Bioinstructive Naringin‐Loaded Micelles for Guiding Stem Cell Osteodifferentiation. Issue 19 (14th August 2018)

• Record Type: Journal Article
• Authors: Lavrador, Pedro; Gaspar, Vítor M.; Mano, João F.
• Is Part Of: Advanced healthcare materials. Volume 7:Issue 19(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-08-14
• Subjects: controlled release -- human adipose‐derived mesenchymal stem cells -- naringin -- osteogenic differentiation -- polymeric micelles; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201800890
• Languages: English
• ISSNs: 2192-2640

Abstract

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 1 H NMR and attenuated total reflectance Fourier transformed infrared (ATR‐FTIR) spectroscopy. The resulting mPEGMSPLA copolymer self‐assembles into monodispersed polymeric micelles (≈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. Abstract : Naringin is a naturally occurring flavanone with promising potential to bioinstruct stem cells toward osteogenic lineages. Naringin‐loaded methoxy‐poly(ethylene glycol)–maleimide–thiol–poly(l ‐lactide) nanomicelles' administration to human adipose‐derived mesenchymal stem cells (hASCs) allows to rapidly induce hASC differentiation and augments the pro‐osteogenic effect over that of free drug and standard induction methods, thus indicating their potential to enhance stem cell–based bone regeneration.