Photobiomodulation in dental implant stability and post-surgical healing and inflammation. A randomised double-blind study

Clin Oral Impl Res. 2023;34:137–147. | 137wileyonlinelibrary.com/journal/clr Received: 27 April 2022 | Revised: 22 August 2022 | Accepted: 1 December 2022 DOI: 10.1111/clr.14026 ORIGINAL ARTICLE Photobiomodulation in dental implant stability and postsurgical healing and inflammation. A randomised doubleblind study Gisela C. V. Camolesi1,2 | José M. SomozaMartín1,2 | Maria D. ReboirasLópez1,2 | Fabio CamachoAlonso3 | Andrés BlancoCarrión1,2 | Mario PérezSayáns1,2 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2022 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd. 1Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, University of Santiago de Compostela, Santiago de Compostela, Galicia, Spain 2Health Research Institute of Santiago (IDIS) (ORALRES), Santiago de Compostela, Spain 3Department of Oral Surgery, University of Murcia, Murcia, Spain Correspondence Mario PérezSayáns, Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, University of Santiago de Compostela, Entrerríos s/n, Santiago de Compostela C.P. 15782, Spain. Email: [email protected] Funding information Nueva Galimplant; University of Santiago de Compostela, Grant/Award Number: U S C - 2 0 1 9 - C E 1 7 8 Abstract Background: The aim of this randomized clinical trial was to evaluate the effect of diode laser photobiomodulation (PBM) on postsurgical healing, inflammation and implant stability. Methods: Forty dental implants were inserted into 13 patients. The implants were randomly divided into two groups. The test group (PBM+) underwent two sessions of PBM (combined diode laser of 630 and 808 nm), the first of which after surgery, and the second, 7 days after the surgical procedure. The control group (PBM−) received simulated laser treatment. The implant stability quotient (ISQ) was determined immediately after the surgical procedure, and 7 days, 4 and 8 weeks later. Postsurgical inflammation was assessed following the criteria described by Bloemen and Cols. Healing was calculated using the healing index (HI). Results: No differences were found in terms of the mean values of implant stability between the test and control groups over time. Only two of the implants (18.2%) from the PBM− group were classified with the maximum healing index (HI = 5), whereas in the PBM+ group, nine implants (45%) were classified with the aforementioned index (P < 0.0001). Using the logistic regression, it was determined that the nonapplication of the laser in the PBM− group caused an OR of 4.333 times of presenting inflammation (IC95% 1.150– 16.323; P = 0.030). Conclusions: The application of 808 nm infrared laser for bone tissue, and 630 nm for mucosal tissue in two sessions is considered to be an effective way of reducing inflammation and improving early healing. More studies are needed to confirm these results. KEYWORDS mucosal healing, mucosal inflammation, osseointegrated dental implants, photobiomodulation 16000501, 2023, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/clr.14026 by Consorcio Interuniversitario Do Sistema Universitario De Galicia (Cisug), Wiley Online Library on [23/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 138 | CAMOLESI et al. 1 | INTRODUCTION Osseointegrated dental implants are used for replacing lost teeth and they offer a high success rate (Howe et al., 2019). Bone quantity and quality are predictive factors in achieving proper primary stability and in defining whether rehabilitation should be carried out with early or immediate loading (Elias et al., 2012; Monje et al., 2019; Shokri & Daraeighadikolaei, 2013). The clinical success of a dental implant over time is determined by bone quantity, bone quality, and, in particular, adequate osseointegration (Fornaini et al., 2015; Mills et al., 2018). The primary stability of dental implants is defined by the biomechanical stability that is obtained when inserting the implant. Secondary stability occurs later on, and it depends on osseointegration, that is to say the bone formation process in the boneimplant interface (Monje et al., 2019; Shokri & Daraeighadikolaei, 2013). Lowlevel laser therapy (LLLT) or photobiomodulation (PBM) has been proposed as a method that could be used to enhance the bone cicatrisation process by reducing the healing time for osseointegration in preclinical