Abstract
Aim
To evaluate the effectiveness of platelet-rich fibrin (PRF) and low-level laser therapy (LLLT) on donor site healing after vascularized interpositional periosteal connective tissue (VIP-CT) flap.
Materials and methods
For the present clinical study, the selected patients requiring VIP-CT flap were randomly assigned into either of the two treatment groups (VIP-CT/PRF and VIP-CT/LLLT). For VIP-CT/PRF, palatal donor site treated with platelet-rich fibrin (PRF, n = 15) after harvesting VIP-CT flap; and for VIP-CT/LLLT, palatal donor site treated with low-level laser therapy (LLLT, n = 16) after harvesting VIP-CT flap.
Results
The mean thickness of palatal mucosa at surgical site was increased from 2.91 ± 0.65 to 2.93 ± 0.55 mm after 1 week and to 3.02 ± 0.55 mm after 12 weeks while in PRF-treated site, while in LLLT-treated sites, palatal mucosal thickness decreased after 1 week from 3.35 ± 0.56 mm to 1.83 ± 0.48 mm and then increase to 3.35 ± 0.55 mm after 12 weeks, and the mean difference was significantly higher for PRF-treated group compared to LLLT-treated group. In regard to contour, absence of hypertrophic tissue was observed in VIP-CT/LLLT compared with VIP-CT/PRF group (40% of patients, p = 0.003) at 4 weeks. “Absence” of pain and burning sensation were observed as early as at 1 week in LLLT-treated palatal donor sites compared to PRF-treated palatal donor site after VIP-CT. Improvement in post-surgical complications like ecchymosis, tissue necrosis, swelling, and infection were observed almost 100% at 4 weeks in both the groups.
Conclusion
Favourable clinical outcomes in terms of tissue thickness, consistency, color, contour, scar, pain, and burning sensation and patient comfort were obtained in both LLLT- and PRF-treated donor palatal sites at 12 weeks. Non-significant increase in tissue thickness was observed compared to baseline in PRF-treated donor sites at 12 weeks compared to LLLT-treated donor sites.
Clinical significance
Both low-level laser therapy (LLLT) using 940 nm wavelength and autologous platelet-rich fibrin (PRF) can be utilized to enhance early wound healing and reduce the palatal donor site morbidity.
Keywords: Laser, Low-level laser therapy, Palate, Platelet-rich fibrin, VIP-CT flap
Introduction
Palate is the most common donor site for procurement of soft tissue grafts required to restore the morphological alterations in anterior maxillary regions due to tooth extractions, trauma, periodontal diseases and/or developmental ridge defects, where augmentation procedures are often necessary to achieve rehabilitation of the large volume defects [1]. Vascularized interpositional periosteal connective tissue (VIP-CT) flap, introduced by Sclar et al. in 2003 [2], allows the clinician to perform a large volume soft tissue augmentation in esthetic sites in single procedure within 6 to 9 months, along with minimal postsurgical shrinkage and primary closure of donor site while maintaining an intact vascular supply to provide excellent esthetics blending at the recipient site [2]. However, VIP-CT flap results in various complications including pain, inflammation, bleeding, flap necrosis, infection, and delayed wound healing in the palatal donor site [3]. To overcome complications on palatal donor sites after procurement of free gingival graft/ connective tissue graft (CTG/FGG), several techniques and products have been used for example homeostatic, mechanical barriers, bioactive materials, antibacterial, antiseptic agents’ herbal products, PRF, and lasers [1, 4, 5].
Platelet-rich-fibrin (PRF), an immune, second-generation platelet concentrate obtaining on a single fibrin membrane where all the constituents of a blood sample are substantial to healing and immunity, is one of many biologic approaches that aims to promote healing by favourably upregulating the wound microenvironment to facilitate wound healing. When PRF was placed after the FGG/CTG palatal donor site was obtained, hemostasis occurred quickly [6, 7]. After harvesting subepithelial connective tissue graft (SCTG), Yen et al. [8] assessed the effectiveness of PRF on the healing of the palatal donor site. They found that PRF enhances soft tissue healing and the regeneration of palatal tissue thickness at 6-week intervals at both the clinical and histologic levels.
For more than 50 years, low-level laser therapy (LLLT) has been utilized for a variety of treatments, including the management of periodontal inflammation, bone healing, and pain relief. Besides increasing microangiogenesis and hastening wound healing by combating the inflammatory process, LLLT has also been shown that LLLT to alleviate pain [9]. According to Ozcelik et al. [10], LLLT therapy reduced the postoperative morbidity of the palate following soft tissue harvesting. To the best of author’s knowledge until now, no published data reported the comparison of PRF and LLLT after CTG, FGG, or VIP-CT flap on donor site healing. Therefore, primary aim of the present clinical trial was to evaluate the effectiveness of PRF and LLLT on donor site healing.
Materials and method
Present parallel double arm randomized clinical study was conducted in the Department of Periodontology, Saraswati Dental College and Hospital, Lucknow (UP), India, from December 2018 to November 2020 to evaluate the efficacy of LLLT and PRF on donor site healing after VIP-CT flap. The study protocol was conducted in accordance with the ethical principles described in the declaration of Helsinki 1998 revised 2013 after approval from the Institutional Research & Development Committee (IRDC/2018/MDS/15) and Institutional Human Ethics Committee (IHEC/2018/MDS/15), and the trial was also registered with concerned organization (CTRI/2020/12/029619).
Sample size determination
The sample size of the study was calculated using G power analysis, at a confidence interval of 95%, margin of error 5%. The alpha error was 0.05 and beta error was 0.20 the power of the study was kept at 80% with effect size of 0.47, degree of freedom 28. The sample size came to 31.
Patient selection
For the present study a total of 40 (both male & female) non-alcoholic, non-smoking (self-reported) patients with no contributory medical history were recruited among those visiting the outpatient Department of Periodontology based on the following inclusion and exclusion criteria.
Inclusion criteria
Motivated and compliant patients of both genders within age group of 18 years to 55 years, maintaining good oral hygiene during phase I therapy that requires VIP-CT flap procedure for soft tissue augmentation in maxillary anterior region (e.g. aesthetic ridge defects, immediate placement in extraction socket in anterior region to prevent buccal plate resorption, or any aesthetic defect due to pathological bone resorption in maxillary anterior region etc.); patients having adequate palatal dimensions for connective tissue procurement (high or U-shaped palatal vault) and minimum 3 mm thickness of palatal mucosa near med-palatal aspect [11, 12]; systemically healthy patients with no contraindication for periodontal surgery.
