Effects of Laser Stimulation on Wound Healing of Human Palatal Tissue

• Sponsor: University of Manitoba (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03741062
• Collaborator: (none)
• Enrollment: 11
• Location: 1
• Arms: 2
• Actual Duration (Months): 15.6
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the effects of photobiomodulation (PBM) with an Er:YAG laser on the palatal donor site following subepithelial connective tissue graft (SECTG) surgery. Patient-centred outcomes and wound healing will be compared between a control group, who receives no laser treatment, and the test group receiving PBM therapy. It is hypothesized that laser stimulation will have a beneficial effect on the patient's post-operative experience as well as the healing of the tissues.

Condition or Disease	Intervention/Treatment	Phase
Healing Surgical Wounds; Pain Measurement	Device: J. Morita AdvErl Evo Er:YAG laser; Device: Control	N/A

Detailed Description

The study is a randomized clinical trial comparing palatal donor sites that receive PBM with an Er:YAG laser and palatal donor sites receiving no additional treatment, following SETG surgery. A computerized randomization program will assign patients to one of two groups. Participants will be block-randomized to ensure balance between the operators.

The palate is anesthetized with 2% lidocaine (1:100000 epinephrine) by greater palatine nerve block, nasopalatine nerve block, and local infiltration. The thickness of the tissue at donor site of the palate is measured by transgingival probing ("bone sounding"). The palatal tissue is harvested from the area bordered mesially by the root of the canine and distally by the palatal root of the first molar, extending laterally to approximately 2 mm from the gingival margin and medially far enough to obtain an adequate area of tissue for the required size of the graft while ensuring not to encroach on the palatal neurovascular bundle.

A horizontal incision, corresponding to the necessary length of the graft, is made at 90 degrees to the bone approximately 2 mm from the gingival margin. Within this first incision, the scalpel is angled at approximately 135 degrees and a split-thickness dissection of the palatal tissue is extended medially. As the scalpel is advanced, the angle of the blade is further flattened until it is nearly parallel to the surface of the bone. The incision is extended until the necessary dimensions of the graft tissue are reached. Incisions are then made to the bone at the mesial, distal, and medial borders of the graft. The donor tissue is detached from the bone with a periosteal elevator and placed on a saline-soaked gauze.

The length, width, and thickness of the graft, the thickness of the remaining flap of palatal tissue, and the length of the palatal incision will be measured with digital calipers to the nearest 0.1 mm. The palatal incision will be closed with cyanoacrylate. Immediately following completion of the surgical procedure, Group A will receive PBM of the donor site and Group B will receive sham treatment with the laser unit turned off. The parameters used for PBM will be those shown to induce maximal proliferation of gingival fibroblasts using an Er:YAG laser: Energy [80 mJ], Duration [30 s], and Pulse Rate [25 Hz].

Post-operatively, both groups receive 2 g of Amoxicillin (or 600 mg of Clindamycin in cases of penicillin allergies) and the standard post-surgical instructions given to patients at the Graduate Periodontics clinic. Patients are then provided a Visual Analog Scale (VAS) questionnaire to rate their pain from 0-10 each night for 1 week and 30 Ibuprofen (200 mg) tablets.

