3D micromesh-based hybrid bioprinting: multidimensional liquid patterning for 3D microtissue engineering

Bioprinting has been widely used to fabricate tissue engineering scaffolds and develop in vitro tissue/tumor models. Bioprinting has enabled the fabrication of complex 3D structures using different polymers and hydrogels. However, relatively low resolution and long fabrication times due to the extrusion process has resulted in limited practices for cell-based applications. Here, we present a 3D hybrid-micromesh assisted bioprinting (Hy-MAP) method that combines digital light projection (DLP) 3D-printed micromesh scaffold structures and sequential hydrogel patterning. This novel method of bioprinting enables rapid cell coculture through the allowance of various methods, including injection, dipping and draining. This approach enables the construction of mesoscale (1-50 mm) complex 3D hydrogel structures by extending the micropost-based patterning that has been demonstrated in 2D microfluidic channels to 3D channel networks. We established the design rules for Hy-MAP through both analytical and experimental investigations of the capillary bursting pressure (CBP) dependence on the size and geometry of the mesh as well as other physical parameters. Vascularized tumor spheroids were formed with Hy-MAP by culturing endothelial cells, stromal cell mixtures and tumor spheroids inside separate but adjacent compartments. The novel approach described in this work will provide an alternative method for fabricating mesoscale implantable tissue engineering constructs and organ-on-a-chip applications.