Abstract
Background
Botulinum toxin type A (BoNT-A) has been increasingly incorporated into multimodal scar management strategies as an adjunctive treatment. However, the additive benefits of BoNT-A when used in combination or sequential therapeutic approaches remain unclear due to limited and heterogeneous evidence.
Methods
A systematic review and meta-analysis of randomized controlled trials was conducted in accordance with the PRISMA guidelines. PubMed, Embase, and the Cochrane Library were searched to identify studies evaluating BoNT-A as an add-on intervention in combination or sequential scar management strategies. Eligible studies compared BoNT-A plus standard scar management with control interventions alone. Primary outcomes included validated scar assessment scores, namely the Vancouver Scar Scale (VSS) and the Stony Brook Scar Evaluation Scale (SBSES). Pooled analyses were performed using mean differences (MDs) with 95% confidence intervals (CIs).
Results
Six randomized controlled trials (RCTs) were included. The pooled analysis suggested that BoNT-A add-on therapy significantly improved scar appearance, with a Mean Difference (MD) of −1.80 for the VSS score and 1.46 for the SBSES score. However, this represents low-certainty evidence.
Conclusion
Current low-certainty evidence suggests that BoNT-A may provide a potential adjunctive benefit for improving scar appearance, particularly in mitigating local mechanical tension. However, because these pooled estimates reflect a composite of heterogeneous treatment paradigms, the findings are suggestive rather than confirmatory and strictly exploratory. Clinical application should remain cautious and individualized, pending further high-quality, standardized RCTs.
Systematic Review Registration
https://www.crd.york.ac.uk/PROSPERO/view/CRD420261354679, PROSPERO CRD420261354679.
Keywords: botulinum toxin type A, combination therapy, meta-analysis, scar management, sequential therapy
Introduction
Scarring is an inevitable consequence of wound healing and represents a common clinical challenge following surgery or trauma (1, 2). Although many scars remain asymptomatic, others may become hypertrophic, widened, or cosmetically unacceptable, leading to functional impairment and significant psychological distress (3–6). The prevention and management of undesirable scars therefore remain an important concern for both patients and clinicians (2, 7). A wide range of therapeutic approaches has been proposed, including silicone-based products, corticosteroid injections, laser therapy, pressure therapy, and surgical revision; however, the clinical outcomes of these interventions are often variable, and no single strategy has been universally accepted as optimal (2, 7–12). As a result, multimodal treatment strategies that combine different therapeutic approaches are increasingly adopted in clinical practice to optimize scar outcomes (2, 7, 10, 12).
Mechanical tension across healing wounds has been recognized as a key factor contributing to pathological scar formation (13–15). Excessive tension can stimulate fibroblast proliferation, promote collagen overproduction, and ultimately result in hypertrophic scarring or scar widening (13–18). Accordingly, therapeutic strategies aimed at reducing wound tension during the early phases of healing have attracted increasing attention (13, 14, 19). Botulinum toxin type A (BoNT-A), a neurotoxin that induces temporary muscle paralysis by inhibiting acetylcholine release at the neuromuscular junction, has emerged as a potential adjunctive treatment for scar management (20–22). Rather than being used as a stand-alone therapy, BoNT-A has most commonly been incorporated into existing scar management protocols, either in combination with standard treatments or as a sequential intervention administered during the perioperative or early postoperative period (20, 21, 23–25). By reducing local muscle activity, BoNT-A may decrease mechanical forces acting on wound edges and thereby facilitate more favorable scar maturation (13, 20, 21, 26).
In recent years, several randomized controlled trials have investigated the use of BoNT-A as an add-on therapy in combination or sequential strategies for scar management in various clinical settings, including postoperative linear scars and facial surgical scars (20, 21, 23–25, 27–31). These studies have suggested that BoNT-A may improve scar appearance, thickness, and pliability when assessed using validated scar evaluation scales. In addition to its mechanical effects, BoNT-A has been reported to exert biological influences on wound healing, such as modulating fibroblast activity and reducing profibrotic signaling pathways (32–34). Despite these promising findings, the available evidence remains fragmented. Most published trials have involved small sample sizes, heterogeneous combination or sequential treatment protocols, and variable follow-up durations, making it difficult to draw definitive conclusions regarding the true add-on benefit of BoNT-A (35, 36).
To date, no comprehensive meta-analysis has systematically synthesized the evidence regarding the add-on effects of BoNT-A when used in combination or sequential therapeutic strategies for scar management (24). As a result, the magnitude of its incremental clinical benefit and the consistency of outcomes across different scar types and anatomical locations remain unclear. A rigorous quantitative evaluation is therefore needed to clarify the role of BoNT-A within multimodal scar management paradigms (35–37).
