Integra-based Reconstruction of Large Scalp Wounds: A Case Report and Systematic Review of the Literature.

BACKGROUND: Large complex scalp wounds that have traditionally required free vascularized tissue transfer have been successfully reconstructed with skin substitutes such as Integra. Although there are multiple reports of Integra-based reconstructions of scalp wounds, there has not been a comprehensive assessment of this body of literature that critically examines this method. Our goal was to conduct a systematic review to determine the effectiveness of Integra-based reconstructions of scalp wounds, with emphasis on large defects.
METHODS: A comprehensive systematic review was completed using key search terms, including Integra, dermal regeneration template, bovine collagen, skin substitute, forehead, and scalp. Selected articles reported characteristics of patients and their reconstructions. The primary outcome measures were wound complications and percent graft take.
RESULTS: Thirty-four articles were included in this systematic review. Wound sizes ranged from 5.7 to 610 cm2, with 35.3% of articles reporting a mean defect size >100 cm2. Thirty-two articles reported mean percent take of skin graft ≥90%. Sixteen articles reported a minor complication. There were no major complications associated with the reconstructions.
CONCLUSIONS: There is a substantial evidence base for the use of Integra to reconstruct scalp wounds. To date, the dermal regeneration template is generally reserved for salvage procedures or when the patient cannot tolerate free tissue transfer. Based on the findings of this systematic review and the authors' clinical experience, Integra can be used to achieve predictable results in large complex scalp defects.

Reconstructive strategies for the management of scalp wounds are varied and determined by defect size, depth, and quality of regional tissue. Small wounds can be addressed with skin grafting and locoregional flaps or in some cases allowed to heal by secondary intention. Closure of larger defects may be facilitated by staged tissue expansion, whereas infected or previously irradiated wounds are best served by free vascularized tissue transfer.[1] These options, however, may not be suitable for all patients.[2,3]

Recently, there have been multiple reports documenting successful use of Integra (Integra LifeScience Corporation, Plainsboro, N.J.) dermal regeneration template in large scalp wounds. Integra is used widely in reconstructive procedures all over the body and is composed of a layer of bovine collagen crosslinked with glycosaminoglycan covered by a silastic membrane.[4] Infiltration of host cells into the collagen matrix forms a neodermis over the course of 3–6 weeks, at which point the silicone membrane is replaced with a split-thickness skin graft.[5] When applied properly, Integra can result in long-term engraftment with excellent cosmetic and functional results.[6,7] To date, there has not been a comprehensive analysis of the literature on the use of Integra for complex scalp wounds that would serve to guide practitioners toward best practices.

We present an illustrative case of Integra-based reconstruction for a large (>100 cm2) complex scalp wound. This is followed by a systematic review to evaluate and synthesize the available literature on Integra-based reconstruction of scalp wounds. We wished to explore whether there was a critical defect size at which Integra was not reliable and thus paid particular attention to large defects, defined in this article as those defects that are ≥100 cm2. Furthermore, we sought to identify factors predisposing Integra-based reconstructions to complication and to identify best practices in the use of Integra for scalp wounds.

CASE PRESENTATION

A 40-year-old man with history of intellectual disability and multiple preexisting medical conditions was referred to the plastic surgery service for definitive management and closure of a large scalp mass with bleeding and foul-smelling discharge (Fig. 1A). Per the patient’s parents, the mass had been present for a year and a half and had grown over that period of time. On physical exam, a large 64 cm2 ulcerated mass was noted over the patient’s forehead and frontal scalp, with additional 1 cm2 lesions on the left temporal region and dorsum of the left hand. A presumptive diagnosis of squamous cell carcinoma was made based on outside hospital records, and the patient was taken to the operating room for definitive management. The scalp mass was excised down to calvaria, resulting in a 144 cm2 scalp defect. The defect was reconstructed with fenestrated Integra after burring the calvaria. A wound vacuum-assisted closure (VAC) was used as the bolster dressing and removed on postoperative day 5. Pathology confirmed the diagnosis of squamous cell carcinoma. On readmission for second-stage reconstruction, the silastic membrane was removed and a healthy granulation bed was noted (Figs. 1B, C). A fenestrated split-thickness skin graft was applied and the patient was discharged home 6 days later. One hundred percent graft take was noted at subsequent clinic visits, with excellent cosmetic and functional results at follow-up at 244 days (Fig. 1D).

