Use of Dermal Substrate for the Treatment of Pediatric Deep Partial-Thickness Burns

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In the United States, about 2 million adults and children experience burn injuries every year.¹ Burns are the fifth most common cause of nonfatal childhood injury and the third most common cause of injury-related death among children.^2,3 Overall, approximately 50% of these injuries require inpatient treatment.¹ The need for admission in pediatric patients depends on burn characteristics, such as the percentage total body surface area (TBSA) burned, whether injuries are circumferential, burn depth or region, pain control, wound care needs, concern for non-accidental trauma, and social factors (such as whether the family feels comfortable caring for the patient at home).

Burn management varies significantly with burn depth being a major determining factor. While superficial burns are managed with local wound care, the mainstay in care for deep partial-thickness to full-thickness burns is early excision and closure, with autografting being the gold standard. Early excision is important, in particular for larger TBSA burns, to decrease infection and overall mortality.⁴ However, closure with autografting creates its own functional consequences due to intrinsic scarring of grafted tissue that can cause significant impairment in growing children.^5-7 In addition, autografting requires creation of a second wound, a donor site, which creates challenges in children with larger burns due to a limited amount of unaffected skin to use for donor sites. The challenges associated with skin grafting prompted the development of "dermal substrates" (DS) by Yannas and Burke in the 1980s that act as both anatomic and functional substitutes for native skin and can be applied as part of a single-stage or 2-stage procedure with subsequent autografting.⁸ DS formulations are varied based on supplier but are often composed of a porous acellular dermal matrix applied directly to the wound bed to achieve vascularization and cellular ingrowth and are incorporated permanently while facilitating healing.^8-10 These products stimulate dermal regeneration and hasten wound healing through the provision of a scaffold of extracellular matrix molecules such as collagen, elastin, and proteoglycans that can promote cellular engraftment, migration, differentiation, and proliferation.¹¹

DS application as an alternative to skin grafting has been shown to be effective in adult patients, but there is limited evidence and published long-term outcomes for pediatric burn patients.^9,12-16 We sought to assess the safety of DS use in pediatric burn patients with deep partial-thickness burns and describe clinical outcomes of those who achieved complete wound healing with either DS use alone or with DS followed by subsequent autografting.

Study overview

We conducted a retrospective review of patients aged less than 18 years who underwent burn excision for deep partial-thickness burns only and application of DS at our American Burn Association-verified pediatric burn center from 2015-2023. Patients were identified through our institutional burn registry and data for all cases were obtained through the electronic medical record. Patients were included if their burn injury was clinically determined to be deep partial-thickness only and they were excluded if any portion of their burn injury was determined to have a superficial partial- or full-thickness component. All patients were independently assessed by both a burn-trained nurse and a burn surgeon to confirm burn depth as well as TBSA burned according to the Lund and Browder chart. Burn depth was determined based on wound appearance, sensation, and bleeding during excision.^17-20 Chart review was performed to include patient demographics, injury details, operative procedures, and postoperative wound characteristics including complications. All patients were between 6 months and 8 years out from injury at the time of data collection. Race, as specified by the patient or caregiver using fixed categories, was collected to describe the cohort. This study was approved by our Institutional Review Board with an appropriate waiver of patient consent.

