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CC BY 4.0 · Journal of Coloproctology 2025; 45(02): s00451809669
DOI: 10.1055/s-0045-1809669
Technical Note

Autologous Nanofragmented Lipoinjection (Nanofat) for the Treatment of Complex Anorectal Fistula Associated with Crohn's Disease

Alexandre Lopes de Carvalho 
1   Department of Colorectal Surgery, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, BA, Brazil
,
Lina Maria Goes de Codes 
1   Department of Colorectal Surgery, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, BA, Brazil
,
Alana Francisca Machado Melo 
1   Department of Colorectal Surgery, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, BA, Brazil
,
Flávia de Castro Ribeiro Fidelis 
1   Department of Colorectal Surgery, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, BA, Brazil
,
Bruna Fernandes Barreiro de Araújo 
1   Department of Colorectal Surgery, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, BA, Brazil
,
Fabio Pereira Soares de Araújo 
2   Department of Plastic Surgery, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, BA, Brazil
,
Tiago Pereira de Castro 
2   Department of Plastic Surgery, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, BA, Brazil
,
José Valber Lima Meneses 
2   Department of Plastic Surgery, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, BA, Brazil
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Funding No fundings were required for this manuscript.
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Abstract

The management of complex anorectal fistulas associated with Crohn's Disease (CD) remains a significant clinical challenge, with current treatments achieving limited success in long-term remission. This article explores the application of autologous nanofragmented lipoinjection (Nanofat) for the treatment of Perianal Fistulizing Crohn's Disease (PFCD). Nanofat, derived from adipose tissue and containing mesenchymal stem cells, offers the potential for tissue regeneration and immune modulation in the inflammatory environment of perianal CD. A patient with a chronic fistula, previously treated with Seton and maintained biologic therapy, underwent liposuction and nanofragmentation of adipose tissue. The resulting Nanofat was injected into the fistula tract following surgical debridement. The patient demonstrated complete healing with no recurrence of symptoms after six months, showcasing the efficacy of this technique. This autologous approach is low-cost, minimally invasive, and reproducible, with promising clinical outcomes. The addition of nanofragmented fat enhances tissue penetration and fat survival compared with traditional Microfat, increasing the chances of successful fistula repair. Further controlled studies comparing Nanofat with other established fistula repair methods are warranted to assess its long-term efficacy and standardize treatment protocols.


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Keywords

Perianal Crohn's disease - Crohn's disease - mesenchymal stem cell - cell regenerative therapy - microfragmented adipose tissue - nanofat

Introduction

The prevalence of Inflammatory Bowel Diseases (IBD) in Brazil and worldwide has been increasing significantly in recent years.[1] [2] Approximately 30% of Crohn's Disease (CD) patients may develop anal fistulas over the course of their lives,[3] with perianal disease being a very debilitating and difficult-to-treat phenotype.

Studies have shown healing rates of anal fistulas associated with CD to be up to ∼50% with the gold standard treatment: biological therapy associated with proctological Examination Under Anesthesia (EUA) in specialized centers, demonstrating that we are still far from achieving acceptable long-term remission rates for perianal disease.[4]

The surgical treatment techniques classically described in the literature for the definitive repair of perianal fistula associated with CD, whether fistulotomies or sphincter-preserving techniques, such as mucosal flap advancement, Ligation of the Intersphincteric Fistula Tract (LIFT) or Video Assisted Anal Fistula Treatment (VAAFT), have not yet achieved the desired efficacy and may evolve with sequelae such as deformities and postoperative incontinence to a greater or lesser degree.

The search for better control of Perianal Fistulizing Crohn's Disease (PFCD) and the progressive increase in the use of cell therapy in several areas of Medicine with encouraging results prompted us to apply autologous lipoinjection with mesenchymal stem cells in our institution. We added Nanofragmentation of the fat graft, as described by Tonnard et al.,[5] [6] to the already described microfragmented graft techniques,[7] [8] with good results.


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Surgical Technique

First, the patient did not have proctitis and was using maintenance doses of infliximab combined with azathioprine, having previously undergone an EUA with a seton in place ([Fig. 1A]). During anesthetic induction, antibiotic prophylaxis with cephalosporin and metronidazole was administered, and spinal anesthesia was administered. The patient was positioned in the supine position and the plastic surgery team performed two small incisions in the suprapubic sulcus 5–6 cm from the midline and injected 0.9% saline solution (∼200–300 ml) with a 1:500,000 dilution of epinephrine through a small-bore cannula. After a few minutes, a 60 ml syringe connected to a 2.5 mm blunt grater-type cannula was inserted through the same incision into the selected area (abdomen) to be liposuctioned ([Fig. 1B]), according to the standardized liposuction technique.[9] [10] [11] A sufficient volume was aspirated to collect ∼40 ml of Nanofat, the amount to be used in the recipient area. The skin incision was closed with 5–0 mononylon.

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Fig. 1 (A): Anal fistula with seton; (B): Lipoaspiration, (C): Emulsification of Microfat to obtain Nanofat, (D): Nanofat injection.

The liposuctioned product was subjected to the decantation process for ∼10 to 15 minutes, in syringes held vertically downwards. Then, after the decantation process and removal of the liquid component from the lower part, the microfragmented fat (Microfat) was transferred to other syringes to undergo nanofragmentation according to the protocol[5] [6] using 1.2 and 2.4 mm Luer-Lok connectors, with 30 passages through each connector ([Fig. 1C]). After the emulsification process, the fatty liquid was passed through a cartridge with a double filter of 400/600 microns, thus obtaining Nanofat. Note the difference between Microfat and Nanofat, with the latter having a more homogeneous consistency and allowing for application in thinner syringes with easier dispersion ([Fig. 2A]). Mesenchymal stem cells isolated from Nanofat ([Fig. 2B]).[5]

Zoom Image
Fig. 2 (A): Microfat left hand side, Nanofat right hand side. (B): Stem Cells collected from Nanofat. Extracted From (5).

