Customization of an Ultrafast Thiol–Norbornene Photo-Cross-Linkable Hyaluronic Acid–Gelatin Bioink for Extrusion-Based 3D Bioprinting

• Published in: Biomacromolecules 2023-11, Vol.24 (11), p.5414-5427
• Main Authors: Xiao, Xiong, Yang, Yuchu, Lai, Yushang, Huang, Ziwei, Li, Chenxi, Yang, Shaojie, Niu, Chuan, Yang, Liping, Feng, Li
• Format: Article
• Language: English
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/acs.biomac.3c00887

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