Keywords
fat grafting - autologous fat transfer - lipofilling - adipose derived stem cells
- volume augmentation - regeneration
Records of adipose tissue transfer have been described for decades dating back to
1893 when Neuber performed the first autologous adipose tissue transfer to a facial
depression scar.[1] However, it was not until the year 1997 that it gained massive popularity when Coleman
described a new advanced technique of fat harvesting that substantially diminished
complications and improved graft survival.[2] Since then, the number of clinical applications for fat grafting has been growing
exponentially not only for volume replacement, but also for tissue quality improvement.[3]
Fat is a readily available tissue that does not trigger an immune response or cause
significant donor site morbidity when harvested.[4] Autologous fat grafts are currently being used in a wide variety of procedures in
both reconstructive and aesthetic plastic surgery. Some of the prominent applications
include primary breast augmentation, breast recontouring, rhinoplasty, facial and
hand rejuvenation, and scars treatment.[3]
[5]
[6]
[7]
[8]
[9]
[10]
[11] In addition, reports of its use in correcting deformities such as Parry–Romberg
syndrome, Poland syndrome, and Dupuytren's contracture have been described.[12]
[13]
[14]
[15]
Despite its widespread use, one of the main dilemmas when grafting fat tissue is the
unpredictable resorption, both in location and extent, resulting in the need for multiple
injections, and in some cases poor aesthetic outcome.[16]
[17] Harvested adipose tissue is composed of mature adipocytes, extracellular matrix,
and a stromal vascular fraction (SVF) that is constituted by several types of cells
including adipose-derived stem cells (ADSCs).[18]
[19] Although remains an area of debate, ADSC-enriched grafts have been associated with
better graft viability and outcome after transplantation.[19]
[20]
[21] Furthermore, different harvesting techniques can result in different outcomes in
regards to fat graft take.[16] Therefore, establishing best-practice guidelines for fat grafting methodology is
of utmost importance moving forward to minimize fat graft loss.
Principles of Fat Grafting
Principles of Fat Grafting
For many decades, fat was considered an inert source of energy. However, studies have
demonstrated that adipose tissue has the potential for proliferation and regeneration.
Almost 50% of the in vivo adipose tissue cells consists of ADSCs, in addition to fibroblasts,
endothelial cells, and pericytes.[22] Those ADSCs are multipotent stem cells that have the potential for both proliferation
and differentiation.[23] This regenerative potential has been demonstrated in several clinical studies involving
angiogenesis, peripheral nerve regeneration, scarring, and osteoarthritis.[24]
[25]
[26]
[27]
[28]
[29]
[30]
When transferred as an avascular graft, three cellular zones are formed. The most
peripheral zone, containing adipocytes that survive the resultant hypoxia; a regenerative
zone, directly underneath containing ADSCs that revascularize and regenerate into
new adipocytes; and a central necrotic zone where no cells survive ([Fig. 1]).[31]
[32]
[33] Since oxygen diffusion is the rate-limiting step, only microdroplets with a regenerative
zone of maximum depth of 1.6 mm are able to fully survive the transfer.[33] Therefore, to ensure minimal necrosis, large graft volumes must be sprinkled in
a three-dimensional (3D) fashion to create microdroplets that do not coalesce ([Fig. 2]).
Fig. 1 Only microdroplets with radii less than 1.6 mm will completely revascularize and
survive.
Fig. 2 Sprinkle micrograft delivery is performed to maximize graft-to-recipient interface.
To understand how much fat can be grafted successfully into a given recipient site,
one should think of a fat graft in the same way we think of the stoichiometry of a
chemical reaction, as explained by Khouri et al.[34] To achieve a revascularized graft–recipient complex (GR), a fat droplet (G) must
combine with a capillary receptor site (R). Therefore, a certain amount of recipient
sites (R) can only accommodate a limited amount of graft (G) without resulting in
graft necrosis ([Fig. 3]). While fat grafting success is frequently measured as graft survival percentage,
this measure tells us nothing about the actual increase in volume. For example, in
a volume augmentation procedure, this measure provides no information on the volume
increase from the original volume at the recipient site.
