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[Display omitted] Implantation of a biomaterial entails a form of injury where the integration of the implant into the host tissue greatly depends on the proper healing of the wound. Wound healing, itself, consists of a number of physiological processes, each occurring within a characteristic time window. A composite, multilayered polymeric drug delivery carrier for adhesion to the wound site and its supply with molecules released at precise time windows at which the stages in the healing process that they target occur is conceptualized here. We also present a simplified version of one such multilayered composite fabricated by a combination of solvent casting and dip coating, comprising the base poly(ε-caprolactone) layer reinforced with hydroxyapatite nanoparticles, poly(glutamic acid) mesolayer and poly- l -lysine surface layer, each loaded with specific small molecules and released at moderately distinct timescales, partially matching the chronology of wound healing. To that end, the base layer proved suitable for the delivery of an anti-inflammatory molecule or an angiogenic agent, the mesolayer appeared appropriate for the delivery of an epithelialization promoter or a granulation factor, and the adhesive surface layer interfacing directly with the site of injury showed promise as a carrier of a vasodilator. The drug release mechanisms were diffusion-driven, suggesting that the drug/carrier interaction is a key determinant of the release kinetics, as important as the nature of the polymer and its hydrolytic degradation rate in the aqueous medium. Morphological and phase composition analyses were performed, along with the cell compatibility ones, demonstrating solid adhesion and proliferation of both transformed and primary fibroblasts on both surfaces of the composite films. The design of the multilayered composite drug delivery carriers presented here is prospective, but requires further upgrades to achieve the ideal of a perfect timing of the sequential drug release kinetics and a perfect resonance with the physiological processes defining the chronology of wound healing. [ABSTRACT FROM AUTHOR]

The recipe for making Turkish coffee in some parts of former Yugoslavia calls for the dilution of the turbid liquid with lukewarm water just before the boiling point is reached. The enigmatic gastronomic purpose of this step notwithstanding, here it is being used as an inspiration for deriving a simple stabilization step for protocols for the synthesis of fine particle colloids. The dilution step inspired by coffee-making was performed in a protocol for the synthesis of hydroxyapatite nanoparticles by their precipitation from supersaturated alkaline aqueous solutions. The implementation of this step in the post-precipitation stage, concurrently with boiling, evidently improved the stability of the nanoparticle colloids. The stabilization effect was limited to the suspensions where the parent solution was equilibrated with the fresh precipitate and was not reproduced in colloids comprising HAp nanoparticles redispersed in deionized water. The dilution step produced a mild and counterintuitive increase in crystallinity, suggesting complex recrystallization mechanisms driven by mutually antagonistic dissolution caused by the dilution and reprecipitation caused by the heating to be responsible for the observed increase in stability. Incongruent dissolution favoring a less entropic surface order and reduced charge screening entailing the expansion of the Debye lengths were suggested as complementary mechanisms explaining the improvements in stability caused by adding this simple and economical, yet very efficacious touch to the synthesis. It is concluded that unconventional protocols in spheres other than the scientific and heritages routinely discarded as disreputable could be sources of insight relevant to a plethora of distant domains and disciplines. [ABSTRACT FROM AUTHOR]

Bioglass presents a standard biomaterial for regeneration of hard tissues in orthopedics and dentistry. The notable osteo-inductive properties of bioglass are largely due to the release of calcium ions from it. However, this release is not easily controllable and can often be excessive, especially during the initial interaction of the biomaterial with the surrounding tissues. Consequently, this excessive release can deplete the calcium content of the bioglass, ultimately reducing its overall bioactivity. In this study, we have tested if applying biopolymer chitosan coatings of different thicknesses would be able to mitigate and regulate the calcium ion release from monodisperse bioglass nanoparticles. Calcium release was assessed for four different chitosan coating thicknesses at different time points over the period of 28 days using a fluorescence quencher. Expectedly, chitosan-coated particles released less calcium as the concentration of chitosan in the coating solution increased, presumably due to the increased thickness of the chitosan coating around the bioglass particles. The mechanism of release remained constant for each coating thickness, corresponding to anomalous, non-Fickian diffusion, but the degree of anomalousness increased with the deposition of chitosan. Zeta potential testing showed an expected increase in the positive double layer charge following the deposition of the chitosan coating due to the surface exposure of the amine groups of chitosan. Less intuitively, the zeta potential became less positive as thickness of the chitosan coating increased, attesting to the lower density of the surface charges within thicker coatings than within the thinner ones. Overall, the findings of this study demonstrate that chitosan coating efficiently prevents the early release of calcium from bioglass. This coating procedure also allows for the tuning of the calcium release kinetics by controlling the chitosan concentration in the parent solution. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is a global public health concern, posing a significant threat to the effectiveness of antibiotics in treating bacterial infections. The accurate and timely detection of antibiotic-resistant bacteria is crucial for implementing appropriate treatment strategies and preventing the spread of resistant strains. This manuscript provides an overview of the current and emerging technologies used for the detection of antibiotic-resistant bacteria. We discuss traditional culture-based methods, molecular techniques, and innovative approaches, highlighting their advantages, limitations, and potential future applications. By understanding the strengths and limitations of these technologies, researchers and healthcare professionals can make informed decisions in combating antibiotic resistance and improving patient outcomes. [ABSTRACT FROM AUTHOR]

The Russian-Ukrainian scientist, G. V. Samsonov left an enormous legacy in materials science, even though a large portion of his and his group's work remained hidden behind the Iron Curtain. One of his crowning theoretical contributions that received but a slight tidbit of resonance in the west was the configurational model of the solid state based on the statistical weight of atoms with stable configuration (SWASC). Only a handful of papers employing this model were published in the western journals since the model was developed, in 1965. Here, the configurational model was tested for its ability to explain the effects of divalent transition elements on solubility of hydroxyapatite when they acted as dopants in it. It is shown that the SWASC values for half-filled d orbitals of transition elements in the ± 5 pm range of ionic radii centered around iron do correlate monotonously with the solubility change induced by the dopant ions relative to the solubility of stoichiometric hydroxyapatite synthesized and analyzed under the same conditions when the solubility values are extrapolated to identical atomic ratios between the dopant ions and the constitutive calcium ions. The effect of SWASC, however, competes with that of the dopant concentration, producing a complex plexus of mutually antagonistic effects. With this work, it is hoped that the interest in the work of G. V. Samsonov and the generation of his Soviet and Yugoslavian scientific contemporaries gets revived and their legacy in the west popularized. [ABSTRACT FROM AUTHOR]

