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Silica Nanoparticles for Drug Delivery
Published in Vladimir Torchilin, Handbook of Materials for Nanomedicine, 2020
Instead of conventional MSN, Kwon et al. used iron oxide nanoparticles as seeds for the ethyl acetate mediated growth of extra-large pore (30 nm) MSN. The large pores allowed for significantly higher protein loading than conventional MSN. Although the extralarge pore MSN induced some reactive oxygen species, no pro-inflammatory cytokines were generated in bone marrow-derived macrophages. These particles were loaded with the cytokine IL-4, which was delivered into macrophages for the purpose of M2 macrophage polarization. On its own, IL-4 has a very short half-life, but sheltering inside the MSN allowed for extended protein release. It was found that IL-4-loaded MSN injected intraperitoneally showed no toxicity and effective M2 macrophage polarization in mice [101].
Regulation of stem cell fate and function by using bioactive materials with nanoarchitectonics for regenerative medicine
Published in Science and Technology of Advanced Materials, 2022
Wei Hu, Jiaming Shi, Wenyan Lv, Xiaofang Jia, Katsuhiko Ariga
Besides the cytokines, macrophage polarization can be directed by biophysical cues such as stiffness, alignment and topography. Chen et al. cultured bone marrow-derived macrophages on PAAm gels with varying stiffness. They found that macrophages showed pro-inflammatory M1 on collagen fibres stiffness-like soft substrates (2.55 ± 0.32 kPa) and anti-inflammatory M2 on osteoid stiffness-like rigid substrates (63.53 ± 5.65 kPa) both in vitro and in vivo. Low-stiffness substrates stimulate macrophages to produce more reactive oxygen species (ROS), promote the activation of NF-κB signalling pathway and contribute to the polarization of the M1 phenotype. Snedeker’s group found that disordered polycaprolactone nanofibers alone direct macrophage polarization to pro-inflammatory M1, which can be enhanced by dynamic mechanical loading [145]. Randomly oriented fibre substrates can enhance tendon fibroblast response to paracrine signals of M1 macrophages, which is manifested in the up-regulation of matrix metalloproteinase (MMP) gene expression [146]. The highly aligned electrospun nanofiber tended to down-regulate the expression of MMPs. Their study indicated that macrophages as mechanosensory cells regulate tendon repair process. By high-throughput screening of 2,160 surface topologies, Alexander’s group found that micropillars 5–10 µm in diameter were more conducive to macrophage attachment [147]. The pillar size and the micropillar density affect the polarization of macrophages and thus can be used to regulate macrophages from pro-inflammatory to anti-inflammatory phenotypes. The balance of macrophage M1 and M2 is important for tissue repair. Smart materials with healing-match regulation of macrophage phenotype are beneficial for the tissue repair. As shown in Figure 6, Gao’s group developed shape-memory polycaprolactone/Au nanorods film whose surface can dynamically change, shifting from a flat surface to a microgroove under near-infrared irradiation [148]. The dynamic change of material surface induced the elongation and phenotype change of macrophages. This consequently upregulated expressions of arginase-1 and IL-10, achieving optimized tissue healing effect. Therefore, biophysical cues including stiffness, alignment and topography provide a new perspective for the design of ‘immune-instructive’ biomaterials for implantable medical devices and tissue repair.