海藻酸钠/明胶复合水凝胶用于3D生物打印的初步研究

doi:10.19438/j.cjoms.2017.05.005

中国口腔颌面外科杂志 ›› 2017, Vol. 15 ›› Issue (5): 402-407.doi: 10.19438/j.cjoms.2017.05.005

海藻酸钠/明胶复合水凝胶用于3D生物打印的初步研究

任荣¹，张剑飞¹，司家文¹，吴稼晟²，李伟²，史俊¹

1.上海交通大学医学院附属第九人民医院·口腔医学院口腔颅颌面科，上海市口腔医学重点实验室，上海 200011;
2.上海交通大学材料科学与工程学院金属基复合材料国家重点实验室，上海 200240

收稿日期:2017-02-13 出版日期:2017-08-30 发布日期:2017-10-27
通讯作者: 李伟， E-mail: liwei1016_2000@sjtu.edu.cn;史俊，E-mail: Dr.shijun.oms.@gmail.com。*共同通信作者
作者简介:任荣（1990-），男，在读硕士研究生，E-mail: renr531201@sina.com
基金资助:
上海交通大学医工交叉项目（YG2015QN22）

Preliminary study of alginate/gelatin composite hydrogel used for 3D bio-printing

REN Rong¹, ZHANG Jian-fei¹, SI Jia-wen¹，WU Jia-sheng², LI Wei², SHI Jun¹.

1.Department of Oral and Craniomaxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine;
Shanghai Key Laboratory of Stomatology. Shanghai 200011;
2.School of Materials Science and Engineering, Shanghai Jiao Tong University, State Key Laboratory of Metal Matrix Composites. Shanghai 200240, China

Received:2017-02-13 Online:2017-08-30 Published:2017-10-27

摘要/Abstract

摘要： 目的：利用天然高分子材料明胶、海藻酸钠的物理、生物学性能及其特殊的交联特性，构建一种可用于3D生物打印的生物墨水，并对其进行制备、表征与分析，为后期的生物打印提供材料基础。方法：根据回顾文献得到的信息，采用比例混合法制备质量比为2∶15、2∶10的2种海藻酸钠/明胶复合水凝胶，分别进行冻干扫描电镜（SEM）微观形貌、溶胀性能、孔隙率分析，3D打印以及利用复合水凝胶进行载ATDC-5小鼠成软骨前体细胞的3D培养等实验，以确定此复合水凝胶的物理特性及生物学特性。结果：顺利构建出海藻酸/明胶复合水凝胶，并对其进行分析，发现2∶10、-20℃组凝胶比2∶15、-50℃组水凝胶拥有更多、更大的孔径。孔隙率实验结果显示，2组海藻酸钠/明胶复合水凝胶的孔隙率在60%~82%之间，均利于细胞培养。溶胀性能测试结果显示，溶胀率均在660%~740%范围，表明此种海藻酸钠/明胶复合水凝胶的亲水性较强，非常有利于细胞增殖。3D打印结果显示，利用此种复合水凝胶可以打印出预先设计的几何形状，且经二价阳离子化学交联后，能够形成具有一定机械强度的水凝胶胶体。细胞培养结果显示，ATDC-5细胞在此种复合水凝胶内培养下，7 d后仍有95%的成活率。结论：此种经明胶改性的海藻酸钠/明胶复合水凝胶具有优良的微观形貌、溶胀性能以及适合的孔隙率，并且具备3D打印能力。尤其是明胶与海藻酸钠质量比为15∶2组，因具有均匀孔径以及能够满足3D打印墨水的性能要求，可考虑作为3D生物打印的“墨水”。

关键词: 海藻酸钠, 明胶, 3D生物打印, 墨水

Abstract: PURPOSE: Based on the physical and biological properties of natural polymer gelatin and sodium alginate and their special crosslinking characteristics, a bio-printing gel was built that can be used for 3D bio-printing. METHODS: Based on review of the literature, two kinds of sodium alginate/gelatin composite hydrogels were produced, whose mass ratio was 2:10 and 2:15, respectively. The hydrogels were studied by scanning electronic microscopic (SEM) microstructure, swelling properties and porosity via freezing-drying method. Then, the hydrogels were used for culturing ATDC-5 cells and 3D printing. RESULTS: The alginate/gelatin composite hydrogel was successfully constructed and a lump of special 3D geometrical shaped gel was constructed. The experimental results showed that 2:10, -20℃ group had more larger aperture than 2:15，-50℃ group. This kind of alginate/gelatin composite hydrogel had porosity between 60% and 82%. The swelling ratio was in the range of 660% to 740%. The composite hydrogel could be used for 3D printing and constructing certain mechanical strength of gel via bivalent cation chemical crosslinking. The mean cell viability was 95%±2.3% by 3D cell encapsulation culture for 1,3,7 days. CONCLUSIONS: This modified alginate/gelatin composite hydrogel could be used as 3D bio-printing ink and had a good application prospect, especially when the gelatin/alginate ratio was 15:2.

Key words: Sodium-alginate, Gelatin, 3D bio-printing, Ink

中图分类号:

R318.08

任荣，张剑飞，司家文，吴稼晟，李伟，史俊. 海藻酸钠/明胶复合水凝胶用于3D生物打印的初步研究[J]. 中国口腔颌面外科杂志, 2017, 15(5): 402-407.

REN Rong, ZHANG Jian-fei, SI Jia-wen，WU Jia-sheng, LI Wei, SHI Jun.. Preliminary study of alginate/gelatin composite hydrogel used for 3D bio-printing[J]. China J Oral Maxillofac Surg, 2017, 15(5): 402-407.

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海藻酸钠/明胶复合水凝胶用于3D生物打印的初步研究

Preliminary study of alginate/gelatin composite hydrogel used for 3D bio-printing

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