Effects of Ipriflavone-Loaded Mesoporous Nanospheres on the Differentiation of Endothelial Progenitor Cells and Their Modulation by Macrophages

• Published in: Nanomaterials (Basel, Switzerland) Vol. 11; no. 5; p. 1102
• Main Authors: Casarrubios, Laura, Polo-Montalvo, Alberto, Serrano, María Concepción, Feito, María José, Vallet-Regí, María, Arcos, Daniel, Portolés, María Teresa
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.04.2021; MDPI
• Subjects: Angiogenesis; Antibodies; Biocompatibility; Biomaterials; Biomedical materials; Blood vessels; Bone resorption; Caveolae; Cell culture; Cell differentiation; Cells (biology); Clathrin; Culture media; Cytokines; Endocytosis; endothelial progenitor cells; Genotype & phenotype; Glycoproteins; Growth factors; Hemopoiesis; Ipriflavone; Macrophages; mesoporous nanospheres; Microscopy; Nanomaterials; Nanoparticles; Nanospheres; Nanotechnology; Osteogenesis; Osteoporosis; Permeability; Phagocytes; Phagocytosis; Progenitor cells; Regeneration; Tissue engineering; Vascular endothelial growth factor; Vascular endothelial growth factor receptor 2; Vascularization; Wound healing; United Kingdom > UK; St Louis Missouri; United States > US; endocytosis; macrophages; mesoporous nanospheres; vascular endothelial growth factor receptor 2; ipriflavone; endothelial progenitor cells
• ISSN: 2079-4991; 2079-4991
• DOI: 10.3390/nano11051102

Angiogenic biomaterials are designed to promote vascularization and tissue regeneration. Nanoparticles of bioactive materials loaded with drugs represent an interesting strategy to stimulate osteogenesis and angiogenesis and to inhibit bone resorption. In this work, porcine endothelial progenitor cells (EPCs), essential for blood vessel formation, were isolated and characterized to evaluate the in vitro effects of unloaded (NanoMBGs) and ipriflavone-loaded nanospheres (NanoMBG-IPs), which were designed to prevent osteoporosis. The expression of vascular endothelial growth factor receptor 2 (VEGFR2) was studied in EPCs under different culture conditions: (a) treatment with NanoMBGs or NanoMBG-IPs, (b) culture with media from basal, M1, and M2 macrophages previously treated with NanoMBGs or NanoMBG-IPs, (c) coculture with macrophages in the presence of NanoMBGs or NanoMBG-IPs, and (d) coculture with M2d angiogenic macrophages. The endocytic mechanisms for nanosphere incorporation by EPCs were identified using six different endocytosis inhibitors. The results evidence the great potential of these nanomaterials to enhance VEGFR2 expression and angiogenesis, after intracellular incorporation by EPCs through clathrin-dependent endocytosis, phagocytosis, and caveolae-mediated uptake. The treatment of EPCs with basal, M1, and M2 macrophage culture media and EPC/macrophage coculture studies also confirmed the angiogenic effect of these nanospheres on EPCs, even in the presence of phagocytic cells.