Nanofat for Injection Laryngoplasty: Office and Operative Results

ABSTRACT

Objective

Nanofat is fat emulsified into micron‐sized particles. Unlike microfat, nanofat increases the release of adipose‐derived stem cells by destroying lipocytes. This study evaluated whether nanofat injection laryngoplasty alone leads to lasting bulking and sustained long‐term voice improvement.

Methods

We retrospectively reviewed patients with glottal insufficiency due to atrophy, paresis, or scarring who underwent operative (n = 13) or office‐based (n = 18) nanofat injection laryngoplasty. The average injected fat volume was 0.5 mL per side. Median follow‐up was 12 ± 4 months. Stroboscopy was used to assess vocal fold closure and vibration. Pre‐ and post‐Voice Handicap Index‐10 (VHI‐10) and Cepstral Spectral Index of Dysphonia scores were compared.

Results

VHI‐10 scores improved significantly from pre‐ to post‐treatment (p < 0.05). Improved glottic closure after nanofat injection correlated with improved voice. Unwanted stiffness was noted in only one case. Unwanted absorption occurred in the first year in nine patients (29%), whereas the remaining patients maintained good long‐term function.

Conclusion

Nanofat‐only lipoinjection is a potential alternative to microfat injection for the treatment of glottal insufficiency. Office‐based nanofat injection using a small‐gauge needle cannula is a practical alternative to operative microfat injection. Early absorption remains a challenge, and targeted overinjection and improved fat processing should be considered to optimize outcomes.

Level of Evidence

Level 4. Retrospective case series.

Nanofat serves as an alternative or adjunct to microfat in patients undergoing injection laryngoplasty. The advantages of nanofat include its favorable safety profile and high procedural and tissue tolerance. There is an absorption rate within one year of 29% which may reduce its effectiveness.

1. Introduction

Glottal insufficiency often causes dysphonia, particularly in the elderly, resulting in a soft, breathy voice. Fat injection laryngoplasty is an effective alternative treatment [1]. Standard preparation involves cutting microfat into 1–2 mm pieces and injecting it using a 16‐gauge needle [2]. Although the outcomes are generally satisfactory [3], variable reabsorption remains a challenge, with one systematic review reporting a 12.6% regression rate [4]. Inconsistencies in microfat preparation have prompted publications to recommend different fat preparation methods [5, 6, 7]. Additionally, the use of large‐bore needles may cause tissue trauma and create larger entry sites.

Nanofat grafting reduces fat to micron‐sized particles—a popular technique in facial plastic surgery [8, 9]. Nanofat is prepared by passing lipoaspirate through 1.2‐ and 1.6‐mm cannulas, followed by filtration at 50 μm [10]. Unlike microfat, nanofat disrupts lipocytes while preserving adipose‐derived stem cells and growth factors [11]. Although it does not provide viable lipocytes for direct volume replacement, nanofat may improve function. Studies have suggested that nanofat has regenerative potential, and preserved stem cells may aid vocal fold regeneration. Despite not having the volume replacement as in microfat transfer, nanofat, by preserving the regenerative potential of stem cells, may result in tissue regeneration and volume replacement. Preliminary studies have shown short‐term viability [12]; however, long‐term data are lacking, which remains a key gap.

Nanofat can be injected through a 27‐gauge needle, causing less trauma and allowing office‐based procedures.

In this study, we reviewed 31 patients who underwent nanofat injection laryngoplasty for vocal atrophy, scarring, or paresis. Clinical, acoustic, and stroboscopic outcomes were analyzed at 1 year to evaluate the long‐term effectiveness of nanofat.

2. Material and Methods

2.1. Patient Selection

This retrospective study analyzed 31 consecutive adult patients who underwent nanofat injection laryngoplasty for glottal insufficiency between August 2021 and June 2025. The study was approved by the Institutional Review Board of Icahn School of Medicine at Mount Sinai (IF2615828).

Indications included bilateral vocal atrophy (n = 14), vocal fold paresis (n = 11), and vocal fold scarring or sulcus scarring (n = 6). There were no cases of vocal fold paralysis. All of the patients have failed prior conservative voice therapy and were requesting additional intervention. Traditional microfat injection laryngoplasty under anesthesia was discussed as the other therapeutic option and the patients opted for nanofat injection laryngoplasty. Table 1 tabulates the patients' diagnosis and demographics.

TABLE 1.

Patient demographics and indications for nanofat.

