Rhinoplasty with Fillers and Fat Grafting

Nonsurgical rhinoplasty is one choice for cases in which open surgery may be harmful, the deformity is not indicated to correct with open surgery, or in patients who have phobia of general anesthesia or any type of surgery. Autologous fat injection or fillers are most common materials currently available in the market. In this article, we explain the indications, contraindications, methods, and complications of this treatment.

Key points

  • The use of fillers and fat graft is used only in cases of mild deformities and it should not be thought that this method can be an alternative to complete rhinoplasty in cases with definite indication.

  • It is very important to pay attention to the microvasculature of the nasal area in injections because if the injection goes into the vessels, it can cause catastrophic events such as blindness or brain damage.

  • Fat injection is a priority over fillers because it provides a larger volume of material and reduces the risk of unintended safety reactions. It is also unlikely to transmit disease. With new technology, it is possible to add cells and use tissue engineering in the fat graft technique, which gives a better chance of success.

Introduction

Today, the number of patients who desire to aesthetically improve the appearance of their nose without having to undergo surgical rhinoplasty has increased. Although surgical rhinoplasty is typically the choice of patients seeking aesthetic improvement of the nasal shape, using an injectable material for fixing irregularities and asymmetries holds great appeal owing to the simplicity of the correction, use of local or no anesthesia, comparatively low cost, and lack of downtime. In the majority of treatments, permanent or semipermanent fillers are injected into the dorsum, tip, and columella.

A noninvasive method for nasal recontouring is to bypass permanent surgical correction, although these modalities are mostly impermanent. In certain cases, secondary rhinoplasty can be an alternative; however, it can be laborious to perform, particularly if the skin is thin. Moreover, the majority of patients decline to undergo a new procedure. ,

There are various surgical and nonsurgical procedures for rhinoplasty. Augmentation can be performed by surgery and multiple graftings, such as cartilage or facial augmentation, permanent implants such as Medpore, poly(methyl methacrylate), silicone, and other materials. Nonsurgical rhinoplasty can also be carried out by injecting fillers (permanent, semipermanent, or resorbable) and with autologous fat transfer. Each procedure has its own advantages and disadvantages.

Numerous techniques have already been used to improve noticeable contour deformities and sharp edges of bone and cartilage to obtain a dorsum with a smoother contour and pad, especially for patients with thin dorsal nasal skin. Autologous and alloplastic materials can cover the underlying osseocartilaginous framework. Temporalis fascia graft, , dermal fat graft, , Erol’s diced cartilage graft, and homografts such as acellular dermis (Alloderm; LifeCell, Branchburg, NJ) are autologous materials that sporadically resorb and lose their ability as a camouflage. , Alloplastic materials such as polytetrafluoroethylene have a high incidence of infection. ,

In rhinoplasty, both autologous grafts and synthetic implants have shown satisfactory outcomes. Synthetic implants, nonetheless, are associated with 2 major complications: displacement and extrusion. With regard to these disadvantages, autologous cartilage and bone grafts are the choice of most patients owing to the excellent biocompatibility and low risk of infection and extrusion. However, inconsistent volume and uncontrollable shape of the graft, an unreliable absorption rate, and possible donor site morbidity are disadvantages of autologous grafting. A meta-analysis reported a number of complications after the implantation of alloplastic materials in rhinoplasty but supported the placement of alloplastic implants in case of unavailability or insufficiency of autogenous materials. At present, there are no established guidelines for transplanting alloplastic materials. The nonsurgical treatment of rhinoplasty sequelae was performed in 1904 by Stein, who injected paraffin to correct a saddle nose deformity ,

Indications for nonsurgical rhinoplasty

Nonsurgical rhinoplasty, known as liquid rhinoplasty, is a general term for the correction of nasal defects. In fact, it is a nonsurgical procedure for corrective treatment of specific nasal areas, including saddle nose, contour deformities, side wall irregularities, hump removal, columella retraction, nasal lengthening, dorsal augmentation, deep radix, nasal tip projection and rotation, nasolabial angle, and asymmetry.

The most common indications for fat injection (or autologous fat transplantation) after rhinoplasty include revision of dorsal, inverted V, stairstep, and saddle nose deformities. In nasal scarring and tight thin skin, fat grafts are useful. Autologous fat grafts are thought to create a space between densely adherent skin and the underlying nasal skeleton, helping to camouflage deformities and making secondary procedures and subsequent dissection significantly easier. , The forehead–glabella–radix complex is another area where injecting fillers or fat and represents an essential triad in rhinoplasty, from which the nasofrontal angle is derived. The radix is a depression at the origin of the nose, and the nasion, or the bridge of the nose, is the depressed part of the nose, and is located 4 mm to 6 mm deep to the glabella, just below the eyebrows. The nasofrontal angle is the transition between the forehead and the dorsum of the nose and can vary from 128° to 140°. However, the ideal angle for women is 134° and for men is 130°.

Fat grafting to the radix may diminish complications of radix augmentation (visibility, resorption, and donor site issues); however, this method provides an easily available solution to the thick nasal base. Increasing the height of nasal radix minimizes the necessary amount for hump or tip modification. This issue is very important in patients with thick nasal skin. Cranial and caudal radix positions provide a longer nasal dorsum with a decreased anterior projection and a shorter nasal dorsum with increased anterior projection, respectively. In addition, a deep and high radix decreases and enlarges the nasofrontal angle, respectively. Variations come with normal aging, especially those influencing bone, muscle, fat, and skin, and are determining factors of the nasofrontal angle. Age also causes the retrusion of the glabella and nasion. Depression in the lower forehead and bossing of the forehead may be present owing to soft tissue atrophy or bony remodeling and hyperinflation of the frontal sinus, respectively. A piriform aperture is an indicator for determining the nasolabial angle. Midface retrusion mainly occurs with aging. This aging process includes the piriform aperture, which remodels posteriorly relative to the upper face, resulting in a loss of bony support for the alar base. In addition to piriform aperture, the anterior–posterior position of the alar base is another criterion affecting the nasolabial angle, which changes with age ( Fig. 1 ).

