posted on 2021-06-11, 16:13authored byMehmet
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.