Spherical Shell Bioprinting to Produce Uniform Spheroids with Controlled Sizes

Area of Science:

• Biotechnology
• Materials Science
• Regenerative Medicine

Background:

• Conventional cell spheroid production is manual, resulting in inconsistent size and shape.
• Inconsistent spheroids limit reliability in cell-based therapeutics and drug screening.
• A need exists for scalable, high-throughput methods for uniform spheroid generation.

Purpose of the Study:

• To develop and validate a bioprinting system for high-throughput, uniform cell spheroid production.
• To achieve precise control over spheroid size and morphology.
• To demonstrate the versatility of the system for various cell types.

Main Methods:

• A spherical shell bioprinting system was implemented using alginate hydrogel shells.
• Cells were encapsulated within alginate shells formed via ion crosslinking with calcium ions.
• Gelatin-based bioinks with embedded cells were used, allowing spontaneous aggregation within shells.
• Cell concentration was adjusted to control spheroid size, with sphericity >0.94 and size deviation ±10 µm.

Main Results:

• The bioprinting system enabled high-throughput generation of uniform cell spheroids.
• Precise control over spheroid size was achieved by adjusting cell concentrations.
• Spheroids maintained high sphericity (>0.94) and minimal size deviation (±10 µm).
• The method was successfully applied to cancer cells, fibroblasts, chondrocytes, and epithelial cells.

Conclusions:

• The developed bioprinting system offers a scalable and reliable method for producing uniform cell spheroids.
• This approach enhances consistency for cell therapy and drug screening applications.
• The system provides a versatile platform for diverse biomedical applications.