Application of many vital hydrophilic medicines have been restricted by blood-brain barrier (BBB) for treatment of brain diseases. In this study, a targeted drug delivery system based on dextran-spermine biopolymer was developed for drug transport across BBB. Drug loaded magnetic dextran-spermine nanoparticles (DS-NPs) were prepared via ionic gelation followed by transferrin (Tf) conjugation as targeting moiety. The characteristics of Tf conjugated nanoparticles (TDS-NPs) were analyzed by different methods and their cytotoxicity effects on U87MG cells were tested. The superparamagnetic characteristic of TDS-NPs was verified by vibration simple magnetometer. Capecitabine loaded TDS-NPs exhibited pH-sensitive release behavior with enhanced cytotoxicity against U87MG cells, compared to DS-NPs and free capecitabine. Prussian-blue staining and TEM-imaging showed the significant cellular uptake of TDS-NPs. Furthermore, a remarkable increase of Fe concentrations in brain was observed following their biodistribution and histological studies in vivo, after 1 and 7 days of post-injection. Enhanced drug transport across BBB and pH-triggered cellular uptake of TDS-NPs indicated that these theranostic nanocarriers are promising candidate for the brain malignance treatment. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2851-2864, 2017.
Among polymers, polyaniline (PANi) has been introduced as a good candidate for muscle regeneration due to high conductivity and also biocompatibility. Herein, for the first time, we report the use of electrospun nanofibrous membrane of PAN-PANi as efficient scaffold for muscle regeneration. The prepared PAN-PANi electrospun nanofibrous membrane was characterized by scanning electron microscopy (SEM), Attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR) and tensile examination. The softer scaffolds of non-composite electrospun nanofibrous PAN govern a higher rate of cell growth in spite of lower differentiation value. On the other hand, PAN-PANi electrospun nanofibrous membrane exposed high cell proliferation and also differentiation value. Thank to the conductive property and higher Young's modulus of composite type due to the employment of PANi, satellite cells were induced into more matured form as analyzed by Real-Time PCR. On the other hand, grafting of composite nanofibrous electrospun scaffold with gelatin increased the surface stiffness directing satellite cells into lower cell proliferation and highest value of differentiation. Our results for first time showed the significant role of combination between conductivity, mechanical property and surface modification of PAN-PANi electrospun nanofibers and provid new insights into most biocompatible scaffolds for muscle tissue engineering. The schematic figure conveys the effective combination of conductive and surface stiffness on muscle tissue engineering.
The increasing demand for biocompatible bone substitutes has made it a priority to tissue engineering and regenerative medicine scientists. Combination of minerals, growth factors, and extracellular matrix (ECM) proteins with nanofibrous scaffolds is a potential promising strategy for bone reconstruction and clinical applications. In this study, nanohydroxyapatite (nHA) was incorporated in electrospun nanofibrous polycaprolactone (PCL) scaffolds coated with fibronectin (Fn). The potential bone regeneration capacities of these scaffolds were evaluated in vitro and in vivo using mouse mesenchymal stem cells (mMSCs). The interconnected pores and proper mechanical characteristics of the fabricated electrospun PCL mats in combination with nHA and Fn provided suitable environment for cell attachment, proliferation, and enhanced osteogenic differentiation. The synergistic effect of Fn and nHA on the both in vitro and in vivo increase of calcium deposition was assessed by biochemical analysis. In addition, alkaline phosphatase (ALP) activity in nHA-incorporated PCL scaffold (PCL/nHA) and Fn-coated PCL/nHA (PCL/nHA/Fn) were significantly higher in comparison to the control group. Quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) analyses of important bone-related genes (ALP, osteocalcin, osteopontin, and Runx2) revealed that Fn has additive effect on promoting the osteogenic differentiation. The aforementioned results indicated that nanofibrous PCL/nHA scaffold coated with Fn is a promising candidate for bone-tissue engineering applications.
The three-dimensional (3D) nano scaffold of the cellulose acetate (CA) containing graphene/cobalt nanocomposite (0.1[Formula: see text]wt.%) was fabricated via electrospinning technique, and its impact on bone regeneration was investigated. Through this aim, bone marrow mesenchymal stem cells are cultured on the CA, and graphene/cobalt (rGO/Co)/CA nanocomposite scaffold surfaces and the samples are treated under low frequency alternative magnetic field (75[Formula: see text]Hz). The scaffolds are characterized using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermal studies (TG/DSC). The proliferation behavior of stem cells on CA, and rGO/Co/CA nano scaffolds are studied by MTT assay, show their biocompability after 14 days of cell seeding. The 6-diamidino-2-phenylindole (DAPI) staining is used to confirm the morality of stem cell for duration of seven days. The nanocomposite scaffold is enhanced for extremely higher proliferation compared to the bare CA scaffold. The acceleration on osteogenic differentiation on the bone mesenchymal stem cell is enhanced within 48[Formula: see text]h when rGO/Co/CA scaffold is placed under alternative current magnetic field (ACMF). Furthermore, the acceleration of the stem cells differentiation for the rGO/Co/CA scaffold under ACMF corresponds to the induced scaffold surface roughness caused by graphene sheets, the metallic behavior of graphene and the responding of the nanocomposite magnetic parts (i.e., cobalt nanoparticles) while applying 75[Formula: see text]Hz frequency. Using reverse transcription polymerase chain reaction (RT-PCR) analysis, the superior effect of ACMF on scaffold contain magnetic graphene nanocomposite is confirmed to produce bone related genes within 14 days.
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