Screening of Active Ingredients for Skin Care in a Microfluidic Skin Organoid Platform

护肤品配方的开发是一项劳力和成本密集型的任务，这主要是因为大量的活性成分(AI)及其组合必须在皮肤组织上进行测试才能生产出高性能的产品。这一耗时的多步骤过程从确定一个有前途的人工智能候选者开始，并继续使用动物模型优化多组分配方。在动物模型上进行实验既昂贵又耗时，而且需要特殊技能。此外，出于伦理考虑，2009年欧盟禁止使用动物模型作为化妆品成分，2019年，加拿大参议院批准了《无残忍化妆品法案》的S-214法案，该法案禁止销售在动物身上测试的化妆品。强烈建议和青睐利用体外皮肤模型，例如多细胞类有机物，器官型微米大小的3D细胞聚集体，复制组织和器官的许多特征。目前，皮肤类有机物模型至少存在以下局限性之一：(I)有机类维度的广泛分布(导致人工智能筛选中的不确定性)；(Ii)有机类生长的环境控制不善；(Iii)生长缓慢；以及(Iv)缺乏高通量的人工智能筛选。拟议合作研究的目标是设计和开发一个皮肤有机化合物芯片微流控平台，以培养大量不同种类的皮肤有机化合物(SOS)，并利用该MF平台高通量筛选多个用于皮肤护理的辅助物质。大量的SOS将从成纤维细胞和角质形成细胞中培养出来，并暴露在视黄醇(维生素A)和维生素C及其混合物中，作为人工智能的代表。用于高通量人工智能筛查的MF平台的开发是朝着制药、化妆品和护肤品领域的成本和能源效益制造迈出的重要一步。这些工业部门在加拿大具有战略重要性，由我们的工业合作伙伴(巴斯夫)在加拿大的11个生产和研发设施代表。拟议的MF技术平台提供了一种开发和优化人工智能系统的方法，从而有助于以时间、劳动力和成本效益的方式探索和开发性能更高的产品。它将使新技术得以扩展，从而增强它们在许可和其他商业活动方面的潜力。

Development of formulations for skin care products is a labor- and cost-intensive task, largely due to a large number of active ingredients (AIs) and their combinations that have to be tested on skin tissue to make a high-performance product. This time-consuming multistep process begins from the identification of a promising AI candidate and continues to optimization of a multicomponent formulation using animal models. Experiments on animal models are expensive, time-consuming, and require special skills. Furthermore, due to the ethical considerations, in 2009 animal models for cosmetic ingredients were banned by the European Union and in 2019, the Senate in Canada approved the S-214 of the Cruelty Free Cosmetics Act that prohibits the sale of cosmetics tested on animals. The utilization of in vitro skin models, e.g., multicellular organoids, organotypic micrometer-size 3D cell aggregates that replicate many features of tissues and organs, is highly recommended and favored. Currently, skin organoid models have at least, one of the following limitations: (i) broad distribution of organoid dimensions (leading to uncertainty in AI screening); (ii) poorly controlled environments for organoid growth; (iii) slow growth; and (iv) the lack of high-throughput AI screening. The objective of the proposed collaborative research is to design and develop a skin organoid-on-a-chip microfluidic platform to grow massive arrays of heterogeneous skin organoids (SOs) and utilize this MF platform for high-throughput screening of multiple AIs for skin care. Massive arrays of SOs will be grown from fibroblasts and keratinocytes, and exposed to Retinol (Vitamin A) and Vitamin C, and their mixtures, acting as representative AIs. The development of the MF platform for high-throughput screening of AIs is a vital step toward cost- and energy-effective manufacturing in the pharmaceutical, cosmetic, and skin care fields. These industrial sectors are of strategic importance in Canada and are represented by 11 production and R&D facilities of our industrial partner (BASF) in Canada. The proposed MF technology platform offers an approach to the development and optimization of AIs, thus contributing to the time-, labor- and cost-effective exploration and development of products with enhanced performance. It will enable the expansion of new technologies, thereby enhancing their potential for licensing and other commercial activities.