GelMA复合凝胶的挤出式3D打印工艺及其性能研究

doi:10.3901/JME.2020.01.196

机械工程学报 ›› 2020, Vol. 56 ›› Issue (1): 196-204.doi: 10.3901/JME.2020.01.196

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GelMA复合凝胶的挤出式3D打印工艺及其性能研究

顾恒^1,2, 连芩^1,2, 王慧超^1,2, 李涤尘^1,2, 靳国瑞³, 崔滨^1,2

1. 西安交通大学机械制造系统国家重点实验室西安 710054;
2. 西安交通大学机械工程学院西安 710049;
3. 西安交通大学生命科学与技术学院西安 710049

收稿日期:2019-02-23 修回日期:2019-07-16 出版日期:2020-01-05 发布日期:2020-03-09
通讯作者: 连芩(通信作者),女,1971年出生,博士,副教授,博士研究生导师。主要研究方向为增材制造与仿生制造。E-mail:lqiamt@mail.xjtu.edu.cn
作者简介:顾恒,男,1995年出生。主要研究方向为生物3D打印。E-mail:825186692@qq.com
基金资助:
科学技术（BWS17J036，18-163-13-ZT-003-011-01）和国家自然科学基金（51835010，51375371）资助项目。

Extrusion 3D Printing Processes and Performance Evaluation of GelMA Composite Hydrogel

GU Heng^1,2, LIAN Qin^1,2, WANG Huichao^1,2, LI Dichen^1,2, JIN Guorui³, CUI Bin^1,2

1. State Key Laboratory for Manufacturing System Engineering, Xi'an Jiaotong University, Xi'an 710054;
2. School of Mechanical Enginnering, Xi'an Jiaotong University, Xi'an 710049;
3. School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049

Received:2019-02-23 Revised:2019-07-16 Online:2020-01-05 Published:2020-03-09

摘要/Abstract

摘要： 甲基丙烯酸酐明胶（Methacrylated gelatin，GelMA）是具有光敏官能团的改性明胶，有良好的生物相容性，广泛用于构建皮肤、神经等软组织支架。然而，光照交联单一成分的GelMA，其力学性能和结构维持性较差，难以通过挤出3D打印成形生物支架。提出一种适用于挤出式打印且力学性能增强的GelMA复合凝胶，其主要成分为GelMA、明胶和海藻酸钠。黏度测试试验筛选出适合挤出3D打印的复合材料配比，3D打印工艺试验研究和分析了打印气压、喷头移动速度、喷头高度、光照条件对挤出连续性和微丝直径的影响。当喷头内径为200 μm时，GelMA复合凝胶实现顺畅出丝（φ293～1 211 μm）的条件为气压在0.05～0.25 MPa，打印速度为1～15 mm/s，喷头高度为200～600 μm，光照强度为70～272.56 mW/cm²。拉伸试验表明光照交联后，复合凝胶较之同浓度GelMA（5%，w/v）的弹性模量提高近1倍，伸长率保持一致。细胞培养试验显示GelMA复合凝胶具有良好的生物相容性，包埋在其内部的人真皮成纤维细胞培养至第7天时存活率达85%。

关键词: 甲基丙烯酸酐化明胶, 复合凝胶, 挤出式生物3D打印, 人真皮成纤维细胞

Abstract: Methacrylated gelatin(GelMA) is a modified gelatin with photosensitive functional groups and has good biocompatibility which is used to construct soft tissue scaffolds such as skin and nerves. However, GelMA hydrogel only UV photocrosslinked has too poor mechanical properties and structural maintenance to construct three-dimensional scaffolds through extrusion-based bioprinting. This study proposes a kind of GelMA composite hydrogel consisting of GelMA, gelatin and sodium alginate which can be extruded and obtained the enhanced mechanical properties. The component ratio of GelMA composite was be determined suitable for extrusion printing through the viscosity test. The process parameters of printing pressure, nozzle moving speed, nozzle height and illumination conditions on extrusion continuity and microfilament diameter were further investigated by 3D printing experiments. When the noozzle with the inner diameter of 200 μm is used, the uniform and smooth filaments (φ293-1 211 μm) of GelMA composite hydrogel can be achieved with the process parameter ranges:the air pressure is 0.05 MPa to 0.25 MPa, the printing speed 1 mm/s to 15 mm/s, the nozzle height 200μm to 600 μm, light intensity 76 mW/cm² to 272 mW/cm². The Young's modulus of GelMA composite hydrogel has been found doubled of that of the GelMA hydrogel under the same UV crosslinking conditions(76 mW/cm²,5 min) with the same concentration(5%,w/v)in the tensile test. Good biocompatibility of GelMA composite hydrogel has been verified by the cell culture in which the survival rate of human dermal fibroblasts embedded reached 85% on day 7.

Key words: GelMA, composite hydrogel, 3D extrusion-based bioprinting, NHDFs

中图分类号:

TG156

顾恒, 连芩, 王慧超, 李涤尘, 靳国瑞, 崔滨. GelMA复合凝胶的挤出式3D打印工艺及其性能研究[J]. 机械工程学报, 2020, 56(1): 196-204.

GU Heng, LIAN Qin, WANG Huichao, LI Dichen, JIN Guorui, CUI Bin. Extrusion 3D Printing Processes and Performance Evaluation of GelMA Composite Hydrogel[J]. Journal of Mechanical Engineering, 2020, 56(1): 196-204.

