Controlled drug delivery from chitosan-coated heparin-loaded nanopores anodically grown on nitinol shape-memory alloy.

Nitinol (NiTi shape-memory alloy) is an interesting candidate in various medical applications like dental, orthopedic, and cardiovascular devices, owing to its unique mechanical behaviors and proper biocompatibility. The aim of this work is the local controlled delivery of a cardiovascular drug, heparin, loaded onto nitinol treated by electrochemical anodizing and chitosan coating. In this regard, the structure, wettability, drug release kinetics, and cell cytocompatibility of the specimens were analyzed in vitro. The two-stage anodizing process successfully developed a regular nanoporous layer of Ni-Ti-O on nitinol, which considerably decreased the sessile water contact angle and induced hydrophilicity. The application of the chitosan coatings controlled the release of heparin mainly by a diffusional mechanism, where the drug release mechanisms were evaluated by the Higuchi, first-order, zero-order, and Korsmeyer-Pepass models. Human umbilical cord endothelial cells (HUVECs) viability assay also showed the non-cytotoxicity of the samples, so that the best performance was found for the chitosan-coated samples. It is concluded that the designed drug delivery systems are promising for cardiovascular, particularly stent applications.

Ecotoxicological Assessment of Potentially Toxic Elements (as, Cd, Ni and V) Contamination in the Sediments of Southern Part of Caspian Sea, the Case of Khazar Abad, Mazandaran Province, Iran.

In this study, the contamination of arsenic, cadmium, nickel and vanadium in the surface sediments of Khazar Abad, in the southern part of the Caspian Sea was analyzed in 2019 using ecotoxicological indices. The geoaccumulation index (Igeo) values showed that the sediment samples of the study area could be classified as 'unpolluted' to 'strongly polluted', while, the values of toxic units (TUs) with an average value of 0.591 indicated that all samples could be classified as 'at low toxicity level'. Moreover, the ecotoxic risk level (TRI) in the studied sediments was classified at the level of 'no toxic risk' for Cd and 'considerable toxic risk' for As and Ni. On the whole, the results showed that the levels of contamination were higher in the areas where industrial, domestic and agricultural wastewater was discharged (i.e. S4, S7, S10, S11 and S12). Finally, to avoid and/or reduce ecotoxicological dangers, periodic monitoring of PTEs in the coastal strip of the southern part of the Caspian Sea is recommended.

Drug-delivery Ca-Mg silicate scaffolds encapsulated in PLGA.

The aim of this work is to develop dual-functional scaffolds for bone tissue regeneration and local antibiotic delivery applications. In this respect, bioresorbable bredigite (Ca7MgSi4O16) porous scaffolds were fabricated by a foam replica method, loaded with vancomycin hydrochloride and encapsulated in poly lactic-co-glycolic acid (PLGA) coatings. Field emission scanning electron microscopy, Archimedes porosimetry and Fourier-transform infrared spectroscopy were used to characterize the structure of the scaffolds. The drug delivery kinetics and cytocompatibility of the prepared scaffolds were also studied in vitro. The bare sample exhibited a burst release of vancomycin and low biocompatibility with respect to dental pulp stem cells based on the MTT assay due to the fast bioresorption of bredigite. While keeping the desirable characteristics of pores for tissue engineering, the biodegradable PLGA coatings modified the drug release kinetics, buffered physiological pH and hence improved the cell viability of the vancomycin-loaded scaffolds considerably.

PLGA-coated drug-loaded nanotubes anodically grown on nitinol.

This study evaluates the use of nanotubes (NTs) as a matrix for local drug delivery modified by a biodegradable polymeric coating on medical-grade nitinol (NiTi alloy) surfaces. For this purpose, NiTi was anodized within parameters that promote the formation of NTs, ultrasonicated, annealed and impregnated with vancomycin hydrochloride. To improve bioperformance, poly(lactic-co-glycolic acid) (PLGA) was also deposited on the drug-loaded NTs. The samples were characterized in terms of structure, wettability, drug delivery, corrosion and cytocompatibility. Scanning electron microscopy and water contact angle measurements signify the formation of open-top homogeneous NTs of 600- 700 nm in length and ~30 nm in diameter with improved hydrophilicity. The bare antibiotic-impregnated NTs exhibit a burst release of about 49% of the loaded drug in the first 6 h of soaking in a physiological medium, followed by the entire drug diffusing out before 96 h. The PLGA coating effectively controls the burst release of vancomycin to 26% and retains almost 50% of the loaded drug beyond 7 days. The kinetics of the different vancomycin-release stages is also correlated to several well-established models. As a comparative criterion of metallic ions leaching kinetics, the corrosion resistance of nitinol is found to be reduced by the formation of the NTs, while the PLGA coating enhances this electrochemical feature. Due to the alteration of the drug delivery and corrosion protection, the PLGA-coated vancomycin-impregnated sample presents a higher dental pulp stem cell viability in comparison to both the bare drug-loaded and non-loaded NTs. In conclusion, PLGA-coated vancomycin-loaded NT-covered NiTi can be effectively used as a controlled drug-delivery device, while having a drug-release dosage within the therapeutic window and a minimal negative effect on biocompatibility.

