KeywordsTemporary fillerHyaluronic acidg-primeCrosslinkedPoly-l-lactic acidCalcium hydroxyapatiteDermal filler pharmacologyNASHAPLLACaHA
16.1 Temporary Dermal Fillers
Temporary dermal fillers are the second most popular nonsurgical aesthetic treatment worldwide (ISAPS 2017). Temporary fillers offer a safe and effective solution to volume loss associated with aging. There are three types of temporary fillers included in this text: hyaluronic acid (HA), calcium hydroxyapatite (CaHA), and ploy-L-lactic acid (PLLA).
16.2 Hyaluronic Acid (HA) Fillers
Hyaluronan, or HA, is a naturally occurring linear polysaccharide that is found in the skin, epithelial, connective, and other tissues. Because it is innate in our skin and lacks a protein component, HA does not require skin allergy testing prior to injection, making it convenient to use (Carruthers and Carruthers 2013). The nature of this glycosaminoglycan is hydrophilic and is able to bind 1000 times its molecular weight in water and this characteristic makes it a good substance for adding volume to skin and facial tissue (Carruthers and Carruthers 2013; Allemann and Baumann 2008). As we age, the amount of naturally occurring HA in human skin decreases and subsequently, we begin to produce less HA. This phenomenon plays an important role in the appearance of aging, wrinkle formation, decreased tissue elasticity, and hydration (Carruthers and Carruthers 2013; Bray et al. 2010).
When in its natural state, HA has an approximate half-life of 24–48 hours before it is broken down and metabolized in the liver into water and carbon dioxide (Carruthers and Carruthers 2013; Bray et al. 2010; Duranti et al. 1998; Reed et al. 1990; Laurent et al. 1991). In human skin, HA is broken down by hyaluronidase and free radicals (Allemann and Baumann 2008; Bray et al. 2010). Natural HA injected into the skin would break down quickly through enzymatic action so would not be appropriate to use for cosmetic purposes because it would not provide a lasting effect in aesthetic patients.
Processes have been developed through the use of available technology, where HA products currently last months to years. The HA molecules are stabilized using crosslinking technology with hydroxyl groups and provide the long-lasting qualities of modern HA fillers. The crosslinking agent in the Restylane® and Juvederm® HA families of products is 1,4-butanediol diglycidyl ether (BDDE) (Allemann and Baumann 2008; Bray et al. 2010; Allergan 2013; Galderma 2018). These processes have made injectable HA stable and more resistant to break down.
The HA filler families are developed using slightly different technologies. The Juvederm® family of products are sterile, biodegradable, non-pyrogenic, viscoelastic, clear, colorless, homogenized gel implant produced by Streptococcus equi bacteria, developed through a fermentation process and crosslinked with BDDE (Allemann and Baumann 2008; Allergan 2013). The Restylane® family of products are made of hyaluronic acid generated by a Streptococcus species of bacteria, also chemically crosslinked with BDDE, stabilized and suspended in phosphate buffered saline (Galderma 2018). Belotero Balance® is a HA product that is sterile, non-pyrogenic, viscoelastic, homogenous, clear gel implant bacterially fermented, manufactured from Streptococcus bacteria, and is crosslinked with BDDE (Flynn et al. 2013).
Physical and chemical properties influence the characteristics of HA fillers. The different attributes of HA fillers include aesthetic indication, injection properties, desired amount of volume, expected outcome, longevity, and side effects. The HA fillers also differ in particle size, crosslinking of the HA molecules, the amount of crosslinking in the product, as well as the G-prime or viscosity of the product. These features of HA products guide the practitioner in choosing the appropriate filler for specific effects (Carruthers and Carruthers 2013; Allemann and Baumann 2008; Flynn et al. 2013).
16.2.1 G-Prime and Particle Size
G-prime is a measurement of the stiffness of the hyaluronic gel product and this characteristic helps determine the appropriate area and depth for placement in the skin. G-prime also contributes to the increased longevity of the effect of the HA products, i.e., the higher the G-prime, the longer the filler might last (Carruthers and Carruthers 2013; Allemann and Baumann 2008; Duranti et al. 1998; Tezel and Fredrickson 2008). Generally, thicker products are not suitable to be placed in the superficial layers of skin due to the possibility of long-lasting swelling, uneven result, and the residual visibility of the product as a bluish tint called the Tyndall effect (Carruthers and Carruthers 2013).
The modern, crosslinked HA dermal fillers of the Belotero®, Juvederm®, and Restylane® families of products are frequently used to replace volume or soften fine lines in the face. These fillers include both crosslinked or high weight, and non-crosslinked or low weight, HA molecules within their gel vehicle. The higher the concentration of crosslinked HA molecules, the longer the effect will last in the skin (Carruthers and Carruthers 2013; Allemann and Baumann 2008; Tezel and Fredrickson 2008).
After injection into the skin, the non-crosslinked hyaluronic acid is quickly broken down and only the crosslinked, larger molecular weight polymers are left behind. The reason for the low weight, non-crosslinked molecules in the product is thought to allow ease of injection through the needle or cannula (Allemann and Baumann 2008; Bray et al. 2010). If the gel consisted of purely large weight, crosslinked molecules, the product would not be conducive to injection through a small caliber needle.
Another relevant aspect of the HA fillers is particle size. A process where the particles are formed into specific sizes is employed by some manufacturers, but other manufacturers use a different method called Hylacross (Juvederm®) to create their products (Allergan 2016). In the sizing method, particle size is created through a process where crosslinked HA is pushed through a customized screen to create different, specific sizes of the particles. Smaller sizes are made into lower G-prime, or less viscous products, whereas the larger particle sizes are made into the higher G-prime or more viscous products (Allemann and Baumann 2008). To date, there is no scientific data on which process yields the preferred longevity profile or outcome.
Various concentrations and particle sizes of HA fillers
Concentration of HA (mg/mL)
Juvederm ultra plus