Controlling cellular organization in bioprinting through designed 3D microcompartmentalization

Abstract

Controlling cellular organization is crucial in the biofabrication of tissue-engineered scaffolds, as it affects cell behavior as well as the functionality of mature tissue. Thus far, incorporation of physiochemical cues with cell-size resolution in three-dimensional (3D) scaffolds has proven to be a challenging strategy to direct the desired cellular organization. In this work, a rapid, simple, and cost-effective approach is developed for continuous printing of multicompartmental hydrogel fibers with intrinsic 3D microfilaments to control cellular orientation. A static mixer integrated into a coaxial microfluidic device is utilized to print alginate/gelatin-methacryloyl (GelMA) hydrogel fibers with patterned internal microtopographies. In the engineered microstructure, GelMA compartments provide a cell-favorable environment, while alginate compartments offer morphological and mechanical cues that direct the cellular orientation. It is demonstrated that the organization of the microtopographies, and consequently the cellular alignment, can be tailored by controlling flow parameters in the printing process. Despite the large diameter of the fibers, the precisely tuned internal microtopographies induce excellent cell spreading and alignment, which facilitate rapid cell proliferation and differentiation toward mature biofabricated constructs. This strategy can advance the engineering of functional tissues.