Fig. 1
Treatment algorithm for development of patient care treatment plan.

Contraindications

Despite many benefits, injecting fillers or fat grafts to the nose has some limitations and contraindications. Nose injection is an augmentation procedure. Hence, an overprojected nose is not an indication for augmentation. Injection of fillers is typically associated with local and systemic contraindications. An infected area, active viral infections like herpes, necrosis of the skin owing to prior interventions, and pimples are examples of local contradictions. Vasoconstrictors, which are commonly used in local anesthesia, are not appropriate for heavy smokers or patients with cardiovascular diseases.

Nasal anatomy and danger zones

The arterial supply of the nose is provided by branches of carotid arteries, namely, the ophthalmic and facial arteries. The ophthalmic artery is derived from the internal carotid artery, the same as the vessels that come from the cavernous sinus. The central retinal artery is the first intraorbital branch and one of the most important and smaller branches of the ophthalmic artery. The ophthalmic artery has 2 terminal branches: the supratrochlear artery and the dorsal nasal artery. The dorsal nasal artery originates from the orbit above the medial palpebral ligament is divided into 2 main branches. The first passes through the root of the nose, and the second passes along the dorsum of the nose, which supplies its external surface area in its path toward the nasal tip. In addition, the first branch inosculates with the angular artery, whereas the second branch inosculates with both its fellow artery of the other side and the lateral nasal artery, which emanates from the facial artery and ascends along the side of the nose. The lateral nasal artery supplies not only the ala of the nose, but also the dorsum of the nose and inosculates with its fellow and the following branches: the septal and alar branches, the dorsal nasal branch of the ophthalmic artery, and the infraorbital branch of the internal maxillary. The columellar artery is the superior labial branch of the facial artery that runs up the columella, ends, and inosculates in the tip with the lateral nasal branch of facial artery.

The following are the major conclusions achieved from this anatomic review. There is a direct and short connection between the proximal blood supply of the nose and the internal carotid and retinal arteries. During injection in the area of the dorsum, radix, or glabella, this network can be affected by embolization and can cause various calamitous outcomes such as blindness or brain infraction. Embolization of the distal blood supply, which is mostly at the tip and in alar regions, also can give rise to a wide variety of ischemic phenomena.

The cutaneous microvasculature in human skin is organized into 2 horizontally aligned plexuses that include 3 blood vessel segments: arterioles, venules, and the interposed arterial and venous capillaries. Capillary loops are divided into 6 to 8 loops and extend into elongated the dermal papillae, which come directly from the perforating arteries of subcutaneous fat. In this structure, arterioles and venules are directly linked to the upper branchial plexus, where the majority of microvasculature is situated 1 to 2 μm below the epidermal surface. The arteriolar vessels in the papillary dermis vary from 17 to 22 μm in outer diameter, first decreasing to capillaries and then increasing to postcapillary venules (with the diameters from 4 to 6 μm and from 10 to 15 μm, respectively). Many years ago, physiologists came to the conclusion that the skin’s extensive blood supply is beyond its nutritional requirements and postulated that this structure serves to aid in controlling control body temperature.

Postcapillary venules are the largest part of vessels within the papillary dermis and represent the place where inflammatory cells move from the intravascular to the interstitial space and where acute inflammation occurs. ,

The structure of the 2 layers of blood vessel is that the superficial plexus supplied by the vessels from the hypodermis include small conical areas at the center of the vessels feeding from the lower plexus. , Based on the 2-dimensional representation from the surface, the disks forming the borders of each cone create a pattern that is observable during vascular obstruction. This apparent pattern of a disk placed on the surface delineates these conical drainage areas from the superficial plexus to the deep one. For instance, livedo reticularis or mottled skin, which is a vascular reaction pattern, can frequently be observed in cases of skin thromboembolism. The main reason for this pattern is due to the slow flow of blood within the postcapillary venules. Thus, the clinical pattern is related to blood stagnation in the dermal venules, and the bluish discoloration of the skin arises from desaturated blood, optically filtered by the dermis and epidermis ( Figs. 2 and 3 ).

Fig. 2
Main arterial supply to the nose and danger zones regarding fat injection ( arrows ). AA, angular artery; DNA, dorsal nasal artery; FA, facial artery; IOA, infraorbital artery; LA, superior labial artery; LNA, lateral nasal artery; STA, supratrochlear artery.
( From Monreal J. Fat grafting to the nose: personal experience with 36 patients. Aesthetic Plast Surg. 2011;35(5):916; with permission.)

Fig. 3
Arterial anatomy of the face. Although not drawn to scale, this illustration highlights internal carotid artery branches and external carotid artery branches, showing the extensive anastomoses between vascular territories in the face’s nasal region. Filler product has been carried in these anastomotic vessels from the perioral area to the periorbital area, and vice versa. Note that the facial artery has several known branch distribution types. NLF, nasolabial fold.
( From DeLorenzi C. Complications of injectable fillers, part 2: vascular complications. Aesthetic Surg J. 2014;34(4):594; with permission.)

