title: Cohesivity of Hyaluronic Acid Fillers: Development and Clinical Implications of a Novel Assay, Pilot Validation with a Five-Point Grading Scale, and Evaluation of Six U.S. Food and Drug Administration-Approved Fillers.
abstract: BACKGROUND
  Biophysical characteristics of hyaluronic acid gel fillers reflect individual manufacturing processes. They confer rheologic properties that provide scientific rationale with Evidence Level II clinical correlation for selection of appropriate fillers for specific clinical applications. Cohesivity, a key property, maintains gel integrity, contributes to tissue support with natural contours, and diminishes surface irregularities. In this publication, a new, standardized visual assay for hyaluronic acid cohesivity is presented, applied, and discussed.
  
  
  METHODS
  Colored hyaluronic acid gel specimens were automatically extruded under standardized conditions into sterile water stirred at a constant rate. Based on 90 digital images showing ratios of intact to dispersed gel during assay of 10 Communauté Européenne-marked fillers, the five-point visual Gavard-Sundaram Cohesivity Scale was developed. Six plastic surgeons and dermatologists performed pilot validation of the scale, subsequently used to evaluate six U.S. Food and Drug Administration-approved fillers.
  
  
  RESULTS
  Validation of the Gavard-Sundaram Cohesivity Scale showed substantial repeatability and interrater consistency. Mean cohesivity scores from three assays of each tested filler showed significant differences. Cohesivity was high for Cohesive Polydensified Matrix (Belotero Balance), medium-high for Hylacross (Juvéderm Ultra 2/Ultra XC and Ultra 3/Ultra Plus XC), low-medium for Vycross (Juvéderm Voluma), and low for non-animal-stabilized hyaluronic acid (Restylane and Perlane).
  
  
  CONCLUSIONS
  An evidence-based approach requires clinical corroboration of in vitro data. This new, reproducible cohesivity assay may have value together with elasticity (G') and viscosity measurements to understand and leverage distinct tissue distribution patterns and clinical behaviors of different hyaluronic acid products.
  
  
  METHODS
  Therapeutic, V.
authors.affiliation: Rockville, Md.; Dallas, Texas; Darlinghurst, New South Wales, Australia; Darmstadt, Germany; São Paulo, Brazil; Paris, France; and Geneva, Switzerland From Sundaram Dermatology, Cosmetic & Laser Surgery; the Department of Plastic Surgery, University of Texas Southwestern Medical Center; Shape Clinic; Rosenpark Klinik; Departamento de Dermatologia, Escola Paulista de Medicina, Universidad de São Paulo; Plastic, Reconstructive, and Cosmetic Surgery; and Research Department, Anteis, S.A., a wholly owned subsidiary of Merz Pharmaceuticals, GmbH.
authors.forename: Hema
authors.initials: H
authors.lastname: Sundaram
authors.forename: Rod J
authors.initials: RJ
authors.lastname: Rohrich
authors.forename: Steven
authors.initials: S
authors.lastname: Liew
authors.forename: Gerhard
authors.initials: G
authors.lastname: Sattler
authors.forename: Sergio
authors.initials: S
authors.lastname: Talarico
authors.forename: Patrick
authors.initials: P
authors.lastname: Trévidic
authors.forename: Samuel Gavard
authors.initials: SG
authors.lastname: Molliard
mesh_terms: D004548:Elasticity; D006820:Hyaluronic Acid / Q000031:analogs & derivatives / Q000737:chemistry*; D015588:Observer Variation; D010865:Pilot Projects; D015203:Reproducibility of Results; D016037:Single-Blind Method; D013499:Surface Properties; D014481:United States; D014486:United States Food and Drug Administration; D014783:Viscosity
chemical_list: C526061:Juvederm Ultra; C502935:Perlane; D006820:Hyaluronic Acid; C445361:Restylane