Engineering the fate and function of human T-Cells via 3D bioprinting

Area of Science:

• Biomaterials Science
• Immunology
• Biotechnology

Background:

• T-cell immunotherapy shows potential for treating cancer, infections, and autoimmune diseases.
• Current T-cell therapies face limitations due to low *ex vivo* cell expansion and functional deficits.

Purpose of the Study:

• To develop 3D bioprinting systems that mimic *in vivo* lymph structures to modulate T-cell fate and function.
• To compare the efficacy of two distinct biomaterial scaffolds in enhancing T-cell expansion and differentiation.

Main Methods:

• Fabrication of two 3D bioprinting systems using different biomaterials (coaxial alginate fibers and alginate-gelatin scaffolds).
• Mimicking *in vivo* lymph vessel and lymph node formation to modulate T-cell responses.
• Evaluating T-cell expansion, exhaustion levels, and differentiation into memory subsets (Tcm, Tem) compared to standard suspension systems.

Main Results:

• Coaxial alginate fibers significantly promoted T-cell expansion, reduced exhaustion, and facilitated CD4+ T-cell differentiation into central memory-like cells (Tcm) and CD8+ T-cells into effector memory subsets (Tem).
• Alginate-gelatin scaffolds induced a relatively resting state in T-cells.
• Both bioprinting methods demonstrated distinct T-cell modulation compared to standard suspension culture.

Conclusions:

• The coaxial alginate fiber bioprinting system presents a novel approach for T-cell therapy, enhancing cell expansion and function.
• The alginate-gelatin scaffold system offers a valuable tool for creating immune-chips to study immune responses and disease mechanisms.