Efficacy of Nanofat in Wound Healing: A Double-Blinded Randomized Controlled Trial

Abstract

Background:

Nanofat has been shown to contain a variety of growth factors, antiinflammatory mediators, and adipose-derived stem cells, all of which may significantly contribute to the wound healing process. However, there is limited comparative clinical evidence supporting its use. This study aims to evaluate the effects of nanofat on wound healing in abdominoplasty by comparing outcomes between nanofat-treated and -nontreated wounds.

Methods:

A double-blinded randomized controlled trial was conducted using a split-wound model. Each wound was divided and randomized into a nanofat-treated side and a nonnanofat-treated control side. Nanofat was prepared and injected along the wound margins using a standardized dose. Both patients and the surgeons evaluating the wounds were blinded to the treatment allocation. Wound outcomes were assessed 6 months postoperatively using the Observer Scale of the Patient and Observer Scar Assessment Scale.

Results:

Fifty lipoabdominoplasty patients were included in the study. Wound outcomes were significantly better in the nanofat group compared with the nonnanofat group across all assessed parameters, including vascularity, pigmentation, thickness, relief, pliability, surface area, and overall opinion (P < 0.001). No oil cysts or fat necrosis were observed in the nanofat group.

Conclusion:

Nanofat significantly improved wound outcomes in abdominoplasty patients without associated complications such as oil cysts or fat necrosis.

Lipoabdominoplasty scarring is a major concern for patients undergoing abdominoplasty.¹ Although liposuction is often combined with abdominoplasty, the extracted fat is typically discarded. Given the growing evidence supporting the role of nanofat in wound healing,^2–5 the authors see an opportunity to repurpose this otherwise neglected fat to potentially enhance wound outcomes without incurring significant additional costs. However, the evidence supporting nanofat’s efficacy in wound healing remains limited, primarily consisting of case series.^2–5 This lack of robust data raises questions about whether nanofat truly offers therapeutic benefits or merely represents a placebo effect. This study aims to address the uncertainty regarding nanofat’s role in wound healing by conducting a randomized controlled trial to compare wound outcomes with and without the use of nanofat.

PATIENTS AND METHODS

Study Design and Participants

This double-blinded randomized controlled trial included patients aged 18 years or older undergoing standard abdominoplasty. Exclusion criteria were a body mass index of less than 18 kg/m², abnormal abdominal skin lesions, a history of keloids in the abdominal area, prior abdominal liposuction, or inability to participate in a 6-month wound follow-up. All procedures involving human participants were conducted in accordance with the 1964 Declaration of Helsinki and the ethical standards of the surgical center. Written informed consent was obtained from all participants. The study was conducted at the QPrime Surgical Center in Thailand.

Surgical Intervention and Randomization

Before the procedure, a split-wound model was established by dividing the wound in half and randomly assigning 1 side to receive nanofat and the other to serve as the control. General anesthesia was then administered. Fat grafts were harvested from the abdominal area using a blunt-tipped, 2-hole Coleman harvesting cannula connected to a 10-mL syringe. Negative pressure was generated by retracting the syringe plunger. The harvested fat was transferred to blood collection tubes and centrifuged at 3000 rpm for 3 minutes to separate tissue components. After centrifugation, the oil layer at the top and the liquid portion at the bottom were discarded, leaving the middle fat graft layer for processing. To produce nanofat, the fat was repeatedly transferred between 2 connected 10-mL syringes using a female-to-female Luer-Lock connector (Tulip Medical, San Diego, CA). This involved 30 passes through a 2.4-mm connector followed by 30 passes through a 1.2-mm connector. The resulting mixture was then filtered through a metal grid cartridge (400 to 600 µm) to obtain the nanofat.⁶

A standard abdominoplasty procedure was performed, including skin undermining and plication of the rectus abdominis muscle at the midline to correct diastasis recti. Umbilicoplasty was also performed. Before wound closure, nanofat was injected along the upper and lower flap margins on the designated nanofat side, using a standardized dose of 0.5 mL per 2.5 cm. (See Video [online], which demonstrates the nanofat injection along the upper and lower flap margins on the nanofat-treated side. A 2.5-cm needle was used to maintain consistent injection depth, and a 1-mL insulin syringe ensured precise administration of 0.5 mL per injection. The entire needle was inserted, and nanofat was delivered gradually while withdrawing the needle.) A 2.5-cm needle was used to maintain consistent injection depth, and a 1-mL insulin syringe was used to accurately deliver 0.5 mL of nanofat per injection. The entire needle was inserted, and nanofat was injected gradually while withdrawing the needle. Following nanofat injection, the abdominoplasty wound was closed using 2-0 polyglactin 910 (Vicryl; Ethicon, Inc., Somerville, NJ) and 4-0 poliglecaprone 25 (Monocryl; Ethicon) sutures.

