Читать книгу Dermal Fillers for Dental Professionals - Arun K Garg - Страница 10
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A cardinal rule in dentistry also applies to esthetic facial rejuvenation with fillers: Product selection is key to achieving successful results. Yet, there are dozens of filler products for practitioners to choose from, including some autologous agents. A survey of the dermal filler landscape, including a brief history of its evolution, will give the novice esthetic practitioner a bird’s-eye perspective of how the field developed, along with a ground-level understanding of how to quickly navigate the market and make informed choices.
Dermal Filler Classifications
Dermal fillers can be classified in terms of longevity, biodegradability, and mechanism of action.
Longevity
Facial dermal fillers are usually described as short-acting, long-acting, or “permanent,” but there is wide latitude in how these terms are defined. Generally speaking, a short-acting filler can be expected to last up to 1 year, a long-acting filler up to 2 years, and a filler labeled as permanent (an obvious misnomer) for 5 years or more.1,2 In most discussions, duration of effect of a given product is a relative concept that makes reference to other products as the standard of comparison.
Biodegradability
Biodegradability, which has a major impact on a product’s longevity, is another classification that strays into gray territory.3,4 A product or agent can be labeled as (1) a biodegradable filler, (2) a filler with biodegradable particles, or (3) a nondegradable filler. Biodegradable fillers are fully reabsorbed by the body and are consequently short-lived. Fillers with biodegradable particles act by stimulating a response in the body to produce its own collagen before resorbing, which results in a longer-lasting effect. Nondegradable fillers are dual-acting: They induce a foreign-body reaction that stimulates the deposition of new collagen, but the nondegradable particles ultimately become permanently integrated into the connective tissue of the skin.
Mechanism of action
As the discussion of biocompatibility suggests, fillers can also be classified according to their mechanism of action.5,6 In this category, a distinction is made between a volumizer, which is a filler that achieves its effect by taking up space (giving added importance to the amount of product injected), and a stimulator, one that in some way induces the body to produce new collagen. Again, some products fit neatly into one of these two categories, while others fall somewhere in between.
As with dental treatments, a one-size-fits-all approach to facial augmentation will not yield optimal results. As dermal filling options continue to expand and evolve, the clinician must understand the unique properties and characteristics of each product and apply that knowledge to developing an individual treatment plan for each patient. Box 3-1 lists the qualities of an ideal filler product in terms of its safety, effectiveness, and convenience.7–9 The remainder of this chapter explains how each agent available is classified and measures up to the qualities of an ideal filler. For convenience, the discussion proceeds from short-acting to long-acting to permanent fillers, which—not coincidently—corresponds to the order in which they evolved.
BOX 3-1 Properties of the ideal dermal filler
Safety
Nonimmunogenic
Noncarcinogenic
Nonteratogenic
Noninfectious
Efficacy
Long-term benefit
Natural feeling
Nonmigratory
Reproducible results
Practicality
Cost-effective
Easy to use
FDA-cleared
Removable or reversible
Long shelf life
As in dentistry, many products are used off-label by experienced dermatologists; the present discussion is restricted to those that have been cleared by the U.S. Food and Drug Administration (FDA) for specific facial cosmetic indications (Fig 3-1 and Table 3-1).10
FIG 3-1 Dermal filler products have been FDA cleared for specific treatments but are often used off-label in other areas of the face. (Adapted from the American Society of Plastic Surgeons.10)
TABLE 3-1 Dermal fillers approved by the FDA for use in the United States
| Trade name (manufacturer) | Year approved | Approved uses |
| Hyaluronic acid | ||
| Restylane Lyft (Galderma) | 2018 | Deep dermis to superficial subcutis injection for correction of moderate to severe facial folds and wrinkles; subcutaneous to supraperiosteal injection for cheek augmentation and midface deficiencies; subcutaneous injection for correction of volume deficit in the dorsal hand. |