Fig. 1.

Photos of a patient undergoing Integra-based reconstruction of a large scalp defect. The patient is shown preoperatively (A), before removal of the silastic membrane (B), with a healthy granulation bed after removal of the silastic membrane before placement of skin graft (C), and on follow-up 244 days after initial reconstruction (D).

MATERIALS AND METHODS

Literature Search and Study Selection

A systematic literature search was completed according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines (Fig. 1).[8] PubMed and Ovid were queried using the search terms “Integra AND (scalp OR forehead OR head)”, “bovine collagen AND (scalp OR forehead OR head)”, “skin substitute AND (scalp OR forehead OR head)”, and “dermal regeneration template AND (scalp OR forehead OR head)”. Additional references relevant to the review were retrieved from article reference lists. Inclusion and exclusion criteria are presented in Table 1. Two authors independently screened all articles for inclusion or exclusion.

Table 1.

Inclusion and Exclusion Criteria Utilized in This Systematic Review

Data Abstraction and Analysis

Data were abstracted for a variety of preoperative, intraoperative, and postoperative details. Preoperative criteria included mean patient age, mean defect size, and indication for reconstruction. Intraoperative criteria included staging, bone burring, and Integra fenestration. Postoperative criteria included mean time to skin graft, adjuvant radiotherapy, complication, and mean percent graft take. In cases where mean percent take was not reported numerically, qualitative descriptors were used to estimate mean percent take. If graft take was described as “good” or “excellent,” it was converted to a mean percent take of 100%. Other descriptors were converted on a case-by-case basis. Studies not reporting specific patient or procedural details were removed from descriptive analysis for that detail. Given the limitations of the data, quantitative evaluation was not performed.

RESULTS

Study Retrieval and Characteristics

Eighty-six studies were identified through the initial database search, and 2 studies through article reference lists (Fig. 2). Abstracts for 67 studies were screened, and 55 full-text articles were assessed for eligibility. Thirty-four studies met inclusion criteria for qualitative synthesis.[9-43]

Fig. 2.

A PRISMA diagram detailing the method utilized to conduct this systematic review.

Preoperative Wound Characteristics

The leading indication for reconstruction was resection of a malignant skin tumor (67.6%; Table 2). This was followed by trauma (17.6%), failed previous reconstruction (11.8%), burn (8.8%), radionecrosis (5.9%), infection (2.9%), and aplasia cutis congenita (2.9%). Patient age ranged from 0 to 93 years old, with 55.9% reporting a mean age over 65. In general, Integra was selected for reconstruction in elderly patients with multiple comorbidities.

Table 2.

Preoperative Characteristics of Patients Undergoing Integra-based Reconstruction

Defects ranged in size from 5.7 to 610 cm2, with 12 studies reporting a mean defect size >100 cm2 (Table 2). Percent take of Integra and/or skin graft ranged from 50% to 100%, with 94.1% reporting take ≥90%. Mean follow-up was 14 months.

Outcomes of Integra-based Scalp Reconstruction

The most common approach to Integra-based reconstruction is the staged approach, with initial application of the skin substitute followed by a split-thickness skin graft over the revascularized matrix at a later date. In this systematic review, 82.4% of studies utilized a staged approach (Table 3). Overall, staged reconstructions were successful, with 92.9% reporting average percent take ≥90%. Of the 11 staged studies with average defect size ≥100 cm2, all reported percent take >90%.