The main protease (Mpro) of SARS‐COV‐2 plays a vital role in the viral life cycle and pathogenicity. Due to its specific attributes, this 3‐chymotrypsin like protease can be a reliable target for the drug design to combat COVID‐19. Since the advent of COVID‐19, Mpro has undergone many mutations. Here, the impact of 10 mutations based on their frequency and five more based on their proximity to the active site was investigated. For comparison purposes, the docking process was also performed against the Mpros of SARS‐COV and MERS‐COV. Four inhibitors with the highest docking score (11b, α‐ketoamide 13b, Nelfinavir, and PF‐07321332) were selected for the structure‐based ligand design via fragment replacement, and around 2000 new compounds were thus obtained. After the screening of these new compounds, the pharmacokinetic properties of the best ones were predicted. In the last step, comparative molecular dynamics (MD) simulations, molecular mechanics Poisson–Boltzmann surface area calculations (MM/PBSA), and density functional theory calculations were performed. Among the 2000 newly designed compounds, three of them (NE1, NE2, and NE3), which were obtained by modifications of Nelfinavir, showed the highest affinity against all the Mpro targets. Together, NE1 compound is the best candidate for follow‐up Mpro inhibition and drug development studies. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is caused by the inability of the pancreatic beta cells to produce sufficient amounts of insulin, an anabolic hormone promoting the absorption of the blood glucose by various cells in the body, primarily hepatocytes and skeletal muscle cells. This form of impaired metabolism has been traditionally treated with subcutaneous insulin injections. However, because one such method of administration does not directly correspond to the glucose concentrations in the blood and may fail to reduce hyperglycemia or cause hypoglycemia, the delivery of insulin in a glucose-dependent manner has been researched intensely in the present and past. This study tested the novel idea that the supplementation of polymeric reservoirs containing insulin with metallic nanoparticle precursors responsive to the redox effect of glucose could be used to create triggers for the release of insulin in direct response to the concentration of glucose in the tissue. For that purpose, manganese oxide nanoparticles were dispersed inside a poly(ε-caprolactone) matrix loaded with an insulin proxy and the resulting composite was exposed to different concentrations of glucose. The release of the insulin proxy occurred in direct proportion to the concentration of glucose in the medium. Mechanistically, as per the central hypothesis of the study, glucose reduced the manganese cations contained within the metal oxide phase, forming finer and more dissipative zero-valent metallic nanoparticles, thus disrupting the polymeric network, opening up pores in the matrix and facilitating the release of the captured drug. The choice of manganese for this study over other metals was justified by its use as a supplement for protection against diabetes. Numerical analysis of the release mechanism revealed an increasingly nonlinear and anomalous release accompanied by a higher diffusion rate at the expense of chain rigidity as the glucose concentration increased. Future studies should focus on rendering the glucose-controlled release (i) feasible within the physiological pH range and (ii) sensitive to physiologically relevant glucose concentrations. These technical improvements of the fundamental new concept proven here may bring it closer to a real-life application for the mitigation of symptoms of hyperglycemia in patients with diabetes. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HAp) is the major component of all boney tissues in mammals. Because of this omnipresence in the living world, HAp possesses an exceptional biocompatibility. The downside of this omnipresence, however, comes in the form of its mild to moderate biological activities. One means of augmenting these activities involves the doping of HAp with foreign ions. Here, the first synthesis and characterization of HAp doped with germanium ions is being reported. Germanium was deliberately integrated into the crystal lattice of HAp in the form of germanate anions. Approximately two thirds of the germanate ions introduced into the hydrothermal solution got incorporated into the HAp lattice, yielding the approximate stoichiometry of Ca 10-x (PO 4) 5.62+y (GeO 3) 0.38 (OH) 2-z. Germanates replaced the phosphates of stoichiometric HAp and induced the expansion of the HAp lattice both along the screw axis of the calcium ion hexagons and in the direction parallel to the basal plane. Simultaneously, the larger size and the triple valency of the germanate ion as compared to the smaller and trivalent phosphates prompted the bond distortion and charge compensation through defect formation, which reduced the crystallinity and increased the microstrain of the HAp lattice. Vibrational spectroscopic analyses corroborated these crystallographic effects by demonstrating the enhanced heterogeneity of the environments surrounding the active modes after germanate ions were incorporated into HAp. Conforming to La Châtelier's principle, this reduction of the crystallographic order increased the capacity of the material for integration of adventitious carbonates. However, the inclusion of germanate ions induced a partial shift of these carbonates to the hydroxyl channel sites, thus decreasing the ratio of the B-type carbonation to the A-type carbonation. Introduced into HAp, germanium acted as a superb regulator of the particle size and morphology, enhancing their fineness and uniformity. Inclusion of germanate ions also increased the electrophoretic mobility and hydrodynamic surface charge density of the particles by reducing their size and by inducing a more stochastic distribution of terminal ionic groups due to the bending of the crystal facets. Overall, the doping of HAp with germanate ions facilitated the production of narrowly dispersed nanorods with a moderately enhanced structural disorder and with a pronounced potential for the biomedical niche. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HAp), the most abundant biological material among mammals, has been recently demonstrated to possess moderate antibacterial properties. Metagenomics provides a series of tools for analyzing the simultaneous interaction of materials with larger communities of microbes, which may aid in optimizing the antibacterial activity of a material such as HAp. Here, a microbiome intrinsic to the sample of sandy soil collected from the base of an African Natal plum (Carissa macrocarpa) shrub surrounding the children's sandbox at the Arrowhead Park in Irvine, California was challenged with HAp nanoparticles and analyzed with next-generation sequencing for hypervariable 16S ribosomal DNA base pair homologies. HAp nanoparticles overwhelmingly reduced the presence of Gram-negative phyla, classes, orders, families, genera and species, and consequently elevated the relative presence of their Gram-positive counterparts. Thermodynamic, electrostatic and chemical bonding arguments were combined in a model proposed to explain this selective affinity. The ability of amphiphilic surface protrusions of lipoteichoic acid in Gram-positive bacteria and mycolic acid in mycobacteria to increase the dispersibility of the bacterial cells and assist in their resistance to capture by the solid phase is highlighted. Within the Gram-negative group, the variability of the distal, O-antigen portion of the membrane lipopolysaccharide was shown to be excessive and the variability of its proximal, lipid A portion insufficient to explain the selectivity based on chemical sequence arguments. Instead, flagella-driven motility proves to be a factor favoring the evasion of binding to HAp. HAp displayed a preference toward binding to less pathogenic bacteria than those causative of disease in humans, while taxa having a positive agricultural effect were largely captured by HAp, indicating an evolutionary advantage this may have given it as a biological material. The capacity to selectively sequester Gram-negative microorganisms and correspondingly alter the composition of the microbiome may open up a new avenue in environmental and biomedical applications of HAp. [ABSTRACT FROM AUTHOR]

The paper studies one typical interrogation (costituto) from early eighteenthcentury Venetian couriers who walked the republic's overland connection from Cattaro to Istanbul. In considering how time and space are reported in the included primary source, this article looks at how these modes of spatial and temporal representation relate to the structural realities of early modern long-distance travelling, thereby recovering the early modern road with its infrastructure and courier networks as a dynamic locus of contemporary politics. [ABSTRACT FROM AUTHOR]

What strategies can materials scientists employ to combat the global trend in admiration of research accomplishments to the detriment of depreciation of inventive educational efforts? Materials science has and will continue to be a science at a crossroads. Sociology and philosophy of science are studied at universities, but what would be sociologic trends and philosophical principles that apply uniquely to materials science?. [Extracted from the article]

To test if the transit of a nanoparticle across different organs in the body affects its properties at the final destination, we devised an in vitro system that mimics the passage of nanoparticles from the blood to the lung to the brain and, occasionally, back to the blood. Each of the three media provided a unique corona to the nanoparticles, comprising mainly secreted, blood-specific proteins in the plasma and membrane proteins in the lung and the brain. The hard corona changed during the transit of the nanoparticle between different organs. Cellular uptake, antibacterial activity, and drug release kinetics were analyzed to assess the difference in the biological response to nanoparticles depending on the transit route. Drug release assays most consistently demonstrated the effects of the history of the nanoparticle passage across different media on its present properties. Both the uptake analysis and antibacterial assays showed that the key proteins for these two processes in the brain replace their analogues from the lung, but are ineffective in replacing the blood plasma content from the nanoparticle surface. Notwithstanding that some routes can erase the history of the passage of the nanoparticle across different organs, the route traversed by it mostly affects the properties it displays at the destination. A nanoparticle sent to a circular journey through an array of media can have different properties upon its return to the point of origin. History is an essential determinant of the properties of nanoparticles in biological milieus, the memory of which is inscribed in the nanoparticle corona. [ABSTRACT FROM AUTHOR]

Doping hydroxyapatite (HAp) with foreign ions has been increasing in popularity as a chemical approach to augment the existing and impart new properties to it. However, it is uncertain whether this approach can elicit properties strong enough to make HAp competitive for commercial applications in biomedicine and elsewhere. In particular, material properties, such as grain size, morphology, surface charge, porosity, topology and others may prove to be more effective in controlling properties of HAp than the dopant choice and concentration. This study tackles this question through a meta-analysis of the dependence of selected materials properties on dopant concentrations reported across the literature, showing that doping is a convenient way of controlling some, but not all properties in HAp and should be implemented ideally in combination with other structural and compositional factors of influence. This meta-analysis is coupled to a bibliographic analysis of the evolution of trends in terms of the type, frequency and concurrency of dopants in HAp, covering the entire Periodic Table, all 72 elements incorporated into HAp so far and the 1990 – 2019 period split into successive lustra. The study demonstrates a continuously ascending trend in popularity of certain elements, such as Sr, Ce and Se, and a continuously declining trend of others in the past two decades, including F, Y, I, Ti and most lanthanides. For the fourth period transition metals a trend of constancy was observed and for yet other elements, including Ag and Mg, a period of ascent was succeeded by a steady decline, the onset of which coincided in the case of Ag with the peak in the airing of the concerns over its cytotoxicity by the scientific community. Reasons for these trends with respect to most elements are explained and connected with trends governing broader realms of materials science. It is shown that the choice of ions as dopants in HAp is largely driven by broader trends in materials science, rendering the doped HAp a mirror to view these existing and past trends in. Theoretically, by following the historic progression of these trends, a gaze in this mirror could assist in extrapolation of future trends, which normally come at the cost extinguishing some of the existing ones. This immersion in more general developments in materials science opened the path toward drawing connections between the bibliographically assessed geopolitical trends in doped HAp and in broader aspects of the scientific community, including the growing gap between the rich and the poor pervading it. The analysis reported here is conceptually novel and could be applied to numerous other materials. [ABSTRACT FROM AUTHOR]