The objective of the present study was to conduct a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy of BoNT-A as an adjunctive component of combination or sequential therapies for scar management. Specifically, we aimed to compare scar outcomes between BoNT-A–treated and control groups using validated assessment tools, including the Vancouver Scar Scale (VSS) and the Stony Brook Scar Evaluation Scale (SBSES) (38, 39). By synthesizing the available evidence, this study seeks to clarify the incremental benefits of adding BoNT-A to existing scar management strategies and to inform clinical decision-making and future research.
Methods
Meta-analysis was carried out in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)statement. And Our meta-analysis had been registered on the official PROSPERO website with the registration number CRD420261354679.
Protocol and reporting standards
This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study aimed to evaluate the add-on benefits of botulinum toxin type A (BoNT-A) when used in combination or sequential therapeutic strategies for scar management.
Literature search strategy
A comprehensive electronic literature search was performed in the following databases: PubMed, Embase, and the Cochrane Library. A total of 220 records were identified through database searching (PubMed=130, Embase=52, Cochrane=38), and 2 additional records were identified through other sources.
Duplicate records were removed prior to screening. Titles and abstracts were initially screened, followed by full-text review for eligibility. The detailed study selection process is shown in the PRISMA flow diagram (Figure 1). The search utilized Boolean operators and database-specific terms (e.g., MeSH). Full search strings are provided in Supplementary Material S1.
Figure 1.
PRISMA flowchart illustrating the study selection, screening, and inclusion process for the systematic review and meta-analysis.
Inclusion criteria
Eligibility criteria followed the PICOS framework: (P) patients with scars; (I) BoNT-A as an exclusive add-on therapy; (C) identical baseline treatments without BoNT-A; (O) VSS and SBSES scores; (S) pure RCTs. Crucially, “add-on therapy” was strictly defined as applying identical baseline therapies to both arms, isolating BoNT-A as the sole independent variable. Studies were included if they met the following criteria: (1) Study design: randomized controlled trials (RCTs), including parallel-group RCTs or split-scar/split-face randomized self-controlled trials. (2) Population: patients with surgical scars (e.g., post-thyroidectomy, post-sternotomy) or facial postoperative scars (e.g., post-epicanthoplasty medial canthal scars). (3) Intervention: BoNT-A injection used as an add-on treatment, either combined with other scar management approaches or administered in sequential post-treatment strategies (e.g., intraoperative/early postoperative injection). (4) Comparator: placebo or control intervention (e.g., saline injection). (5) Outcomes: studies reporting at least one scar evaluation outcome using validated assessment scales, including: Vancouver Scar Scale (VSS) and Stony Brook Scar Evaluation Scale (SBSES).
Exclusion criteria
Studies were excluded if: (1) Full texts did not provide usable quantitative data for meta-analysis. (2) The data were not generalizable for effect synthesis. (3) The study design was not randomized. According to the PRISMA flow diagram, full-text exclusions were primarily due to non-randomization, lack of usable numerical data, or non-generalizable outcomes.
Study selection
After removing duplicates, 173 records were screened by title and abstract. A total of 128 full-text articles were assessed for eligibility. Ultimately, 6 studies were eligible for quantitative meta-analysis (20, 21, 24, 28, 40, 41).
Data extraction
Data extraction was performed using a standardized data collection form to ensure consistency across included studies. For each eligible trial, we extracted key study characteristics including the first author and year of publication, study design, sample size, scar type, intervention details (including BoNT-A administration strategy and timing), comparator regimen, duration of follow-up, and reported outcome measures. When necessary, numerical outcome data required for meta-analysis were retrieved directly from the text, tables, or figures of the original articles, and all extracted information was cross-checked to minimize errors and ensure accuracy. The overall certainty of evidence for primary outcomes was evaluated using the GRADE framework.
Risk of bias assessment
The methodological quality of the included randomized controlled trials was assessed using the Cochrane Risk of Bias tool. Risk of bias was evaluated across the following domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, completeness of outcome data, selective reporting, and other potential sources of bias. Each domain was judged as having low risk of bias, high risk of bias, or unclear risk of bias according to the information provided in the included studies. A risk-of-bias summary graph was generated to present the overall methodological quality of the included evidence (Figure 2).
Figure 2.
Methodological quality and risk of bias summary graph across the seven bias domains for the six included randomized controlled trials.
