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<hr />Svetlana Tkachenko , Candidate of Medical Sciences, Associate Professor of the Department of Dermatology, Venereology and Medical Cosmetology, Kharkov National Medical University (Kharkov)<hr /> Hyaluronic acid (HA – hyaluronic acid) is a natural polysaccharide that is found in the extracellular matrix of many tissues of the human body. HA was first used commercially in 1942 when Endre Balazs applied for a patent for the use of HA in baked goods as an egg white substitute. Approximately 50% of the total amount of HA in the human body is found in the skin. In its pure form, NA has no immunogenic potential. Early work on pure HA revealed many properties that seemed ideal for use as a filler. However, the rapid resorption of NA in tissues has practically devalued this substance for aesthetic medicine. This initiated numerous studies on slowing the absorption of HA into tissues and soon led to the successful cross-linking of HA, which strongly retained its natural positive characteristics, but was also retained for a long time in tissues. This was the first effective dermal filler, Restylane, approved by the FDA in 2003, revolutionizing the aesthetic market. Beginning in 2003, other HA-based dermal fillers were approved by the FDA, giving physicians a therapeutic choice. All of these drugs do not require preliminary allergy testing, have minimal side effects, and provide a mild, natural result. While early products were produced by isolating HA from animal sources (cockscomb), hyaluronic fillers are now being developed from non-animal sources through bacterial fermentation. Modern formulations differ in many ways, including cross-linking agent, HA concentration, and other characteristics such as gel strength and molecular weight. All other parameters being equal, drugs with a higher percentage of cross-linked HA are much denser and exhibit greater stability. Despite differences in chemical and physical properties, commercially available HA fillers have similar indications for injection into the mid to deep dermis for the correction of moderate to severe facial wrinkles and folds (eg, nasolabial folds).<h2 style="text-align: center;"> Table Comparison of commercial preparations based on hyaluronic acid </h2><table align="center" border="1" cellpadding="0" cellspacing="1" width="100%"><tbody><tr><td style="border: 1px solid" valign="top"></td><td style="border: 1px solid" valign="top"> Restylane®</td><td style="border: 1px solid" valign="top"> Perlane®</td><td style="border: 1px solid" valign="top"> Juvéderm® Ultra/ Ultra Plus</td><td style="border: 1px solid" valign="top"> Prevelle® Silk</td><td style="border: 1px solid" valign="top"> Hydrelle™</td></tr><tr><td style="border: 1px solid" valign="top"> Distributor in the USA</td><td style="border: 1px solid" valign="top"> Medicis</td><td style="border: 1px solid" valign="top"> Medicis</td><td style="border: 1px solid" valign="top"> Allergan</td><td style="border: 1px solid" valign="top"> Mentor</td><td style="border: 1px solid" valign="top"> Coapt Systems</td></tr><tr><td style="border: 1px solid" valign="top"> Crosslinking agent</td><td style="border: 1px solid" valign="top"> 1,4-Butanediol diglycidiether (BDDE)</td><td style="border: 1px solid" valign="top"> 1,4-Butanediol diglycidiether (BDDE)</td><td style="border: 1px solid" valign="top"> 1,4-Butanediol diglycidiether (BDDE)</td><td style="border: 1px solid" valign="top"> divinyl sulfone (DVS)</td><td style="border: 1px solid" valign="top"> Biscarbo diimide (BCDI)</td></tr><tr><td style="border: 1px solid" valign="top"> Total NA concentration (percentage of cross-linked ON)</td><td style="border: 1px solid" valign="top"> 20 mg/mL (&lt;1%)</td><td style="border: 1px solid" valign="top"> 20 mg/mL (&lt;1%)</td><td style="border: 1px solid" valign="top"> 24 mg/mL (6%/8%)</td><td style="border: 1px solid" valign="top"> 5.5 mg/mL (12%)</td><td style="border: 1px solid" valign="top"> 28 mg/mL (N/A)</td></tr><tr><td style="border: 1px solid" valign="top"> Average particle size</td><td style="border: 1px solid" valign="top"> 300 µm</td><td style="border: 1px solid" valign="top"> 750-1000 µm</td><td style="border: 1px solid" valign="top"> Random size and shape</td><td style="border: 1px solid" valign="top"> 350 µm</td><td style="border: 1px solid" valign="top"> 200 µm</td></tr><tr><td style="border: 1px solid" valign="top"> G&#39; module</td><td