Condition	Number
Atrophy	17
Paresis	12
Scar	2
Unilateral	20
Bilateral	11
Age	69 ± 12
Male	26
Female	5

All patients provided written informed consent for nanofat injection laryngoplasty. They underwent prior voice therapy and were counseled on all available surgical options before electing lipoinjection as the primary treatment. Thirteen patients underwent the procedure under general anesthesia in the operating room, whereas 18 underwent office‐based nanofat injection under local anesthesia.

2.2. Administration of Fat

Fat transfer was performed using microlaryngoscopy under general anesthesia or via office injection. A small endotracheal tube was used for operative injections. Suspension laryngoscopy enabled nanofat injection lateral to the vocal ligament. Vocal folds were overinjected by approximately 50%, aiming for 0.5–0.6 cc per fold to account for expected resorption.

For office‐based injections, nanofat was injected via a transcervical approach under fiberscope guidance. The cricothyroid membrane was punctured, and a 23‐gauge needle was placed lateral to the vocal ligament. About 0.5 cc was injected on each side for atrophy or on one side for paresis.

2.3. Preparation of Nanofat in the Office

The fat harvest is performed in the office under sterile conditions by the otolaryngologist. Autologous fat was manually harvested from the patient's abdomen via liposuction using a 3‐mm liposuction cannula. Tumescent infiltration was performed, and a total of 20 mL of fat was harvested. The tumescent solution was removed via gravity and decantation. The fat was emulsified by passing it through a 2.4‐ to 1.2‐mm Luer‐to‐Luer connector between syringes. The fat in the syringe was connected to a final adaptor containing a disposable metal mesh filter, and the emulsified fat was pushed through the filter into a final 10‐mL syringe (Tulip Medical, San Diego, CA). Aliquots of nanofat were subsequently prepared for injection into 1‐mL syringes using a 23‐gauge, 1.5‐in. needle. The procedure time for fat harvest is less than 30 min. After the nanofat is prepared, the fat is immediately injected in the endoscopy suite under local anesthesia. Injection was performed via cricothyroid membrane puncture under fiberscope guidance.

2.4. Clinical and Voice Evaluation

Videostroboscopy, voice assessments, and clinical evaluations were conducted before treatment and approximately 1 year post‐injection. The Voice Handicap Index‐10 (VHI‐10) was administered at baseline and during follow‐up visits.

For acoustic analysis, patients were recorded in a quiet room while repeating the sentence “How hard did he hit him?” from the Consensus Auditory‐Perceptual Evaluation of Voice (CAPE‐V). This voice token was repeated five times within a 10‐s interval. The recordings were made using a microphone positioned 6 in. from the patient's mouth in a room with ambient noise below 55 dB. The recordings were analyzed using the cepstral peak prominence method (ADSV software for analyzing dysphonia in speech and voice, version J3.42; Pentax Medical Computer Speech Laboratory, Montvale, NJ, USA). The Cepstral Spectral Index of Dysphonia (CSID) scores were calculated. The CSID index derived from the CAPE‐V sentences was used [13, 14, 15].

Clinical evaluations were performed to determine whether patients were satisfied with their voice outcomes and whether there was evidence of voice deterioration over time.

2.5. Stroboscopy Analysis

Stroboscopic evaluations were conducted before and after treatment. Both authors (P.W. and A.N.) independently evaluated each stroboscopy examination before and after treatment and rated whether a glottal gap was present during modal phonation. This binary rating (yes or no) assessed the presence of a glottal gap during sustained phonation. The senior author (P.W.) also noted the presence or absence of vocal fold stiffness at the site of nanofat injection.

2.6. Statistical Analysis

Vocal fold closure rating before and after treatment was collected from each rater. CSID scores and VHI‐10 scores were compared before and after treatment (Paired Samples Test, two‐tailed, IBM SPSS Statistics, version 31.0.1.0, IBM Corporation). Pre‐ and post‐treatment measurements were similarly compared for those deemed to have successful one‐year results (n = 22) and those deemed to have failed (n = 9). Analysis compared all nanofat patients, those with successful one‐year results, and those deemed to have failed against the dependent variables of VHI, CSID score, and vocal fold closure.

3. Results

All 31 patients tolerated nanofat injection laryngoplasty. Thirteen patients underwent nanofat injection in the operating room, whereas 18 received it in the office. An average of 0.5 mL of nanofat was injected into each vocal fold. No procedure‐related complications occurred at the donor or recipient sites.

The cohort included 5 females and 26 males. Patient age ranged from 45 to 82 (median, 69 ± 12). The median follow‐up time was 12 ± 4 months. The shorter follow‐up time reflected patients who did not complete the 1‐year follow‐up.

