Longevity of Cross-linked Hyaluronic Acid Filler Depending on Injection Depth: In Vivo Study Using a Small Animal Model

Background: Hyaluronic acid (HA) is the material used most often for soft tissue augmentation. Both agent factors, such as type of fillers and host factors, including technical manipulation, are known to affect the longevity of HA fillers. Although the relationship between longevity and filler composition has been widely studied, quantitative analysis to evaluate the difference in longevity of HA filler depending on injection depth has not yet been reported. Objective: This study estimates injection depth-dependent degradation of HA filler in vivo using a rat model to evaluate its longevity. Methods: Three Sprague-Dawley rats were assigned to each group based on sampling timepoints. Four injections were administered intradermally on one side of the back of rats and four more injections were administered subcutaneously on the other side. Histological specimens from the injected site were obtained at 2 (Group 1), 5 (Group 2), 9 (Group 3), 13 (Group 4), 20 (Group 5), and 33 (Group 6) weeks after initial implantation. External size of the implant site was calculated using caliper measurement at sampling timepoints. Results: Although caliper-based analysis did not reveal a significant difference between intradermal and subdermal sites in all groups (p>0.05), volumetric analysis of histological specimens demonstrated a difference in injection depth-dependent degradation rate. The volume ratio decreased over time in the subdermal injection sites, but it maintained a greater volume ratio than intradermal injection sites during the experiment (Groups 1~6, p< 0.007). At 20 weeks after implantation, approximately half of the HA filler remained in the subdermal injection sites, whereas >80% of the filler was lost from intradermal injection sites. After the initial injection, time taken for the implant volume to reduce to half of its original value at intradermal and subdermal sites was 13 and 20 weeks, respectively. Conclusion: This study demonstrates histological changes occurring in implanted HA filler materials over time and compares the injection depth-dependent longevity of materials. Caliper-based analysis did not show a significant difference between the intradermal and subdermal sites. However, quantitative analysis based on histological volumetric analysis revealed that subdermal injection lasts longer than intradermal injection. (Korean J Dermatol 2020;58(8):516 ~ 524).