2026-06-27T22:58:46Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/80502024-04-16T15:20:29Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Casarrubios Molina, Laura author Polo Montalvo, Alberto author Serrano, María Concepción author Feito Castellano, María José author Vallet Regí, María Dulce Nombre author Arcos Navarrete, Daniel author Portolés Pérez, María Teresa 2023-06-17T09:03:18Z 2023-06-17T09:03:18Z 2021-04-24 2079-4991 10.3390/nano11051102 https://hdl.handle.net/20.500.14352/8050 https://doi.org/10.3390/nano11051102 https://www.ucm.es/valletregigrouphttps://www.mdpi.com/2079-4991/11/5/1102 Angiogenic biomaterials for bone repair are being designed to promote vascularization and optimize tissue regeneration. The use of nanoparticles of bioactive materials loaded with different drugs represents an interesting strategy to stimulate osteogenesis and angiogenesis and to inhibit bone resorption. Ipriflavone (IP) prevents osteoporosis by inhibiting osteoclast activity and promoting preosteoblast differentiation into mature osteoblasts. Since endothelial progenitor cells (EPCs) are involved in the formation of blood vessels which are necessary for tissue regeneration, the isolation and characterization of porcine EPCs have been carried out in this work to evaluate the in vitro effects of unloaded (NanoMBGs) and IP-loaded nanospheres (NanoMBG-IPs) designed to stimulate osteogenesis. Because different signals between vascular and nonvascular cells are also essential to initiate angiogenic events, the potential modulating role of macrophages has been also evaluated by studying the expression of vascular endothelial growth factor receptor 2 (VEFGR2) as a specific marker for EPC differentiation under different culture conditions: a) EPCs in monoculture treated with NanoMBGs or NanoMBG-IPs, b) EPCs treated with conditioned media from basal, proinflammatory M1 and reparative M2 macrophages previously treated with NanoMBGs or NanoMBG-IPs, c) EPCs cocultured with macrophages in the presence of NanoMBGs or NanoMBG-IPs, and d) EPCs cocultured with M2d angiogenic macrophages. Moreover, the endocytic mechanisms by which these nanospheres are incorporated by EPCs have been identified by using six endocytosis inhibitors (i.e. wortmannin, genistein, cytochalasin B, cytochalasin D, phenylarsine oxide and chlorpromazine) and before the addition of NanoMBGs labeled with fluorescein isothiocyanate. The results evidence the great potential of both NanoMBGs and NanoMBG-IPs to enhance VEFGR2 expression, directly related to angiogenesis, after intracellular incorporation by EPCs through different endocytic mechanisms including clathrin-dependent endocytosis, as the main entry mechanism, but also phagocytosis and caveolae-mediated uptake. The treatment of EPCs with culture media from basal, M1 and M2 macrophages and the development of cocultures of EPCs with macrophages in the absence and presence of these nanomaterials have also confirmed the maintenance of their angiogenic effect on EPCs even in the presence of phagocytic cells. eng Atribución 3.0 España Effects of ipriflavone-loaded mesoporous nanospheres on the differentiation of endothelial cells and their modulation by macrophages. journal article URL https://docta.ucm.es/bitstreams/5a312ab9-4012-4b2d-a7a1-be4c25780c49/download File MD5 0c1ca040dec0918a41478f2b7328fca8 4124083 application/pdf nanomaterials-11-01102.pdf