Patients will be followed up with at 1-week, 2-week, and 6-week post-operative appointments. Photographs will be taken at all appointments. At the first appointment, participants will return their completed VAS and any remaining Ibuprofen tablets. The donor site will be examined by a clinician who did not perform the surgery and assessed according to Fickl's Modified Early-Wound Healing Index (MEHI) and Landry's Healing Index (HI). Patients will also answer a modified Oral Impacts on Daily Performance (OIDP) questionnaire. At the 2-week appointment, the palate will again be evaluated by the same operator and assessed according to the MEHI and HI. At the 6-week appointment, the donor site will be anesthetized with local infiltration of 2% lidocaine (1:100000 epinephrine), ensuring not to inject anesthetic into the tissue overlying where the graft was harvested from. Tissue thickness at the donor site will be measured via transgingival probing, in the same method as was used pre-operatively, and a histological specimen of the tissue will be harvested and placed in 10% neutral buffered formalin. Barring any ongoing post-surgical complications at this point, the patient's participation in the study is now complete.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Effects of Er:YAG Photobiomodulation Therapy on Wound Healing of Human Palatal Mucosa After Connective Tissue Graft Harvesting: A Pilot Study
• Actual Study Start Date: Jan 24, 2019
• Actual Primary Completion Date: Mar 17, 2020
• Actual Study Completion Date: May 14, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: J. Morita AdvErl Evo Er:YAG laser Immediately following completion of the surgical procedure, this group will receive photobiomodulation treatment of the palatal tissue donor site with Er:YAG laser according to the parameters recommended by experts in this field and which have shown to induce maximal proliferation of human gingival fibroblasts (Energy Setting: 80 mJ, Pulse Rate: 25 Hz, Duration: 30 s).	Device: J. Morita AdvErl Evo Er:YAG laser; Er:YAG laser perimeters: Energy = 80 mJ Pulse Rate = 25 Hz Duration = 30 s
Sham Comparator: Control This group will receive sham treatment of the palatal tissue donor site. The laser unit will be turned off. The clinician will simulate usage of the Er:YAG laser in a manner that is indistinguishable to the patient from the experimental group.	Device: Control; Sham treatment with laser unit turned off

Outcome Measures

Primary Outcome Measures

1. Self-Reported Patient Discomfort as Assessed by a Visual Analogue Scale [One week]

   At the end of their surgical appointment, patients will be given a Visual Analogue Scale (VAS) questionnaire to rate their post-operative pain by making a mark along a 10-cm line (0 = no pain, 10 = unbearable pain) for each night of the first post-operative week. At the one-week post-operative appointment, the participants will return their VAS questionnaires and their reported post-operative discomfort for each night of the initial post-operative week will be tabulated.

2. Patient Discomfort as Assessed by Analgesic Consumption [One week]

   At the end of their surgical appointment, patients will be provided with a bag of 30 200-mg Ibuprofen tablets. At the one-week post-operative appointment, the participants will return any remaining Ibuprofen tablets and their total analgesic consumption for the initial post-operative week will be tabulated.

3. Self-Reported Patient Discomfort as Assessed by a Oral Impacts on Daily Performance Questionnaire [One Week]

   At the one-week post-operative appointment, patients will complete a modified Oral Impacts on Daily Performance (OIDP) questionnaire to assess the effect of the palatal wound on their oral-health related quality of life during the first post-operative week. They will rate the overall frequency of disruptions that the palatal surgical site had on eating, speaking, oral hygiene, light physical work, participation in regular outings, sleeping, relaxing, smiling and laughing, their mood, and interpersonal interactions by making a mark along a 10-cm line (0 = never, 10 = constantly) for first post-operative week. When applicable, they will also rate the overall severity of the disruptions for these same categories by making a mark along a 10-cm line (0 = barely noticeable, 10 = extremely disruptive) for first post-operative week.

Secondary Outcome Measures

1. Healing of the Palatal Donor Site as Assessed by Histological Analysis [Six weeks]

   At a six-week post-operative appointment, a histological specimen will be harvested with a tissue punch. Samples of laser-treated and non laser-treated palatal tissues will be histologically compared with respect to concentration of inflammatory cells, amount of Type I collagen present, and amount of Type III collagen present.

2. Healing of the Palatal Donor Site as Assessed by the Modified Early-Wound Healing Index [One week, Two weeks]

   At the one-week and two-week post-operative appointments, a clinician who did not perform the surgery and is blinded to which treatment group the patient belongs will assess the donor site according to the Modified Early-Wound Healing Index (MEHI) proposed by Fickl. The clinician will evaluate the palatal tissue donor site and rate it from 1 to 5 (1 = complete flap closure without fibrin line at the palate, 5 = incomplete flap closure with >50% necrosis of the palatal flap tissue). The progression of post-operative healing at one week and two weeks will be compared between experimental and control groups.

3. Healing of the Palatal Donor Site as Assessed by the Healing Index [One week, Two weeks]

   At the one-week and two-week post-operative appointments, a clinician who did not perform the surgery and is blinded to which treatment group the patient belongs will assess the donor site according to the Healing Index (HI) proposed by Landry, Turnbull, and Howley. The clinician will evaluate the palatal tissue donor site and rate it from 1 to 5 (1 = very poor, 5 = excellent) based on the parameters of tissue colour, bleeding response to palpation, presence of granulation tissue, presence of suppuration, exposure of underlying connective tissue, and epithelialization along incision margins. The progression of post-operative healing at one week and two weeks will be compared between experimental and control groups.