studies (Karakaya & Demirbaş, 2020). However, other randomized clinical trials have not confirmed these results (Torkzaban et al., 2018). PBM consists of low energy density laser and/or LED light therapy, so it does not generate heat. To induce photochemical effects and stimulate cell replication (Bayat & Jalalifirouzkouhi, 2017; Karoussis et al., 2017; Santinoni et al., 2021), there is a broad spectrum in terms of wavelength, ranging from red to infrared (6001100 nm) (Qu et al., 2022), nevertheless there is no specific guideline to achieve the best results in terms of osseointegration healing (Kazem Shakouri et al., 2010; Riboldi et al., 2009). The most recent published studies addressing PBM for osseointegration applied a protocol quite similar to the one used in our study (Kinalski et al., 2021; Lobato et al., 2020), however the present study presents as a novelty the use of both frequencies (dual laser, red and infrared wavelength) with the aim of improving the effects at the bone and soft tissue level. Several clinical methods have mentioned the use of invasive techniques to measure the stability of dental implants, such as removal torque or histomorphometric analysis (Matys et al., 2017). However, the Periotest and resonance frequency analysis (RFA) are used more often (Marquezan et al., 2012). RFA analysis is carried out with specific devices with a transducer or “smart peg” being inserted into the implant or abutment to measure and quantify stability. The implant stability quotient (ISQ) is presented using a numerical scale from 0 to 100, and it is translated from an intensity frequency of 3500– 8500 Hz (Torkzaban et al., 2018). Higher ISQ values result in a higher mean stability (Marquezan et al., 2012). Studies evaluating the effect of PBM on the stability of dental implants have reported that the development of secondary stability does not take as long because fibrocartilage callus development increases during the initial stage of bone healing (Kazem Shakouri et al., 2010). Therefore, the boneimplant contact (BIC) factor increased after the laser irradiation on the periimplant site (Lopes et al., 2005; Matys et al., 2018). Using laser after a surgical procedure that involves hard and soft tissues enhances healing and has a biostimulating effect over osteoblastic and fibroblastic proliferation, and osteogenesis (Bozkaya et al., 2021; Chen et al., 2017; Dompe et al., 2020; Tang & Arany, 2013). Moreover, laser reduces inflammation and pain, accelerates wound healing, (AghaHosseini et al., 2012) and stimulates nerve regeneration (Farivar et al., 2014). Although, other clinical studies have not been able to demonstrate differences in the levels of stability of dental implants (Bozkaya et al., 2021; Mandić et al., 2015) or orthodontic miniimplants (MarañónVásquez et al., 2019) between the laser group and the control group, it is important to highlight the great differences between the few existing controlled clinical studies. For example, in the study by Lobato et al. (2020), the implants were placed in fresh sockets, which creates a situation of healing and primary stability very different from that of implants placed in healed sites, as in the study by Kinalski et al. (2021). In relation to the healing of hard tissues, some clinical studies have shown that PBM can reduce the healing time after grafting the extraction socket. Histological evidence suggests that new bone formation in the sockets appeared within 60 days after PBM treatment compared to a minimum of 120 days in the control group (Monea et al., 2015). Moreover, in a computed tomography and histomorphometric analysis of human alveolar bone repair developed by Romão et al. (2015), the relative bone volume was significantly higher in the laser group (P < 0.0001) suggesting that PBM is able to accelerate alveolar bone repair after molar extraction, leading to a more thin and close trabeculae. In molecular terms, the study of Palled et al. (2021) showed a significant rise in osteoprotegerin levels of the test group at 3 months contrary to significant decline in the control group, suggesting that the healing of periimplant hard and soft tissues may be enhanced with the use of PBM during the postoperative period. However, although some studies have been developed in relation to the effect of PBM at the microbiological level (Bozkaya et al., 2021), limited studies have been developed regarding the clinical healing and inflammation around implants after PBM. The aim of this clinical trial was to evaluate the effect of 808 nm diode laser PBM on implant stability using RFA measurements, and the effect of 660 nm diode laser PBM on inflammation and postsurgical healing. 