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The procedure for the preparation of NiZn-ferrite powder with average particle size of 10 nm and saturation magnetization of 50 emu/g by using precipitation reaction between acidified sulphate precursor salts and NH4OH as the precipitating agent in the water-in-oil domain of the microemulsion CTAB/1-hexanol/water at 45°C is presented herein. TEM measurements have revealed relatively uniform morphology of the particles, which are associated in coral-like agglomerates. EDS measurements have been used for qualitative analysis of the sample, whereby FAAS measurement has been performed in order to reveal the proportion of the cations in the sample — Ni : Zn : Fe = 0.17 : 0.18 : 2.64. [ABSTRACT FROM AUTHOR]

Abstract: Stoichiometric nanocrystalline nickel–zinc ferrites were synthesized by a reverse micelle method following a multi-microemulsion approach. Different pH values were chosen for the alkali precipitating reaction during the synthesis of different powders. Synthesized, as-dried and subsequently calcined powders were characterized in terms of their magnetic properties. XRD analyses and specific-surface area measurements were used to determine the average particle sizes of the synthesized samples. DCS and TGA measurements were performed to reveal the phase transitions within the samples at elevated temperatures, whereas TEM was used to view and record the microstructure of the nanosized ferrite samples. A possible mechanism of the formation of the synthesized NiZn-ferrite was also discussed. [Copyright &y& Elsevier]

Watching children play is a favorite pastime for many elderlies. However, due to the growing safety concerns, parents have become increasingly resistant to the idea of having strangers watch their children at parks and playgrounds. This creates an intergenerational gap in communication with potentially detrimental consequences for all social groups. Oral interviews were conducted and written surveys distributed that validated the hesitance of seniors, especially in the United States, to spend time at children's playgrounds despite their finding the vicinity of children stimulating. Behavioral observations were conducted at playgrounds in Irvine, California, to quantify the positive and the negative effects of supervisors' ages on children's play and thus indirectly assess whether there could be mutual benefits of making the presence of older people at playgrounds, which is customary in many countries, more culturally acceptable. Observations focused on the behavior of a pair of siblings showed that there was an increased probability of both conflicts and joyful expressions when the children were in the presence of a middle-aged person than when they were watched over by the elderlies. This has suggested that freer expressions stimulated in the presence of parent-like figures simultaneously induce the undesired and the desired behavioral patterns in the form of propensities for conflict and propensities for expressions of joy, respectively. This has confirmed that the observational stance has a critical effect on the observational outcome and that the age of the watchers has an effect on the behavior of children at play, with the age correlating directly with the calmness of the play, but also with a lower degree of exhilaration. To give a genuine account of a scientific study on children's play, the paper adopts an innovative form, combining rigorous analytics with a poetic triptych that places real-life children characters onto the central stage of the discourse. [ABSTRACT FROM AUTHOR]

Colloidal stability and the regularity of the release kinetics benefit from the high circularity and the narrow size dispersion of polymeric particles as drug delivery carriers. A method for obtaining such particles composed of poly(lactide- co -glycolide) (PLGA), averaging at 1.0 ± 0.3 µm in size, is reported here, along with the analysis of the effects of different synthesis parameters on their morphological characteristics. As in agreement with the classical nucleation theory, the particle size and the degree of cohesion were inversely proportional to supersaturation. Consequently, the optimal conditions for the precipitation of small and narrowly dispersed particles involved an abrupt elevation of supersaturation. Owing to the high colloidal stability of the particles, centrifugation exhibited a counterintuitive effect on them, refining their morphological features and promoting their individuation. Polyvinyl alcohol (PVA) was used as a steric repulsion additive and its effect on the stability of PLGA spheres was concentration-dependent, with the particles aggregating, partially coalescing and losing their distinct features both with no PVA in the system and at PVA concentrations higher than the optimal. At its narrowest, the particle size distribution was bimodal, exhibiting the average circularity of 0.997 ± 0.003 and the average roundness of 0.913 ± 0.054. PLGA spheres were loaded with an inhibitor of EhCP4, a cysteine protease from E. histolytica , a parasite causing amoebic dysentery in the tropical and developing world. The burst release of the drug at early time points was followed by a zero-order release period, yielding a biphasic profile that can be of benefit in the delivery of anti-infective agents. The release profile fitted poorly with the Hixson-Crowell kinetic model and excellently with the Higuchi and the Korsmeyer-Peppas ones, indicating that the release is conditioned by diffusion rather than by the degradation of the polymer. The release and the erosion proceeded independently from one another, suggesting that the pore formation, water penetration and swelling are the primary driving forces for the release of the drug. [ABSTRACT FROM AUTHOR]

