Abstract
Background
Peri-implant soft tissue plays a vital role in both the aesthetic appearance and long-term health of implants. Free gingival grafts (FGGs) with epithelium remain the gold-standard surgical approach for obtaining keratinized tissue width. However, FGG harvest from the palatal donor site typically results in extensive wound dimensions, significantly contributing to postoperative discomfort in patients. This study aimed to investigate the efficacy of α-cyanoacrylate tissue adhesive (CTA) application in wound closure for improving soft tissue healing at donor sites.
Methods
Sixty subjects who underwent FGG procedures were recruited and randomly allocated into 3 groups. Group A (n=20) sites were treated with sutures and a gelatin sponge. Group B (n=20) sites were treated with sutures combined with a gelatin sponge and CTA. Group C (n=20) sites were treated with CTA alone. The perception of pain (assessed by the visual analog scale (VAS) at standardized intervals: 1, 2, 3, 5, 7, and 14 days), consumption of analgesic drugs (monitored over 14 days), wound closure time (measured intraoperatively), early-wound healing index (EHI, evaluated on days 5 and 14), incidence rates of complications (monitored up to day 14), and willingness to undergo reoperation (assessed on day 14) were recorded.
Results
VAS scores indicated lower pain levels in Group C than in Group A on postoperative days 5 and 7 (P<0.05). Healing assessments indicated better EHI scores for Group C than for Group A (P<0.05). Furthermore, the analysis revealed that patients in Group C experienced a significantly shorter wound closure time than did those in Group A and Group B (P<0.001). The consumption of analgesic drugs, willingness to undergo reoperation, and incidence rates of complications remained statistically comparable among the groups (P>0.05).
Conclusion
These preliminary findings suggest that the application of CTA serves as a viable alternative for palatal donor site closure, offering the distinct practical advantage of significantly shortening wound closure time and improving specific early wound healing parameters, with comparable overall complication rates and patient receptiveness.
Keywords: Cyanoacrylate tissue adhesive, Free gingival grafting, Healing of the donor site, Peri-implant soft tissue
Introduction
Mucogingival surgical approaches for managing keratinized tissue deficits have evolved significantly [1]. While recently utilized to augment keratinized tissue width surrounding dental implants [2], free gingival grafts (FGGs) remain the established benchmark for enhancing keratinized tissue width, augmenting tissue volume, and maintaining long-term dimensional stability for both natural teeth and implants [1–3].
Nevertheless, FGG procedures necessitate harvesting tissue from a donor site, typically the palate. This creates a secondary surgical wound that considerably elevates procedural complexity and patient morbidity [4]. Consequently, clinical outcomes related to palatal donor sites—particularly postoperative wound healing, complications [5], and pain management [6]—constitute a significant knowledge gap.
Specifically, it remains unclear which wound closure technique most effectively minimizes donor-site morbidity without compromising early healing. These challenges have stimulated research into adjunctive therapies to improve wound healing and patient-reported outcomes (e.g., postoperative pain, analgesic consumption, and willingness to undergo reoperation), including the use of cyanoacrylate tissue adhesives (CTA) [7], enamel matrix derivatives [8], absorbable sponges [9], and platelet-rich fibrin [10].
Supported by systematic reviews, CTA is frequently employed as a viable suture alternative due to its combined bacteriostatic and hemostatic properties, demonstrating clinical efficacy in surgical site management and hemorrhage control [11, 12]. CTA application has proven beneficial in treating extraction sockets, fixing mandibular fractures, promoting intraoral wound healing, and facilitating periodontal flap repair [13]. However, its dental applications remain limited to superficial use. Limited evidence has evaluated wound healing and patient-centered outcomes in the palatal donor area when comparing different closure techniques. Furthermore, it is unclear whether CTA applied alone can perform as effectively as or better than traditional sutures combined with hemostatic sponges. Therefore, to address this specific gap, this randomized controlled clinical trial aimed to investigate the efficacy of CTA application—either alone or combined with a gelatin sponge—compared to standard suturing for donor-site wound closure. The primary outcome was the evaluation of postoperative pain via the visual analog scale, while secondary outcomes included wound closure time, early wound healing, and complication rates among the three groups.