2 | MATERIAL AND METHOD 2.1 | Trial design, participants, and setting The study was a randomised, doubleblinded clinical trial comprised of a control group and a test group. Participants were exclusively recruited from the University of Santiago de Compostela's Faculty OneSentence Summary This article is a double blind randomized clinical study that compares the effect of photobiomodulation on bone and tissue healing after implant placement surgery. 16000501, 2023, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/clr.14026 by Consorcio Interuniversitario Do Sistema Universitario De Galicia (Cisug), Wiley Online Library on [23/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 139 CAMOLESI et al. of Dentistry, within the Medicine, Surgery and Oral Implantology Department. The trial was conducted between February 2020 and July 2021, according to the Declaration of Helsinki, as reviewed in 2002. The study was approved by the Local Ethics and Research Committee (Ref. 2019/169) and registered in Clini calTr ials.gov, with the identifier: NCT03796494. All the patients who met the inclusion criteria were fully informed of the characteristics of the study and were invited to participate. Each patient underwent a complete clinical and oral assessment, as well as a radiological study based on conebeam computed tomography (CBCT) (iCATFLX). The tests wed the recommended criteria established in the Spanish CONSORT Statement (Cuschieri, 2019), as shown in Figure 1 and followed the SPIRIT statement. The patients included in this study all met the following inclusion criteria: (1) there was no presence of any systemic diseases which might be considered a contraindication, or if these were present they were controlled; (2) the informed consent form required for participation in the study has been signed; (3) they smoke <5 cigarettes per day; (4) they have sufficient bone quantity to insert 4 × 10 mm implants and ensure that no bone or soft tissue grafts are needed in molar and premolar areas; and (5) they have a minimum primary stability value of 50 ISQ. The exclusion criteria were: (1) they had undergone dental rehabilitation in aesthetic areas 13– 23 and 33– 43; (2) they have implants with mechanical torques inferior to 20 N; (3) they smoke more than 5 cigarettes per day; (4) they are pregnant and/or lactating; (5) they have cancer or a potentially malignant injury in the area where PBM is to be applied. 2.2 | Intervention The patients were distributed into two groups: a test group that received an active application of PBM (PBM+); and a control group that received an inactive/sham application of PBM, or laser in off mode (PBM−). 2.3 | Study products Forty implants with internal hex connection and a diameter of 4 × 10 mm were used. Implants were placed in healed mature bone (more than 6 months after the extractions), according to the manufacturer's guidelines (Model IPX, Nueva Galimplant). The model used was made of Ti IV and it had a macroscopic design that enhances primary stability in any circumstances. In all cases, aesthetical straight abutments were placed with their respective gingival protectors. A diode laser (Laser Duo, MMOSão Carlos) was used with the following parameters: (1) wavelength of 630– 808 nm, (2) output power of 100 mW, (3) continuous mode and (4) dose of 0.1 J/s and (5) handpiece with an output of 3 mm2. 2.4 | Surgical procedures The insertion of implants strictly followed the manufacturer's instructions regarding different bone types. Implants were placed mechanically and always 1 mm below the bone crest. Following the FIGURE 1 The consort flow diagram of subject Progress through the phases of a randomized trial 16000501, 2023, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/clr.14026 by Consorcio Interuniversitario Do Sistema Universitario De Galicia (Cisug), Wiley Online Library on [23/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 140 | CAMOLESI et al. surgical intervention, all of the patients received detailed instructions about oral hygiene; antibiotics (a 750 mg/8 h dose of amoxicillin for 7 days); and painkillers (a 600 mg/8 h dose of ibuprofen for 4 days). No provisional prosthesis was placed during the 8week observation period. 