Scientific articles have been traditionally written from single points of view. In contrast, new knowledge is derived strictly from a dialectical process, through interbreeding of partially disparate perspectives. Dialogues, therefore, present a more veritable form for representing the process behind knowledge creation. They are also less prone to dogmatically disseminate ideas than monologues, alongside raising awareness of the necessity for discussion and challenging of differing points of view, through which knowledge evolves. Here we celebrate 250 years since the discovery of the chemical identity of the inorganic component of bone in 1769 by Johan Gottlieb Gahn through one such imaginary dialogue between two seasoned researchers and aficionados of this material. We provide the statistics on ups and downs in the popularity of this material throughout the history and also discuss important achievements and challenges associated with it. The shadow of Samuel Beckett's Waiting for Godot is cast over the dialogue, acting as its frequent reference point and the guide. With this dialogue presented in the format of a play, we provide hope that conversational or dramaturgical compositions of scientific articles—albeit virtually prohibited from the scientific literature of the day—may become more pervasive in the future. [ABSTRACT FROM AUTHOR]

• Biological and magnetic response of nanoparticles as colloids and powders is compared. • Better uptake of colloids translated to higher cancer cell targeting efficiency. • Powders generally increased temperature in AC magnetic field faster than colloids. • Nanoparticle uptake proved more critical for hyperthermia than heating efficiency. • Parenteral form of delivery is more optimal than administration of dry particulates. Understanding the difference in physicochemical properties and biological response between colloidal and powder formulations of identical materials is important before the given materials are used in a medical milieu. In this study we compared a set of biological effects of colloidal and powder formulations of composite nanoparticles comprising superparamagnetic iron oxide cores and silicate/carbon shells. Magnetic dipole interaction between adjacent nanoparticles was more pronounced in their powders than in their colloidal formulations. Nanoparticles delivered as powders were thus more responsive to the magnetic field, but exhibited reduced uptake in bone and brain cancer cells, including K7M2 osteosarcoma line and U87 and E297 glioblastoma lines. Specifically, while the alternate magnetic field elicited a more rapid heat generation in cell culture media supplemented with the magnetic powders, the nanoparticles dispersed in the same media were uptaken by the cancer cells more copiously. The cellular uptake proved to be more crucial in defining the effect on cell survival, given that suspended formulations elicited a greater degree of cancer cell death in the magnetic field compared to the powder-containing formulations. Because of this effect, colloidal formulations were able to target cancer cells more effectively than the powders: they reduced the viability of all three tested cancer cell lines to a significantly greater degree that the viability of the normal, MDCK-MDR1 cell line. It is concluded that better uptake profile can make up for the lower heating rate in the AC field and lead to a more effective magnetic hyperthermia therapy. These results also demonstrate that the direct delivery of ferrofluids is more optimal than the administration of their constitutive particles as powders. [ABSTRACT FROM AUTHOR]

In the recent years, ferrites have been extending their application niche from the traditional field of soft magnetics to various other fields, including catalysis, gas sensors, energy, biomedicine, and water decontamination. Most of these applications are geared toward single-phase ferrites and their mixtures are rarely investigated. Here, we report on the first study of a triphasic spinel ferrite nanocomposite containing CoFe 2 O 4 , ZnFe 2 O 4 and CuFe 2 O 4 and synthesized using citrate auto-combustion. Detailed characterization of the composite in comparison with its three constitutive ferrites is provided. Interestingly, many of the physical properties of the triphasic nanocomposite are more conducive to adsorption of heavy metals than those of any of the three individual ferrites. These properties include experimental density, surface area and roughness, and microstrain, which were all highest in the nanocomposite. For example, the triphasic nanocomposite displayed a twice higher surface roughness and three times higher surface area than those of CuFe 2 O 4. Further, due to heterogeneous structuring of grain boundaries, the band gap of the nanocomposite was at 2.21 eV lower than that of any individual ferrites comprising it (2.31 – 2.62 eV). Consequently, at 6 × 1010 S-1, the maximum of the optical conductivity versus photon energy dependence was higher and the dielectric constant was lower for the nanocomposite than for any of its constitutive ferrites. The suitability of the nanocomposite to act as an adsorbent of toxic heavy metals was tested on the lead ion. The adsorption of lead increased with pH due to the effects on terminal group configuration, dispersion stability and metal ion speciation. The sorption also increased with the contact time, reaching saturation at 89% of the removal efficiency after 50 min. Adsorption isotherm fitting demonstrated that the ions adsorbed as monolayers on the surface of the nanocomposite. The adsorption process also followed the pseudo-second order kinetic model, with chemisorption as the dominant form of surface binding. The study confirms the potential of the triphasic ferrite nanocomposite to serve as an adsorbent material, given the promising removal efficiencies exhibited under the ambient conditions. This opens the door to a wide range of applications, not restricted to wastewater treatments alone, but also extending to the fields of antimicrobials, dye removal, and photocatalysis. [Display omitted] • A triphasic spinel ferrite nanocomposite containing CoFe 2 O 4 , ZnFe 2 O 4 and CuFe 2 O 4 was synthesized. • Physical properties of thenanocomposite were compared to its individual components. • Physical properties of the nanocomposite were more conducive to adsorption of heavy metals than those of the individual ferrites. • The surface area of the composite improved, being 3 times that of CuFe 2 O 4 and 2 times that of CoFe 2 O 4 value. • The nanocomposite showed adsorption and removal efficiency of toxic lead ion of 89% after 50 min. [ABSTRACT FROM AUTHOR]

Abstract Self-hardening calcium phosphate cements present ideal bone tissue substitutes from the standpoints of bioactivity and biocompatibility, yet they suffer from (a) weak mechanical properties, (b) negligible osteoinduction without the use of exogenous growth factors, and (c) a lack of intrinsic antibacterial activity. Here we attempt to improve on these deficiencies by studying the properties of self-setting Fe-doped bone-integrative cements containing two different concentrations of the dopant: 0.49 and 1.09 wt% Fe. The hardening process, which involved the transformation of Fe-doped β-tricalcium phosphate (Fe-TCP) to nanocrystalline brushite, was investigated in situ by continuously monitoring the cements using the Energy Dispersive X-Ray Diffraction technique. The setting time was 20 min and the hardening time 2 h, but it took 50 h for the cement to completely stabilize compositionally and mechanically. Still, compared to other similar systems, the phase transformation during hardening was relatively fast and it also followed a relatively simple reaction path, virtually free of complex intermediates and noisy background. Mössbauer spectrometry demonstrated that 57Fe atoms in Fe-TCP were located in two non-equivalent crystallographic sites and distributed over positions with a strong crystal distortion. The pronounced presence of ultrafine crystals in the final, brushite phase contributed to the reduction of the porosity and thereby to the enhancement of the mechanical properties. The compressive strength of the hardened TCP cements increased by more than twofold when Fe was added as a dopant, i.e., from 11.5 ± 0.5 to 24.5 ± 2.0 MPa. The amount of iron released from the cements in physiological media steadied after 10 days and was by an order of magnitude lower than the clinical threshold that triggers the toxic response. The cements exhibited osteoinductive activity, as observed from the elevated levels of expression of genes encoding for osteocalcin and Runx2 in both undifferentiated and differentiated MC3T3-E1 cells challenged with the cements. The osteoinductive effect was inversely proportional to the content of Fe ions in the cements, indicating that an excessive amount of iron can have a detrimental effect on the induction of bone growth by osteoblasts in contact with the cement. In contrast, the antibacterial activity of the cement in the agar assay increased against all four bacterial species analysed (E. coli , S. enteritidis , P. aeruginosa , S. aureus) in direct proportion with the concentration of Fe ions in it, indicating their key effect on the promotion of the antibacterial effect in this material. This effect was less pronounced in broth assays. Experiments involving co-incubation of cements with cells in an alternate magnetic radiofrequency field for 30 min demonstrated a good potential for the use of these magnetic cements in hyperthermia cancer therapies. Specifically, the population of human glioblastoma cells decreased six-fold at the 24 h time point following the end of the magnetic field treatment, while the population of the bone cancer cells dropped approximately twofold. The analysis of the MC3T3-E1 cell/cement interaction reiterated the effects of iron in the cement on the bone growth marker expression by showing signs of adverse effects on the cell morphology and proliferation only for the cement containing the higher concentration of Fe ions (1.09 wt%). Biological testing concluded that the effects of iron are beneficial from the perspective of a magnetic hyperthermia therapy and antibacterial prophylaxis, but its concentration in the material must be carefully optimized to avoid the adverse effects induced above a certain level of iron concentrations. Highlights • Self-setting Fe-doped bone cements with two dopant concentrations were prepared. • Cements exhibited osteoinductivity inversely proportional to the Fe ions content. • Cements exhibited antibacterial activity against E. coli , S. enteritidis , P. aeruginosa , S. aureus. • Glioblastoma and bone cancer cell populations declined due to magnetic field treatment. • Effects of Fe are beneficial from the perspective of a magnetic hyperthermia therapy. [ABSTRACT FROM AUTHOR]