| Restylane Refyne (Galderma) | 2016 | Mid-to-deep dermis injection for correction of moderate to severe facial wrinkles and folds. |
| Restylane Defyne (Galderma) | 2016 | Mid-to-deep dermis injection for correction of moderate to severe deep facial wrinkles and folds. |
| Restylane Silk (Galderma) | 2014 | For lip augmentation and dermal implantation and for correction of perioral rhytids. |
| Restylane (Galderma) | 2003 | Mid-to-deep dermis injection for correction of moderate to severe facial wrinkles and folds. |
| Revanesse Versa (Prollenium) | 2018 | Mid-to-deep dermis injection for correction of moderate to severe facial wrinkles and folds. |
| Revanesse Versa Plus (Prollenium) | 2018 | Mid-to-deep dermis injection for correction of moderate to severe facial wrinkles and folds (+ lidocaine). |
| Teosyal RHA 2 (Teoxane) | 2017 | Mid-to-deep dermis injection for correction of moderate to severe dynamic facial wrinkles and folds. |
| Teosyal RHA 3 (Teoxane) | 2017 | Mid-to-deep dermis injection for correction of moderate to severe dynamic facial wrinkles and folds. |
| Teosyal RHA 4 (Teoxane) | 2017 | Deep dermis to superficial subcutaneous tissue injection for correction of moderate to severe dynamic facial wrinkles and folds. |
| Juvéderm Vollure XC (Allergan) | 2017 | Mid-to-deep dermis injection for correction of moderate to severe facial wrinkles and folds. |
| Juvéderm Volbella XC (Allergan) | 2016 | Injection into the lips for lip augmentation and for correction of perioral rhytids. |
| Juvéderm Voluma XC (Allergan) | 2013 | Deep subcutaneous and/or supraperiosteal injection for cheek augmentation for correction of age-related volume deficit in the midface. |
| Juvéderm Ultra (Allergan) | 2006 | Mid-to-deep dermis injection for correction of moderate to severe facial wrinkles and folds, and lip augmentation. |
| Juvéderm Ultra Plus (Allergan) | 2008 | Mid-to-deep dermis injection for correction of moderate to severe facial wrinkles and folds. |
| Belotero Balance (Merz North America) | 2011 | Injection into facial tissue to smooth wrinkles and folds, especially around the nose and mouth. |
| Poly-l-lactic acid (PLLA) | ||
| Sculptra Aesthetic (Galderma) | 2009 | Injection into facial tissue for correction of shallow to deep nasolabial fold contour deficiencies and other facial wrinkles. |
| Calcium hydroxyapatite (CaHA) | ||
| Radiesse (Merz North America) | 2006 | Subdermal injection for correction of moderate to severe facial wrinkles and folds. |
| Radiesse Plus (Merz North America) | 2006 | Subdermal injection for correction of moderate to severe facial wrinkles and folds (+ lidocaine). |
| Polymethylmethacrylate (PMMA) microspheres | ||
| Bellafill (Suneva Medical) | 2006/2014 | Injection into facial tissue for correction of moderate to severe facial wrinkles and folds. In 2014, it was also cleared for moderate to severe pitted atrophic facial acne scars. |
Short-Acting Fillers
The two materials in this category are collagen and hyaluronic acid, both of which are natural components of human tissue.
Collagen
Introduced in the 1970s, injectable fillers made of bovine collagen were the first products to be FDA cleared to smooth the appearance of lines and wrinkles associated with facial aging. Because of public anxiety about the safety of animal-derived products, they became obsolete when human-derived collagen fillers reached the market a few years later. The addition of lidocaine boosted the popularity of collagen fillers, and they would remain the gold standard for the next 20 years.
Human-derived collagen fillers are nonantigenic, safe, and fast-acting, and they require no downtime. The collagen resorbs quickly, however, limiting the duration of their effect to only 3 months. By the late 1990s, this rapid resorption rate sealed their fate, and collagen fillers went the way of other popular 1980s trends like big hair and shoulder pads. Collagen dermal fillers are no longer being manufactured, although even today it is not uncommon for some patients to ask for them by name.
During the same period, neurotoxins were being used to relax and soften the wrinkles caused by the contraction of facial muscles—with excellent results. This breakthrough led to recognition of the different etiologies of the lines formed by movements of expression and the grooves in the skin resulting from a loss of volume associated with aging.11 The former can be temporarily paralyzed with botulinum toxin injections (which is a subject for another time), whereas age-related wrinkles can be smoothed only by restoring the lost volume. This recognition spurred development of new fillers made from a variety of materials.
