Bioinstructive Naringin-Loaded Micelles for Guiding Stem Cell Osteodifferentiation
authors Lavrador, P; Gaspar, VM; Mano, JF
nationality International
journal ADVANCED HEALTHCARE MATERIALS
author keywords controlled release; human adipose-derived mesenchymal stem cells; naringin; osteogenic differentiation; polymeric micelles
keywords OSTEOGENIC DIFFERENTIATION; CONTROLLED-RELEASE; BONE; DELIVERY; PROLIFERATION; DEXAMETHASONE; NANOPARTICLES; METABOLISM; EXPRESSION; FLAVONOIDS
abstract Naringin is a naturally occurring flavanone with recognized neuroprotective, cardioprotective, anti-inflammatory, and antiosteoporotic properties. Herein, the delivery of Naringin-loaded methoxy-poly(ethylene glycol)-maleimide-thiol-poly(L-lactide) (mPEG-MS-PLA) diblock polymeric micelles to human adipose-derived stem cells (hASCs) with the aim to augment its pro-osteogenic effect in these cells is reported for the first time. The synthesis of the diblock copolymer is performed via Michael-type addition reaction between hydrophilic methoxy-poly(ethylene glycol)-maleimide (mPEG-MAL) and hydrophobic thiol-poly(l-lactide) (PLA-SH) and confirmed by H-1 NMR and attenuated total reflectance Fourier transformed infrared (ATR-FTIR) spectroscopy. The resulting mPEG-MS-PLA copolymer self-assembles into monodispersed polymeric micelles (similar or equal to 84.4 +/- 2 nm) and presents a high Naringin encapsulation efficiency (87.8 +/- 4%), with a sustained release profile at physiological pH. Alongside, in vitro data reveal that upon internalization into hASC 2D cultures, Naringin nanomicellar formulations attain a higher pro-osteogenic effect than that of free drug. Notably, these bioactive carriers also induce superior osteopontin expression and increase matrix mineralization in these cells over free drug administration. Overall, such findings support for the first time the use of polymeric nanomicelles for Naringin delivery into hASCs as a valid approach for modulating stem cell osteogenic differentiation.
publisher WILEY
issn 2192-2640
year published 2018
volume 7
issue 19
digital object identifier (doi) 10.1002/adhm.201800890
web of science category Engineering, Biomedical; Nanoscience & Nanotechnology; Materials Science, Biomaterials
subject category Engineering; Science & Technology - Other Topics; Materials Science
unique article identifier WOS:000446822600018
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journal analysis (jcr 2017):
journal impact factor 5.609
5 year journal impact factor 5.849
category normalized journal impact factor percentile 83.503
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