Methods utilizing relatively simple mathematical operations during physical analyses to enable the visualization of otherwise invisible correlations and effects are of particular appeal to researchers and students in pedagogical settings. At the same time, discerning the amorphous phase from its crystalline counterpart in materials is challenging with the use of vibrational spectroscopy and is nowhere as straightforward as in phase composition analytical methods such as X-ray diffraction. A method is demonstrated for the use of first- and second-order differentiation of Fourier transform infrared spectra of calcium phosphates to distinguish their amorphous states from the crystalline ones based on the exact line positioning rather than on comparatively vaguer band broadening and splitting effects. The study utilizes a kinetic approach, focusing on the comparison of spectral features of amorphous precursors annealed in air at different temperatures or aged for different periods of time in an aqueous solution until transforming to one or a mixture of crystalline phases, including hydroxyapatite and α- and β-tricalcium phosphate. One of the findings challenges the concept of the nucleation lag time preceding the crystallization from amorphous precursors as a "dead" period and derives a finite degree of constructive changes occurring at the atomic scale in its course. The differential method for highlighting spectral differences depending on the sample crystallinity allows for monitoring in situ the process of conversion of the amorphous calcium phosphate phase to its crystalline analogue(s). One such method can be of practical significance for synthetic solid state chemists testing for the chemical stability and/or concentration of the reactive amorphous phase in these materials, but also for biologists measuring the maturity of bone and medical researchers evaluating its phase composition and, thus, the state of metabolic and mechanical stability. [ABSTRACT FROM AUTHOR]

Abstract: La0.76Sr0.24MnO3+ δ particles, prepared by performing a traditional, solid-state method of synthesis, were coated by uniform layers of silica via initiating hydrolysis and condensation of TEOS in aqueous–alcoholic alkali environment. The eventually obtained samples exhibited Curie temperature at ∼40 °C, and comprised core-shell particles of ∼250 nm in diameter. By varying stoichiometric ratio of cations within manganite cores of the particles, Curie point of the resulting material can be varied too, thus opening a way for the simple design of biocompatible, temperature-self-regulating particles for application in hyperthermia treatments, with Curie point thereof adjusted to a destined biological context of application. [Copyright &y& Elsevier]

With the onset of the COVID-19 pandemic, the amount of data on genomic and proteomic sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stored in various databases has exponentially grown. A large volume of these data has led to the production of equally immense sets of immunological data, which require rigorous computational approaches to sort through and make sense of. Immunoinformatics has emerged in the recent decades as a field capable of offering this approach by bridging experimental and theoretical immunology with state-of-the-art computational tools. Here, we discuss how immunoinformatics can assist in the development of high-performance vaccines and drug discovery needed to curb the spread of SARS-CoV-2. Immunoinformatics can provide a set of computational tools to extract meaningful connections from the large sets of COVID-19 patient data, which can be implemented in the design of effective vaccines. With this in mind, we represent a pipeline to identify the role of immunoinformatics in COVID-19 treatment and vaccine development. In this process, a number of free databases of protein sequences, structures and mutations are introduced, along with docking web servers for assessing the interaction between antibodies and the SARS-CoV-2 spike protein segments as most commonly considered antigens in vaccine design. [ABSTRACT FROM AUTHOR]

