Skip to main content
2024 BMES Annual Meeting Main banner
Icon Legend
This session is not in your schedule.
This session is in your schedule. Click again to remove it.

Biomaterials

Biomaterials - Poster Session E

Poster C5 - Tunable Collagen I Microgels for T-cell Activation

Saturday, October 26, 2024
10:00 AM - 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapy for liquid cancers such as lymphomas and leukemias. Previous research has indicated that mechano-modulation, or the process by which cells perceive and respond to their mechanical environment, can impact the efficacy of T-cell therapy. In this study, we aim to investigate the role of mechano-modulation on T-cell activation via a new antigen-presenting biomaterial. We have developed artificial antigen-presenting cells composed of collagen I microgels with controllable viscoelasticity, allowing for the generation of tunable T cell populations for adoptive T cell therapy.

Materials and

Methods:  Microgel synthesis: Collagen microgels were formed by water-in-oil emulsion. Methyltetrazine-modified collagen I was first neutralized and rapidly dispersed in surfactant diluted in HFE oil, after which the collagen underwent gelation. After the surfactant layer was removed, the collagen microgels were subsequently conjugated with CD3/CD28 antibodies. Microgel viscoelasticity was tuned by locally cross linking methyltetrazine collagen with bifunctional TCO linkers.
Co-Culture with T-Cells: T-cells were isolated from peripheral blood mononuclear cells and cultured with the microgels for 6 days. At the end of the culture period, confocal images were taken and flow cytometry was performed to assess T-cell differentiation and activation.

Results, Conclusions, and Discussions: The newly proposed microgel synthesis method yielded gels at an average diameter of ~40-90 um. While these gels are still larger than antigen-presenting cells, they exhibit the smallest collagen microgel dimensions that we are aware of.
During co-culture, the microgels successfully activated T-cells, and induced the expression of different T-cell markers based on the degree of cross-linking used. T-cells readily interacted with the microgels, even invading the collagen fibers in some cases. We generally saw a trend of more memory markers expressed by T-cells that were activated by with non cross-linked (faster-relaxing) microgels. On the other hand, T-cells cultured on the cross-linked (slower-relaxing) gels exhibited more effector markers. At this point, trends suggest differential T-cell behavior/activation based on the viscoelasticity of the antigen-presenting microgels.
Though we are using this biomaterial to study T-cell activation, this research presents a novel and broadly relevant biomaterial with potential in a variety of biomedical applications where mechano-modulation must be probed or leveraged for its effect on immune cell behavior.

Acknowledgements (Optional):  The presenting author would like to thank the entirety of the Mooney Lab for their ongoing support and wonderfully welcome environment. Further, I would like to thank the Wyss Institute for funding this project and allowing access to resources through this research experience.