2.5 | Laser irradiation After surgery, half of the implants were randomly assigned to receive a treatment with a low intensity active laser. The test group, PBM+, received intraoral irradiation for 100 s through a handpiece that entered into contact with the mucosa and which was positioned to allow light to enter perpendicularly to the longitudinal axe of the dental implant at 5 mm from the bone crest. Three points were irradiated: the buccal side (4J) and the palatal or lingual side (4J) using the infrared light mode (808 nm), to stimulate bone tissue regeneration; and the occlusal side (2J) using the redlight mode (630 nm), to stimulate mucosal tissue regeneration and antiinflammatory effect. The laser treatment was performed immediately after surgery and it was repeated 7 days later. On each session, safety measures were taken with both the patients and odontologists wearing dark protective glasses. The parameters used for the irradiation were based on previous studies (Chen et al., 2019; Kinalski et al., 2021; Lobato et al., 2020). The total irradiation per session was 10 J during 100 s, the total energy density per session was 33.3 J/cm2, and the total energy density per implant was 66.6 J/cm2. The control group, PBM−, received a sham laser treatment, that is, only the irradiation of the patient was simulated. 2.6 | Measurement of primary and secondary objectives 2.6.1 | Assessment of implants stability Resonance frequency analysis (RFA) was performed using the Osstell™ Mentor device (Integration Diagnostics), and it was conducted by a trained and calibrated operator (GCVC) who was not aware of which side would be irradiated. Measurements were registered immediately following the implant surgery and after 7 days, 4 and 8 weeks. A standardised fixed length device was inserted (Smartpeg™ Integration Diagnostics) and it was screwed into each implant by hand. The transducer probing (Osstell™ Mentor Probe) was carried out by directing the tip of the handpiece to the small magnet located on the upper part of the Smartpeg™ at a distance of 2– 3 mm, until the instrument produced a beep and showed the implant stability quotient (ISQ). These measurements were performed in buccal, lingual, mesial and distal implant surfaces in order to obtaining a global average for the four surfaces. 2.6.2 | Assessment of the healing process of the mucosa The degree of postsurgery inflammation and early healing was assessed by two independent operators (GCVC and MPS). Postsurgical inflammation was assessed subjectively and dichotomously (yes/no), through visual examination, following the criteria described above by Bloemen and Cols (Bloemen et al., 2012). Healing was calculated using the healing index (HI) by Hamzani & Chaushu (2018) and Landry (1988). Table 1 shows the final score HI, that ranges from 0 to 5:0 for poor healing and 5 for excellent healing. The degree of concordance was verified by both researchers, who performed independent evaluations on the total sample, using Cohen's Kappa index (Mandrekar, 2011). The degree of agreement for the inflammation level was 0.91 and >0.90 at all HI levels. 2.7 | Sample size calculation The following statistical criteria were established in order to calculate the sample size: (1) a size of the expected increase or reduction effect on the HI of at least 1.5 at 1 week after surgery, (2) an alpha error of 0.05, and (3) a statistical power of 90%. These criteria were taken into account and the variance contrast for independent samples was applied. It was determined that a sample of 18 implants would be required for each group, that is to say a total of 36 implants. The final sample size was 42, considering an estimated loss of 15%. The sample size was calculated using the G Power 3.1.5 programme. Clinical outcome parameters Score 0 Score 1 Bleeding, spontaneously or on palpation Yes No Granulation tissue Yes No Tissue colour Redder than opposite side tissue Like the opposite side tissue Incision margins Incomplete flap closure/fibrin clot/partial necrosis Complete flap closure/ fine fibrin line Suppuration Yes No TABLE 1 Landry et al.'s healing index, the final score ranges from 0 to 5, where 0 indicates poor healing and 5 indicates excellent healing 16000501, 2023, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/clr.14026 by Consorcio Interuniversitario Do Sistema Universitario De Galicia (Cisug), Wiley Online Library on [23/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 141 CAMOLESI et al. 2.8 | Randomisation Simple randomization was performed for both study groups (PBM+/ PBM−). Briefly, a random number generator (N = 40) was used for the two study groups, using a SPSS 28.0 macro. 