Introduction

The use of an exogenous material to augment soft tissue can be traced back to Neuber in 1893, who used fat transplanted from the arms to correct facial defects. Since that time, substances used to volumize the face have changed rapidly and include both biodegradable and non-biodegradable products. The class of compounds known as non-animal stabilized hyaluronic acids (‘NASHA™’) comprises biodegradable fillers with an average duration of action of 6–12 months. This chapter will review the current NASHA™ products available in the US marketplace and provide injection tips for the most common facial areas injected. Potential complications will be presented, as will advice on how to manage patient expectations.

Background

NASHA™ are commonly used to correct moderate to severe facial lines and restore volume loss that occurs during the natural course of aging. Since the US Food and Drug Administration (FDA) approval of Restylane^® in December 2003, the NASHA™ injectable market has continued to expand. According to the American Academy of Aesthetic Plastic Surgeons, there were approximately 1 315 121 hyaluronic acid (HA) injections performed in 2010 alone, with an estimated $1.9 billion spent on injectables in general. This does not include procedures performed by dermatologists or other healthcare practitioners.

Knowing where to place these fillers is as important as understanding the subtle differences between them. In general, NASHA™ injectables are safe, confer a soft look, and are predictable in their volumizing capacity.

Basic science

HA or hyaluronan is an anionic, hydrophilic, non-sulfated glycosaminoglycan that is abundant in human connective tissue. The chemical structure of this substance is uniform throughout Nature and lacks a protein component allowing it to have little to no potential for immunologic reaction in humans when injected. As one of the chief components of the extracellular matrix, HA stabilizes intercellular structures and forms part of the fluid matrix in which collagen and elastic fibers become embedded. The average 70 kg person has approximately 15 g of hyaluronan in the body, of which one-third is degraded and synthesized daily.

HA contributes to cell proliferation and migration as well as tissue repair. With age, HA concentration in the skin decreases, resulting in reduced dermal hydration, which manifests as an increase in lines and folds. In addition, excessive exposure to ultraviolet B rays causes cells in the dermis to stop producing HA. In its natural form, the half-life of HA is 1–2 days and is metabolized by the liver to carbon dioxide and water. As a compound, it can absorb up to 1000 times its molecular weight in water; its mechanism of action as a filler is mainly through hydration.

The hyaluronic acid molecule is stabilized with cross-linked hydroxyl groups. It is this cross-linking that confers longevity to the product in the skin and the degree of cross-linking one of the distinguishing features of NASHA™ products. Because of this structural matrix, the degradation curve of implanted HA is not linear. Rather, the product retains its effect until the structural complex around the HA molecule is broken down. Once the unbound HA is exposed, efficacy is then lost (Fig. 3.1). As a result, patients will often suddenly notice a change in their appearance rather than experience a gradual loss over time. In addition, patients sometimes feel they look worse after HA injection than they did prior to it; however, this is more of a function of selective memory. This is why taking pre-injection photographs is so important. As with natural hyaluronan, HA fillers can be instantly dissolved with the enzyme, hyaluronidase.

Figure 3.1 Conceptual degradation curve of NASHA™ fillers. Note that the line is not linear, which correlates to the cross-linking agents used to stabilize the filler in the skin. Free hyaluronic acid has a half-life of 1–2 days in human skin.

Choosing the right NASHA™

The main difference between commercially available NASHA™ products on the current US market is the viscosity of the product. The higher the concentration of HA, the stiffer is the product and the longer it lasts in tissue (Table 3.1). The larger the particle and the greater the concentration of the filler, the greater the lift you get. It should be noted, however, that not all of the HA in a given filler is cross-linked. Some is free, fragmented or only lightly cross-linked so that the gel can actually flow out of the syringe with ease. As discussed above, the cross-linking is what confers longevity to the product and this does vary between brands. In Restylane^® and Juvéderm^®, 1,4-butanediol diglycidyl ether is the cross-linking agent, which forms ether linkages in the HA chain. This same type of ether linkage is formed by diglycidyl sulfone found in Prevelle^® Silk. In addition to cross-linking, it is worth mentioning that not all HA products are packaged in the fully hydrated state. As mentioned earlier, NASHA™ fillers create volume via hydration and, for this reason, patients will often look better or more filled 24 hours after treatment with products like Restylane^® and Juvéderm, which are not completely saturated in the syringe. With that in mind, it is prudent not to overcorrect when using NASHA™ products.

Table 3.1 Hyaluronic acid (HA) concentration of commercially available NASHA™ products

^* Even very cohesive products are particulate. The particle sizes of commercially available NASHA™ fillers are shown. In comparison, the particulate sizes of non-NASHA™ products are as follows: Radiesse^® (25–45 µm), Artefill^® (over 30–50 µm), Sculptra^® (40–60 µm), Dermalive^® (20–120 µm).

Patient evaluation

Prior to injection with any dermal filler, a careful patient history should be obtained. Pertinent items to note in this history include a history of herpes simplex virus, pregnancy or breastfeeding, history of keloid formation, presence of any autoimmune disease, and allergy to lidocaine as most of the fillers now come pre-mixed with lidocaine (Box 3.1). A medication history should include use of multivitamins, fish oil, vitamin E, blood thinners, aspirin, ibuprofen, and Gingko biloba, as all of these can predispose the patient to bruising. Unless medically necessary, the patient should be advised to discontinue these medications 14 days prior to treatment. In addition, alcohol use within 48 hours of injection can cause an increase in bruising tendency.

If the patient has had fillers in the past, it is recommended that the physician document how long ago, where the fillers were placed, and if the patient was satisfied with the results. In addition to history, pre-injection photography is a must. These authors prefer at least three views: frontal, left side at an oblique angle, and right side at an oblique angle. If a patient is having a specific area corrected, a closeup picture of that area is also advisable. Informed consent must be obtained and the patient should be aware of the financial cost of the procedure prior to opening the first syringe. We also advise that baseline facial asymmetry be discussed with the patient and noted in the chart. From a physician standpoint, it is important to inform your malpractice coverage carrier of your intention to use fillers as many uses are considered off-label.

Patient preparation

Patients should be asked to remove their makeup and the areas to be injected should be cleansed with alcohol or a skin-cleansing solution that does not stain the skin. If there are any areas of infection, injection should be deferred. If the area is to be marked, these authors recommend using a white eyeliner pencil or an erasable marker. Use of gentian violet can create a tattoo if the needle is inserted through the marked line. Patients should be in a seated or reclined position to maximize comfort while allowing the skin to drape naturally. For this reason, it is not advisable to have the patient lie down as this can distort the natural contours of the face. Hair should be pulled back with a bandana or covered and pulled back with a surgical bonnet. The physician may decide to use a topical or local anesthetic prior to injection. If so, this should be completely removed prior to injection.