Fat Transfer for Face Volume Enhancement

Abstract

The authors discuss the history of fat transfer to the face; how we age; adipose-derived stem cells (ADSCs); stem cell niche therapy, using adipose tissue; benefits of stem cells in a fat transfer; and aging and rejuvenation. Described are structural fat grafting with harvesting refinement and transfer, the influence of local anesthesia on adipose tissue, preoperative care, and postoperative care. The potential areas for facial fat transfer include nasolabial folds, marionette lines, cheeks, infraorbital regions, trough area, chin, glabellar area, temple, forehead, inferior orbital rim, and lips. Graft survival is discussed with unfavorable points to fat grafting and future perspectives for fat harvesting.

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The best art is that in which the hand, the head and the heart of man proceed in accordance – John Ruskin

1 Introduction

The face is one of the most cosmetically sensitive areas of the body: it lets us show emotion and is the part of the body our eyes naturally fix on. During life, the effects of passing years are most quickly evident in this anatomical area, often accelerated by smoking, sun exposure, and other exogenous factors.

2 How Do We Age?

The primary event of facial aging is progressive cell and extracellular matrix atrophy or loss of fullness. The obvious solution for atrophy is the restoration of volume or fullness. Age-related morphologic changes in our face are due largely to fat redistribution. From infancy to adulthood, fat characterizes the face’s shape.

A baby has an identifiable distribution of fat in its chubby cheeks, jowls, and neck rolls. In younger faces, deposits of fat are hidden by fullness that is presumably colloidal fluid held in place by proteins, hormones, and hyaluronic acid. All these substances that impart fullness are present in a young person diffusely from bone to skin but are gradually lost in the natural process of aging. In fact, as a person approaches middle age, fat deposits of the jowl, above the nasolabial fold, in the eyelid, and so forth become more visible as their surrounding fullness disappears. Not only do they become more obvious, but also many of the underlying structures of the face, such as the submaxillary gland and the bony skull, are more discernible as separate entities.

Interestingly, the same young fat distribution occurs again in the older adult, but we ascribe it to loose skin and blame gravity [1, 2]. Indeed, although the plastic surgery literature almost universally acknowledges that atrophy plays a part in facial aging, it places far greater emphasis on the role of descent [3, 4]. Nowadays, gravitational aging is the target for much of conventional aesthetic surgery. The premise of gravitational descent has founded surgical corrections like face, brow, and neck lifts; blepharoplasty; and laser resurfacing to reverse the aging process. These procedures are contingent upon excision and lifting of redundant, prolapsed, or descended tissue. But to consider gravity the exclusive culprit of facial aging and sagging is simplistic. Unfortunately, there are no animal models for gravitational aging; there is tremendous individual variability in the degree of sagging, and age-related fibrosis may counteract increased laxity.

When we look at the results of our past efforts to rejuvenate the face, we can conclude that excisional-based surgery has not truly provided all the answers to facial rejuvenation: a perfectly performed face lift may produce an unnatural surgical result and not a rejuvenated appearance. Clearly, there is more to restore a natural, more youthful facial appearance than what just lifting can provide. A new paradigm has emerged to supplant this established dogma; the face does not descend so much as contract by virtue of volume loss.

Over the past several years, fat grafting has gained tremendous momentum in clinical practice due to its potential applications in trauma [5, 6], reconstructive [7–9], and aesthetic surgery. Two pioneers have led the charge for fat enhancement: Sydney R. Coleman [10] of New York and Roger Amar [11] of France.

3 History

Autologous fat grafting evolved over the twentieth century to become a quick, safe, and reliable method for restoring volume. The history of autologous adipose tissue (lipofilling) began in Europe in 1893 with the presentation of Neuber’s [12] surgical technique at the 22nd Congress of the German Surgical Society. In 1911, Bruning [13] was the first to inject fat in the subcutaneous tissue in order to increase the volume of certain regions of the body. Until the 1980s, it was common to use transplantation of adipose tissue “en bloc” after the removal of a flap of fatty tissue that was empirically applied in the area to be corrected, without considering the vascular supply and consequently without paying attention to anastomosis whatsoever. From the 1980s onward, fat transplantation has been used to an increasing extent, but only to “fill” or “raise” missing or deficient volumes, particularly for aesthetic purposes. In 1995, Coleman [14] published his success by transplanting adipose tissue for aesthetic correction of deformities of the face and described the long-term results that were detected. A few years later, he perfected his technique of adipose tissue transplantation, contributing greatly to the popularity of minimally invasive surgery. Since then, the use of this technique seemed to be essential for the knowledge and skills of a plastic surgeon, as applicable in many fields and adaptable to various clinical situations [15–17].

4 Adipose-Derived Stem Cells (ADSCs)

The most promising research, in the field of regenerative medicine, involves the use of totipotent, pluripotent, and multipotent stem cells: undifferentiated cells with significant self-renewal capacities. Totipotent stem cells, which can be obtained from the blastocyst stage, are capable of triggering various human cell lineages, including human embryonic stem cells (hESCs) [18]; pluripotent stem cells can differentiate into any of the endoderm, mesoderm, or ectoderm germ layers; multipotent stem cells can produce daughter cells of a limited number of lineages, including hematopoietic progenitor cells that can develop into different types of blood cells, but not into cells of other origin [19]. There are still a number of major limitations concerning the therapeutic use of hESCs, including ethical concerns, cell regulation, and gene defects, but lots of clinical trials using adult stem cells have shown they can have beneficial clinical effects.