Ferrites count among the most functionally versatile magnetic materials in use in high technologies. In this study, synthesis, characterization and assessment of potential for use in water remediation of two different types of nanostructured ferrites were performed. Barium hexaferrite (BaFe12O19, BHF) and strontium hexaferrite (SrFe12O19, SHF) nanoparticle preparation using a flash-combustion method was successful. The prepared samples were thoroughly characterized for their microstructure, morphology, elemental composition, functional groups, surface charge density and magnetic, dielectric and optical properties. The hexagonal phase was detected as the primary one in X-ray diffraction patterns, while vibrational spectrophotometry analyses demonstrated the presence of an M-type hexagonal structure. Temperature-dependent ferromagnetic behavior of the nanoparticles was indicated from the χ-T curves, with a slightly higher single transition temperature, Tc, for BHF than for SFH: 675 °C vs. 650 °C. Despite having nanocrystalline structures, both BHF and SHF were identified as hard magnetic materials, with saturation magnetizations of 56.7 and 54.3 emu/g, respectively, and anisotropy fields greater than 9 kOe. Finally, batch adsorption studies were used to remove Pb(II) ions from aqueous solutions at various pHs and contact times using the as-prepared materials as fresh sorbents. The highest adsorption capacity was achieved at pH 7 and after 60 min of the contact time, equivalent to 84% and 80% for BHF and SHF, respectively. Extrinsic microstructural factors, such as particle morphology, surface area and porosity, proved to be more important for promoting the sequestration of Pb(II) than the intrinsic, crystallographic factors. Consequently, BHF performed better as an adsorbent than SHF under all of the tested conditions. The investigated nanostructured hexaferrites also demonstrated an exceptional recycling capacity. [ABSTRACT FROM AUTHOR]

mRNA-lipid nanoparticle (mRNA-LNP) vaccines have proved their efficacy, versatility and unprecedented manufacturing speed during the COVID-19 pandemic. Here we report on the physicochemical properties, thermostability, immunogenicity, and protective efficacy of the nucleoside-modified mRNA-LNP vaccine candidate Iribovax® (also called SNEG2c). Injection of BALB/c mice, rabbits and nonhuman primates with two doses of SNEG2c induced production of high-titers of SARS-CoV-2 spike-specific and receptor-binding domain (RBD)-neutralizing antibodies in immunized animals. In addition to the strong humoral response, SNEG2c elicited substantial Th1-biased T-cell response. Sera from rhesus macaques immunized with a low dose of the vaccine showed robust spike-specific antibody titers 3-24× as high as those in convalescent sera from a panel of COVID-19 patients and 50% virus neutralization geometric mean titer of 1024 against SARS-CoV-2. Strikingly, immunization with SNEG2c completely cleared infectious SARS-CoV-2 from the upper and lower respiratory tracts of challenged macaques and protected them from viral-induced lung and trachea lesions. In contrast, the non-vaccinated macaques developed moderate to severe pulmonary pathology after the viral challenge. We present the results of repeat-dose and local tolerance toxicity and thermostability studies showing how the physicochemical properties of the mRNA-LNPs change over time and demonstrating that SNEG2 is safe, well tolerated and stable for long-term. These results support the planned human trials of SNEG2c. [Display omitted] • Iribovax® is a modified-nucleoside mRNA-lipid nanoparticle vaccine candidate. • Administration of Iribovax® in nonhuman primates induces high titers of neutralizing antibodies. • Iribovax® elicits Th1-biased T cell immunity in mice and clears viral infection in rhesus macaques. • Iribovax® exhibits long-term stability at -20 °C. • Repeat-dose toxicity study demonstrates preclinical safety, supporting the clinical trials. [ABSTRACT FROM AUTHOR]

