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Ultrafine surface features are commonly used to modulate the cellular activity of a variety of materials including ceramics, [1,2] composites, [3,4] nanofibers, [5,6] and polymers. [7,8] However, the main challenge for materials in contact with bone remains the development of a material with both favorable surface and bulk properties to modulate not only cell-substrate interactions but also to ensure the long-term stability of the implant. This challenge has motivated researchers to develop bulk nanostructured materials while applying different surface treatments to improve cellular adhesion and metabolic activities. Here, in a combined approach involving materials science and cell and molecular biology, the responses of pre-osteoblast and fibroblast cell lines to novel nanostructured titanium substrates produced by high-pressure torsion (HPT) is assessed and compared with the cellular activity on coarse-grained, annealed titanium substrates. The degree of osteoblast attachment is notably increased on the HPT-processed titanium substrates. The improved cellular response is attributed to the nanostructured features of the samples, which are characterized by an ultrafine grain size (< 50 nm), and a high degree of surface wettability associated with a distinctive oxide layer formed on the surface. This finding provides a valuable advantage for HPT-processed titanium over conventional and coated titanium implants, as both the mechanical and physical properties, along with biological activities, are improved. The most developed severe plastic deformation (SPD) techniques for producing bulk nonporous samples are equal-channel angular pressing (ECAP) and HPT. [9,10] Recent studies indicate that high pressure during SPD significantly affects the development of the crystal structure and consequently enables the production of materials composed of sub-micrometer-or nanometer-sized metal crystals, both on the surface and in the bulk, that have reduced porosity, cracks, and other macroscopic defects. [11,12] These characteristics make the material very attractive for advanced applications in the aerospace, sport, transportation, and, in particular, medical industries.[13] Along with nanostructured surface features, material processed by HPT has a good combination of high strength and high ductility at room temperature. These are two desirable but rarely co-existing properties important for the longterm stability of metallic implants. [14,15] Although many reports are available on the bulk characterization of these materials, reports detailing the effects of high pressure on the surface properties of nanostructured titanium are mostly fragmented, and its significance with regards to cell-substrate interactions has not been addressed. In this work, commercially pure titanium was used to fabricate substrates with different nano/microstructures through HPT and annealing processes. After fabrication of the substrates, surface characterization was performed by orientation image microscopy (OIM), transmission electron microscopy (T...

BackgroundA folate-receptor-targeted poly (lactide-co-Glycolide) (PLGA)-Polyethylene glycol (PEG) nanoparticle is developed for encapsulation and delivery of disulfiram into breast cancer cells. After a comprehensive characterization of nanoparticles, cell cytotoxicity, apoptosis induction, cellular uptake and intracellular level of reactive oxygen species are analyzed. In vivo acute and chronic toxicity of nanoparticles and their efficacy on inhibition of breast cancer tumor growth is studied.ResultsThe folate-receptor-targeted nanoparticles are internalized into the cells, induce reactive oxygen species formation, induce apoptosis and inhibit cell proliferation more efficiently compared to the untargeted nanoparticles. The acute and toxicity test show the maximum dose of disulfiram equivalent of nanoparticles for intra-venous injection is 6 mg/kg while show significant decrease in the breast cancer tumor growth rate.ConclusionIt is believed that the developed formulation could be used as a potential vehicle for successful delivery of disulfiram, an old and inexpensive drug, into breast cancer cells and other solid tumors.Graphical abstractDisulfiram, an old and inexpensive drug, is encapsulated in folate-targeted PLGA-PEG nanoparticles and delivered into breast cancer cells using passive and active targeting to inhibit tumor growth in mice

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Many approaches have been developed to regenerate biological substitutes for repairing damaged tissues. Guided bone/tissue regeneration (GBR/GTR) that employs a barrier membrane has received much attention in recent years. Regardless of substantial efforts for treatment of damaged tissue in recent years, an effective therapeutic strategy is still a challenge for tissue engineering researchers. The aim of the current study is to fabricate a GBR membrane consisting of polycaprolactone (PCL)/gelatin/chitosan which is modified with different percentages of β-tricalcium phosphate (β-TCP) for improved biocompatibility, mechanical properties, and antibacterial activity. The membranes are examined for their mechanical properties, surface roughness, hydrophilicity, biodegradability and biological response. The mechanical properties, wettability and roughness of the membranes are improved with increases in β-TCP content. An increase in the elastic modulus of the substrates is obtained as the amount of β-TCP increases to 5% (145–200 MPa). After 5 h, the number of attached cells is enhanced by 30%, 40% and 50% on membranes having 1%, 3% and 5% β-TCP, respectively. The cell growth on a membrane with 3% of β-TCP is also 50% and 20% higher than those without β-TCP and 5% β-TCP, respectively. Expression of type I collagen is increased with addition of β-TCP by 3%, while there is no difference in ALP activity. The results indicated that a composite having (3%) β-TCP has a potential application for guided bone tissue regeneration.

This in vitro study aimed to evaluate the physicochemical and biological activity of the polycaprolactone/chitosan/collagen scaffolds incorporated with 0, 0.5, 3, and 6 wt% of graphene oxide (GO). Using standard tests and MG-63 cells, the characteristics of scaffolds were evaluated, and the behavior of osteoblasts were simulated, respectively. A non-significant decrease in nanofibers diameter was noted in scaffolds with a higher ratio of GO. The hydrophilicity and bioactivity of the scaffold surface, as well as cell attachment and proliferation, increased in correspondence to an increase in GO. The higher ratio of GO also improved the osteogenesis activity.GO increased the degradation rate, but it was negligible and seemed not enough to endanger stability. Modifying the scaffolds with GO did not make a significant change to the antibacterial effect.