Ahmed Mokhallalati and Firas Niaimi review the clinical applications for autologous fat transplantation, techniques,  and possible complications

This is the era of cosmetic advancements, where a variety of new procedures have been made widely available to the public. Many non-invasive or minimally-invasive procedures, where downtime is minimal and the cost is reasonable, have enthused people to seek  consultations for these treatments. One particular procedure that is gaining popularity is fat transfers or autologous fat transplantation.

In the world of cosmetic surgery, fat transfer entails removing fat from one area of the body, for example, the abdomen, and injecting it into another, such as the buttocks or breasts. That way, it could act as an alternative to augmentation surgery.

The following article is going to review the clinical applications of autologous fat transplantation, techniques, adipose derived stem cells (ADSC), and possible complications.

A review of literature was conducted to identify publications discussing autologous fat grafting using the following keywords alone and in combination: fat grafting, fat transfer, adipocyte graft, lipotransfer, fat harvesting, processing of fat graft, fate of grafted fat, fat grafting survival,  buttocks augmentation, breast augmentation, hand rejuvenation, fat transfer techniques, adipocyte-derived stem cells, nanofat grafting, microfat grafting, and complications of fat grafting. The search was conducted using Ovid, Pubmed, and Google Scholar engines. The retrieved articles were reviewed, and relevant publications were selected based on the date of publication and the strength of the evidence presented. Only studies published in the last 5 years were included, except for one study published in 1995, as the recommendations of this study still widely used nowadays.

Clinical applications for fat grafting

Although the exact mechanism of fat graft retention remains to be understood, the clinical applications of autologous fat grafting continue to expand. It is indicated in any volume loss due to ageing, infection, scleroderma, trauma and natural irregularity or asymmetry, as well as a lot of other cosmetic applications.

Facial fat transfer

The face is a common area for fat transfer procedures to take place, as micro- and nano-fat grafting can be used. Facial fat transfer can be used as a solo procedure for a filling or a rejuvenating effect, or as an adjuvant procedure to rhytidectomy (commonly referred to as facelift). Facial fat transfers can address certain areas that cannot usually be treated with facelifting alone. Moreover, fat grafting could also be used for volume restoration in any facial asymmetry1.

Fat grafting for volume restoration is popular in the following areas:

  • Lower eyelid and lateral canthus
  • Superior orbital rim/glabella, forehead, temple, and upper eyelid
  • Cheek and perioral area
  • Mandible and chin1.

Appropriate patient selection, detailed knowledge of the anatomy and physiology of the ageing skin and a full understanding of the procedure is of prime importance for effective results.

Breast augmentation

Another indication is breast augmentation for both reconstructive and cosmetic purposes. Its popularity has increased following skin-preserving mastectomy, as well as for correcting asymmetries post-breast masses excision.

Spear SL et al., 2016, reviewed the available literature and concluded that fat grafting is an effective and safe method for breast augmentation, with high satisfaction rates2.

Buttocks augmentation

Buttocks augmentation, another trend that has been influenced by some famous figures, can be achieved either through implants or fat grafting. Fat grafting is often superior to implants, as a well-defined contour can be attained. Furthermore, the complication rate is lower compared to implant-based augmentation3.

Well-contoured buttocks have gained popularity in recent years. Fat injections can be performed in different planes to augment the buttocks and lateral trochanteric areas. They can be injected as an additional procedure along with gluteal implants either concomitantly or as a secondary procedure.

Fat transfer to the hands

Even with the most skilled rejuvenating and lifting procedures to the face, one cannot easily camouflage the signs of ageing in the hands. Fortunately, many methods have been used for hand ageing that include dermal fillers and fat transfer. Compared to dermal fillers, fat grafting has a longer lasting volumetric effect. In addition, it could also improve the quality of the aged and scarred skin4.

Tissue regeneration

Due to the regenerative and remodelling properties of lipo-aspirate, it has been successfully injected for painful scar contractures and nerve entrapments. Additionally, it showed improvement in the management of chronic wounds, burns and post mastectomy pain syndrome5.

Miscellaneous

Lip augmentation using fat transfer has been reported as a safer and more natural procedure compared to other injectable fillers. Sharp-needle intradermal fat grafting (SNIF) is usually used at a very superficial subcutaneous level6.

Calf augmentation using fat has also been attempted to improve the cosmetic appearance of calves, whether for therapeutic or cosmetic reasons.

Fat grafting techniques

Fat grafting has gained popularity as a natural filler to reconstruct soft tissue defects and asymmetries. Many techniques have been used, and many studies have been conducted to improve the intake of fat graft.

