3D bioprinting of shear-thinning hybrid bioink with excellent bioactivity derived from gellan/alginate and thixotropic magnesium phosphate-based gel

2020 
3D bioprinting is expected to become a strong tool for regenerative medicine, but satisfactory bioinks for printing of constructs containing living cells are lacking due to the rigorous requirement of high printability and biocompatibility, which are often contradictory. Here, we report the development of a novel hybrid bioink by combining rigid gellan gum (GG), flexible sodium alginate (SA), and bioactive substance thixotropic magnesium phosphate-based gel (TMP-BG). The ratio of these components was first optimized to obtain satisfactory gelating, mechanical, rheological, and printing properties. The formulated hybrid GG-SA/TMP-BG bioink had a good printability due to the shear-thinning and its multiple cross-linking by Mg2+ and Ca2+. The tunable mechanical performance of hybrid bioink could simulate various extracelluar matrix of the different tissues and support integrity of 3D printing construct. Moreover, the hybrid bioink induced apatite deposition during immersion in simulated body fluid, and also promoted cell proliferation in vitro. MG-63 osteosarcoma cells were dispersed in the bioink and printed into 3D constructs. The cells exhibited good cell survival due to the shear-thinning property of the bioink and the ion concentration used for cross-linking. The proliferation rate of the cells also significantly exceeded those in non-printed samples. Confocal microscopy revealed homogeneous distribution of cells in the printed constructs, and survival for > 7 d. Therefore, this hybrid bioink has good printability, biocompatibility, mechanical support, and bioactivity. With these properties, it is expected to have promising applications in regenerative medicine.
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