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The use of magnetic nanoparticles in association with scaffolds is considered an important way to transform typical passive scaffolds into active scaffolds. Manganese can develop magnetic properties in hydroxyapatites, as can iron, copper, cobalt and samarium, but lacks the high toxicity of these latter compounds. Because the magnetic properties exhibited by transition metal-containing hydroxyapatite are entirely dependent on site occupation and on the formation of magnetic oxides under heating, it is extremely important to understand how manganese behaves when inserted into hydroxyapatite. In this paper, we demonstrated by using X-ray difference Fourier maps that the insertion of Mn into the hydroxyapatite structure induces several perturbations in its hexagonal channels, with a preference for occupying Ca(2) sites, particularly when the hydroxyapatite lattice is poorly ordered and has CO32− inserted at PO43− sites. When CO32− is released at high temperature and the structure is better ordered, Ca(1) sites become more susceptible to occupation by Mn atoms, while the occupation of PO43− sites by MnO43− is reduced. However, with increasing time and calcination temperature, Mn atoms tend to be released from the hydroxyapatite structure in the form of Mn3O4 nanoparticles through the hydroxyl channels, occupying Ca(2) sites in the final stage of the segregation pathway. These findings are fundamental to the development of new strategies to synthesize active hydroxyapatite-based scaffolds under remote control by a magnetic field.

Purpose Recently, two-dimensional (2D) nanomaterials are gaining tremendous attention as novel antibacterial platforms to combat against continuously evolving antimicrobial resistance levels. Among the family of 2D nanomaterials, black phosphorus (BP) nanosheets have demonstrated promising potential for biomedical applications. However, there is a need to gain nanoscale insights of the antibacterial activity of BP nanosheets which lies at the center of technical challenges. Methods Ultra-large BP nanosheets were synthesized by liquid-exfoliation method in the eco-friendly deoxygenated water. Synthesized BP nanosheets were characterized by TEM, AFM, and Raman spectroscopy techniques and their chemical stability was evaluated by EDS and EELS elemental analysis. The antibacterial activity of BP nanosheets was evaluated at nanoscale by the ultramicrotome TEM technique. Further, HAADF-STEM image and EDS elemental line map of the damaged bacterium were utilized to analyze the presence of diagnostic ions. Supportive SEM and ATR-FTIR studies were carried out to confirm the bacterial cell wall damage. In vitro colony counting method was utilized to evaluate the antibacterial performance of ultra-large BP nanosheets. Results Elemental EELS and EDS analysis of BP nanosheets stored in deoxygenated water confirmed the absence of oxygen peak. TEM studies indicate the various events of bacterial cell damage with the lost cellular metabolism and structural integrity. Colony counting test results show that as-synthesized BP nanosheets (100 μg/mL) can kill ~95% bacteria within 12 hours. Conclusion TEM studies demonstrate the various events of E. coli membrane damage and the loss of structural integrity. These events include the BP nanosheets interaction with the bacterial cell wall, cytoplasmic leakage, detachment of cytoplasm from the cell membrane, reduced density of lipid bilayer and agglomerated DNA structure. The EDS elemental line mapping of the damaged bacterium confirms the disrupted cell membrane permeability and the lost cellular metabolism. SEM micrographs and ATR-FTIR supportive results confirm the bacterial cell wall damage.

Ferritin biomineralization is essential to regulate the toxic Fe2+ iron ions in the human body. Unravelling the mechanism of biomineralization in ferritin facilitates our understanding of the cause...

The ions found in biological environment during biomineralization as well as the counterions present in syntheses, i.e., the reagents employed, play an important role in the precipitation and stabilization of apatites. In this work, precipitation of strontium-containing hydroxyapatites at different concentrations (0, 20, 40, 60, 80 and 100% Sr2+) was performed in the presence of two counterions typically present in biological environments: Na+ and Cl−. It was demonstrated that the presence of Na+/Cl− in the synthesis environment led to the precipitation of a biphasic hydroxyapatite (HAp) system formed by two non-miscible phases: Ca-rich HAp and Sr-rich HAp. The biphasic system was observed for intermediate Sr2+ concentrations (20, 40 and 60%) and exhibited greater lattice microstrain compared with the single-phase systems of Ca HAp (0%) and Sr HAp (100%). Although Na+/Cl− were inserted into both Ca- and Sr-rich HAp phases, Cl− ions were preferentially accommodated into the enlarged Sr-rich HAp structure. The presence of Cl− ions in the Sr-rich HAp phase decreased microstrain compared to the Ca-rich phase. After calcination, the biphasic system was transformed into a completely miscible Ca/Sr HAp phase without the formation of other phosphates or oxides.

Background Nanoscale surface roughness has been suggested to have antibacterial and antifouling properties. Several existing models have attempted to explain the antibacterial mechanism of nanoscale rough surfaces without direct observation. Here, conventional and liquid-cell TEM are implemented to observe nanoscale bacteria/surface roughness interaction. The visualization of such interactions enables the inference of possible antibacterial mechanisms. Methods and results Nanotextures are synthesized on biocompatible polymer microparticles (MPs) via plasma etching. Both conventional and liquid-phase transmission electron microscopy observations suggest that these MPs may cause cell lysis via bacterial binding to a single protrusion of the nanotexture. The bacterium/protrusion interaction locally compromises the cell wall, thus causing bacterial death. This study suggests that local mechanical damage and leakage of the cytosol kill the bacteria first, with subsequent degradation of the cell envelope. Conclusion Nanoscale surface roughness may act via a penetrative bactericidal mechanism. This insight suggests that future research may focus on optimizing bacterial binding to individual nanoscale projections in addition to stretching bacteria between nanopillars. Further, antibacterial nanotextures may find use in novel applications employing particles in addition to nanotextures on fibers or films.