Harvesting

There is no significant difference in fat graft survival between the various donor sites. Donor area selection is based on the ease of access, the patient’s preference and the amount of fat needed.

tumescent solution is a dilution of an anaesthetic agent and a vasoconstrictor in a large volume of fluid, typically normal saline. It is used to minimise bleeding and pain and facilitate liposuction. Liposuction can be performed under local, regional or general anaesthesia.

The procedure is executed using a harvesting cannula under a full aseptic technique. Multiple cannulas are available with various sizes and variable designs of perforations and tips.

The term micro-fat grafting refers to the use of smaller cannulas to both harvest and inject the lipo-aspirate, resulting in smaller size fat lobules. It is a modification of the traditional fat grafting.

A literature review demonstrated that a larger diameter cannula enhances fat viability7. A 3-mm cannula is used to obtain a macro-fat graft, while a 2.4 mm cannula, with barbed and bevelled 1 mm ports, is usually used to obtain micro-fat graft. Micro-fat graft can be injected either via a cannula or as a sharp-needle intradermal fat graft (SNIF).

Traditional liposuction is usually used to obtain the fat graft, as opposed to the ultrasound-assisted liposuction and other energy-based liposuction, which results in less fat graft viability6.

Fat processing

Many techniques have been used for processing the harvested lipo-aspirate. Processing methods are expected to isolate the adipose tissue aspirated from the oil, blood and debris as well as other unwanted components of the tumescent fluid in order to improve the viability of the fat graft.

Fat processing techniques vary from simple decantation, which is a separation of the layers after sedimentation, to complex centrifugation. Washing the aspirate with saline, Ringer lactate or other solutions can be used alone or as a complementary procedure. Cotton gauze (Telfa) rolling of the aspirate and filtration are frequently used procedures.

Despite the fact that no single technique has emerged as clearly superior to the others, the literature shows that simple decantation has demonstrated lower graft viability relative to washed and centrifuged aspirate8.

Centrifugation is the most widely used technique for processing the fat and the most commonly used protocol is the one proposed by Coleman, 1995, at a rate of 3000 rpm for three minutes. After centrifugation, three levels can be observed in the tube. The lower one contains blood, debris and water, while the upper is an oil formed by fatty acid breakdown. The middle layer consists of the fat that is meant to be injected8.

Higher rates or a longer duration time of centrifugation have demonstrated a decrease in graft retention9.

Washing was approved to improve fat viability, either with filtration or decantation. Others are rolling the aspirate using specialised gauze pads. There is only limited evidence to support the addition of stromal vascular fraction (SVF) to improve graft viability9.

Delivery

Delivery of the fat lipo-aspirate is considered by some surgeons to be the most important step in the whole process of fat grafting. There is no standardised technique on how to place the fat; however, most surgeons inject in multiple passes and different tissue planes with a small amount of fat in each pass to improve the outcome6.

Recently, overcorrection was found to be no more indicated and lacks scientific support6.

Nano and micro-fat transfers

Depending on the indications of fat grafting, certain modifications can be implemented during the fat preparation, processing and injection. For delicate areas, such as eyelids, the aspirated fat can be injected using smaller cannulas, as small as 0.7 mm in diameter. Lipo-filling with such small cannulas, also called micro-fat grafting, has been used to address fine superficial wrinkles.

To validate the difference between conventional liposuction and micro-fat grafting, a study performed by Alharbi Z, et al., showed that the micro-fat technique improves the fat graft survival rate, with levels of growth factors and ADSCs found in the injected lipo-aspirate10.

As mentioned earlier, SNIF is a technique of superficial intradermal injection of micro-fat, with sharp needles of 23-gauge. SNIF has been introduced as a natural filler to the face and has demonstrated longer lasting results than usual dermal fillers11. It is a safe procedure, with no serious side-effects, such as necrosis or fat emboli. It may, however, result in transient ecchymosis or edema, but with no surface irregularities observed11.

A new concept, nano-grafting, is under experimentation. It involves the use of finer needles to maximise the efficacy of the traditional fat graft and to access more superficial planes. The harvested fat is further emulsified and filtered until a liquid material is obtained. It could be used for skin rejuvenation, but the mechanism of action is yet to be known. Studies of nano-fat showed the death of all adipocytes, with survival of the adipose-derived stem cells (ADSC)12.

Fat grafting survival

Despite the wide use of autologous fat grafting in both cosmetic and reconstructive medicine for the last two decades, a wide range of fat graft retention rates are still reported.

