Synergistic regulation of osteoimmune microenvironment by IL-4 and RGD to accelerate osteogenesis

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Li, Mengting
Wei, Fei
Yin, Xueqiong
Xiao, Lan
Yang, Lan
Su, Jiehua
Weng, Jie
Feng, Bo
Xiao, Yin
Zhou, Yinghong
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The control of early inflammatory reactions and recruitment of progenitor cells are critical for subsequent tissue repair and regeneration after biomaterial implantation. The aim of this study was to design a multi-functional biomaterial with a controlled drug delivery system to create an optimal local environment for early osteogenesis. Here, the anti-inflammatory cytokine IL-4 and pro-osteogenic RGD peptide were assembled layer-by-layer on TiO2 nanotubes. A poly(dopamine) (DOP) coating was employed onto TiO2 nanotubes (T/DOP) to functionalized with IL-4 (T/DOP-IL4). Then, a carboxymethyl chitosan hydrogel layer (CG) was generated on T/DOP-IL4 to control IL-4 release and RGD peptide immobilization. Cell co-culture models were applied to study macrophage polarization on various material surfaces and the regulation of mesenchymal stromal cell (MSC) osteogenic differentiation. Our data suggest that T/DOP-IL4/CG-RGD surfaces developed in this study are multi-functional, and can not only drive phenotypic changes in macrophages (switching to anti-inflammatory M2 phenotype), resulting in the production of reparative cytokines such as IL-10, but also enhance MSC differentiation related to the activation of BMP/SMAD/RUNX2 signaling. This study further confirmed that the introduction of anti-inflammatory cytokine (IL-4) and cell adhesive motif (RGD) onto Ti substrate can work synergistically to generate a more favorable early-stage osteo-immune environment with superior osteogenic properties, thus representing a potential ideal surface for the generation of bone biomaterials.

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Materials Science and Engineering: C
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Biomedical engineering
Materials engineering
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Materials Science, Biomaterials
TiO2 nanotubes
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Li, M; Wei, F; Yin, X; Xiao, L; Yang, L; Su, J; Weng, J; Feng, B; Xiao, Y; Zhou, Y, Synergistic regulation of osteoimmune microenvironment by IL-4 and RGD to accelerate osteogenesis, Materials Science and Engineering: C, 2020, 109, pp. 110508