Institutional dermal substrate use

All burn wounds were initially managed with pain control and debridement. Patients most commonly undergo a sedated debridement for the first dressing shortly after admission, at which time burn depth is assessed. Our center typically uses enzymatic debridement for deep partial-thickness burns with either MediHoney ointment (Integra LifeSciences) or Collagenase SANTYL ointment (Smith and Nephew). If devitalized tissue remains in the wound bed, patients are then treated with excision and DS application. In this cohort, all patients were treated with fetal bovine acellular dermal repair scaffold (Primatrix; TEI Biosciences, Inc). Patients undergo tangential excision of the wound with either sharp excision or hydrosurgery (Versajet Hydrosurgery System; Smith and Nephew). DS is then applied, and the wound is covered with either Xeroform (CardinalHealth) or Adaptic (3M) non-adherent dressing that has been coated in triple antibiotic ointment. The wound is then covered with Kerlix (CardinalHealth) gauze and a tubular net elastic dressing depending on the burn wound location. After 4 to 7 days, the wound is reassessed and, if it is healing appropriately, daily dressing changes as above are pursued until wound closure. Initial dressing changes may require general anesthesia depending on patient age, clinical condition, extent of burn wound, and location of burn wound, though most patients undergo either procedural sedation with ketamine or fentanyl or are given oral multimodal analgesics such as acetaminophen or oxycodone. Daily dressing changes are often completed with oral analgesics or without analgesia. At our institution, DS is applied initially for deep partial-thickness burns requiring excision. These patients are monitored for healing, and if epithelialization is delayed beyond 1 to 2 weeks, the patients then undergo autografting. All patients are subsequently followed in the outpatient setting. Once wound closure is achieved, all patients are seen by a multidisciplinary team including physical and occupational therapy and are instructed in the use of moisturizer, scar massage, silicone sheets, and compression garments as indicated.

Clinical outcomes

The primary outcome for this study was the proportion of each patient's burn wound that healed after DS application, both in patients who healed with DS use alone and in those who required subsequent autografting. We first aimed to determine the percent of patients with deep partial-thickness burns who healed with DS application only. We then looked at patients who did not heal with DS application alone and determined for each patient the percent of their wound that required definitive autografting. For this cohort, we calculated percentage TBSA of the burn wound treated with DS during the index operation and compared it with the percentage TBSA of the burn wound requiring autografting during the subsequent operation.

Secondary outcomes included scar severity as determined by development of burn scar contractures, need for scar release with local tissue rearrangement, and/or need for laser therapy for hypertrophic burn scar formation. Laser therapy is offered to patients for hypertrophic burn scars with functional limitations, including medically intractable pruritis. All patients undergoing laser therapy are treated with a fractional CO2 laser using the following settings of Deep mode, Core of 70 mJ, Core Fluence 396 J/cm², 5% fractional coverage, and 7.8 x 7.8-mm pattern size. Pulse dye laser treatment may be added for patients with hypervascularity of their burn scar. The following settings of Fluence of 5 J/cm² and a pulse duration of 1.5 ms are used for pulse dye laser sessions.

Time to wound closure, defined as epithelialization of all portions of the burn wound(s), and postoperative hospital length-of-stay corrected for percentage of TBSA burned was also evaluated. Patients were considered to have developed a contracture if they had diminished range of motion appreciated by a burn surgeon and/or burn-trained rehabilitation therapist during isolated or composite joint movement of the affected areas. Time to wound healing was determined based on the number of days post-injury that the burn no longer required dressing changes.

Healing after DS was also analyzed by body region treated to determine which body regions had the highest proportion of subsequent autografting required for wound closure. Body regions were divided into the following categories: head/neck, torso, back, genitals/buttocks, arm(s), hand(s), leg(s), and foot/feet.

Statistical analysis

Summary statistics were used to describe the patient characteristics. Continuous variables were analyzed with medians and interquartile ranges, categorical variables with sums and proportions. Patients treated with DS alone were compared with those requiring subsequent autografting with χ² or Fisher exact tests as appropriate. A P value of .05 or less was considered significant. All statistical analysis was conducted using SAS 9.4 (SAS Institute Inc).

Cohort demographics and clinical characteristics

There were 205 patients who met inclusion criteria. Median age at DS application was 3.0 years (IQR 1.5, 8.0 years) among patients treated with DS alone and 5.5 years (IQR 2.5, 9.0 years) among those who required subsequent autografting (P = .012) (Table 1). Most patients were male (60.0%) and White (63.9%). Patients most commonly had scald (47.8%) or flame burns (32.2%). Median TBSA burned was 5.0% (IQR 2.0%, 9.8%) among patients treated with DS alone and 7.4% (IQR 4.8%, 14.8%) among those who required subsequent autografting (P = .017). Intensive care unit admission was more common among patients who required subsequent autografting than those treated with DS alone (37.5% vs 17.9%, P = .040), but there was no significant difference in the proportion of patients requiring mechanical ventilation between groups (P = .182).