Outcomes
The primary outcomes of interest in this meta-analysis were validated scar assessment scores, including the Vancouver Scar Scale (VSS) and the Stony Brook Scar Evaluation Scale (SBSES). These outcomes were selected because they are commonly used clinical instruments for evaluating scar severity, incorporating features such as pigmentation, vascularity, pliability, and scar height or appearance. When studies reported outcomes at multiple follow-up time points, the longest available follow-up was preferentially extracted for quantitative synthesis to reflect the sustained effect of add-on BoNT-A therapy.
Statistical analysis
All continuous outcomes used the same scales and were pooled using the Mean Difference (MD) with corresponding 95% confidence intervals (CIs). To prevent unit-of-analysis errors in split-body designs, the Generic Inverse Variance (GIV) method was applied. Statistical heterogeneity among studies was assessed using the I2 statistic, and heterogeneity was considered substantial when I2 values were high. A random-effects model was applied in the presence of substantial heterogeneity, whereas a fixed-effect model was considered when heterogeneity was low. Subgroup analyses were conducted to explore potential sources of heterogeneity based on different scar settings and treatment contexts, including postoperative linear scars, and established hypertrophic scars or keloids. The pooled effects were summarized using forest plots.
Results
Search results
Figure 1 illustrated the PRISMA flow chart of the study selection process. A total of 222 records were initially identified through database searching and other resources. After removing 49 duplicates, 173 records were screened by title and abstract, resulting in the exclusion of 47 records. Of the remaining 126 full-text articles assessed for eligibility, 120 were excluded (17 lacked usable numerical data, 10 involved non-generalizable data, and 93 were non-randomized designs). Ultimately, six pure RCTs were included. Baseline equivalence for each trial is detailed in Table 1, demonstrating symmetrical baseline therapies across experimental and control arms.
Table 1.
Baseline characteristics and clinical study parameters of the six included randomized controlled trials.
| Study | Year | Design | Scar type | Baseline treatment(control) | Intervention(add-on) | Control | Sample size | Follow-up | Outcomes |
|---|---|---|---|---|---|---|---|---|---|
| Kim sy | 2014 | Split-scar, double-blind rct | Post-thyroidectomy linear scar | Standard postoperative care (silicone gel)+saline injection | Standard postoperative care (silicone gel)+bont-a injection | Saline injection | 15 patients | Up to 6 months | Sbses |
| Bae ds | 2020 | Double-blind, parallel rct | Post-thyroidectomy scar | Conventional management (silicone gel/sheets)+saline injection | Conventional management (silicone gel/sheets)+bont-a injection | Saline injection | 40 patients | Up to 24 weeks | Sbses |
| Huang RL | 2019 | Split-face, double-blind RCT | Post-epicanthoplasty medial canthal scar | Conventional surgical wound care (Control side) | Conventional wound care+BoNT-A injection (Experimental side) | Saline injection | 30 patients | Up to 6 months | VSS |
| Li YH | 2018 | Randomized, double-blind RCT | Post-sternotomy scar | Surgical closure alone (Standard suturing) | Surgical closure+BoNT-A injection | Saline injection | 17 patients | 6 months | VSS |
| Liu D | 2024 | Split-face, double-blind randomized self-controlled trial | Post-epicanthoplasty medial canthal scar | Standard postoperative care (Silicone gel)+Saline injection | Standard postoperative care (Silicone gel)+BoNT-A injection | Saline injection | 20 patients | Up to 6 months | SBSES |
| Atefi N | 2025 | Three-arm, single-blind RCT | Hypertrophic scars and keloids | Standard therapeutic protocol (Specific baseline treatment) | Standard protocol+BoNT-A injection | PDL alone | 10 patients | 1 month after final session | VSS |
BoNT-A, botulinum toxin type A; GIV, generic inverse variance; PDL, pulsed dye laser; RCT, randomized controlled trial; SBSES, Stony Brook Scar Evaluation Scale; SSA, scar scale assessment; VSS, Vancouver Scar Scale.
Risk-of-bias assessment
Figure 2 illustrated the risk-of-bias assessment of the included studies. Among the included randomized controlled trials, the majority adequately described random sequence generation, while one study did not clearly report the method used for randomization. Allocation concealment was insufficiently described in several trials, with only a minority of studies providing explicit information regarding concealment procedures.
Blinding of participants and personnel was judged to be at high risk of bias in most studies, largely due to the difficulty of blinding injection-based interventions. In contrast, blinding of outcome assessment was adequately addressed in all included trials, with outcome evaluators reported to be unaware of treatment allocation. All studies provided complete outcome data, and none of the included trials showed evidence of selective outcome reporting. No other significant sources of bias were identified across the included studies.
Given the limited number of included randomized controlled trials, formal assessment of publication bias was not performed. Based on the GRADE framework, the overall evidence certainty was rated as low, primarily downgraded due to serious risk of bias (lack of blinding) and high inconsistency (substantial heterogeneity). (See Supplementary Material S2).
