Dermal Regeneration Matrix in the Treatment of Acute Complex Wounds

The advent of dermal regeneration matrices (DRMs) was a major advancement in wound treatment. These products were initially used in the management of burn sequelae, and the indication for use was later expanded to other types of injuries, both acute and chronic.

Treatment of patients with complex wounds has changed over time from a simple survival and decreased morbidity to an additional emphasis on functionality and aesthetics.^1-4 Split-thickness skin grafting (STSG) remains the treatment of choice for covering extensive raw areas, even though aesthetic and even functional results may be limited.^2,3,5-8 The formation of hypertrophic scar tissue with limited elasticity after STSG may result in restricted joint mobility.^2,3,5-8

The collaboration of surgeons and basic scientists has resulted in the development of tissue engineering alternatives and synthetic products to manage full-thickness wounds based on the principle of substitution by similar tissues.^5,9-11 Unfortunately, use of DRMs remains limited, even in the supplementary public health system of Brazil, because of the high costs. Dermal regeneration matrices are available in the Brazilian public health system for specific use in the management of burn sequelae.

This case series reports the use of a DRM either 1-mm or 2-mm thick, in a 1-step and 2-step approach, respectively, for the management of acute complex wounds in a private hospital.

This retrospective cohort study included patients with acute complex wounds treated by the author at Rede D’Or São Luiz Hospital (São Paulo, Brazil) between January 2015 and December 2018. Treatment consisted of debridement of devitalized tissue, wound bed preparation, implantation of DRM either 1-mm or 2-mm thick, and STSG. Multiple wounds were included, with no restrictions related to etiology or topography. Exclusion criteria were chronic wounds (ie, more than 3 weeks’ duration before the initiation of treatment), injuries sequelae treatments, and other types of salvage procedures to manage complications.

Negative pressure wound therapy (NPWT) was used in all cases, with dressing changes performed every 4 to 7 days. V.A.C. Therapy System (3M) was used in continuous mode at a pressure level of  −125 mm Hg. A silver-coated foam dressing was used during the initial phase of treatment. A nonadherent polyvinyl alcohol foam dressing was used after the implantation of the DRM and after STSG.

Implantation of the DRM was indicated when the wound was in good condition, that is, once granulation tissue was present and infection treatment was completed. Proper preparation, cleaning, and hemostasis of the wound are recommended before the matrix is applied. It is important to note that DRM is not a substitute for basic debridement, load relief, and local vascularization optimization procedures.

The product used in this case series (MatriDerm; MedSkin Solutions Dr. Suwelack) can be used immediately after removal from the package. No special preparation is required; the matrix is cut to size before application. After the material is placed on the wound, the product is hydrated with saline solution until the product changes color, from white to translucent.

In cases in which it is possible to use 1-mm–thick DRM, STSG is performed simultaneously. The DRM and the skin grafts were fixed with stitches or staples to the margins and the wound site. Routine management for all cases included the complementary use of NPWT to aid fixation and integration of the DRM and skin grafts.

Split-thickness skin grafting should not be performed in the same procedure if a 2-mm–thick DRM is required. In cases in which a 2-mm–thick DRM is required, STSG can be performed 6 to 9 days after application of the matrix. The same steps are used for fixation and NPWT after this stage. In such cases as the current study, NPWT was used to accelerate and improve maturation and integration of the DRM.

The result at 12 months postoperatively was the primary outcome measure. This was assessed using the Vancouver Scar Scale (VSS), which has 4 subscales: pigmentation (0–3), pliability (0–4), vascularization (0–3), and scar height (0–4).¹⁰ In each subscale, normal presentation receives a score of zero. The highest possible score is 14. No other statistical analyses were conducted.

The author chose to include different wound etiologies and topographies. Analysis of functional results, such as angular extension or range of motion, is not included.

Twenty patients (6 female, 14 male) with an average age of 47.3 years (range, 20-74 years) were treated (Table). Trauma was the most frequent etiology, occurring in 8 patients (4 full-thickness burns, 4 degloving injuries). Seven patients presented with complications related to surgical procedures (ie, surgical site occurrence), and there was 1 instance of infection (fasciitis). Two patients presented with open wounds after treatment of infection resulting from diabetic foot syndrome, and 2 were treated for skin necrosis caused by hypertonic solutions extravasation injuries of the upper limbs.

The measurement of the treated wounds varied between 4 cm × 5 cm to 42 cm × 28 cm, in the greatest dimensions. Negative pressure wound therapy was used for all patients in the wound preparation phase. It was also used after DRM implantation (when 2-mm thickness was used) and after STSG.

In 6 cases, DRM that was 1-mm thick was used, and STSG was performed in the same procedure. Visual observation indicated almost 100% integration assessed on postoperative day 5. In 14 cases, DRM that was 2-mm thick was used, and STSG was performed 7 to 9 days later. In all cases, almost 100% integration of the implant was achieved. Patients received a thin STSG, with integration rates close to 100%, assessed on postoperative day 5. Wound healing progression is illustrated in Figure 1 and Figure 2.