Materials and methods
Participants and study design
This study received approval from the Ethics Committee of The Third Hospital of Changsha (KY-EC−2022−004) and was conducted from January 1 to December 31, 2023. All procedures adhered to the principles outlined in the Declaration of Helsinki. All participants provided written informed consent before participating in the study. The demographic characteristics of the study participants are shown in Table 1.
Table 1.
General demographic and clinical baseline characteristics of patients in the three groups
| Characteristics | Group A (n = 20) | Group B (n = 20) | Group C (n = 20) | Statistic | P Value |
|---|---|---|---|---|---|
| Sex, n (%) | χ² = 0.938 | 0.626 | |||
| Male | 9 (45%) | 11 (55%) | 12 (60%) | ||
| Female | 11 (55%) | 9 (45%) | 8 (40%) | ||
| Age (years) | 51.45 ± 15.04 | 49.55 ± 15.42 | 53.70 ± 14.97 | F = 0.376 | 0.688 |
| Graft dimensions (mm) | |||||
| Length | 19.00 ± 7.46 | 16.85 ± 7.03 | 18.60 ± 6.09 | F = 0.552 | 0.579 |
| Width | 4.43 ± 0.88 | 5.03 ± 1.04 | 5.45 ± 1.96 | F = 2.790 | 0.070 |
| Thickness | 4.21 ± 0.80 | 4.18 ± 0.78 | 4.12 ± 0.77 | F = 0.070 | 0.930 |
Data are presented as the mean ± standard deviation (SD) for continuous variables, and as the number (n) and percentage (%) for categorical variables. Differences among the three groups were evaluated using one-way ANOVA (F value) for continuous variables and Pearson’s chi-square test (χ² value) for categorical variables.
A P value < 0.05 indicates statistical significance
The sample size was determined a priori based on the primary outcome (postoperative VAS pain score). Using G*Power software, to detect a clinically significant difference of 1.5 units in VAS scores among the groups with an estimated standard deviation of 1.5, based on data from previous comparable studies [14], a significance level (alpha) of 0.05, and a statistical power of 80%, a minimum of 17 patients per group was required. To accommodate a potential dropout rate of approximately 15%, the enrollment target was set to 20 participants per group. A total of 60 participants who underwent free gingival graft (FGG) surgery were randomly allocated to three groups on the basis of different wound closure techniques at the donor site. The randomization sequence was created using computer-generated random numbers with a 1:1:1 allocation ratio. To ensure strict allocation concealment, sequentially numbered, opaque, sealed envelopes (SNOSE) were utilized and opened by an independent dental assistant only immediately before the donor site wound closure procedure. Furthermore, this study has been retrospectively registered as a clinical trial The Group A (n = 20) sites were treated with sutures and a gelatin sponge.
The Group B (n = 20) sites were treated with sutures combined with a gelatin sponge and CTA. The sites in Group C (n = 20) were treated with CTA alone.
Inclusion criteria
(1) Age over 18 years; (2) stable periodontal condition with a full mouth plaque and a bleeding index of less than 20%; and (3) the need for FGG surgery.
Exclusion criteria
(1) Pregnant or breastfeeding patients; (2) patients with severe periodontal disease with gingival recession and attachment loss; (3) patients with systemic diseases contraindicated for periodontal surgery, such as an HbA1c greater than 6.5; (4) patients on long-term anticoagulant medication; and (5) patients who smoke more than 10 cigarettes per day (Fig. 1).
Fig. 1.
Inclusion and exclusion flowchart
Surgical procedure
All operations were conducted by a single experienced clinician to standardize surgical technique. The graft recipient site was anatomically distinct from the palatal donor area. Local anesthesia was achieved using 2% mepivacaine with 1:100,000 epinephrine. Palatal soft tissue thickness was quantified at mesial, central, and distal aspects of the predetermined harvest zone prior to graft procurement.
