Repair of Facial Dog Bite Wound Utilizing Cryopreserved Umbilical Cord Allograft

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Craniofacial injuries are the most frequently observed traumas of the pediatric population in the United States, with the majority being limited to soft tissue damage.¹ Healing of these acute wounds can be complex, especially if there is significant cutaneous and soft tissue loss. Utilization of graft materials that target multiple mechanisms of wound healing could lead to improved cosmetic results.² Human birth tissue (BT), including amniotic membrane (AM) derived from the placenta and umbilical cord (UC), can be harnessed for wound healing and tissue regeneration due to the inherent growth factors, cytokines, and signaling molecules that enable fetal development.² Reported benefits of AM and UC include the ability to inhibit fibrosis, promote epithelialization, and reduce wound pain. In addition, BT is non-immunogenic and contains both anti-inflammatory and antibacterial properties.^3-6 There are multiple methods of processing and storing of BT for clinical applications, including micronization into powder form, dehydration, chemically crosslinking, cryopreservation, and fresh hypothermic treatment.^2,6,7

In recent decades, given their properties and clinical utility, applications of AM and UC have expanded widely. AM and UC specifically have found success in ophthalmologic procedures as well as the treatment of burns, fistulas, lower extremity ulcers, and chronic wounds.^2,3 While numerous studies have reported the benefit of using ultra-thick AM for chronic wounds to promote healing, few studies have reported its use in the treatment of acute cutaneous and soft tissue wounds.

The authors present a case in which cryopreserved ultra-thick AM was used in the acute setting as a wound dressing in a patient with significant facial soft tissue loss due to a dog bite.

This is a single case report of a patient who presented to an academic tertiary pediatric hospital. IRB exemption was obtained, and operative and postoperative clinic notes were reviewed. Images were obtained with consent from the patient and parents.

A 10-year-old female presented to the emergency department after experiencing a dog bite to her left cheek and upper lip (Figure 1). After cleaning and multilayered primary closure of portions of the laceration, the residual soft tissue defect was approximately 2.5 cm × 3 cm. There was multilayered tissue loss, including a portion of the upper lip and oral commissure.

Figure 1. Facial wound of the left cheek and upper lip with significant cutaneous and soft tissue loss.

A 3-cm × 2.5-cm piece of cryopreserved ultra-thick AM allograft (NEOX 1K, BioTissue, Inc.) was used to cover the area of tissue loss and sutured into place. Antibiotic ointment was applied to the suture lines and a xeroform petrolatum gauze dressing was applied. She was discharged with wound care instructions using dilute hydrogen peroxide, antibiotic ointment, and xeroform dressing changes.

At 1-week follow-up, the wound was healing well with the ultra-thick AM graft still in place (Figure 2). It was noted that she had mild peripheral granulation and early epithelialization without erythema, edema, or purulence. Minimal pain was reported. At 3-week follow-up, the central portion with prior missing tissue had become fully epithelialized with the graft no longer visible. There was noted mild retraction of the lip at the commissure and thickened subcutaneous scarring as expected but causing no functional deficits (Figure 3). Silicone gel and sheeting in addition to daily scar massage was initiated and continued for the next 3 months.

Figure 2. Patient at 1-week follow-up with the cryopreserved umbilical cord allograft present within the wound bed.

Figure 3. Patient at 3-week follow-up with central portion of tissue loss healing with contraction and scarring.

At 4-month follow up, the scar had softened, and the wound was much smaller than the original defect now with full epithelialization (Figure 4). She underwent scar revision surgery, including wedge lip resection, 1 year after the dog bite injury due to retraction of the oral commissure and irregular scar contour, although it was not causing any functional deficit or drooling (Figure 5).

Figure 4. Patient at 4-month follow-up with continued healing of the wound.

Figure 5. Patient undergoing scar revision and wedge lip resection 1 year after initial injury.