Fig. 3 Stoichiometry of fat grafting principle as described by Khory et al in 2017.[34] To create a surviving graft–recipient complex, a unit graft (G) has to interact
with a capillary recipient site (R). If only four recipient sites (4R) are available,
adding 10 grafts (10G) will at best result in four surviving grafts (4RG) and six
necrotic grafts, with 40% graft survival rate. By carefully adding the maximum amount
of grafts a recipient site can tolerate, the procedure will yield 100%graft survival.
Fat Grafting Technique
The process of fat grafting can be arbitrarily divided into five main components—(1)
donor site selection, (2) graft harvesting, (3) graft processing, (4) recipient site
preparation, and (5) graft delivery. Based on the volume harvested, fat grafting can
also be classified into three categories—small volume (< 100 mL), typically for facial
rejuvenation or regenerative purposes; large volume (100–200 mL), primarily for breast
and body contouring; or mega volume (> 300 mL), mainly for gluteal augmentation, breast
augmentation, or breast reconstruction.
Donor Site
When it comes to choosing the donor site, several body areas that uniformly have abundant
fat are suitable for harvesting. A comparison was done by Li et al on fat grafts harvested
from six women using different donor sites including the flanks, upper and lower abdomen,
and lateral and inner thigh. Their results demonstrated no significant differences
among the donor sites in regards to weight, volume, or histological features (including
fibrosis and neovascularization), and concluded that factors such as accessibility
and patient preference should be considered for donor site selection.[35] As a general rule, donor sites that improves body contour are preferred by patients
and are easily accessible by surgeons.
Recipient Site
Determining the capacity of the recipient site is key when planning the amount of
graft to be harvested. Recipient capacity is a function of volume and mechanical compliance.
This is commonly estimated by the palm-and-pinch technique. Laxity and thickness are
approximated by pinching the tissue, whereas the palm estimates the surface area (the
average palm size of a man is 200 cm2).
Recognizing the grafting capacity of a recipient site is vital, and attempting to
graft more is counterproductive. The surgeon must always keep in mind not to graft
beyond what the recipient site can physiologically stretch to accommodate. However,
the key for a successful large volume autologous fat transfer is external volume expansion.
Studies have shown that it can induce adipogenesis, enhance tissue vascularity, and
increase recipient capacity and mechanical compliance, thereby priming the recipient
site for a large volume fat transfer.[36]
[37]
[38]
[39]
[40]
Harvesting, Processing, and Delivery
After selecting the donor site and optimizing the recipient site, determining the
harvesting approach becomes the next step. Direct excision, manual aspiration, and
liposuction are among the techniques described in the literature.[41] For liposuction or manual aspiration to be performed, negative pressures are required.
