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动密集型和成本密集型的任务，主要是因为必须在皮肤组织上测试大量的活性成分（AIs）及其组合，才能制造出高性能的产品。这个耗时的多步骤过程从确定有前途的人工智能候选物开始，并使用动物模型继续优化多组分配方。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，出于道德考虑，欧盟于2009年禁止化妆品成分的动物模型，2019年，加拿大参议院批准了《无残忍化妆品法案》S-214，禁止销售在动物身上进行测试的化妆品。体外皮肤模型的利用，如多细胞类器官，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，是强烈推荐和青睐的。目前，皮肤类器官模型至少存在以下局限性之一：(i)类器官尺寸分布广泛（导致人工智能筛选的不确定性）；（ii）类器官生长环境控制不良；（iii）增长缓慢；（iv）缺乏高通量人工智能筛选。该合作研究的目标是设计和开发一个皮肤类器官芯片微流控平台，以培养大量异质皮肤类器官（SOs）阵列，并利用该MF平台进行高通量筛选用于皮肤护理的多种ai。将从成纤维细胞和角化细胞中培养出大量的SOs，并暴露于视黄醇（维生素A）和维生素C及其混合物中，作为代表性的ai。用于高通量筛选ai的MF平台的开发是制药，化妆品和护肤领域实现成本和能源效益制造的重要一步。这些工业部门在加拿大具有重要的战略意义，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。所提出的MF技术平台为人工智能的开发和优化提供了一种方法，从而有助于在时间、劳动力和成本效益方面探索和开发具有更高性能的产品。它将使新技术得以扩展，从而提高其获得许可和其他商业活动的潜力。

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.