Results of the meta-analysis
Effect on Vancouver scar scale (VSS)
Three studies reported Vancouver Scar Scale (VSS) scores and were included in the meta-analysis, comprising a total of 114 patients, of whom 57 received add-on botulinum toxin type A (BoNT-A) therapy and 57 received control treatment. All included studies compared BoNT-A used in combination or sequential strategies with placebo or standard scar management alone.
Based on a random-effects model, pooled analysis suggested that add-on BoNT-A therapy was associated with a significant improvement in VSS scores compared with the control group [MD = −1.80, 95% CI (−3.54, −0.05), p = 0.04; Figure 3]. Overall, patients treated with BoNT-A showed scar improvements compared with those in the control group.
Figure 3.
Forest plot displaying the comparison of Vancouver Scar Scale (VSS) scores between the experimental (BoNT-A) and control groups.
Substantial heterogeneity was observed among the included studies (I2 = 90%). To explore potential sources of heterogeneity, subgroup analyses were performed according to scar type and treatment context. These subgroup analyses are exploratory and hypothesis-generating, suggesting a potential adjunctive role of BoNT-A across different clinical scenarios.
Effect on stony brook scar evaluation scale (SBSES)
Three studies reported outcomes assessed using the Stony Brook Scar Evaluation Scale (SBSES) and were included in the quantitative synthesis. To rigorously prevent unit-of-analysis errors from split-body designs, data were pooled using the Generic Inverse Variance (GIV) method.
Pooled analysis using a random-effects model showed that add-on BoNT-A therapy was associated with a significantly higher SBSES score compared with control treatment [MD = 1.46, 95% CI (0.55, 2.38), p = 0.002], indicating a robust visual enhancement in scar appearance for patients receiving BoNT-A.
Substantial heterogeneity was observed among the included studies (I2 = 85%). Despite the presence of heterogeneity, all included trials generally favored add-on BoNT-A therapy over control treatment in terms of SBSES improvement (Figure 4).
Figure 4.
Forest plot displaying the comparison of Stony Brook Scar Evaluation Scale (SBSES) scores between the experimental (BoNT-A) and control groups.
Subgroup analysis of VSS
Subgroup analyses were performed according to scar type, including postoperative linear scars and established hypertrophic scars or keloids.
In the subgroup of postoperative linear scars, two studies involving 94 patients were included. The pooled analysis showed that add-on BoNT-A therapy was not associated with a statistically significant improvement in VSS scores compared with the control group [MD = −1.54, 95% CI (−3.91, 0.84), p = 0.20]. Substantial heterogeneity was observed within this subgroup (I2 = 91%).
In the subgroup of established hypertrophic scars or keloids, one study comprising 20 patients was analyzed. The pooled results similarly suggested a statistically significant improvement in VSS scores with add-on BoNT-A therapy compared with control treatment [MD = −2.40, 95% CI (−3.59, −1.21), p < 0.0001]. Importantly, given the limited number of studies included in each comparison, all subgroup findings for both VSS and SBSES should be considered strictly exploratory and hypothesis-generating.
While these exploratory findings suggest a potential therapeutic benefit across different scar types, the limited number of studies per subgroup means these results should be interpreted as hypothesis-generating rather than confirmatory (Figure 5).
Figure 5.
Subgroup analysis of Vancouver Scar Scale (VSS) scores, stratified by scar type (postoperative linear scars vs. established hypertrophic scars/keloids).
Subgroup analysis of SBSES
Subgroup analyses for SBSES outcomes were conducted based on anatomical location, including neck/thyroidectomy scars and epicanthus scars.
For neck/thyroidectomy scars, two studies were pooled. The analysis suggested that add-on BoNT-A therapy resulted in a significantly higher SBSES score compared with control treatment [MD = 1.72, 95% CI (0.19, 3.25), p = 0.03]. Substantial heterogeneity was observed within this subgroup (I2 = 92%).
For epicanthus scars, one study was included. The results showed a significant improvement in SBSES scores favoring the BoNT-A group [MD = 0.98, 95% CI (0.33, 1.63), p = 0.003].
Differences in local mechanical tension between anatomical locations accounted for a substantial portion of the heterogeneity (test for subgroup differences: I2 = 51.3%), indicating that scar location inherently modulates the magnitude of BoNT-A’s efficacy (Figure 6).
Figure 6.
Subgroup analysis of Stony Brook Scar Evaluation Scale (SBSES) scores, stratified by anatomical location (neck/thyroidectomy scars vs. epicanthus scars).