Despite the heterogeneity between the negative pressure values suggested by different
authors, it is well accepted that low vacuum pressure is less traumatic and enhances
graft viability.[42]
Based on the volume of the solution injected into the fat donor site, several liposuction
techniques can be identified including the dry technique, the wet technique, the superwet
technique, and the tumescent technique. The tumescent technique, first introduced
by Klein in 1987, uses large amounts of a very dilute solution, usually lidocaine
with epinephrine, that is injected into the subcutaneous fat compartments until a
swollen state (tumescence) and complete local anesthesia (tumescent local anesthesia)
are achieved.[43] The tumescent solution has to be injected 45 minutes before harvesting to ensure
adequate hydrodissection. The resultant ratio of infiltrate volume to total aspirate
volume is typically 2 to 3:1 L. This technique is considered to be the safest method
of fat removal as associated blood loss is around 1% of the aspirated volume and general
anesthesia is not required.[41]
Proper graft delivery is an extremely important factor that is often underappreciated
in the literature. An even distribution of the fat graft at the recipient site is
the key for a successful injection. A “blunt” tip smaller-gauge cannula is generally
used for reinjecting the graft. The surgeon should inject the fat gently and slowly
to avoid injuries to underlying structures, reduce shear stress, and increase graft
viability. Multiple passes should be performed while depositing small amounts of fat
with each pass at a rate of almost < 0.1 mm/cm. This technique limits fat clumping
and eventual necrosis of the graft.[34]
Clinical Applications
Breast Applications
Ever since the concept of fat grafting to the breast was first introduced in 1895
by Czerny, multiple breast-related applications were described.[44] The technique, however, was not without controversy as many feared its potential
interference with breast cancer screening. In 2007, Rigotti et al published a study
reporting no increase in breast cancer recurrence rate in women who underwent breast
reconstruction using fat grafting.[28] Additional studies have also proven that radiographic follow-up of fat grafted breasts
does not preclude accurate breast cancer screening.[45]
[46] It was not until 2009 when the Fat Grafting Task Force of the American Society of
Plastic Surgeons released a study describing fat grafting along with a statement saying
“[f]at grafting may be considered for breast augmentation and correction of defects
associated with medical conditions and previous breast surgeries; however, results
are dependent on technique and surgeon expertise.”
Augmentation Mammoplasty
When using fat for augmentation, one must always remember that fatty tissue is not
an expander. The capacity of the recipient site must be increased prior to fat grafting
in order for the site to be augmented, particularly for those with very small breasts
or tight skin envelopes. Using external volume expansion prior to grafting is often
advocated with consistent and remarkable results.[47] In recent years, fat grafting for breast augmentation have shown great aesthetic
outcomes with high patient satisfaction in regards to size, shape, and texture of
the breast mound. Li et al, Zheng et al, and Coleman and Saboeiro all reported autologous
fat graft as an effective approach for cosmetic breast augmentation.[48]
[49]
[50]
Breast Reconstruction
Using fat grafting for breast reconstruction is more challenging than primary augmentation
due to the accompanied loss of compliance and vascularity. In addition, the mastectomy
scar and radiation-induced damage result in an environment that is unfavorable for
graft survival. Nonetheless, breast reconstruction with autologous fat transfer offers
the advantage of having a soft, sensate, and a naturally appearing breast mound. The
number of fat grafting sessions required to reconstruct a mastectomy often depends
on the history of breast radiation and the degree of scar tissue from previous failed
reconstructions. Nonirradiated mastectomy with minimal scarring often requires three
consecutive grafting sessions, each three months apart.[34] On the other hand, an irradiated breast generally requires two further sessions,
and additional scarring from prior failed reconstructions might require even more.[34]
Primary reconstruction of the breast is not the only application of autologous fat
grafting following a mastectomy. Secondary contour deformities of the reconstructed
breast are common and often pose a frequent therapeutic challenge to the reconstructive
surgeon.[51] Fat grafting offers a simple solution to restore the normal contour of the breast
following reconstruction. In fact, lipofilling became the workhorse for the correction
of defects and asymmetry following breast cancer surgery.[52]
[53] Another important applications are improving soft tissue coverage following breast
implant placement as well as volume augmentation after autologous flap reconstruction.[52]
[53]
Multiple reasons can lead the patient or the surgeon to the decision of removing an
implant. Despite being a frequently performed plastic surgery procedure, implant-based
breast reconstruction can be associated with considerable revision rates.[54] Several investigators have advocated for autologous fat transfer as an alternative
or an adjunct to a second implantation. Replacing implant volume with autologous fat
can be the simplest solution to several of the implant problems. The resultant cavity
after implant removal is the ideal recipient for fat transfer, particularly when implant
explanation and fat grafting are performed simultaneously during the same procedure.[34] Immediately after removal, the tissues are lax and maximally compliant to accommodate
the grafted fat. However, over time, should the cavity remain empty, the excess skin
folds over and retracts creating deep wrinkles.[34]
Gluteal Augmentation
Gluteal augmentation with autologous fat transfer is an increasingly popular well-established
procedure with the ability to transform the entire body silhouette of the patient.[55] There are several advantages to the use of autologous fat grafting for buttock augmentation.