When dental implants become infected, the progression of the disease is rapid. Commercially available dental implant surfaces can be easily contaminated, resulting in rapid progression of peri-mucositis and peri-implantitis. The aim of this study was to evaluate, in vitro, the pattern of doxycycline release from by dental implants with titanium nanotube surface (DINS) at different pHs to examine novel drug loading and chemical coating techniques. Nine DINS were loaded with doxycycline and subsequently coated with polylactic-co-glycolic acid (PLGA). High-performance liquid chromatography (HPLC) was used to measure the amounts of released doxycycline in a 30-day period. Cytotoxicity of the DINS was evaluated by an assay using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT). The results showed that the experimental DINS coated with doxycycline and PLGA showed a mean drug release during the experimental period for the groups: pH 7.4 (8.39 μg/mL), pH 6.4 (8.63 μg/mL). The pH 5.4 (15.18 μl/mL) doxycycline release from DINS was faster at pH 5.4 than those at pHs 6.4 and 7.4 (P = .0031 and .0034, respectively). This new surface treatment of dental implants with titanium nanotubes and subsequent drug loading demonstrated biocompatibility and sustained doxycycline release over a 30-day period. Additional studies are needed in order to adopt a stable drug release at neutral pH environment while warranting a constant drug release in an acidic pH environment.

Water is ubiquitous in natural systems, ranging from the vast oceans to the nanocapillaries in the earth crust or cellular organelles. In bulk or in intimate contact with solid surfaces, water molecules arrange themselves according to their hydrogen (H) bonding, which critically affects their short- and long-range molecular structures. Formation of H-bonds among water molecules designates the energy levels of certain nonbonding molecular orbitals of water, which are quantifiable by spectroscopic techniques. While the molecular architecture of water in nanoenclosures is of particular interest to both science and industry, it requires fine spectroscopic probes with nanometer spatial resolution and sub-eV energy sensitivity. Graphene liquid cells (GLCs), which feature opposing closely spaced sheets of hydrophobic graphene, facilitate high-resolution transmission electron microscopy (TEM) and electron energy-loss spectroscopy (EELS) measurements of attoliter water volumes encapsulated tightly in the GLC nanovessels. We perform in situ TEM and EELS analysis of water encased in thin GLCs exposed to room and cryogenic temperatures to examine the nanoscale arrangement of the contained water molecules. Simultaneous quantification of GLC thickness leads to the conclusion that H-bonding strengthens under increased water confinement. The present results demonstrate the feasibility of nanoscale chemical characterization of aqueous fluids trapped in GLC nanovessels and offer insights on water molecule arrangement under high-confinement conditions.

This chapter is an introduction to nanocomposite materials and its classifications with emphasis on orthopedic application. It covers different types of matrix nanocomposites including ceramics, metal, polymer and natural-based nanocomposites with the main features and applications in the orthopedic. In addition, it presents structure, composition, and biomechanical features of bone as a natural nanocomposite. Finally, it deliberately presents developing methods for nanocomposites bone grafting.

Emre Firlar,1,2 Meagan Ouy,1 Leigha Covnot,1 Yuan Xing,3 Daniel Lee,1,4 Alessandro Chan,1,4 Yi He,3 Boao Song,2 Solomon Afelik,4 Yong Wang,3 Reza Shahbazian-Yassar,2 Jose Oberholzer,1,3 Tolou Shokuhfar1 1Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA; 2University of Illinois at Chicago, Department of Mechanical and Industrial Engineering, Chicago, IL, USA; 3University of Virginia, Department of Surgery, Charlottesville, VA, USA; 4University of Illinois at Chicago, Department of Surgery, Chicago, IL, USA Background: Islet cell transplantation is one of the key treatments for type 1 diabetes. Understanding the mechanisms of insulin fusion and exocytosis are of utmost importance for the improvement of the current islet cell transplantation and treatment of diabetes. These phenomena have not been fully evaluated due either to the lack of proper dynamic imaging, or the lack of proper cell preservation during imaging at nanoscales. Methods: By maintaining the native environment of pancreatic β-cells between two graphene monolayer sheets, we were able to monitor the subcellular events using in situ graphene liquid cell (GLC)-transmission electron microscopy (TEM) with both high temporal and high spatial resolution. Results: For the first time, the nucleation and growth of insulin particles until the later stages of fusion were imaged at nanometer scales. The release of insulin from plasma membrane involves the degradation of plasma membrane and drastic reductions in the shorter axis of the insulin particles. Sequential exocytosis results indicated the nucleation, growth and attachment of the new insulin particles to the already anchored ones, which is thermodynamically favorable due to the reduction in total surface, further reducing the Gibbs free energy. The retraction of the already anchored insulin toward the cell is also monitored for the first time live at nanoscale resolution. Conclusion: Investigation of insulin granule dynamics in β-cells can be investigated via GLC-TEM. Our findings with this technology open new realms for the development of novel drugs on pathological pancreatic β-cells, because this approach facilitates observing the effects of the stimuli on the live cells and insulin granules. Keywords: transmission electron microscopy, graphene liquid cell, insulin secretion, exocytosis

In the modern construction industry, large gypsum (CaSO4·2H2O) boards are manufactured through a two-step procedure, which features the heating of fine gypsum powders to form the intermediate plast...

The area of cellular interactions of nanomaterials is an important research interest. The sensitivity of cells toward their extracellular matrix allows researchers to create microenvironments for guided stem cell differentiation. Among nanomaterials, graphene, often called the “wonder material,” and its derivatives are at the forefront of such endeavors. Graphene’s carbon backbone, paired with its biocompatibility and ease of functionalization, has been used as an enhanced method of controlled cell proliferation. Graphene’s honeycomb nature allows for compatibility with polymers and biological material for the creation of nanocomposite scaffolds that help differentiation into cell types that have otherwise been proven difficult. Such materials and their role in guiding cell growth can aid the construction of tissue grafts where shortages and patient compatibility create a low success rate. This review will bring together novel studies and techniques used to understand and optimizes graphene’s role in cell growth mechanisms.