Outcomes

Most patients (84.4%) had complete wound closure after treatment with dermal substrate alone (Figure 1 demonstrates healing after DS application in 2 patients). Among the 32 (15.6%) patients who underwent subsequent autografting (Figure 2 demonstrates stages of healing for a patient who required autografting), initial median TBSA burn treated with DS was 5.0% (IQR 2.8%, 9.8%) with subsequent autografting covering a median of 2.5% TBSA burn (IQR 1.0%, 5.3%).  The proportion of wound healing between DS placement and autografting was therefore a median 50.0% (IQR 28.1%, 77.5%) of the area of the original burn. Prior to subsequent autografting in this cohort, the proportion of wound healing after DS application alone ranged from 20.0% to 95.0%. In particular, among the 29 patients who had equal to or greater than 15% TBSA burn, only 8 required subsequent autografting. The proportion of healing after DS application among these 8 patients ranged from 25.0% to 85.3%.

Figure 1. Patients with complete wound healing after dermal substrate application. Patient 1 presented with 1% total body surface area scald burn. (A) Patient 1 after initial debridement on the day of injury. (B) Patient 1 on postoperative day 29 after dermal substrate application. Patient 2 presented with 11% total body surface area flame burn. (C) Patient 2 after initial debridement on the day of injury. (D) Patient 2 on postoperative day 22 after dermal substrate application.

Figure 2. Patient who required autografting after dermal substrate application. Patient presented with 12% total body surface area flame burns. (A) After initial debridement on the day of injury. (B) Postoperative day 8 after dermal substrate application. (C) Postoperative day 3 after autograft placement and day 33 after dermal substrate application. (D) Postoperative day 342 after autograft placement and  day 372 after dermal substrate application.

To control for expected differences in length-of-stay based on the size of the burn, postoperative length-of-stay in days was divided by TBSA burn and calculated from the time of index operation for both groups. Postoperative length-of-stay was significantly longer for patients requiring subsequent autografting (0.4 days/% TBSA vs 0.9 days/% TBSA, P = .002) (Table 2). Time to wound healing was calculated based on date of injury for both groups and was significantly longer for patients requiring subsequent autografting (23.0 days vs 44.0 days, P = .001).

Complications were overall low in both groups. Blood loss was minimal among patients with smaller burns and varied among patients with larger burns. Ultimately, 9 (4.4%) patients required any kind of blood product transfusion at any point during their admission. TBSA burn ranged between 12% and 50%. Patients who required autografting more commonly required a blood transfusion than patients who healed with DS alone (18.8% vs 1.8%; P = .001). Patients who only required DS had lower rates of wound infection (2.9% vs 12.5%, P = .029) and scar contracture (5.8% vs 15.6%, P = .045) compared with those who required subsequent autografting. There was no statistically significant difference in need for scar release with local tissue rearrangement between the groups (P = .196).

All patients who presented with burn wound infection did so within 3 weeks of their injury, including 3 patients who presented to medical attention due to concern for burn wound infection after initial management with over-the-counter therapies. All patients who developed a scar contracture were diagnosed within 5 months of their injury except for 1 patient who was diagnosed at 415 days after injury. This patient's burn injury was over a major joint and their clinical course was complicated by serial healing and wound reopening. The patient was moderately adherent to recommendations for compression garment use.

Laser therapy was used for hypertrophic scar management in 44 patients (21.5%). Patients who required subsequent autografting were more likely to have laser therapy compared with those treated with DS alone (53.1% vs 15.6%, P = .001). Many patients underwent laser therapy for multiple indications, which included functional limitations (n = 39) and medically intractable pruritis (n = 25). While there was no difference in patients who underwent laser therapy for functional limitations between the groups (P = .634), medically intractable pruritis was more common among patients who healed with DS alone (74.1% vs 29.4%, P = .005).

