Clinical efficacy of non-eugenol containing periodontal dressing with and without platelet-rich fibrin on wound healing after surgical gingival depigmentation: a randomized clinical trial

Clinical efficacy of non-eugenol containing periodontal dressing with and without platelet-rich fibrin on wound healing after surgical gingival depigmentation: a randomized clinical trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical efficacy of non-eugenol containing periodontal dressing with and without platelet-rich fibrin on wound healing after surgical gingival depigmentation: a randomized clinical trial Aya Hesham, Marwa Nawawy, Mahmoud Moussa, Mona Darhous This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4843486/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Aim: The study aimed to evaluate the effect of platelet-rich fibrin on wound healing after surgical depigmentation Methodology: Twenty-four patients with gingival pigmentation were recruited and randomly assigned to the control group; non-eugenol periodontal dressing only, or to the test group; L-PRF with periodontal dressing. Gingival depigmentation was done using a combination of scalpel and bur techniques and both groups were covered using periodontal dressing. The healing index, epithelization test and pigmentation recurrence were tested and compared. Results: The healing index in the test group was 91.7% of the patients scored 4 (Very good) on the 5th day, while in the control group, 83.3% scored 2 (poor) on the 5th day and 16.7% were observed to have a score 3 (Good). The epithelization test was the most significant with 100% receiving a negative result in the test group after 5 days with 66.7% completely healed and 33.3% partially healed when compared to 100% of the control group having a positive score (no epithelization). The pigmentation recurrence after 6 months was observed in 66.7% in the test group while only 33.3% in the control group. Conclusion: Using PRF after gingival depigmentation results in better wound healing when compared to using periodontal packs alone. Gingival pigmentation PRF wound healing gingival depigmentation pigmentation recurrence Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 INTRODUCTION The appearance and state of health of the gingiva is of vital importance to a person’s smile (Verma et al., 2013). The colour of the gingiva is one of the most crucial aspects of an attractive smile (Bhusari & Kasat, 2011). The gingival colour varies from one person to another based on physiological or pathological factors which include race/ genetics, medications, infections, trauma, smoking, or medical conditions (Dummett, 1979). It could range from coral pink to brown, blue or black. Physiological pigmentation is not a medical condition and causes no harm to the patient but may cause psychological harm and an unattractive smile especially when coupled with excessive gingival display (Alasmari, 2018). Gingival depigmentation is considered one of the most common periodontal plastic procedures which is concerned with the elimination or reduction of hyperpigmentation (Malhotra et al., 2014). There are various depigmentation techniques available including; scalpel surgery, bur abrasion, cryosurgery, laser ablation, electrosurgery, chemical agents, free gingival grafts and radiosurgery (Bhatsange & Japati, 2011; Malhotra et al., 2014). Each technique has its advantages and disadvantages. The most common disadvantages are post-operative pain, bleeding, delayed wound healing, repigmentation, procedure difficulty, complicated techniques and expensive equipment (Narayankar et al., 2017). Platelet Rich Fibrin (PRF) was first used by Choukroun et al in 2001 in dentistry which is a new generation of platelet concentrates. PRF consists of an autologous leukocyte-platelet-rich fibrin matrix, composed of a tetra molecular structure, with cytokines, platelets, and stem cells within it, that act as a biodegradable scaffold that favours the development of microvascularization and can guide epithelial cell migration to its surface (Dohan et al., 2006). Pigmentation recurrence is one of the most important aspects following the depigmentation procedure. The recurrence is almost present with all types of treatment modalities however, it varies in time and intensity. Repigmentation occurs primarily due to the migration of the melanocytes to the depigmented area (Dummett & Barens, 1971; Murthy et al., 2012). The study was designed to evaluate the effect of L-PRF in regards to post-operative pain and wound healing, epithelization and repigmentation following surgical gingival depigmentation procedure. MATERIALS AND METHODS The study included 24 patients (19 female and 6 male) ages ranging from 18–35 years. The study was done as a randomized controlled clinical trial (ClinicalTrials.gov identifier: NCT04495205), parallel, two-arms, and superiority trial with a 1:1 allocation ratio. Population: The study recruited adult patients who have a gingival pigmentation index score of 2 (Kumar et al., 2012) from the outpatient dental clinics of the Oral Medicine and Periodontology Department, Cairo University and MSA University. Eligibility criteria included patients ages 18–40 years old, systemically healthy, mild to moderate gingival pigmentations, gingival and plaque index 2mm. Smokers, patients taking any medications that could affect healing, previous depigmentation procedures, pregnant or lactating females and have had previous periodontal surgery within 6 months before the start of the trial were excluded. The eligible patients were sat down for an interview to explain the procedure and its objectives, the follow-up periods, post-operative complications and its treatment. Sample size calculation: Based on the study of Chhina et al. in 2019, the VAS was checked at the 1st, and 7th day postoperatively. On the 1st day, 2.5 ± 0.515 of patients reported pain and 0.7 was the clinical most important difference based on expert opinion (Chhina et al., 2019), Using power 80% and p-value: 0.05 as a significance level, the number of patients that were enrolled to the study were 10 in each group with 20% more allocated to overcome dropouts, accordingly the number was 12 in each group with 24 patients in the study. Sample size calculation was achieved using Independent T-test. Randomization, allocation concealment and blinding: Computer-generated randomization (random.org) was used for the patient’s division into two groups from 1 to 12 randomly and equally assigned to both groups. Patients were sequentially numbered and a central telephone was used by (M.D) to inform the operator (A.R) of the allocation of the patients to either group. After re-evaluation, non-surgical periodontal therapy was performed and signed