Abstract：
The FDA Modernization Act 2.0 has brought nonclinical drug evaluation into a new era. In vitro models are widely used and play an important role in modern drug development and evaluation, including early candidate drug screening and preclinical drug efficacy and toxicity assessment. Driven by regulatory steering and facilitated by well-defined physiology, novel in vitro skin models are emerging rapidly, becoming the most advanced area in alternative testing research. The revolutionary technologies bring us many in vitro skin models, either laboratory-developed or commercially available, which were all built to emulate the structure of the natural skin to recapitulate the skin\'s physiological function and particular skin pathology. During the model development, how to achieve balance among complexity, accessibility, capability, and cost-effectiveness remains the core challenge for researchers. This review attempts to introduce the existing in vitro skin models, align them on different dimensions, such as structural complexity, functional maturity, and screening throughput, and provide an update on their current application in various scenarios within the scope of chemical testing and drug development, including testing in genotoxicity, phototoxicity, skin sensitization, corrosion/irritation. Overall, the review will summarize a general strategy for in vitro skin model to enhance future model invention, application, and translation in drug development and evaluation.
摘要：
FDA现代化法案2.0将非临床药物评估带入了一个新时代。体外模型应用广泛,在现代药物开发和评价中发挥着重要作用,包括早期候选药物筛选和临床前药物疗效和毒性评估。在监管指导的推动下，在明确定义的生理学的推动下，新的体外皮肤模型正在迅速出现，成为替代测试研究中最先进的领域。革命性的技术为我们带来了许多体外皮肤模型，实验室开发的或市售的，它们都是为了模仿自然皮肤的结构而建造的，以概括皮肤的生理功能和特定的皮肤病理。在模型开发过程中,如何实现复杂性之间的平衡，可访问性,能力,成本效益仍然是研究人员面临的核心挑战。这篇综述试图介绍现有的体外皮肤模型，将它们对齐在不同的尺寸上，例如结构复杂性，功能成熟度，和筛选吞吐量，并提供其在化学测试和药物开发范围内的各种场景中当前应用的最新信息，包括遗传毒性测试，光毒性，皮肤致敏,腐蚀/刺激。总的来说,这篇综述将总结体外皮肤模型的一般策略，以增强未来的模型发明，应用程序,以及药物开发和评估中的翻译。
