3D Printing of Cell-Laden Microgel-Based Biphasic Bioink with Heterogeneous Microenvironment for Biomedical Applications

A major challenge in 3D extrusion bioprinting is the limited number of bioink that fulfills the opposing requirements for printability with requisite rheological properties and for functionality with desirable microenvironment. Here, this limitation is addressed by developing a generalizable strategy for formulating a cell-laden microgel-based biphasic (MB) bioink. The MB bioink comprises two components, that is, microgels in close-packed condition providing excellent rheological properties for extrusion bioprinting, and a hydrogel precursor that forms a second polymer network to integrate the microgels together, providing post-printing structural stability. This strategy enables the effective printing of a range of hydrogels into complex structures with high shape fidelity. The MB bioink offers great mechanical tunability without compromising printability, and hyperelasticity with superb cyclic compression and stretch endurance. Moreover, the microgels and hydrogel precursor of the MB bioink can encapsulate different types of cells, together creating a heterogeneous cellular microenvironment at microscale. It is successfully demonstrated that hepatocytes and endothelial cells with spatial cell patterning by using MB bioink induce the cellular reorganization and vascularization, leading to enhanced hepatic functions. The proposed MB bioink expands the palette of available bioinks and opens numerous opportunities for the biomedical applications such as tissue engineering and soft robotics.

Automated summary

A generalizable strategy has been developed to formulate a cell-laden biphasic bioink for 3D extrusion bioprinting, which combines microgels with excellent rheological properties for printing and a hydrogel precursor for structural stability. This approach enables the printing of complex structures with high fidelity and offers great mechanical tunability and hyperelasticity, allowing for the encapsulation of different cell types for creating a heterogeneous cellular microenvironment at microscale. The MB bioink shows promise for various biomedical applications such as tissue engineering and soft robotics.