Hyaluronic acid
Hyaluronic acid (HA) is the most popular class of filler in the United States, for several reasons10,11 (Fig 3-2). HA fillers are easy to handle and provide natural-looking results with little downtime. They also boast an important safety advantage over other types of fillers in that they can be immediately and safely reversed with hyaluronidase, making them especially favored by inexperienced clinicians.
FIG 3-2 Percentage of filler procedures performed in the United States in 2018 by agent used. The total number of procedures was 2,676,970. (Source: American Society of Plastic Surgeons.10) CaHA, calcium hydroxyapatite; PRP, platelet-rich plasma; PLLA, poly-l-lactic acid; PMMA, polymethylmethacrylate.
HA was the first filler agent to achieve the definitive rejuvenation effects on static lines and grooves that botulinum toxins have on dynamic lines. Produced naturally by the body and found in high concentrations in the skin, HA binds collagen and water together to provide hydration and augmentation. Like collagen fillers, HA is naturally biocompatible, but it resorbs at a significantly slower rate. Because of its excellent moisture-retention capacity, HA is a key ingredient in many high-end skin care products on the market today.
The first commercially available HA fillers—of which there are many (Figs 3-3 to 3-7)—were FDA cleared in 2003, and in 2018 they accounted for 77% of all dermal filler sales in the United States.10 Juvéderm (Allergan), which is available in several different formulations, is the undisputed market leader, followed by Restylane (Galderma) and Belotero Balance (Merz North America). HA filler products differ in terms of their rheologic and physicochemical properties (eg, degree of HA concentration, particle size, consistency, viscosity, hardness, degree of water solubility, cross-linking technology), which play an important role in HA filler selection, location and plane of injection, and clinical outcomes. In general, more concentrated products with a greater degree of cross-linking (a manufacturing process used to slow resorption rate) provide increased longevity, but they have on occasion been associated with a higher risk for inflammation and nodule formation (Table 3-2).12–14 In addition, a higher G’ (elasticity) means a stiffer gel and a deeper injection plane, and conversely a lower G’ indicates a softer gel and a more superficial plane of injection.3 Skin quality, degree of skin laxity, and anatomical location are some of the clinical factors that must be considered when selecting a product. Understanding the rheologic properties of the various HA products can make esthetic enhancement safer and more predictable.
FIG 3-3 Restylane was the first HA filler to be cleared by the FDA in 2003. In the time since, this manufacturer has launched several other formulations, and today Restylane is the second-best-selling filler in the United States. Restylane Refyne treats mild to moderate lines and wrinkles, while Restylane Defyne is for moderate to severe smile lines. Both fillers last up to 12 months. Restylane Silk was the first HA dermal filler to be approved for lip injection via cannula. It is a smoother, lighter injection that produces fuller and more accentuated lips. Restylane Lyft is a heavier, more concentrated mixture for the back of the hands and face that adds lift and volume to the cheeks.
FIG 3-4 Revanesse Versa (and Versa+) is engineered to minimize swelling and to maintain balance with the water content of the surrounding skin tissue. It is intended for the treatment of lines and folds in the lower face and for adding volume to the lips. Because it will neither increase nor decrease the water in the skin, Versa can help clinicians avoid over- or undertreatment in the area of injection.
FIG 3-5 The Teosyal RHA line of HA products includes the first resilient HA fillers dedicated to facial dynamics. RHA 2, 3, and 4 have malleability properties to avoid resistance to facial movement. RHA 2 is designed for filling dynamic moderate wrinkles such as nasolabial folds, malar deficiencies, and glabella wrinkles. RHA 3 is designed for filling deep wrinkles in areas such as the nasolabial folds and vertical lip lines. RHA 4 is designed to increase volume in extended areas such as the cheeks, upper cheeks, and contours of the face.
FIG 3-6 Juvéderm offers a number of different formulations in its line of HA products, and the company outsells all other brands of dermal fillers in the United States. Vollure is best for treating wrinkles and fine lines in the lower third of the face (nasolabial folds and marionette lines), whereas Voluma is designed to correct age-related volume deficits in the midface (malar region and tear troughs) and chin areas. Volbella restores volume, contour, and symmetry to the lips and smooths perioral rhytids. Ultra XC and Ultra Plus XC both target moderate to severe facial wrinkles and folds in the midface, though Ultra Plus XC has a larger particle size and thus a longer duration of action (9 months vs 12 months). The Juvéderm family of products all contain lidocaine to reduce patient discomfort.
