3D Bioprinting of Methylcellulose/Gelatin-Methacryloyl (MC/GelMA) Bioink with High Shape Integrity

Abstract

The advent of three-dimensional (3D) bioprinting offers a feasible approach to construct complex structures suitable for tissue regeneration, during which cell-laden materials are dispensed on a substrate according to a predesigned structure. However, the lack of ideal printable bioinks with high shape fidelity and improved biological stability remains a major challenge. In this study, methylcellulose/gelatin-methacryloyl (MC/GelMA) bioink with high shape integrity is presented, which takes advantage of the printability of MC and the permanent photo-cross-linking of GelMA under UV irradiation. Although MC demonstrates good printability at room temperature, the lack of cross-linking ability causes distortion and finally dissociation of printed MC in biological media within a few days. However, UV-cross-linked MC/GelMA bioink remains stable in biological media over a period of several months. The shape integrity of MC/GelMA was systematically characterized in terms of yield stress and complex modulus. Unlike pure MC ink, the MC/GelMA ink demonstrated self-supporting behavior once printed due to the higher complex modulus and yield stress induced by GelMA in the system. Shape integrity of MC/GelMA ink resulted in higher resolution and printability which are evaluated by the successful printing of various 1D, 2D, and 3D constructs. Moreover, human primary osteoblasts encapsulated within the MC/GelMA hydrogel show cell viability of >95%. Overall, this work introduces MC/GelMA bioink with high shape integrity and improved biological stability and highlights the importance of rheological properties and post-cross-linking for fabrication of physiologically scaled tissue implants.

Keywords: 3D bioprinting; GelMA; methylcellulose; shape integrity; shear-thinning.