Factors Influencing Reduced Scar Tissue Formation Following Unilateral Cleft Lip Plastic Surgeries: a Systematic Literature Review

Objectives: Reduction of postoperative scarring after unilateral cleft lip cheiloplasty is a pertinent topic. Smaller scar formation results not only in a better lip function, but also - aesthetics. This systematic review aims to identify various supplementary treatment options which influence favourable scarring outcome after cheiloplasty.

Material and Methods: The systematic review was conducted following PRISMA guidelines and Cochrane methodologies, using databases including PubMed, ScienceDirect, The Cochrane Library, and Google Scholar. Articles published between 2012 and 2024 evaluating supplementary measures for reducing scar tissue post-unilateral cleft lip cheiloplasty were included. Studies were assessed for bias using the Joanna Briggs Institute Critical Appraisal Checklist, and outcomes were measured using Vancouver Scar Scale, Visual Analog Scale, Hollander Wound Evaluation Score, and scar width metrics.

Results: Nine studies were analysed, highlighting platelet-rich plasma and botulinum toxin A as effective in reducing scar width and improving aesthetics. Silicone-based products enhanced wound healing, while non-absorbable sutures and tissue adhesives showed superior outcomes compared to absorbable sutures. Overall, supplementary measures significantly improved postoperative scar appearance.

Conclusions: The use of platelet-rich plasma or botulinum toxin injections in musculus oribucalaris oris during the cheiloplasty significantly improves postoperative scar formation outcome. Wound edges approximation by non-absorbable sutures or tissue glue equally results in smaller scar formation and better aesthetic outcome. Suturing with absorbable sutures increases the incidence of complications and results in poor aesthetics. Postoperative wound care with products containing silicone significantly reduces scarring and aids in aesthetics.

J Oral Maxillofac Res 2025;16(2):e2

doi: 10.5037/jomr.2025.16202

Accepted for publication: 29 June 2025

Keywords: cleft lip; lip plastic; scarring.

INTRODUCTION

A cleft lip is one of the most common congenital craniofacial developmental anomalies, occurring on average in 1 out of 700 newborns [1]. Most cases of this condition are isolated and nonsyndromic, meaning they are not associated with other pathologies. Another portion of cases are related to heredity and syndromes. Thus, it is believed that the aetiology of clefts is multifactorial, potentially influenced by chemical teratogenic substances, ionizing radiation, poor maternal nutrition, harmful parental habits, obesity, hyperthermia, genetic factors, and others [2]. Cleft anomalies develop during critical periods of fetal formation when the embryonic facial processes must merge [3]. Around the sixth week of fetal development, the fusion of the medial and lateral nasal processes and the maxillary processes occur, forming a continuous upper lip, nose, and palate. Failure in the fusion of these processes leads to clefts in the corresponding areas [3].

In each case, the size of the defect and the affected structures vary, but clefts are generally classified as unilateral or bilateral [4]. Based on the degree of severity, clefts can be categorized as hidden, partial, or complete. Since these anomalies are treated solely through surgery, and tissue integrity disruptions are diverse, the choice of specific surgical technique is subjective [5]. In all cases, the goal of surgery is to ensure the integrity of all three layers of the lip (skin, muscle, and mucosa) by removing hypoplastic tissue, approximating wound edges, and restoring function. Proper reconstruction of the continuity of the orbicularis oris muscle is essential during the operation [6]. The recommended timing for cheiloplasty varies between 2 and 12 months of the child’s life [7-9]. Earlier surgery promotes better nasal symmetry and restores feeding function sooner [9]. However, some patients with clefts also have comorbid conditions, which can affect the timing of surgery. Delaying the operation after birth allows for a comprehensive examination of the child’s health and an assessment of other potential congenital anomalies (such as those affecting the heart or kidneys). Additionally, surgery is easier on older patients due to the greater volume of tissue and more pronounced anatomical structures [7]. This supports successful restoration of lip function, but an undesirable complication-hypertrophic scarring-may appear at 3 to 6 months after the intervention [10]. This irregular scar tissue formation, rich in collagen and extracellular matrix proteins, causes various challenges for the patient, their family, and healthcare professionals [10]. Scars interfere with the normal development of surrounding soft tissues, potentially causing deformation of the philtrum, increased asymmetry of the Cupid’s bow, and thinning of the upper lip as the child grows [11]. Bony structures are also affected, with inhibited maxillary development leading to the emergence of a skeletal angle class III malocclusion. Dissatisfaction with facial aesthetics affects both patients and their parents, and healthcare professionals must devote additional time to repeating lip surgeries. This highlights the need for effective strategies to minimize postoperative scar tissue formation during or immediately after primary cheiloplasty.

