Honeycomb-Like Hydrogel Microspheres for 3D Bulk Construction of Tumor Models
Jiachen He,
Chichi Chen,
Liang Chen,
Ruoyu Cheng,
Jie Sun,
Xingzhi Liu,
Lin Wang,
Can Zhu,
Sihan Hu,
Yuan Xue,
Jian Lu,
Huiling Yang,
Wenguo Cui,
Qin Shi
Affiliations
Jiachen He
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu 215031, China; National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu 215031, China
Chichi Chen
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu 215031, China
Liang Chen
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu 215031, China
Ruoyu Cheng
Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China
Jie Sun
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu 215031, China
Xingzhi Liu
School of Nanotech and Nano-Bionics, University of Science and Technology of China, 388 Ruoshui Road, Suzhou, Jiangsu 215123, China
Lin Wang
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu 215031, China
Can Zhu
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu 215031, China
Sihan Hu
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu 215031, China; Department of Orthopedics, Wuxi Ninth People’s Hospital Affiliated to Soochow University, Wuxi, Jiangsu 214026, China
Yuan Xue
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu 215031, China; Department of Orthopedics, Wuxi Ninth People’s Hospital Affiliated to Soochow University, Wuxi, Jiangsu 214026, China
Jian Lu
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu 215031, China
Huiling Yang
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu 215031, China
Wenguo Cui
Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China
Qin Shi
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu 215031, China; National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu 215031, China
A two-dimensional (2D) cell culture-based model is widely applied to study tumorigenic mechanisms and drug screening. However, it cannot authentically simulate the three-dimensional (3D) microenvironment of solid tumors and provide reliable and predictable data in response to in vivo, thus leading to the research illusions and failure of drug screening. In this study, honeycomb-like gelatin methacryloyl (GelMA) hydrogel microspheres are developed by synchronous photocrosslinking microfluidic technique to construct a 3D model of osteosarcoma. The in vitro study shows that osteosarcoma cells (K7M2) cultured in 3D GelMA microspheres have stronger tumorous stemness, proliferation and migration abilities, more osteoclastogenetic ability, and resistance to chemotherapeutic drugs (DOX) than that of cells in 2D cultures. More importantly, the 3D-cultured K7M2 cells show more tumorigenicity in immunologically sound mice, characterized by shorter tumorigenesis time, larger tumor volume, severe bone destruction, and higher mortality. In conclusion, honeycomb-like porous microsphere scaffolds are constructed with uniform structure by microfluidic technology to massively produce tumor cells with original phenotypes. Those microspheres could recapitulate the physiology microenvironment of tumors, maintain cell-cell and cell-extracellular matrix interactions, and thus provide an effective and convenient strategy for tumor pathogenesis and drug screening research.
