Introduction

Full-thickness skin defect occurs by various causes including trauma, burn, and surgery. Such defects can cause esthetic and functional problems. The latter include limited range of motion and joint stiffness because of adhesion and excessive scarring. Later, secondary or tertiary revision can be required. It is important to cover the full-thickness skin defect with minimal esthetic and functional deficits in the early stage to minimize cost. Furthermore, in cases of donor sites for flaps that destroy the normal structure, coverage with minimal deficits can be more significant.

Dermal substitutes share the function of normal dermis. They restore the skin anatomy and physiologic function with their scaffolding properties and facilitate the invasion of normal fibroblasts and capillaries to synthesize new dermis [1]. They also increase the resistance to shear forces, and so could be applicable in around joints [2].

Donor sites for flaps that are too large to achieve primary closure should be covered with a split-thickness skin graft with or without acellular dermal matrix (ADM). Skin grafts with dermal substitutes result in better scar quality, such as elasticity and pliability [3,4,5]. However, these studies were limited in that ADM was applied at different locations and for different wounds.

In this study, we investigated the effectiveness of ADM on scar quality of the skin graft sites of full-thickness skin defects. To avoid bias, we especially focused on the donor sites for the anterolateral thigh flap from the view of results of early outcome of skin graft taken and long-term outcome of scar quality. In all cases, autologous split-thickness skin grafts were performed with 1:1.5 meshed 0.008–0.010-inch-thick skin. In the skin graft with ADM group, 1:1 meshed 0.008–0.013-inch-thick ADM (CGderm®; CGBio, Inc., Seungnam, Korea) was co-grafted. For both objective and subjective evaluations, each graft was assessed with the Vancouver Scar Scale (VSS), the patient scar assessment scale of the Patient and Observer Scar Assessment Scale (POSAS), and by measurement of skin fold compared to the normal side to investigate the degree of contracture.

Patients and Methods

Patient Selection

Approval for the study was from our institutional review board (approval number 13-307). Written informed consent was obtained from all patients. The selected patients had received anterolateral thigh free flaps to cover a defect from 2011 to 2015, and needed a skin graft for the donor site with or without ADM graft. The reason for free flap coverage was related to trauma or malignancy. The patients with more than two flap donors and with an insufficient follow-up period (<6 months) were excluded.

Early and late outcomes of each skin graft were investigated by retrospectively reviewing medical records and clinical photos. Early outcome aspects included whether the skin loss occurred the first time the dressing was changed at the skin graft site, the duration of negative-pressure wound therapy (NPWT), elapsed time in days from graft to removal of stitches, elapsed time in days to achieve complete healing (defined as >80% graft take or change to open dressing), and complications (infections or large skin loss that led to re-operation). Late outcomes were evaluated after a minimum of postoperative 6 months and included the characteristics of the scar (vascularity, pigmentation, pliability, and height) and patient symptoms (itching sensation and pain). Assessments involved the VSS (Table 1) and the patient scar assessment scale of the POSAS (Table 2) [6, 7]. Skin fold was measured to evaluate the elasticity of scar tissue. It was measured using a skin fold caliper and pinching the donor site and normal area of the patient’s thigh (as a control). In each patient, the assessment was performed by two experienced researchers.

Table 1 Vancouver scar scale
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Table 2 Patient scar assessment scale on the Patient and Observer Scar Assessment Scale
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Forty-six patients received reconstruction with anterolateral thigh free flaps from November 2011 to December 2015 at our institution. Among them, donor sites of 17 patients were covered with split-thickness skin grafts only, and those of 29 patients were covered with split-thickness skin grafts and ADM. Of the 17 patients with split-thickness skin grafts, 10 were available for assessment. Of the 29 patients with split-thickness skin grafts and ADM, 20 patients were available due to long-term follow-up loss.

