title: In vivo bio-integration of three hyaluronic acid fillers in human skin: a histological study.
abstract: BACKGROUND
  Hyaluronic acid (HA) formulations are used for aesthetic applications. Different cross-linking technologies result in HA dermal fillers with specific characteristic visco-elastic properties.
  
  
  OBJECTIVE
  Bio-integration of three CE-marked HA dermal fillers, a cohesive (monophasic) polydensified, a cohesive (monophasic) monodensified and a non-cohesive (biphasic) filler, was analysed with a follow-up of 114 days after injection. Our aim was to study the tolerability and inflammatory response of these fillers, their patterns of distribution in the dermis, and influence on tissue integrity.
  
  
  METHODS
  Three HA formulations were injected intradermally into the iliac crest region in 15 subjects. Tissue samples were analysed after 8 and 114 days by histology and immunohistochemistry, and visualized using optical and transmission electron microscopy.
  
  
  RESULTS
  Histological results demonstrated that the tested HA fillers showed specific characteristic bio-integration patterns in the reticular dermis. Observations under the optical and electron microscopes revealed morphological conservation of cutaneous structures. Immunohistochemical results confirmed absence of inflammation, immune response and granuloma.
  
  
  CONCLUSIONS
  The three tested dermal fillers show an excellent tolerability and preservation of the dermal cells and matrix components. Their tissue integration was dependent on their visco-elastic properties. The cohesive polydensified filler showed the most homogeneous integration with an optimal spreading within the reticular dermis, which is achieved by filling even the smallest spaces between collagen bundles and elastin fibrils, while preserving the structural integrity of the latter. Absence of adverse reactions confirms safety of the tested HA dermal fillers.
authors: Faculté de Médecine, Université de Genève, Geneva, Switzerland.
authors: Christian
authors: C
authors: Tran
authors: Pierre
authors: P
authors: Carraux
authors: Patrick
authors: P
authors: Micheels
authors: Gürkan
authors: G
authors: Kaya
authors: Denis
authors: D
authors: Salomon
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes; D001672:Biocompatible Materials; D003094:Collagen / Q000648:ultrastructure; D003879:Dermatologic Agents / Q000494:pharmacology*; D004549:Elastin / Q000648:ultrastructure; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007150:Immunohistochemistry; D008264:Macrophages; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D058628:Myofibroblasts; D012867:Skin / Q000033:anatomy & histology* / Q000187:drug effects* / Q000648:ultrastructure; D013601:T-Lymphocytes; D013997:Time Factors
chemical_list: D001672:Biocompatible Materials; D003879:Dermatologic Agents; C526061:Juvederm Ultra; C584568:belotero balance; D006820:Hyaluronic Acid; D003094:Collagen; D004549:Elastin; C445361:Restylane