Fat

The use of fat grafts for the correction of congenital malformations and intricate traumatic wounds with soft-tissue loss following radical surgery of tumor was proposed for the first time in 1893 by Neuber. This notion was followed by Hollander in 1912, by Neuhof in 1921, and by Josef in 1931 ( Table 1 ). Liposuction and tumescent anesthesia were other techniques introduced by Fisher in 1974 and by Klein in 1985. , In 1919, Bruning used fat injection to correct postoperative cosmetic nasal deformities. However, the technique was not sufficiently accepted owing to the poor survival duration of the fat grafts. ,

Table 1
Summary of literature review
From Kao W-P, Lin Y-N, Lin T-Y, et al. Microautologous fat transplantation for primary augmentation rhinoplasty: long-term monitoring of 198 Asian patients. Aesthet Surg J. 2016;36(6):651–2; with permission.
Authors (Year) Title Application of Fat Grafting Study Duration Total No. of Patients and No. Who Underwent 1, 2, or 3 Sessions; (Mean No. of Sessions) No. of Men/No. Of Women Mean Age, Years (Range) Mean Injection Volume, mL (Range) Mean Follow-up, Months (Range) Primary Results Key Contributions Comments by Authors of the Present Study
Kao et al, 2016 Microautologous Fat Transplantation for Primary Augmentation Rhinoplasty: Long-term Monitoring of 198 Asian Patients Primary augmentation rhinoplasty for aesthetic purposes 4 y 198 patients; 126 (1 session) 70 (2 sessions) 2 (3 sessions); (1.4) 18/180 45.5 (26–58) 3.4 (2.0–5.5) 19 (6–42) Overall satisfaction rate of 63.1% First article to describe a large series of patients who underwent fat grafting in aesthetic primary augmentation rhinoplasty with MAFT MAFT is appropriate for primary augmentation rhinoplasty for aesthetic purposes
Duskova et al (2004) Augmentation by Autologous Adipose Tissue in Cleft Lip and Nose. Final Esthetic Touches in Clefts: Part I Reconstruction in cleft lip and nose to supplement a hypertrophic scarred lip and nasal columella NS 5 patients; (1 session) 3 (2 sessions) 1 (3 sessions) (2) 1/4 NS (26–38) 4.3 (3–6) 22 (NS) All 5 patients have pleasing results Described augmentation of the upper lip and columella by fat grafting is minimally invasive and results in physiologic shapes for the upper lip, nasal columella, and nasolabial angle Small study but with promising results
Cárdenas et al, 2007 Refinement of Rhinoplasty with Lipoinjection As an adjunct to open rhinoplasty 2 y, 3 mo 78 patients 78 (1 session) (1) 7/71 NS (14–56) NS (1–3) 15 (1–36) Results of 68 patients considered excellent, 9 good, 1 unsatisfactory Determined that fat grafting can be applied to refine open rhinoplasty Concludes that fat grafting is an adjunct procedure with open rhinoplasty
Monreal, 2011 Fat Grafting to the Nose: Personal Experience With 36 Patients Primary augmentation, treatment of deformities after rhinoplasty, and in conjunction with rhinoplasty 3 y, 3 mo 36 patients 33 (1 session) 2 (2 sessions) (1.1) NS NS Harvested 3–12 mL for lipoimplantation; 6–12 mL when combined with rhinoplasty 7 (NS-14) 80% (good to high) patient satisfaction, especially for deformities after rhinoplasty Identified nasal danger zones and emphasized the importance of using an 18G, blunt injection needle Only 18 of 36 patients (50%) presented for aesthetic purposes
Clauser et al (2011) Structural Fat Grafting: Facial Volumetric Restoration in Complex Reconstructive Surgery Volumetric restoration in complex reconstructive surgery 4 y, 5 mo 23 patients NA (NA) NS NS 3.4 NS NS Good results and improvements in facial morphology, function, shape, and volume Demonstrated the importance of structural fat grafting in facial volumetric restoration in complex reconstructive surgery Only 23 of 57 fat grafting procedures were discussed
Baptista et al, 2013 Correction of Sequelae of Rhinoplasty by Lipofilling To treat rhinoplasty sequelae, saddle nose, and sequelae of lateral osteotomy sequelae 4 y 20 patients 18 (1 session) 2 (2 sessions) (1.1) NS 53 (NS) 2.1 (1–6) NS (18–24) 18 patients satisfied to very satisfied, 2 required second rhinoplasty Determined that lipofilling could be a simple and reliable alternative to correct imperfections following rhinoplasty Correction of sequelae of rhinoplasty in 20 patients
Erol 2014 Microfat Grafting in Nasal Surgery As microfat transplantation in patients with secondary nasal deformities (group 1 slight irregularities; group 2, marked irregularities; group 3, severe deformities) 5 y 313 patients: 264 group 1 patients (1–3 sessions); 38 group 2 patients (3–6 sessions); 11 group 3 patients (6–16 sessions) (NA) 27/286 25.7 NS 0.3–0.8 mL for minimal irregularities; 1–6 mL for major irregularities NS (12–60) Autologous microfat injection is safe and effective for correcting slight irregularities of the nose Demonstrated that microfat grafting is effective for correcting minor irregularities of the nasal skin and is appropriate for patients who cannot undergo revision rhinoplasty Multiple injections may be necessary for correction of nasal irregularities
Nguyen et al (2014) Autologous Fat Grafting and Rhinoplasty For correction of rhinoplasty sequelae 6 y 20 patients (1 session) 2 (2 sessions)
(1.1)
NS 53 NS 2.1 (1–6) NS (18–24) 18/20 patients satisfied to very satisfied Emphasized the importance of using a 21G, 0.8-mm injection cannula vs an 18G, 1.2 mm cannula Relatively small study size to address correcting the sequelae of rhinoplasty
Huang (2015) Does Sensation Return to the Nasal Tip After Microfat Grafting? Evaluation of severity of numbness in the nasal tip after fat grafting 4 y 30 patients 30 (1 session) (1) 0/30 20 (20–45)

Abbreviations: NA, not applicable; NS, not stated.