Table 3.

Postoperative Characteristics of Patients Undergoing Integra-based Reconstruction

The timing of the second-stage of Integra reconstruction is largely dependent on the state of the granulation bed. If the matrix appears well-vascularized, the skin graft can be applied and expected to heal well. In this systematic review, 82.1% of studies reported a time to second stage ≤30 days (data not pictured). Five studies reported time to second stage >30 days.[12,14,20,24,36,37] All five reported a complication accounting for the delay.

Among staged reconstructions, 53.6% of studies reported complications in at least 1 patient (Table 3). Infection (17.9%) was the most common, followed by delayed healing (10.7%), incomplete adherence of the Integra (10.7%), radionecrosis after postoperative radiotherapy (10.7%), persistent contour defect (7.1%), hematoma (3.6%), seroma (3.6%), wound failure (3.6%), and ectropion (3.6%). Mean percent take for these studies ranged from 50% to 100%, with only 2 studies reporting mean percent take <90%.[22,36] Four studies with mean defect size ≥100 cm2 reported complications.[9,10,22,24]

Seven studies included patients who underwent adjuvant radiotherapy after reconstruction.[12,18,22,24,25,41,42] Four reported subtotal radionecrosis, radiation-induced soft tissue breakdown, with eventual graft take of 100%.[22,25,41,42] In contrast, patients with preoperative radiotherapy of the wound bed had mixed results, with percent take as low as 50%.[10,12,17,22,36]

Six articles utilized a single-stage reconstructive approach.[11,21,27,39-41] Five of the 6 studies did not apply a skin graft,[11,21,39-41] while one applied both Integra and skin graft in the same procedure.[27] One case report performed one-stage reconstruction of a defect ≥100 cm2, reporting a minor infection in the postoperative period.[11] Percent take for one-stage studies was 100%.

Effect of Bone Burring on Integra Scalp Reconstruction

Bone burring of the calvaria before Integra placement encourages vascular ingrowth from the diploë into the construct. Burring was employed in 74.2% of the studies included in this systematic review, with percent take ranging from 50% to 100% (Table 4).[10,12,14,15,17-20,22-24,27,28,30-34,36-38,40] Percent take was >90% in studies not employing bone burring.[9,11,12,16,17,29,35,39,41]

Table 4.

The Effect of Bone Burring on Outcome of Integra-based Reconstruction

Effect of Fenestration and Postoperative Bolster Technique on Integra Scalp Reconstruction

Fenestrating Integra permits the egress of fluids, in theory reducing the risk of seroma or hematoma formation. Nine studies fenestrated the dermal regeneration template, with mean percent take ≥97% (Table 5).[12,13,17,23,24,28,30,38,41] Khan et al[24] and De Angelis et al[41] reported formation of small seroma and hematoma, respectively, not affecting final graft take. The remaining 22 articles using unfenestrated Integra reported percent take ranging from 50% to 100%.[9-11,14-16,18-20,22-25,27,31-35,37,39,42] Fung et al[37] reported hematoma formation under unfenestrated Integra resulting in 90% graft take.

Table 5.

The Effect of Fenestration on Outcome of Integra-based Reconstruction

Studies were divided on the basis of postoperative wound care method to evaluate its impact on outcome of Integra reconstruction (Table 6). VAC was the most common postoperative wound dressing (32%).[19,22,24,27,28,33,35,38] These studies reported percent take of 50–100%, with 87.5% of studies reporting percent take >98%. Bolstered dressings (28%) and silver-impregnated dressing materials (24%) were also popular, with percent take ≥90% in all cases. The remaining studies utilized a range of postoperative dressings. Notably, Gonyon and Zenn[10] were the only authors to report on the use of hyperbaric oxygen in the perioperative management of Integra-based reconstruction.

Table 6.