Exclusion criteria
Patients with any systemic disease /condition or taking any medication that may contraindicate periodontal surgery or can influence the healing of palatal mucosa; Pregnant women or nursing mother or patients taking any kind of tobacco (self-reported); Patients presenting history of any surgery in palate or having any developmental abnormality or stomatological disease in the palatal region; Patients wearing any removable device in the upper arch such as a removable partial denture or orthodontic retainer, presence of any fixed partial denture and participants with tooth malposition.
Study design
For the present clinical study, the selected patients were randomly assigned into either of the two treatment groups of sealed envelopes as given below. These identical looking envelopes were opaque, sealed, and consisted of one of the two treatment modalities. Envelopes for each treatment modalities were equal in number to avoid heterogeneous sample size. Consort chart for the study has been shown in Fig. 1.
Fig. 1.
Consort flow chart
VIP-CT/PRF
Palatal donor site treated with platelet-rich fibrin (PRF) after harvesting VIP-CT flap.
VIP-CT/LLLT
Palatal donor site treated with low-level laser therapy (LLLT) after harvesting VIP-CT flap.
Allocation ratio
The allocation ratio for the study was kept at 1:1. The allocation sequence was done through envelop method. Type of randomization was done through simple randomization. An organizing clerk was employed for allocation of participants. A recording clerk recorded the parameters.
Calibration and training
The calibration of the principal investigator was done by the research head that had conducted various research studies and has thorough knowledge of the subject. Research head that was trained in accordance with the recommended methods for basic oral health surveys was appointed to act as a validator for the survey team.
Pilot study
Pilot study consisting of 5 participants was done for examiner calibration and training of recording clerks has been done at the same time. The team of the survey consisted of administrators, coordinators, examiners, and recorders participated in the pilot study. A pilot study saves precious time, identifies potential difficulties, and prompts modifications that may be necessary before the actual survey is initiated.
Intra-examiner reproducibility using intra-class correlation coefficient (ICC)
The intra-examiner reliability was done using ICC during the pilot study on the basis of tissue thickness, color, and swelling in 5 participants were examined by the investigator on Day one. After 24 h the same 5 patients were re-examined by the observer and scores were given. To reduce the bias and any discrepancy, the participants’ order was rearranged and the participants were sent to the observer by the organizing clerk. The Score for ICC was 1 for all parameters indicating a perfect correlation (absolute agreement). The intra-observer reliability between the observers was calculated using kappa statistics and was found to be + 1 i.e. in perfect agreement [13].
Initial therapy
Patients enrolled for the study underwent phase I therapy. All compliant patients received verbal information regarding the study protocol and written informed consent was obtained from each patient for participation in the study. Patients were asked to remain compliant and maintain meticulous plaque control measures. After phase-I therapy, upper and lower impressions were taken using alginate impression material for preparation of study model/cast, and investigations (blood and radiographic) were advised.
Fabrication of stent
An acrylic stent was fabricated for standardization of all measurements (Fig. 2). The stent was designed to cover palatal surfaces of the donor site and six fixed points at 5 mm and 7 mm from the gingival margin were marked. Holes were prepared on the respected fixed points for measurement soft tissue thickness at various time intervals [14].
Fig. 2.
Fabrication of stent
Essex appliance
The Essex appliance is a light, almost invisible removable plastic appliance that snaps over the teeth. In this study, provisionalization was accomplished initially with an Essex appliance modified to house a pontic tooth or teeth at the graft site and provides full palatal coverage. It provides an esthetic solution for the patient during the initial healing period of 10 to 14 days. Essex appliance was designed with one or more selected pontic tooth/teeth secured at the edentulous site with 1 mm visacryl sheet in the vacuum forming machine. The edentulous space was filled with acrylic tooth/ teeth to match the shade of the adjacent teeth with acrylic resin. Visacryl sheet was heated, and once it was adequately heated, heater was turned off and vacuum was turned on. Simultaneously, lower the heated sheet over the cast and allow it to cool completely under vacuum for maximum adaptation of the material to the tooth portion of the cast. The vacuum formed retainer retrieved from the cast and acrylic resin were removed and pontic tooth/teeth are attached to the vacuum retainer using adhesive agent (Fig. 3). Finally, Essex retainer thus designed was trimmed and adjusted on existing dentition in the oral cavity while taking care of any undercuts, avoiding tissue contact and eliminating any sharp edges [15].
Fig. 3.
Essex appliance
Surgical procedure
After receiving professional cleaning, consisting of scaling and root planing, and individualized oral hygiene instructions, compliant patients were randomly assigned by a member who was blinded to the study into two treatment modalities (VIP-CT/PRF and VIP-CT/LLLT) as discussed above. Before the commencement of surgical procedure, tissue thickness of the palatal mucosa in the donor area was recorded using endodontic K file at six points marked with acrylic stent under local infiltration anesthesia. Oral antisepsis was accomplished using 10 ml of 0.2% chlorhexidine digluconate (Rexidine, Warren pharmaceutical limited, India) solution rinse. Pre-procedural extra oral surface of the patient was swabbed with betadine (5% povidone-iodine).
The operative site was anesthetized with 2% lignocaine HCL with 1:200,000 adrenaline (Lox® Neon pharmaceuticals limited, India) using block technique. After obtaining adequate anesthesia, recipient sites were prepared as per requirement. One skilled masked surgeon (VKB) performed all the surgeries. The surgical process was same for both groups and was carried out according to the method described by Sclar et al. [2], and VIP-CT flap was subsequently obtained from palatal donor site.
Donor and recipient sites were sutured primarily with absorbable sutures using an interrupted suture technique and gentle pressure was applied with moistened gauze for 10 min.
VIP-CT/PRF group
For patient recruited in VIP-CT/PRF group, platelet-rich fibrin (PRF) was prepared as per the protocol given by Choukroun et al., as explained in earlier studies [16–19]. PRF clot thus obtained was placed at the donor site of the palate under the split partial flap after harvesting VIP-CT flap and squeezed using moist gauze piece under the mucosal flap. The fluid obtained during squeezing was thus confined to the treated site. The partial thickness flap was then secured in the place by interrupted sutures using 4–0 black braided silk sutures to obtain primary closure that were removed after 1 week.
VIP-CT/LLLT group
For patient recruited in VIP-CT/LLLT group, photobiostimulation was done on the donor site of the palate at six (6) points approximately 5 mm and 7 mm from the gingival margin on operated surgical sites anterio-posteriorly after repositioning of partial thickness flap [14]. The irradiation was performed using 940 nm InGaAsP diode laser (Epic Biolase) in continuous mode for 10 s at 0.3 W applying total fluence/ energy density (3.82 J/cm2) (Table 1). The hand piece was positioned 1 cm above the wound area, perpendicularly. Laser therapy was initiated in the immediate postoperative period (just after sutures) and LLLT was initiated directly after surgery and was repeated on the third day and then at the end of 1 week and 4 weeks.
