Exploring Exosomes for Pediatric Ischemic Auricular Flap Repair

Summary:

Avulsions of the upper third of the ear often present with skin flaps of compromised vascularity. Although initially viable, these flaps may later develop ischemic changes ranging from epidermolysis to full-thickness necrosis, delaying healing. Angiogenesis, primarily mediated by vascular endothelial growth factor (VEGF), is essential for tissue repair. In children, VEGF promotes endothelial cell migration and proliferation, accelerating wound healing. Currently, VEFG is the primary target of therapeutic angiogenesis approaches, and microRNAs have emerged as key angiogenic regulators. Exosomes have gained relevance in regenerative medicine as paracrine mediators of skin repair. VEGF expression peaks between days 3 and 7 after injury; hypothetically, this VEGF window is considered optimal for delivering proangiogenic exosome cargo directly to the ischemic skin flap. By providing microRNA-mediated proangiogenic signals early in the healing process, exosomes may enhance tissue perfusion and improve flap survival. We report the case of a 10-year-old girl with a partial soft-tissue degloving injury of the upper third of the auricle. The avulsed flap had folded onto itself, causing venous congestion. After repositioning, flap distal congestion persisted and progressed to partial tissue necrosis by postoperative day 3. The wound was treated with Rosa damascena stem cell–derived exosomes, resulting in complete skin regeneration, evident by day 14. This case demonstrated the safe clinical use of Rosa damascena stem cell–derived exosomes in a pediatric posttraumatic ischemic auricular flap, suggesting their potential as a therapeutic option for flap salvage in children. Larger controlled studies are required to confirm efficacy and establish treatment protocols.

Auricular injuries are common in facial trauma due to the ear’s exposed, lateral position and thin skin overlying its cartilaginous framework. The upper third is particularly vulnerable to avulsion, often presenting skin flaps with compromised vascularity. High-energy trauma can forcefully detach skin, disrupting subdermal capillaries and microcirculation, leading to ischemia. The initial appearance of avulsed tissue may be misleading, as skin that appears viable can later develop ischemic changes ranging from epidermolysis to full-thickness necrosis, delaying wound healing.¹

Angiogenesis, primarily mediated by vascular endothelial growth factor (VEGF), is essential for tissue repair. In children, VEGF stimulates endothelial cell migration and proliferation, accelerating repair of tissues damaged by surgery or trauma. Currently, VEFG is the primary target of therapeutic angiogenesis approaches, and microRNAs (miRNAs) have emerged as key angiogenic regulators.²

Exosomes have gained relevance in regenerative medicine as paracrine mediators of skin repair. These nanosized vesicles (30–200 nm) carry messenger RNA, miRNA, and cytokines that regulate cell signaling. Preclinical studies using adipose-derived stem cell exosomes (ADSC-Exos) demonstrate enhanced angiogenesis and tissue regeneration in ischemic flaps and necrotic wounds.³ Pelizzo et al⁴ showed that topical ADSC-Exos restored skin architecture in young animal models, suggesting potential pediatric application. However, adipose tissue harvesting is limited in children, reducing clinical feasibility.⁴

Plant stem cell–derived exosomes such as those from Rosa damascena (RSCEs) contain biomolecules, including RNAs capable of modulating skin cell functions similarly to human exosomes.⁵ This case report explores the therapeutic potential of RSCEs to support tissue regeneration, accelerate healing, and improve the aesthetic outcome in a pediatric auricular skin flap with partial necrosis.

CASE REPORT

A 10-year-old girl presented to the emergency department 1 hour after striking her right ear against a granite wall. Examination revealed a 4 × 2 cm partial soft-tissue degloving injury of the upper third of the pinna, with exposed cartilage and preserved perichondrium (Fig. 1).

Fig. 1.

A 10-year-old girl presenting with shearing-force trauma to her right ear, sustained 1 hour before. She had a partial degloving injury of the upper third of the pinna with the avulsed skin flap folded onto itself. Flap venous congestion can be observed.

The avulsed flap was folded on itself along the upper lateral surface with evident venous congestion. Its distal portion showed an irregular triangular tear measuring 1.8 × 1.2 cm, and the anterior pedicle exhibited a 2-cm transverse transfixing wound at the anterior helix.

Prophylactic intravenous cefazolin (1 g) was administered. After irrigation, the degloved flap was unfolded and repositioned, showing partial improvement in venous congestion. The anterior helix laceration was repaired using a 6-0 Vicryl Rapide suture with stitches placed through both skin and perichondrium to secure the flap in its anatomical position. The patient was discharged with a 5-day course of oral cephalexin. Despite adequate repositioning, distal venous congestion remained.

