Digital light processing-based bioprinting of microtissue hydrogel arrays using dextran-induced aqueous emulsion ink

Abstract

As a microscale three-dimensional bionic model, a microtissue array is a promising method for disease modeling and drug screening. Digital light processing (DLP) 3D bio-printing technology with the capabilities of excellent printing speed and resolution shows great potential for fabricating microtissue arrays. However, the outcomes of the microtissue arrays using DLP are limited by the shortage of biomaterials. In this work, we prepare hydrogel microtissues by combining DLP printing technology with biphasic bio-ink consisting of gelatin methacrylate (GelMA) and dextran. GelMA/ dextran is mixed to form bio-inks with different volume ratios, which can achieve high-precision printing of various patterns. Due to the presence of dextran, the bio-inks form the internal porous structure of the hydrogel in the printed patterns. The pore size is related to the proportion of dextran in bio-inks, and the pore size of hydrogel becomes smaller with the increase of dextran ratio. In addition, the adipose-derived stem cells (ADSCs) cells encapsulated in the porous hydrogels can maintain a high survival rate of 98.01% after 3 days of culture, and the larger pore size in the hydrogels promotes cell migration. Combining the DLP printing system with the porous hydrogel allows multiple micro-size geometric pattern hydrogels to be printed simultaneously to form microtissue arrays. In this study, a new bio-ink suitable for microtissue arrays is proposed, and a simple, accurate, and high-throughput biological manufacturing method for microtissue arrays is developed, thus providing a valuable tool for drug screening and tissue engineering.