written consent was obtained. Due to the nature of the procedure, only the statistician was blinded. Treatment: All eligible patients received non-surgical periodontal therapy followed by adequate oral hygiene measures and then re-evaluated after 6 weeks for their compliance and oral hygiene status. The patients were enrolled into two groups: Control group: Placing L-PRF after surgical depigmentation then covering it with non-eugenol-containing periodontal dressing Test group: Placing non-eugenol-containing periodontal dressing after surgical depigmentation Surgical procedure: The main investigator ( A.R) performed the surgical de-epithelization of the gingiva using high-speed diamond flame/ football stones with feather-like brushing strokes under copious irrigation until the underlying soft connective tissue was exposed. The bur abrasion was done sparing the gingival margins, interdental papilla and any deep areas of pigmentation which were depigmented using a surgical blade no.15 in strokes in one direction till all the visible pigmentations were removed. Then, the area was mopped with a wet gauze to stop the bleeding and the periodontal dressing was applied. Regarding the test group before the administration of anaesthesia, two test tubes of 5 ml blood samples were withdrawn from the patient. The tubes were placed in a centrifuge machine that was set at 2800 rpm for 12 minutes. The prepared PRF was picked up and compressed between two saline-soaked sterile gauze pieces to obtain the PRF membrane. The membrane was then adapted on the surgical site and the excess was trimmed off. The PRF was stabilized in place by crisscross sutures using 5 − 0 resorbable vicryl sutures. Then the periodontal dressing dressing was placed in the same manner as the control group. Wound healing parameters: Wound healing was recorded using healing index (HI) measurement at 3 and 5 days post-operatively (Landry, 1985). Re-epithelization was recorded using an epithelization test by toluidine blue (TB) 5 days post-operatively (Hedge et al., 2006). The re-epithelization was recorded using colour interpretation of a dark blue (royal or navy) stain is considered positive, light blue staining is doubtful and negative when no colour is observed. Pigmentation relapse: The relapse was defined as the reappearance of the pigmentation and was recorded using the gingival pigmentation index 6 months post-operative (Kumar et al., 2012). Data analysis and statistical method: Data presented as mean, standard deviation (SD) and 95% confidence interval. Data was explored for normality using Shapiro-Wilk test. Age data showed a normal distribution while all other data showed a non-normal distribution. Independent t-test was used to compare between tested groups for mean age. Mann-Whitney test was used to compare between the tested groups. Friedmann test was used for comparison between tested periods for each group followed by multiple comparisons with Dunn Bonferroni. The significance level was set at p < 0.05. Statistical analysis was performed with IBM® SPSS®. RESULTS Study patients: Twenty-four medically free patients were enrolled and electronically randomized and allocated to either group. 12 patients were assigned to the control group and 12 in the intervention group. The mean age of the patients was 22.5 ± 4.46 years in the control group and 21.92 ± 3.03 in the intervention group with no statistical significance between them. There were no dropouts and the data of all patients were evaluated in the statistical analysis. Table 1 Demographic data of the patients Group A (Control) Group B (Intervention) p-value Age [Mean (SD)] 22.5(4.46) 21.92(3.03) 0.712 NS Gender [N (%)] Female 9(75) 10(83.3) 0.615 NS Male 3( 25 ) 2(16.7) NS = non-significant Clinical outcomes Healing index (Secondary outcome): The healing index was measured during the 3rd and 5th days postoperatively, which showed statistical significance between the two groups favouring the intervention group. Control group: the healing index was very poor (score 1) for one patient (8.3%), poor (score 2) for 10 patients (83.3%) and good (score 3) for one patient (8.3%) at 3 days post-operative. At 5 days post-operative; the index scores showed a slight improvement of poor (score 2) for 10 (83.3%) patients and 2 patients (16.7%) receiving good (score 3). Intervention group: all 12 (100%) patients had healing scores of good at 3 days post-operative which improved to very good (score 4) for 11(91.7%) patients and good (score 3) for one patient (8.3%) after 5 days. Table 2 Frequency (n) and Percentage (%) of healing index distribution for different tested groups. Healing index Group A (Control) Group B (Intervention) p-value n % n % Day 3 Very poor 1 8.3% 0 0.0% < 0.001* Poor 10 83.3% 0 0.0% Good 1 8.3% 12 100.0% Very good 0 0.0% 0 0.0% Excellent 0 0.0% 0 0.0% Day 5 Very poor 0 0.0% 0 0.0% < 0.001* Poor 10 83.3% 0 0.0% Good 2 16.7% 1 8.3% Very good 0 0.0% 11 91.7% Excellent 0 0.0% 0 0.0% p-value 0.317 NS 0.001* Epithelization test (Toluidine blue test): The epithelization test was performed using Toluidine blue on the 5th day post-operatively. There was statistical significance between the two groups favouring the intervention group. Control group; all 12 (100%) patients had a dark blue colour after the toluidine blue test after 5 days post-operative. Intervention group; 8 (66.7%) patients were found to have light blue colour and 4 (33.3%) had light blue with dark specks after the toluidine blue test 5 days post-operative. Table 3 Frequency (n) and Percentage (%) of Toluidine blue after 5 days for different tested groups. Group A (Control) Group B (Intervention) P value n % n % < 0.001* Toluidine blue after 5 days Light blue 0 0.0% 8 66.7% Light blue with dark specks 0 0.0% 4 33.3% Dark blue 12 100.0% 0 0.0% *=significant, NS = Non-significant Relapse (Repigmentation) after 6 months: The relapse (repigmentation) was measured 6 months post-operatively using the gingival pigmentation index. There was no statistical significance between the two tested groups. In the control group: 33.3% (n = 4) of the patients were observed to have repigmentation while 66.7% (n = 8) of patients were found to have repigmentation in the intervention group. Table (4) Frequency (n) and Percentage (%) of repigmentation after 6 months for different tested groups. Group A (Control) Group B (Intervention) p-value n % n % Repigmentation after 6 months No 8 66.7% 4 33.3% 0.102 NS Yes 4 33.3% 8 66.7% *=significant, NS = non-significant Aesthetics have become an integral part of dentistry nowadays with a remarkable increase in the demand for aesthetic procedures. Dentists are now required to achieve and maintain pristine aesthetics as well as address the biological and functional aspects