Nanocarrier administration has primarily been restricted to intermittent bolus injections with limited available options for sustained delivery in vivo. Here, we demonstrate that cylinder-to-sphere transitions of self-assembled filomicelle (FM) scaffolds can be employed for sustained delivery of monodisperse micellar nanocarriers with improved bioresorptive capacity and modularity for customization. Modular assembly of FMs from diverse block copolymer (BCP) chemistries allows in situ gelation into hydrogel scaffolds following subcutaneous injection into mice. Upon photo-oxidation or physiological oxidation, molecular payloads within FMs transfer to micellar vehicles during the morphological transition, as verified in vitro by electron microscopy and in vivo by flow cytometry. FMs composed of multiple distinct BCP fluorescent conjugates permit multimodal analysis of the scaffold’s non-inflammatory bioresorption and micellar delivery to immune cell populations for one month. These scaffolds exhibit highly efficient bioresorption wherein all components participate in retention and transport of therapeutics, presenting previously unexplored mechanisms for controlled nanocarrier delivery., Nanocarrier administration is often performed via intermittent bolus injection while sustained delivery platforms are rarely reported. Here the authors demonstrate that the cylinder-to-sphere transitions of self-assembled filomicelle scaffolds can be used for sustained delivery with improved resorptive capacity and biocompatibility.

The synthesis of silver-doped hydroxyapatite (Ag-HA) nanobelts as a HA-based antibacterial bioactive material is of great importance due to their being a potential candidate to curb the infections associated with HA implants along with their advantage as a reinforcement in biomaterials. Here, a facile one-step method for synthesizing Ag-doped hydroxyapatite (AgxHA) [Ca10−xAgx(PO4)6(OH)2] (x = 0, 0.2, 0.5) nanobelts using hydrothermal homogeneous precipitation is demonstrated. The samples were characterized using X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDS). Their antibacterial properties against Escherichia coli (E. coli) bacteria and cytotoxicity to Swiss embryonic mouse fibroblast (3T3-J2) cells were evaluated with the help of the disc diffusion method and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell viability assay, respectively. Our study indicates that the increased optimum Ag amount in the HA nanobelt has enhanced its antibacterial properties and bioactivity. The flexibility behavior of an individual multi-layered Ag0.2HA nanobelt was observed by in situ TEM. The novel TEM cyclic compression–bending test results indicate that the Ag0.2HA nanobelt can retain its original shape after eight continuous deformation cycles at an extreme angle, revealing its high flexibility. This study provides new insights into the design of bioactive HA nanobelts with antibacterial properties and opens new opportunities for their load-bearing applications.

Highly flexible multi-layered hydroxyapatite (HA) nanobelts were successfully grown and compared to nanorods. The nanomechanical behaviour of individual HA nanostructures was visualized using in situ TEM. Compression-induced deformation in HA nanobelts can spontaneously recover at a maximal strain of 99.2%, much larger than the 2.63% failure strain observed for traditional HA nanorods.

Hydroxyapatite (HA) exhibits excellent biocompatibility, bioactivity, osteoconductivity, non-toxicity and so on, making it a perfect candidate for biomedical applications. However, HA is not qualified to be used in load-bearing sites due to its poor flexural strength and fracture toughness. Design, synthesis and application of fibrous HA is a promising strategy to overcome the inherent brittleness. This review provides a brief description of HA and hydroxyapatite fiber (HAF), then introduces different synthesis methods of HAF and highlights the inherent merits and drawbacks involved in each method. Finally, the future perspectives in this active research area are given. The purpose of this review is to acquaint the reader with this promising new field of biomaterials research and with emphasis on recent techniques to obtain continuous, uniform and long HAF.

Stem cells are recognized by their self-renewal ability and can give rise to specialized progeny. Hydrogels are an established class of biomaterials with the ability to control stem cell fate via mechanotransduction. They can mimic various physiological conditions to influence the fate of stem cells and are an ideal platform to support stem cell regulation. This review article provides a summary of recent advances in the application of different classes of hydrogels based on their source (e.g., natural, synthetic, or hybrid). This classification is important because the chemistry of substrate affects stem cell differentiation and proliferation. Natural and synthetic hydrogels have been widely used in stem cell regulation. Nevertheless, they have limitations that necessitate a new class of material. Hybrid hydrogels obtained by manipulation of the natural and synthetic ones can potentially overcome these limitations and shape the future of research in application of hydrogels in stem cell regulation.

Ferritin is a protein that regulates the iron ions in humans by storing them in the form of iron oxides. Despite extensive efforts to understand the ferritin iron oxide structures, it is still not clear how ferritin proteins with a distinct light (L) and heavy (H) chain subunit ratio impact the biomineralization process. In situ graphene liquid cell-transmission electron microscopy (GLC-TEM) provides an indispensable platform to study the atomic structure of ferritin mineral cores in their native liquid environment. In this study, we report differences in the iron oxide formation in human spleen ferritins (HSFs) and human heart ferritins (HHFs) using in situ GLC-TEM. Scanning transmission electron microscopy (STEM) along with selected area electron diffraction (SAED) of the mineral core and electron energy loss spectroscopy (EELS) analyses enabled the visualization of morphologies, crystal structures and the chemistry of iron oxide cores in HSFs and HHFs. Our study revealed the presence of metastable ferrihydrite (5Fe2O3·9H2O) as a dominant phase in hydrated HSFs and HHFs, while a stable hematite (α-Fe2O3) phase predominated in non-hydrated HSFs and HHFs. In addition, a higher Fe3+/Fe2+ ratio was found in HHFs in comparison with HSFs. This study provides new understanding on iron-oxide phases that exist in hydrated ferritin proteins from different human organs. Such new insights are needed to map ferritin biomineralization pathways and possible correlations with various iron-related disorders in humans.

