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Alginate-Zein Microcarriers with Tunable Stiffness: Fabrication and Application in 3D Osteosarcoma Modeling
Yijing Li1, Yulin Yang2,3,4, Hongbo Zhang1
1Shanghai Key Laboratory of Multiphase Materials Chemical Engineering, School of Chemical Engineering, School of Mechanical and Power Engineering, East China University of Science and Technology, No.130 Mei Long Road, Shanghai 200237, China.
Researchers engineered alginate-zein (AZ) composite microcarriers using microfluidics to create advanced 3D osteosarcoma models. These models show promise for cancer research and drug screening, with specific microcarriers proving optimal.
Area of Science:
- Biomaterials Engineering
- Cancer Research
- 3D Cell Culture
Background:
- Physiologically relevant 3D in vitro tumor models are crucial for cancer research.
- Engineering microcarriers with specific properties is key to developing these models.
- Osteosarcoma models require tailored microcarrier characteristics.
Purpose of the Study:
- To develop alginate-zein (AZ) composite microcarriers with tunable mechanical properties.
- To construct in vitro 3D osteosarcoma models using these microcarriers.
- To validate the model's utility for drug screening.
Main Methods:
- Utilized a co-axial capillary microfluidic device to fabricate AZ microcarriers with varying alginate-zein ratios.
- Cultured MG-63 cells on microcarriers to form 3D osteosarcoma models.
- Quantified intracellular reactive oxygen species (ROS) and analyzed gene expression (vegf, vim, cdh-2, runx2, cdh-1).
- Validated drug screening potential using doxorubicin.
Main Results:
- AZ microcarriers exhibited high uniformity and monodispersity.
- Cell-microcarrier constructs showed increased intracellular ROS and altered expression of key promalignant genes.
- The model demonstrated enhanced drug resistance, confirming its utility for drug screening.
- Optimal microcarriers (AZ-β, 9:1 zein ratio, 159.73 kPa elastic modulus) were identified.
Conclusions:
- Successfully developed a robust methodology for creating 3D in vitro osteosarcoma models using AZ microcarriers.
- The established model accurately reflects osteosarcoma characteristics and is suitable for therapeutic intervention development and drug screening.
- Tailored microcarrier properties are essential for creating effective 3D tumor models.