Surgical Procedure

We transferred free anterolateral thigh flaps for the reconstruction of defects caused by trauma or after wide excision of malignant skin tumors. The flaps were elevated including the underlying fascia but without harvesting the vastus lateralis muscle in all cases. At the stage of donor site coverage, the skin graft only group was treated by autologous split-thickness skin graft alone. Autologous split-thickness skin grafts (0.008–0.010 inch thick) were harvested from the thigh using an electric dermatome (Zimmer Air Dermatome; Zimmer Inc., Warsaw, Ind., USA). The harvested skin was expanded 1.5 times with a mesh in both the skin graft only group and the skin graft with ADM group. The skin was then fixed to the recipient bed with a skin stapler. The skin graft with ADM group was treated by co-grafting with autologous split-thickness skin graft with ADM. The autologous split-thickness skin graft was harvested and expanded the same way as in the skin graft only group. ADM (CGderm®; CGBio, Inc., Seungnam, Korea) with 0.008–0.013 inch thickness and 1:1 meshed type was rehydrated by submerging it in warm water (<37 °C) for a minimum of 10 min. Rehydrated ADM and split-thickness skin grafts were fixed with a skin stapler. NPWT (CuraVAC®; CGBio, Inc., Seungnam, Korea) was applied to all of the skin graft sites in both the skin graft with ADM group and the skin graft only group with continuous mode at −120 mmHg. We changed the dressing at 4 days postoperatively for the first time and changed it every other day.

Statistical Analyses

VSS scores, skin fold data, and the patient scar assessment scale of the POSAS were compared using Wilcoxon rank-sum test. Continuous variables of demographic data were compared using Student’s T test. For categorical variables of demographic data, Fisher’s exact test was applied. Statistical significance was accepted for values of p < 0.05.

Results

Ten patients were included in the skin graft only group and 20 patients were included in the skin graft with ADM group. There was no statistical difference in sex, age, underlying disease, and size of the defect (i.e., donor site of the anterolateral thigh flap) between the two groups. There was no statistical difference in the early outcomes between the two groups (Table 3). The mean follow-up was 20.5 months (range 7–45 months) in the skin graft only group and 19 months (range 9–36 months) in the skin graft with ADM group. In complications, there was no total skin loss of the grafted site in either group and partial skin loss occurred in 3 patients. Among the 3 cases that required repeated skin grafts, one case (10%) was in the skin graft only group and 2 cases (10%) were in the skin graft with ADM group.

Table 3 Demographic data and the early outcomes of skin grafts
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VSS scores and skin fold ratios are summarized in Table 4. The vascularity subscore was significantly lower in the skin graft with ADM group (1.25; 95% confidence interval [CI], 0.81–1.69) than in the skin graft only group (1.90; 95% CI, 1.16–2.64) (p = 0.003). The total score was significantly lower in the skin graft with ADM group (5.15; 95% CI, 3.88–6.42) than in the skin graft only group (6.20; 95% CI, 4.97–7.43) (p = 0.016). The pigmentation subscore was lower in the skin graft with ADM group (1.80; 95% CI, 1.39–2.21) than in the skin graft only group (1.90; 95% CI, 1.58–2.22), but showed no statistical significance (p = 0.518). The pliability subscore was lower in the skin graft with ADM group (1.25; 95% CI, 0.81–1.69) than in the skin graft only group (1.70; 95% CI, 1.02–2.38), but showed no statistical significance (p = 0.053). The height subscore was lower in the skin graft with ADM group (0.85; 95% CI, 0.36–1.34) than in the skin graft only group (0.90; 95% CI, 0.58–1.22), but showed no statistical significance (p = 0.752). Skin fold calculated as the ratio of the skin fold thickness of the donor site to that of the normal area of the thigh was higher in the skin graft with ADM group than in the skin graft only group, but showed no statistical significance (81.72 vs. 69.92%, p = 0.082).

Table 4 Results of Vancouver scar scale scores and skin fold
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Patient scores of the POSAS are described in Table 5. The total score was significantly lower in the skin graft with ADM group (13.80; 95% CI, 9.77–17.83) than in the skin graft only group (20.70; 95% CI, 10.77–30.63) (p = 0.017). The pain subscore was significantly lower in the skin graft with ADM group (1.50; 95% CI, 0.45–2.55) than in the skin graft only group (2.80; 95% CI, 0.93–4.67) (p = 0.037). The stiffness subscore was significantly lower in the skin graft with ADM group (1.60; 95% CI, 0.66–2.54) than in the skin graft only group (4.90; 95% CI, 1.72–8.08) (p = 0.002). Itching, color, thickness, and irregularity subscores were also lower in the skin graft with ADM group, but showed no statistical significance. Examples from the skin graft only group and the skin graft with ADM group are presented in Figs. 1, 2, 3 and 4.