Free gingival grafts (FGGs) were harvested following Zucchelli et al.‘s protocol [15]. Key steps included: Defining graft dimensions using a foil template corresponding to the recipient bed to ensure that the graft size and thickness were clinically standardized according to the specific anatomical requirements of each recipient site; Executing a coronal horizontal incision with a 15 C blade apical to adjacent teeth’s gingival margins; Creating two vertical incisions orthogonal to the initial horizontal incision; Orienting the blade perpendicularly to palatal bone to achieve target soft tissue thickness; Repositioning the blade parallel to the epithelial surface;
Advancing the blade apically before completing the dissection with a final horizontal incision perpendicular to vertical incisions, releasing the graft.
A periodontal probe was utilized to measure the length, width, and thickness of all harvested grafts and to debride adipose tissue. For palatal wound closure, Group A received an absorbable gelatin sponge (Jinling Pharmaceutical Co., Ltd., Nanjing, China) secured with 5–0 nonabsorbable sling crossed sutures (Yangzhou Yuankang Medical Devices Co., Ltd., Jiangsu, China) anchored to apical soft tissues. Group B underwent identical sponge placement and suturing as Group A, with additional application of α-cyanoacrylate tissue adhesive (Beijing Fuaile Technology Development Co., Ltd., Beijing, China) along wound borders and across the entire sponge surface to create a uniform sealant layer. In contrast, Group C wounds were entirely sealed with CTA without supplementary materials. In edentulous areas for patients in Groups A and B, simple interrupted sutures secured the gelatin sponge, whereas Group C wounds remained exclusively sealed with CTA without any sutures or sponges, regardless of the dentition status.
Postsurgical instructions
Patients were instructed to use chlorhexidine mouth rinses twice daily until suture removal. Ibuprofen (400 mg) was not routinely prescribed postoperatively and was administered only when strictly indicated for unbearable pain. Patients were instructed to take one 400 mg tablet orally every 6 to 8 h as needed, strictly not exceeding a maximum daily intake of 1200 mg (three tablets). Participants received specific guidance to exclusively report palatal pain during visual analog scale (VAS) recordings and to document analgesic consumption along with their willingness to undergo repeat surgical procedures.
Outcome measures
1) Primary outcome measure (Postoperative pain assessment): We evaluated the patients’ subjective pain levels in the three groups on postoperative days 1, 2, 3, 5, 7, and 14 via the visual analog scale (VAS) as an assessment tool. Scores range from 0 to 10, with 0 indicating no pain and 10 indicating the most severe pain; higher scores reflect greater pain intensity. Moreover, the participants recorded their analgesic consumption.
2) Secondary outcome measures:
Evaluation of patients' willingness to undergo reoperation if needed was conducted at the end of the follow-up period on postoperative day 14.
The early wound healing index (EHI) was recorded on the basis of the clinical presentation and the presence of fibrin and necrosis, following the validated methodology originally described by Wachtel et al. [16] (Fig. 2). To minimize detection bias, all clinical outcome assessments, including VAS recording guidance, EHI scoring, and complication assessment, were performed by an independent, trained investigator who was strictly blinded to the patients' group allocation. Level 1: Complete flap closure - no fibrous exudate; Level 2: Complete flap closure - linear fibrous exudate; Level 3: Complete flap closure - mass fibrous exudate; Level 4: Incomplete flap closure - partial tissue necrosis; Level 5: Incomplete flap closure - complete tissue necrosis.
Fig. 2.
Clinical images of groups A, B, C showing the healing results of palatal donor sites: (a) during surgery, (b) 5 days after surgery, and (c) 14 days after surgery
-
(3)
Closure time: Donor site closure duration was measured from the time of treatment of the wound until closure was completed.
-
(4)
Postoperative complications such as severe bleeding for more than 20 min, infection, tearing, and delayed healing were recorded for 14 days postoperatively.
