstrate significantly higher sensitivity. Similarly, other investigation methods (e.g., analysis of biomarkers and ROS activities) did not yield negative results for the test groups. To be specific, out of the 14 investigations related to sensitivity, five reported positive effects [53,55,63,65,70], eight showed no significant difference [58,59,60,61,62,64,67,69], and only one had a negative outcome [56]. Both studies examining DNA damage biomarkers and proteolytic activities within the dentin–pulp complex found no significant difference between the laser-activated and control groups [57,66]. While these outcomes appear encouraging, we were unable to identify any statistically significant impact of contact time, wavelength, fluence, handpiece type, or gel thickness on tooth sensitivity in the analysis conducted on the studies included in this systematic review.

Presently, there is a growing trend towards performing minimally invasive procedures, and hence efforts have been made to decrease the concentrations of HP in bleaching gels, including the incorporation of catalytic nanoparticles, as well as adjusting the duration and frequency of treatment sessions [101,102,103]. Although these modified approaches do not achieve the same level of effectiveness as traditionally applied higher concentrations [104], there is a consensus that prioritizing biological safety is preferable over the speed of the procedure [71]. As noted herein, our statistical analysis showed that the laser-activated groups required lower HP levels to achieve results similar to those of the control groups.

4.3. Pulp Temperature Dynamics and Fluence Considerations in Dental Bleaching Procedures

The duration of a temperature increase and the retention of heat that can potentially cause pulp damage are crucial factors to consider [91]. Indeed, a 5 °C increase with a duration of only 1 min is a critical threshold for maintaining pulp health [30,105]. However, heat dissipation occurs rapidly according to the concept of Tissue Relaxation Time (TRT), which is directly proportional to the square of the diameter of the irradiated tissue, and inversely proportional to its diffusivity [15]. Although the heat transfer through blood flow within the pulp is very low [32], the flow within the periodontal ligament may play a crucial role [106]. Furthermore, a recent spectrophotometric investigation examined the light attenuation of various bleaching gels [15]. This study integrated theoretical calculations based on Kreisler’s research [107], and included calculations of tissue relaxation time [108]. The findings from this investigation demonstrated that for a 1 mm layer of bleaching gel with light attenuation of approximately 80% and a 4 mm target area (calculated mean of pulp area) [109], the maximum acceptable fluence was determined to be 93.5 J/cm².

Additionally, based on prior estimations of approximately 80% light attenuation within the bleaching gels, and the established threshold of 5–10 J/cm² required for photobiomodulation (PBM) [110], and specifically for pulp tissue exposed to HP [13,19,98], we may suggest that a fluence value of 25–50 J/cm² would be the preferable choice for dental bleaching. Under these conditions, concurrent PBM may potentially occur, which could lead to advantageous effects on the dental pulp. Nevertheless, this is a value which should be confirmed by further research.

In the present systematic review, the fluences employed in the studies featured varied between 12.5 and 180 J/cm². Only one clinical and one in vitro study reached the upper limit of this threshold fluence. Importantly, it was evident that studies employing high fluence parameters exhibited more detrimental effects compared to those with lower parameters [54,89]. Notably, only four of the included in vitro studies investigated pulp temperature increases, as shown in Table 7 [76,84,89,91].

Gao’s study [76] utilized a 532 nm wavelength laser with a fluence of 84 J/cm² for 20 s, which resulted in a temperature increase of 5.13 °C. In contrast, Ozyilmaz [91] employed a fluence of 17.7 J/cm² at 980 nm for 20 s, leading to a 6.7 °C temperature rise. However, Hahn’s research [89] applied a fluence of 180 J/cm² at 980 nm for 30 s, resulting in a substantial 14.06 °C temperature increase. Notwithstanding, Al-Karadaghi’s study [84] employed a fluence of 72 J/cm² at 980 nm for 30 s, which resulted in a more modest 2.63 °C temperature increase.

The considerable variance in results can be attributed to various factors, including differences in parameters and methodology [111]. For example, exceptionally lower results may arise from the utilization of a water bath, while excessively higher results might be linked to the direct heat absorption by the thermocouple [112]. Interestingly, in one study (Al-Karadaghi et al.) [84], the temperature was continuously monitored between two laser activation cycles, and it exhibited a decline back to the initial temperature after a resting period of 2.5 min.

4.4. Clinical Considerations

When using laser technology for dental bleaching, certain guidelines should be followed. The laser fluence should not exceed 90 J/cm², and the irradiation duration should be limited to a maximum of 20–30 s per cycle. To ensure an effective decrease in temperature, it is important to observe a minimum resting period of 2.5 min between cycles. Additionally, the contact time per cycle should not exceed 15 min to prevent HP diffusion into the pulp tissue. It should also be noted that a total fluence of approximately 50 J/cm² may have a photobiomodulation (PBM) effect on the pulp of the bleached teeth. These recommendations help ensure the safety and effectiveness of the laser bleaching procedure.

5. Conclusions

In the analysis conducted, laser activation did not significantly improve color compared to non-activated bleaching, but allowed for a significantly shorter gel contact time. Conversely, non-activated bleaching required higher HP doses to achieve similar results. Higher HP concentrations were not correlated to increased sensitivity; sensitivity levels were not notably higher in the non-activated groups, and our analysis did not reveal elevated sensitivities associated with any applied fluence. Prolonged contact times increased morphological changes. Laser and hybrid LED/laser exerted similar results. Laser activation has efficiency benefits with reduced HP usage, and no significant sensitivity concerns. However, treatment duration has to be considered to avoid unwanted changes, and the choice of a researched gel and protocol is crucial for reliable outcomes. Consequently, ongoing research will be seen to be vital for health and safety considerations, and also to provide guidelines in laser-activated bleaching protocols.