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A Premature Infant with Skin Injury Successfully Treated with Bilayered Cellular Matrix
Skin is an important body component that performs many critical functions. First in the line of defense for the immune system, skin helps protect the body from invasion by potentially dangerous substances.1 Body temperature regulation is aided by the skin's ability to excrete moisture and radiate or conduct heat as needed.2 In addition, the skin represents the body's most extensive sense organ for receiving tactile, thermal, and painful stimuli.3
Preterm infants are born with organ systems that have not had an opportunity to develop completely. These underdeveloped organ systems are unable to perform physiologically as well as those of their full-term counterparts. Infants of less than 24-weeks gestation are born with transparent, friable skin that is unable to provide the full range of protective functions intrinsic to fully mature skin. Moreover, the skin of preterm infants is more easily damaged because of the relative thinness of the three skin layers (epidermis, dermis, and subcutaneous fat), limited attachment points of the epidermis to the dermis, and immature production of lipids.4 These deficiencies of the skin’s integrity leave the preterm neonate vulnerable to infectious complications and to disorders involving fluid and electrolyte homeostasis. As a result of these complications, the likelihood of skin breakdown may be increased and wound healing may be impaired.
Interventions in caring for the skin of preterm infants are directed toward minimizing trauma and preventing fluid loss. Application of topical emollients reduces transepidermal water loss and serves as a barrier to irritation.4 Lamb's wool, silicone gel mattresses, and various other support devices are used to relieve pressure as much as possible to prevent the development of decubitus ulcers.5 When ulcers develop, treatment usually is focused on providing meticulous wound care in an effort to control the local wound environment and prevent infection. In most cases, these wounds are allowed to heal by secondary intention. The following case report describes the use of bilayered cellular matrix (BCM) (OrCel™, Ortec International, Inc., New York, NY), to expedite healing of a skin wound in a preterm infant.
Case History
A 2-day-old male neonate born 17 weeks prematurely at 23 weeks gestation was transferred to the authors' neonatal intensive care unit (NICU). The infant weighed 500 grams at the time of NICU admission. He had a denuded left hip wound (see Figure 1) measuring 2.0 cm x 1.5 cm. He also had a small skin tear involving the right axilla. No signs of fluid or electrolyte disturbances were noted. The NICU consulted the Burn and Wound Center, which obtained BCM. Use was on a per patient emergency basis.
Applying BCM involves opening the cassette containing the product and removing the nonadherent backing protecting the fibroblasts. The product is lifted out of the cassette with two noncrushing sterile forceps and draped over the wound bed with the backing protecting the keratinocytes oriented superiorly (see Figure 2). Bilayered cellular matrix conforms easily to the wound. The product is not fragile and maintains structural integrity upon placement on the wound. The porosity of the product allows for fluid absorption and for excess wound fluid passage to the outer dressing. This prevents the BCM from lifting off the wound bed.
Bilayered cellular matrix was applied (see Figures 3 and 4) to the wounds and covered with Xeroform (Kendall, Mansfield, Mass.) gauze dressing. Photographs were taken on day 0 after BCM application. The BCM product was left undisturbed with the overlying dressings in place until day 3 (see Figure 5) with gauze dressing changes performed as needed to maintain a moist environment for BCM and to control contamination from incontinence. On day 4, the wound measurements were reduced to 1.0 cm x 0.5 cm and on day 6 (see Figure 6) continued to have clean granulation tissue present. By day 14 (see Figure 7), both wounds were completely healed. Throughout the course of treatment, no signs or symptoms of infection were observed. Critical care and nutrition management were continued until the baby thrived and he was discharged to his home 3.5 months after birth. Upon discharge (see Figure 8), the cosmetic outcome of the areas was evaluated. The BCM-treated areas were fully epithelialized. Some slight hypopigmentation was noted but no scar tissue was evident.
