Environmental characterization of ferrochromium production waste (refined slag) and its carbonization product.

This paper presents the results of research on the method of utilization of self-disintegrating slags of refined ferrochrome production by autoclave carbonization in carbon dioxide environment. The work has a complex character, including earlier laboratory studies of the slag carbonization process under different conditions, as well as studies of chemical and mineralogical composition of initial waste slags taken from the slag dump and samples of bricks subjected to carbonization. The composition of slags and obtained products was investigated by XRD, DTA, DTG and XRF analyses, which showed that the main phases of the studied samples are dicalcium silicate, montichelite, periclase, magnesiochromite, calcite. Thermal analytical studies showed that magnesium carbonate is present only in the samples of artificially carbonized material. Also, the process of carbonate formation in the thickness of bricks during forced carbonization was investigated. As a result, it was obtained that with increasing CO2 pressure, the amount of bound carbon in the products increases proportionally in all layers. It was determined that the amount of CO2 absorbed during carbonization can reach 20 % of the mass of the initial slag. Stale slag can be used simultaneously as a carbon dioxide absorber and as a building product.

Devices used for photobiomodulation of the brain-a comprehensive and systematic review.

A systematic review was conducted to determine the trends in devices and parameters used for brain photobiomodulation (PBM). The revised studies included clinical and cadaveric approaches, in which light stimuli were applied to the head and/or neck. PubMed, Scopus, Web of Science and Google Scholar databases were used for the systematic search. A total of 2133 records were screened, from which 97 were included in this review. The parameters that were extracted and analysed in each article were the device design, actuation area, actuation site, wavelength, mode of operation, power density, energy density, power output, energy per session and treatment time. To organize device information, 11 categories of devices were defined, according to their characteristics. The most used category of devices was laser handpieces, which relate to 21% of all devices, while 28% of the devices were not described. Studies for cognitive function and physiological characterisation are the most well defined ones and with more tangible results. There is a lack of consistency when reporting PBM studies, with several articles under defining the stimulation protocol, and a wide variety of parameters used for the same health conditions (e.g., Alzheimer's or Parkinson's disease) resulting in positive outcomes. Standardization for the report of these studies is warranted, as well as sham-controlled comparative studies to determine which parameters have the greatest effect on PBM treatments for different neurological conditions.

Engineering a Hybrid Ti6Al4V-Based System for Responsive and Consistent Osteogenesis.

As the aging population increases worldwide, the incidence of musculoskeletal diseases and the need for orthopedic implants also arise. One of the most desirable goals in orthopedic reconstructive therapies is de novo bone formation. Yet, reproducible, long-lasting, and cost-effective strategies for implants that strongly induce osteogenesis are still in need. Nanoengineered titanium substrates (and their alloys) are among the most used materials in orthopedic implants. Although having high biocompatibility, titanium alloys hold a low bioactivity profile. The osteogenic capacity and osseointegration of Ti-based implantable systems are limited, as they critically depend on the body-substrate interactions defined by blood proteins adsorbed into implant surfaces that ultimately lead to the recruitment, proliferation, and differentiation of mesenchymal stem cells (MSCs) to comply bone formation and regeneration. In this work, a hybrid Ti6Al4V system combining micro- and nanoscale modifications induced by hydrothermal treatment followed by functionalization with a bioactive compound (fibronectin derived from human plasma) is proposed, aiming for bioactivity improvement. An evaluation of the biological activity and cellular responses in vitro with respect to bone regeneration indicated that the integration of morphological and chemical modifications into Ti6Al4V surfaces induces the osteogenic differentiation of MSCs to improve bone regeneration by an enhancement of mineral matrix formation that accelerates the osseointegration process. Overall, this hybrid system has numerous competitive advantages over more complex treatments, including reproducibility, low production cost, and potential for improved long-term maintenance of the implant.

Octacalcium Phosphate-Laden Hydrogels on 3D-Printed Titanium Biomaterials Improve Corrosion Resistance in Simulated Biological Media.