The respiratory tract is one of the most accessible ones to exogenous nanoparticles, yet drug delivery by their means to it is made extraordinarily challenging because of the plexus of aerodynamic, hemodynamic and biomolecular factors at cellular and extracellular levels that synergistically define the safety and efficacy of this process. Here, the use of inorganic nanoparticles (INPs) for inhalable diagnostics and therapies of the lung is viewed through the prism of the history of studies on the interaction of INPs with the lower respiratory tract. The most conceptually and methodologically innovative and illuminative studies are referred to in the chronological order, as they were reported in the literature, and the trends in the progress of understanding this interaction of immense therapeutic and toxicological significance are being deduced from it. The most outstanding actual trends delineated include the diminishment of toxicity via surface functionalization, cell targeting, tagging and tracking via controlled binding and uptake, hybrid INP treatments, magnetic guidance, combined drug and gene delivery, use as adjuvants in inhalable vaccines, and other. Many of the understudied research directions, which have been accomplished by the nanostructured organic polymers in the pulmonary niche, are discussed. The progress in the use of INPs as inhalable diagnostics or therapeutics has been hampered by their well-recognized inflammatory potential and toxicity in the respiratory tract. However, the annual numbers of methodologically innovative studies have been on the rise throughout the past two decades, suggesting that this is a prolific direction of research, its comparatively poor commercial takings notwithstanding. Still, the lack of consensus on the effects of many INP compositions at low but therapeutically effective doses, the plethora of contradictory reports on ostensibly identical chemical compositions and NP properties, and the many cases of antagonism in combinatorial NP treatments imply that the rational design of inhalable medical devices based on INPs must rely on qualitative principles for the most part and embrace a partially stochastic approach as well. At the same time, the fact that the most studied INPs for pulmonary applications have been those with some of the thickest records of pulmonary toxicity, e.g. , carbon, silver, gold, silica and iron oxide, is a silent call for the expansion of the search for new inorganic compositions for use in inhalable therapies to new territories. • The most comprehensive review of the use of inorganic nanoparticles (INPs) for inhalable diagnostics and therapies of the lung. • The review provides a historical view of the subject. • The most conceptually and methodologically innovative and illuminative studies are referred to in the chronological order. • Trends in the progress of understanding this interaction of immense therapeutic and toxicological significance are being deduced. [ABSTRACT FROM AUTHOR]

Background Does chemistry govern biology or it is the other way around - that is a broad connotation of the question that this study attempted to answer. Method Comparison was made between the solubility and osteoclastic resorbability of four fundamentally different monophasic calcium phosphate (CP) powders with monodisperse particle size distributions: alkaline hydroxyapatite (HAP), acidic monetite (DCP), β-calcium pyrophosphate (CPP), and amorphous CP (ACP). Results With the exception of CPP, the difference in solubility between different CP phases became neither mitigated nor reversed, but augmented in the resorptive osteoclastic milieu. Thus, DCP, a phase with the highest solubility, was also resorbed more intensely than any other CP phase, whereas HAP, a phase with the lowest solubility, was resorbed least. CPP becomes retained inside the cells for the longest period of time, indicating hindered digestion of only this particular type of CP. Osteoclastogenesis was mildly hindered in the presence of HAP, ACP and DCP, but not in the presence of CPP. The most viable CP powder with respect to the mitochondrial succinic dehydrogenase activity was the one present in natural biological bone tissues: HAP. Conclusion Chemistry in this case does have a direct effect on biology. Biology neither overrides nor reverses the chemical propensities of inorganics with which it interacts, but rather augments and takes a direct advantage of them. Significance These findings set the fundamental basis for designing the chemical makeup of CP and other biosoluble components of tissue engineering constructs for their most optimal resorption and tissue regeneration response. [ABSTRACT FROM AUTHOR]

Changes to the surface composition of hydroxyapatite were measured after incubations in water, in ethanol or in a mixed aqueous-alcoholic medium. Ethanol decreased the surface presence of calcium ions in direct proportion to its amount in the medium. Because of its lower polarity than that of water, ethanol also increased the interfacial energy, in response to which the surface relaxed by rearranging into a more disordered state, as indicated by the increase in the heterogeneity of both calcium and oxygen electronic states. Accordingly, the binding energy of core-level oxygen electrons consistently increased with the concentration of ethanol and was compensated for by the decrease of the corresponding binding energies in calcium atoms, attesting to the weakened ionic bonds at the interface. The weakened ionic bonds increased the metallicity of the calcium ion, which prompted the offset of the valence band edge determined by the Ca 4s electron energy state toward the Fermi level and the conduction band, thus shrinking the band gap and increasing the electrical conductivity of the surface. The surface energy reduction entailing the partial loss of the crystalline order at the surface predisposed the nanoparticles incubated in alcoholic media for diminished sorption of proteins, but also for an augmented osteogenic response. These results demonstrate that surface functionalization of materials for various physicochemical and biological effects could be achieved without the use of chemical ligands. Rather, more economical design techniques stemming from the repertoire of materials science and engineering could be employed with equally satisfactory outcomes. [Display omitted] • XPS was used to measure changes to the surface of HAp at deeper and terminal levels in response to incubation medium. • O 1s binding energy increased with the amount of ethanol in the medium, attesting to weakened ionic bonds at the interface. • Weakened ionic bonds increased the metallicity of calcium ion, which increased the electrical conductivity of the surface. • Ethanol decreases the surface presence of calcium ions on HAp in direct proportion to its amount. • Ethanol increases the interfacial energy and induces surface relaxation into a more disordered state. [ABSTRACT FROM AUTHOR]

[Display omitted] Periodontitis is a chronic infectious and inflammatory disease of periodontal tissues estimated to affect 70–80 % of all adults. At the same time, periodontium, the site of periodontal pathologies, is an extraordinarily complex plexus of soft and hard tissues, the regeneration of which using even the most advanced forms of tissue engineering continues to be a challenge. Nanotechnologies, meanwhile, have provided exquisite tools for producing biomaterials and pharmaceutical formulations capable of elevating the efficacies of standard pharmacotherapies and surgical approaches to whole new levels. A bibliographic analysis provided here demonstrates a continuously increasing research output of studies on the use of nanotechnologies in the management of periodontal disease, even when they are normalized to the total output of studies on periodontitis. The great majority of biomaterials used to tackle periodontitis, including those that pioneered this interesting field, have been polymeric. In this article, a chronological review of polymeric nanotechnologies for the treatment of periodontitis is provided, focusing on the major conceptual innovations since the late 1990s, when the first nanostructures for the treatment of periodontal diseases were fabricated. In the opening sections, the etiology and pathogenesis of periodontitis and the anatomical and histological characteristics of the periodontium are being described, along with the general clinical manifestations of the disease and the standard means of its therapy. The most prospective chemistries in the design of polymers for these applications are also elaborated. It is concluded that the amount of innovation in this field is on the rise, despite the fact that most studies are focused on the refinement of already established paradigms in tissue engineering rather than on the development of revolutionary new concepts. [ABSTRACT FROM AUTHOR]

[Display omitted] Periodontitis is a chronic infectious and inflammatory disease of periodontal tissues estimated to affect 70–80 % of all adults. At the same time, periodontium, the site of periodontal pathologies, is an extraordinarily complex plexus of soft and hard tissues, the regeneration of which using even the most advanced forms of tissue engineering continues to be a challenge. Nanotechnologies, meanwhile, have provided exquisite tools for producing biomaterials and pharmaceutical formulations capable of elevating the efficacies of standard pharmacotherapies and surgical approaches to whole new levels. A bibliographic analysis provided here demonstrates a continuously increasing research output of studies on the use of nanotechnologies in the management of periodontal disease, even when they are normalized to the total output of studies on periodontitis. The great majority of biomaterials used to tackle periodontitis, including those that pioneered this interesting field, have been polymeric. In this article, a chronological review of polymeric nanotechnologies for the treatment of periodontitis is provided, focusing on the major conceptual innovations since the late 1990s, when the first nanostructures for the treatment of periodontal diseases were fabricated. In the opening sections, the etiology and pathogenesis of periodontitis and the anatomical and histological characteristics of the periodontium are being described, along with the general clinical manifestations of the disease and the standard means of its therapy. The most prospective chemistries in the design of polymers for these applications are also elaborated. It is concluded that the amount of innovation in this field is on the rise, despite the fact that most studies are focused on the refinement of already established paradigms in tissue engineering rather than on the development of revolutionary new concepts. [ABSTRACT FROM AUTHOR]