Fat grafting continues to be one of the most common procedures because of the simplicity of fat harvest, the availability of graft materials, and the lack of transplant rejection. Nonetheless, the rates of fat survival and retention cannot be predicted, and various difficulties (eg, abscesses, cysts, nodulation, and neurovascular injury) may arise. Later, after extensive research and improvement of surgical methods, structural fat grafting was recognized as a reliable treatment strategy with satisfactory clinical consequences. In 2007, the idea of microautologous fat transplantation (MAFT) was presented by Lin and colleagues, who suggested that this technique provides reliable results and is feasible in facial rejuvenation ,

Because of its abundance, easy accessibility, lower cost, host compatibility, and repeated harvesting, fat has the potential for becoming the perfect soft tissue filler. Additionally, in comparison with dermal fillers, fat provides similar long-lasting durability with a low cost. ,

Previous investigations have reported a broad variety of indications for fat grafting, including cosmetic improvement, body contouring, scar reconstruction, periocular rejuvenation, progressive hemifacial atrophy, radiation-damaged sites, and fat atrophy in patients infected with the human immunodeficiency virus. In this field, much progress has been achieved; however, tumescence of the base of all these fat graft surgeries is tumescence anesthesia.

In 2009, fat grafting constituted 5.9% of all nonsurgical cosmetic procedures. This technique has widely been applied in the rejuvenation of different parts of the body, the correction of deformities caused by liposuction, and aesthetic refinement of body contours such as the buttocks. The method of fat injection into the nose helps to cover deficiency of a former rhinoplasty or enhance skin thickness in cases with a skeletonized nose or in cases involving congenital, posttraumatic, or traumatic pituitary soft tissue defects. Facial rejuvenation and contour enhancement using fat grafting, as a filler, has shown successful results; therefore, it is a promising method to correct these defects.

Fat is an ideal filler because of the natural integration into tissues, being autologous, and perfect biocompatibility. Fat is also an active and a dynamic tissue that is composed of various cell types, including adipocytes, fibroblasts, myocytes, preadipocytes, and endothelial cells.

Adipose-derived stem cells (ASCs), the same as other mesenchymal stem cells, have the potential for differentiation. In comparison with bone marrow-derived stem cells, ASCs have a greater yield upon isolation and a higher rate of proliferation in culture when. Because of these features and owing to the simplicity of harvesting of these cells in large amounts with minor donor site morbidity, ASCs have been considered to be promising for application in regenerative therapies. ,

Fat Harvesting

In 1987, Coleman introduced a novel technique for fat harvesting. His technique minimized the rate of complications from transferring of fat during liposuction was composed of 3 steps: manual lipoaspiration under low pressure, centrifugation for 3 minutes at 3400 rpm, and reinjection in 3 dimensions. Despite some technical modifications, Coleman technique remained as the gold standard for lipoplasty and lipofilling. Nevertheless, owing to the variability of lipofilling results, it is necessary to optimize the procedure. The long-term results of fat grafting are often unsatisfactory because the partial absorption (up to 70% of the volume of the fat graft) is unpredictable. Previously, resorption rates of 30% to 70% per year have been reported. Therefore, with regard to the unpredictability of success rates of autologous fat grafting, physicians are unable to select the perfect method for harvesting and transferring fat grafts. , , The Coleman technique seems to be standard and favorable for these purposes, though it suffers from some limitations. First, owing to damage caused during the aspiration and centrifugation steps, the number of fat cells decreases; second, cells in direct contact with well-vascularized tissues need to be infiltrated. Third, it is an operator-dependent and time-consuming technique for less experienced surgeons. Many attempts were made toward the alteration of the Coleman technique to improve the survival of the injected fat, atraumatic fat harvesting, fat washing for the removal of inflammatory mediators, incubating fat grafts with different bioactive substances, and centrifugation of fat grafts can be used.

The main techniques for fat harvesting are suction aspiration, syringe aspiration, and surgical excision. Recent experimental and clinical surveys have advocated the direct fat excision overaspiration. In their study, a fat cylinder graft was introduced by Fagrell and colleagues. In this technique, fat is drilled out in cores by a punching device. , In another study, a core graft for block grafting was suggested by Qin and colleagues, , because in this technique, the structure and viability of the harvested fat tissues are preserved without impairment of the adipocytes. Pu and colleagues , observed damaged adipocyte function in conventional liposuction aspirates relative to fresh fatty tissue samples and syringe aspiration of fat. Compared with syringe aspiration, lipoaspiration at a low negative pressure may yield fat faster, particularly when a large volume of fat is required. The high vacuum pressures of conventional liposuction may give rise to functional disruption in the majority of adipocytes. , Cannula size is one of the other main factors affecting the viability of harvested fat. Using large-bore cannulas in the excisional method and fat harvesting can decrease the incidence of cellular rupture and maintain the native tissue structure. Campbell and colleagues, however, found that there is a reverse correlation between damage to cells and the diameter of the instrument used to extract fat. Additionally, Erdim and colleagues reported that using a 6-mm cannula instead of a thinner (4 or 2 mm) cannula can enhance adipocyte viability. Described in the technique proposed by Coleman for fat harvesting, fat is manually suctioned with a 3-mm, 2-hole cannula linked to a 10-mL syringe by removing the plunger. The cannula is then pushed through the harvesting site during digital manipulation by the surgeon to draw back on the syringe plunger and create a gentle negative pressure.

Fat is naturally deposited in different parts of the body. The most suitable site for fat harvesting is identified by the surgeon after a precise examination of the patient. One of the most common sites for fat harvesting is the abdomen, followed by the trochanteric region (saddlebags) and the inside of the thighs and knees. ,

The are 2 methods for harvesting of fat grafts: a wet and a dry method. In the wet method, which was described by Klein and colleagues , in 1993, the donor site is injected with a fluid (Klein’s) solution composed of 0.9% NaCl, epinephrine, and a local anesthetic. Hydrodissection and enlargement of the target fat layer are reported indications of the wet method. Low shear stress has been demonstrated to improve graft survival and, in fact, is a factor affecting adipocyte viability. An alternative to a wet method is the dry method, which is done without the tumescent fluid. However, this method may result in a greater need for analgesics.