Sensitivity analysis
Sensitivity analysis for the VSS outcome (Supplementary Figure S1) was performed by sequentially removing individual studies from the meta-analysis. The overall pooled effect estimates remained stable and statistically significant, suggesting that the statistical computation is not driven by any single trial.
Discussion
In this systematic review and meta-analysis, we comprehensively evaluated the add-on effects of botulinum toxin type A (BoNT-A) when used in combination or sequential strategies for scar management. The pooled results suggested that adjunctive BoNT-A therapy was associated with significantly improved scar outcomes compared with control treatments. Specifically, BoNT-A significantly reduced Vancouver Scar Scale (VSS) scores [MD = −1.80, 95% CI (−3.54, −0.05), p = 0.04] and significantly increased Stony Brook Scar Evaluation Scale (SBSES) scores [MD = 1.46, 95% CI (0.55, 2.38), p = 0.002].
It is critical to acknowledge that the pooled estimates in this meta-analysis reflect a composite of markedly heterogeneous treatment paradigms, rather than a uniform biological or clinical effect. Given the high statistical heterogeneity (I2 up to 90%), our findings cannot be considered robust across all settings. Consequently, the observed add-on effects of BoNT-A should be interpreted as highly context-dependent and exploratory, and generalizable clinical conclusions are not supported at this stage.
Several biological mechanisms may explain the beneficial effects of BoNT-A. Mechanical tension across healing wounds is a well-recognized contributor to hypertrophic scarring and scar widening. BoNT-A reduces muscle activity adjacent to wounds, thereby decreasing tension at the wound edges during the critical phases of healing. In addition, experimental studies have suggested that BoNT-A may inhibit fibroblast proliferation, suppress excessive collagen deposition, and modulate profibrotic signaling pathways.
Substantial heterogeneity stems from anatomical and scar-type variations. BoNT-A shows pronounced efficacy in high-tension areas (e.g., neck, SBSES MD = 1.72) by offloading mechanical stress (Figure 6). Biologically, early postoperative injection acts as a prophylactic mechanomodulator, whereas delayed injection for established scars primarily targets hyperactive fibroblasts.
When interpreting these results, absolute clinical relevance must be considered. An absolute SBSES improvement of 1.46 points (on a strict 5-point scale) represents robust visual enhancement. Conversely, a 1.80-point reduction in VSS (on a 13-point scale) indicates a more modest clinical benefit, highlighting the future need for Patient-Reported Outcome Measures (PROMs).
From a clinical perspective, incorporating BoNT-A into multimodal or sequential scar management strategies may help optimize cosmetic outcomes. However, given the heterogeneity in treatment protocols, clinical application should be individualized, considering scar characteristics, treatment timing, and patient preferences. Furthermore, a critical clinical limitation of our overall pooled analysis is the combination of two fundamentally distinct scenarios: the prevention of postoperative linear scars and the treatment of established hypertrophic scars and keloids. These scenarios represent completely different biological paradigms, with prophylactic mechanical offloading during early wound healing on one hand and therapeutic metabolic modulation of existing fibrotic tissue on the other. Pooling their estimates artificially merges distinct mechanisms. Consequently, the overall pooled effect must be interpreted with extreme caution. The true clinical value of our findings lies strictly within the exploratory subgroup analyses that separate these preventative and therapeutic applications. However, given the limited number of studies included in each comparison, these subgroup findings should be considered strictly exploratory and hypothesis-generating.
This study has critical limitations. Most notably, the lack of participant and assessor blinding in several trials introduces high performance and detection biases for subjective scales (VSS/SBSES). Evaluator expectancy bias may overestimate BoNT-A's true additive efficacy, justifying our “low” GRADE rating. Furthermore, limited RCT availability (n = 6) precluded subgrouping by specific dosing, timings, or distinct baseline therapies (e.g., lasers), which remain vital areas for future large-scale trials.
Future well-designed randomized controlled trials with larger sample sizes are warranted to further clarify the role of BoNT-A. In particular, strictly double-blinded studies should aim to determine the optimal timing, dosage, and injection techniques for BoNT-A, as well as to adopt standardized patient-reported outcome measures and longer follow-up periods. Such efforts would help strengthen the evidence base and refine clinical recommendations.
Conclusion
In conclusion, current low-certainty evidence suggests that BoNT-A may provide a potential adjunctive benefit for improving scar appearance, particularly by effectively acting as a mechanomodulator to offload stress in high-tension regions. However, it must be explicitly acknowledged that these pooled estimates reflect a composite of markedly heterogeneous treatment paradigms rather than a uniform clinical effect. Given the high statistical heterogeneity, these findings should be considered context-dependent, suggestive rather than confirmatory, and remain strictly exploratory at this stage. Consequently, clinical application should be highly cautious and individualized. Further high-quality, rigidly standardized RCTs are required before firm, generalizable clinical recommendations can be made.