4. Healing of the Palatal Donor Site as Assessed by Tissue Thickness [Six weeks]

   At a six-week post-operative appointment, tissue thickness at the donor site will be measured in millimetres via bone sounding with a periodontal probe. This will be compared to pre-operative measurements taken at the site.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• ASA I or II

• Full Mouth Plaque Score (FMPS) < 20%

• Full Mouth Bleeding Score (FMBS) < 20%

Exclusion Criteria:

• Any contraindications for periodontal surgery,

• Anticoagulant usage

• Corticosteroid usage

• Smoking > 10 cigarettes/day.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univerisity of Manitoba, College of Dentistry	Winnipeg	Manitoba	Canada	R3E 0W3

Sponsors and Collaborators

• University of Manitoba

Investigators

• Study Director: Anastasia Cholakis, FRCD(C), University of Manitoba

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 16, 2020

More Information

Publications

• Aguirre-Zorzano LA, García-De La Fuente AM, Estefanía-Fresco R, Marichalar-Mendía X. Complications of harvesting a connective tissue graft from the palate. A retrospective study and description of a new technique. J Clin Exp Dent. 2017 Dec 1;9(12):e1439-e1445. doi: 10.4317/jced.54337. eCollection 2017 Dec.
• Amorim JC, de Sousa GR, de Barros Silveira L, Prates RA, Pinotti M, Ribeiro MS. Clinical study of the gingiva healing after gingivectomy and low-level laser therapy. Photomed Laser Surg. 2006 Oct;24(5):588-94.
• Aoki A, Mizutani K, Schwarz F, Sculean A, Yukna RA, Takasaki AA, Romanos GE, Taniguchi Y, Sasaki KM, Zeredo JL, Koshy G, Coluzzi DJ, White JM, Abiko Y, Ishikawa I, Izumi Y. Periodontal and peri-implant wound healing following laser therapy. Periodontol 2000. 2015 Jun;68(1):217-69. doi: 10.1111/prd.12080.
• Chambrone L, Tatakis DN. Periodontal soft tissue root coverage procedures: a systematic review from the AAP Regeneration Workshop. J Periodontol. 2015 Feb;86(2 Suppl):S8-51. doi: 10.1902/jop.2015.130674. Review.
• Consensus report. Mucogingival therapy. Ann Periodontol. 1996 Nov;1(1):702-6. Review.
• da Silva Neves FL, Silveira CA, Dias SB, Santamaria Júnior M, de Marco AC, Kerbauy WD, de Melo Filho AB, Jardini MA, Santamaria MP. Comparison of two power densities on the healing of palatal wounds after connective tissue graft removal: randomized clinical trial. Lasers Med Sci. 2016 Sep;31(7):1371-8. doi: 10.1007/s10103-016-1988-6. Epub 2016 Jun 25.
• de Medeiros ML, Araújo-Filho I, da Silva EM, de Sousa Queiroz WS, Soares CD, de Carvalho MG, Maciel MA. Effect of low-level laser therapy on angiogenesis and matrix metalloproteinase-2 immunoexpression in wound repair. Lasers Med Sci. 2017 Jan;32(1):35-43. doi: 10.1007/s10103-016-2080-y. Epub 2016 Sep 20.
• Del Pizzo M, Modica F, Bethaz N, Priotto P, Romagnoli R. The connective tissue graft: a comparative clinical evaluation of wound healing at the palatal donor site. A preliminary study. J Clin Periodontol. 2002 Sep;29(9):848-54.
• Dias SB, Fonseca MV, Dos Santos NC, Mathias IF, Martinho FC, Junior MS, Jardini MA, Santamaria MP. Effect of GaAIAs low-level laser therapy on the healing of human palate mucosa after connective tissue graft harvesting: randomized clinical trial. Lasers Med Sci. 2015 Aug;30(6):1695-702. doi: 10.1007/s10103-014-1685-2. Epub 2014 Nov 6.