of every procedure performed (Humagain et al., 2009). Melanin, the most common endogenous pigment, is the main cause for physiological gingival pigmentation. With regards to gingival pigmentation, it is presented as a diffuse light brown to black discoloured patches or strands involving the gingival margin and/or attached gingiva and may even extend to the alveolar mucosa (Nagati et al., 2017). The combined use of bur abrasion and scalpel techniques was chosen in the current study due to the numerous advantages of both techniques which include: the ease of execution, no need for special equipment, time efficiency, fast wound healing, low recurrence rates and economic compared to other techniques. However, both of these methods have drawbacks like increased post-operative pain and bleeding as well as needing the use of periodontal dressing post-operatively (Gul et al., 2019; Suchetha et al., 2018). After gingival depigmentation procedures; an exposed connective tissue wound is created. Whether to cover this wound with a periodontal dressing or not is an ongoing debate. The use of non-eugenol periodontal dressing was due to it being one of the most biocompatible dressings that have adequate mechanical, physical and therapeutic properties (Baghani & Kadkhodazadeh, 2013; Bezawada et al., 2020; Kathariya et al., 2015). The periodontal dressing was removed after 5 days post-operative to avoid delayed healing and increased infection rates due to plaque accumulation around the dressing which is associated with leaving it for long periods (Kathariya et al., 2015). The most significant observation was in the toluidine blue epithelization test after 5 days, which showed that 66.7% of the surgical sites were completely healed and 33.3% were partially healed when compared to 100% of the control group having no healing. These results are per Dahiya et al in 2019 This could be due to the high platelet concentrations of platelets in the PRF that are responsible for the fast regeneration of the epithelium and connective tissue in the PRF-treated sites(Bansal et al., 2016; Dahiya et al., 2019; Debnath & Chatterjee, 2018). The healing index results were in favour of the test group with 100% of the patients scoring 3 (Good) on the 3rd day which improved to 4 (Very good) by 91.7% of the patients on the 5th day. On the other hand in the control group on the 3rd day, 83.3% of the patients received a score of 2 (Poor) which remained unchanged on the 5th day. This is also supported by Dahiya and colleagues in 2019 who reported that on the 3rd day post-operative, 100% of the patients in the PRF group had good healing scores, which improved to very good on the 5th postoperative day. In the non‑eugenol periodontal dressing group, 58.3% of patients had poor healing scores on the 3rd day post-operative which improved to good healing scores in 100% of the patients. The difference in the results for the control groups on the 5th day might be linked to the intensity of the gingival pigmentation that requires deeper tissue removal (Bansal et al., 2016; Dahiya et al., 2019; Debnath & Chatterjee, 2018). Regarding gingival pigmentation recurrence; it was found that the test group showed a higher recurrence rate than the control group but with a decreased intensity than pre-treatment 6 months post-operative. The pigmentation recurrence intensity decreased from a score of 2 on the Gingival pigmentation index to a score of 1. The high repigmentation recurrence in the PRF group might be due to the accelerated wound healing of the PRF which caused a faster regeneration of the melanocytes. However, to the authors’ knowledge, there are no studies in the literature that have tested the recurrence rates after 6 months when using PRF. In the current study, the authors observed that the pigmentation recurrence was detected more in individuals with a darker complexion than fairer complexion and in the anterior region more than posterior region due to sunlight exposure and this is in accordance with a study in 2017 by Hosadurga and co-workers (Hosadurga et al., 2017). The repigmentation mechanism is still not clear but there are a few theories discussed in the literature which may include the genetic predisposition of the individuals, the residual melanocytes, migration of melanocytes from neighbouring sites or sunlight exposure (Hosadurga et al., 2017; Lin et al., 2014; Perlmutter & Tal, 1986). CONCLUSION Within the limitations of this study, we could conclude the following: Using PRF after surgical depigmentation has resulted in significant differences in healing index and epithelization in favour of the test group when compared to using periodontal dressing alone. A higher rate of gingival pigmentation recurrence was observed with the accelerated wound healing of the test group over the control group which is still unclear as to why it occurred. RECOMMENDATIONS Similar RCT studies should be done but with a larger sample size and longer follow-up period. Testing other wound healing accelerating materials, for example, hyaluronic acid or aloe vera in comparison to the PRF after depigmentation procedures. Testing if injection of Vitamin C after depigmentation will result in decreased recurrence rates when using PRF. Declarations Ethical approval: The study was reviewed and approved by the Ethics Committee of Scientific Research - faculty of Dentistry – Cairo University code 4420. Conflict of interest: There is no conflict of interest. Informed consent: All patients gave written consent to participate in the trial. Funding: The authors declare that no funds, grants or other support were received during the preparation of the manuscript. Author Contribution A.H: Responsible for the conception of the work, performed all the practical procedures and wrote the main manuscript.M.N: Supervised the conception of the work, practical procedures and writing of the manuscript.M.M: Supervised the conception of the work, practical procedures and writing of the manuscript.M.D: Supervised the conception of the work and reviewing the manuscript. References Alasmari DS (2018) An insight into gingival depigmentation techniques: The pros and cons. 