This issue has been studied by Eto et al., 2012 and Kato et al., 201413,14. For a better understanding of the survival of fat grafts, they divided the injected fat mass into three zones; the outermost layer or the surviving zone, the inner most layer or the necrotic zone, and the regenerating zone between the two.

In the surviving zone, as it is in direct contact with the receiving area, usually both adipocytes and ADSC survive. Whereas in the regenerating zone, the adipocytes undergo apoptosis (programmed cell death). Owing to their resistance to hypoxia, the ADSCs tend to survive better. Once adipocytes die, they send a series of signals to the ADSCs to initiate differentiation and proliferation into adipocytes. In the necrotic zone, as the name indicates, both adipocytes and ADSCs die to form oily cysts or scar tissue13,14.

Increasing fat graft retention rates poses a particular challenge. Multiple studies have been conducted, and improvement of retention is an ongoing process7–14. Recent reports have supported the enrichment of the lipo-transfer with stromal vascular fraction (SVF) cells or by using other pro-survival additives, for instance, platelet-rich plasma (PRP). In addition, work on optimising the receiving area and improving the post-operative care has gained interest15–17.

Adipose-derived stem cells

Adult stem cells are the most promising cell types for cell-based therapy and regenerative medicine18. By definition, stem cells are cells that have the ability to undergo self-renewal and differentiation. Recently, adipose tissue has been introduced as an ideal source of multipotent stem cells. The ADSCs are considered superior to other mesenchymal stem cells, for example from bone marrow, as ADSCs can be easily and repeatedly harvested using minimally invasive techniques.

ADSCs are multipotent with the ability to differentiate into several cell types of the tri-germ lineages, for example, adipocytes, osteocytes, neural cells, cardiomyocytes, vascular endothelial cells, pancreatic-cells, and hepatocytes. Interestingly, ADSCs have the advantage of low immunogenicity as well as their secretion of trophic factors. Taken together, these particular attributes of ADSCs have pushed them into the field of cosmetic and reconstructive medicine18.

Adipose tissue of the subcutaneous plane is formed mainly by mature adipocytes and a heterogeneous SVF, which contains fibroblasts, endothelial cells, pre-adipocytes, vascular smooth muscle cells, lymphocytes, monocytes, and ADSCs.

Many methods have been tried to isolate ADSCs from adipose tissue. The most widely used relies on two stages. First, collagenase digestion, washing and centrifugation to separate the SVF from mature adipocytes. The next step is to isolate the ADCS from the SVF. Cells within the SVF can be categorised using a number of cell-type specific markers. The precise phenotypic characterization of ADSCs is still unknown. ADSCs show the stem cell-specific combination of surface markers, such as CD90, CD105, CD73, CD44 and CD166, and lack the expression of the hematopoietic markers CD45 and CD3419.

Since the discovery of the exciting potential of stem cells, regenerative and cosmetic medicine have advanced tremendously. The use of ADSCs for fat tissue reconstruction has been used in reconstruction of both breast and soft tissue as well as many cosmetic procedures. ADSCs also have a vital role in wound healing and skin rejuvenation. Theoretically, ADSCs have demonstrated the capability to differentiate into many mature cells in vitro. However, the clinical application of this theory is still limited due to the lack of clear and efficient differentiation protocols for various cell types19.

Complications of fat grafting

Although fat grafting is a minimally invasive procedure, care must be taken not to harm the donor or recipient areas. The most common complications are no, or minimal, graft retention; oil cysts; and calcifications or infection. Most of these complications are related to fat necrosis.

The most catastrophic complication of fat grafting is embolization after intravascular injection of fat. Embolization is a rare complication, usually seen in facial fat grafts, which can result in blindness, stroke or tissue necrosis in facial fat injection. These complications can be avoided by using blunt needles with small boluses of fat20.

Donor site problems are not common. With irregularities of the donor site being the most common. Seroma or hematoma sometimes occur in larger procedures20.

Conclusion

Fat grafting has been widely used as an injectable filler to augment tissue and correct soft tissue defects. Recently, it has been introduced as a stimulant to enhance tissue remodelling and regeneration.

Every step of the fat grafting process has been studied, and practitioners agree on general concepts, but no particular practice has proved its superiority. Still, unpredictable graft retention is the main disadvantage, and many pro-survival additives have been used to improve graft survival such as PRP and SVF cells.

The full potential for ADSC and adipocytes has yet to be explored and understood completely in order to fully benefit from the true potential of autologous fat.