Friedenstein et al. [20] were the first to discover that the bone marrow contains cells able to differentiate into other mesenchymal ones as well as into fibroblasts. A few hours after placing whole bone marrow in plastic culture dishes, they removed the non-adherent cells (and, therefore, most of the hematopoietic cells) and found that although the remaining cells were heterogeneous in appearance, the most tightly adherent cells were spindle shaped. They also found that cells could differentiate into colonies that resembled small deposits of bone or cartilage. These observations were extended by other authors, throughout the 1980s [21], who established that cells isolated according to Friedenstein’s method were multipotent and could differentiate into osteoblasts, chondrocytes, adipocytes, and even myoblasts. These adherent cells are currently referred to as mesenchymal stem cells (MSCs), because of their ability to differentiate into mesenchymal-type cells, or marrow stromal cells; they appear to arise from the complex array of supporting structures in the bone marrow [22].

Bone marrow has been the main source of MSCs, but these cells account for only a small percentage. The other most important source of MSCs is adipose tissue, which not only offers an abundant and easily accessible sample of adipose-derived stem cells (ADSCs) [23, 24] but can also be harvested by minimally invasive procedures and processed for clinical applications in accordance with current Good Manufacturing Practice guidelines (Fig. 30.1). Some in vivo and in vitro studies reported that ADSCs come from vessel-associated pericytes [25], which are in contact with the intimal surfaces of small vessels within the tissue and, if sorted and cultured over the long term, give rise to adherent multi-lineage progenitor cells with MSC features (Fig. 30.2).

Fig. 30.1

Multipotent adipose-derived mesenchymal stem cells (ADSCs)

Fig. 30.2

MSCs and their main differentiation

MSCs are phenotypically heterogeneous in terms of morphology, physiology, and surface antigen expression. No specific marker has yet been identified for them, but they seem to express a large number of adhesion molecules, extracellular matrix proteins, cytokines, and growth factor receptors. As stem cells, they are characterized by their ability to self-renew and differentiate toward multiple cell lineages [26]; a further way of identifying possible MSC populations is by inducing them to differentiate into bone [27], fat, and cartilage in vitro. According to the literature, MSCs from different sources have been successfully differentiated into osteoblasts, chondrocytes [28], adipocytes [29], fibroblasts, myoblasts and cardiomyocytes [30, 31], hepatocytes, tenocytes, and even neurons [32]. Some MSCs are already used for orthopedic, cardiac, and neuro-repair [33], while others are being investigated.

It is known that MSCs are attracted on injured or pathological tissues by means of still unknown mechanisms but that possibly involve chemokines and their receptors [34], as well as adhesion molecules. MSCs are capable of expressing genes of embryonic origin, adhesion molecules, extracellular matrix proteins, collagen, fibronectin, etc.; they secrete several interleukins, such as IL-7, IL-8, IL-10, and IL-11, as well as growth factors stimulating hematopoiesis as SCF (stem cell factor), G-CSF (granulocyte-colony stimulating factor), and countless cytokines [35]. They also support the in vivo homing of HSCs: they secrete stromal-derived factor (SDF-1) which regulates the migration of hematopoietic stem cells expressing the receptor CXCR-4 (CD84) in the bone marrow [36]. Studies concerning the genetic profile of MSCs show a different pattern of gene expression, suggesting the existence of functionally different subpopulations depending on the source.

Clinical applications of MSCs in regenerative and aesthetic medicine seem to be due mainly to their paracrine effect, which means the production of chemical messengers able to spread and change the physiology of surrounding cells and homeostasis of their microenvironment. The most current evidence would be that the strong biological activity (secretion of soluble markers after systemic infusion of MSCs) would supply the lack of typical local engraftment of these cells and that would mean two things:

• 1. The source of MSCs can be important in determining the biological activity because different tissues may originate MSCs with different profiles of cytokine expression.

• 2. The isolation and expansion in culture conditions (seed density, culture medium, serum, added cytokines) may considerably influence the gene expression, reprogramming the bioactivity of these cells.

5 Stem Cell Niche Therapy Using Adipose Tissue

Adipose-derived stem cell niche refers to the complex relationships that ADSCs establish with all of the physiological or ectopic factors contributing to determine their identity and fate. The phenotypical identity of any cell and its reaction to a given stimulus are, therefore, not only determined by the genetic or epigenetic equipment of the cell but also depend on the specific niche context in which it resides. A change in niche parameters or the transplantation of cells into other niches can have a considerable effect on cell physiology and alter its properties.

Research has shown that the signal controlling the embryonic origin of ADSCs and their differentiation in adult adipose tissue include the same pathway as that involved in the homeostasis of other adult and embryonic stem cell populations [37, 38], and their complex mechanism can have different effects depending on the concentration, stage of differentiation, and extrinsic niche factors, such as cell-matrix and cell-cell interactions, presence of vasculature, and type of innervation. Despite extensive research about the intracellular signaling involved in ADSC homeostasis and differentiation, little is known about the role of cell-cell and cell-matrix interactions [39, 40].

Zannettino et al. [41] suggested that ADSCs reside in perivascular niches, which prompts the idea that perivascular structures (cells and extracellular matrix) may provide signals that balance the maintenance of ADSCs in an undifferentiated state and their commitment to differentiation. It has recently been shown that in vitro culture significantly alters the transcriptional phenotype of ADSCs. Freshly isolated stromal vascular fractions (SVF) express hematopoietic markers (CD34) that are lost within a few days of culturing [42]. In line with previously published findings [43], the increased expression of mesenchymal stem cell-associated markers in cultures of human and murine ADSCs has been documented, whereas the longer-term loss of markers of undifferentiated status, such as undifferentiated transcription factor (UTF-1), indicates a shift toward differentiation. Prolonged culturing also significantly downregulated various isoforms of procollagen, matrix metallopeptidases, and inflammatory cytokines, thus indicating adaptation to the artificial environment. Under extreme conditions, it has even been reported that in vitro long-term culturing can induce the neoplastic transformation of ADSCs [44], although it is still unclear whether these changes are reversible or how they may affect the therapeutic potential of the cell.