This systematic review aims to identify the range and determine the impact of supplementary measures that can reduce scar tissue formation following unilateral cleft lip reconstructive surgeries.

MATERIAL AND METHODS

Protocol and registration

The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO). Prospero registration number: CRD42024615327.

The protocol can be accessed at: www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024615327

Focus question

A research question was formulated using the Population, Intervention, Comparison and Outcome (PICO) framework: “Do supplementary measures influence the reduction of scar tissue formation after primary unilateral cheiloplasty?” (Table 1).

Information sources

The search for scientific articles was conducted from October 15, 2022, to October 15, 2024, in databases: PubMed (MEDLINE), the Cochrane Library, and ScienceDirect. Additionally, a literature search was performed in the publicly accessible database “Google Scholar.”

The search focused on articles discussing the effectiveness of supplementary measures in reducing scar tissue formation following unilateral cleft lip plastic surgeries.

Search

The protocol for the systematic review was prepared in advance, following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines [12] and the Cochrane methodological recommendations for systematic reviews [13]. The main search terms utilized included: “(cleft lip) AND (unilateral) AND (scar)”. During the search, relevant articles were also identified from the references in selected publications. The keyword formulations, selection filters applied, and the number of articles found in the databases are provided.

Selection of studies

The search for scientific literature and article selection was conducted by two researchers (D.L. and B.S), in collaboration with two supervisors (J.S.M. and M.L.). Article selection was done in two stages. In the first stage, titles and abstracts of publications were reviewed, selecting those that potentially met the set criteria. Duplicates and publications that did not meet the selection criteria were excluded. In the second stage, full-text articles were analysed, and only those studies meeting the selection criteria were included in the systematic review.

Types of publications

The review focused exclusively on human studies published in English, excluding letters, editorials, PhD dissertations, and abstracts.

Types of studies

The review included clinical trials, controlled clinical trials, randomized clinical trials, and studies not older than 12 years which focused on cleft lip surgeries and the factors influencing reduced scar tissue formation.

Type of population

Patients with congenital unilateral clefts undergoing additional scar-reducing measures.

Inclusion criteria

• Articles examining the effectiveness of additional measures in reducing scar tissue formation after primary unilateral cleft lip surgeries.

• Articles published between 2012 and 2024.

• Articles published in English.

• Clinical studies conducted on humans.

• Clinical, retrospective, and prospective studies.

• Studies with a sample size of 10 or more participants.

Exclusion criteria

• Meta-analyses, systematic reviews, individual case reports, and theses.

• Studies conducted on animals.

• In vitro studies.

• Studies with a sample size smaller than 10.

• Articles not published in English.

• Articles published before 2012.

• Articles that compare only surgical technique methodologies.

• Studies not involving primary cheiloplasty surgeries.

• Studies analysing outcomes of bilateral cleft lip cheiloplasty surgeries.

Sequential search strategy

After the initial literature search, all article titles were filtered to remove publications that weren’t relevant. Following that, studies were disqualified based on information derived from the abstracts. To determine an article’s eligibility, the last step of screening involved reviewing the complete content of the articles.

