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FIGURE 23-9 Measurement of G A force is applied laterally on the top plate The more the gel resists the movement, the harder the gel, the higher the G and cheeks Low G products such as Hylaform and Juv derm Ultra are necessary in areas that require a softer agent, such as the body of the lip or the tear trough As new products reach the market, knowing the G will help practitioners match fillers with indications The concentration of HA in a product is important to consider as well (Table 23-4) Many authorities believe that the higher the concentration of HA, the stiffer the product and the longer its duration This is true in general when comparing products within a brand, for example, when comparing Juv derm 18 to Juv derm 24 However, this does not hold true across brands because not all of the HA in the dermal fillers is cross-linked Many HA fillers contain uncross-linked HA and lightly cross-linked chains and fragments The uncross-linked HA, fragments of HA, and lightly cross-linked HA are included in the overall concentration measurement but only remain in the skin for a limited time and should minimally contribute to the longevity of the filler The uncross-linked HA does help decrease extrusion force and make injection easier, which is the main reason it is included Therefore, the fact that Restylane contains 20 mg of HA/cc and Juv derm contains 24 mg of HA/cc does not give a physician enough information to decide which filler will have longer duration It is actually the amount of modified HA that plays the primary role in duration The type of modification (cross-linking) and the cross-linking agent used is also important Cross-linking can be best visualized by imagining a ladder (Fig 23-10) Each side of the ladder is an HA chain The rungs of the ladder are the cross-links When the rungs of the ladder attach to both sides of the ladder, the agent is considered completely modified However, the cross-linking agent used may incompletely cross-link the chains of HA, leaving the sides of the rungs unattached and resulting in incomplete modification Such a product might not be as durable as a completely modified product In addition, there are two types of rungs in the HA ladder One is called an ether linkage and the other is called an ester linkage Ether linkages are formed by 1,4-butanediol diglycidyl ether (BDDE, the cross-linking agent in Restylane and Juv derm) and divinyl sulfone (DVS, the agent used in Prevelle Silk, Captique, and Hylaform) The cross-linking agent used in Prevelle Dura, 1,2,7,8 diepoxyoctane (DEO), forms both ether and ester linkages (known as double cross-linking ) It is
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gel and a lateral force is applied The measurement of resistance to deformation is known as the elastic modulus or the G (Fig 23-9) Together with the cohesivity of the product, G values could be used to determine the appropriate placement of an HA dermal filler For example, more robust products (higher G values and higher cohesivities) such as Juv derm Ultra Plus and Perlane, in the primary author s opinion, should be used in deeper lines, such as nasolabial folds and marionette lines, as well as to lift the lateral brow, to correct the nasal bridge, to give the ear lobe youthful volume, to evert the nipples, and to raise the nasal tip More fluid products such as Juv derm Ultra and Restylane are better suited to be used over large areas such as the cheekbones
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FIGURE 23-8 Visible lumps of Hylaform in the upper lip
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FIGURE 23-10 Cross-links that occur during the cross-linking process may be complete or incomplete
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TABLE 23-4 Hyaluronic Acid Fillers: Cross-Linking Agents and Concentration of HA PRODUCT Captique Hylaform Juv derm Ultra and Ultra Plus Prevelle Dura Prevelle Silk Restylane and Perlane CROSS-LINKING AGENT DVS DVS BDDE DEO DVS BDDE CONCENTRATION (mg/mL) 45 65 45 65 24 20 45 65 20
unknown at this time what advantages, if any, ether linkages impart to a dermal filler The hydration status of the filler once it is packaged in the syringe also affects filler performance HA is well known to bind up to 1000 times its weight in water The amount of water bound to the HA prior to its packaging in the syringe determines how much more water the filler can absorb once it is injected into the skin In other words, fillers that are completely hydrated in the syringe will bind less water on injection and the volume will expand less upon injection as compared to fillers that are not completely hydrated in the syringe Fillers that are not completely hydrated in the syringe will swell somewhat within 24 hours after correction; therefore, it is prudent to slightly undercorrect with these substances In addition, patients can be told that they will look even better 24 hours after the injection Restylane and Juv derm are not completely hydrated in the syringe while Captique and Hylaform are close to being fully hydrated (Table 23-5) Another process that may affect the performance of the filler is referred to as sizing technology This term is used by Allergan to differentiate Juv derm from the other HA fillers When an HA filler is cross-linked, the chains of modified sugars form a gel In the process of manufacturing Restylane, Restylane Fine Line, Restylane Lip, Restylane