Socially responsible technologies are designed while taking into consideration the socioeconomic, geopolitical and environmental limitations of regions in which they will be implemented. In the medical context, this involves making therapeutic platforms more accessible and affordable to patients in poor regions of the world wherein a given disease is endemic. This often necessitates going against the reigning trend of making therapeutic nanoparticles ever more structurally complex and expensive. However, studies aimed at simplifying materials and formulations while maintaining the functionality and therapeutic response of their more complex counterparts seldom provoke a significant interest in the scientific community. In this review we demonstrate that such compositional simplifications are meaningful when it comes to the design of a solution for osteomyelitis, a disease that is in its natural, non-postoperative form particularly prevalent in the underdeveloped parts of the world wherein poverty, poor sanitary conditions, and chronically compromised defense lines of the immune system are the norm. We show that calcium phosphate nanoparticles, which are inexpensive to make, could be chemically designed to possess the same functionality as a hypothetic mixture additionally composed of: (a) a bone growth factor; (b) an antibiotic for prophylactic or anti-infective purposes; (c) a bisphosphonate as an antiresorptive compound; (d) a viral vector to enable the intracellular delivery of therapeutics; (e) a luminescent dye; (f) a radiographic component; (g) an imaging contrast agent; (h) a magnetic domain; and (i) polymers as viscous components enabling the injectability of the material and acting as carriers for the sustained release of a drug. In particular, calcium phosphates could: (a) produce tunable drug release profiles; (b) take the form of viscous and injectable, self-setting pastes; (c) be naturally osteo-inductive and inhibitory for osteoclastogenesis; (d) intracellularly deliver bioactive compounds; (e) accommodate an array of functional ions; (f) be processed into macroporous constructs for tissue engineering; and (g) be naturally antimicrobial. All in all, we see in calcium phosphates the presence of a protean nature whose therapeutic potentials have been barely tapped into. [ABSTRACT FROM AUTHOR]

Multicomponent, synergistic and multifunctional nanostructures have taken over the spotlight in the realm of biomedical nanotechnologies. The most prospective materials for bone regeneration today are almost exclusively composites comprising two or more components that compensate for the shortcomings of each one of them alone. This is quite natural in view of the fact that all hard tissues in the human body, except perhaps the tooth enamel, are composite nanostructures. This review article highlights some of the most prospective breakthroughs made in this research direction, with the hard tissues in main focus being those comprising bone, tooth cementum, dentin and enamel. The major obstacles to creating collagen/apatite composites modeled after the structure of bone are mentioned, including the immunogenicity of xenogeneic collagen and continuously failing attempts to replicate the biomineralization process in vitro . Composites comprising a polymeric component and calcium phosphate are discussed in light of their ability to emulate the soft/hard composite structure of bone. Hard tissue engineering composites created using hard material components other than calcium phosphates, including silica, metals and several types of nanotubes, are also discoursed on, alongside additional components deliverable using these materials, such as cells, growth factors, peptides, antibiotics, antiresorptive and anabolic agents, pharmacokinetic conjugates and various cell-specific targeting moieties. It is concluded that a variety of hard tissue structures in the body necessitates a similar variety of biomaterials for their regeneration. The ongoing development of nanocomposites for bone restoration will result in smart, theranostic materials, capable of acting therapeutically in direct feedback with the outcome of in situ disease monitoring at the cellular and subcellular scales. Progress in this research direction is expected to take us to the next generation of biomaterials, designed with the purpose of fulfilling Daedalus' dream — not restoring the tissues, but rather augmenting them. [ABSTRACT FROM AUTHOR]

Abstract: Staphylococcus aureus internalized by bone cells and shielded from the immune system provides a reservoir of bacteria in recurring osteomyelitis. Its targeting by the antibiotic therapy may thus be more relevant for treating chronic bone infection than eliminating only the pathogens colonizing the bone matrix. Assessed was the combined osteogenic and antibacterial effect of clindamycin-loaded calcium phosphate nanoparticles of different monophasic compositions on co-cultures comprising osteoblasts infected with S. aureus. Antibiotic-carrying particles were internalized by osteoblasts and minimized the concentration of intracellular bacteria. In vitro treatments of the infected cells, however, could not prevent cell necrosis due to the formation of toxic byproducts of the degradation of the bacterium. Antibiotic-loaded particles had a positive morphological effect on osteoblasts per se, without reducing their viability, alongside stimulating the upregulation of expression of different bone growth markers in infected osteoblasts to a higher degree than achieved during the treatment with antibiotic only. [Copyright &y& Elsevier]

Nanoparticulate composites of hydroxyapatite ( HAp) and chitosan were synthesized by ultrasound-assisted sequential precipitation and characterized for their microstructure at the atomic scale, surface charge, drug release properties, and combined antibacterial and osteogenic response. Crystallinity of HAp nanoparticles was reduced because of the interference of the surface layers of chitosan with the dissolution/reprecipitation-mediated recrystallization mechanism that conditions the transition from the as-precipitated amorphous calcium phosphate phase to the most thermodynamically stable one- HAp. Embedment of 5-10 nm sized, narrowly dispersed HAp nanoparticles within the polymeric matrix mitigated the burst release of the small molecule model drug, fluorescein, bound to HAp by physisorption, and promoted sustained-release kinetics throughout the 3 weeks of release time. The addition of chitosan to the particulate drug carrier formulation, however, reduced the antibacterial efficacy against S aureus. Excellent cell spreading and proliferation of osteoblastic MC3 T3- E1 cells evidenced on microscopic conglomerates of HAp nanoparticles in vitro also markedly diminished on HAp/chitosan composites. Mitochondrial dehydrogenase activity exhibited normal values only for HAp/chitosan particle concentrations of up to 2 mg/cm2 and significantly dropped, by about 50%, at higher particle concentrations (4 and 8 mg/cm2). The gene expression of osteocalcin, a mineralization inductor, and the transcription factor R unx2 was downregulated in cells incubated in the presence of 3 mg/cm2 HAp/chitosan composite particles, whereas the expression of osteopontin, a potent mineralization inhibitor, was upregulated, further demonstrating the partially unfavorable osteoblastic cell response to the given particles. The peak in the expression of osteogenic markers paralleling the osteoblastic differentiation was also delayed most for the cell population incubated with HAp/chitosan particles. Overall, the positive effect of chitosan coating on the drug elution profile of HAp nanoparticles as carriers for the controlled delivery of antibiotics in the treatment of osteomyelitis was compensated for by the lower bacteriostatic efficiency and the comparatively unviable cell response to the composite material, especially at higher dosages. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:567-579, 2014 [ABSTRACT FROM AUTHOR]

Abstract: Development of a material for simultaneous sustained and localized delivery of antibiotics and induction of spontaneous regeneration of hard tissues affected by osteomyelitis stands for an important clinical need. In this work, a comparative analysis of the bacterial and osteoblastic cell response to two different nanoparticulate carriers of clindamycin, an antibiotic commonly prescribed in the treatment of bone infection, one composed of calcium phosphate and the other comprising poly-(D,L-lactide-co-glycolide)-coated calcium phosphate, was carried out. Three different non-cytotoxic phases of calcium phosphate, exhibiting dissolution and drug release profiles in the range of one week to two months to one year, respectively, were included in the analysis: monetite, amorphous calcium phosphate and hydroxyapatite. Spherical morphologies and narrow size distribution of both types of nanopowders were confirmed in transmission and scanning electron microscopic analyses. The antibiotic-containing powders exhibited sustained drug release contingent upon the degradation rate of the carrier. Assessment of the antibacterial performance of the antibiotic-encapsulated powders against Staphylococcus aureus, the most common pathogen isolated from infected bone, yielded satisfactory results both in broths and on blood agar plates for all the analyzed powders. In contrast, no cytotoxic behavior was detected upon the incubation of the antibiotic powders with the osteoblastic MC3T3-E1 cell line for up to three weeks. The cells were shown to engage in a close contact with the antibiotic-containing particles, irrespective of their internal or surface phase composition, polymeric or mineral. At the same time, both types of particles upregulated the expression of osteogenic markers osteocalcin, osteopontin, Runx2 and protocollagen type I, suggesting their ability to promote osteogenesis and enhance remineralization of the infected site in addition to eliminating the bacterial source of infection. [Copyright &y& Elsevier]

In the present study, lanthanum-strontium manganite (LSM) particles were embellished with gold nanoparticles to create a magnetoplasmonic composite core-shell material enabling bimodal heating regimens upon exposure to an alternate current (AC) magnetic field and/or near-infrared (NIR) radiation. The composite particles were prepared by combined solid-state synthesis, mechanochemical processing and wet chemistry. The core crystals were round but faceted, often growing into an equilibrium shape conforming to the Wulff construction and the orthorhombic Pbnm crystal symmetry. They were also multi-domain but nanocrystalline, exhibiting superparamagnetic behavior as the result of evening the local anisotropies by the exchange interaction. The deposition of the gold nanoparticles onto the manganite core resulted in the red shift of the localized surface plasmon resonance due to interfacial effects. This deposition also improved the conditions for colloidal stability in water by increasing the surface charge density in the electric double layer surrounding the particles. The hybrid magnetoplasmonic particles were evaluated for their potential for use in cancer ablation therapies by measuring their aqueous heating dynamics in an ultralow AC magnetic field mimicking the magnetic hyperthermia (MH) condition of deep-seated tumors and the NIR light mimicking the photothermal (PT) condition. Aggregation of spherical, 5–10 nm sized gold nanoparticles on the surface of LSM enhanced their NIR light absorption capacity. The heating of the particle suspensions was more intense in the PT mode than in the MH mode, but the latter mode allowed for the display of the smart, thermostatic behavior by the material. Namely, the stoichiometry of the manganite phase, La 0·76 Sr 0·24 MnO 3 , was adjusted to display the Curie temperature at 45.8 °C after decoration with gold and the thermostatic effect at 43–44 °C, with a potential to prevent the overheating of tissues during the MH treatments of cancer. The bimodal heating potential endows the particles with the ability to be used in personalized cancer therapies. These therapies would be able to adjust in situ the ratio between the two heating modes, one more suitable for superficial ablation (PT) and another one for the treatment of deeper tumors (MH). • Composite magnetoplasmonic particles prepared by combined solid-state synthesis, mechanochemical processing and wet chemistry. • Hybrid particles were evaluated for use in cancer ablation therapies by measuring their aqueous heating dynamics. • Aggregation of 5–10 nm sized Au nanoparticles on the surface of LSM enhanced their NIR light absorption capacity. • PT mode was more intense, but MH mode allowed for smart, thermostatic behavior. • Stoichiometry of the manganite phase was adjusted to T c of 45.8 °C, or 43–44 °C after decoration with Au. [ABSTRACT FROM AUTHOR]

