Rapid and mass manufacturing of soft hydrogel microstructures for cell patterns assisted by 3D printing  

作　　者：Chaofan He Xuechun Chen Yuan Sun Mingjun Xie Kang Yu Jing He Jinwei Lu Qing Gao Jing Nie Yi Wang Yong He 

机构地区：[1]State Key Laboratory of Fluid Power and Mechatronic Systems,School of Mechanical Engineering,Zhejiang University,Hangzhou 310027,China [2]Pharmaceutical Informatics Institute,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China [3]Department of Orthopedic Surgery,The Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310009,China [4]Key Laboratory of Materials Processing and Mold,Zhengzhou University,Zhengzhou 450002,China [5]Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province,College of Mechanical Engineering,Zhejiang University,Hangzhou 310027,China [6]Cancer Center,Zhejiang University,Hangzhou 310058,China [7]State Key Laboratory of Component-Based Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 300072,China

出　　处：《Bio-Design and Manufacturing》2022年第4期641-659,共19页生物设计与制造（英文）

基　　金：sponsored by the National Key Research and Development Program of China (No.2018YFA0703000);the National Natural Science Foundation of China (Nos.T2121004 and U1909218);supported by the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No.ZYYCXTD-D-202002)。

摘　　要：Micro-/nano-patterns on hydrogels are widely used in cell patterning.However,manufacturing molds with traditional lithography is time-consuming and expensive.In addition,the excessive demolding force can easily damage patterns since biocompatible hydrogels are ultra-soft or brittle.Here,we presented a novel method for rapid and mass fabrication of cell patterns.High-precision three-dimensional(3D)printing was used to manufacture a mold with a resolution of 2µm,and the gelatin-based hydrogel was cured by thermal–photo-crosslinking so that the low-concentration and low-substitutionrate hydrogel could be demolded successfully.We found that pre-cooling before illumination made gelatin-based hydrogels resilient due to the partial regain of triple-helix structures.With this method,arbitrarily customized hydrogel patterns with a feature size of 6–80µm can be fabricated stably and at low cost.When cardiomyocytes were seeded on ultra-soft hydrogels with parallel groove structures,a consistent and spontaneous beating with 216 beats per minute(BPM)could be observed,approaching the natural beating rate of rat hearts(300 BPM).Overall,this work provides a general scheme for manufacturing cell patterns which has great potential for cell ethology and tissue repair.

关 键 词：3D printing Gelatin-based hydrogel Cell pattern Cardiomyocytes beating 

分 类 号：R318[医药卫生—生物医学工程]