Graphene and its derivatives: Opportunities and challenges in dentistry.

The emerging science of graphene-based engineered nanomaterials as either nanomedicines or dental materials in dentistry is growing. Apart from its exceptional mechanical characteristics, electrical conductivity and thermal stability, graphene and its derivatives can be functionalized with several bioactive molecules, allowing them to be incorporated into and improve different scaffolds used in regenerative dentistry. This review presents state of the art graphene-based engineered nanomaterial applications to cells in the dental field, with a particular focus on the control of stem cells of dental origin. The interactions between graphene-based nanomaterials and cells of the immune system, along with the antibacterial activity of graphene nanomaterials are discussed. In the last section, we offer our perspectives on the various applications of graphene and its derivatives in association with titanium dental implants, membranes for bone regeneration, resins, cements and adhesives, as well as tooth-whitening procedures.

Development of 3D-printed PLGA/TiO2 nanocomposite scaffolds for bone tissue engineering applications.

Porous scaffolds were 3D-printed using poly lactic-co-glycolic acid (PLGA)/TiO2 composite (10:1 weight ratio) for bone tissue engineering applications. Addition of TiO2 nanoparticles improved the compressive modulus of scaffolds. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) revealed an increase in both glass transition temperature and thermal decomposition onset of the composite compared to pure PLGA. Furthermore, addition of TiO2 was found to enhance the wettability of the surface evidenced by reducing the contact angle from 90.5 ±â€¯3.2 to 79.8 ±â€¯2.4 which is in favor of cellular attachment and activity. The obtained results revealed that PLGA/TiO2 scaffolds significantly improved osteoblast proliferation compared to pure PLGA (p < 0.05). Furthermore, osteoblasts cultured on PLGA/TiO2 nanocomposite showed significantly higher ALP activity and improved calcium secretion compared to pure PLGA scaffolds (p < 0.05).

Bioperformance of chitosan/fluoride-doped diopside nanocomposite coatings deposited on medical stainless steel.

This work focuses on the structure, bioactivity, corrosion, and biocompatibility characteristics of chitosan-matrix composites reinforced with various amounts of fluoride-doped diopside nanoparticles (at 20, 40, 60, and 80 wt%) deposited on stainless steel 316 L. Bioactivity studies reveal that the presence of the nanoparticles in the coatings induces apatite-forming ability to the surfaces. Based on electrochemical impedance spectroscopy and polarization experiments, the in vitro corrosion resistance of the substrate was enhanced by increasing the level of the nanoparticles in the coating. The sample containing 60% of the nanoparticles presented the highest osteoblast-like MG63 cell viability, in comparison to the other prepared and even control samples. Also, the cell attachment on the surfaces was improved with increasing the amount of the nanoparticles in the coatings. It is eventually concluded that the application of chitosan/fluoride-doped diopside nanocomposite coatings improves the bioperformance of metallic implants.

The efficacy of commercial tooth storage media for maintaining the viability of human periodontal ligament fibroblasts.

AIM: To evaluate Save-A-Tooth (SAT), EMT Toothsaver (EMT) and Hank's Balanced Salt Solution (HBSS) for their influence on the viability and proliferative capacity of human periodontal ligament fibroblasts (HPDLFs). METHODOLOGY: Primary HPDLFs were seeded into 96-well cell culture plates and exposed to SAT, EMT, HBSS and water (negative control) for 0.5, 1, 3, 6, 12 and 24 h at room temperature (22 °C). After each exposure time, cell viability was measured through quantifying adenosine triphosphate (ATP) using a luminescent dye. The proliferative capacity was also quantified using the PrestoBlue assay after 12 or 24 h storage in each medium. The data were analysed statistically by two-way anova and post hoc Least Significant Difference (LSD) test (P < 0.05). The morphology of the cells after 12 h storage was also investigated through live/dead viability/cytotoxicity kit together with fluorescence microscopy. RESULTS: There was no significant difference in cell viability amongst HBSS, SAT and EMT groups up to 6 h. SAT was effective in maintaining cell viability only up to 12 h and then became detrimental to HPDLF; after 24 h, the effectiveness of SAT in maintaining cell viability was similar to that of water (P > 0.05). Amongst all the media, only EMT could maintain the proliferative capacity of HPDLFs significantly higher than the negative control, that is water (P < 0.05) after 24 h storage. CONCLUSION: EMT maintained the proliferative capacity of HPDLFs after 24 h storage.