style="border: 1px solid" valign="top"> 660</td><td style="border: 1px solid" valign="top"> 588</td><td style="border: 1px solid" valign="top"> 170/200</td><td style="border: 1px solid" valign="top"> 230-260</td><td style="border: 1px solid" valign="top"> 329</td></tr><tr><td style="border: 1px solid" valign="top"> Lidocaine</td><td style="border: 1px solid" valign="top"> Restylane®-L</td><td style="border: 1px solid" valign="top"> Perlane®-L</td><td style="border: 1px solid" valign="top"> Juvéderm® Ultra XC Juvéderm Ultra Plus XC</td><td style="border: 1px solid" valign="top"> There is</td><td style="border: 1px solid" valign="top"> No</td></tr></tbody></table><div style="clear:both;"></div> Correct selection of the drug is important to achieve optimal results with HA-based dermal fillers. A larger particle size or more viscous HA filler will give better results when injected deep into the dermis. Smaller particle sizes of fillers or lower viscosity of the product are more suitable for superficial wrinkles. Massage is recommended to ensure optimal distribution of the drug in the tissues. Superficial injections should be avoided to minimize the appearance of the Tyndall effect (visual bluishness of the skin caused by superficial placement of filler that scatters blue light), especially in fair-skinned patients. Various injection techniques can be used when working with HA fillers, but the use of the fan technique has led to an increase in the number of side effects [ Dover JS, Rubin MG, Bhatia AC. Review of the efficacy, durability, and safety data of two nonanimal stabilized hyaluronic acid fillers from a prospective, randomized, comparative multicenter study. Dermatol Surg. 2009;35:322-331. Abstract ]. Overcorrection should be avoided and it must be remembered that Restylane, Perlane and Juvederm Ultra/Ultra Plus continue to increase volume for 24 hours after injection. In general, adverse events associated with HA fillers are usually localized, mild to moderate, and temporary. The most common are bruising and erythema after injection, which usually disappear within 1 week [ Lowe NJ, Maxwell CA, Patnaik R. Adverse reactions to dermal fillers: review. Dermatol Surg. 2005;31:1616-1625. Abstract; Narins RS, Bowman PH. Injectable skin fillers. Clin Plast Surg. 2005;32:151-162. Abstract ]. Serious adverse events are rare, but granulomatous reactions to early HA fillers have been described in the literature [ Lupton JR, Alster TS. Cutaneous hypersensitivity reaction to injectable hyaluronic acid gel. Dermatol Surg. 2001;26:135-137 ]. The occurrence of local reactions and side effects are more related to the technique and speed of drug administration than to differences in the fillers themselves [ Glogau RG, Kane MA. Effect of injection techniques on the rate of local adverse events in patients implanted with nonanimal hyaluronic acid gel dermal fillers. Dermatol Surg. 2008;34:S105-S109. Abstract; 23. Dover JS, Rubin MG, Bhatia AC. Review of the efficacy, durability, and safety data of two nonanimal stabilized hyaluronic acid fillers from a prospective, randomized, comparative multicenter study. Dermatol Surg. 2009;35:322-331. Abstract ]. These data confirm the importance of meticulous injection technique to achieve optimal results. One of the advantages of HA-based dermal fillers is that adverse reactions or misplacement of the drug can be mitigated by the introduction of the enzyme hyaluronidase, a soluble protein that breaks down and hydrolyzes HA. There is evidence of successful treatment with this method of superficial placement of the implant (formation of the Tyndall effect) [ Brody HJ. Use of hyaluronidase in the treatment of granulomatous hyaluronic acid reactions or unwanted hyaluronic acid misplacement. Dermatol Surg. 2005;31:893-897. Abstract; Hirsch RJ, Brody HJ, Carruthers JD. Hyaluronidase in the office: a necessity for every dermasurgeon that injects hyaluronic acid. J Cosmet Laser Ther. 2007;9:182-185. Abstract ], persistent granulomatous changes [ Brody HJ. Use of hyaluronidase in the treatment of granulomatous hyaluronic acid reactions or unwanted hyaluronic acid misplacement. Dermatol Surg. 2005;31:893-897. Abstract ] and even injection necrosis [ Hirsch RJ, Brody HJ, Carruthers JD. Hyaluronidase in the office: a necessity for every dermasurgeon that injects hyaluronic acid. J Cosmet Laser Ther. 2007;9:182-185. Abstract ].

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