The inflammatory-associated corrosion of metallic dental and orthopedic implants causes significant complications, which may result in the implant's failure. The corrosion resistance can be improved with coatings and surface treatments, but at the same time, it might affect the ability of metallic implants to undergo proper osteointegration. In this work, alginate hydrogels with and without octacalcium phosphate (OCP) were made on 3D-printed (patterned) titanium alloys (Ti Group 2 and Ti-Al-V Group 23) to enhance their anticorrosion properties in simulated normal, inflammatory, and severe inflammatory conditions in vitro. Alginate (Alg) and OCP-laden alginate (Alg/OCP) hydrogels were manufactured on the surface of 3D-printed Ti substrates and were characterized with wettability analysis, XRD, and FTIR. The electrochemical characterization of the samples was carried out with open circuit potential, potentiodynamic polarization, and electrochemical impedance spectroscopy (EIS). It was observed that the hydrophilicity of Alg/OCP coatings was higher than that of pure Alg and that OCP phase crystallinity was increased when samples were subjected to simulated biological media. The corrosion resistance of uncoated and coated samples was lower in inflammatory and severe inflammatory environments vs. normal media, but the hydrogel coatings on 3D-printed Ti layers moved the corrosion potential towards more nobler values, reducing the corrosion current density in all simulated solutions. These measurements revealed that OCP particles in the Alg hydrogel matrix noticeably increased the electrical charge transfer resistance at the substrate and coating interface more than with Alg hydrogel alone.

Bio-Piezoelectric Ceramic Composites for Electroactive Implants-Biological Performance.

Barium titanate (BaTiO3) piezoelectric ceramic may be a potential alternative for promoting osseointegration due to its piezoelectric properties similar to bone electric potentials generated in loading function. In this sense, the aim of this in vitro study was to evaluate the cellular response of human osteoblasts and gingival fibroblasts as well as the impact on S. oralis when in contact with BaTiO3 functionalized zirconia implant surfaces with piezoelectric properties. Zirconia discs with BaTiO3 were produced and contact poling (piezo activation) was performed. Osteoblasts (hFOB 1.19), fibroblasts (HGF hTERT) and S. oralis were culture on discs. Cell viability and morphology, cell differentiation markers, bacterial adhesion and growth were evaluated. The present study suggests that zirconia composite surfaces with the addition of piezoelectric BaTiO3 are not cytotoxic to peri-implant cells. Also, they seem to promote a faster initial osteoblast differentiation. Moreover, these surfaces may inhibit the growth of S. oralis by acting as a bacteriostatic agent over time. Although the piezoelectric properties do not affect the cellular inflammatory profile, they appear to enable the initial adhesion of bacteria, however this is not significant over the entire testing period. Furthermore, the addition of non-poled BaTiO3 to zirconia may have a potential reduction effect on IL-6 mediated-inflammatory activity in fibroblasts.

Electrochemical and biological characterization of Ti-Nb-Zr-Si alloy for orthopedic applications.

The performance of current biomedical titanium alloys is limited by inflammatory and severe inflammatory conditions after implantation. In this study, a novel Ti-Nb-Zr-Si (TNZS) alloy was developed and compared with commercially pure titanium, and Ti-6Al-4V alloy. Electrochemical parameters of specimens were monitored during 1 h and 12 h immersion in phosphate buffered saline (PBS) as a normal, PBS/hydrogen peroxide (H2O2) as an inflammatory, and PBS/H2O2/albumin/lactate as a severe inflammatory media. The results showed an effect of the H2O2 in inflammatory condition and the synergistic behavior of H2O2, albumin, and lactate in severe inflammatory condition towards decreasing the corrosion resistance of titanium biomaterials. Electrochemical tests revealed a superior corrosion resistance of the TNZS in all conditions due to the presence of silicide phases. The developed TNZS was tested for subsequent cell culture investigation to understand its biocompatibility nature. It exhibited favorable cell-materials interactions in vitro compared with Ti-6Al-4V. The results suggest that TNZS alloy might be a competitive biomaterial for orthopedic applications.

Smart Hydrogels for Advanced Drug Delivery Systems.

