Taskin Mehmet Berat, Tylek Tina, Blum Carina, Böhm Christoph, Wiesbeck Christina, Groll Jürgen
Department 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.
ACS Biomater Sci Eng. 2021 Jul 12;7(7):3166-3178. doi: 10.1021/acsbiomaterials.1c00232. Epub 2021 Jun 11.
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--propylene oxide) prepolymer with isocyanate end groups (NCO-sP(EO--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--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--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--PO) that effectively steered macrophages into a prohealing M2 type, demonstrating additional and robust control over the immunomodulatory feature of the scaffolds.
赋予材料和支架免疫调节特性已发展成为一个非常活跃的研究领域。然而，由于细胞与底物相互作用的复杂性，需要对支架特性进行微调，因此将这种效应与细胞黏附及操控的多功能性相结合仍然具有挑战性。在此，我们报道了将一种著名的生物聚合物明胶与具有异氰酸酯端基的六臂星形聚（环氧乙烷 - 环氧丙烷）预聚物（NCO-sP(EO-PO)）作为反应性预聚物交联剂进行静电纺丝。在加工过程中和加工后，两种组分的共价偶联产生了一种水凝胶纤维网络，该网络在水性和蛋白水解条件下都非常稳定，无需额外交联，并且随着NCO-sP(EO-PO)含量的增加稳定性显著提高。当接种人巨噬细胞时，细胞在纤维上黏附并铺展，并且在所有支架上培养7天后发现细胞具有很高的活力。此外，混合纤维网上调了促愈合基因CD206的表达，同时下调了促炎基因IL-1β和IL-8。值得注意的是，富含NCO-sP(EO-PO)的样品诱导促炎细胞因子IL-1β、IL-6和IL-8的释放显著减少。最后，我们成功地将IL-4偶联到NCO-sP(EO-PO)上，有效地将巨噬细胞引导为促愈合的M2型，证明了对支架免疫调节特性的额外且强大的控制。