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J Periodontol 57(1):48–50. https://doi.org/10.1902/jop.1986.57.1.48 Suchetha A, Shahna N, Bhat D, Apoorva D, S., Sapna N (2018) A review on gingival depigmentation procedures and repigmentation. Int J Appl Dent Sci 4(4):336–341 Verma S, Gohil M, Rathwa V (2013) Gingival depigmentation. Indian J Clin Pract 23(12):801–803 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4843486","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":339788978,"identity":"2948ebda-a6e2-4d8d-b950-2584795f35d7","order_by":0,"name":"Aya Hesham","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEUlEQVRIiWNgGAWjYJACZiBOAGLGhx8qDoBFDjwgUguzscSZAww8IC0JRGphk+Btg2hhwKeFf0byA+aCiro8/mkH2CQk592Rsxc7/BBoi52cbgN2LRI30gyYZ5w5XCxxO4HZonDbM2Me6TQDoJZkY7MDOKy5kWDADHRPYsPtBMYbktsOJ/ZIJ4C0HEjchkOL/I30D8y8/+oS599OYJDgnQPSkv4BrxaDGzlAWxqYEzfcTmCS4G0AacnBb4vhmTcFzDzHDiduBPrFWOLYYWOe2zkFBxIMcPtF7nj6BmaemrrEeUC/PPxQc1iOfXb65g8fKuzkcHpfIIH9B4TF/wHZwTiUgxXiMmsUjIJRMApGAQwAAPSaZNuO5zfzAAAAAElFTkSuQmCC","orcid":"","institution":"October University of Modern Sciences and Arts","correspondingAuthor":true,"prefix":"","firstName":"Aya","middleName":"","lastName":"Hesham","suffix":""},{"id":339788981,"identity":"4c378ed8-4593-41ef-8eac-5a4982d4d65f","order_by":1,"name":"Marwa Nawawy","email":"","orcid":"","institution":"Cairo University","correspondingAuthor":false,"prefix":"","firstName":"Marwa","middleName":"","lastName":"Nawawy","suffix":""},{"id":339788984,"identity":"44cd8080-3f1b-43b2-84d1-367be4826646","order_by":2,"name":"Mahmoud Moussa","email":"","orcid":"","institution":"October University of Modern Sciences and Arts","correspondingAuthor":false,"prefix":"","firstName":"Mahmoud","middleName":"","lastName":"Moussa","suffix":""},{"id":339788987,"identity":"1f76580d-a484-4a5c-a72b-f58e3f3a90d2","order_by":3,"name":"Mona Darhous","email":"","orcid":"","institution":"Cairo University","correspondingAuthor":false,"prefix":"","firstName":"Mona","middleName":"","lastName":"Darhous","suffix":""}],"badges":[],"createdAt":"2024-08-01 15:57:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4843486/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4843486/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":64010125,"identity":"8483d324-af23-4274-9a35-b58bb04d0758","added_by":"auto","created_at":"2024-09-04 23:24:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":644279,"visible":true,"origin":"","legend":"\u003cp\u003ePreoperative clinical pictures of the patient with the extension of the gingival pigmentation on the attached gingiva from the pre-molar region of the right side to the pre-molar region of the left side.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4843486/v1/d30e2f435c0fc215f0664603.png"},{"id":64010119,"identity":"1d893812-de11-4b25-bc84-9f7fadbdec6e","added_by":"auto","created_at":"2024-09-04 23:24:20","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":820179,"visible":true,"origin":"","legend":"\u003cp\u003e(a) clinical picture showing the depigmentation procedure using a high-speed diamond stone. (b) depigmentation of the upper right side. (c) depigmentation procedure completed in the upper arch.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4843486/v1/3ff312fd4c54cba39ad1aeb1.png"},{"id":64010213,"identity":"116f5d4c-eb52-4c98-b5a4-38abb05b4c99","added_by":"auto","created_at":"2024-09-04 23:32:20","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":817194,"visible":true,"origin":"","legend":"\u003cp\u003e(a): the collected blood samples. (b): the placement of the test tubes in the centrifuge. (c): the tube after centrifuging with 3 layers of PRF. (d): the final Platelet Rich Fibrin clot. (e) \u0026amp; (f): PRF clot before pressing them between 2 sterile gauze pieces to create a PRF membrane.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4843486/v1/97d1ab95920fcf877407fdff.png"},{"id":64010120,"identity":"2d4fdeb9-b3a3-4b7c-acc2-567c76ecc4e1","added_by":"auto","created_at":"2024-09-04 23:24:20","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":570325,"visible":true,"origin":"","legend":"\u003cp\u003e(a) clinical picture showing placement of PRF membrane on the depigmented site. (b) Securing the PRF membrane using criss-cross sutures. (c) Placement of periodontal dressing over the depigmented site.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4843486/v1/ed4c936717bdd30a41da73dd.png"},{"id":64010121,"identity":"09b457d9-51c0-44ed-ba0c-995bc2bc0c9b","added_by":"auto","created_at":"2024-09-04 23:24:20","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":507547,"visible":true,"origin":"","legend":"\u003cp\u003e(a): intervention group 3 days post-operative after removal of periodontal dressing. (b): control group 3 days post-operative after removal of periodontal dressing.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-4843486/v1/d4ab1dbc433c366ea2f02cbc.png"},{"id":64010124,"identity":"e0c2f97b-2373-4cac-a8be-4c59e3cd0631","added_by":"auto","created_at":"2024-09-04 23:24:20","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":955991,"visible":true,"origin":"","legend":"\u003cp\u003e(a): intervention group 5 days post-operative. (b): control group 5 days post-operative. (c): intervention group after the toluidine blue test showing a light blue colour which indicates complete wound epithelialization. (d): control group after toluidine blue test showing\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-4843486/v1/abfdc8cac4c288a118623c8b.png"},{"id":64010122,"identity":"8b86a3ac-c2e1-41dc-8b5d-289e4956d073","added_by":"auto","created_at":"2024-09-04 23:24:20","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":446225,"visible":true,"origin":"","legend":"\u003cp\u003e(a): Intervention group at 6 months post-operative showing signs of repigmentation in attached gingiva. (b): Control group at 6 months post-operative showing no signs of repigmentation.\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-4843486/v1/61db7c687f0936699e24ee27.png"},{"id":72651921,"identity":"907930f9-4d10-4bce-834e-3bded99c75f6","added_by":"auto","created_at":"2024-12-30 19:01:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":7486398,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4843486/v1/571cc67b-8453-4fee-b91d-0889763b8a59.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical efficacy of non-eugenol containing periodontal dressing with and without platelet-rich fibrin on wound healing after surgical gingival depigmentation: a randomized clinical trial","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eThe appearance and state of health of the gingiva is of vital importance to a person\u0026rsquo;s smile (Verma et al., 2013). The colour of the gingiva is one of the most crucial aspects of an attractive smile (Bhusari \u0026amp; Kasat, 2011). The gingival colour varies from one person to another based on physiological or pathological factors which include race/ genetics, medications, infections, trauma, smoking, or medical conditions (Dummett, 1979). It could range from coral pink to brown, blue or black. Physiological pigmentation is not a medical condition and causes no harm to the patient but may cause psychological harm and an unattractive smile especially when coupled with excessive gingival display (Alasmari, 2018).