Since the last few decades, the development of smart hydrogels, which can respond to stimuli and adapt their responses based on external cues from their environments, has become a thriving research frontier in the biomedical engineering field. Nowadays, drug delivery systems have received great attention and smart hydrogels can be potentially used in these systems due to their high stability, physicochemical properties, and biocompatibility. Smart hydrogels can change their hydrophilicity, swelling ability, physical properties, and molecules permeability, influenced by external stimuli such as pH, temperature, electrical and magnetic fields, light, and the biomolecules' concentration, thus resulting in the controlled release of the loaded drugs. Herein, this review encompasses the latest investigations in the field of stimuli-responsive drug-loaded hydrogels and our contribution to this matter.

Biomechanical and functional comparison of moulded and 3D printed medical silicones.

Modern 3D printing of implantable devices provides an important opportunity for the development of personalized implants with good anatomical fit. Nevertheless, 3D printing of silicone has been challenging and the recent advances in technology are provided by the systems which can print medical grade silicone via extrusion. However, the potential impacts of the 3D printing process of silicone on its biomechanical properties has not been studied in sufficient detail. Therefore, the present study compares 3D printed and moulded silicone structures for their cytotoxicity, surface roughness, biomechanical properties, and in vivo tissue reaction. The 3D printing process creates increased nanoscale roughness and noticeably changes microscale topography. Neither the presence of these features nor the differences in processes were found to result in an increase in cytotoxicity or tissue reaction for 3D printed structures, exhibiting limited inflammatory reaction and cell viability above the threshold values. On the contrary, the biomechanical properties have demonstrated significant differences in static and dynamic conditions, and in thermal expansion. Our results demonstrate that 3D printing can be used for establishing a better biomechanical microenvironment for the surrounding tissue of the implant particularly for fragile soft tissue like epithelial mucosa without having any negative effect on the cytotoxicity or in vivo reaction to silicone. For engineering of the implants, however, one must consider the differences in mechanical properties to result in correct and personalized geometry and proper physical interaction with tissues.

Biomechanical Properties of Bone and Mucosa for Design and Application of Dental Implants.

Dental implants' success comprises their proper stability and adherence to different oral tissues (integration). The implant is exposed to different mechanical stresses from swallowing, mastication and parafunctions for a normal tooth, leading to the simultaneous mechanical movement and deformation of the whole structure. The knowledge of the mechanical properties of the bone and gingival tissues in normal and pathological conditions is very important for the successful conception of dental implants and for clinical practice to access and prevent potential failures and complications originating from incorrect mechanical factors' combinations. The challenge is that many reported biomechanical properties of these tissues are substantially scattered. This study carries out a critical analysis of known data on mechanical properties of bone and oral soft tissues, suggests more convenient computation methods incorporating invariant parameters and non-linearity with tissues anisotropy, and applies a consistent use of these properties for in silico design and the application of dental implants. Results show the advantages of this approach in analysis and visualization of stress and strain components with potential translation to dental implantology.

Customized Root-Analogue Implants: A Review on Outcomes from Clinical Trials and Case Reports.

(1) It is estimated that 10% of the world's population will need a dental implant in their lifetime. Despite all the advances in the comprehension of dental implant designs, materials and techniques, traditional implants still have many limitations. Customized root-analogue implants are, therefore, gaining increased interest in dental rehabilitation and are expected to not only preserve more hard and soft tissues but also avoid a second surgery and improve patient overall satisfaction. In this sense, the aim of this review was to collect and analyse the clinical trials and case reports on customized root-analogue implants available in the literature; (2) This review was carried out according to the PRISMA Statement. An electronic database search was performed using five databases: PubMed, Google Scholar, Medline, Science Direct, and Scopus. The following keywords were used for gathering data: custom-made, dental implants, root-analogue, anatomical, customized and tooth-like; (3) 15 articles meeting the inclusion criteria-articles reporting clinical trials, case reports or animal studies and articles with root-analogue implants and articles with totally customized implant geometries-were selected for the qualitative synthesis. The design and manufacturing techniques, implant material and surface treatments were assessed and discussed; (4) The performance of some root-analogue implants with specific features (i.e., macro-retentions) was successful, with no signs of infection, periodontitis nor bleeding during the follow-up periods.

Enhancement of Gingival Tissue Adherence of Zirconia Implant Posts: In Vitro Study.