Fat Processing

Sedimentation, filtering, washing, and centrifugation are methods commonly used for the preparation of fat grafts. Lipoaspirate is composed of adipocytes, collagen fibers, blood, and debris; therefore, fat processing is a necessary step in fat grafting. These components often result in inflammation at the recipient site and cause damage to the fat graft. The effects of fat processing with the fat graft preparation methods mentioned create no significant differences in fat retention. However, unlike centrifugation, filtration led to nodule formation. , After centrifugation, 3 layers are observed; the upper layer consists of lipids and can be poured off using absorbent material. The middle layer includes fatty tissue, and the lower layer is composed of blood, tissue fluid, and local anesthetic, which is ejected from the base of syringe. For adipose tissue grafting, the middle layer is routinely used.

Fat Injection

Cannulas with small gauges are believed to minimize trauma to the recipient site and decrease the risks of bleeding, hematoma formation, and poor graft oxygen diffusion. Because revascularization starts at the periphery, the ischemic time is longer in the center of the graft. Accordingly, fat injection is preferred to be performed in multiple small-volume sessions rather than only 1 session.

There is a direct relationship between the nature of the recipient site and the selection of cannula size. Infiltration with cannulas of at least 2.5 mm in diameter can increase the viability of adipose tissue, whereas various needle gauges did not confer significant differences in cell viability. To successfully gain the prolonged survival of autologous fat, it is necessary to use small injections of grafts (thinner than 2–3 mm). An adipose tissue graft obtains its nutrition through plasmatic imbibition from approximately 1.5 mm of its vascularized edge. Hence, fat grafts with a diameter of less than 3 mm can have a better long-term survival rate. In a number of patients, they have remained in place and stable for 10 to 20 years. ,

In a rabbit face model, the placement of fat grafts was investigated in varied tissue planes. The results of morphometric and histologic measurements of transplanted fat grafts suggested the higher survival of fat grafts, especially when placing in supramuscular layer rather than subcutaneous or submuscular layer. These findings verify that fat graft placement in varied tissue planes is favorable for better clinical achievements. , Less fibrous fat has better flow characteristics, allowing for smoother infiltration. Thus, recognition of the flow characteristics of the fat being injected helps to avoid deformities and ensure that samples of similar quality are used symmetrically.

Role of Adipose-Derived Stem Cells

ASCs, similar to bone marrow–derived stem cells, are able to differentiate into several mesodermal tissue types and also indicate similar expression of surface protein marker. , Meanwhile, unlike bone marrow-derived stem cells, ASCs can readily be attained using a standard wet liposuction technique under local anesthesia, without the need for expansion in culture. , For these reasons, ASCs have received attention for their application in cell-based therapies involving the repair and regeneration of damaged tissue. Stem cells isolated from lipoaspirates have the ability to differentiate in vitro into adipocytes, osteocytes, chondrocytes, myocytes, caryomioblasts, and neurons. For isolation of ASC, there are 2 methods: the first method is based on a mechanical and enzymatic procedure, and the second method is exclusively mechanical.

Cell-assisted lipotransfer is a new approach to autologous tissue transfer, first introduced by Matsumoto and colleagues in 2006. Indeed, cell-assisted lipotransfer is the simultaneous transplantation of ASCs and aspirated fat. In this method, ASCs are applied to maximize the effectiveness of autologous lipoinjection, that is, to attain a higher survival rate and the persistence of transplanted fat, as well as to minimize complications from lipoinjection, including fibrosis, pseudocyst formation, and calcification.

Adipose tissue has lately been recognized as a source of ASCs or processed lipoaspirate cells, which are abundant in the lower abdomen and inner thigh. These 2 parts of the body are thought to be the better donor sites for adult ASCs relative to other typical donor sites. This finding means that fat graft not only can serve as a filler, but also can improve the quality of aged and scarred skin. , , Adipose tissue has been considered as a source of stem cells, which are able to differentiate into many other mature cells.

In fat grafting, the regenerative attributes of mesenchymal stem cells has been applied for the treatment of many complications, including long-term ulcerations, skin atrophy owing to radiotherapy, and burn healing. , Using fat in syndromes such as Raynaud phenomenon and unilateral vocal cord paralysis has also been reported.

Methods

Cárdenas and Carvajal presented a procedure using lipoinjection for the refinement of rhinoplasty in 2006. From 78 patients who participated in this study, 61 and 17 were selected for primary and secondary rhinoplasties, respectively, with a follow-up time of 1 to 36 month(s). Before the initiation of open rhinoplasty and at the beginning of the procedure, 1 to 3 mL of autologous fat was injected to the nose through small incisions (0.5 cm). After the amount of fat was determined based on individual patient needs, it was placed in the radix, dorsum sides, and supratip regions. At the end of the rhinoplasty, the fat was injected subcutaneously over the osseocartilaginous framework using a 1-mL syringe. The fat was used as a thin layer of soft tissue to thicken the covering skin and aid in concealing minor imperfections. No minor deformities were observed, and in all the patients, the quality of the skin was improved. The authors reached the conclusion that refinement of rhinoplasty by injecting fat into the nose can serve as a rapid, simple, and inexpensive procedure for obtaining long-term symmetric contours on the nasal dorsum.