The aim of this study was to investigate the influence of fretting motions on the depassivation–repassivation processes occurring in Ti6Al4V alloy, at an in vitro simulated oral environment. Ti6Al4V discs were subjected to fretting–corrosion using a pin-on-disc tribometer. Specimens underwent 2000 motion cycles, with ± 500 µm of fretting stroke, and 8 N of load at frequencies of 1, 2, and 4 Hz. Surface characterization was performed using white-light interferometry and scanning electron microscope. Total mass loss (Kwc), and mass loss due to wear (Kw) and corrosion (Kc) were calculated. Lower potentials were reached at a frequency of 4 Hz. The coefficient of friction was statistically higher (p > 0.05) under 1 Hz (μ = 0.66) as compared to that of 2 and 4 Hz (μ = 0.53; μ = 0.51). Kwc was significantly higher (p

Tissue discoloration in dental implant patients with thin gingival tissue is one of the many causes of dental implants’ revision surgery. Therefore, the purpose of this study is to address this issue by developing a surface that has a “tooth like bright colored” appearance while at the same time enhancing the bone implant integration. A biomimetic surface is fabricated by forming transparent TiO2 nanotubes on zirconia (TTNZ) that can enhance the proliferation and attachment of human mesenchymal stem cells (hMSCs) as compared to roughened ZrO2. This surface treatment was aimed to resolve tissue discoloration and aesthetic appearance problems for dental implant patients, while also enhancing biocompatibility. TiO2 nanotubes (TNTs) were formed using an electrochemical anodization technique in an electrolyte comprised of NH4F, ethylene glycol and water. The presence of TNTs on the ZrO2 substrate was detected by field emission scanning electron microscopy (FESEM). Optical images of longer anodized (20 and 30 min) samples show the white colored appearance characteristic of ZrO2 and FESEM confirmed the presence of TNTs on anodized samples. Surface characteristics of all samples were analyzed using water contact angle analysis, Fourier-transform infrared spectroscopy, white light interferometry and FESEM. Quantitative and qualitative biocompatibility analysis of treated and non-treated ZrO2 surfaces were obtained by performing FESEM, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and fluorescence microscopy. FESEM revealed well-elongated and well-spread cell morphology on the nanotubular surface as compared to roughened ZrO2. Additionally, MTT assay showed a significantly high cell proliferation for anodized Ti–ZrO2 surface as compared to roughened ZrO2 after 7 days of incubation.

Inadequate mechanical properties of pure hydroxyapatite (HA) coating layers make it an unsuitable candidate for many load-bearing orthopedic implants. In this study, Titania nanotubes (TNT) and HA were synthesized using Rapid Breakdown Adonization (RBA) and sol–gel methods, respectively. The sintering process at different temperatures was then conducted for the phase transformation of titanium. HA–TNT mixtures in different quantities and phases were prepared for coating on Co–Cr-based substrates. To optimize the coated HA–TNT composite layer in term of hardness, bonding strength and corrosion potential, empirical models based on Response Surface Methodology (RSM) were developed. The synthesized TNT and HA–TNT coated samples were characterized using X-ray diffraction (XRD), Field Emission Scanning Electron Microscope (FESEM) and Transmission Electron Microscopy (TEM). The predicted models generated by RSM were compared with the experimental results, and close agreement was observed. While the models demonstrate that TNT quantity is a more significant factor than sintering temperature in improving hardness (H), bonding strength (P) and the corrosion potential (Ecorr) of a coated substrate, sintering temperature still has a considerable effect on H and Ecorr. The optimum HA–TNT composite coating layer in terms of the mechanical and electrochemical properties were obtained with a TNT ratio of 1.07 (wt%) at a sintering temperature of 669.11 °C.

This review summarizes the breakthroughs in the field of soft material characterization by in situ liquid-cell transmission electron microscopy (TEM). The focus of this review is mostly on soft biological species such as cells, bacteria, viruses, proteins and polymers. The comparison between the two main liquid-cell systems (silicon nitride membranes liquid cell and graphene liquid cell) is also discussed in terms of their spatial resolution and imaging/analytical capabilities. We have showcased how liquid-cell TEM can reveal the structural details of whole cells, enable the chemical probing of proteins, detect the structural conformation of viruses, and monitor the dynamics of polymerization. In addition, the challenges faced by decoupling electron beam effect on beam-sensitive soft materials are discussed. At the end, future perspectives of in situ liquid-cell TEM studies of soft materials are outlined.

Transmission electron microscopy of whole cells is hindered by the inherently large thickness and low atomic contrast intrinsic of cellular material. Liquid cell transmission electron microscopy allows samples to remain in their native hydrated state and may permit visualizing cellular dynamics in-situ. However, imaging biological cells with this approach remains challenging and identifying an optimal imaging regime using empirical data would help foster new advancements in the field. Recent questions about the role of the electron beam inducing morphological changes or damaging cellular structure and function necessitates further investigation of electron beam-cell interactions, but such comparisons are complicated by variability in imaging techniques used across various studies currently present in literature. The necessity for using low electron fluxes while imaging biological samples requires finding an imaging strategy which produces the strongest contrast and signal to noise ratio for the electron flux used. Here, we experimentally measure and evaluate signal to noise ratios and damage mechanisms between liquid and cryogenic samples of intact cells using multiple electron imaging modalities all on the same instrument and with equivalent beam parameters to standardize the comparison. We also discuss considerations for optimal electron microscopy imaging conditions for future studies on whole cells within liquid environments.