Statistical analysis
All the statistical analyses were performed with SPSS 26.0 (IBM SPSS, Chicago, IL) at a significance level of 0.05 by an independent biostatistician who was blinded to the treatment groups (the data were coded as groups 1, 2, and 3 without revealing the actual interventions). Patient demographics and clinical characteristics at baseline were summarized with descriptive statistics such as the mean, standard deviation (SD), and frequency. To ensure baseline comparability, differences in continuous baseline variables, specifically including graft length, width, and thickness, were statistically evaluated among the three groups. Differences in the VAS score, surgical time, and early healing index among the groups were checked via one-way ANOVA or the Kruskal‒Wallis test for continuous variables on the basis of the normality of the distribution of the variables. For significant overall ANOVA results, Tukey’s HSD (Honestly Significant Difference) post hoc test was strictly applied for subsequent pairwise comparisons. VAS scores and early healing indices are summarized as medians and ranges, whereas surgical times are summarized as the means and standard deviations (SDs). The normality of continuous data was strictly evaluated using the Shapiro-Wilk test. Because the VAS scores were non-normally distributed, they were analyzed using the Kruskal-Wallis test (H value). For significant overall findings, pairwise comparisons among the three groups were subsequently conducted using Dunn’s post hoc test with a Bonferroni correction to adjust the P values and control for the Type I error rate associated with multiple comparisons. Differences in analgesic consumption, willingness to undergo reoperation, and incidence of complications were checked via chi-square tests for categorical variables. However, when the expected cell frequencies were less than 5, Fisher’s exact test was appropriately employed to prevent the violation of chi-square assumptions.
Results
Baseline data analysis
All three treatment groups comprised 20 participants who completed the study without attrition, yielding 100% retention among the 60 enrolled patients. No statistically significant intergroup differences were detected in age, sex distribution, or graft dimensions (length, width, and thickness) at baseline (all P > 0.05). Comprehensive demographic and clinical baseline characteristics are presented in Table 1.
Postoperative pain assessment
Comparative analysis of VAS scores revealed no significant overall differences among groups A, B, and C at postoperative days 1, 2, 3, and 14 (all P > 0.05). However, significant differences were detected on days 5 and 7. Subsequent post hoc pairwise comparisons utilizing Dunn’s test with a Bonferroni correction revealed that patients in group C experienced significantly lower pain levels compared to those in group A on days 5 and 7 (P < 0.05; Table 2). Analgesic consumption patterns, detailed in Table 3, showed no significant variations among the groups throughout the monitoring period (P = 0.882).
Table 2.
Comparison of the visual analog scale (VAS) scores among the three groups
| Group | Day 1 | Day 2 | Day 3 | Day 5 | Day 7 | Day 14 |
|---|---|---|---|---|---|---|
| Group A (n = 20) | 2 (1, 2.45) | 1 (0.625, 2.75) | 1 (0, 1.75) | 0.25 (0, 1.75) | 0 (0, 1) | 0 (0, 0) |
| Group B (n = 20) | 1 (1, 2) | 1 (1, 1.875) | 0.45 (0, 1) | 0 (0, 0.5) | 0 (0, 0) | 0 (0, 0) |
| Group C (n = 20) | 1 (1, 1.75) | 1 (0.625, 1) | 0.25 (0, 1) | 0 (0, 0) | 0 (0, 0) | 0 (0, 0) |
| H Value | 3.058 | 1.67 | 0.712 | 9.49 | 8.762 | 3.579 |
| P Value | 0.217 | 0.434 | 0.7 | 0.009 | 0.013 | 0.167 |
Data are presented as the median with the interquartile range (P25, P75). Differences among the three groups at each time point were evaluated using the Kruskal-Wallis test (H value). A P value < 0.05 indicates statistical significance. For significant overall results (Days 5 and 7), Dunn’s post hoc test with a Bonferroni correction was applied for pairwise comparisons, which confirmed significant differences specifically between Group A and Group C
Table 3.
