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

Joonsu Han, Rimsha Bhatta, Hua Wang

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)355-367
Number of pages13
JournalCellular and Molecular Bioengineering
Volume16
Issue number4
DOIs
StatePublished - Aug 2023

Keywords

  • Bioadhesive
  • Cancer vaccine
  • Dendritic cell
  • Extracellular vesicle
  • Immunotherapy

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • Modeling and Simulation

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