Soltan Nikoo, Ning Liqun, Mohabatpour Fatemeh, Papagerakis Petros, Chen Xiongbiao
College of Dentistry, University of Saskatchewan, 105 Wiggins Road, Saskatoon, Saskatchewan S7N5E4, Canada.
ACS Biomater Sci Eng. 2019 Jun 10;5(6):2976-2987. doi: 10.1021/acsbiomaterials.9b00167. Epub 2019 May 22.
Three-dimensional (3D) bioprinting is a promising technique used to fabricate scaffolds from hydrogels with living cells. However, the printability of hydrogels in bioprinting has not been adequately studied. The aim of this study was to quantitatively characterize the printability and cell viability of alginate dialdehyde (ADA)-gelatin (Gel) hydrogels for bioprinting. ADA-Gel hydrogels of various concentrations were synthesized and characterized using Fourier transform infrared spectroscopy, along with rheological tests for measuring storage and loss moduli. Scaffolds (with an area of 11 × 11 mm) of 1, 2, and 13 layers were fabricated from ADA-Gel hydrogels using a 3D-bioplotter under printing conditions with and without the use of cross-linker, respectively, at room temperature and at 4 °C. Scaffolds were then quantitatively assessed in terms of the minimum printing pressure, quality of strands and pores, and structural integrity, which were combined together for the characterization of ADA-Gel printability. For the assessment of cell viability, scaffolds were bioprinted from ADA-Gel hydrogels with human umbilical vein endothelial cells (HUVECs) and rat Schwann cells and were then examined at day 7 with live/dead assay. HUVECs and Schwann cells were used as models to demonstrate biocompatibility for potential angiogenesis and nerve repair applications, respectively. Our results illustrated that ADA-Gel hydrogels with a loss tangent (ratio of loss modulus over storage modulus) between 0.24 and 0.28 could be printed in cross-linker with the best printability featured by uniform strands, square pores, and good structural integrity. Additionally, our results revealed that ADA-Gel hydrogels with an appropriate printability could maintain cell viability over 7 days. Combined together, this study presents a novel method to characterize the printability of hydrogels in bioprinting and illustrates that ADA-Gel hydrogels can be synthesized and bioprinted with good printability and cell viability, thus demonstrating their suitability for bioprinting scaffolds in tissue engineering applications.
三维（3D）生物打印是一种很有前景的技术，用于用含活细胞的水凝胶制造支架。然而，水凝胶在生物打印中的可打印性尚未得到充分研究。本研究的目的是定量表征用于生物打印的藻酸盐二醛（ADA）-明胶（Gel）水凝胶的可打印性和细胞活力。合成了不同浓度的ADA-Gel水凝胶，并使用傅里叶变换红外光谱进行表征，同时进行流变学测试以测量储能模量和损耗模量。分别在室温及4℃下，使用3D生物绘图仪，在有交联剂和无交联剂的打印条件下，由ADA-Gel水凝胶制备1层、2层和13层的支架（面积为11×11毫米）。然后从最小打印压力、丝和孔的质量以及结构完整性方面对支架进行定量评估，将这些因素综合起来以表征ADA-Gel的可打印性。为了评估细胞活力，用含人脐静脉内皮细胞（HUVECs）和大鼠雪旺细胞的ADA-Gel水凝胶进行生物打印支架，然后在第7天用活/死检测法进行检测。HUVECs和雪旺细胞分别用作模型，以证明在潜在的血管生成和神经修复应用中的生物相容性。我们的结果表明，损耗角正切（损耗模量与储能模量之比）在0.24至0.28之间的ADA-Gel水凝胶在有交联剂的情况下可以打印，其最佳可打印性的特征是丝均匀、孔呈方形且结构完整性良好。此外，我们的结果显示，具有适当可打印性的ADA-Gel水凝胶可以在7天内维持细胞活力。综合来看，本研究提出了一种表征水凝胶在生物打印中可打印性的新方法，并表明ADA-Gel水凝胶可以合成并进行生物打印，具有良好的可打印性和细胞活力，从而证明它们适用于组织工程应用中的生物打印支架。
