Scaled up Microfluidic Screening of Skin Care Ingredients Using Multilayer Skin Spheroids

多组分护肤品的开发是一项时间、劳动力和成本密集型的任务，从识别有前途的单个活性成分（AI）开始，并继续通过使用动物模型优化配方。在动物模型上进行实验是昂贵的，耗时的，并且需要特殊的技能。此外，出于伦理考虑，许多国家禁止使用动物模型来测试化妆品成分，包括加拿大的S-214“无动物化妆品法案”，该法案禁止销售在动物身上试用的化妆品。因此，高度推荐和青睐使用可靠的体外皮肤模型，如多细胞球状体/类器官。在过去的两年中，PI团队与巴斯夫公司合作，设计并开发了一个微流体（MF）平台，用于从人类皮肤成纤维细胞中生长大量皮肤球体阵列。在案例研究中，证明了该MF平台的实用性，用于高通量筛选维生素C对成纤维细胞球体蛋白质产生的影响。目前拟议的一年期研究项目旨在（i）通过用成纤维细胞-角质形成细胞球状体取代成纤维细胞球状体来扩展这种简单的皮肤模型，以更好地复制表皮/真皮皮肤结构，以及（ii）设计和开发MF平台的新操作模式，从而能够扩大多种AI及其组合的用户友好的通量筛选。这种芯片上的皮肤球体平台的开发是化妆品和皮肤护理领域实现时间、成本和劳动力高效制造的重要一步，在制药领域具有潜在应用，对加拿大具有战略重要性。

Development of multicomponent skin care products is a time-, labor- and cost-intensive task that begins from the identification of a promising individual active ingredient (AI) and continues to the optimization of formulations by using animal models. Experiments on animal models are expensive, time-consuming, and require special skills. Furthermore, due to the ethical considerations, the use of animal models for testing cosmetic ingredients is banned by many countries, including Canadian S-214 "The Cruelty Free Cosmetics Act" that prohibits the sale of cosmetics tried on animals. Therefore, the utilization of reliable in vitro skin models such as multicellular spheroids/organoids is highly recommended and favored. Over the past two years, in collaboration with BASF Corporation, the PI group has designed and developed a microfluidic (MF) platform to grow massive arrays of skin spheroids from human dermal fibroblasts. In the case study, the utility of this MF platform was demonstrated for high-throughput screening of the effect of vitamin C on protein production by fibroblast spheroids. The current one-year proposed research project aims at (i) extending this simplistic skin model by replacing of fibroblast spheroids with fibroblast-keratinocyte spheroids to better replicate an epidermal/dermal skin structure and (ii) designing and developing a new mode of operation of the MF platform that would enable scaled up user-friendly throughput screening of multiple AIs and their combinations. The development of this skin spheroid-on-a-chip platform is a vital step toward time-, cost- and labor-effective manufacturing in the cosmetic and skin care fields, with a potential application in the area of pharmaceuticals, which are of strategic importance for Canada.