Fat transfer allows focused augmentation and contouring of the gluteal and thigh region
in addition to reduction of adjacent body regions, thereby resulting in improvement
of the overall body aesthetics.[56] The combination of augmentation adjacent to reduction achieves patients' goals for
“S” curvilinear body contour in ways that cannot be accomplished with any other technique.
Furthermore, the use of autologous fatty tissue avoids implant-associated complications
such as seroma, capsular contracture, migration, or implant exposure.[57]
Several complications are reported in the literature including infection, abscess
formation, contour irregularities, sciatic nerve injury, and rarely fat emboli and
death.[58]
[59] Fatal fat embolism can potentially occur from inadvertent injections in the gluteal
vein plexus. Despite these known complications, with meticulous technique as well
as proper patient selection and perioperative protocols, the procedure can be safely
performed with consistently excellent short- and long-term results and high patient
satisfaction.[56]
Facial Contouring
Several fillers have been proposed to address the soft tissue volume loss in facial
aging. However, the recognition that most of the volume loss is the result of fatty
tissue atrophy has driven surgeons to consider autologous fat transfer as a replacement
in facial rejuvenation procedures. Fat provides a readily available and appealing
tissue for facial transplantation, despite having some limitations in the predictability
of volume maintenance. In most studies, the overall survival rate following fat grafting
has been reported at around 50%, which is not considered an ideal percentage. Various
grafting and injection protocols have been proposed to increase the viability and
the survival of the graft.[60] In 2007, Kaufman et al described several modifications that can potentially improve
graft survival and volume maintenance including ‘‘nontraumatic’' blunt cannula technique
and immediate injection of small amounts in multiple passes.[61] Despite these limitations, reported patient and physician satisfaction regarding
the final cosmetic outcomes of the procedure remain high.[62]
Facial rejuvenation requires both a facelift procedure and lipofilling. When it comes
to facial fat transplant, a thin layer of strategically placed compacted centrifuged
fat can result in excellent graft-to-recipient ratio with high graft survival. In
a recent systematic review of 18 articles investigating autologous fat grafting for
facial rejuvenation, the number of required sessions varied between the studies, ranging
from 1 to 4 sessions with a mean interval of 4.25 months.[63] Furthermore, the subcutaneous space was the primary site of injection with additional
injections most often performed above or just beneath the superficial muscular aponeurotic
system (SMAS). In regards to volumetric analysis, the authors found it impractical
to compare the degree of volume retention between the studies as the face consists
of multiple anatomical units greatly varying in important features such as density.
Moreover, great heterogeneity was found between the studies in regard to injection
site and volumetric assessment; therefore, pooling of volume data was not possible.
Patient satisfaction was reported around 81%, while surgeons reported a good cosmetic
outcome in 89% of the cohort.
Hand Rejuvenation
The appearance of the hands has always been an indicator of someone's true age. Such
age-related changes occur due to both intrinsic and extrinsic factors. With advanced
age collagen depletion and dehydration gradually lead to tissue atrophy and loss of
the subcutaneous fullness in the hands. In turn, these changes result in skin wrinkling
and visibility of the extensor tendons and subcutaneous veins on the dorsum of the
hand.[64] Extrinsic factors, such as photoaging, can lead to irregular pigmentations including
actinic keratosis, seborrhoeic keratosis, solar lentigines, and solar purpura.[64]
The procedure is performed under local anesthesia using blunt cannulas to minimize
the risk of dorsal vein perforation. Generally, 10 to 30 mL of fat is injected to
give the hand a slightly overfilled appearance. Furthermore, injecting a small volume
at the base of the fingers provides a more uniform appearance to the entire hand.[64] In addition to acting as a filler for volume augmentation, the regenerative potential
improves the quality of the soft tissue and the skin making autologous fat transfer
the ideal approach for hand rejuvenation.
