ORGANOTYPIC SKIN CULTURES WITH IMPROVED BARRIERS

许多高度分化的体外表皮和真皮/表皮皮肤 正在开发的模型将非常有用：1） 透皮药物递送系统，2）皮肤移植，和3）真皮 毒性测试 然而，目前的模型都没有准确地 复制了人类皮肤的屏障特性。 除了 无效的障碍研究，这一缺点是显着的，因为它 表明角质形成细胞的基本细胞代谢和生理学 在体外是不正常的。 利用无血清角质形成细胞培养系统，I期研究将 系统地研究所选的各种介质添加剂的效果 特别是为了优化屏障脂质和表皮的形成， 已知在皮肤屏障功能中重要的超微结构。 相 I实验，其中将包括结构评估在轻 和电子显微镜水平，脂质分析，和经表皮 渗透率测量，将证明所提出的实用性 系统 这些研究将为第二阶段的研究奠定基础 这将是对所需营养需求的深入分析， 体外生成具有天然皮肤屏障和功能的皮肤。

Many highly differentiated in vitro epidermal and dermal/epidermal skin models are being developed which would be extremely useful for: 1) transdermal drug delivery systems, 2) skin transplantation, and 3) dermal toxicity testing. However, none of the current models accurately reproduced the barrier properties of human skin. In addition to invalidating barrier studies, this shortcoming is significant since it indicates that the basic keratinocyte cellular metabolism and physiology in vitro is abnormal. Utilizing a serum free keratinocyte culture system, Phase I research will systematically investigate the effect of various media additives chosen specifically to optimize the formation of barrier lipids and epidermal ultrastructure known to be important in the skin barrier function. Phase I experimentation, which will include structural evaluation at the light and electron microscopy levels, lipid analysis, and transepidermal permeability measurements, will demonstrate the utility of the proposed system. These studies will lay the groundwork for Phase II research which will be an in-depth analysis of the nutritional requirements needed to generate skin in vitro with the barrier and function of native skin.