Table 1.
The operating protocols of the LLLT on palatal donor site by 940 nm diode laser are summarized in the table
| Laser technical parameters | |
|---|---|
| Wavelength (nm) | 940 nm |
| Average power (W) | 0.3 W |
| Peak Power (W) | 0.3 W |
| Energy (J) | 3 J/point |
| On time (pulse duration)(ms) | 10 s |
| Emission mode | Continuous wave (CW) |
| Tip size (µ) | 600 µ |
| Spot radius (µ) | 300 µ |
| Spot size (cm2) | 0.5 cm2 |
| Irradiation time (s) | 10 s |
| Distance | 1 cm from the tissue |
| Angulation | 90 degree |
| Energy density/ fluence (J/cm2) | 3.82 J/cm2 |
| Power density (W/ cm2) | 38.2 W/cm2 |
Postoperative instructions
The area was examined for 2 to 3 min after suturing of the area for any fresh bleeding. The patients were given written post-operative instructions and medications. Amoxicillin (500 mg 3 times a day for 5 days) and ibuprofen (3 times a day for 3 days) were prescribed. The patients were refrained from retracting the lips and cheeks and to avoid brushing or flossing in the grafted area for 6 weeks. To achieve chemical plaque control, all the patients were asked to rinse with 0.2% chlorhexidine gluconate solution for 2 weeks. The sutures were removed after 2 weeks post-surgery. Essex appliance was delivered to the patient with minimal soft tissue contact during healing phase, thus preventing the surgical site from undue routine damaging forces. After 3 months, the patient was referred to Department of Prosthodontics for rehabilitation with fabrication of the final prosthesis. The postoperative follow-up was done after 3 months.
Parameters recorded
Following clinical parameters and patient satisfaction response were recorded at baseline (before surgery), 1 week, 4 weeks, and 12 weeks.
Clinical parameters
Palatal tissue thickness was measured at six fixed points (5 and 7 mm from the gingival margin) using an acrylic stent as explained earlier. To standardize the parameter recorded acrylic stent was positioned at various time intervals to mark the points. An endodontic file with rubber cursor was inserted on the marked point perpendicularly until it reaches palatine bone plate under local anesthesia administered using insulin syringe.
Consistency, color match, contour, and scar
The “Modified Manchester Scar Scale (MSS)” was modified to assess consistency, color match, contour, and scar of the palatal wound on the donor site. Consistency was scored as “firm and resilient” and “soft and edematous;” color as “absolute match;” “slight mis-match;” “obvious mis-match,” and “gross mis-match to the surrounding muscosa/skin;” contour as “flush with surrounding skin,” “slightly proud/indented,” “hypertrophic,” and “keloid;” and scar was recorded as “present” and “absent” respectively by visually comparing with the adjacent non-operated site [20].
Patient satisfaction analysis
In form of pain, burning sensation and postoperative discomfort at baseline (after surgery), 1 week, 4 weeks, and 12 weeks. Postoperative pain intensity was assessed using a 100‐mm line VAS Score with two end‐points representing “absent,” and “present.” The participants were asked to rate their pain by placing a mark on the VAS line corresponding to their postoperative pain level [21]. Patient post-operative discomfort was analyzed through air spray for 5 s over the operated site. Sensitivity to air spray was measured as “comfort” and “discomfort” before applying anesthesia to palatal mucosa [22].
Complications
Various complications were evaluated at baseline (after surgery), 1 week, 4 weeks, and 12 weeks. Discoloration of palatal muscosa (Ecchymosis) after surgery is measured visually and recorded as “no ecchymosis,” “mild ecchymosis (patch measuring less than 1 cm),” and “severe ecchymosis (patch measuring more than 1 cm).” The presence of necrosis in the palatal flap was clinically assessed with periodontal probe and recorded as “no necrosis,” “less than 30% of necrosis of the total surface of the elevated flap” and “more than 30% of necrosis of the total surface of the elevated flap” [23]. Swelling and edema assessment and measurement were performed subjectively in the clinical routine and recorded as “no swelling” and edema, “presence of mild swelling, and edema” and “presence of severe swelling and edema seen on palatal site.” Infection was assessed on visual examination and “no pus discharge” and “presence of pus discharge.”
Statistical analysis
Statistical data was analyzed using SPSS (Statistical package for social science) Version 22.0, statistical Analysis Software. The values were represented in number (%) and Mean ± SD. The chi-square test was used to determine the significance of the difference between two independent groups. To carry out the test, the proportion of cases in one group in the various categories was compared with the proportion of cases from the other group. The dependent t-test (also called the paired t-test or paired sample t-test) compared the means of two related groups to determine whether there was a statistically significant difference between these means. The independent t-test, also called the two-sample t-test, independent sample t-test, or Student’s t-test, determined whether there was a statistically significant difference between the means in two unrelated groups. The ANOVA test was used to compare the within group and between group variances among the study groups. ANOVA provided “F” ratio, where a higher “F” value depicted a higher intergroup difference. Tukey’s post hoc analysis for intra group comparison of tissue thickness in PRF and LLLT groups at different time periods. Level of significance “p” was considered statistically very highly significant p < 0.001, and was considered statistically not significant when p > 0.05.
Results
For the current study, 34 (17 in each group) compliant, non-smoker patients were enrolled for the study after initial screening of 40 (18 males and 22 females) patients. However, only total of 31 (15 in VIP-CT/PRF and 16 in VIP-CT/LLLT) patients in each group were able to complete the study and finally analyzed to obtain the results. Out of 34 patients, 3 patients who initially underwent baseline treatment modalities were failed to report during the follow-up period due to COVID-19 pandemic situation. Finally, thirty-one patients (17 women and 14 men), mean age of subjects in VIP-CT/PRF was 30.27 ± 9.60 years, while in VIP-CT/LLLP, the mean age was 29.73 ± 7.95 years completed the study. None of them presented adverse effects to the procedures and/or laser application protocol. The difference in mean ages and gender between the groups was non-significant (p = 0.913 and p = 0.665, respectively).
The mean thickness of palatal mucosa at surgical site was increased from 2.91 ± 0.65 to 2.93 ± 0.55 mm after 1 week and to 3.02 ± 0.55 mm after 12 weeks in PRF-treated site, while in LLLT-treated sites, palatal mucosal thickness decreased after 1 week from 3.35 ± 0.56 mm to 1.83 ± 0.48 mm and then increase to 3.35 ± 0.55 mm after 12 weeks, and the mean difference was significantly higher for PRF-treated group compared to LLLT-treated group (Tables 2 and 3).
