Rosengren Agneta, Faxius Linda, Tanaka Noriho, Watanabe Mika, Bjursten Lars M
Lund University, Department of Experimental Research, Malmö University Hospital, S -205 02 Malmö, Sweden.
J Biomed Mater Res A. 2005 Oct 1;75(1):115-22. doi: 10.1002/jbm.a.30431.
To evaluate the predictive value of cytotoxicity testing, the present study compares the in vivo tissue responses to in vitro cytotoxicity before and after implantation. Material toxicity was caused by addition of the toxic substance Zincdiethyldithiocarbamate (ZDEC) that is used as a standard for in vitro cytotoxicity testing. Polyurethane discs with the addition of 0.5% or 1% ZDEC as well as nontoxic discs were inserted in the abdominal wall of rats for 1 day up to 6 weeks. After explantation the foreign body response was analyzed immunohistochemically. An in vitro reanalysis of the explanted reference materials (RMs) revealed remaining high concentrations of toxic compounds after 1-week implantation, whereas no toxicity was seen after 6 weeks implantation. This was reflected in the foreign body response where a significantly thicker capsule and more inflammatory cells were seen at 1 week for the toxic implants. Over time, with decreasing toxicity, these differences disappeared. Test samples that only were subjected to in vitro extraction with water did not elute toxic compounds to the same extent as the in vivo conditions. It is concluded that many clinically useful implant materials may be unnecessarily rejected due to the results of in vitro tests.
为评估细胞毒性测试的预测价值，本研究比较了植入前后体内组织反应与体外细胞毒性。材料毒性是通过添加有毒物质二乙基二硫代氨基甲酸锌（ZDEC）引起的，该物质用作体外细胞毒性测试的标准。添加了0.5%或1%ZDEC的聚氨酯圆盘以及无毒圆盘被植入大鼠腹壁1天至6周。取出后，通过免疫组织化学分析异物反应。对取出的参考材料（RMs）进行的体外重新分析显示，植入1周后仍有高浓度的有毒化合物，而植入6周后未观察到毒性。这反映在异物反应中，有毒植入物在1周时可见明显更厚的包膜和更多的炎性细胞。随着时间的推移，随着毒性降低，这些差异消失。仅用水进行体外提取的测试样品洗脱的有毒化合物程度与体内情况不同。得出的结论是，由于体外测试结果，许多临床上有用的植入材料可能会被不必要地拒收。