Prevention of bacterial inflammation around dental implants (peri-implantitis) is one of the keys to success of the implantation and can be achieved by securing the gingival tissue-abutment interface preventing penetration of bacteria. Modern dental practice has adopted zirconia abutments in place of titanium, but the adhesion of gingival tissue to zirconia is inferior to titanium. The aim of this study was to assess and improve the adhesion of mucosal tissues to zirconia posts using sol-gel derived TiO2 coating following dynamic mechanical testing. The posts were cultivated with porcine bone-gingival tissue specimens in vitro for 7 and 14 days and then subjected to dynamic mechanical analysis simulating physiological loading at 1 Hz up to 50 µm amplitude. In parallel in silico analysis of stresses and strains have been made simulating "the worst case" when the fixture fails in osseointegration while the abutment still holds. Results show treatment of zirconia can lead to double interface stiffness (static shear stiffness values from 5-10 to 17-23 kPa and dynamic from 20-50 to 60-125 kPa), invariant viscostiffness (from 5-35 to 45-90 kPa·sα) and material memory values (increased from 0.06-0.10 to 0.17-0.25), which is beneficial in preventing bacterial contamination in dental implants. This suggests TiO2-coated zirconia abutments may have a significant clinical benefit for prevention of the bacterial contamination.

Reengineering Bone-Implant Interfaces for Improved Mechanotransduction and Clinical Outcomes.

The number of patients undergoing joint replacement surgery has progressively increased worldwide due to world population ageing. In the Unites States, for example, the prevalence of hip and knee replacements has increased more than 6 and 10 times, respectively, since 1980. Despite advances in orthopaedic implant research, including the development of novel implantable biomaterials, failures are still observed due to inadequate biomechanical compliance at the bone-implant interface. This comprises static and dynamic mechanical mismatch between the bone and the implant surface. The importance and robustness of biomechanical cues for controlling osteogenic differentiation of mesenchymal stem cells (MSC) have been highlighted in recent studies. However, in the context of bone regenerative medicine, it remains elusive how mechanobiological signals controlling MSC osteogenic differentiation dynamics are modulated in their interaction with the bone and with implants. In this review, we highlight recent technological advances aiming to improve host bone-implant interactions based on the osteogenic and mechanoresponsive potential of MSC, in the context of joint replacement surgery. First, we discuss the extracellular and intracellular mechanical forces underlying proper receptivity and stimulation of physiological MSC differentiation and linked osteogenic activity. Second, we provide a critical overview on how this knowledge can be integrated towards the development of biomaterials for improved bone-implant interfaces. Third, we discuss cross-disciplinarily which contributes to the next generation design of novel pro-active orthopaedic implants and their implantation success. Graphical Abstract.

Biomechanical Features of Graphene-Augmented Inorganic Nanofibrous Scaffolds and Their Physical Interaction with Viruses.

Nanofibrous substrates and scaffolds are widely being studied as matrices for 3D cell cultures, and disease models as well as for analytics and diagnostic purposes. These scaffolds usually comprise randomly oriented fibers. Much less common are nanofibrous scaffolds made of stiff inorganic materials such as alumina. Well-aligned matrices are a promising tool for evaluation of behavior of biological objects affected by micro/nano-topologies as well as anisotropy. In this work, for the first time, we report a joint analysis of biomechanical properties of new ultra-anisotropic, self-aligned ceramic nanofibers augmented with two modifications of graphene shells (GAIN scaffolds) and their interaction of three different viral types (influenza virus A, picornavirus (human parechovirus) and potato virus). It was discovered that nano-topology and structure of the graphene layers have a significant implication on mechanical properties of GAIN scaffolds resulting in non-linear behavior. It was demonstrated that the viral adhesion to GAIN scaffolds is likely to be guided by physical cues in dependence on mutual steric factors, as the scaffolds lack common cell membrane proteins and receptors which viruses usually deploy for transfection. The study may have implications for selective viral adsorption, infected cells analysis, and potentially opening new tools for anti-viral drugs development.

Zirconia implants with improved attachment to the gingival tissue.