However, ADSCs can be used in many clinical applications (particularly in the fields of plastic and reconstructive surgery) by means of transplantation without removing them from their fat niche. In addition to molecular and cell biology, the dynamic and regenerative nature of fat grafts has been established in various areas of plastic surgery, and clinical practice has shown that long-term outcomes of fat grafting can include rejuvenation of skin texture [45]. Ultrastructural studies of centrifuged fat have revealed that mature adipocytes show interruptions in their cytoplasmic membrane and various degrees of degeneration including cell necrosis, but the stromal vascular fraction (SVF) appears to be well preserved [46].

Rigotti et al. [47] compared the ultrastructure of mammary radiolesions before, and at different times after fat grafting, and found clear signs of regeneration, with evidence of new adipocytes. Before transplantation, almost all of the adipocytes were seriously damaged by centrifugation, and in the radio-damaged recipient tissue, there were neither mature adipocytes nor differentiating preadipocytes. Reasonable interpretations of these findings are that the differentiating preadipocytes observed after treatment were either committed adipocyte originally embedded within the transplanted fat or endogenous locally present committed adipocyte, activated by the ectopically transplanted fat. The massive survival of ADSCs in fat transplants, despite liposuction and centrifugation procedures, strongly supports the first hypothesis, but the second may be equally valid as it assumes that transplanted fat enriched with ADSCs by centrifugation can behave as an atypical ectopic niche that direct tissue regeneration by modulating endogenous tissue resources.

The term “atypical ectopic niche” could be used as a common paradigm of stem cell-based therapies. It is based on the idea of a “bystander” mechanism in which the stem cells ectopically transplanted into a generic lesion (radiolesion, myocardial infarction, cerebral stroke, etc.) do not replace tissue-specific cells by direct differentiation, but locally form an atypical stem cell niche that suppresses inflammation, promotes neo-angiogenesis, and favors the activation of endogenous stem cell precursors by releasing trophic factors, such as cytokines, proangiogenic molecules, and growth factors. Therefore, adipose tissue can be considered an ideal “biologic product” [48]. The role of this essential component of the stromal fraction of the lipoaspirates argues for a regenerative theory based on angiogenesis imbued by various growth factors, not yet fully identified, released from stem cells. Thus, in addition to the traditional understanding that fat is a high-energy reservoir involved in homeostasis for its ability to bind large amounts of fluids and in the maintenance of thermoregulation, it becomes apparent that it is also a regenerative organ providing the basis for soft tissue regeneration.

According to the sub-mentioned theories, nowadays ADSCs have become one of the most popular adult stem cell populations for research in soft tissue engineering and regenerative medicine applications. Compared with other stem cell sources, they offer several advantages including an abundant autologous source, minor invasive harvesting (liposuction), significant proliferative capacity in culture, and multi-lineage potential. To harvest the adipose tissue, a liposuction procedure is less invasive than bone-marrow aspiration, and the technique produces less patient discomfort and donor site morbidity. Small amounts of adipose tissue yields approximately 5 × 10³ stem cells, which is 500-fold greater than the number of MSCs in 1 g of bone marrow [49].

Numerous preclinical studies have been pursued, with early clinical data appearing in the literature. Fat as a living, free graft does more than just fill the area into which it is placed. Grafted fat affects the tissue into which it is placed in many ways for the life of the patient. It can improve the quality of aged and scarred skin and heal radiation damage and chronic ulcers. Just how grafted fat causes these changes remains unanswered. We know that fat can perform amazing feats in a glass tube and in some animal models, but we have little insight into what happens to fat when it is grafted from one part of the human body to another part. The focus of the near future should be research to explain and expand on future clinical successes.

In addition to the outstanding results of lipotransfer for volume restoration, surgeons have become increasingly interested in the apparent rejuvenative effects on the skin itself. Coleman has noted improved skin quality, with softening of wrinkles, decreased pore size, and improved pigmentation during the first year posttreatment. In fact, analysis of clinical results following both reconstructive and aesthetic surgery reveals that after one or several repeated fat grafting procedures, the trophicity and quality of the recipient site is improved. These changes develop over several months following the fat grafting procedure, with a variable expression, as improvements in skin texture, skin suppleness, skin color, and/or scar quality.

Topographical skin analysis systems such as the recently developed VISIA system (Canfield Imaging Systems) may determine whether the effect from fat grafting is an effective skin rejuvenation technique in comparison to chemical peels and laser resurfacing. Aside from effects on normal, aged skin, when fat has been grafted beneath depressed scars, there was improvement not only in the depression but also in the character of the scar itself, with an apparent transformation to normal-appearing skin. Other authors have reported an adverse range of improvements in soft tissue conditions, including radiation damage, breast capsular contracture, damaged vocal cords, and chronic ulceration, as well as regrowth of calvarial bone. While many of the exact mechanisms for these effects remain to be described, what seems to be at the center of these changes is the presence of adipose-derived stem cells (ASCs).

6 Benefits of Stem Cells in a Fat Transfer

• 1. Grow new blood vessels to nourish the fat.

• 2. Release anti-inflammatory agents to aid healing.

• 3. Generate and release growth factors that support graft survival.

• 4. Improve skin tightening and rejuvenation.

• 5. No risk of allergic or adverse reaction.

• 6. A cutting-edge option used around the world today.

• 7. The therapeutic target is the reconstruction of autologous niches, by simply moving stem cell niches from one connective tissue in which they are abundant into another in which they are scarce.