Data extraction

Data from the articles were selected and collected by filling out tables according to Cochrane recommendations for systematic reviews. The data were organized as follows:

• Primary author;

• Year of publication;

• Type of study;

• Sample size;

• Intervention applied to the experimental group;

• Intervention applied to the control group;

• Outcome assessment criteria;

• Follow-up period.

Data items

Vancouver Scar Scale

This is a tool frequently used in clinical practice and research for evaluating scar appearance. The scale assesses four aspects: pigmentation, vascularity, pliability, and height. Pigmentation is rated from 0 to 2 (0 = normal, 1 = hypopigmentation, 2 =hyperpigmentation). Vascularity is rated from 0 to 3 based on colour (0 = normal, 1 = pink, 2 = red, 3 = purple). Pliability is rated from 0 to 5 (0 = normal, 1 = very soft, 2 = soft, 3 = firm, 4 = very firm, 5 = contracture). Height is rated from 0 to 3 (0 = normal/flat, 1 = 0 to 2 mm, 2 = 2 to 5 mm). Vancouver Scar Scale (VSS) is considered an objective tool for evaluating scar tissue formation and is typically used by qualified evaluators, such as specialists [14].

Visual Analog Scale

For scar appearance evaluation, the Visual Analog Scale (VAS) is represented as a line with “worst imaginable scar appearance” at one end and “best imaginable scar appearance” at the other. The line is divided into a numerical scale, chosen by the author. Evaluators, based on personal judgment, select a point on the line that reflects their assessment. This point has a numerical value that can be assigned to each evaluator’s response. VAS is a recognized evaluation scale used in burn centres, plastic surgery, and dermatology clinics [15]. Its simplicity makes it suitable for assessment by not only specialists but also patients and non-medical evaluators.

Hollander Wound Evaluation Score

This tool evaluates scars based on six criteria: contraction, vascularity, pigmentation, scar thickness, surface smoothness, and pliability. Each criterion is scored from 0 to 1, with higher scores indicating a more pronounced feature.

The Hollander Wound Evaluation Score (HWES) is considered a valuable tool for assessing scar properties during its formation and tracking scar changes after treatment. This tool is used exclusively by specialists, and the results are deemed sufficiently objective [16].

Scar width

Photography

To evaluate changes in scar width following cheiloplasty, scars were photographed at designated follow-up intervals after surgery. For objective data, standardized rulers were placed adjacent to the evaluated area, and the scar was photographed. Using graphics editor software Photoshop CS5 and CS6 (Adobe Systems Inc.; San Jose, USA), the scar width was measured at specific points using the visible standard ruler in the photograph. The results are recorded in centimetres or millimetres [17].

Ultrasound examination

The width of the scar tissue at selected points can also be measured using an ultrasound examination with a frequency of 7.5 to 9 MHz. During the procedure, a static image is captured, showing the connective tissue scar at the evaluation point. A standardized measurement system (integrated into the ultrasound device) is used to measure the width of the scar tissue, and the result is recorded in centimetres or millimetres [18].

The risk of bias assessment

Following the Joanna Briggs Institute (JBI) Critical Appraisal Checklist [19] for randomized controlled trials (Table 2), cohort studies (Table 3), as well as case control studies (Table 4), were used in the assessment of the risk of bias of the included studies under three different categories: high risk when positive answers were less than 49%, moderate risk when the positive answers resulted between 50% and 69%, and low risk when the positive answers were higher than 70%.

Statistical analysis

The level of agreement between the two raters in selecting abstracts and full-text studies was measured using Cohen’s kappa coefficient (κ), which assesses inter-rater reliability beyond chance agreement. A κ value closer to 1.0 indicates strong agreement, while values near 0 suggest minimal agreement. To ensure consistency, reviewers were calibrated by calculating κ values on a randomly selected 10% sample of publications. Any discrepancies in ratings were discussed and resolved through consensus before proceeding with the full review process.