\u003c/p\u003e \u003cp\u003eGingival depigmentation is considered one of the most common periodontal plastic procedures which is concerned with the elimination or reduction of hyperpigmentation (Malhotra et al., 2014). There are various depigmentation techniques available including; scalpel surgery, bur abrasion, cryosurgery, laser ablation, electrosurgery, chemical agents, free gingival grafts and radiosurgery (Bhatsange \u0026amp; Japati, 2011; Malhotra et al., 2014). Each technique has its advantages and disadvantages. The most common disadvantages are post-operative pain, bleeding, delayed wound healing, repigmentation, procedure difficulty, complicated techniques and expensive equipment (Narayankar et al., 2017).\u003c/p\u003e \u003cp\u003ePlatelet Rich Fibrin (PRF) was first used by Choukroun et al in 2001 in dentistry which is a new generation of platelet concentrates. PRF consists of an autologous leukocyte-platelet-rich fibrin matrix, composed of a tetra molecular structure, with cytokines, platelets, and stem cells within it, that act as a biodegradable scaffold that favours the development of microvascularization and can guide epithelial cell migration to its surface (Dohan et al., 2006).\u003c/p\u003e \u003cp\u003ePigmentation recurrence is one of the most important aspects following the depigmentation procedure. The recurrence is almost present with all types of treatment modalities however, it varies in time and intensity. Repigmentation occurs primarily due to the migration of the melanocytes to the depigmented area (Dummett \u0026amp; Barens, 1971; Murthy et al., 2012).\u003c/p\u003e \u003cp\u003eThe study was designed to evaluate the effect of L-PRF in regards to post-operative pain and wound healing, epithelization and repigmentation following surgical gingival depigmentation procedure.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003eThe study included 24 patients (19 female and 6 male) ages ranging from 18\u0026ndash;35 years. The study was done as a randomized controlled clinical trial (ClinicalTrials.gov identifier: NCT04495205), parallel, two-arms, and superiority trial with a 1:1 allocation ratio.\u003c/p\u003e\n\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003ePopulation:\u003c/h2\u003e\n\u003cp\u003eThe study recruited adult patients who have a gingival pigmentation index score of 2 (Kumar et al., 2012) from the outpatient dental clinics of the Oral Medicine and Periodontology Department, Cairo University and MSA University.\u003c/p\u003e\n\u003cp\u003eEligibility criteria included patients ages 18\u0026ndash;40 years old, systemically healthy, mild to moderate gingival pigmentations, gingival and plaque index\u0026thinsp;\u0026lt;\u0026thinsp;1, good oral hygiene, thick gingival biotypes and keratinized gingiva\u0026thinsp;\u0026gt;\u0026thinsp;2mm. Smokers, patients taking any medications that could affect healing, previous depigmentation procedures, pregnant or lactating females and have had previous periodontal surgery within 6 months before the start of the trial were excluded. The eligible patients were sat down for an interview to explain the procedure and its objectives, the follow-up periods, post-operative complications and its treatment.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003ch2\u003eSample size calculation:\u003c/h2\u003e\n\u003cp\u003eBased on the study of Chhina et al. in 2019, the VAS was checked at the 1st, and 7th day postoperatively. On the 1st day, 2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.515 of patients reported pain and 0.7 was the clinical most important difference based on expert opinion (Chhina et al., 2019), Using power 80% and p-value: 0.05 as a significance level, the number of patients that were enrolled to the study were 10 in each group with 20% more allocated to overcome dropouts, accordingly the number was 12 in each group with 24 patients in the study. Sample size calculation was achieved using Independent T-test.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003ch2\u003eRandomization, allocation concealment and blinding:\u003c/h2\u003e\n\u003cp\u003eComputer-generated randomization (random.org) was used for the patient\u0026rsquo;s division into two groups from 1 to 12 randomly and equally assigned to both groups. Patients were sequentially numbered and a central telephone was used by (M.D) to inform the operator (A.R) of the allocation of the patients to either group. After re-evaluation, non-surgical periodontal therapy was performed and signed written consent was obtained. Due to the nature of the procedure, only the statistician was blinded.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n\u003ch2\u003eTreatment:\u003c/h2\u003e\n\u003cp\u003eAll eligible patients received non-surgical periodontal therapy followed by adequate oral hygiene measures and then re-evaluated after 6 weeks for their compliance and oral hygiene status. The patients were enrolled into two groups:\u003c/p\u003e\n\u003cp\u003eControl group: Placing L-PRF after surgical depigmentation then covering it with non-eugenol-containing periodontal dressing\u003c/p\u003e\n\u003cp\u003eTest group: Placing non-eugenol-containing periodontal dressing after surgical depigmentation\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n\u003ch2\u003eSurgical procedure:\u003c/h2\u003e\n\u003cp\u003eThe main investigator ( A.R) performed the surgical de-epithelization of the gingiva using high-speed diamond flame/ football stones with feather-like brushing strokes under copious irrigation until the underlying soft connective tissue was exposed. The bur abrasion was done sparing the gingival margins, interdental papilla and any deep areas of pigmentation which were depigmented using a surgical blade no.15 in strokes in one direction till all the visible pigmentations were removed. Then, the area was mopped with a wet gauze to stop the bleeding and the periodontal dressing was applied.\u003c/p\u003e\n\u003cp\u003eRegarding the test group before the administration of anaesthesia, two test tubes of 5 ml blood samples were withdrawn from the patient. The tubes were placed in a centrifuge machine that was set at 2800 rpm for 12 minutes. The prepared PRF was picked up and compressed between two saline-soaked sterile gauze pieces to obtain the PRF membrane. The membrane was then adapted on the surgical site and the excess was trimmed off. The PRF was stabilized in place by crisscross sutures using 5\u0026thinsp;\u0026minus;\u0026thinsp;0 resorbable vicryl sutures. Then the periodontal dressing dressing was placed in the same manner as the control group.