Touch, Perlane, and Restylane Sub-Q, this gel is extruded through a screen This produces various sizes of the gel that are considered sized The large pieces become Perlane or Restylane Sub-Q, while the small pieces are marketed as Restylane Fine Line or Restylane Lip The medium-sized pieces are Restylane The larger pieces yield products that are best used in the mid to lower dermis while the small pieces such as Restylane Fine Line can be used more superficially The Juv derm family of products is not sized In other words, Juv derm is not pushed through a screen and broken into sized pieces and, therefore, it consists of randomly sized and shaped pieces23 It is unknown at this time what role sizing technology plays, if any, in the performance of a filler There are many factors that must be understood in order to make the most suitable choice of HA filler There are no peer-reviewed publications that review the above mentioned properties so it is difficult at this point to know how important these various characteristics are in choosing a filler More data need to be collected to properly ascertain if, for example, sizing technology makes a difference or if ester bonds last longer than ether bonds These distinctions will become clearer and more important as more HA fillers are introduced onto the market and more data are collected A discussion of the individual HA brands follows HYLAFORM (NO LONGER ON THE MARKET) Overview Although Hylaform is no longer on the market, it will be discussed because it was the first product on the market that used the DVS crosslinking system The knowledge gleaned from this revolutionary agent has led to many spin-off products using similar technology such as Captique and Prevelle Hylaform is an animal-based HA product derived from rooster combs It is produced by cross-linking the hydroxyl groups of HA with DVS to yield a gel-like substance that is sized by
extruding the gel through a sieve in the production process discussed above24 The smallest pieces of the gel are packaged as Hylaform Fine Line, which is indicated for superficial wrinkles, but has never been approved for the US market Hylaform, composed of mediumsized (average size 400 m) particles, is indicated for injection into the middermis for medium facial wrinkles and fine lines Hylaform Plus is composed of larger particles (average size 700 m) and is used for deeper furrows In 2004, the FDA approved two products in this family, Hylaform and Hylaform Plus (Allergan, Irvine, CA), the latter of which remains on the US market The moderate density of cross-linking renders the Hylaform fillers biocompatible, soft, and pliable The G of this filler is low compared to other HA products on the market; therefore, this is the softest HA filler currently on the market This softness makes it an ideal filler for use in the lips The Hylaform products contain 55 mg/mL of crosslinked HA Bene ts Hylaform has a low G , which means that it is not very stiff and has a very natural feel in the skin It is soft and malleable making it ideal for use in the body of the lip, smoker s lines, and the periorbital tear-trough as well as in large areas such as the cheekbones and jowls Hylaform is very easy to inject with a low extrusion force through a 30-gauge needle The side effects of Hylaform are rare, mild, and temporary Drawbacks Side effects, which are rare and relatively mild, typically include bruising, erythema, induration, and pruritus25 The contraindications for Hylaform products are similar to those for most fillers (eg, autoimmune and inflammatory disorders, allergic background, history of anaphylactic reactions, immunosuppressant therapy, and pregnancy or breastfeeding) In addition, patients allergic to products of avian origin (eg, eggs) cannot use these agents25,26 Hylaform is close to being fully saturated with water in the syringe;27 therefore, there is no volume expansion of the filler after injection Additionally, the injection of Hylaform, as with other fillers that do not contain an anesthetic, could be painful However, the softness of Hylaform renders it less painful than other HA fillers to inject The use of topical anesthetics reduces the pain on injection The cosmetic effects of Hylaform and Hylaform Plus are believed to last only about 3 to 4
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