7 Research Directions

The possible application of ADSCs for tissue repair and healing has recently been researched. It has been experienced that

• 1. Local injection of ADSCs into skin ulcers induces rapid healing with less scarring in a rat model.

• 2. Topical administration of ADSCs around the site of primary sciatic nerve repair in rats improves the functional restoration of the sciatic nerve, a result that has been confirmed by gait analysis, electroneurography, and histology.

These therapeutic models may be applicable to clinical situations in which the environment for wound healing is compromised by inadequate blood supply and severely scarred tissue. Gimble et al. have shown that ASCs delivered into an injured or diseased tissue may secrete cytokines and growth factors that stimulate recovery in a paracrine manner. ADSCs modulate the stem cell niche of the host by stimulating the recruitment of endogenous stem cells to the site and promoting their differentiation along the required lineage pathway. In a similar way, ADSCs could provide antioxidants, free radical scavengers at an ischemic site: as a result, toxic substances released into the local environment would be removed, thereby promoting recovery of the surviving cells [23]. Further preclinical and clinical studies need to be performed so that ADSC-based therapies fulfill expectations and can be successfully used to treat disorders for which the present medical and surgical therapies are either ineffective or impractical.

8 Aging and Rejuvenation

Atrophy is the defining feature of aging: it also represents a primary challenge in the evolving quest to find the best approach for rejuvenating aging faces and bodies. Rejuvenation is not about suspension or sagging: it is all about augmentation in order to restore youthful fullness and contour in a natural and aesthetic fashion. One major goal of rejuvenation procedures is to rebalance fat and restore harmony to the face. This can be accomplished by microliposuction of the fatty “hills” and fat transfer to the sunken “valleys.” Restoration of homogeneity to the facial structure reduces the sharp shadows associated with aging.

Augmentation represents the past and the future of rejuvenation. It also holds the key to possible new developments such as tissue repair. Examination of the results over time reveals promising posttreatment changes in the quality of the patient’s skin after the placement of grafted fatty tissue under it. In addition to restoration of youthful contours, intrinsic qualities of skin texture, elasticity, and color return to a more youthful state for an extended period of time. Stem cells have been shown to be present in significant quantities in harvested fatty tissue. Perhaps they are mending the sun-damaged, aging epithelium.

Sagging of the aging face may occur mostly as a result of changes in the fat compartments that are coincident with chronological aging. Localized overabundance of fat may weigh down the tissue. Conversely, an area devoid of fat resembles a deflated balloon by inducing the downward displacement of facial skin. Inelastic recoil due to photodamage compounds this effect. If altered fat distribution underlies differences between the young and the old face, a new model for the youthful countenance might arise.

A young face has a smooth, ample distribution of fat. It resembles a continuous, “gently rolling plain” because the fat is evenly distributed. There is a forward projection with facial arcs highlighting specific areas and causing minimal shadow. In contrast, the aging face has “hills and valleys” producing deep shadows and irregular highlights. In thin individuals, these “hills” of fat may be minor, but in most middle-aged adults, the hills occur in a strip down the central face from mid-cheek to jowl, along the nasolabial and labiomental folds. Fat pocketing can also be seen suborbitally on the lateral zygoma, submentally, and along the neck platysmal bands. Since body fat rises with age, so does facial fat. “Valleys,” in contrast, occur periorbitally and periorally, in the malar, buccal, and temporal areas and on the far lateral cheek.

Fat loss manifests around the mandible and throughout the forehead and scalp. The most common areas of the face which are treated with autologous fat grafts include the nasolabial groove, marionette lines, midface, and lips. Autologous fat performs best in the midface area considering the longevity compared to other more mobile areas such as the lips and marionette grooves.

9 Structural Fat Grafting

9.1 Harvesting

The authors (ADG) started using autologous fat transfer or fat grafting procedures in the last 3 years to provide lasting natural structure and contour changes in the face. Various methods for harvesting and refining autologous fat grafts have been described.

One of the standard procedures, the Coleman technique [50, 51], is based on manual aspiration with syringes to reduce the negative pressure and the centrifugation of the graft. It is also known as structural fat grafting or lipostructure. Various studies have shown that this technique causes little damage to the cells and have demonstrated survival of the tissue transferred. Typically, the authors use 3–10 mL syringes with 16-gauge needles or cannulas to harvest subcutaneous extra fat from the abdomen, lateral or inner thighs, gluteal areas, or medial knees. Current studies have not indicated increased viability from any donor site, so harvesting sites are chosen for ease of accessibility and to improve the patient’s body contours. They are accessed through incisions placed or increases, previous scars, stretch marks, or hirsute areas whenever possible. Anesthetic solution is infiltrated into the sites of fatty tissue removal. During harvesting, we take care to minimize mechanical trauma to the fragile parcels of fat (Fig. 30.3).

Fig. 30.3

(a, b) Fat samples from the abdomen before centrifugation

9.2 Refinement and Transfer

The suctioned fat is specially processed by centrifuging to separate the oil and fluids to isolate the living fat. The centrifugation also concentrates the fatty tissue, associated stem cells, and growth factors from the unwanted fluids, oil, and nonliving components. Our recommended centrifugation speed is 3,000 rpm (1,500 × g) for 3 min. Larger centrifuges can create significantly more gravitational force at 3,000 rpm than the smaller centrifuges commonly used in offices (Fig. 30.4). With the centrifugation, three layers are formed in the syringe: the top one is oily and consists essentially of spilled material traumatized by fat cells; the lower one is the most dense between the three and is formed by blood and saline solution; and finally the middle one contains fat living cells that will be infiltrated in the area to be corrected (Fig. 30.5).

