Title:
Biophysical characteristics of hyaluronic acid soft-tissue fillers and their relevance to aesthetic applications.

Abstract:
The purpose of this study was to present new rheologic data for hyaluronic acid filler products, correlate them with recent tissue integration studies, and provide a scientific rationale for selecting appropriate products for volume replacement within different tissue levels and anatomical zones. A brief overview of the methodology of filler rheology studies and data analysis is provided.
Six U.S. Food and Drug Administration–approved, cross-linked, nonanimal-derived hyaluronic acid filler products and one hyaluronic acid product approved in Europe and elsewhere were studied: one cohesive polydensifiedmatrix hyaluronic acid (Belotero Balance, also known as Belotero Basic), two Hylacross hyaluronicacids (Juvéderm Ultra and Juvéderm Ultra Plus), one Vycross hyaluronic acid (Juvéderm Voluma), and three nonanimal stabilized hyaluronic acids (Perlane, Restylane and Restylane SubQ) [corrected].The elastic modulus, complex viscosity, and viscous modulus of each filler gel were quantified. Tan delta for each filler gel and also for calcium hydroxylapatite filler (Radiesse) was calculated at 0.7 Hz.
Cohesive polydensified matrix hyaluronic acid (Belotero Balance) has the lowest elasticity and viscosity and the highest tan delta. This predicts its soft, flowing qualities and correlates with its homogeneous pattern of tissue integration after intradermal implantation. Nonanimal stabilized hyaluronic acid (Perlane and Restylane) has the highest elasticity and viscosity and low tan delta. This predicts its firm, less flowing qualities and correlates with a bolus-like pattern of tissue integration. Hylacross hyaluronic acid (Juvéderm) has intermediate elasticity, viscosity, and tan delta, correlating with its intermediate pattern of tissue integration.
Rheologic evaluation reliably predicts tissue integration patterns and appropriate clinical applications of the studied fillers. Paradigms of layered filler placement can be designed to optimally address individual patient need.