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Journal ArticleDOI

Prolonged proliferation and delayed senescence of the adipose-derived stem cells grown on the electrospun composite nanofiber co-encapsulated with TiO2 nanoparticles and metformin-loaded mesoporous silica nanoparticles.

TL;DR: In this paper, the effects of poly-e-Caprolactone/Gelatin nanofibers (PCL/GEL NFs) co-encapped with TiO2 nanoparticles (nTiO2) and metformin-loaded mesoporous silica nanoparticles(MET@MSNs) on prolonging the in vitro expansion of human adipose-derived stem cells (hADSCs) without inducing cellular senescence and aging FTIR, BET, FE-SEM, and TEM were applied to characterize the fabricated MET@
About: This article is published in International Journal of Pharmaceutics.The article was published on 2021-05-24. It has received 24 citations till now.
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Journal ArticleDOI
TL;DR: In this article, a hybrid of polycaprolactone and gelatin (PCL/GEL) was used for co-encapsulation of free curcumin (CUR) and CUR-loaded mesoporous silica nanoparticles via electrospinning, resulting in a novel drug-loaded nanofibrous scaffold, CUR/CUR@MSNs-NFs.
Abstract: Electrospun nanofibers (NFs)-based drug delivery approaches are of particular interest as a hopeful implantable nanoplatform for localized cancer therapy and treating tissue defect after resection, allowing the on-site drug delivery with minimal side effect to healthy cells. To maintain therapeutic concentrations of anticancer molecules for a relatively long time through a combination of burst and sustained drug release mechanisms, a hybrid of polycaprolactone and gelatin (PCL/GEL) was used for co-encapsulation of free curcumin (CUR) and CUR-loaded mesoporous silica nanoparticles (CUR@MSNs) via electrospinning, resulting in a novel drug-loaded nanofibrous scaffold, CUR/CUR@MSNs-NFs. The as-prepared MSNs and composite NFs were characterized via TGA, FTIR, FE-SEM, TEM, and BET. In vitro release profile of CUR from CUR/CUR@MSNs-NFs was examined, and the in vitro antitumor efficacy against MDA-MB-231 breast cancer cells was also evaluated through MTT, scratch assay, DAPI staining, and real-time PCR. The results disclosed that the smooth, bead-free, and randomly oriented CUR/CUR@MSNs-NFs displayed a combination of initial rapid discharge and sustained release for CUR, which led to higher cytotoxicity, lower migration as well as a more pronounced effect on apoptosis induction than CUR-NFs and CUR@MSNs-NFs. The present study illustrated that the dual drug release mechanisms through MSN/NF-mediated drug delivery systems might have a highly hopeful application as a localized implantable scaffold for potential postoperative breast cancer therapy.

22 citations

Journal ArticleDOI
TL;DR: In this paper, both free Curc and Curc-loaded mesoporous silica nanoparticles (Curc@MSNs) were integrated into the electrospun polycaprolactone/gelatin (PCL/GEL) nanofibrous scaffolds and characterized via FTIR, BET, FE-SEM and TEM.

19 citations

Journal ArticleDOI
TL;DR: In this paper , a photocurable methacryloxylated silk fibroin hydrogel (Sil-MA) system was developed to accelerate diabetic-wound healing via spatiotemporal immunomodulation.
Abstract: The complicated hyperglycaemic and chronic inflammation of diabetic wounds in orthopaedic surgery leads to dysregulated immune cell function and potential infection risk. Immune interventions in diabetic wounds face a possible contradiction between simultaneous establishment of the pro-inflammatory microenvironment in response to potential bacterial invasion and the anti-inflammatory microenvironment required for tissue repair. To study this contradiction and accelerate diabetic-wound healing, we developed a photocurable methacryloxylated silk fibroin hydrogel (Sil-MA) system, co-encapsulated with metformin-loaded mesoporous silica microspheres (MET@MSNs) and silver nanoparticles (Ag NPs).The hydrogel system (M@M-Ag-Sil-MA) enhanced diabetic-wound healing via spatiotemporal immunomodulation. Sil-MA imparts a hydrogel system with rapid in situ Ultra-Violet-photocurable capability and allows preliminary controlled release of Ag NPs, which can inhibit bacterial aggregation and create a stable, sterile microenvironment. The results confirmed the involvement of Met in the immunomodulatory effects following spatiotemporal dual-controlled release via the mesoporous silica and Sil-MA. Hysteresis-released from Met shifts the M1 phenotype of macrophages in regions of diabetic trauma to an anti-inflammatory M2 phenotype. Simultaneously, the M@M-Ag-Sil-MA system inhibited the formation of neutrophil extracellular traps (NETs) and decreased the release of neutrophil elastase, myeloperoxidase, and NETs-induced pro-inflammatory factors. As a result of modulating the immune microenvironmental, the M@M-Ag-Sil-MA system promoted fibroblast migration and endothelial cell angiogenesis in vivo, with verification of enhanced diabetic-wound healing accompanied with the spatiotemporal immunoregulation of macrophages and NETs in a diabetic mouse model.Our findings demonstrated that the M@M-Ag-Sil-MA hydrogel system resolved the immune contradiction in diabetic wounds through spatiotemporal immunomodulation of macrophages and NETs, suggesting its potential as a promising engineered nano-dressing for the treatment of diabetic wounds in orthopaedic surgery.