Comparison of analgesic consumption among the three groups
| Group | Patients requiring analgesics, n (%) | Patients not requiring analgesics, n (%) | P Value |
|---|---|---|---|
| Group A (n = 20) | 3 (15%) | 17 (85%) | 0.882 |
| Group B (n = 20) | 3 (15%) | 17 (85%) | |
| Group C (n = 20) | 2 (10%) | 18 (90%) |
Data are presented as the number (n) and percentage (%) of patients in each group. Differences among the three groups were evaluated using Fisher’s exact test due to small expected cell counts (< 5)
A P value < 0.05 indicates statistical significance
Willingness to undergo reoperation
When assessing patient receptiveness to future palatal tissue harvest procedures, 16 participants (80%) in group A, 17 (85%) in group B, and 18 (90%) in group C indicated willingness for potential reoperation. There was no statistically significant difference among the three groups (P = 0.676; Table 4).
Table 4.
Comparison of the willingness to undergo reoperation among the three groups
| Group | Willing, n (%) | Not willing, n (%) | P Value |
|---|---|---|---|
| Group A (n = 20) | 16 (80%) | 4 (20%) | 0.676 |
| Group B (n = 20) | 17 (85%) | 3 (15%) | |
| Group C (n = 20) | 18 (90%) | 2 (10%) |
Data are presented as the number (n) and percentage (%) of patients. Because the expected cell counts for the “Not willing” category were less than 5, differences among the three groups were evaluated using Fisher’s exact test instead of the Pearson chi-square test
A P value < 0.05 indicates statistical significance
Early wound healing index
Photographic evaluations of the EHI were conducted on postoperative days 5 and 14 (Fig. 2). On postoperative day 5, initial healing progressed comparably across all groups, with no statistically significant intergroup differences observed (P = 0.382). However, a comparison of the definitive EHI among the three groups on postoperative day 14 revealed a statistically significant overall difference (P = 0.031). Subsequent post hoc pairwise comparisons utilizing Dunn’s test with a Bonferroni correction confirmed that there was a statistically significantly better wound healing condition in group C compared to group A on day 14 (P < 0.05). Group B did not significantly differ from groups A and C (P > 0.05; Table 5).
Table 5.
Comparison of the wound healing conditions among the three groups on postoperative days 5 and 14
| Postoperative Day / Group | EHI 1 | EHI 2 | EHI 3 | EHI 4 | EHI 5 | Median (P25, P75) | H Value | P Value |
|---|---|---|---|---|---|---|---|---|
| Day 5 | 1.924 | 0.382 | ||||||
| Group A (n = 20) | 0 | 2 | 10 | 6 | 2 | 3 (3, 4) | ||
| Group B (n = 20) | 0 | 3 | 11 | 5 | 1 | 3 (3, 4) | ||
| Group C (n = 20) | 0 | 5 | 10 | 5 | 0 | 3 (2.25, 3) | ||
| Day 14 | 6.945 | 0.031 | ||||||
| Group A (n = 20) | 5 | 3 | 8 | 4 | 0 | 3 (1.25, 3) | ||
| Group B (n = 20) | 8 | 7 | 5 | 0 | 0 | 2 (1, 2.75) | ||
| Group C (n = 20) | 9 | 7 | 4 | 0 | 0 | 2 (1, 2) |
Data for the specific EHI categories (1 to 5) are presented as the number of patients (n). The overall EHI score is expressed as the median with the interquartile range (P25, P75). Differences among the three groups were evaluated using the Kruskal-Wallis test (H value). For the significant overall result, Dunn’s post hoc test with a Bonferroni correction was strictly applied for pairwise comparisons, confirming a statistically significant difference specifically between Group A and Group C
A P value < 0.05 indicates statistical significance
Wound closure time
With respect to the time required for suturing and gelatin sponge placement or application of the CTA, group C had a significantly shorter wound closure time (21.05 ± 7.56 s) than did Group A (219.35 ± 63.59 s) and Group B (246.55 ± 74.44 s) (overall P < 0.001). Subsequent post hoc pairwise comparisons utilizing Tukey’s HSD test confirmed that there was no statistically significant difference between Groups A and B (P > 0.05; Table 6).
Table 6.
