The Effects of Subcutaneously Injected Novel Biphasic Cross-Linked Hyaluronic Acid Filler: In Vivo Study

Background Biphasic hyaluronic acid (HA) fillers have been used extensively to improve facial skin. However, in some cases, the skin surface is irregular because of the premature loss of HA solution. We propose a new biphasic filler (G-filler) to overcome this problem by using small particles of HA hydrogel instead of HA solution, which can provide a smooth skin surface and good durability. Method We evaluated the rheologic properties of G-filler and its physiologic effects after subcutaneous injection in a mouse model by histologic analysis. Results The G-filler showed a similar elastic modulus (G′) and complex viscosity ( η *) as the conventional biphasic filler, but had a higher viscous modulus (G″) than the conventional monophasic filler. The highest material elasticity (tan δ ) value and the lowest percentage elasticity value indicate the rheologic properties of G-filler are closer to those of liquids. After subcutaneous injection of G-filler, collagen content (~ 2-fold) and elastin fibers (~ 6.5-fold) were significantly increased at 12 weeks compared to those of the saline group. Fibronectin (~ 2.6-fold) and the laminin-immunolabeled cell number (~ 6-fold) were also significantly increased at 12 weeks. Significant increases in the CD31-immunoreactive cell numbers of the G-filler groups were observed at 2, 6, and 12 weeks (~ 3.7-fold) compared to those of the saline groups. There were no significant differences between the G-filler and saline groups in patterns of skin thickness and inflammatory cell numbers around loading sites. Conclusion These findings demonstrate that the injection of a new biphasic filler with improved rheologic properties can effectively stimulate extracellular matrix production and angiogenesis without safety concerns. No Level Assigned This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors - www.springer.com/00266 .