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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.
Bianco, P.; Robey, P. G. Stem cells in tissue engineering. Nature 2001, 414, 118-121.
Seong, J. M.; Kim, B. C.; Park, J. H.; Kwon, I. K.; Mantalaris, A.; Hwang, Y. S. Stem cells in bone tissue engineering. Biomed. Mater. 2010, 5, 062001.
Bunnell, B. A.; Flaat, M.; Gagliardi, C.; Patel, B.; Ripoll, C. Adipose- derived stem cells: Isolation, expansion and differentiation. Methods 2008, 45, 115-120.
Yang, X.; Li, Y. Y.; Liu, X. J.; Zhang, R. R.; Feng, Q. L. In vitro uptake of hydroxyapatite nanoparticles and their effect on osteogenic differentiation of human mesenchymal stem cells. Stem Cells Int. 2018, 2018, 2036176.
Xu, C.; Xiao, L.; Cao, Y. X.; He, Y.; Lei, C.; Xiao, Y.; Sun, W. J.; Ahadian, S.; Zhou, X. T. Khademhosseini, A. et al. Mesoporous silica rods with cone shaped pores modulate inflammation and deliver BMP-2 for bone regeneration. Nano Res. 2020, 13, 2323-2331.
Li, J. C.; Chen, Y.; Kawazoe, N.; Chen, G. P. Ligand density- dependent influence of arginine-glycine-aspartate functionalized gold nanoparticles on osteogenic and adipogenic differentiation of mesenchymal stem cells. Nano Res. 2018, 11, 1247-1261.
Qin, H.; Zhu, C.; An, Z. Q.; Jiang, Y.; Zhao, Y. C.; Wang, J. X.; Liu, X.; Hui, B.; Zhang, X. L.; Wang, Y. Silver nanoparticles promote osteogenic differentiation of human urine-derived stem cells at noncytotoxic concentrations. Int. J. Nanomedicine 2014, 9, 2469-2478.
Lv, L. W.; Liu, Y. S.; Zhang, P.; Zhang, X.; Liu, J. Z.; Chen, T.; Su, P. L.; Li, H. Y.; Zhou, Y. S. The nanoscale geometry of TiO2 nanotubes influences the osteogenic differentiation of human adipose-derived stem cells by modulating H3K4 trimethylation. Biomaterials 2015, 39, 193-205.
Wang, Q. W.; Chen, B.; Ma, F.; Lin, S. K.; Cao, M.; Li, Y.; Gu, N. Magnetic iron oxide nanoparticles accelerate osteogenic differentiation of mesenchymal stem cells via modulation of long noncoding RNA INZEB2. Nano Res. 2017, 10, 626-642.
Kang, H.; Zhang, K. Y.; Pan, Q.; Lin, S. E.; Wong, D. S. H.; Li, J. M.; Lee, W. Y. W.; Yang, B. G.; Han, F. X.; Li, G. et al. Remote control of intracellular calcium using Upconversion Nanotransducers regulates stem cell differentiation in vivo. Adv. Funct. Mater. 2018, 28, 1802642.
Franz, S.; Rammelt, S.; Scharnweber, D.; Simon, J. C. Immune responses to implants - A review of the implications for the design of immunomodulatory biomaterials. Biomaterials 2011, 32, 6692-6709.
Jin, S. S.; He, D. Q.; Luo, D.; Wang, Y.; Yu, M.; Guan, B.; Fu, Y.; Li, Z. X.; Zhang, T.; Zhou, Y. H. et al. A biomimetic hierarchical nanointerface orchestrates macrophage polarization and mesenchymal stem cell recruitment to promote endogenous bone regeneration. ACS Nano 2019, 13, 6581-6595.
Zhao, D. W.; Liu, C.; Zuo, K. Q.; Su, P.; Li, L. B.; Xiao, G. Y.; Cheng, L. Strontium-zinc phosphate chemical conversion coating improves the osseointegration of titanium implants by regulating macrophage polarization. Chem. Eng. J. 2021, 408, 127362.