17 citations

Journal ArticleDOI
TL;DR: Nanofibers are cutting-edge drug delivery systems that are being utilised to treat a variety of ailments such as cancer, wound dressing, tissue engineering, sensors, etc as discussed by the authors .

13 citations

Journal ArticleDOI
TL;DR: In this paper, ZSM-5 nanozeolite was incorporated into the Poly-e-Caprolactone/Gelatin nanofibers (PCL-GEL NFs) for controlled and sustained release of a natural polyphenol, curcumin (CUR) to enhance the prolonged in vitro expansion of human adipose-derived stem cells (hADSCs) without inducing cellular senescence.

7 citations

References
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Journal ArticleDOI
06 Jun 2013-Cell
TL;DR: Nine tentative hallmarks that represent common denominators of aging in different organisms are enumerated, with special emphasis on mammalian aging, to identify pharmaceutical targets to improve human health during aging, with minimal side effects.

9,980 citations

Journal ArticleDOI
TL;DR: Self-assembled layers of vertically oriented TiO2 nanotubes with defined diameters between 15 and 100 nm are generated and show that adhesion, spreading, growth, and differentiation of mesenchymal stem cells are critically dependent on the tube diameter.
Abstract: We generated, on titanium surfaces, self-assembled layers of vertically oriented TiO2 nanotubes with defined diameters between 15 and 100 nm and show that adhesion, spreading, growth, and differentiation of mesenchymal stem cells are critically dependent on the tube diameter. A spacing less than 30 nm with a maximum at 15 nm provided an effective length scale for accelerated integrin clustering/focal contact formation and strongly enhances cellular activities compared to smooth TiO2 surfaces. Cell adhesion and spreading were severely impaired on nanotube layers with a tube diameter larger than 50 nm, resulting in dramatically reduced cellular activity and a high extent of programmed cell death. Thus, on a TiO2 nanotube surface, a lateral spacing geometry with openings of 30−50 nm represents a critical borderline for cell fate.

1,105 citations

Journal ArticleDOI
07 Jan 2016-Nature
TL;DR: It is reported that basal autophagy is essential to maintain the stem-cell quiescent state in mice and revealed to be a decisive stem- cell-fate regulator, with implications for fostering muscle regeneration in sarcopenia.
Abstract: During ageing, muscle stem-cell regenerative function declines. At advanced geriatric age, this decline is maximal owing to transition from a normal quiescence into an irreversible senescence state. How satellite cells maintain quiescence and avoid senescence until advanced age remains unknown. Here we report that basal autophagy is essential to maintain the stem-cell quiescent state in mice. Failure of autophagy in physiologically aged satellite cells or genetic impairment of autophagy in young cells causes entry into senescence by loss of proteostasis, increased mitochondrial dysfunction and oxidative stress, resulting in a decline in the function and number of satellite cells. Re-establishment of autophagy reverses senescence and restores regenerative functions in geriatric satellite cells. As autophagy also declines in human geriatric satellite cells, our findings reveal autophagy to be a decisive stem-cell-fate regulator, with implications for fostering muscle regeneration in sarcopenia.

963 citations

Journal ArticleDOI
TL;DR: Metformin, which has demonstrated protective effects against several age-related diseases in humans, will be tested in the TAME (Targeting Aging with Metformin) trial, as the initial step in the development of increasingly effective next-generation drugs.

686 citations

Journal ArticleDOI
TL;DR: The exciting progress in the development of MSNs-based effective delivery systems for poorly soluble drugs, anticancer agents, and therapeutic genes are highlighted.

433 citations

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