SECTION OUTLINE
- 1. Classification of Fillers
- 2. Science and Properties of Hyaluronic Acid Fillers
- 3. Guide for Selection and Use of Fillers
- 4. Facial Anatomy for Dermal Fillers
- 5. Facial Assessment
- 6. Patient Selection and Esthetic Consult
- 7. Pre-requisites for Filler Treatment
- 8. Anesthesia
- 9. Filler Injection Techniques
- 10. Fillers for Upper Face—Forehead and Temporal Region
- 11. Fillers for Upper Face—Temples
- 12. Fillers for Upper Face—Eyebrow
- 13. Fillers for Upper Face—Upper Eyelid
- 14. Fillers for Midface—Tear Trough and Infraorbital Areas
- 15. Fillers for Midface—Cheeks
- 16. Fillers for Midface—Tear-Trough and Nose
- 17. Fillers for Midface—Nasolabial Folds
- 18. Fillers for Lower Face—Marionette Lines
- 19. Fillers for Lower Face—Chin
- 20. Fillers for Lower Face—Jawline
- 21. Fillers for Lower Face—Lip Augmentation
- 22. Fillers for Nonfacial Areas and Scars
- 23. Complications of Fillers and their Treatment
- 24. Combination Therapies with Fillers
INTRODUCTION
Esthetic enhancement has been a desire since ancient times of people from various cultures. There are several methods available to improve the facial appearance such as topical and systemic agents, surgical intervention, energy-based devices (like radiofrequency, high intensity focused ultrasound, intense pulse light) and injectables like botulinum toxin and fillers. Fillers by far are the simplest and effective method to get instant results, both for the patient and the treating physician.1 Paraffin was the first injectable substance that was used as dermal filler but its complication of embolization and granuloma formation abandoned its use as dermal filler. However, fillers have been the most popular method since the 1980s when bovine collagen was injected to treat facial lines and creases and to restore volume deficits. It was the first Food and Drug Administration (FDA) approved facial filler and it has been used for almost 30 years.2 It was originally used to treat viral pox scars, acne scars, lipoatrophy, and soft tissue augmentation. Since the augmentation effect lasts only for 6 months and due to its side effects, physicians were on the lookout for more sustainable and effective fillers. An ideal filler has not yet been discovered; however, hyaluronic acid (HA)-based fillers have helped revolutionize the filler market with a number of ideal products available to patients.
CLASSIFICATION OF DERMAL FILLERS
- Based on the origin: Natural/synthetic.
- Based on the source: Autograft/allograft/heterograft.
- Based on effect: Temporary/semi-permanent/permanent.
- Content: Collagen/fat/hyaluronic acid/silicone/peptides.
Based on the Origin
Natural
This group of fillers was the bovine derived collagen products, namely Zyderm® and Zyplast® collagen. The collagen material was derived from a closed herd of cattle and purified for human use. Zyderm® I was first approved by the FDA in 1981 and recommended for injection into the superficial papillary dermis, and was approved for the treatment of superficial lines and wrinkles, as well as shallow acne scars. Zyderm® II, FDA approved in 1983 to treat postacne and traumatic scars on the face, although it worked well for lines and wrinkles. Zyplast® was best injected into the mid-deep dermis and its recommended use was for deep lines and folds.44
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Since Zyderm®/Zyplast® had hypersensitivity concerns, human-derived collagen products were developed, namely CosmoDerm® and CosmoPlast®. These fillers are made from cultured human fibroblasts and were FDA approved in 2003 for facial Esthetic procedures. They do not require intradermal testing, which was a major drawback with bovine collagen.4 These products had longevity of approximately 3 months.
Synthetic
Poly-L-lactic acid (PLLA): Injectable PLLA is biocompatible, biodegradable, biostimulatory, synthetic filler that must be injected into the reticular dermis or subcutaneous fat. PLLA, marketed as Sculptra®, was FDA approved in 2009 as soft tissue augmentation filler.5,6 It stimulates neocollagenesis through fibroblast activation.7 Histological studies show increase in type 1 collagen over 8–30 months after the injection.8,9 It is degraded by nonenzymatic hydrolysis into carbon dioxide and water over 9–24 months. However, due to neocollagenesis the augmentation effect lasts for about 24 months.10 Side effects of Sculptra include immediate effects of swelling, bruising, inflammation, and pruritus which lasts for a few days.11 Long-term effects include foreign 5body granuloma formation and extremely rare effect of anaphylactic reaction has been noted.
