Nipple Reconstruction Using FixNip NRI: A Novel Nipple Reconstruction Implant (First-in-human Trial)

Abstract

Background:

Loss of a nipple after mastectomy can adversely impact a patient’s body image. This trial evaluated the performance and safety of the FixNip Nipple Reconstruction Implant (NRI), a hypodermic nipple structure designed to provide a reliable option for nipple reconstruction.

Methods:

Female patients 22–70 years of age with a history of breast cancer and at least 3 months postmastectomy were eligible. Nipple reconstruction with the FixNip NRI was performed. Patients were followed up for 12 months, with visits at 1 week, and 3, 6, and 12 months post surgery. Follow-up included safety evaluations, nipple projection measurements, and completion of BREAST-Q patient satisfaction questionnaires.

Results:

Twelve FixNip NRIs were implanted in 10 patients. Nipple projection remained stable during 12 months, with mean ± SD projections of 3.4 ± 1.6 mm at 1 week and 3.7 ± 1.6 mm at 12 months. BREAST-Q questionnaires showed medium to high patient satisfaction. No intraoperative adverse events occurred, but 1 implant was removed due to postoperative infection and dehiscence.

Conclusions:

FixNip NRI appears safe and feasible. Removal of the single implant may reflect the learning curve for patient selection and surgical technique. Use of this permanent implant maintained nipple projection for 12 months with medium to high patient satisfaction, suggesting promising outcomes for future reconstructions.

Takeaways

Question: The study aimed to evaluate the safety and effectiveness of the FixNip Nipple Reconstruction Implant (NRI) for restoring nipple projection and patient satisfaction after mastectomy.

Findings: This trial involved implanting FixNip NRIs in 10 female breast cancer survivors, showing stable nipple projection during 12 months (3.4 ± 1.6 mm at 1 wk and 3.7 ± 1.6 mm at 12 mo after surgery). Patient satisfaction, assessed using BREAST-Q questionnaires, was reported at medium to high levels.

Meaning: Nipple reconstruction with the FixNip NRI is safe and maintains stable projection over time, enhancing patient satisfaction after mastectomy.

INTRODUCTION

Nipple reconstruction (NR) serves as a critical and final component of the comprehensive breast reconstruction (BR) process, aiming to restore a woman’s sense of wholeness, psychological and psychosocial well-being, femininity, and personal identity.^1,2 Accordingly, the oncoplastic surgical community is increasingly focused on enhancing aesthetic outcomes to improve patient satisfaction and body image, and to reduce mastectomy-associated depression and anxiety, as well as other psychological and psychosocial complications.^3–5 The influence of an appealing nipple on patient satisfaction has been demonstrated, and NR therefore plays a pivotal role in the restorative care for breast cancer (BC) survivors who have undergone mastectomy.⁶ This is not only of aesthetic significance but also creates a sense of completeness, restores body image, and improves the psychosocial and sexual well-being in women treated for BC.⁷

Nipple flattening and loss of projection are the most common causes of patient dissatisfaction after NR.^6–10 Various causes of nipple flattening have been described, such as inadequate subcutaneous fat, internal and external pressure, poor flap design, delayed healing, and tissue memory.¹¹ The flattening ratio of reconstructed nipples is dependent on several factors, including skin quality, type of BR, and surgical technique. Many methods have been developed to overcome flattening after NR, with several techniques using matrices or other materials to improve the nipple projection.¹² Nonetheless, flattening remains a major concern, and many patients undergo multiple procedures to maintain the desired projection.¹³ Indeed, the authors have described the need for a secondary NR for nipple reprojection, increasing costs for both patients and the healthcare system. Chung et al¹⁴ found that flattening was the reason for dissatisfaction in more than 50% of dissatisfied patients, concluding that nipple projection gradually decreased over time to the point that an additional reconstruction procedure was required.

In the face of ever-increasing numbers of BC surgery, together with the fact that implant-based reconstruction represents the most common mode of reconstruction, the demand for permanent, safe, and durable solutions for NR is increasing. The FixNip Nipple Reconstruction Implant (NRI) is a novel and promising nipple structure that was designed to provide such a durable and reliable solution. This innovative implant was also recently used in the correction of an inverted nipple.¹⁵ This first-in-human trial of the FixNip NRI aimed to test its efficacy and reliability in NR over time.