Table 5 Results of patient scores on the Patient and Observer Scar Assessment Scale
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Fig. 1
figure 1

A 36-year-old female received an anterolateral thigh free flap due to trauma on the right foot. The donor site of the flap was covered with a skin graft with ADM. Eight days after the operation (a) and long-term follow-up at postoperative 2 years (b). The grafted site showed similar color to the adjacent skin and minimal contracture and depression. ADM acellular dermal matrix

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Fig. 2
figure 2

An 80-year-old female received an anterolateral thigh free flap due to trauma on the left foot. The donor site of the flap was covered with a skin graft with ADM. One week after the operation (a) and postoperative 6 months (b) and (c). The pliability of the grafted skin was excellent in the skin graft with ADM. ADM acellular dermal matrix

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Fig. 3
figure 3

A 71-year-old male received an anterolateral thigh free flap due to a third degree burn on the left antetibial area. The donor site of the flap was covered with a skin graft only. Four days after operation (a), postoperative 7 months (b), and postoperative 3 years (c). The grafted skin showed marginal depression, distinguished color and texture to adjacent skin, and contracture

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Fig. 4
figure 4

A 52-year-old male received an anterolateral thigh free flap due to trauma on the right foot. The donor site was covered with a skin graft only. One week after the operation (a) and postoperative 1 year (b) and (c). The grafted site showed a bulging contour due to muscle herniation

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Discussion

Scar tissue is clinically distinguished from normal skin by color, texture, thickness, contraction, and firmness. This leads to cosmetic and functional sequelae and, especially near the joint area, contraction causes limitation in range of motion of joints. Scar evaluation requires control of various conditions, such as age, sex, and other demographics, and the status of the wound. In this study, we controlled the anatomical location, depth of the defect, degree of contamination, and interval to skin graft by evaluating the skin graft sites of the donor for the anterolateral thigh fasciocutaneous free flap. Also, operations were conducted by the same operator who used the same procedure.

The anterolateral thigh flap was first described by Song et al. [8]. It has become widely used in reconstruction because it has a long pedicle with good caliber and a large and pliable skin territory with the ability to design more than one skin paddle and to modify flap thickness [9]. Donor site complications of the anterolateral thigh flap include limited range of motion at the hip and knee joint, compromised muscle strength, impaired wound healing, numbness, and an esthetic problem associated with hypertrophic scarring [9, 10]. However, donor site morbidity is much less than that of other flaps and it is a major advantage of the anterolateral thigh flap. Scarring of the donor site is less noticeable than in other parts of the body, but scar contracture can impair movement, produce symptoms such as pain and itching, and create patient dissatisfaction because of scarring, especially when the donor site is covered with a skin graft.

Dermal substitutes have been used to minimize scar contracture and improve the scar quality [3]. The amount of dermis negatively correlates with the quality of scarring and degree of contracture [11, 12]. Various kinds of dermal substitutes have been developed. These include xenogenic ADMs (Integra®, LifeSciences Corp., Plainsboro, NJ, USA; Matriderm®, Eurosurgical Limited, Guildford, UK) and allogenic ADMs (Alloderm®, LifeCell Corp., Branchburg, NJ, USA; CGderm®, CGBio, Inc., Seungnam, Korea). An ADM is a dermal allograft that is free of immunogenic components; it can augment or replace the dermis at the wound site and better resembles normal skin. It contains collagen and elastin, which control tensile strength and elasticity, proteoglycans that induce angiogenesis, laminin that maintains binding with the connective tissues, and basement membrane that consists of collagen type IV. ADMs or artificial dermal substitutes can be used with split skin grafts to compensate for a limited range of motion and stiffness, especially near the joint area. An assessment of the long-term effectiveness of the Matriderm® bovine-based collagen I, III, and V and elastin hydrolysate-based dermal substitute in acute and reconstructive burn surgery included objective assessments (scar elasticity, vascularization, pigmentation, and surface roughness) and a subjective scar assessment using POSAS [13]. The authors reported that the scar parameters improved in both acute and reconstructive substituted wounds and increased elasticity in substituted scars in a largely expanded autograft. In our study, among the scar parameters, vascularity and the VSS total score, and POSAS pain and stiffness subscore, and total score were significantly higher in the ADM group.

