title: Effects of Different Concentrations of Injectable Collagenase Enzyme on Capsular Tissue Around Silicone Implants: A Preliminary Experimental Study for the Development of a New Treatment Strategy.
abstract: OBJECTIVE
  In recent studies, collagen organization was blamed for the formation of capsular contracture which is still a challenging problem after silicone implant-based breast operations. In this study, effects of different concentrations of collagenase enzyme derived from Clostridium histolyticum on the capsular tissue formation around the silicone implants were investigated. The injectable form of collagenase has a routine clinical use in the treatment of both Dupuytren's and Peyronie's diseases.
  
  
  METHODS
  Thirty-two Wistar albino rats were randomized into four groups. A 2 × 1 × 0.3-cm-sized silicone block was inserted inside a dorsal subcutaneous pocket in all groups. After 2 months of insertion, capsule thicknesses around the implants were detected under ultrasonography. This was followed by injection of isotonic saline, 150, 300, and 600 IU in Gr-1, 2, 3, and 4, respectively. All the animals were sacrificed at the end of the first week for histologic sampling to determine fibroblast proliferation, vessel density of the tissue, necrosis, edema, inflammation, and capsule thickness. All the data were statistically analyzed using Kruskal-Wallis and Mann-Whitney U tests and compared for significance of the results.
  
  
  RESULTS
  There was no significant difference in terms of capsule thinning between the 300 and 600 IU groups but in both groups thinning was significantly higher than the sham group. In the 150 IU group there was no significant thinning as compared to the sham group (p > 0.05). However, complications such as skin necrosis, infection, and seroma formation were seen only in the 600 IU injection group. The optimal safe and effective dose of the enzyme was accepted as 300 IU. The 300 IU injection provided up to 89 % thinning in the capsule tissue. There was thinning of the collagen bundles parallel to capsule thickness. In the 600 IU group, micro-pores were encountered at the thinnest points.
  
  
  CONCLUSIONS
  However, the late results and recurrence rates of capsular contracture were not included in this study; collagenase seemed effective for the reduction of capsular tissue around the implants.
  
  
  METHODS
  This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
authors.affiliation: Department of Plastic Reconstructive and Aesthetic Surgery, Dr. Lütfi Kırdar Kartal Training and Research Hospital, Acıbadem Mh. Gömeç Sk. Sabancı-1 Sitesi 8/16 Kadıköy, Kartal, Istanbul, 34718, Turkey. yesiloglunebil@yahoo.com.
authors.forename: Nebil
authors.initials: N
authors.lastname: Yeşiloğlu
authors.affiliation: Department of Plastic Reconstructive and Aesthetic Surgery, Dr. Lütfi Kırdar Kartal Training and Research Hospital, Acıbadem Mh. Gömeç Sk. Sabancı-1 Sitesi 8/16 Kadıköy, Kartal, Istanbul, 34718, Turkey.
authors.forename: Gökhan
authors.initials: G
authors.lastname: Temiz
authors.affiliation: Department of Plastic Reconstructive and Aesthetic Surgery, Dr. Lütfi Kırdar Kartal Training and Research Hospital, Acıbadem Mh. Gömeç Sk. Sabancı-1 Sitesi 8/16 Kadıköy, Kartal, Istanbul, 34718, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Sarıcı
authors.affiliation: Department of Plastic Reconstructive and Aesthetic Surgery, Bezmialem Vakıf University Medical Faculty, Fatih, Istanbul, Turkey.
authors.forename: Kemalettin
authors.initials: K
authors.lastname: Yıldız
authors.affiliation: Department of Plastic Reconstructive and Aesthetic Surgery, Dr. Lütfi Kırdar Kartal Training and Research Hospital, Acıbadem Mh. Gömeç Sk. Sabancı-1 Sitesi 8/16 Kadıköy, Kartal, Istanbul, 34718, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Şirinoğlu
authors.affiliation: Department of Plastic Reconstructive and Aesthetic Surgery, Dr. Lütfi Kırdar Kartal Training and Research Hospital, Acıbadem Mh. Gömeç Sk. Sabancı-1 Sitesi 8/16 Kadıköy, Kartal, Istanbul, 34718, Turkey.
authors.forename: Emre
authors.initials: E
authors.lastname: Güvercin
authors.affiliation: Department of Plastic Reconstructive and Aesthetic Surgery, Dr. Lütfi Kırdar Kartal Training and Research Hospital, Acıbadem Mh. Gömeç Sk. Sabancı-1 Sitesi 8/16 Kadıköy, Kartal, Istanbul, 34718, Turkey.
authors.forename: Ali Cem
authors.initials: AC
authors.lastname: Akpınar
authors.affiliation: Department of Plastic Reconstructive and Aesthetic Surgery, Dr. Lütfi Kırdar Kartal Training and Research Hospital, Acıbadem Mh. Gömeç Sk. Sabancı-1 Sitesi 8/16 Kadıköy, Kartal, Istanbul, 34718, Turkey.
authors.forename: Gaye Taylan
authors.initials: GT
authors.lastname: Filinte
authors.affiliation: Department of Pathology, Marmara University, Istanbul, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Filinte
mesh_terms: D000818:Animals; D018427:Breast Implants / Q000009:adverse effects*; D017364:Collagenases / Q000008:administration & dosage*; D005260:Female; D057910:Implant Capsular Contracture / Q000188:drug therapy* / Q000209:etiology*; D015552:Injections, Intralesional; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020034:Silicone Gels / Q000009:adverse effects*
chemical_list: D020034:Silicone Gels; D017364:Collagenases
keywords: Breast implants; Capsular contracture; Clostridium histolyticum collagenase; Silicone implants