Platform Technology to Enhance the Growth of Human Tissues In Vitro for Use in Biomedical Research and the Assessment of New Molecular Entities.

在人类使用之前测试分子的活性是开发新药的重要步骤。目前，由于缺乏适当的测试系统，直接评估化合物在人体组织中的活性和毒性非常具有挑战性。使用常规的二维（2D）细胞培养技术对人细胞进行体外生物医学测试是可能的，然而该测定不代表分子在真实的组织中的真实活性。三维（3D）细胞培养从根本上改善了细胞结构和功能，使得能够形成组织样构建体。该项目涉及一种创新方法的设计，将3D细胞培养技术与新型生物反应器的开发相结合，以维持人体组织用于生物医学检测。这是一个跨学科的项目，利用生物医学，化学和工程方面的专业知识。生物反应器内的灌注模式将由流体动力学模拟的数据告知，以控制培养基流量。生物反应器将包含氧气控制机制。我们假设我们的设计将延长慢性暴露研究和测试新化合物的组织模型的可行性。我们将展示其在老年人皮肤模型中的应用，以检查新的衰老清除分子在衰老过程中对提高皮肤质量的慢性作用。

Testing the activity of molecules prior to human use is an essential step in the development of new drugs. Currently it is very challenging to evaluate compound activity and toxicity in human tissues directly due to the lack of appropriate test systems. In-vitro biomedical tests on human cells are possible using conventional two-dimensional (2D) cell culture techniques however the assays do not represent the true activity of molecules in real tissues. Three-dimensional (3D) cell culture radically improves cell structure and function enabling the formation of tissue-like constructs. This project involves the design of an innovative approach to combining 3D cell culture technology and the development of a novel bioreactor to maintain human tissues for biomedical assays. This is an interdisciplinary project drawing on expertise in biomedicine, chemistry and engineering. The mode of perfusion within the bioreactor will be informed by data from fluid dynamic simulations to control media flow. The bioreactor will incorporate oxygen control mechanisms. We hypothesise that our design will extend the viability of tissue models for chronic exposure studies and the testing new compounds. We will demonstrate its application of aged human skin models to examine the chronic effect of new senolytic molecules to enhance skin quality during ageing.