Abstract: Cholecalciferol, vitamin D3, plays an important role in bone metabolism by regulating extracellular levels of calcium. Presented here is a study on the effects of the local delivery of cholecalciferol (D3) using nanoparticulate carriers composed of hydroxyapatite (HAp) and poly(d,l-lactide-co-glycolide) (PLGA). Multifunctional nanoparticulate HAp-based powders were prepared for the purpose of: (a) either fast or sustained, local delivery of cholecalciferol, and (b) the secondary, osteoconductive and defect-filling effect of the carrier itself. Two types of HAp-based powders with particles of narrowly dispersed sizes in the nano range were prepared and tested in this study: HAp nanoparticles as direct cholecalciferol delivery agents and HAp nanoparticles coated with cholecalciferol-loaded poly(d,l)-lactide-co-glycolide (HAp/D3/PLGA). Satisfying biocompatibility of particulate systems, when incubated in contact with MC3T3-E1 osteoblastic cells in vitro, was observed for HAp/D3/PLGA and pure HAp. In contrast, an extensively fast release of cholecalciferol from the system comprising HAp nanoparticles coated with cholecalciferol (HAp/D3) triggered necrosis of the osteoblastic cells in vitro. Artificial defects induced in the osteoporotic bone of the rat mandible were successfully reconstructed following implantation of cholecalciferol-coated HAp nanoparticles as well as those comprising HAp nanoparticles coated with cholecalciferol-loaded PLGA (HAp/D3/PLGA). The greatest levels of enhanced angiogenesis, vascularization, osteogenesis and bone structure differentiation were achieved upon the implementation of HAp/D3/PLGA systems. [Copyright &y& Elsevier]

In the first half of 2009 I organized a series of talks at University of California, San Francisco. The series was dedicated to observing science from a wider perspective and figuring out where its trains and we as scientists in it are heading to. The final presentation in the series I envisaged as the one drawing threads between love and science. However, my aim was neither for that particular talk to be the one of explaining sensations of love using scientific language nor to be based on pastoral and pathetic eruptions of love about science. What I had in mind was a description of an adventurous quest to find love at the core of our scientific endeavors. As my attempts to find an appropriate lecturer failed, I decided to engage myself in such an adventure. This is how this article sprang into life. In it, I slowly tread the way towards realizing that the heart of love beats at the core of the scientific enterprise of humanity. To reach this centre, I have travelled through the intricate forests of discoursing on the concept of experiential co-creation, the uncertainty principle, the dichotomy between Empiricist and Renaissance scientific methods, the tautological character of logical inferences and scientific descriptions as pragmatic sets of metaphors or pointers used in the mutual coordination of experiences at the social level, having ocean waves, seashore pebbles, corals, fish, atoms, gramophones, pine trees and stars passing me by, and yet managed to emerge back to light with the treasure in my hands. [ABSTRACT FROM AUTHOR]

Microelectrophoresis based on the dynamic light scattering (DLS) effect has been a major tool for assessing and controlling the conditions for stability of colloidal systems. However, both the DLS methods for characterization of the hydrodynamic size of dispersed submicron particles and the theory behind the electrokinetic phenomena are associated with fundamental and practical approximations that limit their sensitivity and information output. Some of these fundamental limitations, including the spherical approximation of DLS measurements and an inability of microelectrophoretic analyses of colloidal systems to detect discrete charges and differ between differently charged particle surfaces due to rotational diffusion and particle orientation averaging, are revisited in this work. Along with that, the main prospects of these two analytical methods are mentioned. A detailed review of the role of zeta potential in processes of biochemical nature is given too. It is argued that although zeta potential has been used as one of the main parameters in controlling the stability of colloidal dispersions, its application potentials are much broader. Manipulating surface charges of interacting species in designing complex soft matter morphologies using the concept of zeta potential, intensively investigated recently, is given as one of the examples. Branching out from the field of colloid chemistry, DLS and zeta potential analyses are now increasingly finding application in drug delivery, biotechnologies, physical chemistry of nanoscale phenomena and other research fields that stand on the frontier of the contemporary science. Coupling the DLS-based microelectrophoretic systems with complementary characterization methods is mentioned as one of the prosperous paths for increasing the information output of these two analytical techniques. [ABSTRACT FROM AUTHOR]

Presented is a discourse on the contextual nature of physical qualities. The realistic and observational contexts in which a system exists are demonstrated as equally involved in defining its qualities. Each quality could be consequently considered as natural and experiential at the same time. The subsequently proposed thesis of the contextual co-definition of natural/experiential qualities in the relationship between the human mind and Nature is shown to possess numerous favorable ethical and aesthetical implications. The contextual nature of experiential qualities is further correlated with the holistic character of natural systems and events, which is illustrated by several real-life examples. A systemic approach to knowledge is shown to naturally emanate from the acceptance of the contextual definition of physical qualities and the holistic nature of experiences. Methodological problems of the standard, reductionist explanatory frameworks are additionally discussed with an emphasis on the major descriptive flaws of quantificational approaches and in respect to cybernetic and autopoietic organization of physical and biological systems. [ABSTRACT FROM AUTHOR]

Abstract: Composite particles made by growing nanoscopic silicon wires from the surface of monodispersed, microsized silica beads were tested in this study for their ability to affect the integrity and permeability of an epithelial cell layer. Polyethylene glycol (PEG) is known to sterically stabilize particles and prevent protein binding; as such, it is a routine way to impart in vivo longevity to drug carriers. The effect of the silica beads, both with and without silicon nanowires and PEG, on the disruption of the tight junctions in Caco-2 cells was evaluated by means of: (a) analysis of the localization of zonula occludens-1 (ZO-1), claudin-1 and f-actin; (b) measurements of trans-epithelial electrical resistance (TEER); (c) real-time quantitative RT-PCR analysis of the expression of PKC-α and PKC-z, which regulate the fluidity of cell membranes, and RhoA and Rac1, which are mainly involved in mechanotransduction processes; and (d) drug permeability experiments with fluorescein-sodium. The results have shown that Si-nanowire-coated silica microparticles added to Caco-2 cells in culture lead to alterations in tight junction permeability and the localization of ZO-1 and f-actin, as well as to decreased width of ZO-1 and claudin-1 at the tight junction and increased expression of PKC transcripts. Si-nanowire-coated silica microparticles increased the permeability of Caco-2 cell monolayers to fluorescein-sodium in proportion to their amount. Effects indicative of loosening the Caco-2 cell monolayers and increasing their permeability were less pronounced for PEGylated particles, owing to their greater supposed inertness in comparison with the non-functionalized beads and nanowires. The analyzed Si-nanowire-coated silica microparticles have thus been shown to affect membrane barrier integrity in vitro, suggesting the possibility of using nanostructured microparticles to enhance drug permeability through the intestinal epithelium in vivo. [Copyright &y& Elsevier]

Abstract: In the following respects, tooth enamel is a unique tissue in the mammalian body: (a) it is the most mineralized and hardest tissue in it comprising up to 95wt% of apatite; (b) its microstructure is dominated by parallel rods composed of bundles of 40–60nm wide apatite crystals with aspect ratios reaching up to 1:10,000 and (c) not only does the protein matrix that gives rise to enamel guides the crystal growth, but it also conducts its own degradation and removal in parallel. Hence, when mimicking the process of amelogenesis in vitro, crystal growth has to be coupled to proteolytic digestion of the amelogenin assemblies that are known to play a pivotal role in conducting the proper crystal growth. Experimental settings based on controlled and programmable titration of amelogenin sols digested by means of MMP-20 with buffered calcium and phosphate solutions were employed to imitate the formation of elongated, plate-shaped crystals. Whilst amelogenin can act as a promoter of nucleation and crystal growth alone, in this study we show that proteolysis exerts an additional nucleation- and growth-promoting effect. Hydrolysis of full-length amelogenin by MMP-20 decreases the critical time needed for the protein and peptides to adhere and to cover the substrate. The formation and immobilization of a protein layer subsequently reduces the time for calcium phosphate crystallization. Coupling the proteolytic reaction to titration in the presence of 0.4mg/ml rH174 has been shown to have the same effect on the crystal growth promotion as quadrupling the concentration of rH174 to 1.6mg/ml. Controlling the rate and the extent of the proteolytic cleavage can thus be used to control the nucleation and growth rates in a protein-guided crystallization system. [Copyright &y& Elsevier]

