PMID- 35071924 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220125 IS - 2470-1343 (Electronic) IS - 2470-1343 (Linking) VI - 7 IP - 2 DP - 2022 Jan 18 TI - Fabrication of Size-Controllable and Arrangement-Orderly HepG2 Spheroids for Drug Screening via Decellularized Liver Matrix-Derived Micropattern Array Chips. PG - 2364-2376 LID - 10.1021/acsomega.1c06302 [doi] AB - Three-dimensional (3D) culture via micropattern arrays to generate cellular spheroids seems a promising in vitro biomimetic system for liver tissue engineering applications, such as drug screening. Recently, organ-derived decellularized extracellular matrix emerges as arguably the most biomimetic bioink. Herein, decellularized liver matrix (DLM)-derived micropattern array chips were developed to fabricate size-controllable and arrangement-orderly HepG2 spheroids for drug screening. The porcine DLM was obtained by the removal of cellular components and then ground into powder, followed by enzymolysis. DLM as a coating substrate was compared with collagen type I (Col I) and Matrigel in terms of biological performance for enhancing cell adhesion, proliferation, and functions. Subsequently, we used poly(dimethylsiloxane) (PDMS) to adsorb DLM as the bioink to fabricate micropattern array chips. The optimal shape and size of micropattern were determined by evaluating the morphology, viability, and functions of HepG2 3D cellular aggregates. In addition, drug-susceptibility testing (paclitaxel, doxorubicin HCl, and disulfiram) was performed on this novel platform. The DLM provided the tissue-specific microenvironment that provided suitable supports for HepG2 cells, compared to Col I and Matrigel. A circular micropattern with a diameter of 100 mum was the optimal processing parameter to rapidly fabricate large-scale, size-controllable, and arrangement-orderly HepG2 cellular aggregates with 3D spheroid's shape and high cell viability. Drug screening testing showed that the effect of a drug could be directly demonstrated on-chip by confocal microscopy measuring the viability of spheroids. We provide a novel platform for the large-scale generation of HepG2 spheroids with uniform size and arrangement, thus bringing convenience, reducing error, and increasing reproducibility for a rapid drug discovery by fluorescence quantitative analysis. This methodology may be possible to apply in advancing personalized medicine and drug discovery. CI - (c) 2022 The Authors. Published by American Chemical Society. FAU - Zhu, Xinglong AU - Zhu X AD - Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. FAU - Wu, Qiong AU - Wu Q AD - Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. AD - Laboratory of Liver Transplantation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. FAU - He, Yuting AU - He Y AD - Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. FAU - Gao, Mengyu AU - Gao M AD - Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. AD - Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. FAU - Li, Yi AU - Li Y AD - Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. AD - Precision Medicine Key Laboratory, West China Hospital, Sichuan University, Chengdu 610041, China. FAU - Peng, Wanliu AU - Peng W AD - Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. FAU - Li, Shengfu AU - Li S AD - Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. FAU - Liu, Yong AU - Liu Y AD - Department of Burn and Plastic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. FAU - Zhang, Rundong AU - Zhang R AD - West China School of Medicine, Sichuan University, Chengdu 610041, Sichuan Province, China. FAU - Bao, Ji AU - Bao J AUID- ORCID: 0000-0001-8413-3270 AD - Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. LA - eng PT - Journal Article DEP - 20220103 PL - United States TA - ACS Omega JT - ACS omega JID - 101691658 PMC - PMC8772313 COIS- The authors declare no competing financial interest. EDAT- 2022/01/25 06:00 MHDA- 2022/01/25 06:01 PMCR- 2022/01/03 CRDT- 2022/01/24 08:57 PHST- 2021/11/09 00:00 [received] PHST- 2021/12/20 00:00 [accepted] PHST- 2022/01/24 08:57 [entrez] PHST- 2022/01/25 06:00 [pubmed] PHST- 2022/01/25 06:01 [medline] PHST- 2022/01/03 00:00 [pmc-release] AID - 10.1021/acsomega.1c06302 [doi] PST - epublish SO - ACS Omega. 2022 Jan 3;7(2):2364-2376. doi: 10.1021/acsomega.1c06302. eCollection 2022 Jan 18.