Printable and biocompatible hydrogels for residual-free and high-throughput printing patient-derived organoid biochips

Abstract

Organoid biochips can replicate the micro-environment and functional traits of human organs in vitro, reflecting the physiological and pathological features of the human body. It provides a new platform for disease modeling and drug screening. However, the manual process of organoid cultivation and biochip construction using decellularized extracellular matrix-based gel is typically complex, expensive, and time-consuming (at least one month), which significantly hinders practical application. Here, we introduce a micro-needle-based pneumatic printing strategy for residual-free and high-throughput construction of patient-derived organoid biochips. By developing printable and biomimetic hydrogels, biopsy samples of cancer tissues can be effectively processed into discrete cells. Patient-derived colorectal cancer (CRC) cells in carboxymethylcellulose (CMC) and sodium alginate modified by adhesion sites exhibit high viability at 92%. Through a microneedle, the cell-ink utilization exceeds 90%. Especially, the organoid biochips can effectively be fabricated, and single cells in biochips can proliferate and differentiate into organoids with typical morphology. Finally, the patient-derived CRC organoids are used as the biochips for drug testing, which give the personalized drug screening information in a week. Overall, through the microprinting strategy and biomimetic hydrogels, the utilization rate of cells and the construction efficiency of organoid chips can be improved. This work provides a new approach for high-throughput printing patient-derived organoid biochips in precision medicine.