title: Validation of a small animal model for soft tissue filler characterization.
abstract: BACKGROUND
  Rigorous preclinical testing of soft tissue fillers has been lacking. No animal model has emerged as an accepted standard to evaluate tissue filler longevity.
  
  
  OBJECTIVE
  To validate a small animal model to compare soft tissue filler degradation and tissue reaction.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Otolaryngology-Head and Neck Surgery, School of Medicine, Stanford University, Stanford, California, USA.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Hillel
authors.forename: Zayna
authors.initials: Z
authors.lastname: Nahas
authors.forename: Shimon
authors.initials: S
authors.lastname: Unterman
authors.forename: Branden
authors.initials: B
authors.lastname: Reid
authors.forename: Joyce
authors.initials: J
authors.lastname: Axelman
authors.forename: Damon
authors.initials: D
authors.lastname: Sutton
authors.forename: Christine
authors.initials: C
authors.lastname: Matheson
authors.forename: Jennifer
authors.initials: J
authors.lastname: Petsche
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Elisseeff
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D003357:Cosmetic Techniques; D004195:Disease Models, Animal; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D016018:Least-Squares Analysis; D008279:Magnetic Resonance Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001672:Biocompatible Materials; D006820:Hyaluronic Acid