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3D Bioprinted Vascularized Tumour for Drug Testing
Seokgyu Han1, Sein Kim2, Zhenzhong Chen1
1School of Mechanical Engineering, Sungkyunkwan University, Suwon 16419, Korea.
Abstract:
An in vitro screening system for anti-cancer drugs cannot exactly reflect the efficacy of drugs in vivo, without mimicking the tumour microenvironment (TME), which comprises cancer cells interacting with blood vessels and fibroblasts. Additionally, the tumour size should be controlled to obtain reliable and quantitative drug responses. Herein, we report a bioprinting method for recapitulating the TME with a controllable spheroid size. The TME was constructed by printing a blood vessel layer consisting of fibroblasts and endothelial cells in gelatine, alginate, and fibrinogen, followed by seeding multicellular tumour spheroids (MCTSs) of glioblastoma cells (U87 MG) onto the blood vessel layer. Under MCTSs, sprouts of blood vessels were generated and surrounding MCTSs thereby increasing the spheroid size. The combined treatment involving the anti-cancer drug temozolomide (TMZ) and the angiogenic inhibitor sunitinib was more effective than TMZ alone for MCTSs surrounded by blood vessels, which indicates the feasibility of the TME for in vitro testing of drug efficacy. These results suggest that the bioprinted vascularized tumour is highly useful for understanding tumour biology, as well as for in vitro drug testing.
Insights
Bioprinting creates a tumor microenvironment (TME) with blood vessels and controllable size. This 3D model accurately predicts anti-cancer drug efficacy, improving in vitro cancer research.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Drug Discovery
Background:
- In vitro drug screening lacks tumor microenvironment (TME) complexity.
- Accurate drug response requires controlled tumor size and vascularization.
- Current models fail to fully replicate in vivo tumor conditions.
Purpose of the Study:
- To develop a bioprinting method for recapitulating the TME.
- To create a controllable multicellular tumor spheroid (MCTS) model.
- To assess the efficacy of combined anti-cancer drug treatment in a bioprinted TME.
Main Methods:
- Bioprinting a blood vessel layer using fibroblasts and endothelial cells in a hydrogel.
- Seeding glioblastoma (U87 MG) MCTSs onto the vascularized layer.
- Evaluating drug response to temozolomide (TMZ) and sunitinib in the bioprinted TME.
Main Results:
- Vascular sprouts grew from the engineered blood vessel layer, surrounding MCTSs.
- Tumor spheroid size increased due to vascularization.
- Combined TMZ and sunitinib treatment showed enhanced efficacy compared to TMZ alone in vascularized tumors.
Conclusions:
- The bioprinted TME model successfully mimics tumor vascularization and growth.
- This 3D model provides a feasible platform for in vitro anti-cancer drug efficacy testing.
- The bioprinted vascularized tumor is valuable for studying tumor biology and drug development.
