An Overview of Soft Tissue Fillers for Cosmetic Dermatology: From Filling to Regenerative Medicine

Abstract

Hyaluronic acid (HA)-based injectable filling agents are at the forefront of the current demand for noninvasive dermatological procedures for the correction of age-related soft tissue defects. The present review aims to summarize currently available HA-based products and critically appraise their differences in rheological nature and clinical application. Linear HA (LHA) gels may be supplemented with amino acids, lipoic acid, vitamins, nucleosides, or minerals for synergistic antiaging and antioxidant benefits (polycomponent LHA). HA hydrogels can be generated via chemical or physical crosslinking, which increases their elasticity and decreases viscosity. The performance of crosslinked fillers depends on HA concentration, degree of crosslinking, elastic modulus, cohesivity, and type of crosslinking agent employed. PEG-crosslinked LHA displays improved elasticity and resistance to degradation, and lower swelling rates as compared to BDDE-crosslinked LHA. Physical crosslinking stabilizes HA hydrogels without employing exogenous chemical compounds or altering hyaluronans' natural molecular structure. Thermally stabilized hybrid cooperative HA complexes (HCC) are a formulation of high- and low-molecular-weight (H-HA and L-HA) hyaluronans, achieving high HA concentration, low viscosity with optimal tissue diffusion, and a duration comparable to weakly cross-linked gel. Our critical analysis evidences the importance of understanding different fillers' properties to assist physicians in selecting the most appropriate filler for specific uses and for predictable and sustainable results.

Keywords: crosslinking; filler; hyaluronic acid; hydrogel.

Figure 1

Linear hyaluronic acid is constituted by a repeating disaccharide structure of D-glucuronic acid and N-acetyl-D-glucosamine, linked by alternating beta-1,4 and beta-1,3 glycosidic bonds.

Figure 2

Crosslinking with 1,4-butanediol diglycidyl ether (BDDE). The epoxide groups located at the two ends of the molecule preferentially create an ether bond with the most accessible primary alcohol in the LHA backbone.

Figure 3

LHA crosslinking with PEG (x) is based on the formation of ether bonds with PEG’s epoxide groups: the reaction consists of the deprotonation of a hydroxyl group on LHA (m,n) the epoxide ring opening, and the formation of a stable C–O–C bond.