BACKGROUND: Gingival tissue attachment is known to be important for long-term prognosis of implants. This in vitro study evaluated the gingival attachment to zirconia implants and zirconia implants modified with sol-gel derived TiO2 coatings. METHODS: Zirconia endodontic posts (n = 23) were used to function as implants that were inserted into the center of full-thickness porcine gingival explants (n = 31). The tissue/implant specimens were then individually placed at an air/liquid interface on a stainless-steel grid in cell culture wells containing a nutrient solution. The tissue cultures were incubated at 37°C in a 5% CO2 environment and at days 7 and 14, the specimens were harvested and analyzed by dynamic mechanical analysis (DMA) measurements under dynamic loading conditions mimicking natural mastication. Specimens were also analyzed by immunohistochemical staining identifying the laminin (Ln) γ2 chain specific for Ln-332, which is known to be a crucial molecule for the proper attachment of epithelium to tooth/implant surface. RESULTS: Tissue attachment to TiO2 -coated zirconia demonstrated higher dynamic modulus of elasticity and higher creep modulus, meaning that the attachment is stronger and more resistant to damage during function over time. Laminin γ2 was identified in the attachment of epithelium to TiO2 -coated zirconia. CONCLUSIONS: Both DMA and histological analysis support each other, so the gingival tissue is more strongly attached to sol-gel derived TiO2 -coated zirconia than uncoated zirconia. Immunohistochemical staining showed that TiO2 coating may enhance the synthesis and deposition of Ln-332 in the epithelial attachment to the implant surface.

Novel laser surface texturing for improved primary stability of titanium implants.

Recently, the production of well-defined patterned surfaces with random or regular micro and nano-features has brought new opportunities for research and development in the field of tissue engineering and regenerative medicine. Among advanced micro and nano processing technologies, laser surface texturing (LST) stands out due to its simplicity, flexibility, precision, reproducibility and relatively low cost. This work studies the development of patterned surfaces controlled by of LST into biomedical grade V titanium, Ti-6Al-4V-alloy. We present different cross-hatched micropatterns followed by the characterisation of surface morphology and topography. Structural integrity of the produced patterns is evaluated by friction tests against bone, mimicking the insertion of an implant. Wettability is studied as it is crucial for protein adsorption and cell adhesion. The results show that the surface topography obtained using different patterning plans influences the wetting behaviour and the coefficient of friction against bone.

Metallurgical Gallium Additions to Titanium Alloys Demonstrate a Strong Time-Increasing Antibacterial Activity without any Cellular Toxicity.

Orthopedic metallic devices are often related with devasting complications due to acute prosthetic joint infections. Gallium (Ga) antibacterial activity has been demonstrated by the evidence that Ga in solution ionizes in a Ga3+ trivalent form that replace Fe3+ thus arresting metabolism. However, it is not clear whether such effect is restricted only to Ga3+ release laps. Accordingly, here we investigated Ga addition into titanium alloys using metallurgical methods, thus realizing intermetallides of a very high stability that contain Ga in the range of 1, 2, 20, and 23% wt. ICP-OES analysis confirmed that Ga ions were not released from the specimens regardless of the Ga amount. These alloys ensured long-lasting Ga effect toward multidrug resistant Staphylococcus aureus, whose metabolic activity was reduced of >80% in comparison with controls. Finally, specimens cytocompatibility was confirmed by direct and indirect contact evaluations with mature osteoblasts and preosteoblasts progenitor cells.

The Importance of Controlled Mismatch of Biomechanical Compliances of Implantable Scaffolds and Native Tissue for Articular Cartilage Regeneration.

Scaffolds for articular cartilage repair have to be optimally biodegradable with simultaneous promotion of hyaline cartilage formation under rather complex biomechanical and physiological conditions. It has been generally accepted that scaffold structure and composition would be the best when it mimics the structure of native cartilage. However, a reparative construct mimicking the mature native tissue in a healing tissue site presents a biological mismatch of reparative stimuli. In this work, we studied a new recombinant human type III collagen-polylactide (rhCol-PLA) scaffolds. The rhCol-PLA scaffolds were assessed for their relative performance in simulated synovial fluids of 1 and 4 mg/mL sodium hyaluronate with application of model-free analysis with Biomaterials Enhanced Simulation Test (BEST). Pure PLA scaffold was used as a control. The BEST results were compared to the results of a prior in vivo study with rhCol-PLA. Collectively the data indicated that a successful articular cartilage repair require lower stiffness of the scaffold compared to surrounding cartilage yet matching the strain compliance both in static and dynamic conditions. This ensures an optimal combination of load transfer and effective oscillatory nutrients supply to the cells. The results encourage further development of intelligent scaffold structures for optimal articular cartilage repair rather than simply trying to imitate the respective original tissue.

