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Received: 2023-10-17

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Bio-Design and Manufacturing  2016 Vol.-1 No.-1 P.

http://doi.org/10.1631/bdm.2400108


Bioprinted integrated gradient biomechanical signal-tailored osteosarcoma model: advancing insights into tumor development and drug screening


Author(s):  Xuelian Mi, Ya Ren, Hanbo Wang, Lei Qiang, Weiqing Kong, Hui Wang, Xue Yang, Yihao Liu, Han Yang, Di Xiao, Zhenjiang Ma, Guoxing Xu, Changru Zhang, Jinwu Wang

Affiliation(s):  Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan, China; more

Corresponding email(s):   zcr_ecust@163.com, wangjw-team@shsmu.edu.cn

Key Words:  3D bioprinting, Gradient biomechanical signal-tailor, Osteosarcoma model, Tumor development, Drug screening


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Abstract: 
In current osteosarcoma research and drug screening, in vitro 3D models are favored for overcoming the limitations of traditional models. In in vitro 3D models, tumor microenvironment simulation, especially mechanical microenvironment, is crucial for tumor biological effects. However, current in vitro tumor model construction for osteosarcoma is often limited to a single mechanical signal, which fails to simulate the diversity of osteosarcoma mechanical stimuli. In this study, we utilized embedded bioprinting technology and multiple response properties of calcium ions in soft stiffness systems, hard stiffness systems, and osteosarcoma cell biological functions to construct an integrated gradient biomechanical signal-tailored osteosarcoma model. Specifically, we achieved this by printing a fibrinogen bioink containing calcium ions and osteosarcoma tumor spheroids within an extracellular matrix composed of methacryloylated alginate, methacryloylated gelatin, and thrombin, which is rich in polysaccharides and proteins and exhibits self-healing properties. In vitro and in vivo studies showed that the integrated gradient biomechanical signal-tailored osteosarcoma model enhanced tumor stemness, proliferation and migration, successfully reproduced the nest-like structure of cancer, and provided an in vitro research platform closer to a natural tumor. In conclusion, this study proposes a novel integrated gradient biomechanical signal-tailored osteosarcoma model construction system that provides a new strategy for the clinical understanding of tumor development, drug screening, and exploration of drug resistance and metastasis mechanisms.

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