FIG 3-7 Belotero Balance is formulated with a lower viscosity than many of the other HAs, making it suitable for perioral rhytids, tear troughs, and atrophic scars. It is FDA approved for the correction of moderate to severe facial wrinkles and folds.
TABLE 3-2 Concentration of hyaluronic acid in commercial HA dermal filler products12,13
Long-Acting Fillers
This category includes commercial products made of poly-l-lactic acid (Fig 3-8) and calcium hydroxyapatite (Fig 3-9) as well as cells harvested from the patient’s own fat and blood tissues.
FIG 3-8 Sculptra Aesthetic is the only dermal filler made of poly-l-lactic acid (PLLA), a synthetic polymer, that has been cleared by the FDA and is sold in the United States. It is intended for soft tissue augmentation and correction of shallow to deep skin depressions and contour deficiencies. Unlike most of the other dermal fillers, the effects of Sculptra are not apparent until about 4 weeks after the initial injection.
FIG 3-9 Radiesse and Radiesse (+) are the first and only FDA-cleared calcium hydroxyapatite dermal fillers sold in the United States. Radiesse is indicated for midface and lower face wrinkles and folds and lasts for about 1 year.
Calcium hydroxyapatite
Commonly employed in dentistry as a bone grafting substitute, calcium hydroxyapatite (CaHA) was FDA cleared as a dermal filler agent in 2006. Unlike its predecessors, CaHA fillers provide immediate volume replacement while also stimulating a response in the body to produce its own collagen, resulting in a longer-lasting effect. CaHA is nonallergenic and inherently biocompatible, and it has a well-established safety profile. When used as a dermal filler, CaHA usually lasts for a minimum of 1 year before it is fully resorbed by the body.
Currently, only one CaHA dermal filler product is FDA cleared for use in the United States. Radiesse (Merz North America) consists of 30% synthetic CaHA microspheres suspended in a 70% aqueous carboxymethylcellulose gel carrier. The soluble carrier distributes the CaHA microspheres and gradually dissipates, while the microspheres induce neocollagenesis via fibroblast activation. Radiesse has a high G’ and is highly viscous compared to other dermal fillers, a property that allows it to remain in place when it is injected and not migrate.6 In 2009, a protocol for mixing Radiesse with lidocaine was approved by the FDA. This formulation significantly increases patient comfort during the injection process.
Poly-l-lactic acid
Poly-l-lactic acid (PLLA) is a synthetic polymer that is probably familiar to most readers as a key component of Vicryl sutures (Ethicon). Indeed, polylactides have a long history of safe use in a number of biomedical pins, plates, and screws, in addition to sutures. First FDA cleared as a dermal filler in 2009, PLLA is unique among commercially available fillers in a number of ways.15 First, PLLA is not a volumizer in the technical sense because it does not achieve its effect by taking up space. Its singular mechanism of action is the stimulation of neocollagenesis, which means that it restores but does not replace lost volume. Consequently, its full effects are gradual, requiring 3 to 4 injections at least 4 to 6 weeks apart. However, many patients continue to see improvement 2 years after the initial injection.
Second, the injection protocol is less convenient and more technique-sensitive than that of other fillers. The freeze-dried PLLA powder must be reconstituted in sterile water at least 24 hours before the scheduled injection in order to form a suspension. To ensure a uniform concentration, PLLA should be injected at room temperature to avoid the risk of an uneven response. Also, because the effects of the filler are delayed, it is essential not to overcorrect, which puts patients at increased risk of developing minute palpable nodules at the injection site that can last as long as 1 year.16 Over time, the PLLA microparticles are metabolized by the body and expelled as carbon dioxide.
Sculptra Aesthetic (Galderma) is the only PLLA dermal filler available in the United States. It is primarily indicated for broad dermal correction rather than smoothing individual rhytids and is contraindicated in and around the lips. With regard to the procedures described in this text, Sculptra is ideal for augmentation of the malar areas and the chin.
