Biomaterial Substrate-Mediated Multicellular Spheroid Formation and Their Applications in Tissue Engineering

Area of Science:

• Biomaterials Science
• Cell Biology
• Tissue Engineering

Background:

• Three-dimensional (3D) multicellular spheroids better mimic in vivo physiology than traditional 2D cell cultures.
• Various methods exist for spheroid generation, with substrate-derived spheroids possessing unique formation mechanisms.
• Substrate-mediated spheroid formation offers advantages for biomimetic cell-cell interactions and improved functionalities.

Purpose of the Study:

• To review the formation of biomaterial substrate-mediated multicellular spheroids.
• To highlight applications of these spheroids in tissue engineering and cancer research.
• To discuss the self-assembly of co-spheroids for recapitulating cell interactions.

Main Methods:

• Focus on chitosan substrate-derived mesenchymal stem cell (MSC) spheroids.
• Description of tumor spheroids formed on chitosan and hyaluronan substrates.
• Exploration of self-assembly processes for substrate-derived multicellular spheroids (co-spheroids).

Main Results:

• Chitosan substrate-derived MSC spheroids exhibit enhanced regenerative capacities.
• Tumor spheroids on chitosan and hyaluronan substrates serve as in vitro models for cancer research and drug screening.
• Co-spheroids demonstrate recapitulation of heterotypic cell-cell interactions and crosstalk.

Conclusions:

• Substrate-derived multicellular spheroids represent a novel 3D cell culture category.
• These spheroids offer biomimetic cell-cell interactions, enhanced functionalities, and imaging possibilities.
• Applications span regenerative medicine, in vitro tumor modeling, and drug discovery.