All patients reported immediate short‐term improvement in vocal function, as evidenced by improved VHI‐10 scores and patient satisfaction, including reduced vocal fatigue and effort. VHI‐10 recordings were performed serially at 1 months, 3 months, 6 months and 1 year. In general, the VHI‐10 results followed the clinical response with the failure patients showing initial improvements in the VHI followed by increasing VHI in the failure group.

Three short‐term failures with residual breathiness were reported at the 3‐month follow‐up. At the 1‐year follow‐up, an additional six patients reported unsatisfactory voice quality after initial improvement. The remaining patients achieved satisfactory and durable voice results. Thus, the overall clinical failure rate in this group was 29% (9/31), whereas 71% (22/31) reported satisfactory voice outcomes at 1 year.

Table 2 shows the pre‐ and post‐treatment VHI and CSID scores, and glottal gap findings on stroboscopy for the entire cohort and subgroups of responders versus non‐responders. The VHI‐10 scores significantly improved after treatment (p < 0.05). Complete glottic closure was achieved in 24 of 31 patients after the procedure, whereas only 11 of 31 patients achieved complete closure before surgery. The CSID score improved after treatment; however, the difference was not significant.

TABLE 2.

Tabulation of pre‐ and post‐operative VHI, CSID score, and closure on videostroboscopy.

	Pre‐treatment	Post treatment, 12 ± 4 months
Complete closure on stroboscopy All patients n = 31	11, 12	24*, 23*
Complete closure on stroboscopy Non‐responders n = 9	3, 5	5, 5
Complete closure on stroboscopy Responders n = 22	8, 8	19*, 18*
VHI All patients n = 31	18	14*
VHI Non‐responders n = 9	31	23
VHI Responders n = 22	15	12*
CSID score All patients n = 31	19	16
CSID score Non‐responders n = 9	52	45
CSID score Responders n = 22	41	45

Note: Closure is rated by rater 1 (PW) and rater 2 (AN).

^* p < 0.01 Paired Sample Test (two sided, Estimate effect sizes using standard deviation of the difference).

In the subgroup analysis, responders showed significant improvement in vocal fold closure and VHI‐10 scores, whereas non‐responders showed no change (Table 2). The CSID scores did not change significantly before or after treatment in either responders or non‐responders.

Figures 1 and 2 show stroboscopy montages with pre‐ and post‐operative findings from a successful patient. Figures 3 and 4 show the pre‐ and post‐operative stroboscopy findings in a non‐responder. The responder showed better closure post‐treatment at 13 months, whereas the non‐responder had a persistent glottal gap.

FIGURE 1.

Preoperative video montage showing incomplete closure in an 82‐year‐old male.

FIGURE 2.

Postoperative video montage of the same patient as Figure 1, showing complete closure 13 months after office‐based Nanofat injection.

FIGURE 3.

Stroboscopy video montage showing a patient with incomplete closure before nanofat injection.

FIGURE 4.

Stroboscopy video montage of the same patient as Figure 3 at 3 months post‐injection. There is continued incomplete closure.

Stroboscopy demonstrated excellent supple vibration with minimal evidence of stiffness at the injection side. Unwanted stiffness unrelated to the pre‐operative scar was noted in only one patient and was rated as mild. The other two cases of stiffness were observed in patients with existing scars, and reduced amplitude was present before surgery.

4. Discussion

Fat injection has been used to treat glottic insufficiency for many decades [16]. Numerous studies have evaluated the efficacy of microfat [17, 18]. A major limitation is the unpredictable nature of microfat graft retention [19]. This has prompted some researchers to advocate for special preparation techniques, including careful patient selection and the use of adjunctive agents such as steroids and insulin [20, 21].

Nanofat has been increasingly accepted as an alternative to microfat. In the facial plastic surgery literature, its ability to be injected into the dermal layer has prompted consensus documents regarding its use [10, 22]. The concept of using the stromal fraction devoid of lipocytes, while preserving regenerative cellular components, was first popularized by Tonnard in 2013 [8]. Injection laryngoplasty using nanofat is a logical extension of this technique in the larynx [12]. Although nanofat is not thought to be a volumizing agent, our patients with successful outcomes show better closure and improved volume after nanofat injection. This suggests tissue regeneration due to the properties of nanofat. The short and long‐term failure patients suggest that the initial injection of the nanofat may have been the effect of volume from the nanofat injection, but in the long‐term failure patients, the volume effect from the initial nanofat injection was absorbed. In patients with long‐term failure, it may be necessary to reconsider volume agent in addition to nanofat alone. Nanofat appears to be well tolerated and demonstrates short‐term improvements on stroboscopy, patient‐reported outcomes, and objective voice measures. This study aimed to determine whether nanofat alone can serve as a safe, long‐term alternative to microfat in patients with glottic insufficiency.

