EAGER: Collaborative Research: Embedded Section-by-Section Bioprinting (ESB) of Large-Scale Cellular Human Tissue Constructs

Embedded 3D bioprinting has been extensively utilized to fabricate human organ and tissue analogs; however, creating human tissue constructs with large scale and high cell viability remains a significant challenge. The research goal of this EArly-concept Grant for Exploratory Research (EAGER) project is to establish a new embedded section-by-section bioprinting process aimed at achieving a high cell viability during the fabrication of large-scale human tissue constructs. In this new process, a human-relevant sized construct will be segmented into multiple smaller sections and sequentially printed within a support bath using a short nozzle. Between sections, a special material will be added to the support bath, and its viscosity and flow behavior will be adjusted by changing the temperature. The expected outcomes of this project are 1) identifying cell damage mechanisms in this 3D bioprinting process and 2) elucidating cell damage during the addition of support bath materials. This new 3D bioprinting strategy will facilitate the reconstruction of full-scale human organs and tissues for diverse biomedical applications. The education goal is to enhance the biomanufacturing training through outreach activities, such as bioprinting demonstrations to K-12 students, bioprinting-related curricula for undergraduates and graduates, biomanufacturing-themed activities to attract talented students. This project aims to advance and surpass the state-of-the-art embedded 3D bioprinting processes by ensuring a high initial cell viability of over 80 percent when producing human tissue constructs with dimensions exceeding 20 mm along the printing orientation. Three integrated research objectives will be pursued, including 1) establish a theoretical platform through mechanics modeling and experimentation to identify the cell damage mechanisms at the cellular level and during bioextrusion; 2) elucidate thermal damage to living cells via numerical simulation, modeling, and experiments to optimize key conditions when adding support bath materials; and 3) evaluate the capability of the proposed embedded section-by-section bioprinting process to print large-scale cellular human tissues. The knowledge gained from this project will jump-start the development of advanced support bath materials and innovative 3D bioprinting processes for tissue engineering in the future. 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.