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Groove structure of porous hydroxyapatite scaffolds (HAS) modulates immune environment via regulating macrophages and subsequently enhances osteogenesis

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Abstract

Researches have revealed the vital roles of the generated immune environment via the response of immune cells growing on biomaterial surfaces in the bone healing process. HAS and novel constructed microgrooved patterns of HAS (HAS-G) are widely used as biocompatible ceramic, especially as a mimic of the natural bone matrix. However, it is unclear whether osteoimmune response induced by HAS and HAS-G affects the osteogenic differentiation of bone marrow stromal cells (BMSCs). RAW264.7 cells were seeded on different surface of materials and cytokines released by macrophages were detected by enzyme-linked immunosorbent assay. The cell viability and mitochondrial function of macrophages seeded on different surface of materials were detected. Then, the effects of modified inflammatory microenvironment by macrophages on osteogenesis of BMSCs were measured by performing ALP staining, Alizarin Red S staining, and western blot. We confirmed that HAS-G is more favorable for RAW cell attaching and subsequently regulated the expression and release of cytokines/chemokines. Decrease in interleukin-6 (IL-6) release was further confirmed for contributing significantly to improve mitochondrial function in RAW cells. HAS-G-conditioned medium promoted osteogenic differentiation in BMSCs and was reversed by IL-6 addition. Decrease in IL-6 contributes to downregulation of miR-214 and subsequently upregulated p38/JNK pathway, which is potentially contributes to osteogenic promotion by HAS-G. This study is the first report to reveal the effects of HAS-G on osteogenesis via immune response, which could lead to a new insight into novel material for the advantage of biomaterials for tissue engineering applications.

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Acknowledgements

Thanks for the English editing from Dr. Huimin Shi at Sichuan University.

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Author notes

  1. Chenglong Li and Lu Yang have contributed equally to this work.

Authors and Affiliations

  1. Stomatology department, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, No. 32 West Second Section, First Ring Road, Chengdu, 610072, Sichuan, China

    Chenglong Li, Xiaohua Ren, Mu Lin, Xiliang Jiang & Yandong Mu

  2. School of Medicine, University of Electronic Science and Technology of China, No. 4, Section 2, Jianshe North Road, Chengdu, 610054, Sichuan, China

    Chenglong Li, Lu Yang, Xiaohua Ren & Yandong Mu

  3. Department of Periodontics, West China School and Hospital of Stomatology, Sichuan University, Chengdu, China

    Daonan Shen

  4. Key Laboratory of Advanced Technologies of Materials (MOE), School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, China

    Taotao Xu

  5. Southwest Medical University, Luzhou, Sichuan, China

    Jing Ren, Lijuan Huang, Wei Qing & Jiajun Zheng

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  1. Chenglong Li
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Contributions

CL, YM, and LY contributed to conception, design, and acquisition of data. XR, ML, XJ, and DS contributed to acquisition, analysis, and interpretation of data. TX, JR, LH, WQ, and JZ contributed to cell culture, molecular-related experiments.

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Correspondence to Yandong Mu.

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775_2019_1687_MOESM1_ESM.pdf

Supplementary figure S1. The effect of different patterns of materials on proliferation. A. cell cycle was analyzed by flow cytometry. B. the distribution of cell cycle phases was quantified. Supplementary figure S2. The effect of modified microenvironment on cell viability was analyzed with the supplementary of IL-1β, IL-6 or TNF-α. To quantitative measure IL-1β, IL-6 or TNF-α, ELISA was performed. Supplementary figure S3. The effect of IL-6 on miR-214 expression in macrophages adherent on different patterns of materials. A. miR-214 expression was measured in macrophages attached to different patterns of materials. *P < 0.05, vs. HAS group. B. addition of IL-6 reversed the downregulation of miR-214 by CM. *P < 0.05, vs. CM group. (PDF 119 kb)

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Li, C., Yang, L., Ren, X. et al. Groove structure of porous hydroxyapatite scaffolds (HAS) modulates immune environment via regulating macrophages and subsequently enhances osteogenesis. J Biol Inorg Chem 24, 733–745 (2019). https://doi.org/10.1007/s00775-019-01687-w

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  • DOI: https://doi.org/10.1007/s00775-019-01687-w

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