Autologous fat
Encouraged by publicity of the broad versatility of stem cells, more patients are choosing fat harvested from their own body as a dermal filler over commercial options. Autologous fat transfer (AFT), also known as lipofilling, is a low-risk procedure that offers a number of advantages that many patients find attractive. First, fat grafts not only have an immediate volumizing effect on grooves and wrinkles, but stem cells that exist in the fat tissue are a rich source of growth factors that stimulate new collagen production. Second, most patients are delighted to be relieved of the extra fat around their abdomen or thighs. Third, because the filler consists of the patient’s own cells, the risk of an allergic reaction is nonexistent. So far, however, most studies report disappointing long-term outcomes, mostly because of unpredictable resorption of up to 70% of the volume of the fat graft.17,18 Furthermore, there is strong disagreement among clinicians as to the ideal method for harvesting and handling the fat grafts.18 Therefore, its long-term results are variable and unpredictable.
Allofill (Biologica Technologies) is an off-the-shelf fat allograft that is available for patients who wish to avoid the pain, cost, and recovery time associated with the harvesting of autologous fat through liposuction. It offers all the benefits of AFT minus the guarantee of nonimmunogenicity, as it is sourced from donated tissue.
Platelet-rich plasma
Another autologous dermal filler option, platelet-rich plasma (PRP) offers all the benefits of lipofilling but without the drawbacks associated with fat graft harvesting.19 Commonly used in dental (and other) surgical procedures to promote healing, PRP is inherently biocompatible and delivers an abundance of stem cells and other growth factors. Because it requires only a simple venipuncture procedure, it is significantly less painful, less invasive, and less expensive to harvest than autologous fat (Figs 3-10 and 3-11). Adding PRP to facial lipofilling can reduce recovery time and improve the overall esthetic outcome.
FIG 3-10 Application of PRP through a needleless syringe following microneedling therapy.
FIG 3-11 PRP requires a venipuncture to draw the patient’s blood but eliminates the cost of using a commercial product.
Permanent Fillers
The “holy grail” among dermal filler manufacturers is a product that boasts the safety profile of HAs but without resorption, and promises a permanent (5+ years) improvement in facial appearance. Today, only one agent has been shown to approach that ideal.
Polymethylmethacrylate
To date, the only “permanent” filler material approved by the FDA is composed of polymethylmethacrylate (PMMA), a nonbiodegradable, biocompatible, synthetic polymer that is also used in various medical materials and devices, including dental prostheses. A PMMA dermal filler is made of tiny microspheres carried in a collagen gel. When injected, it initiates a foreign-body reaction that eventually leads to the production of new collagen. The collagen carrier provides immediate volume and lift in the short term, while the nonbiodegradable PMMA microspheres have a long-term “bulking” effect.20
Bellafill (Suneva Medical) was the first (and so far only) PMMA dermal filler to be FDA cleared (under a different trade name) for the correction of folds and wrinkles (Fig 3-12). It consists of 20- to 50-µm microspheres of PMMA suspended in a bovine collagen gel carrier, which acts as a glue, preventing the microspheres from clumping and allowing for new tissue ingrowth. Because the collagen is derived from an animal source, skin allergy testing is required 4 weeks prior to treatment. The collagen carrier is absorbed within 1 month of injection and replaced by the patient’s connective tissue within 3 months.21 The inherent downside to a “permanent” filler is that it is less forgiving when mistakes are made or complications arise.
FIG 3-12 Bellafill is a unique, dual-acting dermal filler indicated for deep folds in the midface and lower face and to treat moderate to severe pitted atrophic facial acne scars. Composed of sterile PMMA microspheres suspended in a purified bovine collagen gel carrier, it works by adding both immediate lift from the collagen and long-term (up to 5 years) volume correction from the production of new collagen supported by the microsphere matrix. Because it contains bovine collagen, a skin test is required before use.
Conclusion
Understanding the active components in dermal fillers and their properties allows clinicians to make informed decisions about the products that are currently available and new ones on the horizon. Obviously, clinical factors are equally important. When selecting a dermal filler product, key factors include treatment area, degree of volume loss, and longevity. Furthermore, the rheologic properties of each dermal filler material narrow its applicability. In general, a thinner, more supple filler is used for minor rhytids, lips, scars, and frown lines, while a structure-oriented filler is best for high-volume-loss rhytids, chins, and malar regions. All of these qualities are discussed in detail in later chapters, which cover the step-by-step injection procedures, beginning with the esthetic consultation.
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