Fig. 30.4

(a, b) Centrifuge machine (central rotor and sleeves)

Fig. 30.5

Fat samples from the abdomen post-centrifugation

Both the upper and the lower layers are removed, respectively, using absorbent wicks (Codman neuropads) with the plunger and, after exerting a slight pressure, in the syringe remains the only intermediate layer. It is necessary to isolate the adipocytes to be transplanted, as much as possible, in order to decrease the adipocytes to be transplanted in order to decrease inflammatory response after replanting; if many cellular debris are present in the recipient site, they develop an intense inflammatory reaction with the activation of cells of flogosis that are recalled to clean the affected area. Some studies also point to the importance of the fourth layer (so-called pellets), in the superficial part of the lipoaspirates, as a key source of mesenchymal stem cells and endothelial cells (Fig. 30.6).

Fig. 30.6

(a, b) Removal of the upper and the lower layers in every sample of centrifuged fat

Then, the refined fat is transferred into a 1 or 3 mL Luer-Lock syringe and we carefully place it into the areas to be treated. The transfer of the harvested fat to 1 mL syringes and blunt cannulas of various curves and sizes offers precise placement of small 0.1 mL aliquots of fat. The placement cannulas are of a much smaller gauge than the harvesting cannulas: the gauge used can range from 14 gauge to 21 gauge. (The most useful size of cannula for placement in the face is 17 gauge.) The most suitable lengths for use in facial procedures are from 5 to 9 cm. However, larger-bore cannulas can be used for corporal fat grafting, and smaller gauges may be appropriate in areas such as in the lower eyelids. For various situations in the face and body, cannulas with different tip shapes, diameters, lengths, and curves can be used. Using blunt cannulas allows placement of the fat parcels in a more stable or precise placement and less traumatic manner. However, less blunt cannulas may give us more control for placement in the immediate subdermal plane, in fibrous tissue, and in scars. A cannula with pointed or sharp elements can be used to free up adhesions (Fig. 30.7).

Fig. 30.7

(a–e) Transfer of the fat into Luer-Lock syringe

Placement of the refined fat into the recipient site is the most challenging part of fat grafting. Fat parcels should be positioned to ensure uniform survival, stability, and integration into the surrounding recipient tissue. The key of fatty tissue placement is maximization of the surface area of contact between the harvested fat and the recipient tissues. On the other hand, injection of a mass of fat into any site may result in areas of fat that are too far from vascularized tissue to have a source of nutrition or respiration. In this event, much of the tissue will die or resorb. This may result in irregularities. We advance the infiltration cannula through the tissue to the appropriate plane. Once the cannula is in the desired location, we press the plunger of the 1-mm syringe slightly while the cannula is being withdrawn. Then, the authors leave fatty tissue in the pathway of the retreating cannula, permitting more stable and regulated placement and minimizing the potential for irregularities or clumps of tissue.

Placement of minuscule amounts of fatty tissue with each pass is critical to successful structural fat grafting. To maximize the surface contact area, the largest amount of tissue that should be placed in the face with each withdrawal is 1/10 mL and much smaller aliquots (the maximum placed should be closer to 1/30 mL or even 1/50 mL per withdrawal) should be placed in specific areas, such as the periorbital region. Placing the fatty parcels with a blunt cannula that causes minimal disruption of the natural tissue planes facilitates better fat adherence to the recipient site. The surgical technique we used is a multilayered full facial augmentation using relatively high volumes of fat. Full facial rejuvenation is performed more often to maintain or establish normal facial proportions. When fat is used for regional augmentation, such as the midface, small volumes of fat are injected to this area compared with the volume that would have been used if they were a part of full facial augmentation. With full facial augmentation, we inject larger volumes to each region because adjacent areas are also treated.

There are key regions of the face that must be augmented with fat to create a more youthful appearance. Primary areas of treatment include the midface: infraorbital region (which is the major support area of the eyelid and face), anterior and lateral cheek, brow and upper eyelid, prejowl sulcus, and mandibular angle. Proper augmentation of the midface also blends into the lateral eyebrow, the anterior and inferior temple, and the submalar regions. Other key regions are the lateral jawline, the temporal fossa with the lateral eyebrow, the perioral region (lips, nasolabial fold, and prejowl), and the glabella.

The authors’ patients’ ages ranged between 18 and 88 years old in both females and males. Autologous fat grafting can be performed on a patient before facelift or blepharoplasty surgery and may prolong the need for such procedures.

The most successful areas of fat grafting are the more static ones such as the tear trough deformity, the midface, the upper malar region, the jawline, the temporal fossa, the mandible, and the lateral eyebrow. Fat grafts that are placed in the perioral region are viable, but the result is less predictable because of the mobility associated with the area. This results in shearing forces, which limit the angiogenesis to the graft. The best candidates for fat grafting are younger (<50 years old), healthy, nonsmokers, and with thicker skin and good overall skin elasticity. Smoking decreases the revascularization potential for the graft. Thinner, inelastic skin in older patients also does not contain optimal vascular supply and may require more than one treatment session for adequate results.

10 Influence of Local Anesthesia on Adipose Tissue

The most common modality the authors use for harvesting fat is local anesthesia with sedation. There have been concerns about the effect of local anesthetics such as lidocaine on the viability of fat grafts harvested by any kind of liposuction since such an agent is routinely used for analgesia of the donor site. Such a concern is based on an in vitro study reported by Moore et al. that lidocaine may inhibit a variety of adipocyte functions in tissue culture. However, the effect is found to be totally reversible once the agent has been washed out [52]. The viability and differentiation of preadipocytes are also found to be impaired but only after being isolated from fat tissue and then exposed directly to a higher concentration of lidocaine (2 %) in vitro for 30 min. The effect is thought to be independent of lipophilic properties and the resulted in vivo concentration of lidocaine may be different due to dilution effects [53]. However, Shoshani et al. [54] demonstrate, in an animal study, that local anesthetic solution, consisted of lidocaine (0.06 %) and epinephrine (1:1,000,000), does not alter the viability fat grafts based on a histological study in vivo. Therefore, a commonly used tumescent solution with low concentration of lidocaine (0.05 % or less) and only a short exposure to adipose tissue (less than 20 min) can be used for analgesia of the fat graft donor site without very much harmful effects to adipocytes or preadipocytes.

