The Collagenase of the Bacterium Clostridium histolyticum for the Treatment of Capsular Fibrosis after Silicone Implants
The Collagenase of the Bacterium Clostridium histolyticum for the Treatment of Capsular Fibrosis after Silicone Implants
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DOI：
10.1097/prs.0000000000001698
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发表时间：
2015-11-01
影响因子：
3.6
通讯作者：
Pomahac, Bohdan
中科院分区：
文献类型：
--
作者：
Fischer, Sebastian;Hirsch, Tobias;Pomahac, Bohdan
背景：包膜挛缩中纤维化包膜的主要成分是胶原。溶组织梭菌的胶原酶是美国食品药品监督管理局批准用于治疗掌腱膜挛缩的，可能能够溶解硅胶植入物周围的纤维化包膜。方法：在微型硅胶植入体植入后120天，作者进行了体外研究（n = 14）以寻找最佳剂量，随后进行了体内研究（n = 36）评价应用方法和效果。数据分析涉及囊厚度和胶原密度的组织学测量; 7-T磁共振成像为基础的体内成像;和聚合酶链反应分析的炎症，促纤维化，抗纤维化markers.Results：与对照组相比，每个剂量显示显着薄胶囊后，在体外孵育。在0.3、0.9和1.8 mg/ml孵育后，分别有0、1（7%）和11例（80%）发生皮肤消化。在体内应用表明，剂量依赖性减少胶囊的形成，这是更突出的较低的胶囊部分，通过磁共振成像。注射0.3 mg/ml和0.9 mg/ml后，分别在2例（17%）和6例（50%）病例中观察到体内皮肤穿孔。胶原酶注射后10天，促纤维化和炎症标志物显著上调。溶组织剂能够溶解硅胶植入物周围的纤维化包膜。发生皮肤穿孔最有可能是由于胶囊完全消化后的机械刺激。需要进一步的研究为安全的临床应用铺平道路。
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.