For quantitative synthesis, a SPSS^® Statistics version 29.0 (IBM Corp.; Armonk, NY, USA) was used. A significance threshold of P < 0.05 was used for all statistical tests.

RESULTS

Study selection

Following PRISMA guidelines a total of 1,413 studies were initially identified through database searches, including 114 from PubMed, 854 from Google Scholar, 422 from ScienceDirect, and 23 from the Cochrane Library. After removing 67 duplicates, 1,346 studies remained for screening. During the screening process, 1,194 studies were excluded based on their titles, and 67 were excluded after reviewing their abstracts. This left 85 full-text articles to be assessed for eligibility. Ultimately, 9 studies met the inclusion criteria and were included in the systematic review (Figure 1). The level of agreement between 2 authors (D.L. and B.S.) in the selection of abstracts was measured at κ = 0.71.

Study exclusion

After full-text review, 76 were excluded for the following reasons: 9 were unavailable in full text or not published in English, 39 did not study unilateral cleft lip, 17 focused on secondary cheiloplasty, and 11 evaluated only different surgical intervention methods.

Study characteristics

The literature review includes nine scientific articles: seven randomized clinical trials (Refahee et al. [20], Sonane et al. [21], Chang et al. [22], Lu et al. [23], Luthra et al. [24], Nosheen Jan et al. [25], James et al. [26]), one case-control study Chang et al. [27], and one retrospective clinical study Halli et al. [28]. All articles analysed the effectiveness of additional measures in reducing scar tissue formation after primary cleft lip plastic surgeries. One study evaluated the effect of platelet-rich plasma (PRP) injections in the operated area [20]; three studies examined the effectiveness of botulinum toxin A [21-23]; one study compared a silicone-based ointment with a silicone dressing [27]; and four studies analysed the impact of different types of surgical sutures or tissue adhesives on postoperative scarring [24-26,28].

Risk of bias within the studies

Following the JBI Critical Appraisal Checklist, all studies were assessed, regarding randomized clinical trials, two studies [22,26] were rated as low-risk (high-quality studies), five studies [20,21,23-25] were classified as moderate-risk (Table 5). For the retrospective cohort study [28], it was classified as moderate-risk (Table 6), while for the case control study [27], it was rated moderate-risk as well for systematic errors (Table 7).

Results of individual studies

Impact of platelet concentrates on scar tissue formation

Refahee et al. [20] conducted a randomized clinical trial to analyse the effectiveness of platelet-rich plasma (PRP) in reducing scar tissue formation following primary cleft lip plastic surgeries. A total of 24 patients participated in the study. After a comprehensive clinical examination, the patients were randomly assigned to two groups.

The first (experimental) group included 12 patients with unilateral cleft lip who underwent cleft lip plastic surgery using the Millard technique, along with an injection of platelet-rich plasma (PRP) after the procedure. The second (control) group consisted of 12 patients with unilateral cleft lip who received only the Millard technique surgery without PRP injection. For the experimental group, approximately 1 ml of PRP was injected into the orbicularis oris muscle near the surgical site immediately after surgery.

Six months post-surgery, scar width was measured using ultrasound and photography.

The ultrasound measurements indicated that the postoperative scar tissue width in the control group averaged 4.96 (0.93) mm, while in the experimental group it was 3.8 (0.89) mm. Evaluating the patients’ photographs six months after surgery revealed that the scar width at two measured points was significantly smaller in the experimental group: 0.83 (0.23) mm in the first point for the experimental group compared to 1.49 (0.44) mm in the control group, P = 0.0001; and 1.02 (0.1) mm in the experimental group at the second point compared to 2.28 (0.98) mm in the control group, P = 0.0003 (Table 8).

The effect of botulinum toxin injections into the orbicularis oris muscle on scar formation after cleft lip surgery

Three included studies analysed the effect of botulinum toxin injections into the orbicularis oris muscle on scar formation after unilateral cheiloplasty [21-23].

