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Bio-Design and Manufacturing  2023 Vol.6 No.5 P.550–562

http://doi.org/10.1007/s42242-023-00251-5


3D bioprinting of complex biological structures with tunable elastic modulus and porosity using freeform reversible embedding of suspended hydrogels


Author(s):  Zhuang Chen, Chuanzhen Huang, Hanlian Liu, Xu Han, Zhichao Wang, Shuying Li, Jun Huang & Zhen Wang

Affiliation(s):  Centre for Advanced Jet Engineering Technology (CaJET), Key Laboratory of High-Efficiency and Clean Mechanical Manufacture (Ministry of Education), National Experimental Teaching Demonstration Center for Mechanical Engineering (Shandong University), School of Mechanical Engineering, Shandong University, Jinan 250061, China; more

Corresponding email(s):   huangchuanzhen@ysu.edu.cn

Key Words:  Bioink, Freeform reversible embedding of suspended hydrogels (FRESHs) printing, 3D extrusion cell-laden printing, Tissue engineering, Tunable elastic modulus and porosity


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Zhuang Chen, Chuanzhen Huang, Hanlian Liu, Xu Han, Zhichao Wang, Shuying Li, Jun Huang & Zhen Wang . 3D bioprinting of complex biological structures with tunable elastic modulus and porosity using freeform reversible embedding of suspended hydrogels[J]. Journal of Zhejiang University Science D, 2023, 6(5): 550–562.

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Abstract: 
Three-dimensional (3D) bioprinting has been used widely for the construction of hard tissues such as bone and cartilage. However, constructing soft tissues with complex structures remains a challenge. In this study, complex structures characterized by both tunable elastic modulus and porosity were printed using freeform reversible embedding of suspended hydrogels (FRESHs) printing methods. A mixture of alginate and gelatin was used as the main functional component of the bioink. Rheological analysis showed that this bioink possesses shear thinning and shear recovery properties, supporting both cryogenic and FRESH printing methods. Potential printing capabilities and limitations of cryogenic and FRESH printing were then analyzed by printability tests. A series of complex structures were printed by FRESH printing methods which could not be realized using conventional approaches. Mechanical tests and scanning electron microscopy analysis showed that the printed structure is of excellent flexibility and could be applied in various conditions by adjusting its mechanical modulus and porosity. L929 fibroblast cells maintained cell viability in cell-laden-printed structures, and the addition of collagen further improved the hydrogels’ biocompatibility. Overall, all results provided useful insight into the building of human soft tissue organ blocks.

山东大学陈壮&燕山大学黄传真等 | FRESH打印具有可调弹性模量和孔隙率的复杂生物结构

本研究论文聚焦于使用悬浮水凝胶的自由形式可逆嵌入(FRESH)打印方法打印具有可调弹性模量和孔隙率的复杂结构。目前,三维(3D)生物打印已被广泛用于构建硬组织,如骨骼和软骨。然而,构建具有复杂结构的软组织仍然是一个挑战。FRESH打印方法可以克服重力对打印结构的影响,有望成为制备复杂软组织的关键手段。本研究以海藻酸盐和明胶作为墨水基底,通过FRESH方法进行载细胞打印。首先,设计并制备了具有可调孔隙率和机械性能的生物墨水,通过FRESH方法在明胶颗粒支撑浴中进行挤出打印。使用流变仪测量墨水的流变性能对打印性进行了分析,并通过模拟进一步分析了油墨的挤出状态。此外,力学测试结果和微观形貌分别显示出打印结构具有可调的弹性模量和孔隙率。通过对FRESH工艺进行优化,实现了一系列复杂结构的打印。最后使用L929成纤维细胞进行载细胞打印,细胞在7天培养中表现出高的活力和良好的增殖特性。所有结果表明,设计的生物墨水具有良好的生物和机械性能,并且可以通过添加细胞相容性材料进一步提高细胞活力,在软组织的打印中显示出良好的潜力。

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