title: The biological basis for poly-L-lactic acid-induced augmentation.
abstract: BACKGROUND
  Granulomatous reactions to poly-L-lactic acid (PLLA)-based filler have been described previously. Neither the biological background of these partly late-onset reactions or the desired augmenting effect of PLLA has been studied to date. Histological studies have revealed foreign body reactions and foreign body giant cell formation.
  
  
  OBJECTIVE
  The aim of this study was to increase our knowledge about the biological mechanisms behind the augmenting effect of PLLA-based filler.
  
  
  METHODS
  We characterised the cell infiltrate and collagen type of PLLA-treated tissue by immunofluorescence staining. The expression of genes related to collagen metabolism was determined.
  
  
  RESULTS
  CD68(+) macrophages were found next to PLLA. CD90(+) fibroblasts were found alongside. αSMA-positive structures indicated myofibroblasts and neovascularisation. Substantial collagen type III deposition was detected next to PLLA particles and collagen type I was found at the periphery of PLLA encapsulations. mRNA expression for collagen type I and III transcripts, as well as for TGFβ1 and TIMP1, was upregulated significantly.
  
  
  CONCLUSIONS
  PLLA-induced augmentation is most likely based on capsule formation orchestrating macrophages, (myo-)fibroblasts, and collagen type I and III fibres. We observed considerably slower degradation of PLLA particles than described previously. Thus PLLA particles were still retrievable 28 months after subcutaneous application.
authors.affiliation: Division of Dermatology, Department of Environmental Medicine and Health Theory, University of Osnabrück, Sedanstraße 115, 49090 Osnabrück, Germany. Electronic address: pstein@uos.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Stein
authors.affiliation: Division of Animal Physiology, Department of Biology/Chemistry, University of Osnabrück, Barbarastraße 11, 49076 Osnabrück, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Vitavska
authors.affiliation: Institute for Dermatopathology, Kleiner Biergrund 31, 63065 Offenbach, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kind
authors.affiliation: Division of Biomedical Science, Department of Human Sciences, University of Osnabrück, Albrechtstraße 28, 49076 Osnabrück, Germany.
authors.forename: Willi
authors.initials: W
authors.lastname: Hoppe
authors.affiliation: Division of Animal Physiology, Department of Biology/Chemistry, University of Osnabrück, Barbarastraße 11, 49076 Osnabrück, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Wieczorek
authors.affiliation: Division of Dermatology, Department of Environmental Medicine and Health Theory, University of Osnabrück, Sedanstraße 115, 49090 Osnabrück, Germany.
authors.forename: Nanna Y
authors.initials: NY
authors.lastname: Schürer
mesh_terms: D001706:Biopsy; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D003357:Cosmetic Techniques; D000067548:Dermal Fillers / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005858:Germany; D006801:Humans; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D019344:Lactic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011091:Polyesters; D011108:Polymers / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D040521:Subcutaneous Tissue / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D015854:Up-Regulation
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D000067548:Dermal Fillers; D011091:Polyesters; D011108:Polymers; D012333:RNA, Messenger; C508960:TGFB1 protein, human; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D019344:Lactic Acid; C033616:poly(lactide)
keywords: (Myo-)fibroblasts; Collagen type I; Collagen type III; Filler; Macrophages; Poly-l-lactic acid