Abstract: The concept of zeta-potential has been used for more than a century as a basic parameter in controlling the stability of colloidal suspensions, irrespective of the nature of their particulate ingredients—organic or inorganic. There are prospects that self-assembly of peptide species and the protein–mineral interactions related to biomineralization may be controlled using this fundamental physicochemical parameter. In this study, we have analysed the particle size and zeta-potential of the full-length recombinant human amelogenin (rH174), the main protein of the developing enamel matrix, in the presence of calcium and phosphate ions and hydroxyapatite (HAP) particles. As calcium and phosphate salts are introduced to rH174 sols in increments, zeta-potential of the rH174 nanospheres is more affected by negatively charged ions, suggesting their tendency to locate within the double charge layer. Phosphate ions have a more pronounced effect on both the zeta-potential and aggregation propensity of rH174 nanospheres compared to calcium ions. The isoelectric point of amelogenin was independent on the ionic strength of the solution and the concentration of calcium and/or phosphate ions. Whereas rH174 shows a higher affinity for phosphate than for calcium, HAP attracts both of these ions to the shear plane of the double layer. The parallel size and zeta-potential analysis of HAP and rH174 colloidal mixtures indicated that at pH 7.4, despite both HAP and rH174 particles being negatively charged, rH174 adsorbs well onto HAP particles. The process is slower at pH 7.4 than at pH 4.5 when the HAP surface is negatively charged and the rH174 nanosphere carries an overall positive charge. The results presented hereby demonstrate that electrostatic interactions can affect the kinetics of the adsorption of rH174 onto HAP. [Copyright &y& Elsevier]

Abstract: Objective: A single Pro-70 to Thr (p.P70T) mutation of amelogenin is known to result in hypomineralised amelogenesis imperfecta (AI). This study aims to test the hypothesis that the given mutation affects the self-assembly of amelogenin molecules and impairs their ability to conduct the growth of apatite crystals. Design: Recombinant human full-length wild-type (rh174) and p.P70T mutated amelogenins were analysed using dynamic light scattering (DLS), protein quantification assay and atomic force microscopy (AFM) before and after the binding of amelogenins to hydroxyapatite crystals. The crystal growth modulated by both amelogenins in a dynamic titration system was observed using AFM. Results: As compared to rh174 amelogenin, p.P70T mutant displayed significantly increased sizes of the assemblies, higher binding affinity to apatite, and decreased crystal height. Conclusion: Pro-70 plays an important structural role in the biologically relevant amelogenin self-assembly. The disturbed regularity of amelogenin nanospheres by this single mutation resulted in an increased binding to apatite and inhibited crystal growth. [Copyright &y& Elsevier]

Abstract: Human dental enamel forms over a period of 2–4 years by substituting the enamel matrix, a protein gel mostly composed of a single protein, amelogenin with fibrous apatite nanocrystals. Self-assembly of amelogenin and the products of its selective proteolytic digestion are presumed to direct the growth of apatite fibers and their organization into bundles that eventually comprise the mature enamel, the hardest tissue in the mammalian body. This work aimed to establish the physicochemical and biochemical conditions for the growth of apatite crystals under the control of a recombinant amelogenin matrix (rH174) in combination with a programmable titration system. The growth of apatite substrates was initiated in the presence of self-assembling amelogenin particles. A series of constant titration rate experiments was performed that allowed for a gradual increase of the calcium and/or phosphate concentrations in the protein suspensions. We observed a significant amount of apatite crystals formed on the substrates following the titration of rH174 sols that comprised the initial supersaturation ratio equal to zero. The protein layers adsorbed onto the substrate apatite crystals were shown to act as promoters of nucleation and growth of calcium phosphates subsequently formed on the substrate surface. Nucleation lag time experiments have showed that rH174 tends to accelerate precipitation from metastable calcium phosphate solutions in proportion to its concentration. Despite their mainly hydrophobic nature, amelogenin nanospheres, the size and surface charge properties of which were analyzed using dynamic light scattering, acted as a nucleating agent for the crystallization of apatite. The biomimetic experimental setting applied in this study proves as convenient for gaining insight into the fundamental nature of the process of amelogenesis. [Copyright &y& Elsevier]

In the past few hundred years, science has exerted an enormous influence on the way the world appears to human observers. Despite phenomenal accomplishments of science, science nowadays faces numerous challenges that threaten its continued success. As scientific inventions become embedded within human societies, the challenges are further multiplied. In this critical review, some of the critical challenges for the field of modern chemistry are discussed, including: (a) interlinking theoretical knowledge and experimental approaches; (b) implementing the principles of sustainability at the roots of the chemical design; (c) defining science from a philosophical perspective that acknowledges both pragmatic and realistic aspects thereof; (d) instigating interdisciplinary research; (e) learning to recognize and appreciate the aesthetic aspects of scientific knowledge and methodology, and promote truly inspiring education in chemistry. In the conclusion, I recapitulate that the evolution of human knowledge inherently depends upon our ability to adopt creative problem-solving attitudes, and that challenges will always be present within the scope of scientific interests. [ABSTRACT FROM AUTHOR]

Scientific method is presented not as a means for investigating a true and objective character of universal reality, but as a metaphorical tool applied for mutual co-ordination of experiences. By acknowledging the co-orientational and metaphoric roots of science, religion, arts, and ordinary linguistic communications alike, potential for their fruitful interdependent application becomes apparent. References to the paradigms of constructivism and objectivism are drawn in parallel in outlining the tracks along which the proposed concept of co-creation of experiential qualities is arrived at. Systemic reasoning based on analogies between different levels of complexity of natural systems emanates as an imaginative aspect of creative thinking. [ABSTRACT FROM AUTHOR]

Abstract: Self-assembly is a ubiquitous physicochemical phenomenon. It is inherent to molecular recognition effects in the biological domain, and thus presents a basis for understanding the constitution and dynamic organization of living beings. However, it is argued in this paper that the very notion of self-assembly presents an incorrect and misleading one for the physical effects that it stands for. Self-assembly presents a misnomer as each self-assembly process not only depends on, but also includes a certain degree of ordering in the immediate surrounding of the ‘self-assembling’ entities. Claims are provided to support the idea that every self-assembly process is, in fact, a co-assembly event, as it implies mutual changes and structuring of both the ‘self-assembled’ system and its nearest surrounding. This point of view is related to the systemic observation that there could be no physical qualities independent on the context of their existence. In order to illustrate that the concept of co-assembly presents only an instance of a more profound and systemic philosophy of life, the examples of the interplay between internal and external factors of development are provided from the fields of quantum and classical physics, biology, evolutionary theory and psychology. [Copyright &y& Elsevier]

Abstract: Additional effects on the previously reported procedure of precipitation of narrowly dispersed and well-defined, brick-shaped cholesterol particles, including non-solvent addition rate, temperature, solvent purity, aging treatments, ultrasound agitation and fine mechanical effects were investigated. Based on the presented results, significant morphological sensitivity of cholesterol precipitation processes upon variations from the standard established procedure of crystallization is induced. However, the tendency of cholesterol to crystallize in the form of biaxially grown particles was evidenced as dominating the precipitation processes, irrespective of any modifications of experimental parameters involved in the preparation procedure investigated hereby. Prolonged aging time and temperature effects lead to “face-to-face” aggregation of particles, promoted by the discrepancy in surface charges between particle sides and faces. In light of these observations, the mechanism of precipitation of cholesterol is further discussed. [Copyright &y& Elsevier]

Abstract: Whereby cholesterol presents one of the major fatty substances in human body, carboxymethyl cellulose is a water-soluble derivative of cellulose, the most abundant dietary fiber. Whereas on one hand in vivo precipitation of cholesterol is the major cause of atherosclerosis, dietary fibers are on the other hand known for their ability to clean the fatty plaque deposited on intestinal pathways, and prevent its build-up in other critical areas within the organism. In this work, a method for the preparation of a composite material comprising cholesterol and carboxymethyl cellulose from 1-hexanol/water biphase mixtures is reported. Specificity of the interaction between the composite components in the given conditions of synthesis inhibits the tendency of solid cholesterol to adopt typical plate- or needle-shaped morphologies. Instead, control of the thixotropic behavior of the constituent polymer phase leads to the formation of bubbling, multi-layered cholesteric films. In view of the major illnesses that involve biological precipitation of cholesterol crystals, these findings may be considered as pointing towards the interactional specificity of potential chemotherapeutic and/or nutritional significance. Scanning electron microscopy, thermal and diffractometric analyses were performed as parts of the characterization of the prepared material. [Copyright &y& Elsevier]