参考文献

[1] LEE K Y,MOONEY D J. Hydrogels for tissue engineering[J]. Chemical Reviews,2001,101(7):1869-1880.
[2] HE Y,YANG F F,ZHAO H M,et al. Research on the printability of hydrogels in 3D bioprinting[J]. Scientific Reports,2016,6:29977.
[3] 王身国. 组织工程细胞支架及其相关技术研究[J]. 中国组织工程研究与临床康复,2001(16):16-17. WANG Shenguo. Tissue engineering cell scaffold and related technology research[J]. Chinese Journal of Tissue Engineering Research and Clinical Rehabilitation,2001(16):16-17.
[4] PEREIRA R F,BARRIAS C C,GRANJA P L,et al. Advanced biofabrication strategies for skin regeneration and repair.[J]. Nanomedicine,2013,8(4):603-621.
[5] NICHOL J W,KOSHY S,BAE H,et al. Cell-laden microengineered gelatin methacrylate hydrogels[J]. Biomaterials,2010,31(21):5536-5544.
[6] YUE K,SANTIAGO T D,ALVAREZ M M,et al. Synthesis,properties,and biomedical applications of gelatin methacryloyl (GelMA) hydrogels[J]. Biomaterials,2015,73:254-271.
[7] PEPELANOVA I,KRUPPA K,SCHEPER T,et al. Gelatin-methacryloyl (GelMA) hydrogels with defined degree of functionalization as a versatile toolkit for 3D cell culture and extrusion bioprinting[J]. Bioengineering,2018,5(3):55-69.
[8] Van DEN B A I,BOGDANOV B,De ROOZE N,et al. Structural and rheological properties of methacrylamide modified gelatin hydrogels[J]. Biomacromolecules,2000,1(1):31-38.
[9] KLOTZ B J,GAWLITTA D,ROSENBERG A J W P,et al. Gelatin-methacryloyl hydrogels:Towards biofabrication-based tissue repair[J]. Trends in Biotechnology,2016,34(5):394-407.
[10] ZHU W,QU X,ZHU J,et al. Direct 3D bioprinting of prevascularized tissue constructs with complex microarchitecture[J]. Biomaterials,2017,124:106-115.
[11] LUIZ E B,JULIANA C C,VIJAYAN M,et al. Direct-write bioprinting of cell-laden methacrylated gelatin hydrogels[J]. Biofabrication,2014,6(2):024105.
[12] MONTEIRO N,THRIVIKRAMAN G,ATHIRASALA A,et al. Photopolymerization of cell-laden gelatin methacryloyl hydrogels using a dental curing light for regenerative dentistry[J]. Dental Materials Official Publication of the Academy of Dental Materials,2017,34(3):389-399.
[13] LIN CH,SU JJ-M,LEE SY,et al. Stiffness modification of photopolymerizable gelatin-methcrylate hrdrogels influences endothelial differentiation of human mesenchymal stem cells[J]. Tissue Eng. Regen. Med.,2018,12(1):2099-2111.
[14] BILLIET T,GEVAERT E,DE S T,et al. The 3D printing of gelatin methacrylamide cell-laden tissue-engineered constructs with high cell viability[J]. Biomaterials,2014,35(1):49-62.
[15] YIN J,YAN M,WANG Y,et al. 3D bioprinting of low concentration cell-laden gelatin methacrylate (GelMA) bioinks with two-step crosslinking strategy[J]. ACS Appl. Mater. Interfaces,2018,10(8):6849-6857.
[16] GUISEPPE M D,LAW N,WEBB B,et al. Mechanical behaviour of alginate-gelatin hydrogels for 3D bioprinting[J]. Journal of the Mechanical Behavior of Biomedical Materials,2017,79:150-157.
[17] 金乐,熊卓,刘利,等. 基于活塞挤出的组织工程支架低温沉积制造工艺[J]. 清华大学学报,2009(5):652-655. JIN Le,XIONG Zhuo,LIU Li,et al. Low temperature deposition manufacturing process of tissue engineering scaffold based on piston extrusion[J]. Journal of Tsinghua University,2009(5):652-655.
[18] COIMBRA P,FERNANDES D,FERREIRA P,et al. Solubility of Irgacure^®;2959 photoinitiator in supercritical carbon dioxide:Experimental determination and correlation[J]. Journal of Supercritical Fluids,2008,45(3):272-281.
[19] WANG Z,TIAN Z,MENARD F,et al. Comparative study of gelatin methacrylate hydrogels from different sources for biofabrication applications[J]. Biofabrication,2017,9(4):044101.
[20] FIDKOWSKI C. Endothelialized microvasculature based on a biodegradable elastomer[J]. Tissue Eng,2005,11:302-309.
[21] ANNABI N,NICHOL J W,ZHONG X,et al. Controlling the porosity and microarchitecture of hydrogels for tissue engineering[J]. Tissue Engineering Part B:Reviews,2010,16(4):371-383.
[22] MANDAL B B,KUNDU S C. Cell proliferation and migration in silk fibroin 3D scaffolds[J]. Biomaterials,2009,30(15):2956-2965

GelMA复合凝胶的挤出式3D打印工艺及其性能研究

Extrusion 3D Printing Processes and Performance Evaluation of GelMA Composite Hydrogel

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