Calcium hydroxylapatite: Calcium hydroxylapatite (CaHA) is a biocompatible, biodegradable, resorbable, and biostimulatory filler that contains microspheres which can stimulate the endogenous production of collagen.12 Histopathologically, they appear bluish and round or oval in shape and packed together, 25–40 µm and surrounded by fibrin fibers and mild cellular infiltrate. These microspheres are degraded by enzymatic process and disappear clinically by 9–12 months.13 It has been used in cases of lipoatrophy of HIV, hand rejuvenation, and lip augmentation. There are reports of nodule formation after lip injections. Migration to a distant location from the injection site, a foreign body granulomatous reaction, seen as blue-gray microspheres in the extracellular matrix or within multinucleated giant cells has also been reported.14
Polymethyl methacrylate: Polymethyl methacrylate (PMMA) is rigid, transparent and colorless, thermoplastic permanent skin filler with low cost, easy accessibility, and potential to achieve lasting results. It has been used as an injectable filler to treat hollows and reduce rhytids. ArteFill® became the first and only permanent injectable wrinkle filler to receive FDA approval in 2006. ArteFill® is a third-generation polymeric microsphere-based filler, following its predecessor Artecoll®. It has been approved for the treatment of nasolabial folds. ArteFill® consists of PMMA microspheres (20% by volume), 30–50 μm in diameter, suspended in 3.5% bovine collagen solution (80% by volume), and 0.3% lidocaine. The collagen carrier is absorbed within 1 month after injection and completely replaced by the patient's own connective tissue within 3 months.15
First-generation polymerized PMMA microspheres (Arteplast) are purified with diameter greater than 20 μm, which may produce foreign body granulomas, larger microsphere (second generation Artecoll) of 30–50 µm resist phagocytosis; however, it was demonstrated that giant cell reaction still occurs with larger particles.16,17 Complications of PMMA injection were classified as nodular masses, inflammation, allergies, and skin hypopigmentation.18
Polyacrylamide hydrogel: Aquamid is a biocompatible and nonabsorbable hydrogel consisting of 97.5% water and 2.5% cross-linked polyacrylamide gel (PAAG). The gel is manufactured through polymerization of the acrylamide monomers and N,N’-methylenbisacrylamide.19 PAAG is available in more than 40 countries worldwide (Europe, Asia, the Middle East, and Latin America) and awaiting FDA approval. After injection, the implant is encapsulated and surrounded by fibroblasts and microphages, theoretically preventing migration. It is used for treating various rhytides (deep rhytides and folds), facial contouring, and correction of HIV lipoatrophy. It usually lasts for about 1 year after injection.20 There have been reported cases of inflammation, nodule and granuloma formation, and delayed hypersensitivity reactions of Aquamid injections.21
Polyvinylpyrrolidone-silicone suspension: It is a permanent filler comprised of particles of polymerized silicone elastomer, 100–600 μm in size, dispersed in a carrier of polyvinylpyrrolidone. It has been used for lip augmentation and the correction of facial rhytids. It is injected into the subcutaneous plane and this avoids any phagocytosis due 6to its large particle size. Cases of foreign body granuloma formation, swelling, and induration have been reported.22,23
Polyalkylimide gel: Polyalkylimide gel is a permanent hydrophilic translucent gel filler composed of a hydrophilic biopolymer with 96% sterile water and 45% polyalkylimide polymer (Alcamid®), and different from polyacrylamide. It has been used for lipoatrophy of HIV, skeletal deformities such as pectus excavatum. Complications noted with this filler include swelling, bruising, and nodule formation. 24-26
Based on the Source
Autograft
Fat, dermal graft: Fat grafts are taken from the lower abdomen and inner thigh especially in younger patients. When processed with proper centrifugation they can reliably produce purified fat, concentrated growth factors, and adipose-derived stem cells.27
Allograft
Allograft includes fascia (cadaver).
Heterograft
Heterografts include fibroquel which is bovine derived.3
Based on Effect
Temporary fillers are fillers which last for >12 months, such as HA fillers. Semi-permanent fillers last for 1–2 years and permanent fillers more than 2 years (Table 2).3
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Based on Content
Hyaluronic acid based fillers are one of the most popular and widely used materials in esthetic procedures. HA was first discovered by two American scientists, Carl Meyer and John Palmer. This polymer also known as Hyaluronan, is the most abundant glycosaminoglycans found in the human dermis. It is a ubiquitous component of all membrane connected tissue. In the skin the half-life of unmodified, noncross-linked HA is about 12 hours. Therefore to increase longevity when injected into the skin HA is cross-linked. Currently there are a large number of dermal fillers available to the physician based on various cross-linked HA technologies. Some 7of these technologies include VYCROSS (Allergan Inc.), NASHA (Galderma Pharma), CPM (Merz Pharmaceuticals) and OXIFREE technology (Kylane laboratories).6 The main differentiators for HA fillers are: Source of HA; concentration of HA in each syringe being utilized; the particulate size of the HA; whether the HA is cross-linked; the type of cross-linking agent used in the HA; whether the HA is monophasic or biphasic; and whether there is an anesthetic in the HA syringe.4
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- Lemperle G, Nacul AM, Fortes FB. Can injection of PMMA-microspheres cause hypercalcemia? Clin Cases Miner Bone Metab. 2015;12(1):82–3.
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- Ersek RA, Beisang AA 3rd. Bioplastique: a new texture copolymer microparticle promises permanence in soft-tissue augmentation. Plast Reconstr Surg. 1991;87(4):693–702.
- Margolis DM. Treatment for lipoatrophy: facing the real costs. AIDS. 2007;21:1819–20.
- Karim RB, de Lint CA, van Galen SR, et al. Long-term effect of polyalkylimide gel injections on severity of facial lipoatrophy and quality of life of HIV-positive patients. Aesthetic Plast Surg. 2008;32(6):873–8.
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