• Enwemeka CS, Parker JC, Dowdy DS, Harkness EE, Sanford LE, Woodruff LD. The efficacy of low-power lasers in tissue repair and pain control: a meta-analysis study. Photomed Laser Surg. 2004 Aug;22(4):323-9.
• Fickl S, Fischer KR, Jockel-Schneider Y, Stappert CF, Schlagenhauf U, Kebschull M. Early wound healing and patient morbidity after single-incision vs. trap-door graft harvesting from the palate--a clinical study. Clin Oral Investig. 2014 Dec;18(9):2213-9. doi: 10.1007/s00784-014-1204-7. Epub 2014 Feb 23.
• Heidari M, Paknejad M, Jamali R, Nokhbatolfoghahaei H, Fekrazad R, Moslemi N. Effect of laser photobiomodulation on wound healing and postoperative pain following free gingival graft: A split-mouth triple-blind randomized controlled clinical trial. J Photochem Photobiol B. 2017 Jul;172:109-114. doi: 10.1016/j.jphotobiol.2017.05.022. Epub 2017 May 18.
• Hürzeler MB, Weng D. A single-incision technique to harvest subepithelial connective tissue grafts from the palate. Int J Periodontics Restorative Dent. 1999 Jun;19(3):279-87.
• Khan I, Arany P. Biophysical Approaches for Oral Wound Healing: Emphasis on Photobiomodulation. Adv Wound Care (New Rochelle). 2015 Dec 1;4(12):724-737. Review.
• Kong S, Aoki A, Iwasaki K, Mizutani K, Katagiri S, Suda T, Ichinose S, Ogita M, Pavlic V, Izumi Y. Biological effects of Er:YAG laser irradiation on the proliferation of primary human gingival fibroblasts. J Biophotonics. 2018 Mar;11(3). doi: 10.1002/jbio.201700157. Epub 2017 Nov 2.
• Landry RG, Turnbull RS, Howley T. Effectiveness of benzydamyne HCl in the treatment of periodontal post-surgical patients. Res Clin Forums. 10:105-118, 1988.
• Mei CC, Lee FY, Yeh HC. Assessment of pain perception following periodontal and implant surgeries. J Clin Periodontol. 2016 Dec;43(12):1151-1159. doi: 10.1111/jcpe.12618. Epub 2016 Nov 2.
• Ogita M, Tsuchida S, Aoki A, Satoh M, Kado S, Sawabe M, Nanbara H, Kobayashi H, Takeuchi Y, Mizutani K, Sasaki Y, Nomura F, Izumi Y. Increased cell proliferation and differential protein expression induced by low-level Er:YAG laser irradiation in human gingival fibroblasts: proteomic analysis. Lasers Med Sci. 2015 Sep;30(7):1855-66. doi: 10.1007/s10103-014-1691-4. Epub 2014 Nov 28.
• Ozcelik O, Cenk Haytac M, Kunin A, Seydaoglu G. Improved wound healing by low-level laser irradiation after gingivectomy operations: a controlled clinical pilot study. J Clin Periodontol. 2008 Mar;35(3):250-4. doi: 10.1111/j.1600-051X.2007.01194.x.
• Pippi R. Post-Surgical Clinical Monitoring of Soft Tissue Wound Healing in Periodontal and Implant Surgery. Int J Med Sci. 2017 Jul 18;14(8):721-728. doi: 10.7150/ijms.19727. eCollection 2017. Review.
• Pourzarandian A, Watanabe H, Ruwanpura SM, Aoki A, Ishikawa I. Effect of low-level Er:YAG laser irradiation on cultured human gingival fibroblasts. J Periodontol. 2005 Feb;76(2):187-93.
• Tonetti MS, Jepsen S; Working Group 2 of the European Workshop on Periodontology. Clinical efficacy of periodontal plastic surgery procedures: consensus report of Group 2 of the 10th European Workshop on Periodontology. J Clin Periodontol. 2014 Apr;41 Suppl 15:S36-43. doi: 10.1111/jcpe.12219.
• Woodruff LD, Bounkeo JM, Brannon WM, Dawes KS, Barham CD, Waddell DL, Enwemeka CS. The efficacy of laser therapy in wound repair: a meta-analysis of the literature. Photomed Laser Surg. 2004 Jun;22(3):241-7.
• Zucchelli G, Mounssif I. Periodontal plastic surgery. Periodontol 2000. 2015 Jun;68(1):333-68. doi: 10.1111/prd.12059. Review.

