Noh Insup, Kim Nahye, Tran Hao Nguyen, Lee Jaehoo, Lee Chibum
1Department of Chemical and Biomolecular Engineering, Seoul National University of Science and Technology, Seoul, 01811 Republic of Korea.
2Convergence Institute of Biomedical Engineering and Biomaterials, Seoul National University of Science and Technology, Seoul, 01811 Republic of Korea.
Biomater Res. 2019 Feb 6;23:3. doi: 10.1186/s40824-018-0152-8. eCollection 2019.
After recognition of 3D printing and injectable hydrogel as a critical issue in tissue/organ engineering and regenerative medicine society, many hydrogels as bioinks have been developed worldwide by using polymeric biomaterials such as gelatin, alginate, hyaluronic acid and others. Even though some gels have shown good performances in 3D bioprinting, still their performances do not meet the requirements enough to be used as a bioink in tissue engineering.
In this study, a hydrogel consisting of three biocompatible biomaterials such as hyaluronic acid (HA), hydroxyethyl acrylate (HEA) and gelatin-methacryloyl, i.e. HA-g-pHEA-gelatin gel, has been evaluated for its possibility as a bioprinting gel, a bioink. Hydrogel synthesis was obtained by graft polymerization of HEA to HA and then grafting of gelatin- methacryloyl via radical polymerization mechanism. Physical and biological properties of the HA-based hydrogels fabricated with different concentrations of methacrylic anhydride (6 and 8%) for gelatin-methacryloylation have been evaluated such as swelling, rheology, morphology, cell compatibility, and delivery of small molecular dimethyloxalylglycine. Printings of HA-g-pHEA-Gelatin gel and its bioink with bone cell loaded in lattice forms were also evaluated by using home-built multi-material (3D bio-) printing system.
The experimental results demonstrated that the HA-g-pHEA-gelatin hydrogel showed both stable rheology properties and excellent biocompatibility, and the gel showed printability in good shape. The bone cells in bioinks of the lattice-printed scaffolds were viable. This study showed HA-g-pHEA-Gelatin gel's potential as a bioink or its tissue engineering applications in injectable and 3D bioprinting forms.
在3D打印和可注射水凝胶被视为组织/器官工程及再生医学领域的关键问题之后，全球已利用诸如明胶、藻酸盐、透明质酸等聚合生物材料开发了许多作为生物墨水的水凝胶。尽管一些水凝胶在3D生物打印中表现出良好性能，但它们的性能仍不足以满足在组织工程中用作生物墨水的要求。
在本研究中，对一种由透明质酸（HA）、丙烯酸羟乙酯（HEA）和甲基丙烯酰化明胶这三种生物相容性生物材料组成的水凝胶，即HA-g-pHEA-明胶水凝胶，作为生物打印凝胶（生物墨水）的可能性进行了评估。通过HEA接枝到HA上，然后通过自由基聚合机制接枝甲基丙烯酰化明胶来合成水凝胶。对用不同浓度（6%和8%）的甲基丙烯酸酐进行甲基丙烯酰化制备的基于HA的水凝胶的物理和生物学性质进行了评估，如溶胀、流变学、形态学、细胞相容性以及小分子二甲基草酰甘氨酸的递送。还使用自制的多材料（3D生物）打印系统对负载有骨细胞的HA-g-pHEA-明胶水凝胶及其生物墨水进行了点阵形式的打印评估。
实验结果表明，HA-g-pHEA-明胶水凝胶具有稳定的流变学性质和优异的生物相容性，并且该凝胶具有良好的可打印形状。点阵打印支架生物墨水中的骨细胞具有活性。本研究显示了HA-g-pHEA-明胶水凝胶作为生物墨水在可注射和3D生物打印形式中的组织工程应用潜力。