Wound healing based on body region

Wound healing was assessed for the entire cohort based on body region treated with separate consideration for head/neck, torso, back, genitals/buttocks, arm(s), hand(s), leg(s), and foot/feet (Figure 3). The most common body regions treated with DS in this cohort were arms (n = 123) and the least common were the genitals/buttocks (n = 19). Overall, subsequent autografting was most commonly required to the arm(s) (n = 13), leg(s) (n = 12), and torso (n = 9). The body region with the greatest proportion of patients requiring subsequent autografting after DS application was genitals/buttocks (4/19, 21.1%). Burn regions with the lowest proportion of patients requiring subsequent autografting after DS application were the head/neck (3/76, 3.9%), hand(s) (3/92, 3.3%), and foot/feet (0/30, 0%).

Figure 3. Number of cases requiring autografting after dermal substrate application by body region.

In this study of pediatric burn patients with deep partial-thickness injuries treated with a single dermal substrate, wound closure after index operation for DS application was high, postoperative hospital length-of-stay corrected for total body surface area burned was short, and complication rates were low. Among the small proportion of patients who required subsequent autografting, only 50% of the original burn wound required autografting. Our findings provide valuable insight into the use of DS in pediatric burn patients with deep partial-thickness burns.

The majority of our cohort underwent treatment with DS alone, highlighting the feasibility and effectiveness of DS in managing a significant proportion of deep partial-thickness burn injuries in children. The median age at the time of DS application was 3.0 years, underscoring the applicability of DS even in our younger patients. Our findings align with previous studies demonstrating that DS can be used as a primary intervention for acute burn care in adults and adds to the currently limited literature addressing DS use in children.^16,21,22 DS are a heterogeneous group of products, and patients in our study received a single product that has been studied primarily in case reports or in recent larger studies from our institution.^9,10,16,23 A recent systematic review of burn reconstruction methods found only one high-quality study of bioengineered skin substitute, which demonstrated reduced morbidity and improved long-term recovery in extensive full-thickness burns.^24,25 A randomized pediatric clinical trial of 20 patients treated with a different DS than was used in our patients, Integra dermal regeneration template, demonstrated improved scar outcomes among patients treated with this product compared with patients who underwent primary autografting.²⁶ Another study of the DS MatriDerm demonstrated similar outcomes in scar characteristics between patients treated with DS and those treated with split-thickness skin grafts.³ These are consistent with our findings of overall low frequency of contracture development, and specifically lower frequency of contracture development among patients treated with DS alone.

Notably, patients requiring autografting had larger median TBSA burns, more commonly needed blood transfusion, and were more likely to require intensive care unit admission, suggesting that their burns could have been more extensive or that the circumstances of their burn injuries required a higher level of care. Furthermore, the longer postoperative length-of-stay per TBSA burned and time to wound healing in the autografted group underscore the increased complexity of cases requiring this intervention. Longer length-of-stay and time to wound healing among patients who underwent subsequent autografting compared with those who underwent DS application alone are expected given that autografted patients had 2 operations and we typically wait around 2 weeks to assess the effectiveness of DS in promoting healing before committing a patient to autografting.

Among our patients, upfront use of DS spared most children the morbidity of autografting and enabled minimization of donor sites among the fraction who did require autografting. While the majority of patients healed their burn wounds after treatment with DS alone, among those who required autografting, donor site size was typically decreased due to the median 50% wound closure after DS use alone. This intermediate healing status suggests that DS contributed meaningfully to wound closure, particularly because every patient who underwent subsequent autografting had at least 20% wound closure after DS use with some as high as 95%. Most patients in our cohort had smaller TBSA burns, but among the few who had burns equal to or greater than 15% TBSA, there was either complete wound healing with DS application or a minimum of 25% wound closure with DS use alone. This suggests that DS may be an impactful treatment option for larger burns where donor sites are scarcer.  