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n\u003ch2\u003eWound healing parameters:\u003c/h2\u003e\n\u003cp\u003eWound healing was recorded using healing index (HI) measurement at 3 and 5 days post-operatively (Landry, 1985). Re-epithelization was recorded using an epithelization test by toluidine blue (TB) 5 days post-operatively (Hedge et al., 2006). The re-epithelization was recorded using colour interpretation of a dark blue (royal or navy) stain is considered positive, light blue staining is doubtful and negative when no colour is observed.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003ch2\u003ePigmentation relapse:\u003c/h2\u003e\n\u003cp\u003eThe relapse was defined as the reappearance of the pigmentation and was recorded using the gingival pigmentation index 6 months post-operative (Kumar et al., 2012).\u003c/p\u003e\n\u003cdiv id=\"Sec10\" class=\"Section3\"\u003e\n\u003ch2\u003eData analysis and statistical method:\u003c/h2\u003e\n\u003cp\u003eData presented as mean, standard deviation (SD) and 95% confidence interval. Data was explored for normality using Shapiro-Wilk test. Age data showed a normal distribution while all other data showed a non-normal distribution. Independent t-test was used to compare between tested groups for mean age. Mann-Whitney test was used to compare between the tested groups. Friedmann test was used for comparison between tested periods for each group followed by multiple comparisons with Dunn Bonferroni. The significance level was set at \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Statistical analysis was performed with IBM\u0026reg; SPSS\u0026reg;.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n\u003ch2\u003eStudy patients:\u003c/h2\u003e\n\u003cp\u003eTwenty-four medically free patients were enrolled and electronically randomized and allocated to either group. 12 patients were assigned to the control group and 12 in the intervention group. The mean age of the patients was 22.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.46 years in the control group and 21.92\u0026thinsp;\u0026plusmn;\u0026thinsp;3.03 in the intervention group with no statistical significance between them. There were no dropouts and the data of all patients were evaluated in the statistical analysis.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003eTable 1\u003c/div\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eDemographic data of the patients\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGroup A (Control)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGroup B (Intervention)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep-value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eAge [Mean (SD)]\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.5(4.46)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e21.92(3.03)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.712 NS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eGender [N (%)]\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9(75)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e10(83.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.615 NS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3(\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2(16.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n\u003cp\u003eNS\u0026thinsp;=\u0026thinsp;non-significant\u003c/p\u003e\n\u003cp\u003eClinical outcomes\u003c/p\u003e\n\u003cdiv id=\"Sec14\" class=\"Section3\"\u003e\n\u003cdiv id=\"Sec15\" class=\"Section4\"\u003e\n\u003ch2\u003eHealing index (Secondary outcome):\u003c/h2\u003e\n\u003cp\u003eThe healing index was measured during the 3rd and 5th days postoperatively, which showed statistical significance between the two groups favouring the intervention group.\u003c/p\u003e\n\u003cp\u003eControl group: the healing index was very poor (score 1) for one patient (8.3%), poor (score 2) for 10 patients (83.3%) and good (score 3) for one patient (8.3%) at 3 days post-operative. At 5 days post-operative; the index scores showed a slight improvement of poor (score 2) for 10 (83.3%) patients and 2 patients (16.7%) receiving good (score 3).\u003c/p\u003e\n\u003cp\u003eIntervention group: all 12 (100%) patients had healing scores of good at 3 days post-operative which improved to very good (score 4) for 11(91.7%) patients and good (score 3) for one patient (8.3%) after 5 days.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eFrequency (n) and Percentage (%) of healing index distribution for different tested groups.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth colspan=\"2\" rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eHealing index\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGroup A (Control)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGroup B (Intervention)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003ep-value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003en\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e%\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003en\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e%\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"5\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDay 3\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVery poor\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.3%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"5\" align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePoor\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e83.3%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.0%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGood\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.3%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100.0%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVery good\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.0%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eExcellent\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.0%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"5\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDay 5\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVery poor\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"5\" align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePoor\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e83.3%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.0%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGood\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16.7%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.3%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVery good\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e91.7%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eExcellent\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.0%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003ep-value\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.317 NS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.001*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\n\u003ch2\u003eEpithelization test (Toluidine blue test):\u003c/h2\u003e\n\u003cp\u003eThe epithelization test was performed using Toluidine blue on the 5th day post-operatively. There was statistical significance between the two groups favouring the intervention group.