Fabrication of liver microtissue with liver decellularized extracellular matrix (dECM) bioink by digital light processing (DLP) bioprinting

Qijiang Mao; Yifan Wang; Yang Li; Sarun Juengpanich; Wenhuan Li; Mingyu Chen; Jun Yin; Jianzhong Fu; Xiujun Cai

doi:10.1016/j.msec.2020.110625

Fabrication of liver microtissue with liver decellularized extracellular matrix (dECM) bioink by digital light processing (DLP) bioprinting

Mater Sci Eng C Mater Biol Appl. 2020 Apr:109:110625. doi: 10.1016/j.msec.2020.110625. Epub 2020 Jan 7.

Authors

Qijiang Mao¹, Yifan Wang², Yang Li³, Sarun Juengpanich⁴, Wenhuan Li⁵, Mingyu Chen⁴, Jun Yin⁶, Jianzhong Fu⁷, Xiujun Cai⁸

Affiliations

¹ Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310028, China; Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310028, China; Zhejiang University Innovation Center of Minimally Invasive Technology and Medical Equipment, Hangzhou 310028, China.
² Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310028, China; Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310028, China; Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases, Hangzhou 310028, China.
³ The State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou 310028, China; Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou 310028, China.
⁴ Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310028, China; Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310028, China.
⁵ Department of General Surgery, The First People's Hospital of Wenling, Taizhou 318000, China.
⁶ The State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou 310028, China; Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou 310028, China. Electronic address: junyin@zju.edu.cn.
⁷ The State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou 310028, China; Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou 310028, China. Electronic address: fjz@zju.edu.cn.
⁸ Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310028, China; Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310028, China; Zhejiang University Innovation Center of Minimally Invasive Technology and Medical Equipment, Hangzhou 310028, China; Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases, Hangzhou 310028, China. Electronic address: srrsh_cxj@zju.edu.cn.

PMID: 32228893
DOI: 10.1016/j.msec.2020.110625

Abstract

As one of the most effective treatments of end-stage liver disease, liver transplantation still suffers from a shortage of donor organs or a low degree of engraftment. Thus, alternatives to liver transplantation, such as liver support systems, have to be extensively explored. In this study, a novel liver microtissue with an inner gear-like structure, which achieved a larger body surface area, was designed and manufactured to improve hepatic functional restoration. The liver-specific bioinks were developed by combining photocurable methacrylated gelatin (GelMA) with liver decellularized extracellular matrix (dECM), and human-induced hepatocytes (hiHep cells) were encapsulated to form cell-laden bioinks. The mechanical properties, swelling, and cytocompatibility of GelMA/dECM bioinks were carefully characterized before 3D printing. Then, the digital light process (DLP)-based bioprinting was used to fabricate the liver microtissue, and liver dECM was found to improve both the printability and cell viability of GelMA bioinks. hiHep cells were also found to spread farther and have better hepatocyte-specific functions (albumin secretion and urea) in the liver microtissue when liver dECM was added to the GelMA bioinks. Our results provide a promising liver dECM-based cell-laden bioink for liver microtissue fabrication, which would be a potential liver tissue engineering product to help restore hepatic functions.

Keywords: Bioink; Decellularized extracellular matrix (dECM); Digital light process (DLP); Liver microtissue; hiHep cell.

MeSH terms

Animals
Bioprinting*
Cell Line
Cell Survival
Extracellular Matrix / chemistry*
Hepatocytes / cytology
Hepatocytes / metabolism*
Humans
Printing, Three-Dimensional*
Sus scrofa
Swine
Swine, Miniature
Tissue Engineering*
Tissue Scaffolds / chemistry*