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Citation
Tags
HERO ID
8029189
Reference Type
Journal Article
Title
Nano-particle mediated M2 macrophage polarization enhances bone formation and MSC osteogenesis in an IL-10 dependent manner
Author(s)
Mahon, OR; Browe, DC; Gonzalez-Fernandez, T; Pitacco, P; Whelan, IT; Von Euw, S; Hobbs, C; Nicolosi, V; Cunningham, KT; Mills, KHG; Kelly, DJ; Dunne, A
Year
2020
Is Peer Reviewed?
Yes
Journal
Biomaterials
ISSN:
0142-9612
EISSN:
1878-5905
Volume
239
Page Numbers
119833
Language
English
PMID
32062479
DOI
10.1016/j.biomaterials.2020.119833
Web of Science Id
WOS:000518868700002
Abstract
Engineering a pro-regenerative immune response following scaffold implantation is integral to functional tissue regeneration. The immune response to implanted biomaterials is determined by multiple factors, including biophysical cues such as material stiffness, topography and particle size. In this study we developed an immune modulating scaffold for bone defect healing containing bone mimetic nano hydroxyapatite particles (BMnP). We first demonstrate that, in contrast to commercially available micron-sized hydroxyapatite particles, in-house generated BMnP preferentially polarize human macrophages towards an M2 phenotype, activate the transcription factor cMaf and specifically enhance production of the anti-inflammatory cytokine, IL-10. Furthermore, nano-particle treated macrophages enhance mesenchymal stem cell (MSC) osteogenesis in vitro and this occurs in an IL-10 dependent manner, demonstrating a direct pro-osteogenic role for this cytokine. BMnPs were also capable of driving pro-angiogenic responses in human macrophages and HUVECs. Characterization of immune cell subsets following incorporation of functionalized scaffolds into a rat femoral defect model revealed a similar profile, with micron-sized hydroxyapatite functionalized scaffolds eliciting pro-inflammatory responses characterized by infiltrating T cells and elevated expression of M1 macrophages markers compared to BMnP functionalized scaffolds which promoted M2 macrophage polarization, tissue vascularization and increased bone volume. Taken together these results demonstrate that nano-sized Hydroxyapatite has immunomodulatory potential and is capable of directing anti-inflammatory innate immune-mediated responses that are associated with tissue repair and regeneration.
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