Sonane et al [21] conducted a randomized clinical trial to evaluate the effectiveness of temporary paralysis of the orbicularis oris muscle induced by botulinum toxin A in reducing scar tissue formation after unilateral cleft lip surgeries. The study included 22 patients, with 12 patients in the experimental group receiving botulinum toxin A injections and 10 patients in the control group receiving saline injections into the orbicularis oris muscle. Cheiloplasty in both groups was performed using the “crossed triangular flaps” method. Botulinum toxin injections were administered immediately post-surgery at four points, 0.5 mm from the wound edges, into the orbicularis oris muscle.

The VAS, VSS, and scar width measurements from standardized ruler-assisted photography were used to evaluate outcomes. Six months post-cheiloplasty, the average VAS score in the experimental group was significantly better - 6.77 (0.65) compared to 5.46 (0.35) in the control group, with a P-value of 0.01. In photographs, scar width measured at two points was significantly lower in the experimental group (P < 0.01). At the first point, the result was 0.395 (0.23) mm in the experimental group, compared to 0.514 (0.34) mm in the control group. At the second point, it was 0.424 (0.42) mm in the experimental group versus 0.511 (0.26) mm in the control group (Table 8).

On average, the VSS scale scores were 1.708 (0.64) in the experimental group and 1.65 (0.86) in the control group. No statistically significant differences were observed between groups in VSS scale results (P = 0.32).

Chang et al. [22] also conducted a randomized clinical trial investigating the effectiveness of botulinum toxin in reducing scar tissue formation after primary cheiloplasty. A total of 59 patients with unilateral cleft lip were included, with 30 randomly assigned to the experimental group and 29 to the control group. Both groups underwent cheiloplasty using a modified rotation flap technique. After surgery, botulinum toxin A solution was injected at four points, 0.5 mm from the wound edges, in the experimental group, while only saline solution was injected in the control group.

To assess postoperative scars, VSS and VAS scales were used, and scar width was measured from photographs with a specialized ruler. Results were evaluated six months after the intervention. The VSS scores showed no statistically significant difference between the experimental and control groups - 2.7 (1.29) in the experimental group and 2.76 (1.44) in the control group, P > 0.05. The VAS score, however, was significantly better in the experimental group - 8.43 (0.56) compared to 7.19 (0.95) in the control group, P < 0.001. Scar width in the experimental group was significantly smaller at both measured points: 0.33 (0.11) mm at the first point compared to 0.45 (0.11) mm in the control group, P < 0.001, and 0.33 (0.13) mm at the second point compared to 0.47 (0.13) mm in the control group, P < 0.001 (Table 8).

Lu et al. [23] conducted a randomized clinical trial examining the effect of botulinum toxin A on reducing postoperative scar formation after primary unilateral cleft lip plastic surgery. All patients underwent primary cheiloplasty using a modified rotation flap technique. After surgery, the first group (Group A), consisting of 24 patients, received botulinum toxin A injections in the nasolabial fold at three points on both sides of the defect. The second group (Group B), with 31 patients, received botulinum toxin A injections of the same concentration at two points 0.5 cm away from the surgical wound edges on both sides.

The evaluation used VSS and measured scar width from photographs with a standard ruler. Two points were selected in the photos: the first point 1 mm above the vermilion border and the second point below the nasal opening. No statistically significant differences were observed between groups. After six months, the scar width in Group A was 0.59 (0.5) mm at the first point and 0.96 (0.1) mm in Group B, P = 0.147. At the second point, Group A showed 0.65 (0.51) mm, and Group B showed 0.8 (1.1) mm, P = 0.49. After 12 months, the first point in Group A measured 0.42 (0.59) mm and 0.36 (0.36) mm in Group B, P = 0.631. The second point in Group A was 0.42 (0.59) mm and 0.35 (0.37) mm in Group B, P = 0.615. The VSS scores also showed no statistically significant difference between groups: 3.2 (1.35) in the first group and 2.87 (0.88) in the second group, P = 0.472 (Table 8).

