All experimental procedures were approved by the Institutional Animal Care and Use Committee of Medytox Inc. (Approval No. A-2018-010, Approval Date. 20 July 2018) before study initiation. Six- to seven-week-old female hairless mice (SKH1-Hrhr) were purchased from Orient Bio, Inc. (Seongnam-si, Korea) and housed in individually ventilated cage (IVC) racks with free access to standard rodent feed (R+40RMM-10, SAFE, Augy, France) and water. The animals were placed under a controlled environment with a 12 h light/dark cycle at 23 ± 3 °C and relative humidity of 55 ± 15%. The dermal filler was administered subcutaneously at a dose of 100 μL in the dorsal skin of the hairless female mice (n = 8 mice per group). After anesthetic injection in each mouse, the filler volume was measured using a PRIMOS Lite system (Canfield Scientific Inc., Parsippany-Troy Hills, NJ, USA) at 0, 1, 4, 7, 21, and 28 days and monthly from 2 to 18 months. The filler image was recorded using a PRIMOS 5.8E system (Canfield Scientific Inc. Parsippany-Troy Hills, NJ, USA) on day 0 and at the other time points. The change in volume and height was quantitatively determined according to the 3D (3 dimensional) analysis for the filler image under the skin. The minimum detectable value for the filler volume was 3 mm3 (0.003 cm3). The PRIMOS system is a fast and accurate method for measuring filler volume in humans and animals [19,20,21,22].

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