Graphene-Augmented Nanofiber Scaffolds Trigger Gene Expression Switching of Four Cancer Cell Types.

Three-dimensional (3D) customized scaffolds are anticipated to provide new frontiers in cell manipulation and advanced therapy methods. Here, we demonstrate the application of hybrid 3D porous scaffolds, representing networks of highly aligned self-assembled ceramic nanofibers, for culturing four types of cancer cells. Ultrahigh aspect ratio (∼107) of graphene augmented fibers of tailored nanotopology is shown as an alternative tool to substantially affect cancerous gene expression, eventually due to differences in local biomechanical features of the cell-matrix interactions. Here, we report a clear selective up- and down-regulation of groups of markers for breast cancer (MDA-MB231), colorectal cancer (CaCO2), melanoma (WM239A), and neuroblastoma (Kelly) depending on only fiber orientation and morphology without application of any other stimulus. Changes in gene expression are also revealed for Mitomycin C treatment of MDA-MB231, making the scaffold a suitable platform for testing of anticancer agents. This allows an opportunity for selective "clean" guidance to a deep understanding of mechanisms of cancer cells progressive growth and tumor formation without possible side effects by manipulation with the specific markers.

Hybrid graphene-ceramic nanofibre network for spontaneous neural differentiation of stem cells.

A challenge in regenerative medicine is governed by the need to have control over the fate of stem cells that is regulated by the physical and chemical microenvironment in vitro and in vivo. The differentiation of the stem cells into specific lineages is commonly guided by use of specific culture media. For the first time, we demonstrate that human mesenchymal stem cells are capable of turning spontaneously towards neurogenic lineage when seeded on graphene-augmented, highly anisotropic ceramic nanofibres without special differentiation media, contrary to commonly thought requirement of 'soft' substrates for the same purpose. Furthermore, pro-inflammatory gene expression is simultaneously suppressed, and expression of factors promoting focal adhesion and monocytes taxis is upregulated. This opens new possibilities of using local topo-mechanical cues of the 'graphenized' scaffold surfaces to guide stem cell proliferation and differentiation, which can be used in studies of neurological diseases and cell therapy.

Influence of specimens' geometry and materials on the thermal stresses in dental restorative materials during thermal cycling.

OBJECTIVES: Thermal cycling is widely used to simulate the aging of restorative materials corresponding to the changes of temperature in the oral cavity. However, test parameters present in literature vary considerably, which prevents comparison between different reports. The aim of this work is to assess the influence of the specimens' geometry and materials on the thermal stresses developed during thermal cycling tests. MATERIALS AND METHODS: Finite elements method was used to simulate the conditions of thermal cycling tests for three different sample geometries: a three-points bending test sample, a cylinder rod and more complex shape of a restoration crown. Two different restorative systems were considered: all-ceramic (zirconia coupled with porcelain) and metal-ceramic (CoCrMo alloy coupled with porcelain). The stress state of each sample was evaluated throughout the test cycle. RESULTS: The results show that the sample geometry has great influence on the stress state, with difference of up to 230% in the maximum stress between samples of the same composition. The location of maximum stress also changed from the interface between materials to the external wall. CONCLUSIONS: Maximum absolute stress values were found to vary between 2 and 4MPa, which might not be critical even for ceramics. During multi-cycle testing these stresses would cause different fatigue in various locations. The zirconia-based specimens and zirconia-based restoration (crown) exhibited the most similar stress states. Thus it might be recommended to use these geometries for fast screening of the materials for this type of restorations. CLINICAL SIGNIFICANCE: The selection of specimens' geometry and materials should be carefully considered when aging conditions close to clinical ones want to be simulated.