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Repairing and replacing of tumor tissues have been grown due to the genetic changes and environmental factors. Conventional cancer therapies apply the systemic approaches for delivery of anticancer agents in which normal and cancer cells are not discriminated. Therefore, the risk of cancer recurrence in the resection site increases. In this paper, we studied a graphene reinforced gelatin hydrogel for tissue engineering and local controlled release of chemotherapeutic agents. Protein-integrated graphene (PIG) synthesized by ultrasonic-supported technique was incorporated into gelatin matrix, where the swelling ratio of hydrogels decreased with increasing the PIG concentration. In hydrogels, doxorubicin (DOX) was released in a controlled and pH-sensitive manner and the release rate was controlled by PIG concentration. The effect of PIG on the controlled release system was detected in MCF-7 cell viability. Moreover, 3D tumor spheroid test studied the extracellular matrix (ECM) and cell aggregation as an in vivo model. Generally, we introduced a novel hydrogel nanocomposite, which is a suitable candidate for post-surgery treatment and localized therapy.

Bone is known as the most prevalent, metastatic site of breast cancer; however, it's mechanism details are unknown, so developing a suitable scaffold for bone defect regeneration and sustain drug release after tumor resection can considerably inhibit the tumor recurrence after a while. Here, synthesized gelatin/beta-tricalcium phosphate (β-TCP) nanocomposite scaffold loaded with zoledronic acid (ZA) drug with different β-TCP concentrations, crosslinker and varying drug doses were investigated to highlight their effect on biological properties of the scaffold contained bone cells. The scanning electron microscopy (SEM) illustrated porous structure (50–200 µm) of gelatin reinforced with β-TCP spherical nanoparticles (around 90 nm diameter) that could be a proper matrix for bone cells proliferation. In vitro biological analysis by cytotoxicity assay (MTT test) as well as osteoblast cell line (G292) attachment test showed that the scaffolds were biocompatible and non-toxic. Also, higher β-TCP nanoparticle concentration enhanced the rate of cell proliferation on the scaffold. Further investigations indicated that the type of cell seeding into porous scaffolds should be considered as a significant parameter in cell behavior on the scaffold. The better cell attachment was observed in agarose gel wells in comparison with the petri dish one. Nanocomposite samples were loaded with ZA drug and its effects on the cell proliferation were investigated in vitro and in vivo as well. Histopathological results showed that the new bone formation was established more than 75% in the whole area of the defect after 3 and 4 months. For the first time, nanoscaled β-TCP/gelatin composite was proposed as a potential for controlled drug release and local resected tumor treatment. All findings besides in vitro and in vivo analyses, recommend gelatin/nano beta-tricalcium phosphate/drug scaffolds as a promising three-dimensional environment for repairing the resected bone tissue in primary or metastatic bone sites.

Circulating tumor cells are of utmost importance among various biomarkers in liquid biopsies as a prognosis indicator of metastasis as well as in chemotherapeutic monitoring. This study introduces an efficient tool composed of soft nano/hybrid immune microgels for magnetic isolation of targeted tumor cells. The development process involves the in situ synthesis of magnetic nanoparticles within the three-dimensional matrix of thermoresponsive microgels. Surface modification and anti-EpCAM conjugation are adjusted by changing the temperature, and a conjugation efficiency of around 70% is achieved by using a protein G linker. Anti-EpCAM-conjugated nano/hybrid magnetic microgels are used to isolate EpCAM-expressing breast adenocarcinoma MCF-7 cells from culture media and whole blood with an efficiency of 75 and 70%, respectively. Furthermore, we demonstrate the ability of the hybrid microgels to isolate cancer cells with a purity of 65% and culture the cells post-isolation for further drug studies. The multifunctional hybrid microcarriers reported in this work can be potentially used for continuous monitoring of cancers and in personalized medicine.