2.9 | Blinding All of the assessments of the results of this study were double blinded because neither the patients (due to the use of a placebo) nor the evaluators (who were not involved in the LLLT process) knew which treatment had been assigned to each patient. 2.10 | Statistical analysis The collected data was analysed using the SPSS software programme, version 24.0 (SPSS Inc.). The IQS data for primary and secondary stability was presented using central tendency measurements (mean) and variation (SD and CI of 95%). The variance was analysed in order to examine changes to the ISQ during the observation period. The statistical significance of the differences amongst the observed parameters for IQS between the groups at each observation point was analysed using the T test for unpaired groups. Contingency tables were created and the Chi Square and Kruskal Wallis tests were applied to study the differences between the groups in terms of postsurgery healing and inflammation. A multiple sequential logistic regression was employed to determine the risk (OR) of inflammation associated with the use of PBM. The statistical significance of all tests was defined as P < 0.05. 3 | RESULTS 3.1 | Sample description The sample was comprised of five male (38.4%) and eight female subjects (61.5%). Regarding the number of implants, a total of 40 implants were inserted, in 13 patients: 20 using PBM and 20 without using it. With regards to the area, 28 of the implants were placed in the jaw (70%), 37 (92.5%) with a coarse periodontium, and 36 (90%) with bone type IIIIIIV. Table 2 shows the complete sample data. 3.2 | Primary and secondary stability The primary basal implant stability which was measured using the ISQ scale, showed results of 71.5 ± 8.8. The average basal stability for the abutment was 71.9 ± 5.9, without significant differences. The average stability 7 days after the laser application was 68.3 ± 8.6 for the PBM− group, and 71.2 ± 5.9 for the PBM+ group (P = 0.228). After 4 weeks, the values became closer in both groups: 69.5 ± 7.4 for PBM− and 69.7 ± 3.5 for PBM+ (P = 0.908). After 8 weeks, the highest level of stability for the ISQ scale was achieved without differences between both groups: 72.3 ± 7.4 for PBM− and 72.5 ± 4.3 for PBM+ (P = 0.938). 3.3 | Postoperative inflammation A postoperative inflammation assessment was carried out 7 days after the clinical trial, the Figure 2 present the clinical aspect of the Landry et al. Healing Index(HI). The dichotomous method showed that the PBM+ group presented inflammation in seven implants (35%), while the PBM− group presented inflammation in 14 implants (70%) (P = 0.028). The healing index (HI) revealed variable healing levels in both groups. Nevertheless, the PBM+ group implants showed better early healing (Table 3). Only two of the implants (18.2%) from the PBM− group were classified with the maximum healing index (HI = 5), whereas in the PBM+ group, nine implants (45%) were classified with the aforementioned index (P < 0.0001). Considering HI as a quantitative variable, the PBM− group showed an average healing of 2.1 ± 1.2, while PBM+ showed an average HI of 4.10 ± 0.9 (P < 0.0001). Using the logistic regression, it was TABLE 2 Full description of the sample variants Variable PBM− n (%) PBM+ n (%) Pvalue Sex Men 5 (25) 5 (25) 1.000 Woman 15 (75) 15 (75) Localisation Maxillary 6 (30) 6 (30) 1.000 Mandible 14 (70) 14 (70) Abutment type Straight 12 (60) 7 (35) 0.113 Slim 8 (40) 13 (65) Periodontal phenotype Fine 2 (10) 1 (5) 0.548 Thick 18 (90) 19 (95) Bone type I 3 (15) 1(5) 0.292 IIIIIIV 17 (85) 19 (95) Visual examination Without inflammation 6 (60) 13 (65) 0.027 With inflammation 14 (40) 7 (35) HI 16 (30) 0 (0) <0.001 210 (50) 1 (5) 32 (10) 5 (25) 40 (0) 5 (25) 5 2 (0) 9 (45) Bold means that the have been statistically significant difference. 