Proangiogenic effect and underlying mechanism of holmium oxide nanoparticles: a new biomaterial for tissue engineering.

Publisher: BioMed Central Country of Publication: England NLM ID: 101152208 Publication Model: Electronic Cited Medium: Internet ISSN: 1477-3155 (Electronic) Linking ISSN: 14773155 NLM ISO Abbreviation: J Nanobiotechnology Subsets: MEDLINE

Original Publication: London : BioMed Central, 2003-

Tissue Engineering*/methods ; Human Umbilical Vein Endothelial Cells* ; Holmium*/chemistry ; Cell Movement*/drug effects ; Biocompatible Materials*/chemistry ; Biocompatible Materials*/pharmacology ; Neovascularization, Physiologic*/drug effects; Humans ; Animals ; Mice ; Metal Nanoparticles/chemistry ; Oxides/chemistry ; Oxides/pharmacology ; Ephrin-B2/metabolism ; Signal Transduction/drug effects ; Male ; Nanoparticles/chemistry

Background: Early angiogenesis provides nutrient supply for bone tissue repair, and insufficient angiogenesis will lead tissue engineering failure. Lanthanide metal nanoparticles (LM NPs) are the preferred materials for tissue engineering and can effectively promote angiogenesis. Holmium oxide nanoparticles (HNPs) are LM NPs with the function of bone tissue "tracking" labelling. Preliminary studies have shown that HNPs has potential of promote angiogenesis, but the specific role and mechanism remain unclear. This limits the biological application of HNPs.
Results: In this study, we confirmed that HNPs promoted early vessel formation, especially that of H-type vessels in vivo, thereby accelerating bone tissue repair. Moreover, HNPs promoted angiogenesis by increasing cell migration, which was mediated by filopodia extension in vitro. At the molecular level, HNPs interact with the membrane protein EphrinB2 in human umbilical vein endothelial cells (HUVECs), and phosphorylated EphrinB2 can bind and activate VAV2, which is an activator of the filopodia regulatory protein CDC42. When these three molecules were inhibited separately, angiogenesis was reduced.
Conclusion: Overall, our study confirmed that HNPs increased cell migration to promote angiogenesis for the first time, which is beneficial for bone repair. The EphrinB2/VAV2/CDC42 signalling pathway regulates cell migration, which is an important target of angiogenesis. Thus, HNPs are a new candidate biomaterial for tissue engineering, providing new insights into their biological application.
(© 2024. The Author(s).)

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81600904 National Natural Science Fund; B090916004 Development and Application of 3D Printing Personalized Oral Medical Products, Major Science and Technology Project of Guangdong Province

Keywords: Angiogenesis; CDC42; EphrinB2; Holmium oxide nanoparticles; Migration

W1XX32SQN1 (Holmium)
0 (Biocompatible Materials)
0 (Oxides)
0 (Ephrin-B2)

Date Created: 20240620 Date Completed: 20240621 Latest Revision: 20240623

20240623

PMC11191282

10.1186/s12951-024-02642-x

38902755