Sebastian Fischer1, Tobias Hirsch, Yannick Diehm, Jurij Kiefer, Ericka M Bueno, Maximilian Kueckelhaus, Thomas Kremer, Christoph Hirche, Ulrich Kneser, Bohdan Pomahac. 1. 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.
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.
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: Yannick Fabian Diehm; Katharina Marstaller; Anna-Maria Seckler; Martin Reinhold Berger; Michael Zepp; Matthias Martin Gaida; Julia Thomé; Dimitra Kotsougiani-Fischer; Ulrich Kneser; Sebastian Fischer Journal: Breast Cancer Date: 2022-02-07 Impact factor: 4.239
Authors: Yannick F Diehm; Dimitra Kotsougiani-Fischer; Elena Porst; Valentin Haug; Laura C Siegwart; Daniel Overhoff; Ulrich Kneser; Sebastian Fischer Journal: PLoS One Date: 2022-07-06 Impact factor: 3.752
Authors: Sebastian Fischer; Christoph Hirche; Yannick Diehm; Kristo Nuutila; Jurij Kiefer; Emre Gazyakan; Ericka M Bueno; Thomas Kremer; Ulrich Kneser; Bohdan Pomahac Journal: PLoS One Date: 2016-05-27 Impact factor: 3.240
Authors: Denis V Krakhotkin; David J Ralph; Gideon A Blecher; Volodymyr A Chernylovskyi; Francesco Greco; Evgeny E Bakurov; Ruslan A Bugaev Journal: Asian J Androl Date: 2021 Mar-Apr Impact factor: 3.285