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Inducing Immunomodulatory Effects on Human Macrophages by Multifunctional NCO-sP(EO-stat-PO)/Gelatin Hydrogel Nanofibers

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posted on 11.06.2021, 16:13 authored by Mehmet Berat Taskin, Tina Tylek, Carina Blum, Christoph Böhm, Christina Wiesbeck, Jürgen Groll
Endowing materials and scaffolds with immunomodulatory properties has evolved into a very active field of research. However, combining such effects with multifunctionality regarding cell adhesion and manipulation is still challenging due to the intricate nature of cell–substrate interactions that require fine-tuning of scaffold properties. Here, we reported electrospinning of a well-known biopolymer, gelatin, together with six-arm star-shaped poly­(ethylene oxide-stat-propylene oxide) prepolymer with isocyanate end groups (NCO-sP­(EO-stat-PO)) as a reactive prepolymer cross-linker. Covalent coupling of two components during and after processing yielded a network of hydrogel fibers that was remarkably stable under aqueous and also proteolytic conditions without the need for extra cross-linking, with a significant increase in stability with increasing NCO-sP­(EO-stat-PO) content. When seeded with human macrophages, cells adhered and spread on the fibers and were found highly viable after 7 days of culture across all scaffolds. Furthermore, hybrid fibrous meshes upregulated the expression of a prohealing gene, CD206, while downregulating proinflammatory genes, IL-1β and IL-8. Markedly, NCO-sP­(EO-stat-PO)-rich samples induced a significantly reduced release of proinflammatory cytokines, IL-1β, IL-6, and IL-8. Finally, we successfully conjugated IL-4 to NCO-sP­(EO-stat-PO) that effectively steered macrophages into a prohealing M2 type, demonstrating additional and robust control over the immunomodulatory feature of the scaffolds.