Hyaluronic acid (HA) fillers have been gaining popularity over the last decade. In fact, in 2005, HA fillers accounted for over 92% of all dermal filler treatments in the United States. The ease of administration, their superior effectiveness, and impressive safety profile all contributed to their popularity. In this article, we will discuss about the rheology, pharmacology, and applications of hyaluronic acid-based fillers. We will also discuss about the regulations that govern the use of hyaluronic acid dermal fillers, as well as their physical characteristics. At the same time, we will consider other classes of dermal fillers that are commonly used. By providing a background to hyaluronic acid fillers, we hope to promote safe and judicious use of dermal fillers.
Pharmacology of hyaluronic acid fillers
Hyaluronic acid in the body
Found naturally in the extracellular matrix, hyaluronic acid is a glycosaminoglycan (GAG) polymer that contains repeat disaccharide units of N-acetylglucosamine and glucuronic acid. The polymers vary significantly in length. The behavior of hyaluronic acid in the tissues is greatly influenced by their molecular weight. For example, hyaluronic acid polymers that have a low weight may promote angiogenesis and inflammation, whereas hyaluronic acid of high molecular weight has the opposite action, decreasing angiogenesis and inflammation. Around 50% of the body’s total hyaluronic acid is found in the skin. On a cellular level, hyaluronic acid functions as a scaffold for the extracellular matrix, allowing cellular regeneration and movement. At the same time, they also provide turgor, hydration and rigidity. Hyaluronic acid plays a vital role in shielding the skin against free radical damage (especially against UVA & UVB). The tissue metabolism of hyaluronic acid occurs rapidly, with around 1/3 of the total body hyaluronic acid being turned over every day.
The manufacturing method can affect the properties of hyaluronic acid (including concentration, particle size, and the degree of cross linking). The level of hyaluronic acid is determined by the enzymes that decompose it (e.g. hyaluronidases HYAL 1, HYAL 2, and HYAL 3) and those that synthesize it (synthase HAS 1, HAS 2, and HAS 3). Clinically, hyaluronidase is used to enhance the penetration of local anesthetic, infusions, and intramuscular and subcutaneous injections. Plus, it helps to decrease swelling. In addition, the enzymes are used off label in cosmetic procedures to dissolve hyaluronic acid-based fillers. Hyaluronidase is categorized based on the origin and mechanism of action, e.g. microbial (Hyaluronate lyase), leech or hookworm (endo-Beta-D-glucuronidase) and mammalian (endo-Beta- N-acetylhexosaminidase).
In general, human and microbial hyaluronidase tends to be safer and have a reduced risk of immunogenicity.
Hyaluronic acid is a natural substance that can be found in the skin. To improve its performance, hyaluronic acid is often cross-linked using proteins (such as 1, 4-BDDE) during the manufacturing process. This increases the resistance of hyaluronic acid to decomposition, thereby increasing its duration of action. Most hyaluronic acid fillers are able to last for at least a few months in the skin. Hyaluronic acid dermal fillers vary greatly in terms of their rheological properties due to the different technologies used in the manufacturing process. The most appropriate dermal filler should be chosen based on the location of treatment. In addition to conventional hyaluronic acid fillers, there are many non-hyaluronic acid fillers that have a longer duration of actions. Plus, some of these fillers are able to promote collagen regeneration. To obtain optimal results, practitioners should use the most suitable dermal filler which has desired properties for a particular indication.