3D printed TCP-based scaffold incorporating VEGF-loaded PLGA microspheres for craniofacial tissue engineering.

OBJECTIVE: Vascularization is a critical process during bone regeneration/repair and the lack of tissue vascularization is recognized as a major challenge in applying bone tissue engineering methods for cranial and maxillofacial surgeries. The aim of our study is to fabricate a vascular endothelial growth factor (VEGF)-loaded gelatin/alginate/ß-TCP composite scaffold by 3D printing method using a computer-assisted design (CAD) model. METHODS: The paste, composed of (VEGF-loaded PLGA)-containing gelatin/alginate/ß-TCP in water, was loaded into standard Nordson cartridges and promptly employed for printing the scaffolds. Rheological characterization of various gelatin/alginate/ß-TCP formulations led to an optimized paste as a printable bioink at room temperature. RESULTS: The in vitro release kinetics of the loaded VEGF revealed that the designed scaffolds fulfill the bioavailability of VEGF required for vascularization in the early stages of tissue regeneration. The results were confirmed by two times increment of proliferation of human umbilical vein endothelial cells (HUVECs) seeded on the scaffolds after 10 days. The compressive modulus of the scaffolds, 98±11MPa, was found to be in the range of cancellous bone suggesting their potential application for craniofacial tissue engineering. Osteoblast culture on the scaffolds showed that the construct supports cell viability, adhesion and proliferation. It was found that the ALP activity increased over 50% using VEGF-loaded scaffolds after 2 weeks of culture. SIGNIFICANCE: The 3D printed gelatin/alginate/ß-TCP scaffold with slow releasing of VEGF can be considered as a potential candidate for regeneration of craniofacial defects.

Development of a DNA-liposome complex for gene delivery applications.

The association structures formed by cationic liposomes and DNA (Deoxyribonucleic acid)-liposome have been effectively utilized as gene carriers in transfection assays. In this research study, cationic liposomes were prepared using a modified lipid film hydration method consisting of a lyophilization step for gene delivery applications. The obtained results demonstrated that the mean particle size had no significant change while the polydispersity (PDI) increased after lyophilization. The mean particle size slightly reduced after lyophilization (520±12nm to 464±25nm) while the PDI increased after lyophilization (0.094±0.017 to 0.220±0.004). In addition. The mean particle size of vesicles increases when DNA is incorporated to the liposomes (673±27nm). According to the Scanning Electron Microscopy (SEM) and transmission electron microscopy (TEM) images, the spherical shape of liposomes confirmed their successful preservation and reconstitution from the powder. It was found that liposomal formulation has enhanced transfection considerably compared to the naked DNA as negative control. Finally, liposomal formulation in this research had a better function than Lipofectamine® 2000 as a commercialized product because the cellular activity (cellular protein) was higher in the prepared lipoplex than Lipofectamine® 2000.

Is cell viability always directly related to corrosion resistance of stainless steels?

It has been frequently reported that cell viability on stainless steels is improved by increasing their corrosion resistance. The question that arises is whether human cell viability is always directly related to corrosion resistance in these biostable alloys. In this work, the microstructure and in vitro corrosion behavior of a new class of medical-grade stainless steels were correlated with adult human mesenchymal stem cell viability. The samples were produced by a powder metallurgy route, consisting of mechanical alloying and liquid-phase sintering with a sintering aid of a eutectic Mn-Si alloy at 1050 °C for 30 and 60 min, leading to nanostructures. In accordance with transmission electron microscopic studies, the additive particles for the sintering time of 30 min were not completely melted. Electrochemical impedance spectroscopic experiments suggested the higher corrosion resistance for the sample sintered for 60 min; however, a better cell viability on the surface of the less corrosion-resistant sample was unexpectedly found. This behavior is explained by considering the higher ion release rate of the Mn-Si additive material, as preferred sites to corrosion attack based on scanning electron microscopic observations, which is advantageous to the cells in vitro. In conclusion, cell viability is not always directly related to corrosion resistance in stainless steels. Typically, the introduction of biodegradable and biocompatible phases to biostable alloys, which are conventionally anticipated to be corrosion-resistant, can be advantageous to human cell responses similar to biodegradable metals.