16000501, 2023, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/clr.14026 by Consorcio Interuniversitario Do Sistema Universitario De Galicia (Cisug), Wiley Online Library on [23/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 142 | CAMOLESI et al. determined that the nonapplication of the laser in the PBM− group caused an OR of 4.333 times of presenting inflammation (IC95% 1.150– 16.323; P = 0.030). 3.4 | Adverse events No adverse events related to the use of PBM were observed, except for the inflammatory processes that are associated with the surgical procedure itself. 4 | DISCUSSION PBM is a noninvasive therapy that uses photochemical and biological interactions to generate energy to help speed up cellular reparation and regeneration processes (Hamblin, 2017). Reports of the use of LLLT after implant surgery have been experiencing an increase, this is due to the demand for better and more predictable results in terms of healing and postoperative inflammation (Bozkaya et al., 2021; Gholami et al., 2019a). To the best of these authors' knowledge, and as reported in a recent systematic review (Qu et al., 2022), this is the first study analyzing the effects of diode laser irradiation at wavelengths of 808 and 630 nm combined, in an attempt to achieve a significant therapeutic effect with respect to improvement in implant stability, inflammation and tissue healing, respectively. With regards to the biological processes that take place following dental implant surgery, that is to say, osseointegration; although primary stability is achieved, nonetheless, in the first days following the implant placement the bone suffers restructuration, therefore a temporary reduction in implant stability is expected (Insua et al., 2017). Gum healing can take place either by first intention— when the implant stays submerged and edgetoedge suturing is performed— or by second intention— when a healing abutment is placed on the implant, to prevent the edges from moving closer. First intention healing usually results in faster healing and it has a lower risk of infection compared to second intention healing (Pippi, 2017). After having placed oneabutmentonetime implants with a successful primary stability, it was observed that PBM+ group was less affected by inherent adverse biological processes inherent to the surgical procedure. The average stability remained wellbalanced in all of the ISQ measurements, recording results similar to those obtained by Torkzaban et al. (2018). In their revision, Gholami et al. (2019b) reported that some studies observed increased bone activity at metabolic and cellular levels of the irradiated bone, as well as faster bone regeneration. Regarding the measurements made in this study, the mean stability values progressed equally in both groups throughout the study, except on the seventh day compared to the immediate postoperative period in the same group. The same results were observed in the studies by GarcíaMorales et al. (2012), Matys et al. (2019) and Torkzaban et al. (2018) that is to say, in the PBM+ group, the tendency to reduce implant stability was slower in the measurements made in the first 10– 15 days. This may be justified by the increased bone activity associated with PBM, which accelerates both bone remodelling and the implant osseointegration process (GarcíaMorales et al., 2012). After the reduction of the initial stability, both groups experienced a progressive increase in ISQ and at week 8 they reached values very similar to the initial ones. The reduction process followed by increased implant stability has also been reported in other studies (Matys et al., 2019; Torkzaban et al., 2018). Animal model studies have reported a significant increase in osseointegration in PBM+ groups, using an infrared wavelength (Khadra et al., 2004; Lopes et al., 2005; Maluf et al., 2010; Pereira et al., 2009). In our study, the application of PBM did not significantly improve the final stability of the dental implant in the long term, given that after 8 weeks, there were no significant differences between the two groups in terms of the average stability values, and this was also observed in FIGURE 2 Clinical aspect of the Landry et al. healing index (HI), where 0 indicates poor healing and 5 indicates excellent healing 16000501, 2023, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/clr.14026 by Consorcio Interuniversitario Do Sistema Universitario De Galicia (Cisug), Wiley Online Library on [23/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 143 CAMOLESI et al. other studies with the similar monitoring time (Bozkaya et al., 2021; GarcíaMorales et al., 2012; Lopes et al., 2005; Mandić et al., 2015; Torkzaban et al., 2018). The inflammation and healing responses obtained for the PBM+ group in the objective assessment and HI were considerably better than those obtained for the PBM− group. 