Hierarchical Hydrogels with Ordered Micro-Nano Structures for Cancer-on-a-Chip Construction
Luyao Zhu,
Changmin Shao,
Hanxu Chen,
Zhuoyue Chen,
Yuanjin Zhao
Affiliations
Luyao Zhu
Department of Clinical Laboratory, Institute of Translational Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008 Nanjing, China; State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
Changmin Shao
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325001, China
Hanxu Chen
Department of Clinical Laboratory, Institute of Translational Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008 Nanjing, China; State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
Zhuoyue Chen
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
Yuanjin Zhao
Department of Clinical Laboratory, Institute of Translational Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008 Nanjing, China; State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China; Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing 210023, China
In the drug therapy of tumor, efficient and stable drug screening platforms are required since the drug efficacy varies individually. Here, inspired by the microstructures of hepatic lobules, in which hepatocytes obtain nutrients from both capillary vessel and the central vein, we present a novel hierarchical hydrogel system with ordered micro-nano structure for liver cancer-on-a-chip construction and drug screening. The hierarchical hydrogel system was fabricated by using pregel to fill and replicate self-assembled colloidal crystal arrays and microcolumn array template. Due to the synergistic effect of its interconnected micro-nano structures, the resultant system could not only precisely control the size of cell spheroids but also realize adequate nutrient supply of cell spheroids. We have demonstrated that by integrating the hierarchical hydrogel system into a multichannel concentration gradients microfluidic chip, a functional liver cancer-on-a-chip could be constructed for high-throughput drug screening with good repeatability and high accuracy. These results indicated that the hierarchical hydrogel system and its derived liver cancer-on-a-chip are ideal platforms for drug screening and have great application potential in the field of personalized medicine.
