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.

当有可靠且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 ISO 10993 标准不鼓励使用动物试验。体外重建人表皮 (RhE) 检测的循环验证研究被用作兔皮肤刺激测试的潜在替代品。RhE 分析能够准确识别稀释医疗器械提取物中的强刺激物。然而，RhE 组织能否准确预测兔皮肤贴片或皮内刺激试验的结果存在一些不确定性。为了解决这个问题，本文提供了循环法和后续后续研究的体内数据。后续研究包括同时体外RHE模型和体内测试循环赛聚合物样品的和双的结果在体外/体内目前市售的医疗器械部件/材料的测试。我们的结果首次表明，对于纯化学品和医疗器械提取物，兔皮内试验比兔皮肤斑贴试验对刺激活性的检​​测更敏感。研究表明，RhE 模型产生的结果与兔皮内刺激试验的结果基本相同。因此，得出的结论是，RhE体外模型可以替代体内兔皮内刺激试验，用于评估医疗器械的刺激潜力。