Comparison of the wound closure time among the three groups
| Group | Time (seconds) | F Value | P Value |
|---|---|---|---|
| Group A (n = 20) | 219.35 ± 63.59 | 94.282 | < 0.001 |
| Group B (n = 20) | 246.55 ± 74.44 | ||
| Group C (n = 20) | 21.05 ± 7.56 |
Data are presented as the mean ± standard deviation (SD). Differences among the three groups were evaluated using one-way ANOVA (F value). Because the overall P value was highly significant. Tukey’s HSD post hoc test was applied for pairwise comparisons, confirming a statistically significant difference between Group C and the other two groups, while Groups A and B did not differ significantly
A P value < 0.05 indicates statistical significance, and P < 0.001 is reported for highly significant results
Incidence rates of complications
Postoperative bleeding manifested in one patient each in groups A and B. Delayed healing occurred in one patient from groups A and B, and two patients from group C. Additionally, infection occurred in one patient in group A. Intergroup differences in the overall incidence rates of complications were not statistically significant (P = 0.851; Table 7).
Table 7.
Comparison of the incidence rates of complications among the three groups
| Group | Hemorrhage, n (%) | Infection, n (%) | Tearing, n (%) | Delayed Healing, n (%) | P Value |
|---|---|---|---|---|---|
| Group A (n = 20) | 1 (5%) | 1 (5%) | 0 (0%) | 1 (5%) | 0.851 |
| Group B (n = 20) | 1 (5%) | 0 (0%) | 0 (0%) | 1 (5%) | |
| Group C (n = 20) | 0 (0%) | 0 (0%) | 0 (0%) | 2 (10%) |
Data are presented as the number (n) and percentage (%) of patients. The P value represents the comparison of the overall complication incidence among the three groups. Because the expected cell counts for these rare complications were less than 5, differences were evaluated using Fisher’s exact test instead of the Pearson chi-square test
A P value < 0.05 indicates statistical significance
Discussion
This randomized clinical trial evaluated postoperative pain as the predefined primary outcome, alongside secondary clinical and patient-centered outcomes (early wound healing, closure time, and complications) following CTA application for donor site closure. Wound closure represents a critical determinant of postoperative tissue healing [17]. Absorbable hemostatic sponges constitute widely employed local hemostatic agents with well-documented efficacy [18], justifying the selection of the gelatin sponge as the experimental control. No significant intergroup differences existed regarding patient baseline characteristics or graft dimensions, indicating that these variables were unlikely to confound the observed outcomes.
Regarding the primary outcome, Group C demonstrated statistically significantly lower VAS scores than Group A on postoperative days 5 and 7. Consistent with Basma [19], palatal donor site protection positively influences postoperative pain and discomfort. Shanmugam et al. hypothesize this VAS reduction may be associated with the adhesive’s sealing effect on exposed nerve endings [20]. Aligning with Tavelli et al. [7, 14] and Kulkarni et al. [21], less palatal pain was reported when an adhesive was used for flap closure versus sutures. This difference may potentially stem from CTA’s sealing properties, whereas sutures might induce foreign body reactions.
Conversely, Margalida [22] found no statistically significant intergroup differences in pain or healing. Importantly, while the statistical differences in our study on days 5 and 7 were significant, the absolute median VAS scores were universally low across all groups. The minimal difference of 0.25 to 0.5 points falls below the widely accepted minimal clinically important difference (MCID) of 1.0 to 1.5 units for acute pain [14]. This lack of a clinically meaningful difference perfectly explains the lack of significant variations in analgesic consumption, which aligns with Oladega [23].
Furthermore, despite Basma noting differences in patients’ willingness to undergo repeat surgery [19], our universally low pain scores likely contributed to the similar patient receptiveness across all groups.
Furthermore, the wound closure time was significantly shorter in Group C compared to Groups A and B. Echoing Soni and Chrysi [24, 25], CTA’s primary benefit was time savings. However, it must be acknowledged that this significant reduction is methodologically inherent, as the complete absence of knot-tying and suturing in the CTA-only group naturally reduces the procedural duration. Therefore, rather than strictly demonstrating biological superiority, this highlights a substantial practical benefit. Time efficiency increased with incision length since application time remains minimally affected by size. Additionally, CTA exhibits favorable operational handling properties, including flowability and rapid setting [26].
