Hybrid 3D microfluidic bioprinting for the engineering of cancer models and tissue substitutes

Abstract

3D bioprinting is at the forefront of tissue engineering to fabricate complex constructs resembling functional tissues. However, the inability to produce heterogeneous tissues and the lack of spatio-temporal control over the release of bioactive factors are greatly limiting clinical translation. Herein, the combination of 3D bioprinting with high-throughput dispensing using a custom microfluidic system and nanoclay-based inks is presented. This approach was found to enhance printability, retention, and controlled release of bioactive factors. Advanced tissue models were developed to resemble cancer and skeletal tissue, while studying the effect of anti-cancer (Doxorubicin) and pro-osteogenic growth factors (bone morphogenetic protein-2, BMP-2), respectively. The engineering of a new nanoclay ink allowed the sustained release, making it suitable for long-term applications. These findings suggest that by combining 3D bioprinting and high-throughput delivery of nanoclay-based inks a new platform for the engineering of functional tissue constructs can be assembled, offering significant advancements in regenerative medicine.