We were interested in nanofat because it has the potential to retain more fat‐derived stem cells than microfat. Nanofat is mechanically processed from microfat, resulting in minimal viable adipocytes. However, the preparation method allows for the survival of adipose‐derived stem cells, growth factors, and other factors. Growth factor injections have demonstrated efficacy in treating vocal atrophy and scarring [23]. Basic science studies have shown that nanofat is an ample source of pluripotent stem cells and growth factors [24]. Stem cell therapy has not been easily applied in injection laryngoplasty. Fat is a well‐known stem cell reservoir used for injection laryngoplasty, and the ability to deliver these components may provide an alternative to traditional fillers using microfat.

The traditional technique of fat injection relies on microfat and minute adipose tissue fragments to bolster the vocal fold and improve glottic closure. Although effective, variability in fat retention has spurred the pursuit of alternative methods [25]. In the facial plastic surgery literature, refinements in fat preparation have promoted the use of nanofat [26]. Although microfat may increase volume, nanofat is thought to improve texture. This effect may be attributed to better retention of adipose‐derived stem cells [27].

In this study, we observed significant volume loss in 9 of the 31 patients during the first year, resulting in a 29% failure rate at 1 year. This corresponded to stroboscopic evidence of a persistent glottal gap. Importantly, mucosal pliability was excellent, with only 1 of 31 patients showing residual hyperemia and mild stiffness compared with pre‐operative findings. Rather, progressive volume loss in these nine patients prompted the declaration that the procedure did not achieve the goal of long‐term voice improvement at 1 year. Despite these failures, 22 of the 31 patients showed long‐term improvement in glottal function at 1 year, including improvement in VHI‐10 scores and complete glottic closure on stroboscopy.

A major advantage of using nanofat is its ability to be delivered through small‐gauge needles, which reduces vocal fold trauma and complications. A needle size comparable to that commonly used in office‐based injection laryngoplasty allows the procedure to be performed in an office setting. In this cohort, we performed injections in 18 patients in an office setting without general anesthesia or sedation.

Alternative approaches to fat grafting have been described in the literature [22, 28, 29, 30]. These techniques include combining micro‐ and nanofat, reducing the lipid fraction [31], and using other processing techniques. Undoubtedly, combining pluripotent stem cells with nanofat, along with viable transplanted lipocytes, may improve graft retention and long‐term volumization [24, 26, 32]. In the next stage, we plan to add platelet‐rich plasma [33, 34] to the fat graft to improve survival and long‐term tissue augmentation. We will continue to use nanofat injection as the primary treatment for glottic insufficiency in patients with atrophy, paresis, paralysis, or mild vocal fold scarring, while optimizing its efficacy using techniques described in the literature.

The limitations of this study include the heterogeneous etiology of glottic insufficiency in our cohort undergoing injection laryngoplasty. Furthermore, the retrospective design limited the ability to adjust for confounding variables. The lack of statistical significance in CSID scores is not surprising, as cepstral scores primarily reflect roughness rather than breathiness. Furthermore, VHI‐10 score improvements were just above the threshold for clinical significance (18–14). Caution should be exercised when interpreting these results. Given the variability in all fat injection results, a longer follow‐up beyond 1 year is necessary to fully assess durability.

Despite these limitations, we are encouraged by the safety profile and reasonable durability of nanofat in this cohort. Nanofat for injection laryngoplasty requires further investigation. Future investigations should combine other regenerative medicine strategies, including matrices, growth factors, and refined fat preparation, to improve long‐term outcomes in the treatment of glottic insufficiency.

5. Conclusion

Nanofat serves as an alternative or adjunct to microfat in patients undergoing injection laryngoplasty. The advantages of nanofat include its favorable safety profile and high procedural and tissue tolerance. Patients receiving nanofat injections retained mucosal pliability and achieved excellent short‐term improvement. However, the 1‐year results were limited by significant graft resorption in 29% of patients. The remaining patients demonstrated sustained voice improvement without significant volume loss. Stroboscopy showed good closure of the glottal gap after nanofat injection laryngoplasty in the responders. Additionally, the procedure can be performed in an office setting. Future studies may combine tissue‐engineering strategies that retain stem cells using nanofat with the traditional volume effects of microfat to optimize outcomes.

Funding

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Woo P. and Nourmahnad A., “Nanofat for Injection Laryngoplasty: Office and Operative Results,” Laryngoscope Investigative Otolaryngology 11, no. 4 (2026): e70511, 10.1002/lio2.70511.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.