In this study, a co-precipitation method was applied to synthesize the ZnFe2O4 and ZnFe2O4 Hydrxoapatite (HAp) nanostructures. The microstructure and morphological characteristics of the nanoparticles were studied and well discussed. A dose-dependent biological evaluation comprising of their minimum inhibitory concentration (MIC) antibacterial features as well as their magnetic characteristics were analyzed. The results of vibrating-sample magnetometer (VSM) showed nanoscaled ZnFe2O4 HAp had lower saturation magnetization as well as higher coercive field than ZnFe2O4, which enables the ZnFe2O4 HAp nanoparticles to stimulate cell proliferation, differentiation and adhesion. A remarkable inhibitory effect of the nanoscaled ZnFe2O4 HAp was recognized on bacterial proliferation and growth in the optimal dose, 0.078 mg/L. Besides, a dose-dependent cytocompatibility tests of the nanoparticles on the HEK normal cell and G292 cancer cell was assessed by 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide assay (MTT). All nanoparticles were cytocompatible and no cytotoxicity effect on normal and cancer cells was observed in the dose-dependent test. In addition, an in vitro test of the drug release from drug-loaded ZnFe2O4-HAp nanocarrier were investigated and well described. The Inhibitory effect of the drug-loaded ZnFe2O4-HAp nanoparticles was investigated in-vitro so that the nanoparticle possessed the ability for inhibiting cancer cell proliferation and growth. By the increment of the nanoparticles concentrations, G292 cancer cell proliferation was inhibited, while, HEK normal cell proliferation was stimulated. Conclusively for the first time, a robust composite based nanostructure as a promising material was developed for multiple applications of bone filler, drug delivery and cancer treatment.

Magnetic nanomaterials have drawn ample attention in the field of biotechnology due to their excellent magnetic properties and biocompatibility. These materials have been widely used for exosome isolation, DNA separation, magnetic resonance imaging, and drug delivery. However, their application in cell isolation has been limited due to the lack of efficient antibody conjugation and instability in aqueous solutions. In this study, we produced hybrid maghemite nanorod/immuno-microgels with high capturing capacity for cell isolation and enumeration. Lepidocrocite (γ-FeOOH) and maghemite (γ-Fe2O3) nanorods with controlled morphology are synthesized using hydrolysis method. The effects of the different synthesis conditions on morphology, phase composition, and magnetic properties of lepidocrocite are studied to determine the best synthesis conditions. We coat the nanorods with chitosan and attach them to the poly(N-isopropylacrylamide-co-acrylic acid) (PNIPAM-AA) microgel through chemical bonding to form a nano/hybrid microstructure. Our results suggest that the hybrid magnetic microgels have more antibody binding capacity and higher cancer cell capturing rate compared to pristine maghemite nanorods. In addition, new cell magnetometery method was applied for cancer cell quantification after capturing step in which different magnetized labelled cells were correlated to the saturation magnetization. In this method, higher concentrations of the primary cell suspension resulted in more binding of the magnetic immuno-microgels to the cells which was shown as saturation magnetization drop in the microgel-cell complex.

Currently, surgical operations, followed by systemic drug delivery, are the prevailing treatment modality for most diseases, including cancers and trauma-based injuries. Although effective to some extent, the side effects of surgery include inflammation, pain, a lower rate of tissue regeneration, disease recurrence, and the non-specific toxicity of chemotherapies, which remain significant clinical challenges. The localized delivery of therapeutics has recently emerged as an alternative to systemic therapy, which not only allows the delivery of higher doses of therapeutic agents to the surgical site, but also enables overcoming post-surgical complications, such as infections, inflammations, and pain. Due to the limitations of the current drug delivery systems, and an increasing clinical need for disease-specific drug release systems, hydrogels have attracted considerable interest, due to their unique properties, including a high capacity for drug loading, as well as a sustained release profile. Hydrogels can be used as local drug performance carriers as a means for diminishing the side effects of current systemic drug delivery methods and are suitable for the majority of surgery-based injuries. This work summarizes recent advances in hydrogel-based drug delivery systems (DDSs), including formulations such as implantable, injectable, and sprayable hydrogels, with a particular emphasis on stimuli-responsive materials. Moreover, clinical applications and future opportunities for this type of post-surgery treatment are also highlighted.