Table 2.
Intergroup comparison of tissue thickness at different timelines using independent t-test
| Timelines | Groups | Number | Mean | Std. deviation | Std. error mean | p-value |
|---|---|---|---|---|---|---|
| Baseline | VIP-CT/PRF | 15 | 2.912 | 0.649 | 0.195 | 0.106 (NS) |
| VIP-CT/LLLT | 16 | 3.350 | 0.560 | 0.168 | ||
| One week | VIP-CT/PRF | 15 | 2.931 | 0.552 | 0.166 | 0.000** |
| VIP-CT/LLLT | 16 | 1.834 | 0.478 | 0.144 | ||
| Four weeks | VIP-CT/PRF | 15 | 3.012 | 0.545 | 0.164 | 0.374 (NS) |
| VIP-CT/LLLT | 15 | 3.213 | 0.493 | 0.148 | ||
| Twelve weeks | VIP-CT/PRF | 15 | 3.015 | 0.555 | 0.167 | 0.170 (NS) |
| VIP-CT/LLLT | 15 | 3.350 | 0.548 | 0.165 |
*p < 0.05 is statistically significant, **p < 0.01 is statistically highly significant; NS, not significant
Table 3.
Tukey’s post hoc analysis for intra group comparison of tissue thickness in PRF and LLLT groups at different time periods
| Dependent variable | (I) Groups | (J) Groups | Mean difference (I-J) | Std. error | p-value |
|---|---|---|---|---|---|
| VIP-CT/PRF | Baseline | 1 week | − 0.01970 | 0.24624 | 1.000 |
| 4 weeks | − 0.10000 | 0.24624 | 0.977 | ||
| 12 weeks | − 0.10303 | 0.24624 | 0.975 | ||
| 1 week | 4 weeks | − 0.08030 | 0.24624 | 0.988 | |
| 12 weeks | − 0.08333 | 0.24624 | 0.986 | ||
| 4 weeks | 12 weeks | − 0.00303 | 0.24624 | 1.000 | |
| VIP-CT/LLLT | Baseline | 1 week | 1.51515* | 0.22232 | 0.000** |
| 4 weeks | 0.13636 | 0.22232 | 0.927 | ||
| 12 weeks | 0.00000 | 0.22232 | 1.000 | ||
| 1 week | 4 weeks | − 1.37879* | 0.22232 | 0.000** | |
| 12 weeks | − 1.51515* | 0.22232 | 0.000** | ||
| 4 weeks | 12 weeks | − 0.13636 | 0.22232 | 0.927 |
*p < 0.05 is statistically significant, **p < 0.01 is statistically highly significant
The intergroup comparison of patient esthetic parameters viz. color, contour, consistency, and scar match between VIP-CT/PRF and VIP-CT/LLLT are summarized in Table 4 (Fig. 4a to h). Results revealed 100% absolute match in both the groups at baseline and 12 weeks for all esthetic parameters. At 4 weeks, absence of hypertrophic tissue was observed in VIP-CT/LLLT compared with VIP-CT/PRF group (40% of patients, p = 0.003); 56.2% of patients presented a perfect match color in VIP-CT/LLLT while none of VIP-CT/PRF patients had this characteristic (p = 1); “soft and edematous” tissue was not observed in VIP-CT/LLLT compared with VIP-CT/PRF (20% of patients, p = 0.534).
Table 4.
Patient esthetic parameters
| Parameters | VIP-CT/PRF (N = 15) | VIP-CT/LLLT (N = 16) | Chi-square | p-value | ||||
|---|---|---|---|---|---|---|---|---|
| No | % | No | % | |||||
|
Color: ▪ Absolute match ▪ Slight mismatch ▪ Obvious mismatch ▪ Gross mismatch |
Baseline | Absolute match | 15 | 100 | 16 | 100 | NA | NA |
| 1st week | Slight mismatch | 7 | 46.7 | 10 | 62.5 | 0.536 | 0.608 | |
| Obvious mismatch | 8 | 53.3 | 6 | 37.5 | ||||
| 4th week | Absolute match | 0 | 0 | 9 | 56.2 | 3.32 | 1 | |
| Slight mismatch | 7 | 46.7 | 7 | 43.8 | ||||
| Obvious mismatch | 8 | 53.3 | 0 | 0 | ||||
| 12th week | Absolute match | 15 | 100 | 16 | 100 | NA | NA | |
|
Contour: ▪ Flush with surrounding skin ▪ Slightly proud/indented ▪ Hypertrophic ▪ Keloid |
Baseline | Flush with surrounding skin | 15 | 100 | 16 | 100 | NA | NA |
| 1st week | Slightly proud/ indented | 7 | 46.67 | 9 | 56.25 | 13.39 | 0.004 | |
| Hypertrophic | 8 | 53.33 | 7 | 43.75 | ||||
| 4th week | Flush with surrounding skin | 0 | 0 | 9 | 56.25 | 9.81 | 0.003 | |
| Slightly proud/ indented | 9 | 60 | 7 | 43.75 | ||||
| Hypertrophic | 6 | 40 | 0 | 0 | ||||
| 12th week | Flush with surrounding skin | 15 | 100 | 16 | 100 | NA | NA | |
|
Consistency: ▪ Firm and Resilient ▪ Soft and edematous |
Baseline | Firm and resilient | 15 | 100 | 16 | 100 | NA | NA |
| 1st week | Firm and resilient | 3 | 20 | 5 | 31.25 | 0.386 | 0.534 | |
| Soft and Edematous | 12 | 80 | 11 | 68.75 | ||||
| 4th week | Firm and resilient | 12 | 80 | 16 | 100 | 1.048 | 0.306 | |
| Soft and Edematous | 3 | 20 | 0 | 0 | ||||
| 12th week | Firm and resilient | 15 | 100 | 16 | 100 | NA | NA | |
|
Scar match: ▪ Present ▪ Absent |
Baseline | Present | 15 | 100 | 16 | 100 | NA | NA |
| 1st week | Present | 8 | 53.33 | 7 | 43.75 | 13.1 | 0.007 | |
| Absent | 7 | 66.67 | 9 | 56.25 | ||||
| 4th week | Present | 6 | 40 | 7 | 43.75 | 11.73 | 0.009 | |
| Absent | 9 | 60 | 9 | 56.25 | ||||
| 12th week | Present | 15 | 100 | 16 | 100 | NA | NA | |
Fig. 4.