PATIENTS AND METHODS

This study was a prospective, open-label, single-arm multicenter study examining the use of the FixNip NRI for reconstruction of the nipple. The study evaluated the long-term safety and performance of the FixNip NRI in patients undergoing NR after breast conservation surgery or mastectomy. The study received approval from the Israeli Ministry of Health and the ethics committees at both participating study sites: Sheba Medical Center, Tel Hashomer, and Assuta Hospital, Ramat Hahayal, both located in Israel.

All patients participating in the study provided written informed consent. The rights, safety, and well-being of study participants were protected in accordance with the ethical principles laid down in the Declaration of Helsinki and all local/national regulations.

Female patients 22–70 years of age with a history of BC who had undergone complete mastectomy followed by reconstruction at least 3 months before study enrollment consented to participate in the study. Patients were excluded if they had active malignant disease, an active infection within the last 30 days, or a history of capsular contracture of Baker grade III/IV. Furthermore, a pinch test was performed before the procedure at the site of the intended nipple location, requiring a minimum result of 15 mm. Patient demographics, comorbidities, and relevant history, including the type of BR, were recorded at the screening visit. After screening and consent, either unilateral or bilateral NR was performed.

The NR procedure was performed using the FixNip NRI, an implantable hypodermic, silicone implant specially designed for aesthetic improvement of the female nipple. It is composed of a “floral-shaped” nitinol frame with a silicone capping, which allows for anchoring of the implant to the adjacent tissue and encapsulation of the nitinol frame, and leads to a softer feel (Fig. 1). Before the procedure, measurements were taken to optimize implant positioning and symmetry with the contralateral breast and nipple–areola complex. The site was aseptically prepared, and local anesthesia was administered (lidocaine and adrenaline diluted in saline 0.9%). Thereafter, a small periareolar incision (15–25 mm) was made, and a 5-mm “pocket” was created by blunt dissection in the subcutaneous plane, followed by thorough hemostasis. Next, the implant was folded and inserted into the pocket. Once placed at the desired position, a further check was carried out to ensure that there were no folds and that the implant was flat within the dissected pocket. Finally, the incision was sutured in 2 layers using absorbable Vicryl and Monocryl sutures (Ethicon, Somerville, NJ), and the site was dressed with a soft nonadherent dressing. The FixNip NRI insertion steps are illustrated in Figure 2.

Fig. 1.

The FixNip NRI is composed of a “floral-shaped” nitinol frame with a silicone overmolding.

Fig. 2.

Steps for insertion of the FixNip NRI device. A, A 15- to 25-mm incision a few millimeters from the intended margin of the reconstructed nipple–areola complex. B, The FixNip NRI is placed 3–6 mm from the incision. C, A 5-mm deep flap in the subcutaneous plane is developed. The FixNip NRI implant is folded (D) and placed in the pocket (E). F, The incision line is sutured with layers in the usual manner.

After the NR procedure, patients were followed up for 12 months, with visits at 1 week and 3, 6, and 12-months after surgery. Nipple projection was measured at the time of each follow-up examination and compared with baseline. Nipple projection was measured directly on the breast using a ruler or a caliper, extending from the base to the apex of the nipple. To determine device success, nipple projection was measured at 12 months and compared with the 1-week projection measurement, which served as the baseline projection. In addition, at each follow-up visit, photographs of the reconstructed nipples were captured to systematically document and monitor changes in their appearance and projection over time.

A module BREAST-Q questionnaire (NR module) was also completed at each follow-up visit to assess the level of overall satisfaction with the cosmetic results and with various aspects of the reconstructed nipple, including the procedure itself, size, softness, symmetry, sensation, and appearance. The BREAST-Q scale ranges from 1 to 5, where 1 represents the lowest level of satisfaction or quality of life and 5 indicates the highest level of satisfaction or quality of life. To assess safety, the occurrence of adverse events was recorded throughout the study period.

All data were captured and analyzed using Microsoft Excel. Statistical analysis focused on nipple projection and its maintenance over time, with procedure duration and patient satisfaction also being analyzed. Continuous data were presented as mean and SD or range, and categorical data as frequency and percentages.