• Responsible Party: Brian Wiens, Principal Investigator, University of Manitoba
• ClinicalTrials.gov Identifier: NCT03741062
• Other Study ID Numbers: B2018:100
• First Posted: Nov 14, 2018
• Last Update Posted: Nov 10, 2020
• Last Verified: Oct 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Brian Wiens, Principal Investigator, University of Manitoba: Laser Therapy; Low-Level Light Therapy; Periodontics; Oral Surgery; Palate; Palate, Hard
• Additional relevant MeSH terms: Wounds and Injuries; Surgical Wound

Study Results

Participant Flow

Arm/Group Title	J. Morita AdvErl Evo Er:YAG Laser	Control
Arm/Group Description	Immediately following completion of the surgical procedure, this group will receive photobiomodulation treatment of the palatal tissue donor site with Er:YAG laser according to the parameters recommended by experts in this field and which have shown to induce maximal proliferation of human gingival fibroblasts (Fluence: 6.3 J/cm2, Energy Setting: 80 mJ, Pulse Rate: 25 Hz, Duration: 30 s). J. Morita AdvErl Evo Er:YAG laser: Er:YAG laser perimeters: Fluence = 6.3 J/cm^2 Energy = 80 mJ Pulse Rate = 25 Hz Duration = 30 s	This group will receive sham treatment of the palatal tissue donor site. The laser unit will be turned off. The clinician will simulate usage of the Er:YAG laser in a manner that is indistinguishable to the patient from the experimental group. Control: Sham treatment with laser unit turned off
Period Title: Overall Study
STARTED	5	6
COMPLETED	4	6
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	J. Morita AdvErl Evo Er:YAG Laser	Control	Total
Arm/Group Description	Immediately following completion of the surgical procedure, this group will receive photobiomodulation treatment of the palatal tissue donor site with Er:YAG laser according to the parameters recommended by experts in this field and which have shown to induce maximal proliferation of human gingival fibroblasts (Fluence: 6.3 J/cm2, Energy Setting: 80 mJ, Pulse Rate: 25 Hz, Duration: 30 s). J. Morita AdvErl Evo Er:YAG laser: Er:YAG laser perimeters: Fluence = 6.3 J/cm^2 Energy = 80 mJ Pulse Rate = 25 Hz Duration = 30 s	This group will receive sham treatment of the palatal tissue donor site. The laser unit will be turned off. The clinician will simulate usage of the Er:YAG laser in a manner that is indistinguishable to the patient from the experimental group. Control: Sham treatment with laser unit turned off	Total of all reporting groups
Overall Participants	4	6	10
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	58.5	62.3	60.8
Sex: Female, Male (Count of Participants)
Female	4 100%	3 50%	7 70%
Male	0 0%	3 50%	3 30%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Count of Participants)
Canada	4 100%	6 100%	10 100%

Outcome Measures

1. Primary Outcome

Title	Self-Reported Patient Discomfort as Assessed by a Visual Analogue Scale
Description	At the end of their surgical appointment, patients will be given a Visual Analogue Scale (VAS) questionnaire to rate their post-operative pain by making a mark along a 10-cm line (0 = no pain, 10 = unbearable pain) for each night of the first post-operative week. At the one-week post-operative appointment, the participants will return their VAS questionnaires and their reported post-operative discomfort for each night of the initial post-operative week will be tabulated.
Time Frame	One week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	J. Morita AdvErl Evo Er:YAG Laser	Control
Arm/Group Description	Immediately following completion of the surgical procedure, this group will receive photobiomodulation treatment of the palatal tissue donor site with Er:YAG laser according to the parameters recommended by experts in this field and which have shown to induce maximal proliferation of human gingival fibroblasts (Fluence: 6.3 J/cm2, Energy Setting: 80 mJ, Pulse Rate: 25 Hz, Duration: 30 s). J. Morita AdvErl Evo Er:YAG laser: Er:YAG laser perimeters: Fluence = 6.3 J/cm^2 Energy = 80 mJ Pulse Rate = 25 Hz Duration = 30 s	This group will receive sham treatment of the palatal tissue donor site. The laser unit will be turned off. The clinician will simulate usage of the Er:YAG laser in a manner that is indistinguishable to the patient from the experimental group. Control: Sham treatment with laser unit turned off
Measure Participants	4	6
Day 1	4.90	2.45
Day 2	3.30	0.83
Day 3	2.93	0.72
Day 4	2.75	0.40
Day 5	2.65	0.32
Day 6	2.65	0.16

