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Nanofibrillar Cellulose Hydrogels with Anionic Surface Modifications for Modulating Macrophage Phenotype in 3D
Maria Heilala1, Rita Turpin2, Nikolaos Pahimanolis3
1Department of Applied Physics, Aalto University. P.O. Box 15100, FI-00076 Aalto, Espoo Finland.
ACS Applied Materials & Interfaces
|July 3, 2025
Summary
Researchers developed plant-derived hydrogels to culture M2 macrophages in 3D. Phosphorylated nanofibrillar cellulose (NFC) hydrogels enhanced M2 macrophage markers and altered cytokine profiles, offering a xeno-free scaffold for immunological research.
Area of Science:
- Biomaterials Science
- Immunology
- Cell Biology
Background:
- Anti-inflammatory M2 macrophages are crucial in tissue repair and cancer, but 2D cultures limit understanding their modulation for immunotherapy.
- There's a need for scalable, animal-free 3D hydrogels to model macrophage behavior.
- Plant-derived nanofibrillar cellulose (NFC) offers a promising biomaterial for 3D cell culture.
Purpose of the Study:
- To investigate NFC-based hydrogels for creating 3D in vitro models of M2-like macrophages.
- To assess the impact of NFC phosphorylation on macrophage phenotype and function.
- To establish a xeno-free, bioactive scaffold for macrophage research.
Main Methods:
- Fabrication of 3D hydrogels using plant-derived nanofibrillar cellulose (NFC) with varying modifications (native, carboxylate, sulfate, phosphorylated).
- Culture of human blood monocytes in 3D NFC hydrogels and 2D cultures.
- Flow cytometry analysis for M2 macrophage marker (CD206) expression.
- Cytokine profiling (TNF-α, IL-1β, IL-10) of cultured macrophages.
Main Results:
- 3D phosphorylated NFC hydrogels significantly enhanced CD206 expression in M2-like macrophages compared to other NFC modifications and 2D cultures.
- CD206 upregulation in phosphorylated NFC was comparable to IL-4-induced M2a macrophages.
- Macrophages in phosphorylated NFC hydrogels exhibited altered cytokine profiles, with higher IL-1β and IL-10 secretion than 2D cultures.
- Phosphorylation of NFC controlled monocyte-to-M2 macrophage conversion without external polarization factors.
Conclusions:
- NFC-based hydrogels, particularly phosphorylated NFC, can effectively guide monocyte differentiation into M2-like macrophages in a 3D xeno-free environment.
- Surface chemistry of NFC hydrogels plays a critical role in matrix-guided macrophage polarization.
- These findings support the development of advanced 3D in vitro models for immunological research and therapeutic strategies.