Figure showing pre- and post-operative images of both the groups. a Pre-operative VIP-CT/PRF site. b VIP-CT flap approximated on VIP-CT/PRF recipient site. c PRF placed on VIP-CT/PRF donor site. d First-week post-operative of VIP-CT/PRF site. e Pre-operative VIP-CT/LLLT site. f VIP-CT flap rotated and repositioned on VIP-CT/LLLT recipient site. g LLLT on palate immediately after suturing on VIP-CT/LLLT donor site. h LLLT on palate at the end of 1-week of VIP-CT/LLLT site
Intergroup comparison of patients’ comfort parameters using VAS score in terms of pain and burning sensation, post-operative discomfort, ecchymosis, tissue necrosis, swelling, and infection are summarized in Table 5. Analysis of all patient’s comfort parameters revealed 100% absence of any sign and symptom in both the groups at baseline and 12 weeks. “Absence” of pain and burning sensation were observed as early as at 1 week in LLLT-treated palatal donor sites compared to PRF-treated palatal donor site after VIP-CT. Improvement in post-surgical like ecchymosis, tissue necrosis, swelling, and infection was observed almost 100% at 4 weeks in both the groups, except for mild ecchymosis in 0.7% subjects in PRF-treated palatal donor sites revealed “presence” of post-surgical complications at 4 weeks.
Table 5.
Patient comfort parameters
| Parameters | VIP-CT/PRF (N = 15) | VIP-CT/LLLT (N = 16) | Chi-square | p-value | ||||
|---|---|---|---|---|---|---|---|---|
| No | % | No | % | |||||
|
Pain and Burning Sensation: (VAS) ▪ Present ▪ Absent |
Baseline | Absent | 15 | 100 | 16 | 100 | NA | NA |
| 1st week | Absent | 4 | 26.67 | 16 | 100 | 15.231 | 0 | |
| Present | 11 | 73.33 | 0 | 0 | ||||
| 4th week | Absent | 15 | 100 | 16 | 100 | NA | NA | |
| 12th week | Absent | 15 | 100 | 16 | 100 | NA | NA | |
|
Post-operative discomfort: (VAS) ▪ Comfort ▪ Discomfort |
Baseline | Comfort | 15 | 100 | 16 | 100 | NA | NA |
| 1st week | Comfort | 8 | 53.33 | 8 | 50 | 0.786 | 0.375 | |
| Discomfort | 7 | 46.67 | 8 | 50 | ||||
| 4th week | Comfort | 10 | 66.67 | 16 | 100 | 3.474 | 0.062 | |
| Discomfort | 5 | 33.33 | 0 | 0 | ||||
| 12th week | Comfort | 15 | 100 | 16 | 100 | NA | NA | |
|
Ecchymosis: ▪ No Ecchymosis ▪ Mild Ecchymosis |
Baseline | No ecchymosis | 15 | 100 | 16 | 100 | NA | NA |
| 1st week | No ecchymosis | 0 | 0 | 16 | 100 | 1.048 | 0.306 | |
| Mild ecchymosis | 15 | 100 | 0 | 0 | ||||
| 4th week | No ecchymosis | 14 | 93.3 | 16 | 100 | 1.048 | 0.306 | |
| Mild ecchymosis | 1 | 0.7 | 0 | 0 | ||||
| 12th week | No ecchymosis | 15 | 100 | 16 | 100 | NA | NA | |
|
Tissue Necrosis: ▪ No sign ▪ Less than 30% ▪ More than 30% |
Baseline | No sign | 15 | 100 | 16 | 100 | NA | NA |
| 1st week | No sign | 14 | 93.3 | 16 | 100 | 1.048 | 0.306 | |
| Less than 30% | 1 | 0.7 | 0 | 0 | ||||
| 4th week | No sign | 15 | 100 | 16 | 100 | NA | NA | |
| 12th week | No sign | 15 | 100 | 16 | 100 | NA | NA | |
|
Swelling: ▪ No sign ▪ Mild ▪ Severe |
Baseline | No sign | 15 | 100 | 16 | 100 | NA | NA |
| 1st week | No sign | 14 | 93.3 | 16 | 100 | 1.048 | 0.306 | |
| Mild | 1 | 0.7 | 0 | 0 | ||||
| 4th week | No sign | 15 | 100 | 16 | 100 | NA | NA | |
| 12th week | No sign | 15 | 100 | 16 | 100 | NA | NA | |
|
Infection: ▪ No pus discharge ▪ Presence of pus discharge |
Baseline | No pus discharge | 15 | 100 | 16 | 100 | NA | NA |
| 1st week | No pus discharge | 14 | 93.3 | 16 | 100 | 1.048 | 0.306 | |
| Presence of pus discharge | 1 | 0.7 | 0 | 0 | ||||
| 4th week | No pus discharge | 15 | 100 | 16 | 100 | NA | NA | |
| 12th week | No pus discharge | 15 | 100 | 16 | 100 | NA | NA | |
Discussion
Palatal morbidity is frequently observed phenomena after VIP-CT flap for predictable large soft tissue augmentation in a single procedure. The present study investigated the donor site clinical healing, patient satisfaction, and post-operative discomfort after VIP-CT flap surgery either using LLLT or PRF. Previous studies have evaluated the effect of PRF after CTG and/or FGG procedures on donor site healing [8, 10, 22, 24]. Studies have also evaluated effect of LLLT after CTG or FGG procedures on palatal healing [14, 25, 26]. However, until now no published data reported the comparative evaluation of PRF and LLLT after VIP-CT flap on donor site healing. To the best of our knowledge, this was the first randomized clinical study that evaluated the effects of LLLT and PRF after VIP-CT flap at donor site on the palate.
In-concurrence to Dias et al. [14], soft tissue thickness (TT) was measured using endodontic K-file marked with the help of acrylic stent at baseline, 1 week, 4 weeks, and 12 weeks in LLLT- or PRF-treated donor sites. No significant difference was observed between the two groups at baseline. Within the group, there was non-significant increase in tissue thickness from baseline to 1 week and then to 4- and 12-weeks interval in PRF-treated group. Whereas, in LLLT-treated group, intra-group comparison showed significant decrease from baseline to 1 week, and then statistically significant increase was observed at 4 weeks followed by non-significant increase at 12 weeks interval but similar to that at baseline. Similarly, Dias et al. [14] also reported lower mean tissue thickness values compared to baseline values in LLLT-treated donor sites after CTG. Whereas, Femminella et al. [27], Ustaoglu et al. [22], and Keceli et al. [28] reported higher mean tissue thickness values compared to baseline values in PRF-treated donor sites after CTG and/or FGG treated donor sites at 21 days.