Transmission electron microscopy of whole cells is hindered by the inherently large thickness and low atomic contrast intrinsic of cellular material. Liquid cell transmission electron microscopy allows samples to remain in their native hydrated state and may permit visualizing cellular dynamics in-situ. However, imaging biological cells with this approach remains challenging and identifying an optimal imaging regime using empirical data would help foster new advancements in the field. Recent questions about the role of the electron beam inducing morphological changes or damaging cellular structure and function necessitates further investigation of electron beam-cell interactions, but is complicated by variability in imaging techniques used across various studies currently present in literature. The necessity for using low electron fluxes for imaging biological samples requires finding an imaging strategy which produces the strongest contrast and signal to noise ratio for the electron flux used. Here, we experimentally measure and evaluate signal to noise ratios and damage mechanisms between liquid and cryogenic samples for cells using multiple electron imaging modalities all on the same instrument and with equivalent beam parameters to standardize the comparison. We also discuss considerations for optimal electron microscopy imaging conditions for future studies on whole cells within liquid environments.

Lack of bioactivity and monomer toxicity are limiting factors of polymethyl methacrylate (PMMA) bone cement in orthopedic applications. Herein, we address these shortcomings by proposing two-dimensional magnesium phosphate (MgP) nanosheets and hydroxyapatite (HA) nanofibers as novel fillers in PMMA bone cement nanocomposites. Two-dimensional MgP nanosheets and one-dimensional HA nanofibers were synthesized by tuning the crystallization of the sodium-magnesium-phosphate ternary system and hydrothermal homogeneous precipitation, respectively. We show that MgP nanosheets exhibit antibacterial properties against Escherichia coli (E. coli). In addition, HA nanofibers with high level of bioactivity are the proper choice to induce cell viability in the nanocomposite. Results indicate that the combination of both fillers can act as deformation locks enhancing the compressive strength of the nanocomposites. The synthesized nanocomposite possesses excellent bioactivity, mechanical properties, and cytocompatibility potentially opening new paradigm in the design of next generation bone cement composites.

Made available in DSpace on 2018-12-11T17:17:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-04-01 National Science Foundation Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Federación Española de Enfermedades Raras Fundació Catalana de Trasplantament After insertion into bone, dental implants may be subjected to tribocorrosive conditions resulting in the release of metallic ions and solid wear debris, which can induce to peri-implant inflammatory reactions accompanied by bone loss, and ultimately implant loosening. Despite the promising ability of TiO2 nanotubes (NTs) to improve osseointegration and avoid infection-related failures, the understanding of their degradation under the simultaneous action of wear and corrosion (tribocorrosion) is still very limited. This study aims, for the first time, to study the tribocorrosion behavior of bio-functionalized TiO2 NTs submitted to two-cycle sliding actions, and compare it with conventional TiO2 NTs. TiO2 NTs grown by anodization were doped with bioactive elements, namely calcium (Ca), phosphorous (P), and zinc (Zn), through reverse polarization anodization treatments. Characterization techniques such as scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and scanning transmission electron microscopy (STEM), were used to characterize the films. Tribocorrosion tests were carried out in artificial saliva (AS) by applying two cycles of reciprocating sliding actions. The open circuit potential (OCP) was monitored before, during, and after both cycles of sliding, during which the coefficient of friction (COF) was calculated. The resulting wear scars were analyzed by SEM and EDS, and wear volume measurements were performed by 2D profilometry. Finally, the mechanical features of TiO2 NTs were accessed by nanoindentation. The results show that bio-functionalized TiO2 NTs display an enhanced tribocorrosion performance, ascribed to the growth of a nano-thick oxide film at Ti/TiO2 NTs interface, which significantly increased their adhesion strength to the substrate and consequently their hardness. Furthermore, it was discovered that during tribo-electrochemical solicitations, the formation of a P-rich tribofilm takes place, which grants both electrochemical protection and resistance to mechanical wear. This study provides fundamental and new insights for the development of multifunctional TiO2 NTs with long-term biomechanical stability and improved clinical outcomes. CMEMS – Center of MicroElectroMechanical Systems Department of Mechanical Engineering University of Minho IBTN/BR Brazilian Branch of the Institute of Biomaterials Tribocorrosion and Nanomedicine Faculty of Sciences UNESP – Universidade Estadual Paulista Brazilian Center for Research in Physics Directory of Life Sciences Applied Metrology National Institute of Metrology Quality and Technology Postgraduate Program in Translational Biomedicine University of Grande Rio Department of Mechanical Engineering University of Minho Department of Bioengineering University of Illinois at Chicago IBTN/US American Branch of the Institute of Biomaterials Tribocorrosion and Nanomedicine University of Illinois at Chicago Department of Materials Engineering KU Leuven Falex Tribology N.V, Wingepark 23B Faculdade de Ciências Departamento de Física UNESP – Universidade Estadual Paulista IBTN/BR Brazilian Branch of the Institute of Biomaterials Tribocorrosion and Nanomedicine Faculty of Sciences UNESP – Universidade Estadual Paulista Faculdade de Ciências Departamento de Física UNESP – Universidade Estadual Paulista National Science Foundation: 1564950 CNPq: 490761/2013-5 CAPES: 99999.008666/2014-08 Federación Española de Enfermedades Raras: POCI-01–0145-FEDER-006941 Fundació Catalana de Trasplantament: SFRH/BD/88517/2012 Fundació Catalana de Trasplantament: UID/EEA/04436/2013

