RESUMEN
Mesoporous bioactive glass nanoparticles (MBGNs) doped with therapeutical ions present multifunctional systems that enable a synergistic outcome through the dual delivery of drugs and ions. The aim of this study was to evaluate influence of co-doping with strontium and magnesium ions (SrMg-MBGNs) on the properties of MBGNs. A modified microemulsion-assisted sol-gel synthesis was used to obtain particles, and their physicochemical properties, bioactivity, and drug-loading/release ability were evaluated. Indirect biological assays using 2D and 3D cell culture models on human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and endothelial EA.hy926 cells, respectively, were used to determine biocompatibility of MBGNs, their influence on alkaline phosphatase (ALP) production, calcium deposition, and cytoskeletal organization. Results showed that Sr,Mg-doping increased pore volume and solubility, and changed the mesoporous structure from worm-like to radial-dendritic, which led to a slightly accelerated drug release compared to pristine MBGNs. Biological assays confirmed that particles are biocompatible, and have ability to slightly induce ALP production and calcium deposition of hBM-MSCs, as well as to significantly improve the proliferation of EA.hy926 compared to biochemical stimulation via vascular endothelial growth factor (VEGF) administration or regular media. Fluorescence staining revealed that SrMg-MBGNs had a similar effect on EA.hy926 cytoskeletal organization to the VEGF group. In conclusion, Sr,Mg-MBGNs might be considered promising biomaterial for biomedical applications.
Asunto(s)
Regeneración Ósea , Sistemas de Liberación de Medicamentos , Vidrio , Magnesio , Células Madre Mesenquimatosas , Nanopartículas , Estroncio , Humanos , Regeneración Ósea/efectos de los fármacos , Nanopartículas/química , Estroncio/química , Estroncio/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Porosidad , Magnesio/química , Vidrio/química , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Línea Celular , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Proliferación Celular/efectos de los fármacosRESUMEN
Recently, many studies have shown various beneficial effects of polyphenol resveratrol (Res) on human health. The most important of these effects include cardioprotective, neuroprotective, anti-cancer, anti-inflammatory, osteoinductive, and anti-microbial effects. Resveratrol has cis and trans isoforms, with the trans isoform being more stable and biologically active. Despite the results of in vitro experiments, resveratrol has limited potential for application in vivo due to its poor water solubility, sensitivity to oxygen, light, and heat, rapid metabolism, and therefore low bioavailability. The possible solution to overcome these limitations could be the synthesis of resveratrol in nanoparticle form. Accordingly, in this study, we have developed a simple, green solvent/non-solvent physicochemical method to synthesize stable, uniform, carrier-free resveratrol nanobelt-like particles (ResNPs) for applications in tissue engineering. UV-visible spectroscopy (UV-Vis) was used to identify the trans isoform of ResNPs which remained stable for at least 63 days. The additional qualitative analysis was performed by Fourier transform infrared spectroscopy (FTIR), while X-ray diffraction (XRD) determined the monoclinic structure of resveratrol with a significant difference in the intensity of diffraction peaks between commercial and nano-belt form. The morphology of ResNPs was evaluated by optical microscopy and field-emission scanning electron microscope (FE-SEM) that revealed a uniform nanobelt-like structure with an individual thickness of less than 1 µm. Bioactivity was confirmed using Artemia salina in vivo toxicity assay, while 2,2-diphenyl-1-picrylhydrazylhydrate (DPPH) reduction assay showed the good antioxidative potential of concentrations of 100 µg/ml and lower. Microdilution assay on several reference strains and clinical isolates showed promising antibacterial potential on Staphylococci, with minimal inhibitory concentration (MIC) being 800 µg/ml. Bioactive glass-based scaffolds were coated with ResNPs and characterized to confirm coating potential. All of the above make these particles a promising bioactive, easy-to-handle component in various biomaterial formulations.