Observations on Wound Healing and Sensory Changes Following Secretome Injection for Nipple Tip Necrosis: A Case Report

Article information

J Wound Manag Res. 2025;21(3):154-159

Publication date (electronic) : 2025 October 30

doi : https://doi.org/10.22467/jwmr.2025.03293

Fellicia Naurah Andryas, Andi Salsabilah, Yuri Karisma Putra, Muhammad Irsyad Kiat

The Clinic Beautylosophy Cipete, DKI Jakarta, Indonesia

Corresponding author: Fellicia Naurah Andryas, MD The Clinic Beautylosophy Cipete, Jl. Abdul Majid Raya No. 40D, RT 007/RW 002, Cipete Selatan, Kec. Cilandak, Kota Jakarta Selatan, DKI Jakarta 12410, Indonesia E-mail: fellicia@theclinic.co.id

Received 2025 April 24; Revised 2025 June 28; Accepted 2025 June 30.

Abstract

Introduction

With rapid advances and increased accessibility of aesthetic surgery, breast surgery ranked as the second most common procedure globally in 2023, according to the International Society of Aesthetic Plastic Surgery. Postpartum body restoration is a key driver for breast surgery, as age and hormonal changes during pregnancy can affect skin and breast parenchyma, altering the position and shape of the nipple-areola complex (NAC), resulting in breast ptosis [1]. Various breast surgery techniques exist for different goals and desired outcomes, and their selection depends on the extent of ptosis. Mastopexy restores and improves the position of the NAC, while simultaneous augmentation-mastopexy effectively addresses both breast size and shape. Augmentation-mastopexy techniques, including autologous and implant-based augmentation, have developed remarkably during the last two decades. Implant-based mastopexy is preferred in cases of severe ptosis, poor skin elasticity, or when substantial skin excision is required [2].

Breast surgery carries the risk of complications such as hematoma, implant malposition, sensory changes, and necrosis, which can lead to poor aesthetic outcomes including asymmetry and patient dissatisfaction. Management of breast tissue necrosis typically involves skin grafts or flap reconstruction, particularly in cases of extensive tissue loss [3]. However, there is an increasing demand for less invasive approaches to reduce recovery time and minimize scarring, while optimizing both functional and aesthetic outcomes. For this reason, stem cell-based treatments including secretome, have gained popularity for investigation as novel management methods. Secretome contains trophic factors released by mesenchymal stem cells (MSCs). MSCs are non-hematopoietic and plastic-adherent cells that exhibit a fibroblast-like phenotype. Secretome contains both soluble components such as growth factors, cytokines, chemokines, and hormones, as well as non-soluble elements that are contained within extracellular vesicles. Rich in bioactive molecules that promote cell proliferation, differentiation, migration, and tissue repair, secretome shows potential in managing necrosis [4]. This study presents a case of accelerated nipple tip necrosis healing following augmentation-mastopexy with secretome injection, demonstrating its ability to enhance recovery and outcomes. The patient provided written informed consent for the publication and the use of her images.

Case

A 35-year-old female patient presented with grade 3 bilateral breast ptosis, wishing for breast volume augmentation and elevation of the NAC (Fig. 1). Her previous medical history included two cesarean sections (6 and 3 years prior) with both children breastfed for more than 12 months, and a weight loss of 20 kg 1 year prior. A plan for bilateral augmentation-mastopexy was proposed to the patient, and written informed consent was obtained for the surgery. After careful preoperative markings, 5 cm incisions were made at each inframammary fold (IMF) to create pockets for implant insertion. Bilateral 305 cc round silicone implants were inserted after dissecting the subglandular plane and the pockets were closed with interrupted sutures. During pocket dissection and implant insertion, bleeding occurred in the right breast pocket with difficult hemostasis. After implant placement and control of bleeding, Wise pattern mastopexy incisions were drawn, and incisions were made along the markings. The NACs were elevated by 7 cm with a new NAC diameter of 4.2 cm. With de-epithelialization, the medial and lateral flaps were elevated while preserving supero-medial pedicles, and the flaps were then fixated and sutured.

Fig. 1.

Before (upper row) and immediately after (lower row) augmentation-mastopexy. A 35-year-old female patient presented with grade 3 bilateral breast ptosis. (A) Right lateral view. (B) Anterior view. (C) Left lateral view. After insertion of 305 cc implants, Wise pattern incisions were made, and the nipple-areola complexes were elevated by 7 cm to a new diameter of 4.2 cm. (D) Right lateral view of the right nipple. (E) Anterior view. (F) Left lateral view.