11 Preoperative Care

The procedure should be carried out after careful client selection and preoperative assessment for safe and optimum outcome. If the patient is on aspirin or is a smoker, these practices should be stopped for at least 2 weeks before the procedure. The clients should be advised not to use any nonsteroidal drug as it can act as a precipitating factor for bleeding or bruising. If they use warfarin, the INR should be between 1 and 1.5 before procedure and make sure that they have meticulous preoperative hemostasis.

Pre- and postoperative photographs are a must. In addition to that, markings are placed on the skin as the ultimate three-dimensional guide to placement of fatty tissue. They indicate the areas of tissue placement and could be considered a temporary map to delineate the volumes of placement within a certain area to create specific contour changes. Preoperative planning is the key to a successful result and a satisfied patient. When possible, incisions are placed in wrinkle lines, folds, or hair-bearing areas such as the eyebrow. This facilitates placement of the fatty tissue in at least two directions, but the placement of fat from two or more directions can be dangerous in some areas and unnecessary in others.

12 Potential Areas for Facial Fat Transfer

Although fat transfer can be used to augment any depressed area on the face, the most commonly addressed areas are the following:

• 1. Nasolabial folds marionette lines

• 2. Cheeks and infraorbital regions

• 3. Trough area

• 4. Chin

• 5. Glabellar area, temple, and forehead

• 6. Inferior orbital rim

• 7. Neck

• 8. Lips

These areas can be addressed individually or sometimes together to achieve the desired result.

13 Inferior Orbital Rim

The inferior orbital rim stands as the most technically difficult area to achieve a consistently excellent result. Care must be taken not to place the fat with too large a bolus per cannula pass, into the wrong plane, or with too large a total volume, all of which can lead to a complication that is not easy to rectify. From our experience, we have found that approaching the inferior orbital rim from a lateral canthal entry point with placement of fat in a parallel orientation to the inferior orbital rim can predispose toward the development of contour irregularities. Placement of fat should be approached so that the cannula is directed at the inferior orbital rim from a perpendicular direction. As the cannula is directed toward the eye, the index finger of the nondominant hand is used to protect the globe during the infiltration. The nondominant hand also provides tactile feedback to ensure the cannula tip is in the immediate supraperiosteal plane. The cannula tip should pass back and forth across the inferior orbital rim against the periosteum placing 0.03–0.05 mL per cannula pass. It is always better to attempt a more conservative approach, especially when addressing the inferior orbital rim, because placing additional fat is a very easy task, whereas removal of excessive fat is a difficult venture. Placement of fat in the immediately subdermal plane not only provides structural support to the skin, to help eliminate wrinkles and reduce pore size, but also affects skin color.

14 Nasojugal Groove

The bony nasojugal groove is the triangular bony fossa bordered superiorly by the medial inferior orbital rim and medially by the nasal sidewall. For the purposes of fat injection, the authors make a distinction between the nasojugal groove, defined by the bony landmarks and the tear trough, which is a superficial visible depression. Nasojugal groove injection is done in a deep supraperiosteal plane using the bony landmarks as a guide. In contrast, filling of the tear trough is done in a more superficial plane, but still below the orbicularis oculi muscle. This decision as to whether to add tear trough filling to the surgical plan is dictated by the presence of a visible depression and the surgeon’s experience and preference. Filling of the nasojugal groove can be done through entry point with 1–2 mL of fat, placing 0.1 mL per pass.

15 Supraorbital Area: Lateral Brow, Upper Eyelids, and Temples

A definite fullness of the supraorbital region is essential for a sensual, healthy appearance. Unlike the brow and temples, the frontal region is difficult to rejuvenate with structural fat grafting because the forehead is more dynamic. The brow is defined as the soft tissue that resides principally inferior and deep to the hair-bearing portion of the eyebrow and superior to the upper eyelid itself. With advancing age, the brow deflates, revealing a more skeletonized superior orbital rim. The aging forehead is especially affected by the active and intrinsic action of the frontalis muscle as it becomes less opposed by diffuse fullness; this results in wrinkles or creases that are created by intrinsic tone of the frontalis muscle. Placement of fat into the brow, subcutaneously and into the muscle, can restore the youthful convexity and highlight in this area. In contrast to the inferior orbital rim, fat can be placed from a lateral entry site passing parallel to the orbital rim. Approximately 2 mL of fat can be injected with 0.1 mL per pass.

16 Lateral Canthus

At times a small depression remains visible or becomes exaggerated, at the lateral canthus following superior and inferior orbital rim injections. Approaching this area with the smaller 0.9 mm spoon tip cannula facilitates placement of fat into the lateral canthus where tenacious retaining fibers traversing the lateral canthus create more resistance to injection. Only 0.5 mL should be placed into the lateral canthus with 0.05 mL fat per pass.

17 Anterior Cheek

The focus of anterior cheek augmentation is along the soft tissue, linear depression that runs from superomedial to inferolateral corresponding with the malar septum. The cannula should be passed back and forth across the malar septum filling the entire cheek with an emphasis on the malar depression, which is usually the area of greatest volume loss. In some patients a bit of resistance may be encountered as the cannula passes through the malar septum. It is important that the cannula be pushed through the septum layering fat medial to and across it. A total of 3 mL of fat on average should be placed with 0.1 mL per pass. Fat is infiltrated into all three tissue planes (deep, middle, and superficial), crossing gradually from one tissue plane to the next so that it is equally distributed. By placing small aliquots of fat across the entire malar depth, the surgeon can ensure that each parcel of fat has maximal contact with the surrounding tissue for optimal nourishment/blood supply that can translate into improved viability of the transferred adipocytes.