The Effect of Postoperative Wound Care Method on Outcome of Integra-based Reconstruction

DISCUSSION

There is a substantial body of literature supporting the use of Integra in a wide variety of reconstructive settings, including trauma, burns, and postoncologic resection.[6,7] Its popularity is largely due to its ability to provide effective and immediate closure to wounds without significant associated donor site morbidity and with low risk for scar contracture or hypertrophy.[44] Staging permits the use of Integra in poorly vascularized wounds, as the split-thickness skin graft is applied after neovascularization of the dermal regeneration template by host vessels.[5] Functional and cosmetic results are often excellent.[6,7,45,46] Of the 34 articles included in this review, 32 reported success rates ≥90%.

The initial impetus for reviewing the literature on scalp reconstruction using Integra was to determine if there was a maximal wound size where the dermal regeneration template could reliably be used. We found that relatively large scalp wounds can be successfully treated with Integra-based reconstruction as demonstrated by the presented case. Twelve studies reported mean defect size >100 cm2 across one- and two-stage reconstruction (Table 2). Eleven of these studies reported a mean percent take of ≥90%. We also found that large scalp wounds do not seem to have significantly more complications. Including both one- and two-stage reconstructions, approximately 41.7% of studies with large mean defect size reported at least one complication. This is comparable to the 45.5% of studies with smaller defects that reported complications. Thus, we believe that wound size alone should not prohibit the selection of Integra as a reconstructive option.

Although Integra can be effective in some types of poorly vascularized wound beds, our experience suggests that preoperative radiotherapy is a relative contraindication to its use. There is substantial evidence to suggest that irradiation reduces number and function of cells critically involved in wound healing.[47-49] Given that the revascularization of Integra is dependent on host cell migration and proliferation, we feel that preoperative radiotherapy’s effect on the wound bed predisposes Integra reconstruction to failure. Although there are isolated reports of successful use of Integra in irradiated scalp wounds, the extent of radiation damage was variable.[10,12,17,22] Mean percent graft take for these patients ranged from 50% to 100%, and at least one patient experienced 30% breakdown by 22 months.[12] Although we do not recommend the use of Integra in irradiated wounds, it may be possible to achieve stable coverage in areas with limited damage. Hyperbaric oxygen may improve outcomes in selected cases, though we do not believe it can be applied in a predictable fashion.[10,12] In the senior author’s practice, microsurgical free flap reconstruction in large previously irradiated scalp defects is preferred.

Interestingly, postoperative irradiation after Integra-based reconstruction appears to be well tolerated. Seven studies included patients who underwent adjuvant radiotherapy of the reconstruction site.[12,18,22,24,25,41,42] Although some patients experienced mild acute radiodermatitis and/or radionecrosis, outcomes were largely good with reported mean percent take of graft in excess of 95%. This demonstrates the durability of Integra reconstruction and suggests that Integra is a viable reconstructive approach to wounds that may require future adjuvant radiotherapy.

The standard approach to Integra reconstruction requires 2 stages: the Integra forms a neodermis via ingrowth of host vessels, followed by the application of a thin split-thickness skin graft at a later date. The benefits of staging include the ability to use Integra in poorly vascularized wounds, where the direct application of a skin graft might otherwise fail. This staged approach was used by 82.4% of studies in this review, with the majority reporting time to second stage of <30 days (Table 3). Of these staged studies, 53.6% reported complications (Table 3). The need for multiple operations, however, can carry significant risk for some patients. Additionally, donor sites for skin grafts of appropriate size may be limited. Accordingly, 6 studies employed a single-stage reconstructive approach, ranging in publication date from 2004 to 2015.[11,21,27,39-41] Navsaria et al[11] were the first to describe single-stage Integra reconstruction in a patient with a full-thickness burn of the scalp, ear, face, and left arm. Foregoing a skin graft altogether, Navsaria et al[11] applied Integra followed by hair micrografting directly into the dermal regeneration template 12 days later. Despite a minor infection in the postoperative period, the patient achieved 100% graft take on follow-up. Although results of the one-stage procedures are positive, this is likely due to relatively small wound sizes. In general, it is the authors’ opinion that a staged procedure should be used when possible, as it provides effective and durable results for all defect sizes.