At postoperative day 3, necrosis was evident in the distal triangular portion of the flap (Fig. 2). After superficial debridement, 1 mL of RSCEs (ASCEplus Dermal Signal Kit SRLV, ExoCoBio, Seoul, Korea) was applied to the entire wound surface and covered with a nonadherent 3M Adaptic dressing (Systagenix, Quincy, MA) for 5 days.

Fig. 2.

Day 3 postoperative: irregular necrosis was observed in the distal triangular portion of the repositioned flap. After superficial debridement, 1 mL of RSCEs (ASCEplus Dermal Signal Kit SRLV, ExoCoBio) was applied to the entire wound surface.

By day 8, a dry eschar was observed covering the previously necrotic area. On day 14, sutures and the detached eschar were removed, revealing complete early regeneration of the skin and deeper soft-tissue layers (Fig. 3). By day 20, the scar was barely perceptible, and the patient and her parents expressed high satisfaction with the aesthetic outcome (Fig. 4).

Fig. 3.

On postoperative day 14, sutures and a detached eschar were removed exposing a complete early regeneration of the skin and deeper soft-tissue layers. The wound had completely healed.

Fig. 4.

By postoperative day 20, the scar was barely perceptible, and the patient and her parents expressed high satisfaction with the aesthetic outcome.

DISCUSSION

No standardized guidelines exist for managing degloving injuries. General principles prioritize preservation of viable tissue, but distal necrosis may still occur even when pedicled flaps are properly repositioned. Random-pattern skin flaps, dependent on the subdermal plexus, are especially prone to ischemia due to twisting, stretching, or pedicle injury. In this case, vascular compromise was likely caused by both flap folding and the transfixing wound across the pedicle.

Preclinical studies indicate that exosomal miRNAs regulate key pathways in the inflammatory, proliferative, angiogenic, and remodeling phases of healing. ADSC-Exos carry differentially expressed miRNAs that enhance vascularization in poorly angiogenic skin flaps improving survival. Pu et al³ showed that ADSC-Exos promote angiogenesis and repair ischemia-reperfusion–injured flaps in murine models. In vitro data suggest that RSCEs accelerate wound closure by stimulating fibroblast proliferation and migration, whereas bioinformatic analysis of their RNA cargo indicates that miRNA-23 contributes to their proangiogenic effects.⁵

Kim et al⁶ demonstrated Rosa damascena extract increased epidermal growth factor and VEGF expression, promoting early angiogenesis and faster wound healing in mice, with statistically significant results. More recently, RSCEs were applied safely in a case of partial ischemic loss of a nasal skin flap, supporting angiogenesis and soft-tissue regeneration.⁷

In children, traumatic wounds greater than 3 cm often heal slowly, and thin auricular skin with limited soft-tissue reserve further complicates the management of traumatic avulsions.⁸ Standard care for this injury would include debridement of necrotic tissue with possible skin grafting or flap advancement to cover exposed cartilage. Given the patient’s age, the high risk of scar deformity associated with the flap’s ischemic location, and the available supporting evidence, RSCEs were used off-label as a last-resort nonsurgical intervention to stimulate angiogenesis, support tissue repair, and reduce the risk of cartilage exposure, scarring, and auricular deformity.

Ongoing clinical studies aim to define optimal exosome therapy protocols for skin injury and wound healing. Animal data show improved healing with topical or dressing-based delivery. Proposed guidelines suggest dosing from daily to weekly, depending on therapeutic goals. A single early application may be sufficient to promote tissue regeneration, as was seen in this case.⁹

VEGF peaks between days 3 and 7 postinjury, coinciding with granulation tissue formation, making this VEGF window optimal for delivering proangiogenic exosomes cargo directly to the ischemic skin flap.^9,10 In this case, RSCEs were applied on day 3, within this theoretical window. However, it remains uncertain whether similar healing would have occurred without intervention.

Although exosome therapy is promising, commercial preparations remain off-label for skin injuries. Long-term safety data are limited, and cost may restrict access, especially with repeated applications. Randomized controlled trials are needed to confirm efficacy and establish standardized protocols.

CONCLUSIONS

Ischemic flap failure remains a significant risk in reconstructive and aesthetic surgery. Preclinical studies show that exosomes enhance angiogenesis, mitigate ischemic damage, and promote tissue repair. In this case, RSCEs were safely used to salvage a posttraumatic ischemic auricular flap in a child, highlighting their potential as an adjunct therapy to improve flap survival and healing.

DISCLOSURE

The authors have no financial interest to declare in relation to the content of this article.

PATIENT CONSENT

Parents or guardians provided written consent for the use of the patient’s image.