The patient complied to postoperative care instructions, including the use of petroleum jelly gauze and breast support for 6 weeks. At 1-week follow-up, minimal subdermal hematoma, skin peeling, and hypoesthesia on the right new NAC were reported. The hematoma did not require invasive interventions; it was adequately treated with 200 IU/g topical heparin sodium gel, applied thinly three times daily on the affected area. Sensory function was evaluated by comparing light touch and pressure perceptions between the nipple tip, areola, periareolar region, and the sternum. By the second week (Fig. 2), nipple tip necrosis with a depth of 3 mm was noted on the right NAC (Fig. 3). No perception of light touch and pressure was found in the right NAC while the left NAC displayed decreased perception. The patient received a subcutaneous injection of 1.5 mL ReGeniC secretome (Kalbe Farma) in the right periareolar region after surgical debridement (Fig. 4). Complete epithelization occurred a week post-injection. By 2 months, though slight hypopigmentation remained, normal sensory function returned to both NACs. On inspection, the new NACs appeared asymmetrical in height, with the right NAC visually shorter compared to the left (Fig. 5), but the patient was satisfied with the overall results.

Fig. 2.

Two-week follow-up. Black necrotic tissue was observed on the right nipple tip. At this time, the patient also reported persistent decreased sensation in the right nipple tip, confirmed through a basic sensory assessment by the surgeon. (A) Right oblique view. (B) Anterior view. (C) Left oblique view.

Fig. 3.

Right nipple tip necrosis before wound debridement. After antiseptic preparation, wound debridement was performed to remove necrotic tissue from the right nipple tip, together with removal of cutaneous sutures on both breasts.

Fig. 4.

Immediately after wound debridement. Wound debridement was uneventful, with minimal bleeding observed at the right nipple tip. Following debridement, 1.5 mL of ReGeniC secretome (Kalbe Farma) was administered via subcutaneous injection in the right periareolar region. (A) Right lateral view. (B) Anterior view. (C) Left lateral view.

Fig. 5.

Two-month follow-up. At the 2-month follow-up, normal wound healing was observed, with the patient reporting hyperesthesia of the right nipple tip. (A) Right oblique view. (B) Anterior view. (C) Left oblique view.

Discussion

Simultaneous augmentation-mastopexy is often selected to improve the youthful appearance of breasts that have been affected by aging, hormonal fluctuation, or weight loss. In general, up to 16.7% of patients who have undergone this surgery experience complications, including displacement and asymmetry, infection, and hematoma, with 25% of affected patients requiring at least one reoperation [5]. Sensory disturbances are also frequent [5,6]. It is the third most common adverse event within 30 days after breast augmentation and also the first most common to occur within 5 years after surgery [7].

At 1 week postoperatively, our patient developed hematoma, skin peeling, and hypoesthesia of the right NAC, progressing to nipple tip necrosis with persistent hypoesthesia by week 2. Intraoperatively, significant bleeding had occurred in the right breast pocket for which hemostasis was difficult to achieve, likely compromising tissue perfusion and NAC viability. Excessive intraoperative bleeding can impair blood supply, contributing to tissue necrosis and sensory deficits. The risk of NAC ischemia increases with larger implants, extensive tissue excision, and significant NAC transposition [3]. In cases where tissue necrosis is extensive, surgical intervention may be required. In this case, necrosis was managed with surgical debridement followed by a subcutaneous injection of 1.5 mL secretome. This combined approach aimed to promote tissue regeneration and accelerate recovery [4].

Wound healing is a complex process that involves four distinct and overlapping stages: hemostasis, inflammation, proliferation, and remodeling [8]. The hemostasis phase is immediately activated after wounding, triggering the clotting cascade that causes blood vessels to constrict for up to 10 minutes. During this time, platelets rapidly gather and form a primary fibrin or hemostatic plug to stop the bleeding. Inflammation begins within the first 24 hours and typically lasts for 2 to 5 days. In the early inflammation phase, neutrophils play a key role as a chemoattractant, drawing immune cells like macrophages, T-cells, and more neutrophils to the site. The proliferation phase begins around 3 to 10 days after the injury and can take several days or even weeks to complete. During this time, various growth factors, angiogenic signals, and anti-inflammatory cytokines are released, promoting the growth and specialization of endothelial cells, keratinocytes, and fibroblasts. Remodeling is the last stage of wound healing, starting around day 21 and potentially lasting up to a year. In this phase, granulation tissue formation concludes, and the scar begins to mature [9].