Declaration of interest None

References:

  1. Buckingham ED. Fat transfer techniques: general concepts. Facial Plastic Surgery. 2015 Feb;31(01):022-8
  2. Spear SL, Coles CN, Leung BK, et al. The safety, effectiveness, and efficiency of autologous fat grafting in breast surgery. Plastic and Reconstructive Surgery Global Open. 2016 Aug;4(8)
  3. Sinno S, Chang JB, Chaudhry A, et al. Determining the Safety and Efficacy of Gluteal Augmentation: A Systematic Review of Outcomes and Complications. Plastic and reconstructive surgery. 2014 Oct 1;134(4S-1):130.
  4. Butterwick K, Sadick N. Hand Rejuvenation Using a Combination Approach. Dermatologic Surgery. 2016 May 1;42:S108-18
  5. Hsu VM, Stransky CA, Bucky LP, et al. Fat grafting’s past, present, and future: why adipose tissue is emerging as a critical link to the advancement of regenerative medicine. Aesthetic surgery journal. 2012 Sep 1;32(7):892-9
  6. Serra-Renom JM, Serra-Mestre JM. Fat Grafting: Principles and General Concepts. InAtlas of Minimally Invasive Facelift 2016 (pp. 11-16). Springer International Publishing
  7. Gir P, Brown SA, Oni G, et al. Fat grafting: evidence-based review on autologous fat harvesting, processing, reinjection, and storage. Plastic and reconstructive surgery. 2012 Jul 1;130(1):249-58
  8. Coleman SR. Long-term survival of fat transplants: controlled demonstrations. Aesthetic plastic surgery. 1995 Sep 1;19(5):421-5
  9. Cleveland EC, Albano NJ, Hazen A. Roll, spin, wash, or filter? Processing of lipoaspirate for autologous fat grafting: an updated, evidence-based review of the literature. Plastic and reconstructive surgery. 2015 Oct 1;136(4):706-13
  10. Alharbi Z, Opländer C, Almakadi S, et al. Conventional vs. micro-fat harvesting: how fat harvesting technique affects tissue-engineering approaches using adipose tissue-derived stem/stromal cells. Journal of Plastic, Reconstructive & Aesthetic Surgery. 2013 Sep 30;66(9):1271-8
  11. Zeltzer AA, Tonnard PL, Verpaele AM. Sharp-needle intradermal fat grafting (SNIF). Aesthetic Surgery Journal. 2012 Jul 1;32(5):554-61.
  12. Tonnard P, Verpaele A, Peeters G, et al. Nanofat grafting: basic research and clinical applications. Plastic and reconstructive surgery. 2013 Oct 1;132(4):1017-26
  13. Eto H, Kato H, Suga H, et al. The fate of adipocytes after nonvascularized fat grafting: evidence of early death and replacement of adipocytes. Plastic and reconstructive surgery. 2012 May 1;129(5):1081-92
  14. Kato H, Mineda K, Eto H, et al. Degeneration, regeneration, and cicatrization after fat grafting: dynamic total tissue remodeling during the first 3 months. Plastic and reconstructive surgery. 2014 Mar 1;133(3):303e-13e
  15. Kølle SF, Fischer-Nielsen A, Mathiasen AB, et al. Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival: a randomised placebo-controlled trial. The Lancet. 2013 Oct 4;382(9898):1113-20
  16. Tanikawa DY, Aguena M, Bueno DF, et al. Fat grafts supplemented with adipose-derived stromal cells in the rehabilitation of patients with craniofacial microsomia. Plastic and reconstructive surgery. 2013 Jul 1;132(1):141-52
  17. Serra-Mestre JM, Serra-Renom JM, Martinez L, et al. Platelet-rich plasma mixed-fat grafting: a reasonable prosurvival strategy for fat grafts?. Aesthetic plastic surgery. 2014 Oct 1;38(5):1041-9
  18. Frese L, Dijkman PE, Hoerstrup SP. Adipose tissue-derived stem cells in regenerative medicine. Transfusion Medicine and Hemotherapy. 2016 Jul 26;43(4):268-74
  19. Wankhade UD, Shen M, Kolhe R, et al. Advances in adipose-derived stem cells isolation, characterization, and application in regenerative tissue engineering. Stem cells international. 2016 Feb 11;2016
  20. Yoshimura K, Coleman SR. Complications of fat grafting: how they occur and how to find, avoid, and treat them. Clinics in plastic surgery. 2015 Jul 31;42(3):383-8


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