Fibrosis and Scars
The cicatrix-to-matrix concept was first described by Khouri et al where the authors
explained how autologous fat transfer can turn tight fibrous tissue into loose recipient
matrix.[65] The application of this new approach provides a valuable regenerative alternative
to flap surgery in the treatment of scar contractures and fibrous tissue.
Scar Contractures
Percutaneous aponeurotomy and lipofilling (PALF) is a fat grafting technique that
relies primarily on maximizing the recipient site's capacity to accept and support
the graft. The subcutaneous aponeurosis is the restrictive underlying scar or the
subcutaneous fascia that limits tissue advancement and primary closure at defect sites.
By percutaneously meshing the restrictive scar and expanding the resultant microcavities
with fat grafting, the cicatrix can be transformed into fat-filled matrix. For proper
3D release, the expansion must be made via staggered nicks in multiple planes with
different directions wherever restrictive fibers prevent expansion, thus increasing
the surface area and allowing further tissue advancement. This generates a scaffold
of small pockets or gaps, interspersed with thin connective bands of the original
scar, that are ideal for seeding with autologous fat to regenerate the defect. The
loosened scar becomes softer and closer to the surrounding fatty tissue. To correct
volume deficiencies, the process is repeated a few months later leading to substantial
volume gain and the potential to eliminate the scar completely. Percutaneous mesh
expansion should not be confused with relaxing incisions, which create large gaps
where the grafts may collect in large deposits and die due to inadequate graft–recipient
interface.
The procedure has been performed on scars and defects located in several body parts
including the trunk, breasts, extremities, and face.[65] In addition, multiple pathologies were successfully treated such as burn scar contractures,
breast agenesis, posttraumatic scars, and Dupuytren's contracture.[34] When performing PALF to treat Dupuytren's contracture, it is important to remember
that the key is strong digital extension when releasing the cord, to avoid damage
to the neurovascular structures.[66] Forceful extension tenses the cords before the neurovascular structures become tight,
thereby selectively cutting the restrictive fibers with the needle during the expansion.[66] Moreover, studies have shown that abdominal adipose tissue has an inhibitory effect
on Dupuytren's fibroblasts.[67]
Radiation Defects
Radiation therapy results in the destruction of both cancer cells and ADSCs alike,
leaving behind a tissue with poor regenerative capabilities and a hostile environment
for engraftment. While the first round of fat grafting results in poor survival, subsequent
rounds are met with better graft take due to the abundance of ADSCs in the liposuctioned
fat. With each fat grafting session, the content of the tissue becomes richer and
richer in stem cells and eventually more and more approaching the normal tissue in
both properties and cellular content. The procedure is best performed immediately
after the radiation before the fibrosis sets in.
Future Applications
The regenerative potential and the relative ease by which ADSCs are obtained have
encouraged a large number of experiments to study their reconstructive potential.
Cultured ADSCs have shown massive differentiation potential in vitro. Besides the
logical mesenchymal tissues such as bone, cartilage, and adipose tissue, ADSCs have
also shown paracrine and differentiation potential in skin tissue engineering and
nerve reconstruction.[68]
[69] The full therapeutic potential of such differentiation capabilities remains an area
of debate. While some researchers suggest that ADSCs exert their therapeutic potential
through differentiation into a specific cell type in target tissue, others contradict
this suggestion by arguing that despite the phenotypic differentiation, the newly
formed target cells lack full functionality.[70]
Studies focusing on the use of ADSCs in tissue engineering have also been reported
in the literature. Many aspects of the procedure still need to be investigated and
established such as the biocompatible scaffold, the seeding process, vascularization,
and the use of ADSCs (differentiated or undifferentiated, alone or in combination
with other cell types).[71]
[72] The main dilemma is achieving vascularization after in vivo implantation. Multiple
approaches to form a viable, organized vascular network have been proposed such as
incorporating biomaterials with favorable angiogenic properties, using mechanical
stimulation, as well as using 3D cell printing.
