Customization\nof an Ultrafast Thiol–Norbornene\nPhoto-Cross-Linkable Hyaluronic Acid–Gelatin Bioink for Extrusion-Based\n3D Bioprinting

Abstract

Light-based three-dimensional (3D) bioprinting has been\nwidely\nstudied in tissue engineering. Despite the fact that free-radical\nchain polymerization-based bioinks like hyaluronic acid methacrylate\n(HAMA) and gelatin methacryloyl (GelMA) have been extensively explored\nin 3D bioprinting, the thiol–ene hydrogel system has attracted\nincreasing attention for its ability in building hydrogel scaffolds\nin an oxygen-tolerant and cell-friendly way. Herein, we report a superfast\ncuring thiol–ene bioink composed of norbornene-modified hyaluronic\nacid (NorHA) and thiolated gelatin (GelSH) for 3D bioprinting. A new\nfacile approach was first introduced in the synthesis of NorHA, which\ncircumvented the cumbersome steps involved in previous works. Additionally,\nafter mixing NorHA with macro-cross-linker GelSH, the customized NorHA/GelSH\nbioinks exhibited fascinating superiorities over the gold standard\nGelMA bioinks, such as an ultrafast curing rate (1–5 s), much\nlowered photoinitiator concentration (0.03% w/v), and flexible physical\nperformances. Moreover, the NorHA/GelSH hydrogel greatly avoided excess\nROS generation, which is important for the survival of the encapsulated\ncells. Last, compared with the GelMA scaffold, the 3D-printed NorHA/GelSH\nscaffold not only exhibited excellent cell viability but also guaranteed\ncell proliferation, revealing its superior bioactivity. In conclusion,\nthe NorHA/GelSH system is a promising candidate for 3D bioprinting\nand tissue engineering applications.