RESULTS

Twelve FixNip NRIs were implanted in 10 female patients. All underwent surgical procedures between October 2019 and July 2021. All patients completed the 1-week and 3-month follow-up visits. One patient was lost to follow-up at 6 months but completed the 1-year follow-up, and all 10 patients completed the 1-year follow-up visit.

Patient characteristics are shown in Table 1. The mean patient age was 51.8 years (range, 38–66 y), and the mean body mass index was 23.6 kg/m². Two patients (20.0%) reported hypertension, and 1 (10.0%) had diabetes mellitus. None of the patients received chemotherapy, but 1 underwent radiotherapy to 1 breast. None of the patients were smokers. The average pinch test was 17.5 mm for the right breast and 22.0 mm for the left breast.

Table 1.

Characteristics of Patients Undergoing NR With the FixNip NRI^*

Variable	Mean (Range) or n/N (%)
Age, y	51.8 (38–66)
Female	10/10 (100)
Body mass index, kg/m2	23.6 (19.8–25.6)
Hypertension	2/10 (20.0)
Diabetes mellitus	1/10 (10.0)
S/P chemotherapy†	0/10 (0.0)
Pinch test (right), mm	17.5 (15 and more)
Pinch test (left), mm	22.0 (15 and more)
S/P mastectomy (patients)	10/10 (100)
Unilateral FixNip NRI procedure (breast)	8/12 (66.7)
Bilateral FixNip NRI procedure (breast)	4/12 (33.3)
S/P radiation‡ (time to FixNip) (breast)	1/12 (8.3)

^*Twelve FixNip implants were implanted in 10 female patients. Thus, N is 10 or 12 for patient-level or breast-level characteristics, respectively.

^†Status 3 years after chemotherapy.

^‡Status 3 years after radiation.

S/P, status post.

All patients had undergone mastectomy with the removal of the nipple–areola complex as a treatment for BC and had BR surgery. Three breasts were reconstructed using autologous flaps, and the remaining 9 were reconstructed using silicone implants. One patient underwent a surgical attempt to reconstruct the nipple using a skin flap 2 months before the study, which resulted in a complete loss of projection a few weeks after surgery. The other 9 patients did not undergo any NR procedure before the study. All patients were successfully implanted with the FixNip NRI under local anesthesia, in an average 20-minute procedure per breast.

No intraoperative adverse events were reported. Related postoperative adverse events occurred in 1 (10.0%) patient in 1 reconstruction (8.3%). This event included a local infection after the implantation of the device in a previously radiated breast, which was then treated with antibiotics and removal of implant.

Representative images of patients after the FixNip NRI procedure at various time points, demonstrating natural and consistent results, are presented in Figures 3 and 4. Nipple projection over time is presented in Figure 5; 1 device that was removed due to local infection was excluded from the projection measurements to provide an accurate evaluation of maintenance of nipple projection when the implant remained in place. At 1 week after procedure, mean ± SD nipple projection was 3.4 ± 1.6 mm (range, 2–5 mm). The mean projection was 3.6 ± 1.6 mm at 6 months (range, 2–5 mm) and remained 3.7 ± 1.6 mm at 12 months (range, 1.5–5 mm). The results therefore demonstrate that nipple projection was not only maintained but also increased during the 12 months of the study.

Fig. 3.

Representative photographs at (A) 6 months after the procedure and (B) at the final follow-up visit 12 months after FixNip reconstruction.

Fig. 4.

Representative photographs at (A) 1 week after the procedure, (B) 6 months after the procedure, and (C) the final follow-up visit 12 months after FixNip reconstruction. D, FixNip reconstruction after makeup, demonstrating the future tattoo.

Fig. 5.

Illustration of nipple projection over time. A, Mean nipple projection over time. B, Nipple projection over time for individual patients, showing the overall trend of increased projection (please note that patient number 0110 underwent a bilateral procedure.)

Patient-reported medium satisfaction results for their reconstructed nipples are presented in Figure 6. All patients completed the BREAST-Q questionnaire at 12 months after the procedure. According to the questionnaire, most patients (8 of 10) were satisfied with overall NR and would recommend NR with FixNip to other women. Patients gave high ratings (>4–5) to the procedure itself, the overall appearance, and symmetry. Softness and sensation were the least favored criteria (rated 3.0–3.5). As part of the BREAST-Q questionnaire, a positive effect on sex life was noted by 4 of 10 patients, with the other 6 patients reporting no effect.