Abstract: Uniform crystalline colloidal cholesterol particles of narrow size distribution were obtained by precipitation. The method consisted of adding a miscible non-solvent (water) into cholesterol solutions of different alcohols and acetone, without any additives. The properties of the resulting particles depended in a sensitive way on the concentration of all reactants, temperature, pH, ionic strength, and aging time. The major observed effects were due to the solubility of cholesterol, which was strongly affected by the solvent mixture and temperature. Precipitation in 1-propanol/water system yielded stable dispersions of well-defined particles, which were used to evaluate the effects of different experimental parameters on their properties. Aging of stable dispersions resulted in multi-layered aggregation of the primary platelets, the degree and rate of which process was strongly affected by temperature. Finally, it was shown that the colloidal cholesterol particles could be coated with homogeneous silica layers in order to alter their surface characteristics. [Copyright &y& Elsevier]

Crystallization of cholesterol in chemical conditions that involve the presence of emulsions of three different types of surface active agents - cationic, anionic, and nonionic - was investigated by means of scanning and transmission electron microscopic analyses. In contrast with the previous attempts to modify the typical plate- and needle-shaped character of biaxially grown cholesterol crystals, the present study indicates that spherical templates of fine emulsion droplets may impose spherical morphologies to cholesterol particles nucleated within. [ABSTRACT FROM AUTHOR]

Abstract: Reverse micelles present self-assembled multi-molecular entities formed within specific compositional ranges of water-in-oil microemulsions. The structure of a reverse micelle is typically represented as nano-sized droplet of a polar liquid phase, capped by a monolayer of surfactant molecules, and uniformly distributed within a non-polar, oil phase. Although their role in serving as primitive membranes for encapsulation of primordial self-replicating chemical cycles that anticipated the very origins of life has been proposed, their first application for ‘parent(hesis)ing’ chemical reactions with an aim to produce ‘templated’ 2D arrays of nanoparticles dates back to only 25 years ago. Reverse micelles have since then been depicted as passive nano-reactors that via their shapes template the growing crystalline nuclei into narrowly dispersed or even perfectly uniform nano-sized particles. Despite this, numerous examples can be supported, wherefrom deviations from the simple unilateral correlations between size and shape distribution of reverse micelles and the particles formed within may be reasonably implied. A rather richer, dynamical role of reverse micelles, with potential significance in the research and design of complex, self-assembly synthesis pathways, as well as possible adoption of their application as an aspect of biomimetic approach, is suggested herein. [Copyright &y& Elsevier]

Abstract: Lanthanum-strontium manganites were synthesized using co-precipitation method with a reverse micellar microemulsion. Either oxalic acid, sodium hydroxide or tetramethylammonium hydroxide was used for the precipitation of precursor cations in a form that was subsequently calcined under various conditions in order to obtain perovskite manganite phase. Correlations between the properties of the synthesized powder and the calcination conditions have been put forth. The properties of the microemulsion-assisted synthesized material were compared with the samples prepared by following the supposedly similar chemical recombinations in bulk solutions, with an aim to challenge the fact that microemulsions in general have only templating effects on the morphology of co-precipitated powder. TEM measurements, X-ray diffraction analyses and magnetic measurements were used in order to gain an insight into the mentioned difference, which is an important one for the future understanding of the role that reverse micelles play in the processes of materials synthesis. [Copyright &y& Elsevier]

Abstract: Nanostructured lanthanum–strontium manganites were synthesized using two different co-precipitation approaches, one in bulk solution, and the other in reverse micelles of CTAB/1-hexanol/water microemulsion. In both cases, precursor cations were precipitated by using oxalic acid. The properties of the materials synthesized by using these two methods were compared in order to reveal potential advantages of the microemulsion-assisted approach. The influence of the annealing conditions on the properties of synthesized manganites was investigated by using X-ray diffraction, transmission electron microscopy, differential thermal analysis, thermogravimetric analysis and magnetic measurements. [Copyright &y& Elsevier]

Silica-coated lanthanum–strontium manganite particles with La0.76Sr0.24MnO3+δ stoichiometric formula, exhibiting Curie temperature at ∼40°C, were prepared by using a traditional solid-state method of synthesis of magnetic ceramic particles, followed by milling and a low-temperature coating procedure in an aqueous alcoholic alkali medium. The properties of the obtained material establish it as a potential candidate for self-regulated power-absorbing and temperature-controlling materials in hyperthermia treatments. Moreover, core-comprising LaSr–manganites with different stoichiometries, ranging from La0.5Sr0.5MnO3+δ to LaMnO3+δ, were synthesized, with magnetic and structural properties examined thereof. Herein reported findings can potentially be used in the preparation of silica-coated magnetic particles with designable Curie temperature, offering a wide range of possibilities of adapting the material to practical instrumental setups in drug delivery and hyperthermia treatments. [ABSTRACT FROM AUTHOR]

Abstract: Nanostructured NiZn ferrites were synthesized using two different techniques: first, a precipitation procedure in the reverse micelles of a CTAB/1-hexanol/H2O microemulsion, and second, precipitation in a bulk aqueous solution. XRD measurements, magnetic measurements, TEM imaging, analytical measurements and thermal analyses were used in an attempt to reveal the chemical pathway that leads to the formation of NiZn ferrite in the microemulsion and in the bulk aqueous solution. It was found that reverse micelles do not act as inert nano-sized reactors that influence only morphological properties of the synthesized powders, but have a decisive influence on the identity of the final product when compared to the non-microemulsion procedure, and therefore present the molecular structures which are actively engaged in the chemical pathway according to which the herein presented room temperature synthesis of NiZn ferrite nanoparticles takes place. The influence of the initial pH on the chemical pathway of reverse-micellar synthesis and the morphology of the synthesized particles was discussed after initially it was found that the pH of the precipitation ought to be higher than 8 in order to obtain the desired ferrite as a final product. [Copyright &y& Elsevier]

Reverse micelles as nanosized aqueous droplets existing at certain compositions of water-in-oil microemulsions are widely used today in the synthesis of many types of nanoparticles. However, without a rich conceptual network that would correlate the properties and compositions of reverse micellar microemulsions to the properties of to-be-obtained particles, the design procedures in these cases usually rely on a trial-and-error approach. As like every other science, what is presently known is merely the tip of the iceberg compared to the uninvestigated vastness still lying below. The aim of this article is to present readers with most of the major achievements from the field of materials synthesis within reverse micelles since the first such synthesis was performed in 1982 until today, to possibly open up new perspectives of viewing the typical problems that nowadays dominate the field, and to hopefully initiate the observation and generation of their actual solutions. We intend to show that by refining the oversimplified representations of the roles that reverse micelles play in the processes of nanoparticles synthesis, steps toward a more complex and realistic view of the concerned relationships can be made. The first two sections of the review are of introductory character, presenting the reader with the basic concepts and ideas that serve as the foundations of the field of reverse micellar synthesis of materials. Applications of reverse micelles, other than as media for materials synthesis, as well as their basic structures and origins, together with experimental methods for evaluating their structural and dynamic properties, basic chemicals used for their preparation and simplified explanations of the preparation of materials within, will be reviewed in these two introductory sections. In Secs. 3 and 4, we shall proceed with reviewing the structural and dynamic properties of reverse micelles, respectively, assuming that knowledge of both static and dynamic parameters of microemulsions and changes induced thereof, are a necessary step prior to putting forth any correlations between the parameters that define the properties of microemulsions and the parameters that define the properties of materials synthesized within. Typical pathways of synthesis will be presented in Sec. 5, whereas basic parameters used to describe correlations between the properties of microemulsion reaction media and materials prepared within, including reagent concentrations, ionic strength, temperature, aging time and some of the normally overlooked influences, will be mentioned in Sec. 6. The whole of Sec. 7 is devoted to reviewing water-to-surfactant molar ratio as the most often used parameter in materials design by performing reverse micellar synthesis routes. The mechanisms of particle formation within precipitation synthesis in reverse micelles is discussed in Sec. 8. Synthesis of composites, with special emphasis on silica composites, is described in Sec. 9. All types of materials, classified according to their chemical compositions, that were, to our knowledge, synthesized by using reverse micelles up-to-date, will be briefly mentioned and pointed to the corresponding references in Sec. 10. In Sec. 11, some of the possible future directions for the synthesis of nanostructured materials within reverse micelles, found in combining reverse micellar syntheses and various other synthesis procedures with the aim of reaching self-organizing nanoparticle systems, will be outlined. [ABSTRACT FROM AUTHOR]