In 2011, Juan Monreal performed an investigation on 33 patients with nasal deformity. In his study, 15 cases were injected with 6- to 12-mL fat grafts, instead of cartilage or prosthesis, on the nose to complete deficient bone. However, in 18 cases, 3- to 12-mL fat grafts were used for patients with or without previous surgery as the unique method of improving nasal aesthetics. For the 33 cases, 36 procedures were undertaken, with a maximum follow-up period of 14 months (mean, 7 months). Changes in volume and shape of the nose, aesthetic improvement, and patient satisfaction were analyzed by comparing preoperative with postoperative control photographs. The results of nasal lipoimplantations showed that patients with a previous surgery had a bit more swelling and ecchymosis than those who refused the primary surgical rhinoplasty. After 4 to 5 months, none of the patients observed alterations in contour or volume. Because of the use of the small volumes of fat, it was difficult to determine the percentage of final graft take, which was 60% and 75% in cases who refused primary and secondary surgical rhinoplasty, respectively. Patient satisfaction was estimated to be good to excellent in 80% of cases, especially in cases of postrhinoplasty deformity. Monreal concluded that fillers or fat grafts cannot be a substitute for a surgical technique, and their results will never be more favorable. However, autologous fat grafting can serve as a first-line nonsurgical alternative to the reconstruction of nasal shape, particularly for patients who refuse primary and secondary surgical rhinoplasties and accept the limitations inherent to the technique. The aesthetic nasal and paranasal units can be considered as a whole or as aesthetic subunits separately, if necessary. Moreover, surgical rhinoplasty can be combined with lipoimplantation in different areas of nose, including the dorsum, radix, glabella, or premaxillary, to change the volume and shape of these areas without using cartilage grafts or solid prostheses.

In 2012, Baptista and colleagues assessed “correction of sequelae of rhinoplasty by lipofilling.” A total of 20 patients participated in their study and received an injection of 1 to 6 mL of adipose tissue to the nose. Based on their results, surgical sequela was corrected in 15 cases after primary rhinoplasty and in 5 cases after secondary rhinoplasty, with an interval of at least 1 year after the first or last procedure. They applied different cannula sizes for fat collection and injection, that is, 11G (3 mm) and 7G (1.7 mm) cannula in 10 patients and 14G (2 mm) and 21G (0.8 mm) in another 10 patients, for harvesting and injecting, respectively. Based on the location of the nasal defect, the insertion points were in the glabellar region at the base of the ala nasi or the columella. The injection plane is normally performed in contact with the periosteum, but the recent use of microcannula allows for injections in the superficial musculoaponeurotic system or in the direct subdermal plane. Patient follow-up appointments were at 2 weeks, 2 months, and 18 months. The results were evaluated based on patients’ satisfaction and surgeons’ comments with regard to comparison of preoperative and postoperative photos at 18 months. “In patients who have undergone multiple operations, microinjection of adipose tissue can be a simple and reliable alternative for correction of imperfections following rhinoplasty.”

In 2014, Erol conducted a research of autologous microfat grafting in nasal surgery. In his 5-year survey, microfat grafting was applied to treat 313 patients with secondary nasal malformation and minor skin deformities or severe nasal skin damage. Extra harvested fat at each patient’s first injection session was cryopreserved for later injection. The minimal malformations were corrected by the injection of 0.3 to 0.8 mL of microfat during each session. However, for the maximal deformities or defects, 1 to 6 mL of microfat was used for each session. The most frequent areas for fat harvesting were the abdomen and flanks, followed by the trochanteric region, buttocks, or medial thigh. Fat was obtained through a small incision from patients under general anesthesia via a 10-mL syringe and 3-mm cannula; local anesthetic was not used for donor sites. Sealed Luer-Lok syringes were then centrifuged at 3000 rpm for 3 minutes. The upper (containing liquid lipid) and lower (containing aqueous) layers were discarded, and 1 g of first-generation cephalosporin was added to each 100 g of centrifuged fat tissue.

Protocol for Freezing and Thawing

After the injection of the required amount of fat or tissue cocktail, the excessive fat was cryopreserved. Samples were transferred to sterile tubes of different sizes (10, 20, or 50 mL), labeled, and frozen at −196°C in a liquid nitrogen tank. The cryopreserved graft samples were first placed in a UF 601 medical refrigerator (−80°C; Electrolux, Stockholm, Sweden), and then were taken from the medical refrigerator and transferred to a standard refrigerator (−15°C) 12 hours before subsequent procedures and finally thawed gradually at room temperature for 1 hour before injection. There are many controversies over fat freezing, and some researchers refuse to use frozen fat.

The patient’s nasal area was marked for injection while the patient was standing. The recipient sites received a local anesthesia, consisting of a mixture of 0.5% bupivacaine (20 mL), adrenaline (0.50 mg), physiologic serum (30 mL), and triamcinolone acetonide (20 mg), to diminish post-treatment edema and ecchymosis and also to create vessel vasoconstriction to minimize the risk of microembolism.

Injections were carried out depending on the thickness of the skin with an intravenous cannula (22G or 24G). The correction of minor malformations was performed with the injection (1–3 times) of 0.3 to 0.8 mL of cryopreserved microfat graft material. However, major malformations or defects were corrected by the injection (3–6 times) of 1 to 6 mL of the graft material. Meanwhile, for patients with severe nasal irregularities with damaged skin, cryopreserved microfat graft material was injected at 2-month intervals (6–16 times).

Repeated injections of the cryopreserved fat were conducted, if required. Intradermal or subcutaneous injection of tiny amounts of fat was performed depending on the injection site. Patients who required repeated injections received a local anesthetic and evaluated by comparing their pretreatment and posttreatment photographs. For patients with minor irregularities, 1 to 3 injections of microfat were necessary, whereas cases with multiple and severe irregularities required 3 to 6 injections. The patients were highly satisfied with the injections. Another group of patients who had severe traumatic skin damage needed 6 to 16 injections for reconstruction. Each patient’s skin damage was repaired after repeated injections. Autologous microfat grafting seems to be a safe and efficient procedure for the correction of not only minor irregularities of nasal skin, but also severely damaged skin on the nose.