The combination of an intense absorption of visible light and p-type semiconducting nature makes spinel cobalt oxide (Co 3 O 4) a very attractive material for various optoelectronic applications. However, the traditional methods for its synthesis have been either time- and energy-consuming or relying on toxic chemicals. To solve this issue, a simple, facile, and eco-friendly method of synthesis was successfully developed to obtain spinel Co 3 O 4 nanoparticles. The novel method for obtaining pure and monophasic Co 3 O 4 reported here is based on the thermal decomposition of hexaaquacobalt(II) D-camphor10-sulfonate at 900 °C. This fast solid-state synthesis route overcomes the disadvantages of many combustion methods, most critically by avoiding the use of toxic organic solvents. The synthesized material was subjected to a detailed characterization to assess its potential for use as a nanocatalyst. The band gap measurements indicated the presence of two band gaps, one at 2.10 eV and another at 1.22 eV, confirming the purity and semiconducting properties of the sample. The electrochemical studies demonstrated a significant enhancement in the electron transfer kinetics with the addition of the synthesized Co 3 O 4 to the carbon-paste electrode, leading to an enhanced electrocatalytic performance. These prominent functional properties, suitable for a wide range of technological applications, pave way for the implementation of the reported method for the synthesis of Co 3 O 4 on a larger industrial scale. [Display omitted] [ABSTRACT FROM AUTHOR]

Scientific papers written as dialogues evoke Platonist philosophical discourses and are foreseen as elementary forms of expression in neoclassical scientific renaissance. Here we report on a study of the Brazil nut effect in a series of macroscopic and microscopic systems in the form of a play in three acts. The nut effect predicting the segregation of smaller grains at the bottom of the mixture and larger ones at the top was observed in a polydisperse mix of manually shaken playground pebbles, albeit following different kinetics than in an agitated pile of chess pieces. Common sense predicts that vertical, gravity-driven segregation in colloidal dispersions with heterogeneous particle size distributions is such that larger particles would settle toward the bottom and the lighter ones cream at the top. Here we refute this expectation and demonstrate that segregation of colloidal particles in the vertical direction conforms to the Brazil nut effect when the agitation is delivered in the forms of vortex mixing or audio vibration, but not when the colloids are manually shaken. The effect is demonstrated on aqueous dispersions of hydroxyapatite and iron oxide nanoparticles. Kinetic experiments showed that segregation increases with the agitation time in mixtures of pebbles and with the post-agitation aging time in fine particle colloids. The particle size gradient established due to agitation-induced segregation led to a corresponding gradient in optoelectronic properties—band gap, conductivity, lattice acoustics—in the vertical direction of the colloidal column for both types of nanoparticles. Such morphological gradients induced by the Brazil nut effect can be harnessed as affordable and facile templates for the synthesis of functionally gradient materials. Discussion of the mechanism and the application potential of the observed effect in colloidal and coarse systems is enriched with a literature review of this curious effect and entwined with the literary elements of the dramaturgical narrative involving a family of scientist in exile from mainstream scientific institutions: the mother, the father, an elementary school boy and a kindergarten girl. The narrative conforms in its structure to the shape of a Brazil nut and presents the first research study whose findings are enacted through a dream. The play questions the humaneness and creative prospects of modern science and celebrates children's science projects performed with meager resources and a plentiful of imagination, showing that they could be gateways to important scientific discoveries. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that has caused the recent coronavirus disease (COVID-19) global pandemic. The current approved COVID-19 vaccines have shown considerable efficiency against hospitalization and death. However, the continuation of the pandemic for more than two years and the likelihood of new strain emergence despite the global rollout of vaccination highlight the immediate need for the development and improvement of vaccines. mRNA, viral vector, and inactivated virus vaccine platforms were the first members of the worldwide approved vaccine list. Subunit vaccines. which are vaccines based on synthetic peptides or recombinant proteins, have been used in lower numbers and limited countries. The unavoidable advantages of this platform, including safety and precise immune targeting, make it a promising vaccine with wider global use in the near future. This review article summarizes the current knowledge on different vaccine platforms, focusing on the subunit vaccines and their clinical trial advancements against COVID-19. [Display omitted] [ABSTRACT FROM AUTHOR]