\u003c/p\u003e\n\u003cp\u003eControl group; all 12 (100%) patients had a dark blue colour after the toluidine blue test after 5 days post-operative.\u003c/p\u003e\n\u003cp\u003eIntervention group; 8 (66.7%) patients were found to have light blue colour and 4 (33.3%) had light blue with dark specks after the toluidine blue test 5 days post-operative.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eFrequency (n) and Percentage (%) of Toluidine blue after 5 days for different tested groups.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGroup A (Control)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGroup B (Intervention)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP value\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eToluidine blue after 5 days\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLight blue\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e66.7%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLight blue with dark specks\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33.3%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDark blue\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100.0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.0%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\n\u003cp\u003e*=significant, NS\u0026thinsp;=\u0026thinsp;Non-significant\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\n\u003ch2\u003eRelapse (Repigmentation) after 6 months:\u003c/h2\u003e\n\u003cp\u003eThe relapse (repigmentation) was measured 6 months post-operatively using the gingival pigmentation index. There was no statistical significance between the two tested groups.\u003c/p\u003e\n\u003cp\u003eIn the control group: 33.3% (n\u0026thinsp;=\u0026thinsp;4) of the patients were observed to have repigmentation while 66.7% (n\u0026thinsp;=\u0026thinsp;8) of patients were found to have repigmentation in the intervention group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;(4)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrequency (n) and Percentage (%) of repigmentation after 6 months for different tested groups.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Taba\" border=\"1\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGroup A (Control)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGroup B (Intervention)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003ep-value\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003en\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eRepigmentation after 6 months\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e66.7%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33.3%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.102 NS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33.3%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e66.7%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\n\u003cp\u003e*=significant, NS\u0026thinsp;=\u0026thinsp;non-significant\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAesthetics have become an integral part of dentistry nowadays with a remarkable increase in the demand for aesthetic procedures. Dentists are now required to achieve and maintain pristine aesthetics as well as address the biological and functional aspects of every procedure performed (Humagain et al., 2009).\u003c/p\u003e\n\u003cp\u003eMelanin, the most common endogenous pigment, is the main cause for physiological gingival pigmentation. With regards to gingival pigmentation, it is presented as a diffuse light brown to black discoloured patches or strands involving the gingival margin and/or attached gingiva and may even extend to the alveolar mucosa (Nagati et al., 2017).\u003c/p\u003e\n\u003cp\u003eThe combined use of bur abrasion and scalpel techniques was chosen in the current study due to the numerous advantages of both techniques which include: the ease of execution, no need for special equipment, time efficiency, fast wound healing, low recurrence rates and economic compared to other techniques. However, both of these methods have drawbacks like increased post-operative pain and bleeding as well as needing the use of periodontal dressing post-operatively (Gul et al., 2019; Suchetha et al., 2018).\u003c/p\u003e\n\u003cp\u003eAfter gingival depigmentation procedures; an exposed connective tissue wound is created. Whether to cover this wound with a periodontal dressing or not is an ongoing debate. The use of non-eugenol periodontal dressing was due to it being one of the most biocompatible dressings that have adequate mechanical, physical and therapeutic properties (Baghani \u0026amp; Kadkhodazadeh, 2013; Bezawada et al., 2020; Kathariya et al., 2015). The periodontal dressing was removed after 5 days post-operative to avoid delayed healing and increased infection rates due to plaque accumulation around the dressing which is associated with leaving it for long periods (Kathariya et al., 2015).\u003c/p\u003e\n\u003cp\u003eThe most significant observation was in the toluidine blue epithelization test after 5 days, which showed that 66.7% of the surgical sites were completely healed and 33.3% were partially healed when compared to 100% of the control group having no healing. These results are per Dahiya et al in 2019 This could be due to the high platelet concentrations of platelets in the PRF that are responsible for the fast regeneration of the epithelium and connective tissue in the PRF-treated sites(Bansal et al., 2016; Dahiya et al., 2019; Debnath \u0026amp; Chatterjee, 2018).\u003c/p\u003e\n\u003cp\u003eThe healing index results were in favour of the test group with 100% of the patients scoring 3 (Good) on the 3rd day which improved to 4 (Very good) by 91.7% of the patients on the 5th day. On the other hand in the control group on the 3rd day, 83.3% of the patients received a score of 2 (Poor) which remained unchanged on the 5th day. This is also supported by Dahiya and colleagues in 2019 who reported that on the 3rd day post-operative, 100% of the patients in the PRF group had good healing scores, which improved to very good on the 5th postoperative day. In the non‑eugenol periodontal dressing group, 58.3% of patients had poor healing scores on the 3rd day post-operative which improved to good healing scores in 100% of the patients. The difference in the results for the control groups on the 5th day might be linked to the intensity of the gingival pigmentation that requires deeper tissue removal (Bansal et al., 2016; Dahiya et al., 2019; Debnath \u0026amp; Chatterjee, 2018).