Kornstein and Nikfarjam published an article entitled, “Fat Grafting to the Forehead/Glabella/Radix Complex and Pyriform Aperture: Aesthetic and Anti-Aging Implications” in 2015. Participants in their study were divided into 2 groups: the first group included patients who underwent fat grafting alone (FG group; n = 26), and the second group consisted of patients who underwent fat grafting plus rhinoplasty (FG + R group; n = 19). The mean follow-up of the first and second groups was 3.3 and 5.2 years, respectively. Tumescent fluid was used to infiltrate donor sites. Also, the harvested fat samples were centrifuged. The main objective was to achieve a homogeneous paste with the ability to be readily and predictably injected. To provide cannula access, a 16G needle was used instead of incisions. Subsequently, fat was injected in small aliquots using a 17G side port, bullet-tip cannula. The cannula tip was placed to a depth of palpating bone. Next, tiny aliquots of fat were injected to preserve close contact with sufficient vascular supply, the same as skin grafting. Fat (virtually 20 cm 3 ) was then injected into the lower forehead and nasofrontal regions until the achievement of aesthetic end point of a lateral-to-lateral and cranial-to-caudal gentle convexity. The mean nasofrontal angle in the 2 groups (FG and FG + R) decreased by 2.0° ( P = .005 and P = .011, respectively). However, the nasolabial angle increased by 2.3° ( P = .006) in the FG group and by 6.0° ( P = .026) in the FG + R group. Fat grafting to the forehead–glabella–radix complex and pyriform aperture can act as a reliable technique for favorable modification of both the nasofrontal and nasolabial angles. This method helps to improve the interaction between the nose and the adjacent facial features, which ultimately maximizes the overall aesthetics.

Numerous techniques are available for fat injection and are discussed in various investigations. In a previous study of 198 Asian patients undergoing augmentation rhinoplasty, Kao and colleagues in 2016 used MAFT-GUN, an adjustable device applied for delivering different sizes of fat parcels. He augmented these particles to the nose from nasal tip to an area approximately 15 mm above the interconthal line. The total volume of fat was injected into upper, middle, and lower zones on the nasal dorsum.

Initially, fat was harvested from the lower abdomen by injecting tumescent fluid into the harvesting area. The volumes of lipoaspirate and tumescent fluid was approximately equal, to ensure that fat represented a major proportion of the lipoaspirate. To mitigate damage to the lipoaspirate, a 10-mL syringe plunger, which was connected to a liposuction cannula, was pulled back to approximately 2 to 3 mL for preserving a negative pressure of 270 to 330 mm Hg. Lipoaspirates were purified by centrifugation at approximately 1200× g for 3 minutes. In this method, owing to environmental exposure and manual manipulation, graft contamination was minimized. Separation of the lipoaspirate into layers was facilitated by centrifugation. The upper and middle layers contained oil from ruptured fat cells and purified fat, respectively, whereas the lower layer was composed of blood, cellular debris, and fluid. A transducer was then used to transfer the purified fat into a 1-mL Luer-slip syringe. The purified fat-containing syringe was loaded into a MAFT-Gun, which was connected to an 18G blunt-tip cannula. Fat parcels of 0.0067 mL (1/150 mL) to 0.0056 mL (1/180 mL), with each trigger deployment, were transferred by the device set by adjusting a dial. At the nasal tip, a single puncture incision was induced with a #11 scalpel blade, and it was infiltrated with 2% lidocaine HCl (0.3–0.5 mL) with a 1:50,000 concentration of epinephrine. Subsequently, fat was transferred by depressing the trigger, while pulling out the MAFT-Gun. Fat was carefully injected into 2 to 3 layers of the nasal dorsum, that is, from the deep areolar plane to the vascular/fibromuscular plane to the subcutaneous areolar plane. During MAFT, the surgeon used their nondominant hand to apply downward traction to 3 zones of the nose, first on the middle third of the nose while grafting the upper third and second on the lower third of the nose (the nasal tip) while grafting the middle third. Finally, after transferring fat to the nasal tip, the insertion point was closed using a nonabsorbable suture (6-0). The rate of fat retention was estimated to be 50% or less at 6 months postoperatively. After monitoring for an average of 19 months, patients were satisfied with the outcome. The satisfaction rate for those who underwent 1 session of MAFT was acceptable, but it was excellent for those who underwent 2 or 3 sessions.

In a pilot study by Lin and collogues in 2017, nasal dorsum contouring using fat injection was analyzed. In this study, 13 patients were evaluated and received fat injection using a MAFT-Gun for the first time. The patients were 12 females and 1 male, and their mean age was 34.03 ± 7.28 years (range, 22–47 years). Reconstructions of 3-dimensional photography images, which were taken before fat injection and 3 months later, were performed with 3dMDvultus software. In total, 26 scans were obtained from all the patients and were analyzed. The results were reported as mean ± standard deviation. The amount of fat injected for nasal dorsum augmentation was 1.67 ± 0.95 mL (range, 0.6–3.3 mL). Based on calculation using the 3dMDvultus software, the volume changes were 0.74 ± 0.42 mL and 0.74 ± 0.43 mL for the first and second measurements, respectively. Also, the intraobserver consistency measured by Cronbach α = 0.96 ( P <.001) was high. Based on the 3-dimensional images, the mean volume change and the mean retention rate was 0.74 ± 0.42 mL (range, 0.21–1.53 mL) and 44.54%, respectively.

The impact of fat grafting on edema and ecchymoses in primary rhinoplasty was studied by Gabrick and coworkers in 2019. They applied Telfa-rolling technique for fat processing. Using a 19G needle and 1-mL syringes, the fat was injected into the deep surface of the periosteum of the nasolabial fold and medial canthal areas. The harvested fat averaged 3.7 mL and ranged from 1 to 21 mL. All patients had autologous fat grafting to these areas (100%) and some to additional facial regions. The researchers came to the conclusion that autologous fat grafting is a helpful supplementary method for primary rhinoplasty. Furthermore, in this method, resolution of postoperative bruising occurs rapidly in the immediate postoperative period.