Metals and metal oxides have subpar antibacterial activities compared to those of small-molecule antibiotics, yet there are hopes that with proper compositional and structural adjustments this gap might be bridged. In this study, titanium dioxide (TiO 2) nanoparticles were mechanically activated and combined with particulate silver through simple reduction process elicited by UV irradiation and assisted with the ultrasound. The resulting powders in various combinations (Ag vs. no Ag, activated vs. non-activated) were characterized using a range of experimental techniques and assessed for their antibacterial activities. The preparation procedure presented in this work prevails over the disadvantages of many chemical routes, most critically by avoiding the use of toxic substances. The mechanical activation did not reduce the particle size or crystallinity of TiO 2 nor did it consistently alter the bandgap, yet it enabled the doubling of the amount of silver incorporable into the material. Further, while both mechanical activation and the addition of silver in the amount not exceeding 0.5 wt% produced barely detectable structural changes in the material, they both augmented its antibacterial activity. The precursor TiO 2 powder produced no inhibition zone against any of the four bacterial species tested, while the mechanical activation of TiO 2 led to the formation of distinct inhibition zones against each of the four bacterial species tested. The addition of silver to activated TiO 2 further widened the inhibition zones and it also imparted the antibacterial activity to non-activated TiO 2. The boost in the antibacterial activity achieved by the short mechanical activation was of a similar magnitude as the boost obtained after the addition of silver. The antibacterial activity was not different for different species when no silver was added to the system. However, with the addition of silver, species selectivity was obtained, as the composites were more effective against the two Gram-negative species (Escherichia coli and Klebsiella pneumoniae) than against the two Gram-positive ones (Staphylococcus aureus and Bacillus subtilis). The antibacterial activity increased with the addition of silver in the broth assay, but it was mediocre compared to that detected in the agar assay, attesting to the poor dispersability of the powders and their best performance when the bacterial cells migrate to the composite surface than vice versa. The findings of this study give hope that with appropriate microstructural or compositional alterations, the antibacterial activity of metal oxide powders and inorganic materials in general can be made comparable to that of small-molecule antibiotics. [Display omitted] • The mechanical activation of TiO 2 as an prerequisite for antibacterial activity • Ag distribution over TiO 2 surface by ultrasonically-assisted chemical precipitation • Homogeneous Ag deposition onto TiO 2 at a low net concentration • The mechanical activation doubled the amount of Ag incorporable into TiO 2 • The mechanical activation and addition of Ag augmented TiO 2 antibacterial effect. [ABSTRACT FROM AUTHOR]

In recent years, the idea that Vitamin C (Vit-C) could be utilized as a form of anti-cancer therapy has generated many contradictory arguments. Recent insights into the physiological characteristics of Vit-C, its pharmacokinetics, and results from preclinical reports, however, suggest that high-dose Vit-C could be effectively utilized in the management of various tumor types. Studies have shown that the pharmacological action of Vit-C can attack various processes that cancerous cells use for their growth and development. Here, we discuss the anti-cancer functions of Vit-C, but also the potential for the use of Vit-C as an epigenetic regulator and immunotherapy enhancer. We also provide a short overview of the current state of systems for scavenging reactive oxygen species (ROS), especially in the context of their influencing high-dose Vit-C toxicity for the inhibition of cancer growth. Even though the mechanisms of Vit-C action are promising, they need to be supported with robust randomized and controlled clinical trials. Moreover, upcoming studies should focus on how to define the most suitable cancer patient populations for high-dose Vit-C treatments and develop effective strategies that combine Vit-C with various concurrent cancer treatment regimens. [ABSTRACT FROM AUTHOR]

In recent decades, scientific and medical communities have continuously sought new methods and chemistries to improve the treatment of cancer. Among many types of nanoparticles considered as carriers for drug delivery, the protein ones count among the safest. The present study aimed to investigate the physicochemical and biological effects of the supplementation of albumin nanoparticles with doxorubicin (DOX). DOX was co-precipitated with albumin in a desolvation process and entrapped inside the cross-linked albumin nanoparticles, where it disrupted the protein structure at various levels: (a) it reduced the particle size distribution homogeneity; (b) it extended the peptide bond length; (c) it lowered the thermal stability of albumin; (d) it lowered the crystallinity of the protein. Physicochemical mechanisms underlying these changes are discussed. The drug release was incomplete under the physiological conditions, but the nanoparticles fully released their chemotherapeutic payload when pH was decreased by a single unit from the physiological value. Because the extracellular pH of tumors is usually by a single pH unit lower than that of healthy tissues, this environmentally responsive drug delivery system composed of albumin nanoparticles may be applicable in the targeting of cancer cells. In vitro assays against human lung cancer cells demonstrated that DOX released from albumin nanoparticles had a four times higher apoptotic activity than the equivalent concentration of free DOX. The ability of albumin to prevent the agglomeration of partially hydrophobic DOX and release it at a sustained, zero-order rate over the first 12 h of incubation, with no burst effect, explains this ability to augment the activity of DOX against the lung cancer cells. [ABSTRACT FROM AUTHOR]

