title: Efficacy and Safety of the Collagenase of the Bacterium Clostridium Histolyticum for the Treatment of Capsular Contracture after Silicone Implants: Ex-Vivo Study on Human Tissue.
abstract: BACKGROUND
  The fibrotic capsule that surrounds silicone implants consists mainly of collagen. The FDA-approved collagenase of the bacterium clostridium histolyticum provides a reasonable treatment option. Safety and efficacy at the female breast site must be evaluated before clinical utilization.
  
  
  METHODS
  We incubated 20 samples of fibrotic capsule as well as 12 full thickness skin grafts harvested from the female breast site for 24 hours with different doses of collagenase. Outcome measures involved histological assessment of thickness and density of the capsule tissue as well as the skin grafts. Furthermore, we performed a collagen assay and immunohistochemistry staining for collagen subtypes.
  
  
  RESULTS
  Collagenase treatment was able to degrade human capsule contracture tissue ex-vivo. The remaining collagen subtype after degradation was type 4 only. 0.3 mg/ml of collagenase was most effective in reducing capsule thickness when compared with higher concentrations. Of note, effectiveness was inversely related to capsule density, such that there was less reduction in thickness with higher capsule densities and vice versa. Furthermore, the application of 0.3mg/ml collagenase did not lead to thinning or perforation of full thickness skin grafts.
  
  
  CONCLUSIONS
  Adjustment of collagenase dose will depend on thickness and density of the contracted capsule. A concentration of 0.3mg/ml seems to be safe and effective in an ex-vivo setting. The remaining collagen subtype 4 is suitable to serve as a neo-capsule/acellular tissue matrix. Collagenase treatment for capsular contracture may soon become a clinical reality.
authors.affiliation: Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.|Department of Hand-, Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Fischer
authors.affiliation: Department of Hand-, Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hirche
authors.affiliation: Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.|Department of Hand-, Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Diehm
authors.affiliation: Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Kristo
authors.initials: K
authors.lastname: Nuutila
authors.affiliation: Department of Hand-, Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany.
authors.forename: Jurij
authors.initials: J
authors.lastname: Kiefer
authors.affiliation: Department of Hand-, Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany.
authors.forename: Emre
authors.initials: E
authors.lastname: Gazyakan
authors.affiliation: Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Ericka M
authors.initials: EM
authors.lastname: Bueno
authors.affiliation: Department of Hand-, Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kremer
authors.affiliation: Department of Hand-, Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kneser
authors.affiliation: Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Bohdan
authors.initials: B
authors.lastname: Pomahac
mesh_terms: D018427:Breast Implants / Q000009:adverse effects*; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D057910:Implant Capsular Contracture / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D003012:Microbial Collagenase / Q000494:pharmacology* / Q000627:therapeutic use; D020034:Silicone Gels / Q000009:adverse effects*; D012867:Skin / Q000187:drug effects / Q000378:metabolism
chemical_list: D020034:Silicone Gels; D003094:Collagen; D003012:Microbial Collagenase