The effect of different postoperative wound coverings on scar formation

One included study compared the effect of covering the postoperative wound with a silicone-based ointment versus a silicone dressing on scar tissue formation after unilateral cleft lip plastic surgeries [27].

Chang et al. [27] conducted a retrospective clinical study comparing the effectiveness of a silicone-based ointment and a silicone dressing in reducing scar formation after primary cheiloplasty. The study included 62 patients who underwent primary lip repair using the Mohler technique. In the control group, silicone dressing was applied at night after cheiloplasty, while in the experimental group, a silicone-based ointment was applied twice daily to the postoperative area. Outcomes were assessed using VSS, VAS, and measurements of scar width from photographs.

Six months post-surgery, the VSS score was similar between the experimental and control groups: 2.2 (1.74) in the experimental group and 2.76 (1.44) in the control group, with P = 0.189. The VAS score was 7.19 (0.95) in the control group and 7.14 (0.9) in the experimental group, with P = 0.374. Scar width measurements from photographs were also similar in both groups: at the first measured point, the experimental group had a scar width of 0.4 (0.15) mm compared to 0.45 (0.11) mm in the control group, with P = 0.205. At the second measured point, scar width in the experimental group was 0.49 (0.37) mm compared to 0.47 (0.13) mm in the control group. No statistically significant difference was observed between the groups (P = 0.074) (Table 8).

The effect of different wound closure methods on scar formation after unilateral cleft lip surgeries

Four studies compared the effect of different wound closure methods on scar formation after unilateral cleft lip plastic surgeries [24-26,28].

Luthra et al. [24] compared the impact of 6-0 non-absorbable sutures (nylon or polyamide) and 6-0 absorbable sutures (Vicryl Rapide^®) on postoperative scar formation. The study included 20 patients who underwent unilateral cleft lip cheiloplasty using the modified Millard technique. Postoperative wounds were closed with randomly selected types of sutures. Non-absorbable sutures were removed a week post-surgery, while absorbable sutures were left to dissolve naturally. Scar evaluation used the VSS and VAS scales. A year post-surgery, results were significantly better in the group with non-absorbable sutures, showing smoother scars, less pigmentation, and elasticity closer to that of normal skin (P < 0.05) (Table 8).

Nosheen Jan et al. [25] compared the impact of cyanoacrylate (tissue adhesive) and 6-0 polypropylene sutures on scar formation. The study involved 300 patients who underwent unilateral cleft lip cheiloplasty using the modified Mohler technique. All patients had the wound closed in layers with absorbable sutures, but the epidermal closure method was randomly assigned between non-absorbable 6-0 sutures (control group, 150 patients) and tissue adhesive (experimental group, 150 patients). Scar assessments after six months used the VAS and HWES scales. The VAS score in the control group was 14.59 (13) versus 14.52 (12.64) in the experimental group, with no significant difference (P = 0.08). On the HWES scale, the control group scored 5.47 (0.59) and the experimental group 5.6 (0.49), again showing no significant difference (P = 0.069). Notably, the suture group had a significantly higher likelihood of developing hypertrophic scars (P < 0.001), as well as more frequent wound infections (P = 0.009) and a need for revision (P = 0.017) (Table 8).

Halli et al. [28] evaluated postoperative scar appearance using different wound closure techniques. Both groups underwent unilateral cheiloplasty using the Millard technique. In one group, the mucosa and muscle were closed with absorbable sutures, and the skin was closed with 6-0 Prolene^® sutures. In the other group, absorbable sutures were used for the mucosa and muscle, but synthetic tissue adhesive was applied to the skin edges. Eighteen months post-surgery, five evaluators assessed scars using the VAS scale. The mean VAS score was 15.04 in the suture group and 15.96 in the adhesive group, with no significant difference between groups (P > 0.05). The time required to close the skin with sutures was, on average, 7.45 minutes, while tissue adhesive closure took 4.34 minutes, a statistically significant difference (P < 0.01) (Table 8).