Liquid cell electron microscopy is an imaging technique allowing for the investigation of the interaction of liquids and solids at nanoscopic length scales. Such in situ observations are increasingly in-demand in an array of fields, from biological sciences to medicine to batteries. Graphene liquid cells (GLCs), in particular, have generated a great interest as a low-scattering window material with the potential for increasing the quality of both imaging and spectroscopy. However, preserving the stability of the liquid and of the sample in the GLC remains a considerable challenge. In the present work we encapsulate water and hydroxyapatite (HAP), a pH-sensitive biological material, in GLCs to observe the interactions between the graphene, HAP, and the electron beam. HAP was chosen for several reasons. One is its ubiquity in biological specimens such as bones and teeth, and the second is the presence of phosphate ions in common buffer solutions. Finally, there is its sensitivity to changes in pH, which result from beam-induced hydrolysis in liquid cells. A dynamic process of dissolution and recrystallization of HAP was observed, which correlated with the production of H+ ions by the beam during imaging. In addition, a large increase in the stability of the GLC under irradiation was noted. Specifically, no stable hydrogen bubbles were detected under the electron fluxes routinely exceeding 170 e− Ĺ−2 s−1. With the measured threshold dose for the bubble formation in pure water equaling 9 e− Ĺ−2 s−1, it was concluded that the presence of HAP increases the resistance of water against radiolysis in the GLC by more than an order of magnitude. These results confirm the possibility of using biological materials, such as HAP, as stabilizers in liquid cell electron microscopy. They outline a potential route for stabilization of specimens in liquid cells through the addition of a scavenger of reactive species generated by the beam-induced hydrolysis of water. These improvements are essential for enhancing both the resolution of imaging and the available imaging time, as well as avoiding the beam-induced artifacts. [ABSTRACT FROM AUTHOR]

A simple and green chemical method has been developed to synthesize stable bare and capped silver nanoparticles based on the reduction of silver ions by glucose and capping by poly(α,γ, l-glutamic acid) (PGA). The use of ammonia during synthesis was avoided. PGA has had a dual role in the synthesis and was used as a capping agent to make the silver nanoparticle more biocompatible and to protect the nanoparticles from agglomerating in the liquid medium. The synthesized PGA-capped silver nanoparticles in the size range 5-45 nm were stable over long periods of time, without signs of precipitation. Morphological examination has shown that the silver nanoparticles had a nearly spherical, multiply twinned structure. The effects of the reaction temperature and the reaction time during the synthesis were investigated too. The biocompatibility of the PGA-capped silver nanoparticles is discussed in terms of in vitro toxicity with human intestinal Caco-2 cells. The samples were characterized by UV-Visible spectroscopy, field emission scanning electron microscopy, transmission electron microscopy, and zeta potential measurements. [ABSTRACT FROM AUTHOR]