65% of the PBM+ group's implants did not present with any subjective inflammation, and 45% of the same group attained the maximum score in the HI scale. It was not possible to carry out a comparative analysis given that no prior studies in which the effect of PBM on gum TABLE 3 Descriptive classification of each implant according to healing index (HI) Tissue colour Presence of bleeding Presence of granulation tissue Incision margin Presence of suppuration Total score (HI) Inflammation visual evaluation Case 1 0 1 0 0 1 2 Yes Case 2 0 1 0 1 1 3 No Case 3 0 0 0 1 1 2 No Case 4 0 1 1 0 1 3 No Case 5 0 0 0 0 1 1 No Case 6 0 0 1 0 1 2 Yes Case 7 0 1 0 0 1 2 Yes Case 8 0 0 1 0 1 2 Yes Case 9 0 0 0 0 1 1 Yes Case 10 0 0 0 0 1 1 Yes Case 11 0 1 0 0 1 2 Yes Case 12 0 0 0 0 1 1 Yes Case 13 1 1 1 1 1 5Yes Case 14 0 1 0 0 1 2 Yes Case 15 0 1 0 0 1 2 Yes Case 16 1 1 1 1 1 5Yes Case 17 0 1 0 0 1 2 Yes Case 18 0 0 0 0 1 1 Yes Case 19 0 0 0 0 1 1 Yes Case 20 0 1 0 0 1 2 Yes Case 21 1 1 1 1 1 5Yes Case 22 0 1 0 0 1 2 Yes Case 23 0 1 0 1 1 3 Yes Case 24 0 1 1 0 1 3 Yes Case 25 1 1 1 1 1 5No Case 26 1 1 1 1 1 5No Case 27 0 1 1 1 1 4 No Case 28 0 1 1 1 1 4 No Case 29 1 1 1 1 1 5No Case 30 0 1 1 1 1 4 No Case 31 1 1 1 1 1 5No Case 32 1 1 1 1 1 5No Case 33 0 1 1 0 1 3 Yes Case 34 0 1 1 1 1 4 Yes Case 35 1 1 1 1 1 5No Case 36 1 1 1 1 1 5No Case 37 0 0 1 1 1 3 Yes Case 38 1 1 1 1 1 5No Case 39 0 1 1 1 1 4 No Case 40 0 0 1 1 1 3 Yes 16000501, 2023, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/clr.14026 by Consorcio Interuniversitario Do Sistema Universitario De Galicia (Cisug), Wiley Online Library on [23/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 144 | CAMOLESI et al. postoperative implant surgery healing and inflammation were assessed were found. The healing scale applied (HI) was evaluated in studies that tested the effect of PBM on gum healing and inflammation following dental extraction (Hamzani & Chaushu, 2018). This better inflammatory and healing response with the application of PBM seems to be related to possible antimicrobial effects, thus in the study by Bozkaya et al., the PBM+ group presents a significant reduction in the level of periodontal pathogenic bacteria when compared to the PBM− group (Bozkaya et al., 2021). Furthermore, several studies have reported an increase in growth factors and antiinflammatory molecules in PBM+ groups (Gokmenoglu et al., 2014; Hamblin, 2017; Memarian et al., 2018; Tsai & Hamblin, 2017). This therefore justifies the results obtained in this study, given that the acceleration of osteogenic signalling and bone and mucosa vascularisation favours healing processes (Insua et al., 2017). In addition, accelerating the healing of the surgery wound and reducing the inflammatory process could may help to prevent marginal bone loss (Fernandes et al., 2021), which would increase the chance of dental implant survival (AguirreZorzano et al., 2013; Insua et al., 2017). In this study, we used the combined application of short and long wavelengths as recommended by Qu et al. (2022), to verify whether this protocol may produce more significant therapeutic effects. PBM therapy was applied on two separate occasions. The dose applied in each session was 13.32 J/cm2, with longer wavelength (808 nm), for bone tissue and 6.66 J/cm2, with shorter wavelength (660 nm), for mucosal tissue. These values are within the therapeutic window range and they are compatible with those found in the scientific literature (Carroll et al., 2014; Gholami et al., 2019b). The control of employed energy level is essential, given that a weak stimulation may not activate a cellular response, and, likewise, a high stimulation may inhibit or even deactivate the cellular response (Dompe et al., 2020; Gholami et al., 2019a; Lima et al., 2020; Na et al., 2018), meaning that there is an optimum stimulation within an energetic density range (dose). This dose, which is known as the therapeutic window, biphasic dose response, or ArndtSchulz curve (Dompe et al., 2020; Huang et al., 2011; Lima et al., 2020), is the responsible for cellular