Mahon, O. R.; Browe, D. C.; Gonzalez-Fernandez, T.; Pitacco, P.; Whelan, I. T.; Von Euw, S.; Hobbs, C.; Nicolosi, V.; Cunningham, K. T.; Mills, K. H. G. et al. Nano-particle mediated M2 macrophage polarization enhances bone formation and MSC osteogenesis in an IL-10 dependent manner. Biomaterials 2020, 239, 119833.
Chen, Z. T.; Klein, T.; Murray, R. Z.; Crawford, R.; Chang, J.; Wu, C. T.; Xiao, Y. Osteoimmunomodulation for the development of advanced bone biomaterials. Mater. Today 2016, 19, 304-321.
Pajarinen, J.; Lin, T.; Gibon, E.; Kohno, Y.; Maruyama, M.; Nathan, K.; Lu, L.; Yao, Z. Y.; Goodman, S. B. Mesenchymal stem cell-macrophage crosstalk and bone healing. Biomaterials 2019, 196, 80-89.
Mantovani, A.; Biswas, S. K.; Galdiero, M. R.; Sica, A.; Locati, M. Macrophage plasticity and polarization in tissue repair and remodelling. J. Pathol. 2013, 229, 176-185.
Martinez, F. O.; Sica, A.; Mantovani, A.; Locati, M. Macrophage activation and polarization. Front. Biosci. 2008, 13, 453-461.
Wei, Y. J.; Tsai, K. S.; Lin, L. C.; Lee, Y. T.; Chi, C. W.; Chang, M. C.; Tsai, T. H.; Hung, S. C. Catechin stimulates osteogenesis by enhancing PP2A activity in human mesenchymal stem cells. Osteoporos. Int. 2011, 22, 1469-1479.
Chen, C. H.; Ho, M. L.; Chang, J. K.; Hung, S. H.; Wang, G. J. Green tea catechin enhances osteogenesis in a bone marrow mesenchymal stem cell line. Osteoporos. Int. 2005, 16, 2039-2045.
Jiang, Y.; Ding, S. J.; Li, F.; Zhang, C.; Sun-Waterhouse, D.; Chen, Y. L.; Li, D. P. Effects of (+)-catechin on the differentiation and lipid metabolism of 3T3-L1 adipocytes. J. Funct. Foods 2019, 62, 103558.
Furuyashiki, T.; Nagayasu, H.; Aoki, Y.; Bessho, H.; Hashimoto, T.; Kanazawa, K.; Ashida, H. Tea catechin suppresses adipocyte differentiation accompanied by down-regulation of PPARγ2 and C/EBPα in 3T3-L1 cells. Biosci. Biotechnol. Biochem. 2004, 68, 2353-2359.
Huang, J.; Wang, Y.; Xie, Z.; Zhou, Y.; Zhang, Y.; Wan, X. The anti- obesity effects of green tea in human intervention and basic molecular studies. Eur. J. Clin. Nutr. 2014, 68, 1075-1087.
He, J. T.; Xu, L.; Yang, L.; Wang, X. F. Epigallocatechin gallate is the most effective catechin against antioxidant stress via hydrogen peroxide and radical scavenging activity. Med. Sci. Monit. 2018, 24, 8198-8206.
Ma, B. J.; Wang, S.; Liu, F.; Zhang, S.; Duan, J. Z.; Li, Z.; Kong, Y.; Sang, Y. H.; Liu, H.; Bu, W. B. et al. Self-assembled copper-amino acid nanoparticles for in situ glutathione "AND" H2O2 sequentially triggered Chemodynamic therapy. J. Am. Chem. Soc. 2019, 141, 849-857.
Xu, C. N.; Wang, Y. B.; Yu, H. Y.; Tian, H. Y.; Chen, X. S. Multifunctional Theranostic nanoparticles derived from fruit-extracted Anthocyanins with dynamic disassembly and elimination abilities. ACS Nano 2018, 12, 8255-8265.