In this study, the EHI was significantly better in Group C than in Group A, while Group B did not significantly differ from the others. This improved early healing could potentially stem from the elimination of suture thread knots, which might otherwise irritate peri-tissue, as well as the prevention of inflammatory agent infiltration via oral secretions and knot spaces inherent to interrupted sutures [27].
CTA appeared to aid early healing compared to standard sutures, which contrasts with some reports of similar healing between sutures and CTAs [24]. We hypothesize that tissue adhesive coverage may facilitate palatal wound healing and reduce patient morbidity.
Although intergroup differences in complication rates lacked statistical significance, no infections occurred in Groups B or C. This may relate to the physical sealing effect of CTA and gelatin sponges preventing oral fluid and bacterial ingress [27]. Kulkarni reported reduced clinical inflammation using CTA [21]. Previous reports suggested CTA exhibits antimicrobial properties against gram-positive organisms, potentially arising from its strong electronegative charge [28].
Postoperative bleeding occurred in one patient each from Groups A and B; both cases were associated with food consumption, aligning with Griffin’s finding that bleeding relates more to postoperative irritation or trauma rather than surgical technique [29].
Furthermore, while platelet-rich fibrin (PRF) has been effectively utilized as an autologous hemostatic biomaterial in oral soft tissues to promote healing [30], CTA provides a distinct operational advantage by offering reliable and immediate mechanical hemostasis without the necessity for venous blood collection and centrifugation [19, 31]. However, delayed healing occurred in two patients from Group C and one each from Groups A and B, which may relate to the early loss risk of CTA correlated with interfacial adhesion strength.
Several limitations of this study must be acknowledged. First, the small sample size of 20 participants per group, while adequately powered for the primary VAS outcome, limited the statistical power to detect significant differences in less frequent secondary outcomes such as complication rates, and restricts the generalizability of the findings. Second, regarding blinding limitations, surgeons and patients could not feasibly be blinded during wound closure interventions. This inherent lack of blinding introduces potential performance bias and detection bias (e.g., subjective patient perception of pain). However, a blinded end-point assessment design was strictly implemented for EHI scoring and statistical analysis to mitigate these limitations.
Furthermore, while the short-term safety of CTA is well established, our 14-day follow-up precludes the evaluation of long-term biocompatibility, which remains a limitation and warrants further longitudinal investigation.
In conclusion, these preliminary findings suggest that cyanoacrylate tissue adhesives have the potential to serve as a viable alternative to gelatin sponges and sutures for palatal donor site closure. While the overall complication rates and clinically meaningful pain levels did not differ significantly among the techniques, the application of CTA offers the distinct operational advantage of significantly shortening wound closure time and may facilitate better specific early wound healing parameters.
Acknowledgments
Clinical trial number
Not applicable.
Abbreviations
- FGG
Free gingival graft
- CTA
α-cyanoacrylate tissue adhesive
- VAS
Visual analog scale
- EHI
Early-wound healing index
Authors' contributions
Tingyan Zeng wrote the main manuscript text. Haiyan Yu prepared figures and tables. Hong Xu analyzed the results. All authors reviewed the manuscript.
Funding
The work was supported by Guidance science and technology project of Changsha Science and Technology Bureau (Grant: kzd21093 and Grant: kzd2501059).
Data availability
The experimental data used to support the findings of this study are available from the corresponding author upon request.
Declarations
Ethics approval and consent to participate
This study was approved by the Ethics Committee of The Third Hospital of Changsha. All methods were carried out in accordance with Declaration of Helsinki.
Consent for publication
All the authors confirming that WRITTEN INFORMED consent was obtained from all subjects and/or their legal guardian(s).
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The experimental data used to support the findings of this study are available from the corresponding author upon request.