New nanofluidic LC-TEM devices enable controlling and understanding electron irradiation history effects on liquid samples., In situ liquid cell transmission electron microscopy (LC-TEM) allows dynamic nanoscale characterization of systems in a hydrated state. Although powerful, this technique remains impaired by issues of repeatability that limit experimental fidelity and hinder the identification and control of some variables underlying observed dynamics. We detail new LC-TEM devices that improve experimental reproducibility by expanding available imaging area and providing a platform for investigating electron flux history on the sample. Irradiation history is an important factor influencing LC-TEM results that has, to this point, been largely qualitatively and not quantitatively described. We use these devices to highlight the role of cumulative electron flux history on samples from both nanoparticle growth and biological imaging experiments and demonstrate capture of time zero, low-dose images on beam-sensitive samples. In particular, the ability to capture pristine images of biological samples, where the acquired image is the first time that the cell experiences significant electron flux, allowed us to determine that nanoparticle movement compared to the cell membrane was a function of cell damage and therefore an artifact rather than visualizing cell dynamics in action. These results highlight just a subset of the new science that is accessible with LC-TEM through the new multiwindow devices with patterned focusing aides.

While 3D printing of rechargeable batteries has received immense interest in advancing the next generation of 3D energy storage devices, challenges with the 3D printing of electrolytes still remain. Additional processing steps such as solvent evaporation were required for earlier studies of electrolyte fabrication, which hindered the simultaneous production of electrode and electrolyte in an all-3D-printed battery. Here, a novel method is demonstrated to fabricate hybrid solid-state electrolytes using an elevated-temperature direct ink writing technique without any additional processing steps. The hybrid solid-state electrolyte consists of solid poly(vinylidene fluoride-hexafluoropropylene) matrices and a Li+ -conducting ionic-liquid electrolyte. The ink is modified by adding nanosized ceramic fillers to achieve the desired rheological properties. The ionic conductivity of the inks is 0.78 × 10 -3 S cm-1 . Interestingly, a continuous, thin, and dense layer is discovered to form between the porous electrolyte layer and the electrode, which effectively reduces the interfacial resistance of the solid-state battery. Compared to the traditional methods of solid-state battery assembly, the directly printed electrolyte helps to achieve higher capacities and a better rate performance. The direct fabrication of electrolyte from printable inks at an elevated temperature will shed new light on the design of all-3D-printed batteries for next-generation electronic devices.

The advent of nanotechnology has offered the development of promising new weapons against various cancers, including malignant brain tumors. From the bioengineering point of view, nanoparticles (NPs) exhibit many properties which enhance their suitability as therapeutic agents. A wide variety of NPs have been created, with ingenious strategies for binding and destroying cancer cells, including glioblastoma and medulloblastoma. This chapter discusses basic bioengineering principles, as well as in vitro and in vivo studies of NPs, as related to neuro-oncology. Critical issues such as NP delivery into brain tissue (across the blood-brain barrier (BBB) or by convection-enhanced delivery), toxicity, and binding to tumor cells in vivo, are beginning to be addressed. If the BBB is intact, NPs may be transported across it by means of adsorptive-mediated transcytosis, receptor-mediated endocytosis, or receptor-mediated transcytosis. Experimental studies of NPs should be standardized, in order to facilitate rational comparison of their therapeutic potential. There is a pressing need for more clinical trials aimed at evaluating the safety and efficacy of this form of therapy, which holds great potential for patients with malignant brain tumors.

Made available in DSpace on 2018-12-11T17:12:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-09-15 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) The decoration of titanium (Ti) implant surfaces with TiO2 nanotubes has emerged as a promising strategy to improve osseointegration and avoid infection. Nevertheless, it has been reported that nanotubular films are prone to peeling off from the Ti substrate due to the poor interfacial adhesion. The knowledge on the interfacial properties of such interface, although not well explored, is crucial for understanding the mechanisms behind the poor adhesion problem of these films and to further achieve an easy and effective solution to solve it. This paper is focused on the bio-functionalization of TiO2 nanotubular films with zinc (Zn) as an antimicrobial and bone healing agent, together with two major components of bone matrix, namely calcium (Ca) and phosphorous (P). The main aim is, for the first time, the thorough characterization of the interface between TiO2 nanotubes and the Ti substrate, along with the better understanding of the bio-functionalization mechanisms of TiO2 nanotubes and their influence on the interfacial features of the films. TiO2 nanotubes were successfully synthesized by two-step anodization and their bio-functionalization with Ca, P and Zn was achieved by reverse polarization anodization treatments. The in-depth characterization of the morphological and chemical features of TiO2 nanotubes was carried out along their length by scanning transmission electron microscopy (STEM) and energy dispersive X-ray spectroscopy (EDS), before and after bio-functionalization treatments. STEM images showed that the interface between conventional TiO2 nanotubes and Ti is non-continuous due to the existence of a hollow space. However, bio-functionalized TiO2 nanotubes evidenced an interface with different features, due to the formation of an interfacial oxide film as a consequence of anodization, with a thickness comprised between 230 and 250 nm. The results presented in this work may inspire the emergence of novel surface treatment strategies seeking the long-term performance of metallic-modified osseointegrated implants. CMEMS – Center of MicroElectroMechanical Systems Department of Mechanical Engineering University of Minho, Azurém IBTN/BR – Brazilian Branch of the Institute of Biomaterials Tribocorrosion and Nanomedicine Faculty of Sciences UNESP – Universidade Estadual Paulista Brazilian Center for Research in Physics Directory of Life Sciences Applied Metrology National Institute of Metrology Quality and Technology Postgraduate Program in Translational Biomedicine University of Grande Rio Institute of Biomedical Sciences UFRJ – Federal University of Rio de Janeiro Department of Materials Engineering KU Leuven Faculdade de Ciências Departamento de Física UNESP – Universidade Estadual Paulista Department of Bioengineering University of Illinois at Chicago IBTN/US – American Branch of the Institute of Biomaterials Tribocorrosion and Nanomedicine University of Illinois at Chicago IBTN/BR – Brazilian Branch of the Institute of Biomaterials Tribocorrosion and Nanomedicine Faculty of Sciences UNESP – Universidade Estadual Paulista Faculdade de Ciências Departamento de Física UNESP – Universidade Estadual Paulista CNPq: 490761/2013-5 CAPES: 99999.008666/2014-08