The effects of adding Al2O3 nanoparticles on the microstructure, tribological, magnetic, and corrosion properties of CuFe-Al2O3 nanocomposites were investigated in this work. The mixture of Cu-25 wt.% Fe powder with 5 vol.% Al2O3 was mechanically milled. X-ray diffraction results revealed that after 60 h of mechanical alloying, CuFe solid solution was formed. Magnetic hysteresis loops of the mechanically alloyed powders were extracted at room temperature. The morphology and elemental analysis of the sintered specimens were studied by field emission scanning electron microscope (SEM). It was observed that uniform distribution and embedding of Al2O3 nanoparticles in the CuFe alloy matrix in nanocomposites were achieved, which exhibited excellent performances. Tribological properties were evaluated through a pin-on-disk wear test, and it was found that by the addition of Al2O3 nanoparticles to CuFe alloy, the weight loss rate was reduced by 30%. The existence of Al2O3 nanoparticles in the matrix of CuFe alloy causes the wear mechanism change from adhesive to abrasive, which means a considerable wear resistance was obtained in nanocomposites. The corrosion properties of the sintered samples in a solution of 3.5% NaCl were studied by potentiodynamic polarization. With the addition of Al2O3 nanoparticles, the corrosion rate of the alloy was reduced by 75%.

Hyperthermia treatment of different cancers based on magnetic nanoparticles has gained significant attention in recent years. In this work, biocompatible maghemite (γ-Fe2O3) nanorods were synthesized by dehydroxylation of lepidocrocite (γ-FeOOH) nanorods, using hydrolysis of ferrous salts in the presence of urea followed by calcination at 300 °C for 3 h. Maghemite nanospheres were also synthesized by oxidation of co-precipitated magnetite (Fe3O4) nanoparticles, followed by heat treatment at 250 °C for 3 h. The samples were analyzed by X-ray diffraction, vibrating sample magnetometry, and field emission scanning electron microscopy techniques. Cell viability of nanorods and nanospheres before and after applying a magnetic field was studied by MTT assay on G292 cell lines as a candidate of osteosarcoma 2D-cultured model. The heating capacity of the rod-like and spherical magnetic nanoparticles (MNP) was evaluated under a magnetic field using a solid state induction heating equipment. Moreover, the minimal inhibitory concentration (MIC) antibacterial activity of magnetic nanorods and nanospheres was investigated. The results showed that cell proliferation gradually increased in the presence of both maghemite nanorods and nanospheres compared to the control sample. However, cell viability decreased after applying hyperthermia treatment as indicative of cell apoptosis. Quantification of antibacterial properties also showed the MIC behavior of both nanoparticles at a concentration of 0.078 mg/ml.

We report on facile synthesis and characterization of phosphate-functionalized polymer dots (PDs) by doping tributyl phosphate (TBP) in a semiconducting polymer poly[9,9-dioctylfluorenyl-2,7-diyl)-co-1,4-benzo-{2,10-3}-thiadiazole)] (PFBT). Then, the prepared TBP@PFBT PDs were used to develop a very high sensitive probe for detection Fe3+, Cu2+ ions and Cytochrome c based on aggregation induced fluorescence off mechanism. The PDs exhibited a linear dynamic range for Fe3+ from 0.1 to 2 nM with a detection limit of 30 pM and for Cu2+ from 2.0 to 50.0 nM with a detection limit of 0.35 nM. Meanwhile, this probe showed a linear dynamic range for Cyt c from 175 to 1750 pM with a detection limit of 32.7 pM. The TBP@PFBT PDs is a simple, one-step, fast, non-invasive, label-free, and inexpensive probe that is capable of online apoptosis monitoring response to drugs with an ever-present opportunity to contribute in a variety of in-vitro and in-vivo biological applications. We also obtained sharp, specific 2D and 3D imaging results for early stage apoptosis in breast cancer cells. Moreover, this technique possesses the advantage of rapid determination of Fe3+ ion in biological or environmental samples. Importantly, this label-free assay provides short determination time of only a few min, easy operation and very low LOD allowing 100–4000 times increased in sensitivity over previously reported probes, together with high selectivity without need to using biorecognition elements like enzymes, antibodys and/or aptamers. Such excellent features make the TBP@PFBT PDs an excellent probe for successful apoptosis imaging in live cells.

