High-throughput Spheroid Bioprinting Technology for Scalable Fabrication of Tissues

ROJECT SUMMARY/ABSTRACT The ability to bioprint cellular aggregates, such as spheroids, in a high-throughput manner into desired patterns or cellular microenvironments is crucial to facilitate fabrication of scalable constructs with cell densities similar to that of native tissues and organs. Despite the progress in spheroid bioprinting technologies, the major shortcomings associated with them, such as poor positioning of spheroids, significant loss of viability and structural integrity, poor repeatability of the process when using non-uniform size spheroids, inability to form complex 3D shapes, and most importantly, the lack of scalability, limit their translation. In this project, we propose a highly unique technology, henceforth referred as “high-throughput spheroid (HTS) bioprinting,” that enables simultaneous bioprinting of several spheroids with an order of magnitude size range and minimal cellular damage, at a high positional precision and an unprecedented speed. The proposed technology is highly versatile and enables the bioprinting of complex structures either (1) onto the surface of gel substrates (i.e., hydrogels) in a scaffold-based manner or (2) within support baths (i.e., sacrificial microgels) in a scaffold-free manner for scalable fabrication of tissues. In Specific Aim 1, we propose to develop HTS bioprinting, which has the capability of depositing several spheroids simultaneously on 3D gel substrates, thus bioprinting a complete layer of the 3D tissue at once in a rapid fashion (i.e., 100 spheroids can be bioprinted in