Ejima, H.; Richardson, J. J.; Liang, K.; Best, J. P.; van Koeverden, M. P.; Such, G. K.; Cui, J. W.; Caruso, F. One-step assembly of coordination complexes for versatile film and particle engineering. Science 2013, 341, 154-157.
Zhou, J. J.; Lin, Z. X.; Ju, Y.; Rahim, M.; Richardson, J. J.; Caruso, F. Polyphenol-mediated assembly for particle engineering. Acc. Chem. Res. 2020, 53, 1269-1278.
Nairz, M.; Weiss, G. Iron in infection and immunity. Mol. Aspects Med. 2020, 75, 100864.
Agoro, R.; Taleb, M.; Quesniaux, V. F. J.; Mura, C. Cell iron status influences macrophage polarization. PLoS One 2018, 13, e0196921.
Wang, Y. Q.; Zhang, J.; Zhang, C. Y.; Li, B. J.; Wang, J. J.; Zhang, X. J.; Li, D.; Sun, S. K. Functional-protein-assisted fabrication of Fe-gallic acid coordination polymer nanonetworks for localized photothermal therapy. ACS Sustainable Chem. Eng. 2018, 7, 994- 1005.
Liu, F. Y.; He, X. X.; Chen, H. D.; Zhang, J. P.; Zhang, H. M.; Wang, Z. X. Gram-scale synthesis of coordination polymer nanodots with renal clearance properties for cancer theranostic applications. Nat. Commun. 2015, 6, 8003.
Kong, Y.; Ma, B. J.; Liu, F.; Chen, D.; Zhang, S.; Duan, J. Z.; Huang, Y.; Sang, Y. H.; Wang, J. J.; Li, D. et al. Cellular stemness maintenance of human adipose-derived stem cells on ZnO nanorod arrays. Small 2019, 15, 1904099.
Zhang, S. L.; Li, J.; Lykotrafitis, G.; Bao, G.; Suresh S. Size-dependent endocytosis of nanoparticles. Adv. Mater. 2009, 21, 419-424.
Zou, W.; Rohatgi, N.; Brestoff, J. R.; Li, Y. J.; Barve, R. A.; Tycksen, E.; Kim, Y.; Silva, M. J.; Teitelbaum, S. L. Ablation of fat cells in adult mice induces massive bone gain. Cell Metab. 2020, 32, 801-813. e6.
Zhang, K. Y.; Jia, Z. F.; Yang, B. G.; Feng, Q.; Xu, X.; Yuan, W. H.; Li, X. F.; Chen, X. Y.; Duan, L.; Wang, D. P. et al. Adaptable hydrogels mediate cofactor-assisted activation of biomarker-responsive drug delivery via positive feedback for enhanced tissue regeneration. Adv. Sci. 2018, 5, 1800875.
Feng, Q.; Xu, J. K.; Zhang, K. Y.; Yao, H.; Zheng, N. Y.; Zheng, L. Z.; Wang, J. L.; Wei, K. C.; Xiao, X. F.; Qin, L. et al. Dynamic and cell- infiltratable hydrogels as injectable carrier of therapeutic cells and drugs for treating challenging bone defects. ACS Cent. Sci. 2019, 5, 440-450.
Wood, M. J.; Leckenby, A.; Reynolds, G.; Spiering, R.; Pratt, A. G.; Rankin, K. S.; Isaacs, J. D.; Haniffa, M. A.; Milling, S.; Hilkens, C. M. U. Macrophage proliferation distinguishes 2 subgroups of knee osteoarthritis patients. JCI Insight 2019, 4, e125325.
Fan. F. Y.; Sang, L. X.; Jiang M. Catechins and their therapeutic benefits to inflammatory bowel disease. Molecules 2017, 22, 484.
Cuzzocrea, S.; Mazzon, E.; Dugo, L.; Genovese, T.; Di Paola, R.; Ruggeri, Z.; Vegeto, E.; Caputi, A. P.; Van de Loo, F. A. J.; Puzzolo, D. et al. Inducible nitric oxide synthase mediates bone loss in ovariectomized mice. Endocrinology 2003, 144, 1098-1107.