18 Lateral Cheek

The lateral cheek is centered over the bony zygomatic arch, which can be palpated to guide placement of fat. The lateral cheek is filled across all three tissue planes with the same technique outlined for anterior cheek augmentation, placing 0.1 mL per pass in a progressive fashion from deep to superficial. One to 3 mL of fat can be placed depending on the aesthetic end point desired. When necessary, based on patient evaluation, lateral cheek filling should be tapered into the submalar region (Figs. 30.8, 30.9, and 30.10).

Fig. 30.8

(a) Preoperative patient. (b) One month postoperative following full-face augmentation with autologous fat grafting

Fig. 30.9

(a) Preoperative patient. (b) Markings. (c) Two months postoperative after full-face fat transfer. Note the higher cheek bones, fuller midface, and improved blend between her lower eyelid and upper cheek. The face looks brighter and fresher

Fig. 30.10

(a) A young patient with preoperative markings in the periocular area and midface. (b) Surgical fat grafting procedure to enhance infraorbital area and cheek region volume. (c) Preoperative. (d) Two months postoperative after superior bilateral blepharoplasty and full-face fat grafting. The appearance seems to be more youthful and healthier

19 Buccal Region and Lips

The buccal region tends to be more important to fill in the very gaunt individual. If a facelift in which dissection will extend out to the buccal region is being performed, concurrent fat grafting cannot be done. The buccal region is forgiving and it is unlikely to show contour deformities. As a baseline, for mild buccal hollowing, 3 mL of fat should be placed per side. The fat is placed in a deep subcutaneous plane and it is layered with 0.1 mL per pass. In patients who have significant buccal volume loss, up to 7 mL of fat may be placed per side. In patients with a thin face, even if the buccal region does not appear deficient, be conscious of the fact that as fat is placed in the adjacent areas (cheek, submalar, and jawline) buccal hollowing will be accentuated.

Structural fat grafting to the lips can produce long-lasting enhancement of the upper and lower lip with purely autologous material. Fullness should be placed primarily below the vermillion and mucosa to create a structural expansion of them: this expansion advances the vermillion to evert the lip. Almost of the grafted fat should be infiltrated into the most superficial level, immediately deep of the vermillion and mucosa.

20 Prejowl Sulcus/Anterior Chin

The prejowl sulcus is defined as the depression immediately anterior to the jowl. This is an important area to fill both in younger patients with a minimal jowl and in older patients who will be undergoing concurrent facelifting.

In the younger patient, volume restoration to the prejowl sulcus is often sufficient for masking the jowl and recreating a youthful jawline. In patients with more advanced signs of aging where the facelift is the primary treatment for the jowl, filling the prejowl sulcus will produce a more ideal result. Microliposuction of the jowl is a simple, adjunctive procedure that can further enhance the overall aesthetic outcome. When addressing the prejowl sulcus, 3 mL of fat is injected into the prejowl sulcus with 0.1 mL per pass. The fat should be layered in multiple planes from supraperiosteal to subcutaneous. Volume loss in the prejowl sulcus should be thought of as a process or radial contraction resulting in a deficiency on the lateral and inferior border of the mandible. Correction of this to reestablish a smoothly contoured jawline requires layering of fat along the arc of contraction, from lateral to inferior mandibular border. Individuals with a mild degree of microgenia can obtain increased anterior projection with fat grafting to the mentum. In the patients whose primary need is anterior chin projection, alloplastic implants provide a more predictable and effective correction (Fig. 30.11, 30.12, 30.13, 30.14, 30.15, 30.16, 30.17, 30.18, 30.19, 30.20, and 30.21).

Fig. 30.11

(a) Preoperative. (b) One month postoperative following facial fat grafting in the nasolabial fold, prejowl sulcus, and anterior chin

Fig. 30.12

(a) Preoperative. (b) Three months postoperative after full-facial fat augmentation with particular attention to the mandible and midface. Notice how the shadowing in the upper cheek area is now effaced thanks to the improved facial volume

Fig. 30.13

(a) Preoperative patient with early development of nasolabial folds. (b) Marking. (c) One year postoperative following fat grafting that was injected into depressed areas at her cheeks

Fig. 30.14

(a) Preoperative female patient. Instead of seeing the lower eyelid area as an eyebag that needs removal, more often than not, it is too hollow that would benefit from filling with fat to achieve the desired results for rejuvenation. (b) Marking. (c) Postoperative following fat transfer to her face including her lower eyelid area. The patient’s initially flattened cheek appearance has been converted to a more youthful convex appearance since having fat grafting

Fig. 30.15

(a) Preoperative female. (b) Postoperatively, the jawline and cheek are enhanced

Fig. 30.16

(a) Preoperative. (b) One year postoperative after fat grafting has restored a normal jaw line after aging

Fig. 30.17

(a) Preoperative. (b) Postoperative following full-face augmentation with particular attention to the lower face (nasolabial folds, marionette lines, cheeks, infraorbital regions, chin, and lips). The patient had a remarkably long-lasting rejuvenation with small amounts of fat into most areas of her face

Fig. 30.18

(a) Preoperative middle-aged male. (b) Postoperative with improved face shape and fresh appearance

Fig. 30.19

(a) Preoperative female. (b) Postoperative with restoration of fullness to her cheeks and her lower eyelids

Fig. 30.20

(a) Preoperative young female. (b) Postoperative after secondary rhinoplasty, blepharoplasty, and fat transfer

Fig. 30.21

(a) Preoperative. (b) Two months postoperative showing satisfactory results after facelift, blepharoplasty, and subsequent fat grafting

21 Postoperative Care

At the conclusion of the surgery, there is no need for dressings or bandages on the harvest or recipient sites following isolated fat grating procedures. Head elevation and icing for 48–72 h will reduce and expedite resolution of postoperative edema. Beyond the first few postoperative days, the cheek area may feel a bit flushed or sore, but this effect will gradually decrease with time. Patients generally have very little discomfort in the face other than a tight sensation and are more apt to be aware of soreness and pain at the harvest sites. Patients are encouraged to rest the week following fat grafting and not engage in any excessive activities that require Valsalva or bending over.

