Macrophage phenotype switch by sequential action of immunomodulatory cytokines from hydrogel layers on titania nanotubes

作者：Chen, Junhong; Li, Mengting; Yang, Congling; Yin, Xianzhen; Duan, Ke; Wang, Jianxin; Feng, Bo^*

来源：Colloids and Surfaces B: Biointerfaces , 2018, 163: 336-345.

DOI：10.1016/j.colsurfb.2018.01.007

• Titania nanotubes
• Hydrogel
• Inflammatory cytokine
• Controlled release
• Macrophage polarization

Inflammatory response occurring between tissues and implants after implantation has attracted increasing attention because it can cause local tissue necrosis and even implant failure. Macrophages play a key role in all stages ofinflammation. Pro-inflammatory (M1) and anti-inflammatory (M2) macrophages comprise two main phenotypes and the switch from M1 to M2 at specific time points is important for wound healing and tissue regeneration. Therefore, we hypothesized that biotnaterial systems capable of facilitating macrophage phenotype switching should attenuate inflammation and enhance healing. To this end, a system of double hydrogel layers on titania nanotubes (TNT) was prepared as reservoir to modulate the release of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma). In this system, IL-4, an anti-inflammatory cytokine, was loaded in TNT and IFN-gamma, a pro-inflammatory cytokine, was located between two hydrogel layers of chitosan/beta-glycerophosphate disodium and carboxymethyl chitosan/genipin. IFN-gamma released rapidly in 3 days, whereas IL-4 exhibited a sustained release profile. In culture with mesenchymal stem cells and macrophages, this system displayed good cytocompatibility and significantly promoted cell proliferation. Macrophage phenotype switch was determined by ELISA, FACS and PCR. The results manifested that IFN-gamma released from the system stimulated switching of macrophages to M1 in 3 days, whereas sustained release of IL-4 polarized macrophages to M2 after 4 days. This system can modulate macrophage phenotype switching from M1 to M2 by sequential action of the two cytokines, and might be used to research immune response between tissues and implants. The present study also provided a novel strategy for designing functional biomaterials.

• 出版日期2018-3-1
• 单位西南交通大学