Color, contour, and consistency were evaluated using Manchester Scar Scale between PRF and LLLT-treated donor sites. Results revealed “absolute match,” “flush with surrounding skin” contour and “firm and resilient” consistency in 100% of subjects in both the experimental groups at baseline and 12 weeks interval. Within the groups, absolute color match was not observed during the healing phase at PRF-treated sites until 12 weeks, in contrast to LLLT-treated sites where “absolute match” as observed in 56% of the subjects at 4 weeks. Similar to present study, Ustaglo et al. [22] also did not observe 100% color match at 3 weeks interval; however, Heidari et al. [29] reported better wound color pattern in the LLLT-treated group was on palatal donor site healing.
Between group comparison at 1 week, shown 53% of the subjects at PRF sites with “hypertropic contour” compared to 43% of subjects treated with LLLT, and the difference between the two was statistically significant (p = 0.004). At the end of 4th week, none of the subjects in PRF-treated sites revealed “flush with surrounding skin” compared to 56% of LLLT-treated subjects. The difference between the groups was statistically significant (p = 0.003). Similarly, even after PRF therapy on palate donor site, 20% of subjects in PRF-treated group reported “soft and edematous” consistency compared to LLLT-treated group, whereas 100% “firm and resilient” consistency was observed at 4th week. To the best of authors’ knowledge, no published data reported changes in the consistency using PRF or LLLT. Patarapongsanti et al. [21] showed complete epithelization in 88% in PRF-treated patient postoperatively after FGG. The present study was in line with Heidari et al. [29], where LLLT could promote re-epithelization of FGG donor site at 100% laser-treated donor sites presented after 21 days. Also, both at baseline and 12 weeks interval, none of the patients presented scars at the donor site in any of the experimental groups. PRF-treated sites show better healing of scars at the end of 4th week, and 60% of subjects treated with PRF did not show any scar compared to 56% of subjects treated with LLLT (p = 0.009).
The present study showed how severe pain was measured in the Visual Analog Scale (VAS) preoperatively, but after the application of LLLT, there was marked reduction in pain at 4th week. In the present study, pain and burning sensation between PRF and LLLT groups revealed 100% “comfort” in both the groups at baseline, 4 week and 12 weeks. Within the group, significant difference was revealed between the groups with 100% subjects of LLLT group with “comfort,” while only 26.6% subjects of PRF group showed with “comfort” at 1st week visit. Consistently, Ozcelik et al. [10] reported that the use of 810 nm diode laser for biostimulation after harvesting the FGG resulted in less postoperative pain and discomfort than the controls.
Postoperative complications were defined as ecchymosis, tissue necrosis, swelling, and infection. It is notable that 93.3% of the patients treated with PRF showed “no sign” of postoperative complications. Only 0.7% of the patients showed “mild sign” of complications while 0.0% of subjects in LLLT-treated showed “no sign” of complications. None of the complications significantly influenced the outcome of the surgical procedures. The difference proportion of all the complications between PRF and LLLT group was statistically not significant (p = 0.306). Zucchelli et al. [3], in their study on 50 patients treated with FGG techniques, found necrosis in 28% of the patients in the TD group. At 4 weeks, scar at incision line showed better outcomes for PRF-treated donor sites than LLLT-treated donor sites. These better outcomes in PRF-treated donor palatal sites may be attributed to better wound healing properties and increasing the bulk on the operative site. High density of fibrin fibres provides additional stability of the wound and promotes rapid neoangiogenesis [17]. Furthermore, PRF releases large amounts of the three main growth factors transforming growth factor beta-1 (TGF beta-1), platelet-derived growth factor AB (PDGF-AB), vascular endothelial growth factor (VEGF), and important coagulation matricellular glycoprotein (thrombospondin-1, TSP-1) for at least 7 days [30], which boosts hemostasis and wound healing by promoting immune system activation, cell migration, and proliferation. PRF is a promising material for all forms of superficial cutaneous and mucosal healing because to its mechanical function, quick angiogenesis-promoting ability, and easier remodelling of fibrin in a more resistant connective tissue [7].
Post-operatively better results were obtained as early as 1st week after VIP-CT flap in terms of consistency, color match, contour, pain, and burning sensation and patient comfort in LLLT-treated donor palatal sites compared to PRF-treated donor palatal sites. LLLT is effective in the fibroblastic stage of wound healing, with enhancement of fibroblast activity, angiogenesis, and epithelial proliferation [31]. The inflammation of tissues following laser application enhances the ability to increase cell proliferation and angiogenesis and thus increased the speed of improvement [32]. LLLT on the donor palatal site after VIP-CT flap may have influenced the tissue erythema and angiogenesis during healing process. Anti-inflammatory and tissue repair properties of LLLT lead to decreased postoperative discomfort and the number of analgesics required by the patients. But the results were non-significantly greater than the PRF-treated sites.
For the present study, a total of 4 sessions initiated directly after surgery and was repeated on the third day and then at the end of 1 week and 4 weeks. LLLT is based on photobiostimulation effect which promotes wound healing and anti-inflammatory effect, and reduces pain by stimulating tissues without producing irreversible changes. The molecular absorption of laser light increases cellular metabolism, followed by the stimulation of photoreceptors in the mitochondrial respiratory chain, leads to cellular ATP levels, the release of growth factors, and the induction of fibroblasts and collagen synthesis [33]. The biostimulatory effects of LLLT is influenced by the type of laser, the emission wavelength, energy dose, and transmission mode, and it is necessary to establish the optimal treatment parameters for different LLLT. As per manufacture instruction diode laser used in the study i.e. Epic 10 (Biolase, Inc., Irvine, CA, USA) is designed to provide near-infrared laser energy with a wavelength of 940 nm to a tissue surface for the temporary pain relief when applied with deep tissue hand-piece provided for extra-oral pain relief [34]. For the present study, surgical hand-piece /delivery system without external fiber optic tip was used at a distance of 1 cm from the target tissue giving effective spot radius of 0.5 cm2 with energy density of 3.82 J/cm2 in non-contact mode at 0.3 W for 10 s at four sessions in line with Dias et al. [14] Laser treatment was carried out with adequate eye protection for the patient, operator, and the assistant. It is increasingly apparent that light-biologic tissue interactions can evoke pathophysiologic (disease) and anatomy-specific responses.