Ferrites have found extensive uses in electrical, chemical and mechanical engineering, but their potential as biomaterials remains largely unexplored. Here we report on the use of a flash method based on urea decomposition to synthesize four different compositions of cobalt and zinc ferrite, including monophasic CoFe 2 O 4 , ZnFe 2 O 4 and Co 0.5 Zn 0.5 Fe 2 O 4 , and CoFe 2 O 4 /ZnFe 2 O 4 nanocomposite. Zn-ferrite nanoparticles were approximately the same size as those of Co-ferrite, but were better dispersed, rougher, more crystalline and less pronouncedly faceted. The mixed, monophasic Co 0.5 Zn 0.5 Fe 2 O 4 composition was morphologically most similar to single-phase Co-ferrite. In the biphasic mixture of CoFe 2 O 4 and ZnFe 2 O 4 , smooth and polydisperse Co-ferrite grains were coated by finer, cuboid and monodisperse Zn-ferrite nanoparticles. The porosity and the roughness of this composition were the highest, and so was its coercivity owing to the shielding of the ferrimagnetic Co-ferrite grains by the paramagnetic Zn-ferrite nanoparticles. Expectedly, the highest saturation magnetization (66.3 emu/g) was detected in Co-ferrite and the lowest (2.8 emu/g) in Zn-ferrite. Co-ferrite also exhibited the highest magneto-crystalline anisotropy, remanence and hysteresis loop area, while the highest exchange bias and susceptibility were found in the mixed, Co 0.5 Zn 0.5 Fe 2 O 4 composition. All four ferrite compositions were biocompatible with human fibroblasts, but they demonstrated different antibacterial activities against Gram-negative E. coli and Gram-positive S. aureus, with the biphasic mixture of CoFe 2 O 4 and ZnFe 2 O 4 being more effective than Co 0.5 Zn 0.5 Fe 2 O 4 , CoFe 2 O 4 or ZnFe 2 O 4. Further, all the compositions were more active against both bacterial species under visible light than in the dark, indicating the photocatalytic formation of electron-hole pairs and reactive oxygen species that exert a damaging effect on the bacterial cells as the prime mechanism of action. • Monophasic CoFe 2 O 4 , ZnFe 2 O 4 and Co 0.5 Zn 0.5 Fe 2 O 4 , and CoFe 2 O 4 /ZnFe 2 O 4 nanocomposite were synthesized and characterized. • CoFe 2 O 4 /ZnFe 2 O 4 nanocomposite contained Co-ferrite grains coated by Zn-ferrite nanoparticles, leading to high coercivity. • Biphasic mixture of CoFe 2 O 4 and ZnFe 2 O 4 had the highest antibacterial activity. • Photocatalytic formation of electron-hole pairs and reactive oxygen species is the prime mechanism of antibacterial action. • High biocompatibility of the examined compositions might encourage their use for numerous biomedical applications. [ABSTRACT FROM AUTHOR]

Functional nanomaterials have held a steady position at the frontier of materials science and engineering in the 21st century. "Molecular Designing of Nanoparticles with Controlled Morphological and Physicochemical Characteristics and Functional Materials Based on Them" was the title of the research project funded by the Ministry of Education, Science and Technological Development of the Republic of Serbia and performed between 2011 and 2019 in the interdisciplinary area of nanoscience and nanotechnologies. Research activities within this program were divided into five interrelated topics: 1) from molecules to nanoparticles; 2) advanced ceramics with improved functional properties; 3) electrode materials for lithium-ion batteries; 4) nano-calcium phosphate in preventive and regenerative medicine; 5) biodegradable microand nano-particles for the controlled delivery of medicaments. This report gives an insight into this bibliographically most impactful Serbian national project on nanotechnologies executed within the aforementioned nine-year cycle, 2011-2019, focusing here only on the results achieved in the past three years. The project provided an outstanding and internationally recognized contribution to synthesis, characterization and functional design of a number of materials systems, including pure and lanthanide-doped hydroxyapatite, zinc oxides, sodium cobaltates, lithium iron pyrophosphates, lithium iron silicates and a number of polymeric systems. [ABSTRACT FROM AUTHOR]

Physical adsorption of lipase from Thermomyces lanuginosus onto single-layer sheets of graphene oxide (GO) was studied using the response surface methodology to evaluate the physicochemical factors – temperature, pH, ionic strength, and concentration – affecting the enzymatic activity and the immobilization efficiency. The immobilization efficiency and the activity of the enzyme were inversely proportional to each other. Specifically, higher pH values increased the immobilization efficacy, but produced changes in the aggregation state and secondary structure of the enzyme, thus decreasing its activity. Lower pH values, in turn, reduced the immobilization efficacy, but increased the activity of the adsorbed lipase. The adsorbed and the free lipase were followed during 600 ns and 3.5 μs, respectively, in molecular dynamics (MD) simulations. MD trajectories showed that irreversible adsorption freezes the enzyme in a state with a correctly opened catalytic cavity, while the active site remains without a direct interaction with the GO adsorbent. In contrast to the interfacial activation of lipases in a hydrophobic environment, where the catalytic pocket attaches to the hydrophobic surface, the adsorption onto GO made the active site of the lipase accessible by altering the tertiary structure of the enzyme, leading to a higher catalytic efficiency. Experimental investigations confirmed that the physical adsorption onto GO induces tertiary structure changes in the lipase and protects it from H 2 O 2 by accepting the oxidative damage upon itself. In summary, the physical adsorption of the lipase onto GO is mainly affected by pH and could possibly provide a spreadable and robust catalytic interface for biotechnological applications. [ABSTRACT FROM AUTHOR]

