The Basic Science of Dermal Fillers: Past and Present Part I: Background and Mechanisms of Action

Within the last decade, dermal fillers have exponentially risen in popularity, with over 1.7 million procedures performed in 2009 alone.¹ This trend has undoubtedly been compelled by an aging population seeking minimally invasive rejuvenation. Despite the millions of cosmetic procedures performed and the variety of dermal fillers available today, there is a lack of cosmetic procedural training during dermatology residency. Only 15.2% of recent graduates report performing more than 10 dermal filler procedures during their entire residency.² Dermatologists perform 48% of all cosmetic procedures in the United States,³ and most get training in soft tissue augmentation after residency directly from industry-sponsored workshops, continuing medical education, or observerships. Despite a plethora of publicity and literature regarding the clinical and safety outcomes of dermal fillers, there is a relative paucity of literature geared towards the general dermatologist regarding the basic science of fillers in the setting of cosmetic use. Therefore, we believe that it is necessary to discuss the different types of dermal fillers (Table 1), to discuss the mechanism whereby they produce their filler effect, and (in Part II) to review their possible complications.

The use of silicone as a dermal filler is not Food and Drug Administration (FDA)-approved and is most often used in an off-label capacity in microdroplet form (Silikon 1000^® or Adato Sil OI 5000^®, bauschsurgical.com). It is important to recall silicone's role as a contouring agent and the lessons learned from its pitfalls. Silicone was first used for body contouring in the 1940s in Germany, Switzerland, and Japan, gaining popularity in the United States in the 1950s.⁴ At that time, liquid silicone, also known as Dow Corning 360^®, was contaminated with heavy metals and often combined with inflammation-inducing chemicals to promote fibroblast formation.⁵ It was injected in large quantities of up to 2 L at a time. Unfortunately, this practice frequently resulted in permanent deformation, chronic inflammation, migration, ulceration, granulomas, infection, and sometimes even death.⁴ A purified and sterilized form of liquid silicone was manufactured by Dow Corning, and its safety as a soft tissue filler was investigated from 1965 to 1981. Failure to prove its safety and controversy regarding autoimmune reactions to silicone breast implants prevented silicone from ever gaining FDA approval for use as a soft tissue filler. However, silicone is still used for cosmetic purposes in microdroplet technique by a limited number of practitioners in the United States.⁶ The most commonly used product is Silikon 1000 (Alconretina.com), a purified polydimethylsiloxane "silicone oil" that is FDA-approved for use in vitreoretinal surgery for post-operative retinal tamponade and in cases of CMV retinitis.⁷

Mechanism of Action
Medical-grade silicone causes immediate volume displacement and provides its filler effect by inducing granuloma formation and local fibrosis. The silicone particles have an irregular surface and are unable to be phagocytized by macrophages. This eventually leads to formation of foreign body granulomas.⁸ After injection, silicone fluid disperses as microdroplets into surrounding tissue. At 1 month, a monolayer of fibroblasts and collagen encapsulates each microdroplet. From 3 to 6 months, macrophages and giant cells surround the microdroplets in addition to further collagen deposition.⁹ At 9 months, granulomatous nodules surrounded by strands of fibrous tissue are present around the implant.⁸

Collagen
The calfskin-derived collagens Zyderm^® and Zyplast^® (Allergan, Irvine, CA) were introduced in 1981 and were the only