Immediately after the Nanofat collection, the patient was repositioned to the lithotomy position. The seton performed in a proctological examination under prior anesthesia was removed, after adequate identification of the external and internal orifices. Vigorous curettage of the entire tract was performed for cleaning, removal of granulation tissue, and de-epithelialization. Then, a 0.9% saline solution was injected into the tract for cleaning.

The external cutaneous orifice was resected, and its area was enlarged. Subsequently, the internal orifice was treated and closed using separate stitches with absorbable Polyglactin 3.0 thread. Finally, Nanofat was injected using blunt microcannulas fractionally measuring 1.8 to 2.0 mm and retroinjected, totaling a volume of 40 ml, half of which was injected into the topography of the internal orifice and the other half in multiple injections parallel to the fistulous tract ([Fig. 1 D]), with the aim of Nanofat always being in close contact with the fistula, since the effect of stem cells is more effective locally.[12] The patient was discharged from the hospital in less than 24 hours and continued antibiotic therapy with quinolone and metronidazole for another 14 days. At the end of 6 months, he was asymptomatic, and the surgical site was completely healed ([Fig. 3]).

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Fig. 3 Wound healed.

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Discussion

Stem cell therapy is currently gaining increasing attention and represents a search for better results in the treatment of PFCD. It is part of the sphincter-sparing techniques and finds a great application in PFCD given the continuous and disordered pro-inflammatory environment associated with local immune dysfunction in perineal CD and the immunomodulatory and regenerative capacity of cell therapy. In PFCD, we have an increase in the pro-inflammatory cytokines IL-8, IL 1-b, IL-6 and IL-13, a reduction in IL 17-a and an increase in matrix metalloproteinases 3 and 9.[13] Fat-derived mesenchymal stem cells can suppress the proliferation of activated T lymphocytes and NK cells with a reduction in pro-inflammatory mediators such as TNF-a, IL-6, IL12, IL1-b and an increase in anti-inflammatory mediators such as IL-10.[14] There is still no standardization in the literature on which is the best source of stem cells, whether derived from bone marrow or adipose tissue, whether there are advantages to the graft being heterologous or autologous, as well as the number of cells used in each application.

This is a relatively low-cost surgical technique, since the graft is autologous and easy to obtain, requiring only one combined surgical procedure, through a reproducible technique. It does not require high-cost materials such as allogeneic grafts or autologous cell cultures obtained in vitro.

In addition, the autologous lipoinjection surgical procedure has low morbidity, with reports of mild local pain and small local abscesses with reduced frequency. In cases of recurrence, the procedure can also be performed again without major technical difficulties. The healing rates of fistulas range from 51% to 60% and the clinical response rate is up to 80%.[7] [8] [15]

The addition of nano-fragmented fat (Nanofat) provides a more homogeneous, emulsified graft with better fluidity and better tissue penetration capacity when compared with Microfat. Fat particles depend on the diffusion of nutrients during their initial incorporation phase before revascularization. Therefore, more emulsified grafts tend to distribute more easily, thus avoiding central necrosis zones in the injected fat pockets, increasing the probability of particle survival. Fat graft survival benefits from smaller particles and smaller fat aliquots injected per passage. Since fat graft survival becomes more predictable with the use of smaller fat particles, better fat survival also results in less fat necrosis and greater viability.

Therapy with nano-fragmented autologous lipoinjection (Nanofat) with stem cells in patients with PFCD appears to be safe and promotes fistula healing after the removal of the setons and closure of the internal orifice. Studies with control groups using other definitive fistula repair techniques such as mucosal flap advancement, LIFT and VAAFT, associated or not with autologous lipoinjection, are necessary to better evaluate the effectiveness of this innovative technique.

Ethical Approval

I am writing to inform you that the article titled “Autologous Nanofragmented Lipoinjection (Nanofat) for the Treatment of Complex Anorectal Fistula Associated with Crohn's Disease” has received approval from the Ethics Committee of the Hospital Universitário Professor Edgard Santos (HUPES). The approval was granted under the protocol number 6.444.094.


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Conflicts of Interests

There are no conflicts of interest.


Address for correspondence

Alexandre Lopes de Carvalho, MD
Department of Colorectal Surgery, Professor Edgard Santos University Hospital, Federal University of Bahia
Salvador, BA
Brazil   

Publication History

Received: 02 April 2025

Accepted: 22 May 2025

Article published online:
26 June 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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Bibliographical Record
Alexandre Lopes de Carvalho, Lina Maria Goes de Codes, Alana Francisca Machado Melo, Flávia de Castro Ribeiro Fidelis, Bruna Fernandes Barreiro de Araújo, Fabio Pereira Soares de Araújo, Tiago Pereira de Castro, José Valber Lima Meneses. Autologous Nanofragmented Lipoinjection (Nanofat) for the Treatment of Complex Anorectal Fistula Associated with Crohn's Disease. Journal of Coloproctology 2025; 45: s00451809669.
DOI: 10.1055/s-0045-1809669

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Zoom Image
Fig. 1 (A): Anal fistula with seton; (B): Lipoaspiration, (C): Emulsification of Microfat to obtain Nanofat, (D): Nanofat injection.
Zoom Image
Fig. 2 (A): Microfat left hand side, Nanofat right hand side. (B): Stem Cells collected from Nanofat. Extracted From (5).
Zoom Image
Fig. 3 Wound healed.