Photoclick polysaccharide-based bioinks with an extended biofabrication window for 3D embedded bioprinting

Although significant breakthroughs have been achieved in constructing complex tissue/organ models in vitro, the progress of 3D bioprinting has long been subjected to trade-offs between the printability and biocompatibility of bioinks. Methacrylated hyaluronic acid (HAMA) has been widely adopted for 3D bioprinting due to its limited immunogenicity and simple synthetic method. However, the challenges arising from HAMA are its limited mechanical properties, low printing resolution, inhomogeneity networks, and the accumulation of reactive oxygen species (ROS) during polymerization. Here, these limitations are addressed by developing a thiol-norbornene photoclick polysaccharide-based bioink (HC-HN), which is prepared through the modification of hyaluronic acid with norbornene functional groups (Nor) and cysteamine hydrochloride (Cys). Compared with traditional HAMA, the HC-HN bioink via a step-growth polymerization mechanism can realize increased viscoelastic properties, reduced ROS accumulation, and superior shape fidelity in a range of complex structures by 3D embedded bioprinting. To further confirm its potential in 3D bioprinting applications, the HC-HN bioink is employed to print a liver model in vitro, which shows higher albumin secretion and urea production. Furthermore, a markedly increased sensitivity to drug-induced hepatotoxicity is observed in the bioprinted liver model compared to the 2D culture. Therefore, the proposed photoclick HC-HN bioink expands the palette of available polysaccharide-based bioinks and greatly extends the biofabrication window to broaden the application opportunities of 3D bioprinting.