2. Primary Outcome

Title	Patient Discomfort as Assessed by Analgesic Consumption
Description	At the end of their surgical appointment, patients will be provided with a bag of 30 200-mg Ibuprofen tablets. At the one-week post-operative appointment, the participants will return any remaining Ibuprofen tablets and their total analgesic consumption for the initial post-operative week will be tabulated.
Time Frame	One week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	J. Morita AdvErl Evo Er:YAG Laser	Control
Arm/Group Description	Immediately following completion of the surgical procedure, this group will receive photobiomodulation treatment of the palatal tissue donor site with Er:YAG laser according to the parameters recommended by experts in this field and which have shown to induce maximal proliferation of human gingival fibroblasts (Fluence: 6.3 J/cm2, Energy Setting: 80 mJ, Pulse Rate: 25 Hz, Duration: 30 s). J. Morita AdvErl Evo Er:YAG laser: Er:YAG laser perimeters: Fluence = 6.3 J/cm^2 Energy = 80 mJ Pulse Rate = 25 Hz Duration = 30 s	This group will receive sham treatment of the palatal tissue donor site. The laser unit will be turned off. The clinician will simulate usage of the Er:YAG laser in a manner that is indistinguishable to the patient from the experimental group. Control: Sham treatment with laser unit turned off
Measure Participants	4	6
Mean (Full Range) [analgesic tablets]	10.5	6.0

3. Primary Outcome

Title	Self-Reported Patient Discomfort as Assessed by a Oral Impacts on Daily Performance Questionnaire
Description	At the one-week post-operative appointment, patients will complete a modified Oral Impacts on Daily Performance (OIDP) questionnaire to assess the effect of the palatal wound on their oral-health related quality of life during the first post-operative week. They will rate the overall frequency of disruptions that the palatal surgical site had on eating, speaking, oral hygiene, light physical work, participation in regular outings, sleeping, relaxing, smiling and laughing, their mood, and interpersonal interactions by making a mark along a 10-cm line (0 = never, 10 = constantly) for first post-operative week. When applicable, they will also rate the overall severity of the disruptions for these same categories by making a mark along a 10-cm line (0 = barely noticeable, 10 = extremely disruptive) for first post-operative week.
Time Frame	One Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	J. Morita AdvErl Evo Er:YAG Laser	Control
Arm/Group Description	Immediately following completion of the surgical procedure, this group will receive photobiomodulation treatment of the palatal tissue donor site with Er:YAG laser according to the parameters recommended by experts in this field and which have shown to induce maximal proliferation of human gingival fibroblasts (Fluence: 6.3 J/cm2, Energy Setting: 80 mJ, Pulse Rate: 25 Hz, Duration: 30 s). J. Morita AdvErl Evo Er:YAG laser: Er:YAG laser perimeters: Fluence = 6.3 J/cm^2 Energy = 80 mJ Pulse Rate = 25 Hz Duration = 30 s	This group will receive sham treatment of the palatal tissue donor site. The laser unit will be turned off. The clinician will simulate usage of the Er:YAG laser in a manner that is indistinguishable to the patient from the experimental group. Control: Sham treatment with laser unit turned off
Measure Participants	4	6
Frequency of Disruptions to Eating Food	7.52	3.65
Severity of Disruptions to Eating Food	5.25	2.65
Frequency of Disruptions to Speaking	4.73	1.87
Severity of Disruptions to Speaking	3.28	0.55
Frequency of Disruptions when Performing Oral Hygiene	5.18	4.22
Severity of Disruptions when Performing Oral Hygiene	4.40	4.98
Frequency of Disruptions when Performing Light Work	1.30	0.25
Severity of Disruptions when Performing Light Work	0.90	0.35
Frequency of Disruptions when Going Out	2.95	0.38
Severity of Disruptions when Going Out	2.55	0.58
Frequency of Disruptions While Sleeping	6.20	1.62
Severity of Disruptions While Sleeping	3.03	2.20
Frequency of Disruptions While Relaxing	4.53	0.58
Severity of Disruptions While Relaxing	1.33	0.80
Frequency of Disruptions While Smiling and Laughing	7.77	2.22
Severity of Disruptions While Smiling and Laughing	4.70	3.20
Frequency of Disruptions to Patient's Mood	2.83	2.25
Severity of Disruptions to Patient's Mood	1.17	3.30
Frequency of Disruptions to Patient's Personal Interactions	4.23	1.00
Severity of Disruptions to Patient's Personal Interactions	2.90	1.43