Video. This video demonstrates a nanofat injection along the upper and lower flap margins on the nanofat-treated side, using a standardized dose of 0.5 mL per 2.5 cm. A 2.5-cm needle was used to maintain consistent injection depth, and a 1-mL insulin syringe ensured precise administration of 0.5 mL per injection. The entire needle was inserted, and nanofat was delivered gradually while withdrawing the needle.

Download video file ^{(96.2MB, mp4)}

Blinding

Both the patients and the surgeons assessing the wounds were blinded to the nanofat-treated side. To minimize bias, the abdominoplasty wound was sutured by a separate surgeon who was not involved in the nanofat injection.

Outcomes

The primary outcome was measured using the Observer Scale of the Patient and Observer Scar Assessment Scale.⁷ This scale includes 7 items: vascularity, pigmentation, thickness, relief, pliability, surface area, and overall opinion.⁷ Each item is rated on a scale from 1 (normal skin) to 10 (worst scar imaginable). Secondary outcomes included complications related to nanofat injection; specifically, the incidence of oil cysts and fat necrosis.

Statistical Analysis

Data were analyzed using IBM SPSS Statistics (Version 23). Continuous variables are presented as mean ± SD, whereas discrete variables are reported as number (percentage). Normality was assessed using the Shapiro-Wilk test. For nonparametric data, outcomes are expressed as median and interquartile range. The Wilcoxon signed rank test was used to compare the dependent variables. All statistical tests were 2-sided, with a value of P < 0.05 considered statistically significant.

RESULTS

A total of 54 patients participated in the study. Four patients were excluded because of inability to attend the 6-month wound follow-up, leaving 50 patients for the final analysis. The mean age of the participants was 40.2 ± 8.0 years, and the mean body mass index (BMI) was 23.3 ± 2.9 kg/m². No participants had diabetes mellitus (0%), whereas 4 (8%) had hypertension, 4 (8%) had dyslipidemia, and 1 (2%) was a smoker. The weight of tissue resection was 900.0 g (interquartile range [IQR], 645.0 to 1190.0 g), and the mean liposuction volume was 572.2 ± 217.7 mL. The operative time was 230.0 minutes (IQR, 213.75 to 270.0 minutes), and the incision length per side was 24.0 cm (IQR, 21.0 to 26.0 cm).

Table 1 presents the Observer Scale of the Patient and Observer Scar Assessment Scale. Wound outcomes were significantly better in the nanofat group compared with the nonnanofat group across all parameters, including vascularity, pigmentation, thickness, relief, pliability, surface area, and overall opinion (P < 0.001). No oil cysts or fat necrosis were observed in the nanofat group. Examples of wound outcomes at 6 months are shown in Figures 1 through 3.

Table 1.

Observer Scale of the Patient and Observer Scar Assessment Scale at 6 Months Comparing the Nanofat Group with the Nonnanofat Group

Parametera	Nanofat Group (IQR)b	Nonnanofat Group (IQR)b	P
Vascularity	2 (2–3)	4 (4–5)	<0.001
Pigmentation	2 (2–3)	4 (4–5)	<0.001
Thickness	2 (2–3)	4 (3–5)	<0.001
Relief	3 (2–3)	5 (4–5)	<0.001
Pliability	3 (2–3)	4 (4–5)	<0.001
Surface area	2 (2–3)	4 (4–5)	<0.001
Overall opinion	3 (2–3)	4 (4–5)	<0.001

IQR, interquartile range.

^a1 = normal skin, 10 = worst scar imaginable.

^bThe values are presented as median (IQR).

Fig. 1.

Six-month postinjection outcome on the right side of the patient, where nanofat was administered. Note the decrease in vascularity and pigmentation compared with the control side.

Fig. 3.

Six-month postinjection outcome on the left side of the patient, where nanofat was administered. Note the significant reduction in thickness, surface area, and pigmentation compared with the control side.

Fig. 2.

Six-month postinjection outcome on the left side of the patient, where nanofat was administered. Note the reduction in surface area and thickness compared with the control side.

DISCUSSION

Wound outcomes at 6 months were significantly better in the nanofat group. This improvement may be explained by 2 previously proposed hypotheses.^2,3 First, nanofat may shorten the inflammation phase of the wound healing process.³ Studies have shown that nanofat contains numerous up-regulated proteins associated with the inflammatory phase, including those involved in the complement and coagulation cascades, phagocytosis, acute inflammatory response, and interleukin-6 signaling pathways.⁴ Second, nanofat contains adipose-derived stem cells (ADSCs), which may modulate scarring through their diverse properties, such as reducing inflammation, releasing growth factors, and differentiating into various cell types.^2,8 Phenotypic analysis has demonstrated that nanofat contains 3 times the ADSCs of standard lipoaspirate.⁹

A key factor of this study’s success was the standardized dose of 0.5 mL per 2.5 cm of wound length. This dosing approach ensured even distribution of nanofat across the entire wound, unlike previous studies where the dosage was either not clearly defined or applied as a fixed volume regardless of wound length.^2,3,10 Furthermore, the dose used in this study—0.5 mL per 2.5-cm on both the upper and lower flap margins (equivalent to 1 mL per 2.5-cm of total wound length)—was nearly double that used in a prior positive trial (0.5 mL per 2-cm of total wound length).² The dose was also selected because it yielded positive results in the previous trial,² and we found during our pilot study that it was the maximal amount often required to inject before there could be some leakage of the nanofat from the wound area, which showed the redundancy of the injection of nanofat. However, whether the effect is dose-dependent or not still requires further study.