While titanium is the metal of choice for most prosthetics and inner body devices due to its superior biocompatibility, the discovery of Ti-containing species in the adjacent tissue as a result of wear and corrosion has been associated with autoimmune diseases and premature implant failures. Here, we utilize the in situ liquid cell transmission electron microscopy (TEM) in a liquid flow holder and graphene liquid cells (GLCs) to investigate, for the first time, the in situ nano–bio interactions between titanium dioxide nanoparticles and biological medium. This imaging and spectroscopy methodology showed the process of formation of an ionic and proteic bio-camouflage surrounding Ti dioxide (anatase) nanoparticles that facilitates their internalization by bone cells. The in situ understanding of the mechanisms of the formation of the bio-camouflage of anatase nanoparticles may contribute to the definition of strategies aimed at the manipulation of these NPs for bone regenerative purposes.

Made available in DSpace on 2018-12-11T17:08:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-03-31 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The modification of surface features such as nano-morphology/topography and chemistry have been employed in the attempt to design titanium oxide surfaces able to overcome the current dental implants failures. The main goal of this study is the synthesis of bone-like structured titanium dioxide (TiO2) nanotubes enriched with Calcium (Ca) and Phosphorous (P) able to enhance osteoblastic cell functions and, simultaneously, display an improved corrosion behavior. To achieve the main goal, TiO2 nanotubes were synthetized and doped with Ca and P by means of a novel methodology which relied, firstly, on the synthesis of TiO2 nanotubes by anodization of titanium in an organic electrolyte followed by reverse polarization and/or anodization, in an aqueous electrolyte. Results show that hydrophilic bone-like structured TiO2 nanotubes were successfully synthesized presenting a highly ordered nano-morphology characterized by non-uniform diameters. The chemical analysis of such nanotubes confirmed the presence of CaCO3, Ca3(PO4)2, CaHPO4 and CaO compounds. The nanotube surfaces submitted to reverse polarization, presented an improved cell adhesion and proliferation compared to smooth titanium. Furthermore, these surfaces displayed a significantly lower passive current in artificial saliva, and so, potential to minimize their bio-degradation through corrosion processes. This study addresses a very simple and promising multidisciplinary approach bringing new insights for the development of novel methodologies to improve the outcome of osseointegrated implants. CMEMS – Center of Micro Electro Mechanical Systems Department of Mechanical Engineering University of Minho IBTN/US – American Branch of the Institute of Biomaterials, Tribocorrosion and Nanomedicine Department of Mechanical Engineering Michigan Technological University Departmenmt of Restorative Dentistry University of Illinois at Chicago Department of Orthopedic Surgery Rush University Medical Center Department of Biomedical science UIC school of Medicine IBTN/Br – Brazilian Branch of the Institute of Biomaterials Tribocorrosion and Nanomedicine UNESP – Universidade Estadual Paulista Faculdade de Ciências Campus de Bauru Department of Materials Engineering, KU Leuven Department of Bioengineering University of Illinois at Chicago Faculdade de Ciências Departamento de Física UNESP - Universidade Estadual Paulista IBTN/Br – Brazilian Branch of the Institute of Biomaterials Tribocorrosion and Nanomedicine UNESP – Universidade Estadual Paulista Faculdade de Ciências Campus de Bauru Faculdade de Ciências Departamento de Física UNESP - Universidade Estadual Paulista

The lack of osseointegration and implant-related infections are two major complications leading to failure of dental and orthopedic implants. Therefore, the development of effective titanium (Ti) implant surfaces able to display enhanced osteogenic activity and antimicrobial properties is required. In particular, titanium dioxide (TiO2) nanotubes (NTs) have demonstrated promising features to modulate biological responses, as they may be easily tailored to achieve multiple functions. This work aims to study the ability of bio-functionalized TiO2 NTs to induce osseointegration, and concomitantly, to avoid infection. TiO2 NTs were bio-functionalized with calcium (Ca), phosphorous (P) and zinc (Zn), by reverse polarization anodization. Morphological and topographical features of NTs were observed through scanning electron microscopy (SEM), while surface chemistry was investigated by X-ray photoelectron spectroscopy (XPS). Biocompatibility studies were conducted with MG-63 and human mesenchymal stem cells (hMSCs) through MTT assay. Furthermore, cell morphology and cytoskeleton organization were observed by SEM and laser scanning confocal microscopy (LSCM). The osteoblastic differentiation capacity of hMSCs was studied by real-time PCR, as well as their angiogenesis ability by measuring the total release of vascular endothelial growth factor (VEGF). Finally, viability of Staphylococcus aureus (S. aureus) was assessed by live/dead bacterial viability assay. Results show that bio-functionalized TiO2 nanotubular surfaces are biocompatible and modulated cell morphology. In particular, NTs enriched with Ca, P, and Zn, induced to significantly up-regulated levels of bone morphogenetic protein 2 (BMP-2) and osteopontin (OPN) genes of hMSCs, when compared to conventional NTs. TiO2 nanotubular surfaces induced hMSCs to release a higher amount of VEGF, and significantly reduced the bacterial viability, both when compared to adequate Ti controls. In conclusion, the superimposition of TiO2 nanotubular-textured surfaces and their enrichment with Ca, P, and Zn, is a very promising approach for the development of novel bio-selective implant surfaces able to improve osseointegration and avoid infection., The authors acknowledge the financial support from FCT by the doctoral grant (Ref. SFRH/BD/88517/2012), CAPES (Proc. 99999.008666/2014-08), CNPq (Proc. 490761/2013-5) and UNESP. Also, the authors would like to thank Rio de Janeiro cell bank (BCRJ, Rio de Janeiro, Brasil) for all the support provided for biological experiments, as well Fernando Almeida for technical assistance at confocal microscope in CENABIO-UFRJ (Rio de Janeiro, Brasil). Tolou Shokuhfar especially thanks to US National Science Foundation NSF-DMR CAREER award # 1564950., info:eu-repo/semantics/publishedVersion