Single-stage ADM and autograft is difficult because it could require a longer period of stabilization for revascularization because of the increased diffusion distance for nutrients and oxygen to the autograft [14, 15]. To compensate for this, we applied NPWT on the graft site. NPWT minimizes shearing between the graft and wound bed and prevents formation of fluid and seroma to promote proper contact between the graft and the recipient bed [16, 17]. NPWT also increases wound blood flow [18]. Thus, application of negative-pressure therapy facilitates imbibition, inosculation, and neovascularization, which leads to increased graft take and survival [16, 19, 20]. Our data of early outcomes of skin grafts revealed no statistically significant differences in graft take and healing process between the skin graft only group and the skin graft with ADM group. The data indicate minimal disadvantage of ADM and autograft in one stage with NPWT in the healing process with minimal scar formation and more desirable esthetic results expected.

Bioemen et al. [20] compared the combinations of a dermal substitute (Matriderm®), split-thickness skin graft, and NPWT in acute burn wounds. In scar quality, scars treated with dermal substitution and NPWT were significantly more elastic compared to scars treated with dermal substitute alone. They showed no significant differences in take rate of autografts with or without dermal substitute using NPWT. They explained that the removal of toxic products from bacteria and lysosomal enzymes from dead autologous cells that may degrade collagen present in the substitute through action of topical negative-pressure therapy. It causes a slower degradation of the substitute and improvement in scar outcome. In our study, we investigated elasticity by measuring the skin fold of the scar. The skin graft with ADM group showed superior skin fold data to the skin graft only group, but showed no statistical difference. (p = 0.082). However, in the Vancouver Scar Scale, the vascularity subscore and total score were statistically superior in the skin graft with ADM group compared to the skin graft only group (p = 0.003 and p = 0.016 each).

To evaluate the scar quality, we used two representative scar scales, VSS and POSAS. VSS, which was developed by Sullivan et al. in 1990, calculates subscores in four categories (vascularity, pigmentation, pliability, and height of the scar) and aggregates the scores [6]. POSAS was developed more recently, in 2004, as an attempt to emphasize the importance of the subjective symptoms of patients that include pain and urtication, which had not been considered in previous scar assessment scales. Both are widely used scar assessment scales [7]. There has been a tendency in previous studies to assess widespread operative scars with VSS [21], so we used VSS and the patient component of the POSAS in our study.

Excessive scarring could limit the range of motion, even in the absence of muscle or ligament injury. The split-thickness skin graft could adhere to the underlying fascia or muscle layer, which could limit hip and knee range of motion [10]. Use of an ADM with a split-thickness skin graft could mitigate scar contracture and improve the range of motion. In support of this scenario, the skin fold ratio (skin graft site to normal control) was higher in the ADM group, although it was not statistically different from the skin graft only group.

The ADM was used for 20 patients who consented to its use. All 10 patients in the skin graft only group had rejected the use of ADM, typically because of the expensive cost. The small patient numbers in the skin graft only group are a limitation of this study.

Several prior studies have also compared the skin graft outcome and scar quality in the skin graft only and skin graft with ADM graft groups. But, our study has a notably strong point—we compared the skin graft outcome and scar quality on the donor sites from anterolateral thigh free flaps located at a similar anatomical position with a similar defect depth. So, we controlled for other variables that could affect the short- and long-term outcomes of the skin graft.

Several studies have reported that split-thickness skin grafts with ADM graft show better scar quality in burn wounds [3, 4, 22,23,24], but the intervals from the initial event that generated defect to the time of coverage were diverse, and there may have been difficulty in controlling the status of the wound bed. In our study, we covered the donor site of the anterolateral thigh flap immediately with the skin graft, so the wound bed of each case was similar.

Also, with the use of two scar scales, VSS and POSAS, we could evaluate the scar quality both objectively and subjectively. This is the first time to evaluate the scar quality of ADM grafts at similar anatomical sites, degree of contamination, and wound depth performed by a single surgeon with objective and subjective scar assessment.

Conclusion

As a large anterolateral thigh flap is harvested to cover the large defect, the donor site would arise close to the knee joint. Furthermore, because it cannot be closed primarily, the defect should be covered with a skin graft. This would limit the range of motion and produce an esthetically undesirable scar. Co-grafting with ADM can improve scar quality in subjective and objective aspects. The possibility of a delay in graft take can be compensated for by NPWT at the skin graft site.