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

Mengting Li; Fei Wei; Xueqiong Yin; Lan Xiao; Lan Yang; Jiehua Su; Jie Weng; Bo Feng; Yin Xiao; Yinghong Zhou

doi:10.1016/j.msec.2019.110508

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

Mater Sci Eng C Mater Biol Appl. 2020 Apr:109:110508. doi: 10.1016/j.msec.2019.110508. Epub 2019 Nov 29.

Authors

Mengting Li¹, Fei Wei², Xueqiong Yin³, Lan Xiao², Lan Yang⁴, Jiehua Su², Jie Weng⁵, Bo Feng⁶, Yin Xiao⁷, Yinghong Zhou⁸

Affiliations

¹ Hainan Provincial Fine Chemical Engineering Research Center, Hainan University, Haikou, Hainan 570228, China; Key Laboratory of Advanced Technology for Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China; The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology, Australia.
² Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia; The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology, Australia.
³ Hainan Provincial Fine Chemical Engineering Research Center, Hainan University, Haikou, Hainan 570228, China.
⁴ Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia; Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China; The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology, Australia.
⁵ Key Laboratory of Advanced Technology for Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
⁶ Key Laboratory of Advanced Technology for Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China. Electronic address: fengbo@swjtu.edu.cn.
⁷ Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia; Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China; The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology, Australia. Electronic address: yin.xiao@qut.edu.au.
⁸ Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia; Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China; The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology, Australia. Electronic address: yinghongzhou@qut.edu.au.

PMID: 32228925
DOI: 10.1016/j.msec.2019.110508

Abstract

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.

Keywords: IL-4; Immune microenvironment; Osteogenesis; RGD; TiO(2) nanotubes.

MeSH terms

Animals
Coculture Techniques
Hydrogels* / chemistry
Hydrogels* / pharmacology
Interleukin-4* / chemistry
Interleukin-4* / pharmacology
Macrophages / immunology
Mesenchymal Stem Cells / immunology*
Mice
Nanotubes / chemistry*
Oligopeptides* / chemistry
Oligopeptides* / pharmacology
Osteogenesis / drug effects
Osteogenesis / immunology
RAW 264.7 Cells
Stem Cell Niche / drug effects
Stem Cell Niche / immunology*
Titanium* / chemistry
Titanium* / pharmacology

Substances

Hydrogels
Il4 protein, mouse
Oligopeptides
titanium dioxide
Interleukin-4
arginyl-glycyl-aspartic acid
Titanium