Engineering Bone-Mimetic Microspheres to Recapitulate the Tumor Microenvironment for In Vitro Osteosarcoma Modeling

Area of Science:

• Biomaterials Engineering
• Cancer Biology
• Microfluidics

Background:

• Osteosarcoma (OS) is an aggressive bone cancer.
• Current 3D models lack the native tumor microenvironment, hindering research.
• Need for physiologically relevant models for OS drug development.

Purpose of the Study:

• Develop bone-mimetic microspheres for osteosarcoma modeling.
• Utilize droplet microfluidics for scaffold fabrication.
• Evaluate OS cell behavior on the novel microsphere platform.

Main Methods:

• Fabricated bone-mimetic microspheres (MSHA) using microfluidics.
• MSHA composed of gelatin methacryloyl, PEGDA, and nano-hydroxyapatite (nHA).
• Cultured MNNG/HOS OS cells on MSHA and assessed bioactivity, stemness, migration, and invasion.

Main Results:

• Efficient, scalable production of uniform MSHA microspheres.
• OS cells on MSHA showed high viability and formed tumor spheroids.
• Enhanced OS cell migration, invasion, and biomarker expression compared to 2D cultures.
• Nano-hydroxyapatite incorporation amplified malignant phenotypes via ECM-receptor and calcium signaling pathways.

Conclusions:

• Microfluidics-fabricated MSHA microspheres serve as effective biomimetic 3D scaffolds.
• These scaffolds show promise for osteosarcoma progression studies.
• The platform is suitable for osteosarcoma drug screening applications.