HP-NTU Digital Manufacturing Corporate Lab, Nanyang Technological University (NTU), 65 Nanyang Avenue, 637460, Singapore.
Singapore Centre for 3D Printing (SC3DP), School of Mechanical and Aerospace Engineering, Nanyang Technological University (NTU), 50 Nanyang Avenue, 639798, Singapore.
J Mater Chem B. 2022 Aug 10;10(31):5989-6000. doi: 10.1039/d2tb00442a.
Material jetting bioprinting is a highly promising three-dimensional (3D) bioprinting technique that facilitates drop-on-demand (DOD) deposition of biomaterials and cells at pre-defined positions with high precision and resolution. A major challenge that hinders the prevalent use of the material jetting bioprinting technique is due to its limited range of printable hydrogel-based bio-inks. As a proof-of-concept, further modifications were made to gelatin methacrylate (GelMA), a gold-standard bio-ink, to improve its printability in a thermal inkjet bioprinter (HP Inc. D300e Digital Dispenser). A two-step modification process comprising saponification and heat treatment was performed; the GelMA bio-ink was first modified a saponification process under highly alkali conditions to obtain saponified GelMA (SP-GelMA), followed by heat treatment an autoclaving process to obtain heat-treated SP-GelMA (HSP-GelMA). The bio-ink modification process was optimized by evaluating the material properties of the GelMA bio-inks rheological characterization, the bio-ink crosslinking test, nuclear magnetic resonance (NMR) spectroscopy and the material swelling ratio after different numbers of heat treatment cycles (0, 1, 2 and 3 cycles). Lastly, size-exclusion chromatography with multi-angle light scattering (SEC-MALS) was performed to determine the effect of heat treatment on the molecular weight of the bio-inks. In this work, the 4% H2SP-GelMA bio-inks (after 2 heat treatment cycles) demonstrated good printability and biocompatibility (in terms of cell viability and proliferation profile). Furthermore, thermal inkjet bioprinting of the modified hydrogel-based bio-ink (a two-step modification process comprising saponification and heat treatment) direct/indirect cell patterning is a facile approach for potential fundamental cell-cell and cell-material interaction studies.
材料喷射生物打印是一种极具前景的三维（3D）生物打印技术，它能够以高精度和高分辨率在预定位置按需喷射（DOD）生物材料和细胞。限制材料喷射生物打印技术广泛应用的一个主要挑战是其可打印的水凝胶基生物墨水范围有限。作为概念验证，进一步修改了明胶甲基丙烯酸盐（GelMA），一种金标准生物墨水，以提高其在热喷墨生物打印机（HP Inc. D300e 数字分配器）中的打印性能。进行了两步修饰过程，包括皂化和热处理；首先将 GelMA 生物墨水在高碱性条件下进行皂化处理，得到皂化 GelMA（SP-GelMA），然后进行热处理，在高压釜中进行处理，得到热处理的 SP-GelMA（HSP-GelMA）。通过流变特性、生物墨水交联测试、核磁共振（NMR）光谱和不同热处理循环次数（0、1、2 和 3 次）后材料溶胀率来评估 GelMA 生物墨水的材料性能，优化生物墨水修饰过程。最后，通过凝胶渗透色谱与多角度光散射（SEC-MALS）来确定热处理对生物墨水分子量的影响。在这项工作中，4% H2SP-GelMA 生物墨水（经过 2 次热处理循环）表现出良好的可打印性和生物相容性（细胞活力和增殖情况）。此外，经过两步修饰（皂化和热处理）的改性水凝胶基生物墨水的热喷墨生物打印可直接/间接进行细胞图案化，这是一种用于潜在的基础细胞-细胞和细胞-材料相互作用研究的简单方法。
