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

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.

A Review on the Design of Hydrogels With Different Stiffness and Their Effects on Tissue Repair

“…The change of macrophage phenotype is related to matrix stiffness. On the surface of the high stiffness matrix, macrophages are pro-inflammatory phenotype, while on the surface of low stiffness matrix, macrophages are anti-inflammatory phenotype ( Trel’ová et al, 2019 ; Taskin et al, 2021 ). Changes in macrophage phenotypes, in turn, alter the expression of related cytokines, which can affect the bone microenvironment ( YlÖstalo et al, 2012 ; Liu et al, 2018 ; Esser-von Bieren, 2019 ).…”

A bionic controllable strain membrane for cell stretching at air–liquid interface inspired by papercutting

“…Doryab et al developed a hybrid biphasic membrane (composed of gelatin and PCL) for an in vitro cell stretch model of the lung cultured under ALI conditions [45]. Taskin et al electrospun various ratios of six-arm star-shaped poly (ethylene oxide-propylene oxide) prepolymers with isocyanate end groups (NCO-sP [EO-stat-PO]) to stabilize gelatin as a bioactive component within nanofibrous hydrogel scaffolds [46]. Zamprogno et al used biofilms made of lung ECM, collagen and elastin proteins for stretch culture [39].…”

Roles of biomaterials in modulating the innate immune response in ocular therapy

“…Frontiers in Drug Delivery frontiersin.org was suggested that the honeycomb-like texture can promote filopodia formation, which is associated with RhoA/ROCK signaling pathways, and can induce M2 polarization (Zhu et al, 2021). Moreover, a study reported that fibrous meshes of gelatin hydrogel nanofibers mimicking ECM promoted macrophage adhesion and differentiation into M2 phenotypes, with upregulation of CD206 expression and downregulation of IL-1β and IL-8 in in vitro culture (Taskin et al, 2021).…”