Validation of a Small Animal Model for Soft Tissue Filler Characterization


  • This study was supported by a grant from Kythera Pharmaceuticals, which also provided the dermal fillers. Drs. Elisseeff and Hillel previously held a licensed patent agreement with Kythera Pharmaceuticals.

Address correspondence and reprint requests to: Jennifer H. Elisseeff, PhD, Associate Professor, Department of Biomedical Engineering, Johns Hopkins University, 400 N. Broadway, Smith 5035, Baltimore, MD 21231, or e-mail:



Rigorous preclinical testing of soft tissue fillers has been lacking. No animal model has emerged as an accepted standard to evaluate tissue filler longevity.


To validate a small animal model to compare soft tissue filler degradation and tissue reaction.


Preliminary experiments compared caliper with magnetic resonance imaging volumetric analysis. Next, four hyaluronic acid (HA) fillers were injected into the dermis of Sprague–Dawley rats. The three dimensions of the implants were measured at day 0, day 1, and monthly for 1 year or complete resorption of the filler. Volumetric, histologic, and statistical analyses were performed.


Magnetic resonance imaging results validated caliper-based volumetric measurements. Histology demonstrated injections in the subcutaneous space just deep to the dermis and panniculus carnosus. High- and very high-concentration HA fillers maintained significantly greater volumes and volume ratios than low-concentration HA fillers throughout the duration of the study.


The rat subcutis model demonstrated the ability to differentiate between HA fillers with different residence times. The caliper-based rat-subcutis method demonstrated consistent volumetric analysis and correlated with human residence times of HA fillers. These quantitative results validate the rat subcutis model as an expedited preclinical model for HA fillers.