James et al. [26] in randomized clinical trial, the impact of synthetic tissue adhesives and 5-0 Prolene^® sutures on scar appearance after unilateral cheiloplasty was studied. A total of 38 patients participated, with 73.3% undergoing the Millard technique and 26.3% the T. Randall technique. After three months, scars were evaluated using the VAS and HWES scales. In the group with 5-0 Prolene^® sutures, the VAS score was 7.65 (1.45), while in the tissue adhesive group, it was 8.6 (1.12), P = 0.052. The HWES score for the suture group was 4.5, compared to 5 (0.9) in the adhesive group, P = 0.152. No statistically significant difference was observed between groups, with a complication rate of 5.3%. One complication was noted in each group (Table 8).

DISCUSSION

This literature review analysed nine publications [20-28], all examining supplementary measures aimed at achieving a more aesthetically pleasing scar appearance following primary unilateral cleft lip plastic surgery. The study reviewed publications that helped clarify and summarize the methods for improving postoperative scar appearance and demonstrated their effectiveness.

The effect of platelet concentrates on scar tissue formation

PRP consists of a high concentration of platelets, which, when activated, stimulate the production of growth factors such as platelet-derived growth factor, transforming growth factor-β, endothelial growth factor, insulin-like growth factor 1, epidermal growth factor, and epithelial cell growth factor [29]. These growth factors participate in various wound healing phases, initiating and regulating cell chemotaxis, mitosis, differentiation, angiogenesis, and epithelialization [30]. Upon activation, platelets attract undifferentiated cells to the newly forming matrix, promote cell division, inhibit cytokine release, and reduce inflammation, creating favourable conditions for healthy tissue regeneration and reducing the likelihood of scar formation. This effect of platelet concentrates has been discussed in the treatment of skin defects in various body areas [31-33]. This literature review identified one publication that examined the effectiveness of PRP in reducing scar tissue formation after primary unilateral cheiloplasty [20]. Six months after surgery, the width of scar tissue in the experimental group was significantly smaller than in the control group. This suggests that PRP, by promoting skin regeneration and healing, may reduce scar formation.

The effect of botulinum toxin on scar tissue formation

The skin above the upper lip is at high risk for scar tissue development following primary cheiloplasty due to repeated contractions of the orbicularis oris muscle during activities such as eating, breastfeeding, drinking, and expressing emotions. These movements create tension forces that interfere with optimal postoperative wound healing [34]. The orbicularis oris muscle, when contracting, exerts tension along the suture line, and repeated microtrauma can lead to an increased inflammatory response, resulting in fibrotic tissue and poorer postoperative aesthetics. One way to reduce these forces that hinder skin healing is through botulinum toxin A injections into the orbicularis oris muscle [35]. The injection blocks acetylcholine release, the main neurotransmitter at the neuromuscular junction, leading to temporary muscle paralysis. This reduces tension on the sutured skin above the muscle, allowing smoother tissue healing and a smaller postoperative scar [36].

This literature review identified three publications examining the effect of botulinum toxin A on scar formation [21-23]. In two studies, Sonane et al. [21] and Chang et al. [22], both VAS and VSS results were significantly better in the experimental groups than in the control groups, which received saline injections. In the study by Lu et al. [23], both groups received botulinum toxin A injections, but the number of injection points differed (two points on each side for one group and three for the other). Evaluation included VSS scores and scar width measurements at two zones. Although no statistically significant difference was observed between the groups, the scar appearance and width in both groups were similar to the results of previous studies where botulinum toxin was used as an additional measure. Thus, regardless of the number of injection points, the positive effect of botulinum toxin on reducing scar tissue formation was observed in all included clinical studies.