22 Graft Survival

The longevity of grafted fat, though one of the important questions, is still awaiting a definite answer. There are very few human studies regarded survival of grafted fat and even those studies lack depth and number. Research by Rieck and Schlaak [55] concluded that fat transferred into subcutaneous tissue and muscle demonstrated 30 and 6 % survival, respectively, after 6 months [51]. Sadick and Hundgins [56] were only able to objectively demonstrate viable fat in one of six patients, who had gluteal fat grafts to the nasolabial fold, after 12 months. The study published by Kaminer and Omura [57] reported fat graft survival for more than 5 years. Nevertheless, they stressed the use of touch-up procedures to improve the quality and longevity of results. Few other studies reported mean survival of less than 2 years.

The authors’ clinical experience is satisfactory: a durable result can persist for a minimum of 12 months without any trend toward reabsorption; on average, approximately 32 % of the injected volume remains at 16 months; and microaugmentation and smaller-size injections seem to help promote better fat survival. It tends to last the longest in the cheek areas and midface and less long in the nasolabial or smile regions. The temple areas are variable and the eyelid regions seem to persist. To obtain long-term survival of transplanted autologous fatty tissue, the harvested and processed fatty tissue parcels must remain viable before implantation.

23 Unfavorable Points to Fat Grafting

Complications of fat grafting can be classified as acute or late. Acute complications include bleeding/hematoma, the frequency of which can be lessened with the use of a blunt cannula, and temporary injury to an underlying nerve or muscle. Fat is not intentionally placed into muscles, but occasionally edema in the area can inhibit or alter normal muscle movement. As the edema resolves, patients generally recover completely. The most devastating and fortunately rare complication is an intravascular embolization: fat embolism, where some of the injected fat enters the bloodstream, is a rare and serious complication and can result in stroke or heart attack. This has never occurred when using a blunt cannula. Therefore, sharp needles are discouraged, except when placing fat directly into the dermis. In addition, large boluses of fat should not be injected and injection guns should not be used when grafting fat.

Late complications include infections, which can result in resorption of the grafted fat. Strict sterile technique must be employed and cannulas that penetrate the oral mucosa should be considered. Despite this, the most common problems with fat grafting are aesthetic ones. You may have too little fat tissue reimplanted or too much. You may also be happy with the results for several weeks or months, but then have most of the transferred fat be absorbed.

However, the answer to fat absorption is not simply injecting large amounts of fat the first time, assuming some of it will not last. Placing too much fat in a particular area can overwhelm the growth of new blood vessels and the fat cells can all die at once, leading to irregularities or migration of fat out of the area where you want it.

Other risks include an allergic reaction to the anesthesia or local anesthetic, bad bruising, and asymmetry. Occasionally, bruising caused by a ruptured superficial blood vessel at the treatment site may be permanent.

There are patients in whom fat grafting is not realistic, such as patients with low body fat, long distance runners, those in advanced age, and those who have HIV-associated lipodystrophy. These patients can withstand large volumes and concentrations of synthetic injectable volumizers such as calcium hydroxylapatite (Radiesse) and poly-l-lactic acid (Sculptra). Both Radiesse and Sculptra are approved in the USA by the FDA for correction and restoration of facial fat loss (lipoatrophy). These patients can take high volumes of fillers, typically 3–4 times the amount used in the aging-face population.

24 Future Perspectives for Fat Harvesting

Tremolada et al. [58] proposed an innovative system, named Lipogems (formerly Lipostem), providing a non-expanded, ready-to-use fat product. The fat tissue obtained is highly enriched in pericyte-like elements by mild mechanical forces from human lipoaspirates. Lipogems is fast and safe without stem cell expansion and manipulation. Fat product centrifugation or subfractional harvesting is not required. Human lipoaspirate processing with the Lipogems device is performed by the surgeon at the bedside and consists in a two-step adipose cell cluster size reduction in a disposable, full immersion, closed system, which avoids the use of any enzyme (i.d. collagenase), therefore improving the preservation of cell surface – extracellular matrix – microenvironment. Histological and immunohistochemical analysis showed that Lipogems cell products contain a high frequency of pericytes and MSCs and low level of hematopoietic-like elements.

MSCs are highly positive for standard surface markers, such as CD44, CD73, CD90, CD105, CD146, and CD166, with approximately 50 % co-expression of CD34 and CD45. Gene expression analysis confirmed an enhancement of adipose tissue genes (VEGF, KDR, HGF) promoting vasculogenesis and capillary formation, compared to cell products obtained by enzymatic digestion.

Furthermore different from the lipoaspirate, the Lipogems product can be cryopreserved without losing its ability to release MSC, enabling banking applications of Lipogems processed adipose tissue products. Thus, Lipogems-treated adipose tissue may represent a powerful and innovative source of MSCs and object of study for future clinical trials (Table 30.1).

Table 30.1 Comparison between Lipogems and lipoaspirate