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

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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.