Effect of Hyaluronic Acid-Hydroxyapatite Filler on Collagen and Elastic Fiber Regeneration in a Nude Mouse Model

Abstract

Introduction: Compared to pure hyaluronic acid filler, cross-linked hyaluronic acid (HAc) filler has superior biocompatibility and longevity as long-lasting effective dermal fillers. Herein, we investigated effects and longevity of HAc-hydroxyapatite (HAp) filler on collagen and elastic fiber regeneration in a nude mouse model.

Methods: Six-week-old female BALB/c-nude mice were classified into 5 groups: normal skin, Radiesse, Restylane, HAc-nanoHAp, and HAc-microHAp. Fillers (200 μl) were injected to evenly fill the backs of mice. Filler volume was compared by MRI after 0, 1, 4, 8, and 12 weeks. Skin biopsies were performed to investigate collagen and elastic fiber synthesis after filler injections. Western blot analysis, real time-PCR, and immunohistochemistry were used to investigate protein and gene expression changes. Organ (liver, lung, spleen, and kidney) toxicity of HAc-nanoHAp was determined by hematoxylin & eosin staining after 12 weeks.

Results: Results of these analyses suggest that HAc-nanoHAp and HAc-microHAp hydrogels had good longevity and promoted collagen and elastic fiber formation via the TGF-ß pathway.

Conclusion: HAc-HAp filler could play an important role in collagen and elastic fiber regeneration. Further research should focus on the role of hyaluronic acid and hydroxyapatite composite fillers in photoaging in animal models and effects on skin, including on elasticity and tension strength.