The application of nanofat in lipoabdominoplasty wounds is straightforward and practical. Because abdominoplasty is typically performed in conjunction with liposuction, the harvested fat—ordinarily discarded—can be repurposed for wound improvement. This study provides a standardized and reproducible method for nanofat application, making it accessible for routine practice. In addition, the process is cost-effective, as it uses fat that would otherwise be wasted.

The use of nanofat in this study has several limitations. First, the quality of the nanofat depends on the quality of the patient’s fat. In thinner patients, particularly those with a body mass index of less than 18 kg/m², the amount of available fat may be limited. In addition, different fat donor sites may yield varying amounts of ADSCs,¹¹ potentially affecting outcomes. Therefore, the results of this study are specific to using the abdomen as the donor site. Second, the accuracy of the results relies on proper fat harvesting and meticulous fat processing.¹² The Coleman harvesting technique used in this study has been shown to produce higher viable adipocyte counts compared with conventional liposuction.¹² Consequently, the findings are applicable specifically to the harvesting and nanofat processing methods described here. Third, achieving consistent results requires a standardized dose and technique for nanofat injection to ensure even distribution throughout the wound. Therefore, patient selection, fat harvesting, processing, and injection techniques are all critical to the study’s outcomes. Attention to detail in each step is essential to replicate the results.

In some cases, there is a notable observation that the nanofat improves the wounds along the lateral aspects, but not in the paramedian incision areas, despite being injected from the midline to the most lateral aspect of the wounds. The lack of response in these higher tension closure zones may be attributed to the significant impact of mechanical stress on wound scarring.^13–15 First, the wounds convert mechanical cues to biochemical signals that stimulate scarring.^13,14 Second, some of these signals are outside the scope of the nanofat involvement in wound healing.¹³ For example, there is an elevation of the expression of fibrotic genes, such as transforming growth factor-β, α-smooth muscle actin, and collagen I, affecting fibroblasts.^13,14 Also, there is a decrease in cellular apoptosis promoting hypertrophic scars.¹⁵ Third, some signals could decrease the effect within the scope of the nanofat such as the growth factor involvement.¹³ The mechanical stress can promote the myofibroblasts that generate high amounts of extracellular matrix with a pathologic structure and alterations in growth factor–binding capacity.¹⁶ This higher tension and additional biochemical signals may limit the effect of nanofat.

The nanofat could shorten the inflammation phase of the wound healing process, make the wound heal faster, and accelerate scar remodeling.^3,17,18 A previous study confirmed this hypothesis and found a significant reduction in the erythema index measured by spectrophotometry comparing nanofat-treated and -nontreated wounds at 3 months and 6 months.³ Moreover, the use of nanofat was found to result in earlier appearance of organized and mature forms of collagen and a significant increase in collagen distribution at 4 and 6 months.¹⁷ We also observed in this study that the wound in the nanofat-treated side tended to heal faster, which resulted in positive consequences that could be a prophylactic effect against bad scarring. For example, faster wound closure decreased the chance of wound dehiscence, which required the wound healing process to restart. Reduced pliability and thickness decreased the patients’ urge to touch or scratch the wounds, thereby reducing the risk of additional trauma. These circumstances are not the direct way to the lasting aesthetic benefit of the wound, but there are some circumstances around which the nanofat could indirectly contribute to the lasting aesthetic effect of the scar.

This study aimed to investigate the true nature and results of using nanofat in wound healing. This study found that the wound in the nanofat-treated side was significantly different from the nontreated side. However, the number of differences was not very powerful. For example, the median overall opinion was 3 in the nanofat group and 4 in the nonnanofat group. The median difference was 1 of 10 points. In the same way, the median vascularity was 2 in the nanofat group, compared with 4 in the nonnanofat group. The median difference was 2 of 10 points. Therefore, there were differences, but the differences might not be powerful enough to demonstrate all the changes that are easily noticeable in photographs. The wound evaluation by photographic assessment contained limitations and was the reason why this study used clinical judgment of the wounds that required in-person contact for the wound assessment.¹⁹ Furthermore, these significant differences and gentle improvements of using nanofat have also been found and demostrated in previous studies.^2,3,20

CONCLUSIONS

Wound outcomes were significantly better in the nanofat group compared with the nonnanofat group. No oil cysts or fat necrosis were observed in the nanofat group.

DISCLOSURE

The authors have no potential conflicts of interest with respect to the research, authorship, or publication of this article. All instruments described in the study were purchased by the authors without corporate involvement.

ACKNOWLEDGMENT

The authors would like to thank the Pheu Ter Foundation for supporting this study.