Complex wounds, including facial dog bites, require health care providers to identify treatments that not only provide wound closure but also result in optimal reconstructive and functional outcomes. While synthetic skin substitutes do exist, they lack a resemblance to natural skin due to an absence of a basement membrane and multiple layers of tissue being absent.⁶ Synthetic skin substitutes are not optimal for restoration of volume, but instead serve as a scaffold with a defined thickness that can impede regenerative healing due to reduced matrix degradability and potential foreign body response.⁸ On the contrary, various benefits of human BT allografts make them a useful tool in wound therapy.^3,7

Human ultra-thick AM specifically has been shown to promote epithelialization as it contains numerous growth factors, including epidermal growth factor, keratinocyte growth factor, and basic fibroblast growth factor.⁹ These growth factors enhance the epithelial cells’ ability to proliferate, migrate, and differentiate, thus promoting regenerative wound healing.³

Furthermore, ultra-thick AM has anti-inflammatory properties, rendering it a useful tool for wound healing. Inflammation is a key stage in wound healing, but its chronicity can lead to delayed healing and excessive scarring. This process can be mitigated by inhibiting the production of pro-inflammatory cytokines.³ In addition, AM has been shown to promote apoptosis of activated but not resting pro-inflammatory cells and reduce macrophage expression of pro‑inflammatory cytokines, such as TNF‑α and interleukin (IL)‑6.¹⁰

In addition to its anti-inflammatory properties, the use of ultra-thick AM has also been shown to reduce pain in chronic wounds.¹¹ The reduction in pain can potentially be attributed to the fact that the AM serves as a barrier by covering exposed nerve endings and that dressing changes with AM are less frequent compared to most other wound care regimens.^3,6 The reduction in pain may also be attributed to its anti-inflammatory actions, which reduce pro-inflammatory stimuli to nociceptor neurons. For example, Acevedo et al reported that in the treatment of chronic and ischemic wounds, patients treated with ultra-thick AM not only had expedited wound closure but also notable reduction in pain within 1-7 days after application.¹¹

One of the most attractive factors about ultra-thick AM in reconstructive surgery is its potential to inhibit or at least lessen fibrosis. The anti-inflammatory and anti-scarring actions of human AM can be attributed to the HC-HA/PTX3 complex located in the stroma of the AM and UC.⁷ HC-HA/PTX3 has been shown to directly exert anti-scarring actions by inhibiting pSMAD2/3 nuclear translocation, suppressing the TGF-β1 promoter activity by cultured human fibroblasts, preventing α-SMA expression, and reducing myofibroblast differentiation.¹²

While the use of human AM and UC has increased greatly over the past few years, there is still limited literature on the use of cryopreserved ultra-thick AM for acute wounds.² Every trauma injury is unique and may require various tools and techniques for reconstruction. This case highlights that cryopreserved ultra-thick AM is effective and useful as a wound dressing material and promotes regenerative healing.

Limitations of this study are those inherent to a case report. As this study only follows 1 patient, broad conclusions and recommendations are difficult to make. A cause-effect relationship cannot be firmly established from these findings.

Human birth tissue is an effective adjunct treatment in acute wound management. Full epithelialization and good healing resulted in this case of soft tissue loss due to a facial dog bite injury, which was repaired using primary closure and a human birth tissue membrane for the area of tissue loss. This case demonstrated specifically that ultra-thick AM is an effective adjunctive treatment modality for wound care and may potentially enhance tissue reconstruction in the acute trauma setting, likely due to its non-immunogenic, anti-inflammatory, and antibacterial properties. Prospective studies are indicated to determine the degree of enhancement that birth tissue may have on acute wound care.

Authors: Addison Yee, BS¹; Kyle P. Davis, MD^2,3; Zachary Anderson, MD^2,4; and Larry Hartzell, MD^2,5

Affiliations: ¹University of Arkansas for Medical Sciences College of Medicine, Little Rock, AR; ²Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, AR; ³Department of Otolaryngology, Saint Louis University School of Medicine, St. Louis, MO; ⁴Peak ENT, Provo, UT; ⁵Division of Pediatric Otolaryngology, Arkansas Children's Hospital, Little Rock, AR

Disclosure: The authors disclose no financial or other conflicts of interest.

Correspondence: Larry Hartzell, MD, 1 Children's Way, Slot 836, Department of Otolaryngology: Pediatric division, Little Rock, AR 72202; LDHartzell@uams.edu

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