Discussion
Bilayered cellular matrix is a layered, cultured cell allograft consisting of viable keratinocytes and fibroblasts obtained from donor neonatal foreskins. The fibroblasts are seeded onto the porous inner surface of a cross-linked bovine collagen sponge matrix. These cells proliferate and migrate to form a dermal layer component. The nonporous outer surface of the matrix is laminated with polymerized type 1 collagen and seeded with donor keratinocytes. Once applied to a wound site, BCM adheres to the wound and promotes the ingrowth of fibrovascular tissue. Bilayered cellular matrix promotes rapid wound healing that is believed to be mediated by cytokines and growth factors stimulated by the allogeneic fibroblasts and keratinocytes in the BCM wound healing agent. The utility of BCM in promoting wound healing has been demonstrated in a variety of clinical conditions.6
Wounds in premature infants are generally managed conservatively and allowed to heal by secondary intention. Two literature references were found describing the use of biologic dressings to manage premature infant skin injury.7,8
Ng et al7 reported that meticulous skin care with normal saline washes and the use of a "second skin dressing" covered with sterile gauze twice daily resulted in rapid formation of a membranous-like fibrous tissue layer covering denuded areas in an 875-g infant born at 27 weeks gestation with severe congenital absence of skin. This infant was noted at birth to have extensive areas of skin loss involving an estimated body surface area of 24% distributed mainly over his scalp and extremities but sparing most of his chest and abdomen. The lesions consisted of raw denuded surfaces that exposed the underlying blood vessels. Had this patient survived, he would most likely have required skin grafting because of the extent of his injuries.
In patients with gastroschisis and omphalocele whose silastic prostheses became detached before complete abdominal closure, biologic dressings of porcine skin or amniotic membrane xenografts have been attempted to affect wound closure. Over a 2-year period, Seashore et al8 treated a total of 11 gastroschisis patients and 5 omphalocele patients with biologic dressing. Of the 11 gastroschisis patients, nine were treated with porcine skin and two were treated with amniotic membrane xenografts. One patient, who also had patent ductus arteriosis and intractable congestive heart failure, died on day 30 after having had porcine skin dressings applied on the 14th day. Dressings were used a mean of 31 days in the six patients who were treated with dressings until the wounds were completely healed. In these patients, wound closure was complete by a mean of 45 days. The remaining four patients were treated with biologic dressings for a mean of 17.5 days before undergoing surgical closure of the defect. In the five patients with intact omphaloceles in whom biologic dressings were used for all or part of their treatment course, the average time until complete closure was 55 days.
Although the use of biologic wound healing agents has been described in the literature as a secondary treatment of gastroschesis and omphaloceles in premature infants, the patient described in this case represents the first report of a specific biologic dressing with viable cells being used to treat an isolated skin wound in a preterm infant.
Though similar in character to the wounds of the patient described by Ng et al, the case patient's injury was not as extensive nor is it comparable in severity to the integument disruption seen with gastroschesis and omphalocele. Nevertheless, a favorable outcome (complete wound closure by day 14) was obtained at the hip wound site. Furthermore, BCM, in contrast to the xenografts used for the gastroschesis and omphalocele patients, requires only a single application.
In the opinion of the attending clinicians caring for the case patient, BCM application facilitated wound healing when compared to the healing times of similar lesions seen in the neonatal intensive care unit. However, the lack of a control wound makes it impossible to determine definitively if complete wound closure occurring in 14 days with BCM represents accelerated healing. The result obtained in this case suggests that controlled trials are warranted to determine if BCM accelerates wound healing and reduces the need for more invasive wound treatments compared to meticulous wound care strategies in preterm infants. Cases of gastroschisis and omphalocele requiring secondary wound closure strategies might also represent a clinical setting where care of preterm infants will be improved by the use of BCM.
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7. Ng PC, Lee CH, To KF, et al. Severe congenital absence of skin in a preterm infant. J Paediatr Child Health. 1999;35:306-308.
8. Seashore JH, MacNaughton RJ, Talbert JL. Treatment of gastroschisis and omphalocele with biologic dressings. J Pediatr Surg. 1975;10:9-17.
