Evaluation of Hyaluronic Acid Filler Injections in Mice Over 28 Days: A Controlled In Vivo Study.

[BACKGROUND] Initial and early swelling post injection of hyaluronic acid (HA) filler are considered to affect outcomes and complications in patients; however, the contribution of HA filler type to swelling postinjection remains undetermined. Here, initial and early swelling post injection of HA fillers manufactured via different crosslinking technologies was evaluated in mice.

[METHODS] Mice received injections of HA fillers or controls: High Concentration Equalized (HICE), Stabilized High Concentration Equalized (S-HICE), High molecular Ideal, VYCROSS, NASHA, HICE control, non-HICE control, or no HA control. Initial and early swelling were evaluated via magnetic resonance imaging and collagen deposition via histological evaluation over 28 days.

[RESULTS] Mice (N = 65) were allocated to 13 groups (per group, n = 5) to receive subcutaneous injections of HA filler or control. Maximum swelling in descending order was High molecular Ideal, 290%; non-HICE control, 256%; VYCROSS 1, 249%; S-HICE 2, 248%; S-HICE 1, 238%; S-HICE 3, 226%; VYCROSS 2, 210%; HICE 1, 203%; HICE 2, 184%; NASHA 1, 174%; HICE control, 159%; NASHA 2, 148%; and no HA control, 100.0%. The mean (SD) collagen area in the residual substance ranged from 2525 (3612) µm/HPF (high-power field [×400]) for NASHA 2 to 18,870 (4544) µm/HPF for S-HICE 2. The mean (SD) collagen area around the substance ranged from 9879 (2923) µm/HPF for VYCROSS 1 to 15,248 (7005) µm/HPF for S-HICE 3.

[CONCLUSIONS] HA fillers manufactured via different crosslinking technologies may lead to different levels of initial and early swelling and collagen stimulation over 28 days.