I-Corps: Spheroidal engineered tissues for more efficient drug discovery

I-Corps：球形工程组织可提高药物发现效率

• 批准号: 2107931
• 负责人: Elizabeth Lipke
• 金额: $ 5万
• 依托单位: Auburn University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2107931&HistoricalAwards=false
• 关键词: Corps; Spheroidal; engineered; tissues; more

The broader impact/commercial potential of this I-Corps project is the development of a drug testing model that enables pharmaceutical companies to eliminate ineffective drug candidates at much earlier stages in the research and development (R&D) process. For the past 10 years, pharmaceutical companies have been experiencing a decrease in R&D returns on drug development. One of the reasons for the decrease, is that most of the drugs entering clinical trials fail in this final and most costly stage. Currently, screening begins with 2-Dimensional (2D) cell cultures and progresses to animal models. Both systems have inherent deficiencies in replicating human disease. The proposed technology uses more effective 3D tissue models for drug screening by providing a more physiologically-relevant drug response while being compatible with currently available, high-throughput screening platforms. This technology has the potential to increase the work efficiency of researchers and other end-users, reduce false positive drug candidates at early stages to increase R&D returns for the pharmaceutical companies, and reduce healthcare costs for patients. In addition, the proposed technology may enable faster development of new therapies.This I-Corps project is based on the development of advanced 3D cell-laden hydrogel microspheroids for drug screening. Currently used models for pre-clinical drug testing have inherent deficiencies in replicating human disease. 3D spheroidal cell aggregates have been established as more effective models for cancer drug screening; However, existing systems lack the homogeneity, cellular microenvironmental control, and total cell numbers needed to perform high fidelity endpoint screening assays and obtain the quality and types of information that researchers require. In addition, many types of cancer cells do not consistently form 3D aggregates. Therefore, there is a need for more advanced 3D spheroidal models that can support high cell density, multiple cell types, and modulation of cellular microenvironment. Using a custom-developed microfluidic encapsualtion platform, cell-laden microspheroids may be produced at an extremely fast speed using photocrosslinkable hydrogel materials. Compared to self-aggregation and other competing technologies, the proposed technology may provide greater flexibility to manipulate the cellular microenvironment, such as stiffness, and may include multiple supporting cell types, such as highly important stromal and immune cells. Additionally, higher numbers of cells may be included per well compared to cell aggregates, making highly sensitive endpoint analyses feasible on a per well basis.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这个I-Corps项目的更广泛的影响/商业潜力是开发一种药物测试模型，使制药公司能够在研究和开发（R D）过程的早期阶段淘汰无效的候选药物。在过去的10年里，制药公司一直在经历药物开发的研发回报下降。减少的原因之一是大多数进入临床试验的药物在最后和最昂贵的阶段失败。目前，筛选从二维（2D）细胞培养开始，并发展到动物模型。这两种系统在复制人类疾病方面都有固有的缺陷。所提出的技术使用更有效的3D组织模型进行药物筛选，提供更生理相关的药物反应，同时与目前可用的高通量筛选平台兼容。这项技术有可能提高研究人员和其他最终用户的工作效率，减少早期阶段的假阳性候选药物，以增加制药公司的研发回报，并降低患者的医疗成本。此外，拟议的技术可能使新疗法的开发更快。这个I-Corps项目是基于开发用于药物筛选的先进的3D细胞负载水凝胶微球体。目前用于临床前药物测试的模型在复制人类疾病方面具有固有缺陷。3D球状细胞聚集体已被建立为癌症药物筛选的更有效模型;然而，现有系统缺乏进行高保真终点筛选测定并获得研究人员所需信息的质量和类型所需的均匀性、细胞微环境控制和总细胞数量。此外，许多类型的癌细胞并不一致地形成3D聚集体。因此，需要能够支持高细胞密度、多种细胞类型和细胞微环境调节的更先进的3D球状模型。使用定制开发的微流体纯化平台，可以使用可光交联的水凝胶材料以极快的速度产生载有细胞的微球体。与自聚集和其他竞争技术相比，所提出的技术可以提供更大的灵活性来操纵细胞微环境，例如刚度，并且可以包括多种支持细胞类型，例如高度重要的基质细胞和免疫细胞。此外，与细胞聚集体相比，每孔可包含更多的细胞，使得每孔高灵敏度终点分析成为可能。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。