Funding Statement
The author(s) declared that financial support was not received for this work and/or its publication.
Footnotes
Edited by: Ovunc Akdemir, Reconstructive and Aesthetic Surgery Istanbul Aydın University, Türkiye
Reviewed by: I-Chang Lai, China Medical University Hospital, Taiwan
Antony Barbosa, PUC MINAS, Brazil
Data availability statement
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.
Author contributions
YM: Conceptualization, Investigation, Writing – original draft, Writing – review & editing, Data curation, Formal analysis, Methodology, Project administration. WQ: Conceptualization, Investigation, Writing – original draft, Writing – review & editing, Software.
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declared that generative AI was not used in the creation of this manuscript.
Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpain.2026.1844493/full#supplementary-material
References
- 1.Mustoe TA, Cooter RD, Gold MH, Hobbs FD, Ramelet AA, Shakespeare PG, et al. International clinical recommendations on scar management. Plast Reconstr Surg. (2002) 110(2):560–71. 10.1097/00006534-200208000-00031 [DOI] [PubMed] [Google Scholar]
- 2.Gold MH, Berman B, Clementoni MT, Gauglitz GG, Nahai F, Murcia C. Updated international clinical recommendations on scar management: part 1–evaluating the evidence. Dermatol Surg. (2014) 40(8):817–24. 10.1111/dsu.0000000000000049 [DOI] [PubMed] [Google Scholar]
- 3.Wu J, Zou J, Yang Q, Wang H, Tian H, Chen L, et al. The effects of scar in psychological disorder: a bibliometric analysis from 2003 to 2022. Int Wound J. (2024) 21(1):e14373. 10.1111/iwj.14373 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Mathew M, DiBartolomeo G, Stone RC. Biopsychosocial impact of keloids on quality of life. JAAD Rev. (2024) 2:13–9. 10.1016/j.jdrv.2024.08.010 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Ariza A, Sanabria A. Impact of scar on quality of life in well-differentiated thyroid carcinoma: a systematic review. OTO Open. (2025) 9(3):e70155. 10.1002/oto2.70155 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Fang X, Wang Y, Chen H, Yan Z, Jin S, Wu Y, et al. Hypertrophic scarring and keloids: epidemiology, molecular pathogenesis, and therapeutic interventions. MedComm (2020). (2025) 6(10):e70381. 10.1002/mco2.70381 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Shin J, Kim Y, Kim H, Park J, Yi H. Postoperative scar management. KMJ. (2025) 40(2):96–105. 10.7180/kmj.25.107 [DOI] [Google Scholar]
- 8.O'Brien L, Jones DJ. Silicone gel sheeting for preventing and treating hypertrophic and keloid scars. Cochrane Database Syst Rev. (2013) 2013(9):Cd003826. 10.1002/14651858.CD003826.pub3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Tian F, Jiang Q, Chen J, Liu Z. Silicone gel sheeting for treating keloid scars. Cochrane Database Syst Rev. (2023) 1(1):Cd013878. 10.1002/14651858.CD013878.pub2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.De Decker I, Hoeksema H, Verbelen J, Vanlerberghe E, De Coninck P, Speeckaert MM, et al. The use of fluid silicone gels in the prevention and treatment of hypertrophic scars: a systematic review and meta-analysis. Burns. (2022) 48(3):491–509. 10.1016/j.burns.2022.03.004 [DOI] [PubMed] [Google Scholar]
- 11.De Decker I, Beeckman A, Hoeksema H, De Mey K, Verbelen J, De Coninck P, et al. Pressure therapy for scars: myth or reality? A systematic review. Burns. (2023) 49(4):741–56. 10.1016/j.burns.2023.03.007 [DOI] [PubMed] [Google Scholar]