Fillers

According to American Society of Plastic surgeons’ reports, filler procedures increased from 650,000 in 2000 to 2.3 million procedures in 2014. The role of fillers in nasal reshaping continues to be explored and filler injection is not considered standard of care for the long-term management of nasal defects. Therefore, there are great controversies surrounding this subject.

In a 20-year retrospective study in 1986, Webster and associates introduced a procedure, microdroplet silicone injection into the nasal bridge, for the correction of postsurgical nasal defects. Although favorable results were recorded in the study, many physicians have remained skeptical about silicone injections owing to atrocious complications reported from the 1960s and 1970s.

In 1981, bovine collagen injections became popular among cosmetic surgeons, starting with Zyderm collagen (Allergan, Inc, Irvine, CA). From that time on, various new products entered the market. One of the most popularized products is hyaluronic acid (HA), so-called hyaluronan, which is a high-molecular-weight linear polysaccharide containing alternating d -glucuronic acid and N -acetylglucosamine.

During an analysis of bovine vitreous in 1934, Meyer and Palmer described HA as a natural sugar found in the skin and tissues. They also explained that this naturally occurring substance performs not only physical (such as lubrication) functions, but also and chemical functions, which act as essential vital substrates for numerous biological processes, such as fertility, embryogenesis, morphogenesis, cellular migration, inflammation, and wound healing. HA in its natural state is a perfect filler material, but has an extremely short half-life. To retard natural turnover and enhance its lifespan, manufacturers have attempted to modify the chemistry of HA by crosslinking chains using different dispersants such as 1,4-butanediol diglyceryl ether. Minimal modification of the material enabled manufacturers to produce HA products that can be well-tolerated by the immune system, as well as are durable and nonreactive.

The initial attempts at manufacturing HA were based on the use of animal-sourced raw materials and plagued by protein contamination issues. Accordingly, Lancefield groups A and C Streptococcus equi subspecies zooepidemicus , which naturally produce a pure hyaluronate mucoid capsule, were used for the development of commercial sources of hyaluronates. Hence, bacterial broths were a suitable source for the production of large quantities of relatively pure hyaluronates because they needed only purification of quite simple bacterial protein contaminants instead of the complex proteins that contaminated mammalian or avian sources. Serious attempts were made to extend HA lifespan in tissues by development of products with more crosslinks between chains, but it decreased tissue tolerance owing to increased immune-mediated adverse events. Therefore, a balance is required whereby natural HA chemical structure was increased enough from its natural state, to minimize its susceptibility to breakdown. Even though HA is recognized as the dominant filler product for volumizing tissues, there are many dermal filler materials. Silicone oils, poly(methyl methacrylate) microspheres, polyacrylamide, and other materials, alone or in combination with resorbable components, are examples of permanent dermal fillers.

There are different physical features associated with injectables. Viscosity and elasticity are 2 important attributes in a filler. Viscosity is a measure of the gel’s ability to resist sheering forces. , In other words, it is resistance ability of a material to a pressure applied to it, which denotes that it is less probable to spread. Products with low viscosity are more readily spread, whereas products with high viscosity have tendency to stay put, which allows for more precise sculpting. Elasticity refers to the material’s ability to resist malformation when force is applied. Fillers with high elasticity offer more lift and support, and require smaller amounts to achieve correction. Fillers having both features, viscosity and elasticity, are more appropriate for nonsurgical rhinoplasty. The 2 features have also investigated in 6 cross-linked HA products, including Restylane, Restylane Sub-Q (Q-Med, Uppsala, Sweden), Perlane, Juvederm Ultra, Juvederm Ultra Plus, and Juvederm Voluma (Allergan, Pringy, France) and also calcium hydroxylapatite (CaHA) and CaHA lidocaine mixture, according to the guidelines provided by the US Food and Drug Administration. Based on the data from this investigation, the products were divided into 3 groups of high, medium, and low viscosity and elasticity. The first (high) group included undiluted Radiesse. Radiesse mixed with 0.3% lidocaine and 3 HA products such as Restylane, Perlane, and Restylane Sub-Q (unavailable in the United States) were in the second (medium) group. Juvederm Ultra, Juvederm Ultra Plus, and Juvederm Voluma (unavailable in the United States) were other HA products included in the third (low) group. The viscosity and elasticity of each product can be modified by its dilution with lidocaine or saline, which is a very popularized strategy. Overdilution may, however, result in the need for more injection of product at the target site. Contour alteration with a very small amount of filler is advantageous. Therefore, care should be taken about diluting the natural product of the dermal filler because the injection of larger amounts of materials may cause a higher occurrence of vascular complications.

In a filler, hydrophilicity is an important factor that is needs to be considered. Although being shown to be desirable in filler rhinoplasty, the hydrophilic effect of HA products may clinically be disadvantageous. For instance, the expansion arises from the leakage of water into the tissues may enhance the potential for compression of dermal and subdermal vessels, which is likely results in vascular compromise. Among the HA products, Restylane and Perlane have less hydrophilicity than Juvederm Ultra and Ultra Plus.

For nonsurgical rhinoplasty, CaHA can serve as a filler of choice. Its longevity (averaging roughly 9–12 months) and moldability are very similar to those of a perfect filler, particularly for this application. However, the replacement of HA products with hyaluronidase makes them appealing to aesthetic physicians who had less experience in nonsurgical rhinoplasty.

Successful injection of CaHA (Radiesse, Merz, San Mateo, CA) for the correction of the internal nasal valve collapse has previously been reported. Radiesse is a suspension of CaHA microspheres (30%; 25–45 μm) in glycerin, carboxymethyl cellulose, and water mixture. Owing to similarity with the mineral portion of human bone and teeth, CaHA is fully biocompatible. Radiesse was first approved as a radiologic marker and for use in vocal fold augmentation, and later in 2006, it was approved by FDA for cosmetic applications ( Tables 2 and 3 ).

Apr 19, 2021 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Rhinoplasty with Fillers and Fat Grafting
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