In contrast to FGG and CTG, VIP-CT flap may cause more morbidity and discomfort for the patient in the palatine region that sometimes may causes donor site sloughing, bleeding, dehiscence or necrosis, swelling and infection [2]. In the present study both the groups, LLLT and PRF-treated donor palatal site revealed no complications after VIP-CT. LLLT therapy needs dose calibration, knowledge of power setting and require a learning curve for a particular unit, and PRF therapy on donor site requires invasion of another operating site by needle prick, chair side availability of compatible table top centrifuge, training and extra space in clinical setup. Both the groups have their own advantage and disadvantage but in the present study, individually both modalities have presented good results after VIP-CT flap on palatal site after 12 weeks. Studies have shown that palatine mucosa can heal quickly within 20 to 60 days [35], and the rate of healing is further accelerated with LLLT and PRF after VIP-CT.
However, in spite of favourable result, there are few limitations of the study. These include small sample size, lack of negative control, and short-term follow-up, and conducted at single center only. Furthermore, the LLLT therapy was given at first day, 3-day, 1-week, and 4-week intervals, which coincides with the patient routine follow-up appointment instead of every alternate day for 1 week due to patient’s financial issues and inability for frequent visits.
Conclusion
Within limitations, it can be concluded that in the present patient-centered study, favourable final clinical outcomes in terms of tissue thickness, consistency, color, contour, scar, pain, and burning sensation and patient comfort were obtained in both LLLT- and PRF-treated donor palatal sites at 12 weeks. More tissue thickness was observed compared to baseline in PRF-treated donor sites; in contrast the final tissue thickness obtained in case of LLLT-treated donor sites at 12 weeks where the final outcome results were comparable to baseline.
Author contribution
| Contributor 1 Sadaf Mukhtyar | Contributor 2 Vivek Kumar Bains | Contributor 3 Chetan Chandra | Contributor 4 Ruchi Srivastava | |
|---|---|---|---|---|
| Concepts | √ | √ | ||
| Design | √ | √ | ||
| Definition of intellectual content | √ | √ | √ | √ |
| Literature search | √ | |||
| Clinical studies | √ | √ | ||
| Experimental studies | √ | √ | √ | √ |
| Data acquisition | √ | |||
| Data analysis | √ | √ | √ | |
| Statistical analysis | √ | |||
| Manuscript preparation | √ | √ | ||
| Manuscript editing | √ | √ | ||
| Manuscript review | √ | √ | √ | √ |
| Guarantor | √ |
Funding
This work belongs to the Department of Periodontology, Saraswati Dental College & Hospital, Lucknow (UP), India. Infrastructural support to conduct the study was provided by the institute.
Data availability
The authors confirm that the required data for the support of the study are available in the article. Additional data can be availed from corresponding author upon reasonable request.
Declarations
Conflict of interest
The author declare no competing interests.
Footnotes
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Contributor Information
Sadaf Mukhtar, Email: drsadaf323@gmail.com.
Vivek Kumar Bains, Email: doc_vivek76@yahoo.co.in.
Chetan Chandra, Email: chetanchandra321@gmail.com.
Ruchi Srivastava, Email: drruchi117@gmail.com.
References
- 1.Shanmugam M, Kumar TS, Arun KV, Arun R, Karthik SJ. Clinical and histological evaluation of two dressing materials in the healing of palatal wounds. J Indian Soc Periodontol. 2010;14:241–244. doi: 10.4103/0972-124X.76929. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Sclar AG (2003) Vascularized interpositional periosteal-connective tissue (VIP-CT) flap. In: Soft Tissue and Esthetic Considerations in Implant Dentistry. Chicago, Quintessence Int, 163–187.
- 3.Zucchelli G, Mounssif I, Mazzotti C, Montebugnoli L, Sangiorgi M, Mele M, Stefanini M. Does the dimension of the graft influence patient morbidity and root coverage outcomes? A randomized controlled clinical trial. J Clin Periodontol. 2014;41:708–716. doi: 10.1111/jcpe.12256. [DOI] [PubMed] [Google Scholar]
- 4.Rossmann JA, Rees TD. A comparative evaluation of hemostatic agents in the management of soft tissue graft donor site bleeding. J Periodontol. 1999;70:1369–1375. doi: 10.1902/jop.1999.70.11.1369. [DOI] [PubMed] [Google Scholar]
- 5.Kim CS, Jang YJ, Choi SH, Cho KS. Long-term results from soft and hard tissue augmentation by a modified vascularized interpositional periosteal-connective tissue technique in the maxillary anterior region. Int J Oral Maxillofac Surg. 2012;70:484–491. doi: 10.1016/j.joms.2011.02.105. [DOI] [PubMed] [Google Scholar]
- 6.Dohan DM, Rasmusson L, Albrektsson T. Classification of platelet concentrates: from pure platelet-rich plasma (PPRP) to leucocyte and platelet-rich fibrin (L-PRF) Trends Biotechnol. 2009;27:158–167. doi: 10.1016/j.tibtech.2008.11.009. [DOI] [PubMed] [Google Scholar]
- 7.Jain V, Triveni MG, Kumara TB, Mehta DS. Role of platelet-rich-fibrin in enhancing palatal wound healing after free graft. Contemp Clin Dentistry. 2012;3:240–243. doi: 10.4103/0976-237X.101105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Yen CA, Griffin TJ, Cheung WS, Chen J. Effects of platelet concentrate on palatal wound healing after connective tissue graft harvesting. J Periodontol. 2007;78:601–610. doi: 10.1902/jop.2007.060275. [DOI] [PubMed] [Google Scholar]
- 9.Ihsan FR. Low-level laser therapy accelerates collateral circulation and enhances microcirculation. Photobiomodulation, Photomed Laser Surg. 2005;23:289–294. doi: 10.1089/pho.2005.23.289. [DOI] [PubMed] [Google Scholar]
- 10.Ozcelik O, Seydaoglu G, Haytac CM. Diode laser for harvesting de-epithelialized palatal graft in the treatment of gingival recession defects: a randomized clinical trial. J Clin Periodontol. 2016;43:63–71. doi: 10.1111/jcpe.12487. [DOI] [PubMed] [Google Scholar]
- 11.Reiser GM, Bruno JF, Mahan PE, Larkin LH. The subepithelial connective tissue graft palatal donor site: anatomic considerations for surgeons. Int J Periodontics Restorative Dent. 1996;16:130–137. [PubMed] [Google Scholar]