- 12.Di Serio S, Congiu M, Minnucci S, Scalise V, Mourad F. Current physical therapy for skin scar management: a scoping review. J Clin Med. (2025) 14(17):5920. 10.3390/jcm14175920 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Yin J, Zhang S, Yang C, Wang Y, Shi B, Zheng Q, et al. Mechanotransduction in skin wound healing and scar formation: potential therapeutic targets for controlling hypertrophic scarring. Front Immunol. (2022) 13:1028410. 10.3389/fimmu.2022.1028410 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Cao X, Wu X, Zhang Y, Qian X, Sun W, Zhao Y. Emerging biomedical technologies for scarless wound healing. Bioact Mater. (2024) 42:449–77. 10.1016/j.bioactmat.2024.09.001 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Zhou CJ, Guo Y. Mini review on collagens in normal skin and pathological scars: current understanding and future perspective. Front Med (Lausanne). (2024) 11:1449597. 10.3389/fmed.2024.1449597 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Zhang X, Lan D, Ning S, Jia H, Yu S. Botulinum toxin type A prevents the phenotypic transformation of fibroblasts induced by TGF-β1 via the PTEN/PI3 K/akt signaling pathway. Int J Mol Med. (2019) 44(2):661–71. 10.3892/ijmm.2019.4226 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Zhang S, Li K, Yu Z, Chai J, Zhang Z, Zhang Y, et al. Dramatic effect of Botulinum toxin type A on hypertrophic scar: a promising therapeutic drug and its mechanism through the SP-NK1R pathway in cutaneous neurogenic inflammation. Front Med (Lausanne). (2022) 9:820817. 10.3389/fmed.2022.820817 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Thanasarnaksorn W, Pomsoong C, Kanjanasirirat P, Jearawuttanakul K, Borwornpinyo S, Hongeng S, et al. Investigating the impact of botulinum toxin type a on the migration of normal human dermal fibroblasts: an in vitro wound healing assay. J Cosmet Dermatol. (2024) 23(10):3189–94. 10.1111/jocd.16406 [DOI] [PubMed] [Google Scholar]
- 19.Chu H, Zhen M, Bie F, Xie J, Chen L, Wang P. Advances in hypertrophic scar animal model research: a multidimensional analysis from traditional models to emerging technologies. Regenesis Repair Rehabilitation. (2026) 2(1):1–13. 10.1016/j.rerere.2025.12.002 [DOI] [Google Scholar]
- 20.Kim YS, Lee HJ, Cho SH, Lee JD, Kim HS. Early postoperative treatment of thyroidectomy scars using botulinum toxin: a split-scar, double-blind randomized controlled trial. Wound Repair Regen. (2014) 22(5):605–12. 10.1111/wrr.12204 [DOI] [PubMed] [Google Scholar]
- 21.Bae DS, Koo DH, Kim JE, Cho JM, Park JO. Effect of Botulinum toxin A on scar healing after thyroidectomy: a prospective double-blind randomized controlled trial. J Clin Med. Mar. (2020) 9(3):868. 10.3390/jcm9030868 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Hu L, Zou Y, Chang S-J, Qiu Y, Chen H, Gang M, et al. Effects of Botulinum toxin on improving facial surgical scars: a prospective, split-scar, double-blind, randomized controlled trial. Plast Reconstr Surg. (2018) 141(3):646–50. 10.1097/prs.0000000000004110 [DOI] [PubMed] [Google Scholar]
- 23.Dadaci M, Yildirim MEC, İnce B. Effects of Botulinum toxin on improving facial surgical scars: a prospective, split-scar, double-blind, randomized controlled Trial. Plast Reconstr Surg. (2019) 143(1):237e–8e. 10.1097/prs.0000000000005136 [DOI] [PubMed] [Google Scholar]
- 24.Huang RL, Ho CK, Tremp M, Xie Y, Li Q, Zan T. Early postoperative application of Botulinum toxin type A prevents hypertrophic scarring after epicanthoplasty: a split-face, double-blind, randomized trial. Plast Reconstr Surg. (2019) 144(4):835–44. 10.1097/prs.0000000000006069 [DOI] [PubMed] [Google Scholar]
- 25.Chen Z, Chen Z, Pang R, Wei Z, Zhang H, Liu W, et al. The effect of botulinum toxin injection dose on the appearance of surgical scar. Sci Rep. (2021) 11(1):13670. 10.1038/s41598-021-93203-x [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Tollefson TT, Senders CM, Sykes JM, Byorth PJ. Botulinum toxin to improve results in cleft lip repair. Arch Facial Plast Surg. (2006) 8(3):221–2. 10.1001/archfaci.8.3.221 [DOI] [PubMed] [Google Scholar]
- 27.Sonane J, Sharma RK, John JR, Sharma R. Botulinum toxin for a better scar in cleft lip surgery: a prospective randomized control trial. J Craniofac Surg. (2022) 33(1):198–202. 10.1097/scs.0000000000007836 [DOI] [PubMed] [Google Scholar]
- 28.Li YH, Yang J, Liu JQ, Xie ST, Zhang YJ, Zhang W, et al. A randomized, placebo-controlled, double-blind, prospective clinical trial of Botulinum toxin type A in prevention of hypertrophic scar development in median sternotomy wound. Aesthetic Plast Surg. (2018) 42(5):1364–9. 10.1007/s00266-018-1187-x [DOI] [PubMed] [Google Scholar]