Complication rates were low among this cohort of patients primarily treated with DS alone, and all adverse events were more common among children who required subsequent autografting. Children are at high risk for developing contractures while healing burn wounds since they are prone to higher TBSA burns and deeper injuries as compared with adults due to their smaller body size and relatively thinner skin.^1,28 Nearly all contractures that developed in this cohort did so within the first 6 months after injury, making this period of time critical for monitoring scar progression for patients at the highest risk for contracture development. Children are also uniquely vulnerable to sequelae from contractures due to their ongoing bodily growth. Contractures can limit functional outcomes, in addition to affecting cognitive and emotional development, making minimization of this complication important. Contracture occurred in less than 10% of the overall population but in over 15% of patients who required subsequent autografting. These data demonstrate return to functional baseline for most children after DS application alone for deep partial-thickness burns with minimal functional impact, making a compelling argument for using this treatment for burn wound management. Furthermore, in this cohort, less than 5% of patients developed a wound infection; however, patients treated with DS alone had significantly lower wound infection rates than those patients who required subsequent autografting. All patients who developed a wound infection did so within 3 weeks of sustaining their injury, which suggests that while wound infection was rare, patients who did develop an infection may have had more difficulty with DS adherence and thus required additional intervention since all infections occurred within the critical 2 to 3-­week period post-injury where need for autografting is determined. This highlights the importance of minimizing wound infection in order to help prevent need for autografting among children treated with upfront DS.

DS application frequency varied by body region. In this cohort of patients, children most frequently had DS application to their extremities and least commonly had DS application to their genitals/buttocks. This is likely in part due to a low threshold at our institution to apply DS to deep partial-thickness injuries of the extremities. Low rates of DS application to the perineum are likely due to a higher threshold to operate on burns of the genitals/buttocks. Our practice is to allow burns in this region time to heal without surgery and instead utilize serial dressings, given low need for optimal cosmesis as well as challenges with friction and hygiene. Despite low DS application rates to the genitals/buttocks, this region had the highest proportion of patients who needed subsequent autografting, suggesting the overall difficulty with wound healing in this region of the body especially in pediatric patients.

There are some notable limitations to this study. Since this was a retrospective study, we were limited to the information recorded in the chart. Our clinical practice improved to better integrate collection of scar characteristics and functional outcomes throughout the study window. However, due to high missingness of scar characteristic data among earlier patients, scar measurements could not be reported in all patients. Improving consistency in outpatient data collection regarding scar appearance, functional outcomes, and the psychosocial impacts of burn scars can help direct resources for optimizing patient care and is an area of active quality improvement at our institution. Similarly, although nutritional status is known to impact wound healing, at our center, nutritional parameters are recorded for critically ill patients but are not routinely recorded for all floor patients so they cannot be reported due to a high degree of nonrandom missingness. Additionally, our institution primarily used a single brand of dermal substrate during this time frame for deep partial-thickness burns, which may limit generalizability of our findings for institutions that use different products. However, this consistency in using the same product throughout this study provides meaningful information for its use within our institution to discuss with patients and families and represents the largest study to date of pediatric patients treated with this particular product.¹⁶

Furthermore, while burn depth at our institution is assessed independently by burn-trained nurses and experienced burn-specialized surgeons based on sensation, appearance, and bleeding during excision, no designated instruments are used to determine burn depth, and it is thus possible that portions of burn wounds had depth imperfectly recorded. Burn cases are typically performed by 2 burn surgeons, who each independently verify burn depth and suitability of the wound bed for DS application. Clinical assessment of burn depth remains the most common method for assessing burn depth worldwide, making our findings using this technique generalizable.^17-20 To reduce the likelihood of variability in burn depth affecting our data, only patients with isolated deep partial-thickness wounds were included, and any patient with superficial partial- or full-thickness burns were excluded from our analysis. Finally, given the overall low number of patients requiring subsequent autografting at our institution, expanding research to include multi-institutional data can facilitate a more robust comparison of patients who required autografting to identify independent predictors of failure of wound closure with DS alone.

Children with deep partial-thickness burn injuries treated with dermal substrates alone had a high proportion of wound healing and low rates of complications. Although some patients may require subsequent autografting after dermal substrate application, the proportion of the wound requiring autografting was half the size of the original wound. The frequency of autografting did not seem to vary greatly based on the body region initially treated with dermal substrate, aside from burns to the genitals/buttocks. Finally, the overall rate of complications, including hypertrophic scar formation requiring either reconstruction or laser treatment, was lower in patients treated with dermal substrate alone compared with those patients requiring subsequent autografting.