- 12.Harris RJ (1992) The connective tissue and partial thickness double pedicle graft: a predictable method of obtaining root coverage. J Periodontol 63:477–486 [DOI] [PubMed]
- 13.Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159–174. doi: 10.2307/2529310. [DOI] [PubMed] [Google Scholar]
- 14.Dias SB, Fonseca MV, Santos NC, et al. Effect of GaAlAs low-level laser therapy oh the healing of human palate mucosa after connective tissue graft harvesting: Randomized Clinical Trial. Lasers Med Sci. 2015;30:1695–1702. doi: 10.1007/s10103-014-1685-2. [DOI] [PubMed] [Google Scholar]
- 15.Sheridan JJ, Ward W, McMinn R. Essix retainers: fabrication and supervision for permenant retention. J Clin Orthodontics. 1993;27:37–45. [PubMed] [Google Scholar]
- 16.Singh D, Jhingran R, Bains VK, Madan R, Srivastava R. Efficacy of platelet-rich fibrin in interdental papilla reconstruction as compared to connective tissue using microsurgical approach. Contemp Clin Dent. 2019;10:643–651. doi: 10.4103/ccd.ccd_936_18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Kumar A, Bains VK, Jhingran R, Srivastava R, Madan R, Rizvi I. Patient-centered microsurgical management of gingival recession using coronally advanced flap with either platelet-rich fibrin or connective tissue graft: a comparative analysis. Contemp Clin Dent. 2017;8:293–304. doi: 10.4103/ccd.ccd_70_17. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Agarwal SK, Jhingran R, Bains VK, Srivastava R, Madan R, Rizvi I. Patient-centered evaluation of microsurgical management of gingival recession using coronally advanced flap with platelet-rich fibrin or amnion membrane: a comparative analysis. Eur J Dent. 2016;10:121–133. doi: 10.4103/1305-7456.175686. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Gupta SJ, Jhingran R, Gupta V, Bains VK, Madan R, Rizvi I. Efficacy of platelet-rich fibrin vs. enamel matrix derivative in the treatment of periodontal intrabony defects: a clinical and cone beam computed tomography study. J Int Acad Periodontol. 2014;16(3):86–96. [PubMed] [Google Scholar]
- 20.Beausang E, Floyd H, Dunn KW, Orton CI, Ferguson MW. A new quantitative scale for clinical scar assessment. Plast Reconstr Surg. 1998;102:1954–1961. doi: 10.1097/00006534-199811000-00022. [DOI] [PubMed] [Google Scholar]
- 21.Patarapongsanti A, Bandhaya P, Sirinirund B, Khongkhunthian S, Khongkhunthian P. Comparison of platelet-rich fibrin and cellulose in palatal wounds after graft harvesting. J Investig Clin Dent. 2019;10(4):12467–12489. doi: 10.1111/jicd.12467. [DOI] [PubMed] [Google Scholar]
- 22.Ustaoglu G, Esra E, Tunali M. Low-level laser therapy in enhancing wound healing and preserving tissue thickness at free gingival graft donor sites: a randomized, controlled clinical trial. Photomed Laser Surg. 2017;35(4):223–230. doi: 10.1089/pho.2016.4163. [DOI] [PubMed] [Google Scholar]
- 23.Zorzano LAA, Fuente AMGDL, Mendia XM. Complications of harvesting a connective tissue graft from the palate. A retrospective study and description of a new technique. Int J Clin Exp Med. 2017;9:1439–1445. doi: 10.4317/jced.54337. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Reddy S, Prasad MGS, Singh S, Krishnanand P, Bhowmik N, Ashwini N. Enhancing palatal wound healing by using platelet rich fibrin membrane as fibrin bandage. Int J Appl Dent Sci. 2015;1:02–04. [Google Scholar]
- 25.Fahimipour F, Mahdian M, Houshmand B, Asnaashari M, Sadrabadi AN, Farashah SEN, et al. The effect of He-Ne and Ga-Al-As laser light on the healin of hard palate mucosa of mice. Lasers Med Sci. 2012;28:93–100. doi: 10.1007/s10103-012-1060-0. [DOI] [PubMed] [Google Scholar]
- 26.Firat ET, Dag A, Gunay A, Kaya B, Karadede MI, Kanay BE, et al. The effect of low-level laser therapy on the healing of hard palate mucosa and the oxidative stress status of rats. J Oral Pathol Med. 2014;43:103–110. doi: 10.1111/jop.12106. [DOI] [PubMed] [Google Scholar]
- 27.Femminella B, Iaconi MC, Tullio M, et al. Clinical comparison of platelet rich fibrin and a gelatin sponge in the management of palatal wounds following epithelialized free gingival graft harvest: a randomized clinical trial. J Periodontol. 2016;87:103–113. doi: 10.1902/jop.2015.150198. [DOI] [PubMed] [Google Scholar]
- 28.Keceli HG, Aylikci BU, Koseoglu S, et al. Evaluation of palatal donor site haemostasis and wound healing after free gingival graft surgery. J Clin Periodontol. 2015;42:582–589. doi: 10.1111/jcpe.12404. [DOI] [PubMed] [Google Scholar]
- 29.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;172:109–114. doi: 10.1016/j.jphotobiol.2017.05.022. [DOI] [PubMed] [Google Scholar]
- 30.Dohan D, Donsimoni JM, Navarro G, Gaultier F. Platelet concentrates. Part 1: Technologies. Implantodontie. 2003;12:5–16. [Google Scholar]
- 31.Moslemi N, Heidari M, Fekrazad R, Nokhbatolfoghahaie H, Yaghobee S, Shamshiri A, et al. Effect of 660nm low power laser on pain and healing in palatal donor sites a randomized controlled clinical trial. J Dent Med. 2014;27:71–77. [Google Scholar]
- 32.Ahad A, Tasneem S, Lamba AK, Khan S. Healing of self-inflicted thermal injury of palatal mucosa by low-level laser therapy. Spec Care Dent. 2017;37:314–317. doi: 10.1111/scd.12256. [DOI] [PubMed] [Google Scholar]
- 33.Hamblin MR, Demidova TN. Mech Low Level Light Ther. 2006;6140:614001–614012. doi: 10.1117/12.646294. [DOI] [Google Scholar]
- 34.AlGhamdi KM, Kumar A, Moussa NA. Low-level laser therapy: a useful technique for enhancing the proliferation of various cultured cells. Lasers Med Sci. 2012;27:237–249. doi: 10.1007/s10103-011-0885-2. [DOI] [PubMed] [Google Scholar]
- 35.Thoma DS, Sancho PM, Ettlin DA, Hämmerle CH, Jung RE. Impact of a collagen matrix on early healing, aesthetics and patient morbidity in oral mucosal wounds—a randomized study in humans. J Clin Periodontol. 2012;39:157–165. doi: 10.1111/j.1600-051X.2011.01823.x. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The authors confirm that the required data for the support of the study are available in the article. Additional data can be availed from corresponding author upon reasonable request.