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Bio-adhesive Macroporous Hydrogels for In Situ Recruitment and Modulation of Dendritic Cells

  • SI: 2023 CMBE Young Innovators
  • Published:
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Abstract

Introduction

Biomaterials that enable in situ recruitment and modulation of immune cells have demonstrated tremendous promise for developing potent cancer immunotherapy such as therapeutic cancer vaccine. One challenge related to biomaterial scaffold-based cancer vaccines is the development of macroporous materials that are biocompatible and stable, enable controlled release of chemokines to actively recruit a large number of dendritic cells (DCs), contain macropores that are large enough to home the recruited DCs, and support the survival and proliferation of DCs

Methods

Bio-adhesive macroporous gelatin hydrogels were synthesized and characterized for mechanical properties, porous structure, and adhesion towards tissues. The recruitment of immune cells including DCs to chemokine-loaded bioadhesive macroporous gels was analyzed. The ability of gels loaded with granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor extracellular vesicles (EVs) to elicit tumor-specific CD8+ T cell responses was also analyzed.

Results

Here we develop a bioadhesive macroporous hydrogel that can strongly adhere to tissues, contain macropores that are large enough to home immune cells, are mechanically tough, and enable controlled release of chemokines to recruit and modulate immune cells in situ. The macroporous hydrogel is composed of a double crosslinked network of gelatin and polyacrylic acid, and the macropores are introduced via cryo-polymerization. By incorporating GM-CSF and tumor EVs into the macroporous hydrogel, a high number of DCs can be recruited in situ to process and present EV-encased antigens. These tumor antigen-presenting DCs can then traffic to lymphatic tissues to prime antigen-specific CD8+ T cells.

Conclusion

This bioadhesive macroporous hydrogel system provides a new platform for in situ recruitment and modulation of DCs and the development of enhanced immunotherapies including tumor EV vaccines. We also envision the promise of this material system for drug delivery, tissue regeneration, long-term immunosuppression, and many other applications.

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Data Availability

Raw data can be accessed upon request, and will be published upon the acceptance of the manuscript.

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Acknowledgements

The authors would like to acknowledge the financial support from NSF DMR 2143673 CAR, NSF GCR 2121003, R01CA274738, NIH R21CA270872, and the start-up package from the Department of Materials Science and Engineering at the University of Illinois at Urbana-Champaign and the Cancer Center at Illinois. Han J. acknowledges the support from the Cancer Scholars for Translational and Applied Research (C*STAR) Program (CST EP082021). Bhatta R. acknowledges the support from the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (T32EB019944).

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Correspondence to Hua Wang.

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The authors (Joonsu Han, Rimsha Bhatta, and Hua Wang) declare no competing financial interests.

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This paper does not involve any research of human subjects. For studies involving mice, the ethical principles established by the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 8523, revised 2011) were followed.

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Han, J., Bhatta, R. & Wang, H. Bio-adhesive Macroporous Hydrogels for In Situ Recruitment and Modulation of Dendritic Cells. Cel. Mol. Bioeng. 16, 355–367 (2023). https://doi.org/10.1007/s12195-023-00770-2

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