- 29.Elshahed AR, Elmanzalawy KS, Shehata H, ElSaie ML. Effect of botulinum toxin type A for treating hypertrophic scars: a split-scar, double-blind randomized controlled trial. J Cosmet Dermatol. (2020) 19(9):2252–8. 10.1111/jocd.13627 [DOI] [PubMed] [Google Scholar]
- 30.Tawfik AA, Ali RA. Evaluation of botulinum toxin type A for treating post burn hypertrophic scars and keloid in children: an intra-patient randomized controlled study. J Cosmet Dermatol. Apr. (2023) 22(4):1256–60. 10.1111/jocd.15634 [DOI] [PubMed] [Google Scholar]
- 31.Wang J, Huang L, Li J, Xu R, Guo T, Huang T, et al. Efficacy and safety of sequential treatment with botulinum toxin type A, fractional CO2 laser, and topical growth factor for hypertrophic scar management: a retrospective analysis. Sci Rep. (2024) 14(1):27233. 10.1038/s41598-024-78094-y [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Shi J, Zhang S, Zhang Z, Xu J, Chen Y, Sun S. Efficacy of triamcinolone acetonide combined with botulinum toxin A in the treatment of hypertrophic scars and keloids: a meta-analysis. Burns. (2024) 50(9):107250. 10.1016/j.burns.2024.08.016 [DOI] [PubMed] [Google Scholar]
- 33.Huang SH, Wang WC, Chuang HY, Yang SM, Yang SY, Wu SH. Enhanced scar reduction with triamcinolone acetonide and Botulinum toxin A combination therapy compared to Botulinum toxin A monotherapy: a translational pilot study. Aesthet Surg J. (2025) 45(10):1073–85. 10.1093/asj/sjaf094 [DOI] [PubMed] [Google Scholar]
- 34.Won P, Cooper M, Gillenwater TJ, Yenikomshian HA. Treatment of hypertrophic burn scars with Laser therapy: a review of adverse events. Ann Plast Surg. (2023) 91(6):715–9. 10.1097/sap.0000000000003712 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Oosterhoff TCH, Beekman VK, van der List JP, Niessen FB. Laser treatment of specific scar characteristics in hypertrophic scars and keloid: a systematic review. J Plast Reconstr Aesthet Surg. (2021) 74(1):48–64. 10.1016/j.bjps.2020.08.108 [DOI] [PubMed] [Google Scholar]
- 36.Haji Mohammadi A Seirafianpour F Khosravi M Jafarzadeh ANeshastesaz Kashi H Baradaran H et al. A systematic review of comparative clinical trials on the efficacy, safety, and patient satisfaction of ablative and non-ablative laser therapies for atrophic, hypertrophic, and keloid scars. Lasers Med Sci. (2025) 40(1):280. 10.1007/s10103-025-04519-3 [DOI] [PubMed] [Google Scholar]
- 37.Szlachcikowska D, Mazurek K, Magiera M, Jama G, Tabęcka-Łonczyńska A. Current insights and future directions in scar management and skin regeneration. Int J Mol Sci. (2025) 26(21):10636. 10.3390/ijms262110636 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Sullivan T, Smith J, Kermode J, McIver E, Courtemanche DJ. Rating the burn scar. J Burn Care Rehabil. (1990) 11(3):256–60. 10.1097/00004630-199005000-00014 [DOI] [PubMed] [Google Scholar]
- 39.Singer AJ, Arora B, Dagum A, Valentine S, Hollander JE. Development and validation of a novel scar evaluation scale. Plast Reconstr Surg. (2007) 120(7):1892–7. 10.1097/01.prs.0000287275.15511.10 [DOI] [PubMed] [Google Scholar]
- 40.Liu D, Ou Y, Luo L, Wu M, Zhang Y, Chen L, et al. The efficacy and safety of Botulinum toxin type A in prevention of hypertrophic scars after epicanthoplasty: a split-face double-blinded randomized controlled trial. Aesthetic Plast Surg. (2025) 49(5):1227–38. 10.1007/s00266-024-04498-w [DOI] [PubMed] [Google Scholar]
- 41.Atefi N, Jafari MA, Roohaninasab M, Dehghani A, Jafarzadeh A, Peighambari SB, et al. Evaluating the effectiveness and safety of pulsed dye laser alone, the combination of pulsed dye laser and botulinum toxin type A, and the combination of pulsed dye laser and triamcinolone injection in the treatment of hypertrophic and keloid scars: a three-arm randomized controlled clinical trial. Lasers Med Sci. (2025) 40(1):92. 10.1007/s10103-025-04338-6 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.