Skin is widely used as a drug delivery route due to its easy access and the possibility of using relatively painless methods for the administration of bioactive molecules. However, the barrier properties of the skin, along with its multilayer structure, impose severe restrictions on drug transport and bioavailability. Thus, bioengineered models aimed at emulating the skin have been developed not only for optimizing the transdermal transport of different drugs and testing the safety and toxicity of substances but also for understanding the biological processes behind skin wounds. Even though in vivo research is often preferred to study biological processes involving the skin, in vitro and ex vivo strategies have been gaining increasing relevance in recent years. Indeed, there is a noticeably increasing adoption of in vitro and ex vivo methods by internationally accepted guidelines. Furthermore, microfluidic organ-on-a-chip devices are nowadays emerging as valuable tools for functional and behavioural skin emulation. Challenges in miniaturization, automation and reliability still need to be addressed in order to create skin models that can predict skin behaviour in a robust, high-throughput manner, while being compliant with regulatory issues, standards and guidelines. In this review, skin models for transdermal transport, wound repair and cutaneous toxicity will be discussed with a focus on high-throughput strategies. Novel microfluidic strategies driven by advancements in microfabrication technologies will also be revised as a way to improve the efficiency of existing models, both in terms of complexity and throughput.

中文翻译：

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皮肤毒性、透皮转运和伤口修复的皮肤模型

皮肤被广泛用作药物输送途径，因为它易于接近并且可以使用相对无痛的方法来施用生物活性分子。然而，皮肤的屏障特性及其多层结构对药物转运和生物利用度施加了严格的限制。因此，开发了旨在模拟皮肤的生物工程模型，不仅可以优化不同药物的透皮运输和测试物质的安全性和毒性，而且可以了解皮肤伤口背后的生物过程。尽管体内研究通常更适合研究涉及皮肤的生物过程，但近年来体外和离体策略已变得越来越重要。事实上，国际公认的指南越来越多地采用体外和离体方法。此外，微流控芯片器官设备如今正在成为功能和行为皮肤模拟的有价值的工具。仍然需要解决小型化、自动化和可靠性方面的挑战，以便创建能够以稳健、高通量的方式预测皮肤行为的皮肤模型，同时符合监管问题、标准和指南。在这篇综述中，将讨论用于透皮运输、伤口修复和皮肤毒性的皮肤模型，重点是高通量策略。由微加工技术进步驱动的新型微流体策略也将被修订，作为提高现有模型在复杂性和吞吐量方面效率的一种方式。