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Intracellular pH-responsive iron-catechin nanoparticles with osteogenic/anti-adipogenic and immunomodulatory effects for efficient bone repair

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Abstract

Osteoimmunomodulation was identified as a new and important strategy to enhance osteogenic differentiation together with other osteogenic approaches. However, approaches regulating osteogenic differentiation and macrophage polarization to remodel an osteoinductive microenvironment are separate and complicated. Therefore, the design and synthesis of one biomaterial that couples the osteogenic performance and immunomodulatory ability is a major challenge for efficient bone repair. In this study, self-assembled iron-catechin nanoparticles (Fe-cat NPs) were designed based on the coordinated reaction between iron ions and catechin and synthesized via a facile one-pot strategy. Interestingly, Fe-cat NPs show intracellular pH-responsive disassembly and release catechin molecules under the low pH of lysosomes after endocytosis. This strategy delivers catechin intracellularly and then enhances the osteogenic differentiation while inhibits the adipogenic differentiation of human adipose-derived stem cells (hADSCs). More importantly, Fe-cat NPs remodel the osteogenic immune microenvironment by resisting inflammation and promoting M2 polarization of macrophages. As a promising metal-organic nanodrug, the intracellular pH-responsive Fe-cat NPs significantly enhance the therapeutic effect of bone regneration by orchestrating osteogenic differentiation and immunomodulation, which may have great potential in bone tissue engineering.

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Acknowledgements

This work was supported by National Key R&D Program of China (No. 2017YFB0405400), National Natural Science Foundation of China (No. 51732007), Major Innovation Projects in Shandong Province (No. 2018YFJH0503), Natural Science Foundation of Shandong Province (No. ZR2020YQ35), Young Elite Scientist Sponsorship Program by CAST, and the Project of “20 items of University” of **an (No. 2018GXRC031). The authors are thankful for the support from the Collaborative Innovation Center of Technology and Equipment for Biological Diagnosis and Therapy in Universities of Shandong, The authors thank Translational Medicine Core Facility of Shandong University for consultation and instrument availability that supported this work.

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Author notes

  1. Chao Liu

    Present address: Present address: Department of Oral Surgery, Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, China

  2. Ying Kong and Feng Liu contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Crystal Materials, Shandong University, **an, 250100, China

    Ying Kong, Feng Liu, Wenhan Wang, Hongru Yang, Yuanhua Sang, Shuhua Wang & Hong Liu

  2. Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, **an, 250012, China

    Bao** Ma

  3. Department of Pharmacology, School of Basic Medical Sciences, Shandong University, **an, 250012, China

    Liang Li

  4. Department of Pathology, **an Women and Children’s Health Hospital, **an, 250000, China

    **aoying Xu

  5. Department of Oral and Maxillofacial Surgery, Qilu Hospital of Shandong University, **an, 250012, China

    Zhaoyang Sun & Chao Liu

  6. Cryomedicine Laboratory, Qilu Hospital of Shandong University, **an, 250012, China

    Dong Li

  7. Neurological Surgery, Qilu Hospital of Shandong University, **an, 250012, China

    Gang Li

  8. Advanced Medical Research Institute, Shandong University, **an, 250100, China

    Shuhua Wang

  9. Institute for Advanced Interdisciplinary Research, University of **an, **an, 250022, China

    Hong Liu

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  1. Ying Kong
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Correspondence to Chao Liu, Shuhua Wang or Hong Liu.

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Intracellular pH-responsive iron-catechin nanoparticles with osteogenic/anti-adipogenic and immunomodulatory effects for efficient bone repair

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Kong, Y., Liu, F., Ma, B. et al. Intracellular pH-responsive iron-catechin nanoparticles with osteogenic/anti-adipogenic and immunomodulatory effects for efficient bone repair. Nano Res. 15, 1153–1161 (2022). https://doi.org/10.1007/s12274-021-3618-2

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