No complications (eg, infection, loss of DRM implants or STSG, inflammatory or allergic reactions) occurred in either treatment group. The VSS scores at 12-month follow-up ranged from zero to 6 (average, 2.25 ± 0.65).

The DRM used in this report has been available in Europe since 2004. It is of bovine origin, containing collagen type I, III, and V derived from the dermis, without cross-linking, associated with alpha elastin hydrolyzed, in a proportion of 3%, derived from the nuchal ligament. The product is macroporous, with pore diameters of 20 µm to 100 µm.^1,5,8,10

The DRM can serve as a structure for dermal regeneration and for modulating scar tissue formation; it also has hemostatic properties.³ The collagen in the product degrades and is reabsorbed within 6 weeks; it is replaced by the autogenous fibroblast that invaded the neodermis.^6,9,11

According to some authors, elastin is the reason for the improved performance of the studied DRM compared with other matrices.^9,12,13 The reduced granulation tissue formation that occurs at the earliest stage of healing results in the formation of collagen with a more random organization.^1,14,15 In humans, there is no proper regeneration or repair of elastin fibers destroyed in a wound.¹⁵ Elastin regulates collagen contraction, interrupts differentiation from fibroblasts to myofibroblasts, and reduces scar tissue formation.¹⁶

For several years, the 1-mm–thick DRM evaluated in the current case series was the only product available for use in a 1-step procedure with STSG.^6,14,16 In 2010, a matrix with similar characteristics (Integra Dermal Regeneration Template Single Layer [Integra LifeSciences]) was released.¹⁵ Other currently available DRMs require 2-stage procedures, whether a single-layer product (eg, the studied DRM of 2 mm thickness), a double-layered product (eg, Integra [Integra LifeSciences], Nevelia [Symatese Aesthetics], Pelnac [Gunze]), or a trilayered product (Oasis Ultra [Smith + Nephew]).

In the current case series, the use of a 1-mm–thick DRM immediately followed by STSG did not result in increased complication rates. Favorable results were observed in the 6 patients treated thus in the current series and have been reported elsewhere.^16,18-20

Results observed in patients treated with the DRM used herein include increased elasticity and pliability, reduction in scar contracture, and optimization of aesthetic and functional results.^1,4,11,21 In the current case series, stable results were observed at a minimum of 18 months postoperatively, and subjective analysis indicated improvement over time, with no wound healing complications.

Previously published studies have reported better results with DRM compared with conventional STSG as measured by VSS scores and joint mobility measures.^{5,15,17,18,22} van Zuijlen and colleagues^7,11 described gains of approximately 30% in extension and elasticity, and of 50% in flexibility using the DRM. In other studies in which factors such as humidity and water loss were analyzed, results also were better with the use of DRM.^2,19

Dermal regeneration matrices can be used to cover tendons, bones, and joint capsules, which avoids the need for more elaborate reconstruction, such as microsurgical flaps.^12,14,17,20 They can also be indicated as a rescue treatment in patients in whom other methods have failed. Use of the product in patients with injuries to the dorsum of the hand, as observed in 3 cases in the current series, anticipated physiotherapeutic rehabilitation process, also avoiding tendon or joint retractions.

Dermal regeneration matrices have low associated morbidity rates and a relatively simple learning curve.^11,21 Another advantage that should be considered is the reduced morbidity for the donor areas, because thinner skin grafts can be used.^5,14,19

Negative pressure wound therapy increases matrix integration rates, shortens time to skin grafting, and reduces associated complications.^3,5,14 The author thinks routine use of NPWT for all patients in this case series was a significant factor in the results achieved and in the absence of complications, even more considering the profile of wounds treated, including high exudative and large wounds in difficult areas.

Costs are a limiting factor in the use of DRM in the management of acute complex wounds. In the initial phases of treatment, costs are higher than other options because of the cost of the product; however, final overall costs are decreased because of shorter wound resolution time, in addition to lower complication and morbidity rates.^4,15,22 Gains in functional improvement in such critical realms, like reliability and movement (eg, joint, dorsum of the hand), compensate for the financial costs associated with the product.^3-5,22

Currently, no tissue-engineered skin substitute meets all the requirements of an ideal substitute, nor can it be used to achieve healing outcomes that are equal or superior to that achieved with autologous tissues.^9,10,21 Health professionals should consider different types of products based on the particular treatment goals ^4,18 To date, no one particular type of DRM has been shown to be superior to any other.^5,7,9

The limitations of this study include the small number of cases, relatively short follow-up period, absence of a control group, and heterogeneity of etiologies. However, the results of the current case series seem to be superior to those of previously published studies in which conventional STSG was used in the management of acute complex wounds.

The current results showed that using DRM and NPWT to treat patients with acute complex wounds that required STSG was a good option to improve healing outcomes. Such treatment is an important option in the armamentarium of reconstructive techniques.