Microfluidic Generation of Viscoelastic Artificial Antigen Presenting Cells for T cell Activation
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Microfluidic Generation of Viscoelastic Artificial Antigen Presenting Cells for T cell Activation


Artificial antigen presenting cells (aAPCs) are engineered platforms for T-cell activation. It has been widely used for the ex vivo generation of tumor-reactive lymphocytes to ample numbers for effective Adopted Cell Transfer (ACT) therapies including Chimeric Antigen Receptor (CAR) T cell therapy.Viscoelastic materials with stress relaxation are closer to living tissues than pure elastic materials, which can be used to tune cell spreading, proliferation, or differentiation. By controlling molecular weight in combination with crosslinker concentration, we can adjust the stress relaxation properties of materials and therefore modulate cell behavior that is cocultured with viscoelastic biomaterials. It has also been found that T cells could sense the mechanical properties of the substrate and show different morphology when cultured on the substrate with different stiffness. Based on the modulation of cell behavior by viscoelastic materials as well as the mechanosensing properties of T cells, a hypothesis could be made that viscoelastic materials may help improve T cell expansion and generate more proliferative T cell subgroups. There are already publications about the cell response to the matrix with different viscoelasticity using alginate hydrogel modified with adhesion molecules. However, no study has been conducted to investigate the T cell response to the viscoelastic properties of aAPCs. This is due to several technical issues including the fabrication of homogeneous, cell-sized alginate microgel, as well as the conjugation of T cell- specific antibodies to the microgel. In this study, we overcame some of the technical issues and successfully fabricated viscoelastic aAPCs using ionically-crosslinked alginate, which can be applied to in vitro T cell activation and expansion. The alginate microbeads are generated using a microfluidic platform and then conjugated with T-cell-specific antibodies by click chemistry. These viscoelastic aAPCs show homogenous size distribution, low cytotoxicity and can be easily dissolved and removed after coculture. The T cell activation rate of these aAPCs is close to widely-used commercial aAPCs like Dynabeads. Therefore, this kind of viscoelastic aAPCs can serve as the platform to study how viscoelastic properties could affect T cell stimulation, and possess the potential to improve the quality of in vitro expanded T cells.

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