Rheologic Profiles Differ Markedly Between Cross-Linked and Non–Cross-Linked HA Fillers, Study Finds

Non–cross-linked and cross-linked hyaluronic acid (HA) dermal fillers demonstrate distinct rheologic behaviors under mechanical stress, with potential implications for product selection and injection depth, according to a comparative analysis of commercially available fillers published online in Journal of Cosmetic Dermatology.

As the use of injectable soft-tissue fillers continues to expand in aesthetic medicine, understanding the biophysical properties that govern filler performance has become increasingly relevant. In this study, investigators evaluated the viscoelastic characteristics of 28 HA fillers, including 3 non–cross-linked fillers (NCFs) and 25 cross-linked fillers (CFs), using oscillatory rheology testing.

Rheologic parameters assessed included storage modulus (G′), loss modulus (G″), loss tangent (tan δ), and complex modulus (G*), measured across a frequency range of 0.1 to 10 Hz to simulate varying degrees of mechanical stress. Compared with CFs, NCFs exhibited substantially greater variability in their rheologic response. Mean percent change in G′ for NCFs was 3263% (range, 1767%–4177%), versus 247.6% (range, 85%–720%) for CFs, resulting in a calculated difference of 3016% (SD, 755; P < .001).

Significant between-group differences were also observed for G″, tan δ, and G*. The percent change difference was 926% (SD, 498) for G″, −154% (SD, 25.8) for tan δ, and 966% (SD, 147) for G*, with all comparisons reaching statistical significance (P < .001).

Based on these findings, the authors concluded that NCFs undergo greater increases in stiffness and viscosity when exposed to mechanical stress, a property that may predispose them to dermal structural support and more superficial or subdermal applications. In contrast, the more stable rheologic behavior of CFs may favor their use in deeper soft-tissue injections aimed primarily at volumization.