Inducing Immunomodulatory Effects on Human Macrophages by Multifunctional NCO-sP(EO-stat-PO)/Gelatin Hydrogel
Mehmet Berat Taskin1, Tina Tylek1, Carina Blum1
1Department of Functional Materials in Medicine and Dentistry at the Institute of Biofabrication and Functional Materials, University of Würzburg and KeyLab Polymers for Medicine of the Bavarian Polymer Institute (BPI), Pleicherwall 2, 97070 Würzburg, Germany.
Abstract:
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.