activation. If stimulation is not achieved or if it was overshot, the PBM protocol would be inadequate and would not work. The absence of a specific PBM protocol has been already highlighted by several authors as a problem (Bozkaya et al., 2021; Khadra et al., 2005; Qu et al., 2022; Woodruff et al., 2004). This is due, among other factors, to the heterogeneity of the characteristics and parameters of the laser devices available on the market (Khadra et al., 2005; Lima et al., 2020). It is important to note that PBM parameters that work on one cell group will not necessarily work on another. In other words, the ideal therapeutic window for hard tissues is not the same as for soft tissues, just as surely the window to produce favorable results for osseointegration in animals does not have the same effectiveness in humans (Chen et al., 2019; Memarian et al., 2018). The main limitation of this study was the impossibility of measuring the ISQ in the period between the second and eighth weeks, considering the time required without mechanical stimulation for implants with deferred load. This measurement could yield more revealing data in the PBM+ group. Other studies with designs that allow ISQ measurements without the need for reversetorque to the implants are necessary. Another limitation inherent to the technology itself lies in the impossibility of evaluating the bone/implant surface (especially in the buccal area) that absorbs/reflects the laser rays. The use of postoperative antiseptics and antibiotics (both medically and ethically necessary) could produce biases based on individual variability. The role of the implant diameter in relation to the crestal bone should be evaluated in more specific studies. 5 | CONCLUSIONS Longterm applications of PBM do not interfere with implant stability, and they may provide a good alternative for professionals that need to increase these values in early phases for prosthodontic reasons. With regards to healing and inflammation, PBM showed excellent results in this study. Therefore, the application of 808 nm infrared laser for bone tissue, and 630 nm for mucosal tissue in two sessions (in the immediate postoperative period and 7 days after) is considered to be an effective way of reducing inflammation and improving early healing of mucosal tissue, but ineffective to increase or accelerate the secondary stability of implants. Longterm monitoring of these implants is required in order to assess the role of PBM in terms of marginal bone loss. AUTHOR CONTRIBUTIONS Gisela Cristina Vianna Camolesi: Conceptualization (equal); data curation (lead); formal analysis (supporting); investigation (equal); methodology (supporting); project administration (equal); resources (equal); validation (equal); writing – original draft (lead). Manuel SomozaMartin: Conceptualization (equal); investigation (equal); methodology (equal); project administration (equal); supervision (equal). M Dolores ReboirasLópez: Data curation (equal); supervision (supporting). Fabio CamachoAlonso: Formal analysis (supporting); validation (supporting); writing – review and editing (supporting). Andrés Blanco Carrión: Formal analysis (equal); methodology (equal); supervision (equal). Mario PérezSayáns: Conceptualization (equal); data curation (supporting); formal analysis (lead); investigation (lead); methodology (lead); project administration (equal); resources (equal); supervision (lead); validation (equal); writing – original draft (supporting); writing – review and editing (lead). FUNDING INFORMATION The study was supported by Nueva Galimplant and the University of Santiago de Compostela (Ref. USC2019CE178). The funding source played no role in the design of this study, the data collection and analyses, the decision to publish, and the preparation of the manuscript. 16000501, 2023, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/clr.14026 by Consorcio Interuniversitario Do Sistema Universitario De Galicia (Cisug), Wiley Online Library on [23/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 145 CAMOLESI et al. CONFLICT OF INTEREST The authors declare that there is no conflict of interest. DATA AVAILABILITY STATEMENT Data available on request from the authors. ORCID Gisela C. V. Camolesi https://orcid.org/0000-0003-0757-638X José M. SomozaMartín https://orcid.org/0000-0001-9386-784X Maria D. 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