It has been shown that the synthesis of TiO2 nanotubes by anodization provides outstanding properties to Ti surfaces intended for dental and orthopedic implants applications. Beyond the very well-known potential of these surfaces to improve osseointegration and avoid infection, the knowledge on the adhesion and degradation behavior of TiO2 nanotubes under the simultaneous action of wear and corrosion is still poorly understood and these are issues of tremendous importance. The main aim of this work is to investigate, for the first time, the tribo-electrochemical degradation behavior of Ti surfaces decorated with TiO2 nanotubes before and after bio-functionalization treatments.Well-aligned TiO2 nanotubes (NTs) were produced containing elements natively present in bone such as calcium (Ca) and phosphorous (P), in addition of zinc (Zn) as an antimicrobial agent and stimulator of bone formation. The synthesis of Ca/P/Zn-doped nanotubes (NT-Ca/P/Zn) was achieved by reverse polarization and anodization treatments applied to conventional TiO2 nanotubes grown by two-step anodization. The nanotube surfaces were analyzed by scanning electron microscopy (SEM) while dark-field scanning transmission electron microscopy (STEM-DF) was used to characterize the Ti/TiO2 nanotubular films interfaces. Tribo-electrochemical tests were conducted under reciprocating sliding conditions in artificial saliva. The open circuit potential (OCP) was monitored before, during and after sliding tests, and the coefficient of friction (COF) values were registered during rubbing action. The wear tracks resulting from sliding tests were characterized by SEM and wear volume measurements were carried out by 2D profilometry.The results show that the tribo-electrochemical behavior of TiO2 nanotubes was significantly improved after bio-functionalization treatments. The higher electrochemical stability and lower mechanical degradation of these films was correlated with their improved adhesion strength to Ti substrate, which is granted by the nano-thick ox, This work was supported by FCT with the reference project UID/EEA/04436/2013 and by FEDER funds through the COMPETE 2020 - Programa Operacional Competitividade e Internacionalizacao (POCI) with the reference project POCI-01-0145-FEDER-006941.The authors also acknowledge the financial support from FCT by the doctoral grant (Ref. SFRH/BD/88517/2012), CAPES (Proc. 99999.008666/2014-08), CNPq (Proc. 490761/2013-5) and UNESP. Also, the authors would like to thank LABNANO/CBPF (Brazilian Center for Research in Physics) for all the support in electron microscopy analyses. Tolou Shokuhfar is especially thankful to US National Science Foundation NSF-DMR CAREER award # 1564950., info:eu-repo/semantics/publishedVersion

Background: Hepatic ischemia reperfusion is one the main causes for graft failure following transplantation. Although, the molecular events that lead to hepatic failure following ischemia reperfusion (IR) are diverse and complex, previous studies have shown that excessive formation of reactive oxygen species (ROS) are responsible for hepatic IR injury. Cerium oxide (CeO2) nanoparticles have been previously shown to act as an anti-oxidant and anti-inflammatory agent. Here, we evaluated the protective effects of CeO2 nanoparticles on hepatic ischemia reperfusion injury. Methods: Male Sprague Dawley rats were randomly assigned to one of the four groups: Control, CeO2 nanoparticle only, hepatic ischemia reperfusion (IR) group and hepatic ischemia reperfusion (IR) plus CeO2 nanoparticle group (IR+ CeO2). Partial warm hepatic ischemia was induced in left lateral and median lobes for 1h, followed by 6h of reperfusion. Animals were sacrificed after 6h of reperfusion and blood and tissue samples were collected and processed for various biochemical experiments. Results: Prophylactic treatment with CeO2 nanoparticles (0.5mg/kg i.v (IR+CeO2 group)) 1 hour prior to hepatic ischemia and subsequent reperfusion injury lead to a decrease in serum levels of alanine aminotransaminase and lactate dehydrogenase at 6 hours after reperfusion. These changes were accompanied by significant decrease in hepatocyte necrosis along with reduction in several serum inflammatory markers such as macrophage derived chemokine, macrophage inflammatory protein-2, KC/GRO, myoglobin and plasminogen activator inhibitor-1. However, immunoblotting demonstrated no significant changes in the levels of apoptosis related protein markers such as bax, bcl2 and caspase 3 in IR and IR+ CeO2 groups at 6 hours suggesting necrosis as the main pathway for hepatocyte death. Conclusion: Taken together, these data suggest that CeO2 nanoparticles attenuate IR induced cell death and can be used as a prophylactic agent to prevent hepatic injury associated with graft failure.

A controlled electron-water radiolysis process is used to generate predictable concentrations of radical and ionic species in graphene liquid cells, allowing the concept of a nanoscale chemical reactor. A differential scanning technique is used to generate the desired time- and space-varying electron dose rate. Precise control of the local concentration of H2 , the dominant radiolysis species, is demonstrated experimentally at the nanometer scale.