\u003c/p\u003e\n\u003cp\u003eRegarding gingival pigmentation recurrence; it was found that the test group showed a higher recurrence rate than the control group but with a decreased intensity than pre-treatment 6 months post-operative. The pigmentation recurrence intensity decreased from a score of 2 on the Gingival pigmentation index to a score of 1. The high repigmentation recurrence in the PRF group might be due to the accelerated wound healing of the PRF which caused a faster regeneration of the melanocytes. However, to the authors\u0026rsquo; knowledge, there are no studies in the literature that have tested the recurrence rates after 6 months when using PRF.\u003c/p\u003e\n\u003cp\u003eIn the current study, the authors observed that the pigmentation recurrence was detected more in individuals with a darker complexion than fairer complexion and in the anterior region more than posterior region due to sunlight exposure and this is in accordance with a study in 2017 by Hosadurga and co-workers (Hosadurga et al., 2017). The repigmentation mechanism is still not clear but there are a few theories discussed in the literature which may include the genetic predisposition of the individuals, the residual melanocytes, migration of melanocytes from neighbouring sites or sunlight exposure (Hosadurga et al., 2017; Lin et al., 2014; Perlmutter \u0026amp; Tal, 1986).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eWithin the limitations of this study, we could conclude the following:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eUsing PRF after surgical depigmentation has resulted in significant differences in healing index and epithelization in favour of the test group when compared to using periodontal dressing alone.\u003c/li\u003e\n \u003cli\u003eA higher rate of gingival pigmentation recurrence was observed with the accelerated wound healing of the test group over the control group which is still unclear as to why it occurred.\u003c/li\u003e\n\u003c/ul\u003e\n\u003ch3\u003eRECOMMENDATIONS\u0026nbsp;\u003c/h3\u003e\n\u003cul\u003e\n \u003cli\u003eSimilar RCT studies should be done but with a larger sample size and longer follow-up period.\u003c/li\u003e\n \u003cli\u003eTesting other wound healing accelerating materials, for example, hyaluronic acid or aloe vera in comparison to the PRF after depigmentation procedures.\u003c/li\u003e\n \u003cli\u003eTesting if injection of Vitamin C after depigmentation will result in decreased recurrence rates when using PRF.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Declarations","content":"\u003col start=\"1\"\u003e\n \u003cli\u003e\u003cstrong\u003eEthical approval:\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eThe study was reviewed and approved by the Ethics Committee of Scientific Research - faculty of Dentistry \u0026ndash; Cairo University code 4420.\u003c/p\u003e\n\u003col start=\"2\"\u003e\n \u003cli\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eThere is no conflict of interest.\u003c/p\u003e\n\u003col start=\"3\"\u003e\n \u003cli\u003e\u003cstrong\u003eInformed consent:\u0026nbsp;\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eAll patients gave written consent to participate in the trial.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants or other support were received during the preparation of the manuscript.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eA.H: Responsible for the conception of the work, performed all the practical procedures and wrote the main manuscript.M.N: Supervised the conception of the work, practical procedures and writing of the manuscript.M.M: Supervised the conception of the work, practical procedures and writing of the manuscript.M.D: Supervised the conception of the work and reviewing the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAlasmari DS (2018) An insight into gingival depigmentation techniques: The pros and cons. 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Int J Appl Dent Sci 4(4):336\u0026ndash;341\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVerma S, Gohil M, Rathwa V (2013) Gingival depigmentation. Indian J Clin Pract 23(12):801\u0026ndash;803\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Gingival pigmentation, PRF, wound healing, gingival depigmentation, pigmentation recurrence","lastPublishedDoi":"10.21203/rs.3.rs-4843486/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4843486/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAim: The study aimed to evaluate the effect of platelet-rich fibrin on wound healing after surgical depigmentation\u003c/p\u003e\n\u003cp\u003eMethodology: Twenty-four patients with gingival pigmentation were recruited and randomly assigned to the control group; non-eugenol periodontal dressing only, or to the test group; L-PRF with periodontal dressing. Gingival depigmentation was done using a combination of scalpel and bur techniques and both groups were covered using periodontal dressing. The healing index, epithelization test and pigmentation recurrence were tested and compared.\u003c/p\u003e\n\u003cp\u003eResults: The healing index in the test group was 91.7% of the patients scored 4 (Very good) on the 5th day, while in the control group, 83.3% scored 2 (poor) on the 5th day and 16.7% were observed to have a score 3 (Good). The epithelization test was the most significant with 100% receiving a negative result in the test group after 5 days with 66.7% completely healed and 33.3% partially healed when compared to 100% of the control group having a positive score (no epithelization). The pigmentation recurrence after 6 months was observed in 66.7% in the test group while only 33.3% in the control group.\u003c/p\u003e\n\u003cp\u003eConclusion: Using PRF after gingival depigmentation results in better wound healing when compared to using periodontal packs alone.\u003c/p\u003e","manuscriptTitle":"Clinical efficacy of non-eugenol containing periodontal dressing with and without platelet-rich fibrin on wound healing after surgical gingival depigmentation: a randomized clinical trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-04 23:24:13","doi":"10.21203/rs.3.rs-4843486/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b1639161-e324-4756-90a7-042169894e22","owner":[],"postedDate":"September 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-12-30T18:53:23+00:00","versionOfRecord":[],"versionCreatedAt":"2024-09-04 23:24:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4843486","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4843486","identity":"rs-4843486","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}