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Evaluation of the In Vivo Kinetics and Biostimulatory Effects of Subcutaneously Injected Hyaluronic Acid Filler

Mochizuki, Masato, M.D.; Aoi, Noriyuki, M.D.; Gonda, Koichi, M.D.; Hirabayashi, Shinichi, M.D.; Komuro, Yuzo, M.D.

Plastic and Reconstructive Surgery: July 2018 - Volume 142 - Issue 1 - p 112–121
doi: 10.1097/PRS.0000000000004496
Experimental: Original Articles

Background: Because subcutaneously injected hyaluronic acid filler is absorbed over 6 months to 1 year after the treatment of facial wrinkles, frequent retreatment may be required. However, persistent long-term effects are often clinically observed when hyaluronic acid filler is injected as a bolus for facial augmentation. Therefore, the authors investigated, over time, the changes in volume and histologic features of subcutaneous bolus injections of hyaluronic acid.

Methods: Hyaluronic acid filler was subcutaneously injected as a bolus into the dorsum of 6-week-old rats. At several time points (immediately after injection and 4, 8, 16, 32, and 64 weeks thereafter), magnetic resonance imaging was introduced to observe morphologic changes and to measure volume. Histologic examination of sectioned tissues was also performed.

Results: The average volume increased for up to 4 weeks after injection and then gradually decreased, with 74.8 percent of the injected volume remaining after 64 weeks, with no statistical difference compared to the initial volume. Histologic analysis revealed that lattice structures were created by fibroblasts and collagen fibers, and blood vessels and adipocytes were also generated in the filler.

Conclusions: Although subcutaneous bolus injections of hyaluronic acid filler exhibited flattening, the total volume was maintained even after 64 weeks. Histologically, hyaluronic acid filler acted as a scaffold for autogenous tissue replacement by means of fibroblast migration and proliferation, collagen induction, and angiogenesis, followed by proliferation of adipocytes. This study demonstrates that the total volume is maintained long-term by replacing part of the injected hyaluronic acid filler with autologous tissues.

Tokyo and Kawasaki, Japan

From the Departments of Plastic, Oral and Maxillofacial Surgery and Plastic Surgery, Teikyo University School of Medicine; and University Hospital, Mizonokuchi.

Received for publication June 23, 2017; accepted January 23, 2018.

Disclosure: The author have no financial interest to declare in relation to the content of this article. No funding was received for this article.

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Noriyuki Aoi, M.D., Department of Plastic, Oral and Maxillofacial Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-Ku, Tokyo 173-8605, Japan,

©2018American Society of Plastic Surgeons