title: The Role of Bacterial Biofilm in Adverse Soft-Tissue Filler Reactions: A Combined Laboratory and Clinical Study.
abstract: BACKGROUND
  The development of chronic nodules and granulomatous inflammation after filler injections has been attributed to bacterial biofilm infection. The authors aimed to investigate the relationship between filler and bacterial biofilm using a combined in vitro and in vivo study.
  
  
  METHODS
  In vitro assays to investigate the ability of filler materials to support the growth of Staphylococcus epidermidis biofilm and the effect of multiple needle passes through a biofilm-contaminated surface were designed. Analysis of clinical biopsy specimens from patients presenting with chronic granulomas following filler administration using a number of laboratory tests for biofilm was performed.
  
  
  RESULTS
  All fillers (i.e., hyaluronic acid, polyacrylamide gel, and poly-L-lactic acid) supported the growth of S. epidermidis biofilm in vitro. Multiple needle passes through a biofilm-contaminated surface resulted in significantly increased contamination of filler material by a factor of 10,000 (p < 0.001). Six clinical samples from five patients all demonstrated bacterial biofilm. The mean number of bacteria was found to be 2.2 × 10 bacteria/mg tissue (range, 5.6 × 10 to 3.7 × 10 bacteria/mg tissue). Microbiome analysis detected a predominance of Pseudomonas, Staphylococcus, and Propionibacterium as present in these samples.
  
  
  CONCLUSIONS
  Filler material can support the growth of bacterial biofilm in vitro. Multiple needle passes can significantly increase the risk of filler contamination. Biofilm appears to be associated with high numbers in clinical samples of patients presenting with chronic granulomatous inflammation. Strategies to reduce the risk of bacterial contamination need to be further studied and translated into clinical practice.
  
  
  METHODS
  Therapeutic, V.
authors.affiliation: Sydney, New South Wales, and Melbourne, Victoria, Australia.|From the Surgical Infection Research Group, Faculty of Medicine and Health Sciences, Macquarie University; and the University of Melbourne.
authors.forename: Mayuran
authors.initials: M
authors.lastname: Saththianathan
authors.affiliation: Sydney, New South Wales, and Melbourne, Victoria, Australia.|From the Surgical Infection Research Group, Faculty of Medicine and Health Sciences, Macquarie University; and the University of Melbourne.
authors.forename: Khalid
authors.initials: K
authors.lastname: Johani
authors.affiliation: Sydney, New South Wales, and Melbourne, Victoria, Australia.|From the Surgical Infection Research Group, Faculty of Medicine and Health Sciences, Macquarie University; and the University of Melbourne.
authors.forename: Alaina
authors.initials: A
authors.lastname: Taylor
authors.affiliation: Sydney, New South Wales, and Melbourne, Victoria, Australia.|From the Surgical Infection Research Group, Faculty of Medicine and Health Sciences, Macquarie University; and the University of Melbourne.
authors.forename: Hongua
authors.initials: H
authors.lastname: Hu
authors.affiliation: Sydney, New South Wales, and Melbourne, Victoria, Australia.|From the Surgical Infection Research Group, Faculty of Medicine and Health Sciences, Macquarie University; and the University of Melbourne.
authors.forename: Karen
authors.initials: K
authors.lastname: Vickery
authors.affiliation: Sydney, New South Wales, and Melbourne, Victoria, Australia.|From the Surgical Infection Research Group, Faculty of Medicine and Health Sciences, Macquarie University; and the University of Melbourne.
authors.forename: Peter
authors.initials: P
authors.lastname: Callan
authors.affiliation: Sydney, New South Wales, and Melbourne, Victoria, Australia.|From the Surgical Infection Research Group, Faculty of Medicine and Health Sciences, Macquarie University; and the University of Melbourne.
authors.forename: Anand K
authors.initials: AK
authors.lastname: Deva
mesh_terms: D000180:Acrylic Resins / Q000009:adverse effects*; D018441:Biofilms; D000067548:Dermal Fillers / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011091:Polyesters / Q000009:adverse effects*; D018461:Soft Tissue Infections / Q000209:etiology*; D013203:Staphylococcal Infections / Q000209:etiology*; D013212:Staphylococcus epidermidis / Q000502:physiology*; D046509:Tissue Culture Techniques
chemical_list: D000180:Acrylic Resins; D000067548:Dermal Fillers; D011091:Polyesters; C016680:polyacrylamide gels; C033616:poly(lactide); D006820:Hyaluronic Acid