title: The Collagenase of the Bacterium Clostridium histolyticum for the Treatment of Capsular Fibrosis after Silicone Implants.
abstract: BACKGROUND
  The main part of the fibrotic capsule in capsular contracture is collagen. The collagenase of the bacterium Clostridium histolyticum is U.S. Food and Drug Administration approved for the treatment of Dupuytren contracture and might be capable of dissolving the fibrotic capsule surrounding silicone implants.
  
  
  METHODS
  One hundred twenty days after insertion of miniature silicone implants the authors performed in vitro studies (n = 14) for optimum dosage-finding and subsequent in vivo studies (n = 36) to evaluate application method and efficiency. Data analysis involved histologic measurements of capsule thickness and collagen density; 7-T magnetic resonance imaging-based in vivo imaging; and polymerase chain reaction analysis of inflammatory, profibrotic, and antifibrotic markers.
  
  
  RESULTS
  Compared with the control group, each dosage showed significantly thinner capsules after in vitro incubation. Skin digestion occurred in 0, 1 (7 percent), and 11 cases (80 percent) after incubation with 0.3, 0.9, and 1.8 mg/ml, respectively. In vivo application showed a dosage-dependent decrease in capsule formation, which was more prominent in lower capsule parts, seen by magnetic resonance imaging. In vivo skin perforation was seen in two (17 percent) and six cases (50 percent) after injection of 0.3 mg/ml and 0.9 mg/ml, respectively. Profibrotic and inflammatory markers were significantly up-regulated 10 days after collagenase injection.
  
  
  CONCLUSIONS
  The collagenase of C. histolyticum is capable of dissolving the fibrotic capsule surrounding silicone implants. Skin perforation occurred most likely because of mechanical irritation after complete digestion of the capsule. Further studies are required to pave the way for safe clinical application.
authors.affiliation: Boston, Mass.; and Ludwigshafen and Bochum, Germany From the Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School; the Department of Hand-, Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg; and the Department of Plastic and Reconstructive Surgery, Burn Centre, BG University Hospital Bergmannsheil, Ruhr University Bochum.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Fischer
authors.forename: Tobias
authors.initials: T
authors.lastname: Hirsch
authors.forename: Yannick
authors.initials: Y
authors.lastname: Diehm
authors.forename: Jurij
authors.initials: J
authors.lastname: Kiefer
authors.forename: Ericka M
authors.initials: EM
authors.lastname: Bueno
authors.forename: Maximilian
authors.initials: M
authors.lastname: Kueckelhaus
authors.forename: Thomas
authors.initials: T
authors.lastname: Kremer
authors.forename: Christoph
authors.initials: C
authors.lastname: Hirche
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kneser
authors.forename: Bohdan
authors.initials: B
authors.lastname: Pomahac
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D018427:Breast Implants / Q000009:adverse effects*; D047009:Hathewaya histolytica; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000473:pathology; D007150:Immunohistochemistry; D057910:Implant Capsular Contracture / Q000473:pathology* / Q000628:therapy; D008279:Magnetic Resonance Imaging / Q000379:methods; D003012:Microbial Collagenase / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D012016:Reference Values; D020034:Silicone Gels / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D020034:Silicone Gels; D003012:Microbial Collagenase