Fig. 6.

BREAST-Q questionnaire at 12 months, showing medium to high rates of patient satisfaction.

DISCUSSION

The FixNip NRI has demonstrated potential as an innovative solution for NR, addressing long-standing challenges in the field. The results of this first-in-human trial are promising, particularly when placed in the context of previous studies evaluating NR outcomes.

Clinical Relevance and Aesthetic Outcomes

Maintaining long-term nipple projection is one of the most critical yet challenging aspects of NR. Previous studies have reported significant flattening of reconstructed nipples over time, often necessitating revision surgery. For instance, Chung et al¹⁴ noted that more than 50% of dissatisfied patients cited loss of projection as the primary concern, often leading to secondary reconstructions. FixNip NRI provides a durable projection, with a mean increase from 3.4 ± 1.6 mm at 1 week to 3.7 ± 1.6 mm at 12 months, thus reducing the likelihood of additional procedures. This durability aligns with goals outlined in the literature advocating for permanent solutions to minimize surgical interventions and associated costs.

The FixNip implant offers a standardized approach without the complications associated with local flaps or fat grafting, such as donor-site morbidity. The study by Bernard and Beran¹³ highlighted autologous fat grafting as a viable but inconsistent method for maintaining projection. FixNip circumvents these by providing structural support while eliminating the variability seen with patient-derived tissues.

Patient Satisfaction and Psychosocial Impact

The psychosocial benefits of NR are well-documented, with studies showing improved body image, self-esteem, and quality of life after reconstruction. The medium to high satisfaction scores in this study, as assessed by the BREAST-Q questionnaire, align with the findings by Santanelli Di Pompeo et al⁶ that an aesthetically pleasing nipple significantly impacts patient satisfaction. Interestingly, FixNip NRI scored well for symmetry, and appearance scores for softness and sensation were lower. This aligns with prior concerns about alloplastic implants lacking tactile qualities compared with autologous tissues. Future research may explore ways to improve sensory outcomes, such as advanced biomaterials or hybrid approaches.

Complications and Safety

Safety remains a key consideration in evaluating novel implants. The study reported 1 (8.3%) postoperative infection requiring implant removal, occurring in a previously irradiated breast. This finding is consistent with previous studies suggesting that radiotherapy can increase the risk of complications in alloplastic reconstructions. Importantly, the absence of other adverse events, including extrusion or displacement of the device design, mitigates these risks. However, larger-scale, multicenter studies with extended follow-up are essential to confirm these safety findings.

Comparison to Other Technologies

Previous innovations, such as the biodesign NR cylinder, have shown potential for maintaining projection but lack the structural stability of the FixNip NRI. Similarly, fat grafting and flap-based techniques have demonstrated variable nipple projection results, highlighting the need for standardized solutions. The FixNip implant’s nitinol framework provides mechanical support, which is an advantage not provided by other available options. This mechanical durability is particularly relevant given the increasing preference for implant-based reconstruction, as noted by Galimberti et al⁹ who reported that implant-based methods dominate modern BR techniques.

Limitations and Future Directions

A limitation of this study includes its small sample size. Although the results are encouraging, larger trials are necessary to validate these findings and assess potential long-term complications. Additionally, studies evaluating the device’s performance in diverse patient populations, including those with thinner skin flaps or prior complications, could help expand its applicability.

Future research may also explore enhancements to the FixNip design, such as incorporating bioengineered materials to improve sensory restoration or developing methods to integrate the implant with tattooed areola reconstruction for more natural outcomes.

CONCLUSIONS

In conclusion, the FixNip NRI is a safe and viable choice for NR. This permanent implant maintains nipple projection to at least 12 months, boasting a notable level of patient satisfaction. In our assessment, the FixNip NRI presents an attractive solution for patients with thicker skin flaps (5 mm and greater), including those who have undergone either alloplastic or autologous reconstruction.

DISCLOSURES

The authors have no financial interest to declare in relation to the content of this article. This study was supported by FixNip Ltd.

ACKNOWLEDGMENT

The authors gratefully acknowledge Rotem Katzenellenbogen, EVP Clinical and Business Development, and Moran Zeevi, Sr. Director Clinical and Medical Affairs at FixNip Ltd.