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Abstract：
The ISO 10993 standards on biocompatibility assessment of medical devices discourage the use of animal tests when reliable and validated in vitro methods are available. A round robin validation study of in vitro reconstructed human epidermis (RhE) assays was performed as potential replacements for rabbit skin irritation testing. The RhE assays were able to accurately identify strong irritants in dilute medical device extracts. However, there was some uncertainty about whether RhE tissues accurately predicted the results of the rabbit skin patch or intracutaneous irritation test. To address that question, this paper presents in vivo data from the round robin and subsequent follow-up studies. The follow-up studies included simultaneous in vitro RhE model and in vivo testing of round robin polymer samples and the results of dual in vitro/in vivo testing of currently marketed medical device components/materials. Our results show for the first time that for both pure chemicals and medical device extracts the intracutaneous rabbit test is more sensitive to detect irritant activity than the rabbit skin patch test. The studies showed that the RhE models produced results that were essentially equivalent to those from the intracutaneous rabbit skin irritation test. Therefore, it is concluded that RhE in vitro models are acceptable replacements for the in vivo rabbit intracutaneous irritation test for evaluating the irritant potential of medical devices.
摘要：
当可靠和经过验证的体外方法可用时，关于医疗器械生物相容性评估的ISO10993标准不鼓励使用动物试验。进行了体外重建人表皮（RhE）测定的循环验证研究，作为兔皮肤刺激测试的潜在替代品。RhE分析能够准确地识别稀释的医疗设备提取物中的强刺激物。然而,对于RhE组织是否准确预测兔皮肤贴片或皮内刺激试验的结果存在一定的不确定性。为了解决这个问题，本文介绍了循环和后续随访研究的体内数据。后续研究包括循环聚合物样品的同时体外RhE模型和体内测试,以及目前市售的医疗装置组件/材料的双重体外/体内测试的结果。我们的结果首次表明，对于纯化学品和医疗器械提取物，皮内兔试验比兔皮肤贴片试验对检测刺激性活性更敏感。研究表明，RhE模型产生的结果基本上等同于皮内兔皮肤刺激测试的结果。因此,结论是，RhE体外模型是评估医疗器械刺激潜力的体内兔皮内刺激试验的可接受替代方法。
