I-Corps: Translation potential of a three-dimensional (3D) microbioreactor for cell and gene therapy manufacturing

Award ID: 2629868

This I-Corps project is based on the development of a miniaturized device for growing cells for cell and gene therapies. Currently, cell and gene therapies including cell therapies for cancer, stem cell-derived beta cells for diabetes, and gene therapies for inherited diseases, offer transformative potential for patients with serious and life-threatening conditions. However, the widespread adoption of these therapies is severely limited by production systems that yield too few cells, produce variable and inconsistent therapeutic products, and result in costs of $300,000 to over $1,000,000 per patient dose making cell and gene therapies among the most expensive medical treatments in the world. This technology aims to address the production barriers through a new class of manufacturing technology that dramatically improves the productivity, consistency, and scalability of cell and gene therapy production. This device has the potential to reduce production costs, enabling more patients to access these life-changing therapies. In addition, the device has the potential to benefit other areas of research that develop methods to regrow, repair, or replace damaged or diseased cells, tissues, and organs. Existing technologies cannot meet the growing demand for scalable, reproducible, and affordable cell manufacturing. This cell culture technology may have the potential to meet the growing demand for cell manufacturing and enable the next generation of cell and gene therapies. This I-Corps project utilizes experiential learning coupled with first-hand investigation of the industry ecosystem to assess the translation potential of a microbioreactor platform for cell and gene therapy manufacturing. Current large-scale cell manufacturing relies on stirred-tank, vertical-wheel, and rocking bioreactors that control bulk culture conditions but fail to regulate the immediate microenvironment surrounding individual cells. This leads to mechanical stress, uncontrolled aggregation, inefficient nutrient transport, low cell yields, and poor batch-to-batch reproducibility. This technology is designed to culture cells inside microscale bioreactors with precisely controlled geometry, which shield cells from shear forces, confine cell masses to ensure efficient diffusion, and provide three-dimensional space for cell growth. This cell-friendly microenvironment has been shown to yield approximately 500 million cells per milliliter, roughly 200-fold higher than conventional stirred-tank bioreactors. In addition, this system may be used for a broad range of therapeutically relevant cell types including cardiomyocytes, beta cells, T cells, endothelial cells, and neural lineages. This technology has the potential to accelerate cell therapy development, reduce manufacturing complexity and cost, and support more flexible and distributed models for producing cell based therapies. 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.

NSF Program Director: Ruth Shuman