Hybrid macroporous gelatin/bioactive-glass/nanosilver scaffolds with controlled degradation behavior and antimicrobial activity for bone tissue engineering.

A new composition of gelatin/bioactive-glass/silver nanoparticle was synthesized and employed to prepare antibacterial macroporous scaffolds with potential applications in bone tissue engineering. A set of macroporous nanocomposite scaffolds were developed from an aqueous solution of gelatin by freeze-drying and crosslinking using genipin at ambient temperature. Silver nanoparticles were successfully synthesized in situ in gelatin solution by heat treatment reduction as a simple and "green" method in which gelatin acted as a natural reducing and stabilizing agent. The effect of the incorporation of the bioactive-glass and the silver nanoparticle concentration on the physicochemical properties of the scaffolds, such as the gel fraction, porosity, in vitro enzyme degradation, morphology, and swelling behavior was studied. Furthermore, the in vitro viability of human mesenchymal stem cells (hMSC) and the antibacterial activity against gram-negative Escherichia coli and gram-positive Staphylococcus aureus were tested on the scaffolds. It was found that upon the addition of silver nanoparticles the porosity, pore size, swelling, and antibacterial properties were enhanced. The silver nanoparticles increased the in vitro enzyme degradation in samples without bioactive-glass; however, the degradation was remarkably reduced by addition of bioactive-glass. In addition, formation of apatite particles, the main inorganic constituent of the bone, on the surface of the bioactive-glass containing scaffolds were confirmed after immersion in simulated body fluid (SBF). The viability of hMSC on the scaffold suggested that gelatin/bioactive-glass/nanosilver scaffolds can be used as an antibacterial scaffolds.

Surface modification of stainless steel orthopedic implants by sol-gel ZrTiO4 and ZrTiO4-PMMA coatings.

In this paper, the biocompatibility of a medical-grade stainless steel coated with sol-gel derived, nanostructured inorganic ZrTiO4 and hybrid ZrTiO4-PMMA thin films is correlated with surface characteristics. The surfaces of the samples are characterized by atomic force microscopy, the sessile drop technique, and electrochemical corrosion experiments. The viability of adult human mesenchymal stem cells on the surfaces after one day of culture is also assessed quantitatively and morphologically. According to the results, both of the coatings improve the hydrophilicity, corrosion resistance, and thereby cytocompatibility of the substrate. Despite the higher corrosion protection by the hybrid coating, the sample coated with the inorganic thin film exhibits a better cell response, suggesting the domination of wettability. In summary, the ZrTiO4-based sol-gel films can be considered to improve the biocompatibility of metallic implants.

Analysis of mercury, selenium, and tin concentrations in canned fish marketed in Iran.

The presence of heavy metals in the environment could constitute a hazard to food security and public health. These can be accumulated in aquatic animals such as fish. In the present paper, three heavy metals (mercury, selenium, and tin) in canned products produced and sold in Iran were studied: longtail tuna, Kawakawa, Kilka, and yellowfin tuna were determined using inductively coupled plasma-optical emission spectrometer and a direct mercury analyzer. Analytical results were validated by spiking the samples with various concentrations of these metals to test recovery. The metal contents, expressed in micrograms per gram, wet weight, varied depending upon the species studied. The levels of Hg ranged from 0.0003 to 0.408 µg/g, the levels of Sn ranged from 0.036 to 0.480 µg/g, while the levels of Se ranged from 0.130 to 4.500 µg/g. Comparative evaluation of these metals in different brands of canned fish showed that the average concentrations of Hg, Sn, and Se of all species is significantly lower than adverse level for the species themselves and for human consumption when compared with FAO/WHO permissible limits. Therefore, their contribution to the total body burden of these heavy metals can be considered as negligibly small.

Analysis of trace elements (Cu, Cd, and Zn) in the muscle, gill, and liver tissues of some fish species using anodic stripping voltammetry.

Heavy metal (Cu, Cd, Zn) concentration of the muscle, gill, and liver of Otolithes rubber, Pampus argenteus, Parastromateus niger, Scomberomorus commerson, and Onchorynchus mykiss are determined by anodic stripping voltammetry method. The results show that the concentration of Cu, Cd, and Zn varied between 0.44 and not detected, 0.585 and 0.001, and 0.450 and 0.005 µg/g, respectively. It is interesting that in O. mykiss, the mean value of copper concentration was more than other marine organisms of this study, while in P. niger, the mean value of copper was minimum. The results of this study indicate that in the different tissues of fish species (O. rubber, P. argenteus, P. niger, S. commerson, and O. mykiss), the concentrations of Cu, Cd, and Zn were significantly lower than the permissible FAO/WHO levels.