Advancing in vitro models for high-throughput 3D bioprinting

Abstract

Three-dimensional in vitro models have been proposed as a solution to reduce the high failure rates in clinical trials. Even so, there is a clear lack of techniques capable of creating these cell culture models in a straightforward, cost-effective, and rapid manner, enabling researchers and companies to perform large-scale screenings. One promising candidate to address this need is three-dimensional bioprinting, a technology that can generate viable constructs using biomaterials, cells, and biological molecules. In this context, CELLINK has developed the BIO CELLX biodispenser, which combines liquid dispensing and bioprinting in a highly automated system, significantly reducing human intervention. Despite its potential, it remains uncertain whether this technology can effectively accelerate the laborious processes currently associated with preclinical stages. This study evaluates the key factors necessary for the implementation of BIO CELLX as a high-throughput bioprinter and explores workflow optimizations that could enhance both the dispensing process and the resulting outcomes. The workflow has been validated for new software release and hardware modifications to achieve full functionality, demonstrating high droplet accuracy and uniform mixing. Results indicate that increasing the number of mixing cycles does not negatively impact cell viability; on the contrary, it enhances homogeneous cell density and overall cell viability. Additionally, the performed experiments suggest that the usage of nozzles with larger diameters, along with adapted dispensing parameters, can improve droplet centralization. This project provides an in-depth analysis, highlighting crucial elements required to achieve a precise and efficient three-dimensional bioprinter.