Ordered micropattern arrays fabricated by lung-derived dECM hydrogels for chemotherapeutic drug screening.

Abstract

Aims:

This study aims to evaluate ECM-coated micropattern arrays derived from decellularization of native porcine lungs as a novel three-dimensional cell culture platform.

Methods:

ECM derived from decellularization of native porcine lungs was exploited to prepare hydrogels. Then, dECM-coated micropattern arrays were fabricated at four different diameters (50, 100, 150 and 200 ​μm) using polydimethylsiloxane (PDMS). Two lung cancer cell lines, A549 and H1299, were tested on a dECM-coated micropattern array as a novel culture platform for cell adhesion, distribution, proliferation, viability, phenotype expression, and drug screening to evaluate the cytotoxicity of paclitaxel, doxorubicin and cisplatin.

Results:

The ECM derived from decellularization of native porcine lungs supported cell adhesion, distribution, viability and proliferation better than collagen I and Matrigel as the coated matrix on the surface. Moreover, the optimal diameter of the micropattern arrays was 100-150 ​μm, as determined by measuring the morphology, viability, proliferation and phenotype of the cancer cell spheroids. Cell spheroids of A549 and H1299 on dECM-coated micropattern arrays showed chemoresistance to anticancer drugs compared to that of the monolayer. The different distributions of HIF-1α, MCL-1 (in the center) and Ki-67 and MRP2 (in the periphery) of the spheroids demonstrated the good establishment of basal-lateral polarity and explained the chemoresistance phenomenon of spheroids.

Conclusions:

This novel three-dimensional cell culture platform is stable and reliable for anticancer drug testing. Drug screening in dECM-coated micropattern arrays provides a powerful alternative to existing methods for drug testing and metabolic profiling in the drug discovery process.

• Authors: Xinglong Zhu, Yi Li, Ying Yang, Yuting He, Mengyu Gao, Wanliu Peng, Qiong Wu, Guangyue Zhang, Yanyan Zhou, Fei Chen, Ji Bao, Weimin Li
• Journal: Materials today. Bio (Mater Today Bio) Vol. 15 Pg. 100274 (Jun 2022) ISSN: 2590-0064 [Electronic] England
• PMID: 35601895 (Publication Type: Journal Article)
• Copyright: © 2022 The Authors.