Others researchers have taken a different approach and focused on the therapeutic
potential that can be exploited from ADSC's paracrine activity. Several studies confirmed
the ability of ADSCs to promote tissue regeneration through their secretion of a multitude
of cytokines and growth factors, particularly in hypoxic conditions.[73] These include angiogenic cytokines such as vascular endothelial growth factor (VEGF),
fibroblast growth factor 2 (FGF-2), and basic fibroblast growth factor (b-FGF) as
well as hematopoietic cytokines such as granulocyte-colony stimulating factor (G-CSF)
and granulocyte/macrophage-colony stimulating factor (GM-CSF).[74] According to the clinical trials database, almost 112 clinical studies are currently
being performed using ADSCs, including diabetic foot, facial rejuvenatoin, Crohn's
disease, and spinal cord injury.[75]
Complications
Donor-site complications are generally minimal and are related to the liposuction
technique. Possible complications include bruising, paresthesia, and damage to the
underlying structures.
When fat grafting the breast, potential complications include fat necrosis, oil cyst
formation, and calcification. In a systematic review performed by Agha et al, the
complications rate in 2,832 fat-grafted breasts was found to be 7.3%. Fat necrosis
accounted for 62% of all complications and was reported in 17 of the 24 studies.[76] Such adverse events can occur at higher rates if large volumes are injected without
adequate distribution or if fat is injected into poorly vascularized regions. In addition,
fat necrosis can result in palpable masses that are indistinguishable on examination
from local recurrence in breast cancer patients resulting in additional imaging and
needle biopsies.[50]
The face is an anatomically complex area of the body, compacted with a multitude of
important structures. Most complications when transplanting fat into the face are
due to injecting fat in critical areas such as the nasolabial folds. Upon injecting
the grafts, increase in local pressure can result in reflux of the fat into the ophthalmic
artery, resulting in blindness or the internal carotid artery causing a stroke.[77] Multiple steps can be undertaken to minimize the risk of such devastating complications
starting by ensuring the absence of blood reflux prior to the injection, injecting
slowly and at a low pressure, and using the blunt-tip cannula.[77]
Limitations
Despite the demonstrated benefits and therapeutic potential of adipose tissue in a
variety of application, its limitations have to be acknowledged and addressed. Perhaps
the most important limitation is the oncological risk when fat grafting the breast.
Even though many studies have shown no increased risk, this remains the most expressed
concern among surgeons and patients.
One of the fundamental limitations is that the amount of tissue transfer is strictly
limited by the amount of fatty tissue available in the patient. Ensuring fat cells
viability is crucial, and while every step in the process of fat grafting is important,
the chances of survival are higher when the graft is less manipulated and delayed
after harvesting. The lack of standardization in harvesting and injection protocols,
combined with the unpredictability of the resorption rate, pose a significant limitation
for graft retention. Furthermore, information regarding long-term viability of the
transferred fat is still unavailable, making long-term results unpredictable. Another
important concern includes lack of a consistent evidence regarding revisions, use
of additional interventions following resorption, and the ever-existing potential
for future injections.
Comparisons between methods tend to vary broadly according to the outcome measured,
thereby limiting the ability to determine the most efficient method for fat grafting.
Moreover, the absence of a standard method to evaluate the viability or the degree
of volume augmentation of the fat graft remains another obstacle in the way of achieving
a universally agreed upon fat grafting protocol.
Conclusion
With its filling and regenerative properties, autologous fat transfer provides a reliable
minimally invasive procedure for many reconstructive and aesthetic procedures. With
the principles of fat grafting well described in the literature, establishing best-practice
guidelines for fat grafting applications should become a priority moving forward.
A very promising area of experimental research in adipose reconstructive medicine
is developing, and more significant applications will soon become available.