The effect of different postoperative wound coverings on scar formation

Silicone is a commonly used non-invasive measure to reduce scar tissue formation [37]. One theory on how silicone prevents scarring is by increasing the skin temperature when covered with a silicone layer (skin temperature rises by approximately 1.7 °C). This increase in temperature significantly enhances collagenase activity, which slows the scarring process, leading to less scar tissue formation [38]. Additionally, it has been shown that applying silicone products on the skin reduces water evaporation, thereby increasing epithelial hydration. Silicone-containing products induce biochemical changes in skin cells, which activate the extracellular matrix synthesis by fibroblasts, promoting epithelialization [39]. Silicone also acts as a barrier, protecting the healing postoperative wound from various microorganisms [40].

This literature review examined the effectiveness of silicone dressings and silicone ointments in reducing scar tissue formation after primary unilateral cleft lip surgery [27]. The results indicated that applying silicone gel twice daily to the surgical area or using silicone dressings at night yielded similar outcomes, with no statistically significant difference between the groups. However, researchers observed that using dressings posed certain challenges. The dressing needed to be secured with adhesive tape, which is inconvenient for the facial area, and changing the tape caused discomfort for the patient, with potential skin allergies [41]. Additionally, the tape frequently came loose during the day due to the child’s movements, posing additional risks, such as accidental ingestion or airway obstruction if the tape entered the respiratory tract.

The effect of different wound closure methods on scar formation

Several techniques can be used for wound edge approximation. While suturing is considered the gold standard, other methods are increasingly described in the scientific literature for treating unilateral cleft lips. Key topics of debate include suture selection and the use of tissue adhesives [42].

This review examined one study [24] that explored the impact of different suture materials on postoperative scarring. It compared the use of absorbable and non-absorbable sutures for closing skin edges after cheiloplasty. A significantly better aesthetic scar outcome was achieved in the group where the skin was closed with non-absorbable sutures. This is explained by the fact that absorbable sutures loosened prematurely, leaving the not fully healed wound unprotected from tensile forces. In contrast, non-absorbable sutures did not transmit tensile forces to the wound for a longer healing period, resulting in less scar formation. However, it should be noted that removing non-absorbable sutures requires sedation in children, whereas absorbable sutures eliminate the need for a second procedure. However, this advantage is debatable, as a more aesthetically pleasing scar may result in fewer long-term issues for the child.

The other three studies in this review compared the use of tissue adhesives and non-absorbable sutures for skin closure after cheiloplasty [25-28]. None of the clinical trials found a statistically significant difference in the appearance of postoperative scars between the two closure methods. Although both methods had a similar effect on scar formation, the authors highlighted other aspects that favour the use of tissue adhesives. These include significantly lower infection rates (due to a barrier protecting the wound from environmental exposure), significantly shorter procedure time, ease of application, less trauma to surrounding tissues, haemostatic effect, and no need for a second procedure to remove sutures. In one study [25], the group using sutures for wound closure also showed a significantly higher need for revision and a higher incidence of hypertrophic scarring.

CONCLUSIONS

To reduce postoperative scar formation, platelet concentrate injections around the wound or botulinum toxin A injections into the orbicularis oris muscle can be administered during surgery. Skin closure of the operated area using non-absorbable sutures or tissue adhesives positively influences scar appearance. Postoperative care of the area with silicone-based products enhances the aesthetic outcome of the surgical site. The results of all studies unequivocally demonstrate the benefits of these supplementary measures for improved cheiloplasty outcomes. Based on scientifically accepted objective criteria for postoperative scar evaluation, platelet concentrate injections significantly reduce scar tissue width. The positive impact of botulinum toxin A is supported by Visual Analog Scale and Vancouver Scar Scale, as well as a reduction in scar width. The significant positive effect of non-absorbable sutures on postoperative appearance is substantiated by Vancouver Scar Scale and Visual Analog Scale. The beneficial effect of tissue adhesives on scar appearance is demonstrated by Visual Analog Scale and Hollander Wound Evaluation Score scale results.

ACKNOWLEDGMENTS AND DISCLOSURE STATEMENTS

The authors report no conflicts of interest related to this study.

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