4. Secondary Outcome

Title	Healing of the Palatal Donor Site as Assessed by Histological Analysis
Description	At a six-week post-operative appointment, a histological specimen will be harvested with a tissue punch. Samples of laser-treated and non laser-treated palatal tissues will be histologically compared with respect to concentration of inflammatory cells, amount of Type I collagen present, and amount of Type III collagen present.
Time Frame	Six weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Healing of the Palatal Donor Site as Assessed by the Modified Early-Wound Healing Index
Description	At the one-week and two-week post-operative appointments, a clinician who did not perform the surgery and is blinded to which treatment group the patient belongs will assess the donor site according to the Modified Early-Wound Healing Index (MEHI) proposed by Fickl. The clinician will evaluate the palatal tissue donor site and rate it from 1 to 5 (1 = complete flap closure without fibrin line at the palate, 5 = incomplete flap closure with >50% necrosis of the palatal flap tissue). The progression of post-operative healing at one week and two weeks will be compared between experimental and control groups.
Time Frame	One week, Two weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Healing of the Palatal Donor Site as Assessed by the Healing Index
Description	At the one-week and two-week post-operative appointments, a clinician who did not perform the surgery and is blinded to which treatment group the patient belongs will assess the donor site according to the Healing Index (HI) proposed by Landry, Turnbull, and Howley. The clinician will evaluate the palatal tissue donor site and rate it from 1 to 5 (1 = very poor, 5 = excellent) based on the parameters of tissue colour, bleeding response to palpation, presence of granulation tissue, presence of suppuration, exposure of underlying connective tissue, and epithelialization along incision margins. The progression of post-operative healing at one week and two weeks will be compared between experimental and control groups.
Time Frame	One week, Two weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Healing of the Palatal Donor Site as Assessed by Tissue Thickness
Description	At a six-week post-operative appointment, tissue thickness at the donor site will be measured in millimetres via bone sounding with a periodontal probe. This will be compared to pre-operative measurements taken at the site.
Time Frame	Six weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse event data was collected for the 6-week period during which the study was conducted for each patient.
Arm/Group Title	J. Morita AdvErl Evo Er:YAG Laser		Control
Arm/Group Description	Immediately following completion of the surgical procedure, this group will receive photobiomodulation treatment of the palatal tissue donor site with Er:YAG laser according to the parameters recommended by experts in this field and which have shown to induce maximal proliferation of human gingival fibroblasts (Fluence: 6.3 J/cm2, Energy Setting: 80 mJ, Pulse Rate: 25 Hz, Duration: 30 s). J. Morita AdvErl Evo Er:YAG laser: Er:YAG laser perimeters: Fluence = 6.3 J/cm^2 Energy = 80 mJ Pulse Rate = 25 Hz Duration = 30 s		This group will receive sham treatment of the palatal tissue donor site. The laser unit will be turned off. The clinician will simulate usage of the Er:YAG laser in a manner that is indistinguishable to the patient from the experimental group. Control: Sham treatment with laser unit turned off
All Cause Mortality
	J. Morita AdvErl Evo Er:YAG Laser		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/6 (0%)
Serious Adverse Events
	J. Morita AdvErl Evo Er:YAG Laser		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	J. Morita AdvErl Evo Er:YAG Laser		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		0/6 (0%)
Injury, poisoning and procedural complications
Inadequate Hemostasis at Donor Site	1/5 (20%)	1	0/6 (0%)	0
Hematoma	1/5 (20%)	1	0/6 (0%)	0

Limitations/Caveats

Small sample size due to early termination of study because of COVID-19 pandemic. Imbalanced distribution of genders between Control and Treatment groups (despite randomization). Lack of standardization in methods for clinical measurements.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.