Tissue overlying denuded bone without pericranium or fascia is unlikely to survive. Under these circumstances, the vessel-rich diploë is often exposed by burring the outer table of the calvaria. This has been shown to promote wound healing and is a relatively benign procedure.[50] It is particularly common when reconstructing defects postoncologic resection, when the thin subcutaneous tissues of the scalp are often removed to achieve adequate margins. Approximately 74.2% of studies in this systematic review burred the calvaria before Integra placement (Table 4). Of the studies employing bone burring, 90.9% reported graft take of ≥90%. Two studies—again Chalmers et al[22] and Elledge et al[36]—reported graft take of <90%. Interestingly, mean percent take of studies not burring bone was also >90%, though it is possible that wounds included in this calculation may have had residual pericranium or other sources of vascular ingrowth. De Angelis et al,[41] for example, covered denuded bone with locoregional pericranial flaps before application of the dermal regeneration template. Although it can have an impact on final contour, in cases where the calvaria is denuded or dessicated, bone burring is the optimal preparation for Integra placement.

Fenestration of Integra permits fluid egress, reducing the risk of hematoma or seroma formation and subsequent graft failure. Only 9 studies in this systematic review employed fenestration, all reporting percent take >97% (Table 5). Khan et al[24] and De Angelis et al[41] reported small seroma and hematoma formation, respectively, in 1 patient with fenestrated Integra that was resolved by evacuation with a syringe, resulting in 100% graft take at follow-up. Studies utilizing unfenestrated Integra reported percent take ranging from 50% to 100%. Fung et al[37] did not fenestrate Integra before application and reported hematoma formation resulting in 10% graft failure. Although fenestration of skin grafts can result in unsatisfactory cosmetic results, Integra’s staged approach permits fenestration without substantial impact on final site appearance. As a result, it is the authors’ opinion that Integra should always be fenestrated before application.

Similar to fenestration, subatmospheric pressures generated by VAC also promotes fluid egress, reduces wound edema, enhances perfusion, and promotes the formation of a granulation bed.[51] Accordingly, it was the most popular bolster method used in this systematic review, including studies with the largest mean defect sizes (Table 6). Cunningham and Marks[35] reported 100% graft take in a patient with a 400 cm2 wound who was treated postoperatively with VAC. Similarly, Konofaos et al[38] reported 98% graft take in a pediatric patient with total scalp avulsion resulting in a 610 cm2 defect. Although beneficial to wounds of all sizes, by assisting with drainage and promoting ingrowth of host vessels, VAC therapy was likely a crucial component of the positive outcomes in these large scalp defects. Given these findings, we believe VAC to be the best way to manage the wound postoperatively when practical.

As highlighted by this systematic review, there is a significant amount of outcomes data for Integra-based scalp reconstructions, the majority of which demonstrate clear and positive results. To date, however, there has been no systematic and critical evaluation of this body of literature. Although we put forth significant effort to extract objective and quantitative data from each of the articles, a limitation of this review is that there was no normalization of the wounds studied. If a consistent preoperative grading scale was available, a more quantitative analysis of outcomes (ie, meta-analysis) may have been possible. Based on our review, much of the existing published data are from salvage therapy cases or situations in which other options are not appropriate. A favorable results profile in these high-risk wounds supports continued use of Integra when the appropriate wound and patient are chosen. Under these circumstances, Integra-based reconstructions of the scalp can be safe, reliable, and esthetic. Although all reconstructive approaches must be chosen on a case-by-case basis, this systematic review and the authors’ experience with Integra suggest that predictable results can be achieved with use of the dermal regeneration template in the scalp.

PATIENT CONSENT

The patient provided written consent for the use of his image.