In vivo assays of graphene and its derivatives are big challenges in biological evaluations because they require simultaneous long-term stability in aqueous dispersion and controllable systemic toxicity. Bifunctional graphene nanosheets which have key function in biomedical area are expected to address this challenge. Here, novel bifunctional graphene nanosheets were successfully synthesized in the presence of Herceptin, a natural antibody, using a facile ultrasonic-assisted method. Graphite layers were successfully exfoliated which resulted excellent stability of separated layers in herceptin solution. In aqueous solution, graphene concentration was effectively controlled by varying the herceptin content and sonication time. Furthermore, the toxicity of graphene was tested in both 2D and 3D spheroid cultures. The results showed that graphene toxicity were considerably reduced in spheroid culture compared to the 2D culture data. Moreover, the toxicity behavior of graphene was dependent on the exposed concentration of graphene that the mortality rate was significantly decreased when the concentration of graphene was below 1 µg/mL. This bifunctional graphene which possessed long-term stability in aqueous solutions and induced slight toxicity offers a promising nanostructure in tumor-targeted drug delivery, regenerative medicine and tissue engineering. This proof-of-concept study demonstrates the feasibility of ultrasonic assisted method in one-step synthesis of bifunctional nanomaterials and biostructures for clinical applications.

Cerium containing coatings are interested because of corrosion and wear resistance characteristics, in another point valve metals have the ability to be treated with plasma electrolytic oxidation (PEO). Different cerium sources, from base metal, pretreatment, post treatment and electrolyte are implemented for Mg alloys. In this research Ti substrates was treated via PEO in less studied, cerium chloride containing electrolytes. Effect of cerium ion concentration was studied on morphology, corrosion and wear properties using SEM, FTIR, polarization, EIS, pin on disk experiments. It was observed that cerium participates in coatings slightly and there is an optimum content for cerium ions in electrolytes which results in improved corrosion and wear properties, mostly from modifying coating roughness and morphology. Addition of cerium ions to electrolyte, first decreases and then increases coating roughness and coefficient of friction.

Alumina nanoparticles were added to CuTiNi alloy to study their effect on microstructure, tribological properties, and corrosion behaviors of the fabricated alloy. A mixture of Cu–20 wt% Ti–10 wt% Ni powder with 0 and 5 wt% alumina was mixed in a high-energy ball mill. Results indicated that CuTiNi solid solution was formed after 40 h of mechanical alloying. Magnetic hysteresis loops of the mechanically alloyed powders were extracted at room temperature. The mechanically alloyed powders were compacted and then conventionally sintered. Tribological properties of sintered samples were evaluated by ball-on-disk wear test. Comparing the wear rate of the nanocomposite with that of CuTiNi alloy indicated that addition of alumina nanoparticles decreased the wear rate by about 40 %. Corrosion behavior of sintered samples studied using cyclic potentiodynamic polarization in 3.5 % NaCl solution revealed that corrosion current density of the nanocomposite was decreased by about 98 % compared to that of CuTiNi alloy.

Droplet-based microfluidic assisted devices have proposed an extensive interest in many applications such as lab-on-a-chip technologies as well as chemical/biological/nanomaterial preparation, chemical engineering, drug delivery, tissue engineering and biosensing. Here, a computational fluid dynamic model was developed for deep understanding of the droplet size and formation in a flow-focusing (FF) microchannel with consideration of the continuous phase (non-Newtonian fluid). The simulations presented an alternative method to achieve insights into this complicated process. In the following for the first time, the role of channel geometry, channel aspect ratio and flow rate ratio on droplet features including the mechanism of droplet formation, diameter/volume of droplet, velocity/amount of droplet formation, and final shape/size of the generated droplets were fully described. These findings could remarkably derive desirable protocols to control droplets characteristics comprising their size and shape in non-Newtonian fluids. Moreover, level set (LS) method was used for scrutinizing the droplet-breaking procedure in the microfluidic FF devices. The results showed that different droplet sizes could be prepared with changing the various parameters, demonstrating many challenges in various applications including lab-on-a-chip, cell encapsulation, drug delivery, tissue engineering, biosensing and bioimaging could be successfully addressed.