Resilient Hyaluronic Acid (RHA®) Fillers

RHA Basic Science and Manufacturing

Resilient Hyaluronic Acid (RHA) is the name given to a collection of hyaluronic acid (HA) products manufactured by Teoxane SA (Geneva, Switzerland) and marketed in the United States by Revance Therapeutics Inc. (Nashville, TN, USA). First introduced to the European market in 2015, the RHA gels were designed to address the current and future needs of health care practitioners and consumers. Treatment with dermal fillers has evolved over time, from an early focus on the direct filling of bothersome static facial lines and folds to a more contemporary view that the treatment approach should be based on an understanding of the three-dimensional anatomic changes that underlie the appearance of the static lines and, furthermore, the selection of products that are designed to complement the face, not only at rest but also, most importantly, in animation.

The prime directive in the design of the RHA collection of products was to create gels that fulfilled two needs, that is, had desirable physical characteristics that enabled a high degree of clinical effectiveness and, at the same time, were highly dynamic, moving seamlessly with facial animation. To create such gels, Teoxane aimed to minimize alteration to the HA chains, limiting tethering of the HA due to crosslinking and minimizing degradation of the HA chains during the manufacturing process.

This unique RHA manufacturing process, termed “Preserved Network Technology” (PNT), begins with exclusively high-molecular-weight HA chains. However, in PNT, the standard butanediol diglycidyl ether (BDDE) crosslinking process has been modified in several ways, including reducing the crosslinking temperature and optimizing other reaction conditions to minimize HA chain degradation during crosslinking and, thus, minimizing the amount of BDDE crosslinking required to create optimal gel characteristics. The end result has been to create RHA gels with extractable HA chains of approximately 600 kD in length (i.e., approximately two to four times the length of the HA chains typically found in similar analyses of other cohesive HA gels) and substantially lower chain modification with BDDE (1.9%–4.0% crosslinking) than other cohesive gels. In preserving the HA chain length and minimizing rigid crosslinkers, the RHA gels rely on the intrinsic three-dimensional nature of the gel network and more dynamic, noncovalent intramolecular bonds to provide the gel structure, extensibility, and cohesivity.

The RHA collection encompasses a range of four products (RHA 1–4) designed to provide progressively increasing levels of tissue support. As will be described later, these products exhibit physical characteristics designed to allow them to be placed more superficially than other products in their class without fear of the product bunching or of an unnatural appearance on facial animation. RHA 1 is formulated with 15 mg/mL HA, approximately 1.9% crosslinked, and designed for placement in the most superficial tissue planes. RHA 2 through 4 contain 23 mg/mL HA and are differentiated by their degree of crosslinking, with RHA 2 being 3.1% crosslinked, RHA 3 being 3.6% crosslinked, and RHA 4 being 4.0% crosslinked. All products in the RHA collection contain 0.3% lidocaine for patient comfort.

RHA 2, 3, and 4 have a unique US Food and Drug Administration indication for the treatment of “dynamic wrinkles and folds,” reflective of the design intent to create a product range that can adapt and integrate with facial movement. In the United States, RHA 2 and 3 are indicated for placement in the mid to deep dermis and are ideal for the treatment of moderate facial wrinkles or folds, whereas RHA 4 is indicated for placement in the deep dermis or superficial subcutaneous planes. However, the physical properties of RHA 4 are such that it can provide support for deep fat pad reflation in areas such as the midface and, given its dynamic properties, can be layered in the superficial plane to provide contour or refill depleted superficial fat pads. This sits in contrast to other products designed for deep placement, which are often palpable or visible upon animation when placed superficially.