A key mechanism that accelerates wound healing is rapid re-epithelialization. Stem cells have gained considerable attention in regenerative medicine due to their ability to differentiate and support tissue repair. As described before, bioactive molecules in MSCs facilitate wound healing by accelerating re-epithelialization, enhancing the formation of granulation tissue, stimulating angiogenesis and decreasing inflammation. In this case study, secretome from human umbilical cord MSCs (UC-MSCs) was used. UC-MSCs stimulate fibroblast proliferation and migration, upregulate scarless healing genes, and modulate extracellular matrix remodeling by increasing matrix metalloproteinase secretion and reducing transforming growth factor-beta expression [4]. Re-epithelialization in acute wounds typically occurs within 2 to 3 weeks. In our patient, secretome accelerated this process, with visible re-epithelialization observed 1 week posttreatment [10], The secretome used in this case is produced at a current good manufacturing practice (cGMP)-certified stem cell manufacturing facility. It has been utilized in regenerative medicine applications, such as treating osteoarthritis, burns, fractures, and wound healing. It is cGMP-certified from the Indonesian Food and Drug Authority and under an operating license from the Indonesian Ministry of Health, which authorizes the manufacturing of clinical-grade stem cells and their derivatives.

In a systematic review by Ducic et al. [7], the total risk of any nerve injury after aesthetic breast surgery ranged from 13.5% to 15.4% with the cutaneous nerve to the NAC being most frequently affected at a rate of 4.6% to 5.3%. The study also reported 35.6% and 17.9% incidence of hypoesthesia and hyperesthesia, respectively. The NAC is primarily innervated by both the anterior and lateral cutaneous branches of the third, fourth, or fifth intercostal nerve. Among these branches, the fourth lateral cutaneous branch is known to be the most consistent nerve supply to the nipple. This nerve takes a subglandular course within the pectoral fascia and reaches the nipple from its posterior surface [11].

We hypothesize that our patient’s postoperative hypoesthesia was caused by direct nerve injury during inframammary incision and/or blunt tissue dissection during dissection of the augmentation pocket. Such nerve trauma may result in stump neuroma (if the nerve is transected), neuroma-in-continuity (partial nerve injury), or compression neuropathy (due to scar formation or edema at anatomically tight areas) [7]. A cadaver study by Schlenz et al. [11] reported that sensory nerves predominantly concentrate at the nipple base, following the major duct system to the posterior nipple surface, making them susceptible to injury during IMF surgical manipulation. It should be noted that some other studies demonstrated no difference in sensibility alterations between inframammary and periareolar approaches [7,12].

Relative implant volume (implant size relative to preoperative breast volume) may also contribute to sensory changes through nerve fiber neurapraxia caused by excessive tension, particularly in smaller breasts [12]. Implant placement can induce traction-stretch neuropathy, further exacerbated by tight cutaneous closure. However, Ducic et al. [7] reported no significant association between implant size, incision type, or implant position and sensory disturbances following breast augmentation.

At 4 weeks post-injection, the patient reported hyperesthesia, suggesting partial nerve injury and possible central sensitization at the spinal cord level. However, sensory assessment was done subjectively, performed by the surgeon using only pressure and light touch with tissue paper. Okwueze et al. [6] similarly noted subjective asymmetry in postoperative breast sensation, though objective measurements using a Pressure-Specified Sensory Device revealed no significant differences. This highlights the significance of objective sensory evaluation, which was not conducted in this case.

Although sensory changes are subjective, the findings suggest that secretome may exert neuroprotective effects, potentially enhancing sensory recovery. Most studies on MSC-derived neuroprotection focus on other organs with no published data to date specifically addressing peripheral nerve regeneration in the skin. The MSC-derived secretome possesses immunomodulatory and neuroregulatory effects. Secretome may offer a promising and practical approach to promote their proliferation and differentiation, potentially helping to prevent or slow the progression of various neurological deficits. MSCs have been demonstrated to express a wide range of neuroregulatory molecules that influence the fate of neural stem cells, as well as play roles in axon guidance, neural cell adhesion, neurite outgrowth, neurotransmitter receptor activity, and the production of neurotrophic factors [10]. Regardless, it is important to note that subjective perceptions do not necessary correlate with objective findings.

This case highlights the complexity of augmentation-mastopexy complications, particularly NAC tissue necrosis and sensory loss. Factors such as implant size, excessive hemostasis, direct and/or indirect nerve damage may compromise tissue viability and function. Early diagnosis and intervention including surgical and/or non-surgical approach, such as the application of stem cell-based therapy, facilitated accelerated wound healing in this patient. Further research is needed to provide additional validation for the observations of this study and explore the potential neuroprotective effects of UC-MSC in preserving cutaneous sensation.

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