Our laboratory is focusing on creating miniaturized tissue constructs containing several layers of human cell types in biomimetic hydrogels (bioinks) on several biochip platforms using “microarray three-dimensional (3D) bioprinting” technology. The microarray 3D bioprinting technology is a robotic microsolenoid valve-driven printing technology manifested on several microarray biochip platforms, including a micropillar chip, a microwell chip, and 384-pillar plates with a flat tip surface or with sidewalls. These 3D-printed tissues with cells obtained from patients can be used as promising disease models for screening therapeutic drugs for individual patients, thereby potentially revolutionizing regenerative medicine, oncology, and drug discovery.
Schematics of microarray 3D bioprinting technology for creating human tissues by dispensing multiple human cell types in biomimetic hydrogels layer-by-layer precisely with printing robots. Miniaturized tissue blocks (as small as 1 mm3 ) can be generated by printing several layers of human cell types in photocrosslinkable hydrogels with extracellular matrices and growth factors onto a 384-pillar plate with sidewalls using S+ microarray spotter. After gelation, the 384-pillar plate containing hundreds of biomimetic conditions will be sandwiched with 384-well plates with growth media for rapidly testing optimum microenvironments to create human tissue replicates. Bioprinted human tissues can be tested with compounds, stained with fluorescent dyes, and scanned with S+ scanner for high-content imagining (HCI) of organ functions as well as predictive assessment of drug toxicity. Thus, our technology has great potentials for applications in tissue engineering and disease modeling for rapidly screening therapeutic drugs and studying toxicology.
Despite recent advances in cell spheroid cultures and large-scale “3D bioprinting”, 3D cell culture platforms are still incapable of rapidly creating highly organized multicellular tissue constructs and/or inapplicable to high-throughput compound screening due to several technical limitations, including the large size of bioprinted tissues, the limited diffusion of nutrients and O2 in the core of bioprinted tissues, time-consuming manual optimization of cellular microenvironments, and difficulty in cell imaging in situ and long-term cell culture. In our research, we overcome these limitations by creating in vivo-like mini-tissues via our microarray 3D bioprinting technology.