A blue calcium phosphate cement with optimal self-hardening properties was synthesized by doping whitlockite (β-TCP) with copper ions. The mechanism and the kinetics of the cement solidification process were studied using energy dispersive X-ray diffraction and it was found out that hardening was accompanied by the phase transition from TCP to brushite. Reduced lattice parameters in all crystallographic directions resulting from the rather low (1:180) substitution rate of copper for calcium was consistent with the higher ionic radius of the latter. The lower cationic hydration resulting from the partial Ca → Cu substitution facilitated the release of constitutive hydroxyls and lowered the energy of formation of TCP from the apatite precursor at elevated temperatures. Addition of copper thus effectively inhibited the formation of apatite as the secondary phase. The copper-doped cement exhibited an antibacterial effect, though exclusively against Gram-negative bacteria, including E. coli , P. aeruginosa and S. enteritidis . This antibacterial effect was due to copper ions, as demonstrated by an almost negligible antibacterial effect of the pure, copper-free cement. Also, the antibacterial activity of the copper-containing cement was significantly higher than that of its precursor powder. Since there was no significant difference between the kinetics of the release of copper from the precursor TCP powder and from the final, brushite phase of the hardened cement, this has suggested that the antibacterial effect was not solely due to copper ions, but due to the synergy between cationic copper and a particular phase and aggregation state of calcium phosphate. Though inhibitory to bacteria, the copper-doped cement increased the viability of human glial E297 cells, murine osteoblastic K7M2 cells and especially human primary lung fibroblasts. That this effect was also due to copper ions was evidenced by the null effect on viability increase exhibited by the copper-free cements. The difference in the mechanism of protection of dehydratases in prokaryotes and eukaryotes was used as a rationale for explaining the hereby evidenced selectivity in biological response. It presents the basis for the consideration of copper as a dually effective ion when synergized with calcium phosphates: toxic for bacteria and beneficial for the healthy cells. [ABSTRACT FROM AUTHOR]

In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly( d , l )-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5- en -3β- yl -acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. 1 H NMR and 13 C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the thermal degradation products and properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA, equaled 7.47 wt.%. The release of A from HAp/Ch-PLGA was sustained, neither exhibiting a burst release nor plateauing after three weeks. Atomic force microscopy and particle size distribution analyses were used to confirm that the particles were spherical with a uniform size distribution of d 50 = 168 nm. In vitro cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye exclusion assays demonstrated that the particles were cytotoxic to the A549 human lung carcinoma cell line (46 ± 2%), while simultaneously preserving high viability (83 ± 3%) of regular MRC5 human lung fibroblasts and causing no harm to primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA particles could be seen as promising drug delivery platforms for selective cancer therapies, targeting malignant cells for destruction, while having a significantly lesser cytotoxic effect on the healthy cells. [ABSTRACT FROM AUTHOR]

Recent developments in bone tissue engineering have led to an increased interest in one-dimensional (1D) hydroxyapatite (HA) nano- and micro-structures such as wires, ribbons and tubes. They have been proposed for use as cell substrates, reinforcing phases in composites and carriers for biologically active substances. Here we demonstrate the synthesis of 1D HA structures using an optimized, urea-assisted, high-yield hydrothermal batch process. The one-pot process, yielding HA structures composed of bundles of ribbons and wires, was typified by the simultaneous occurrence of a multitude of intermediate reactions, failing to meet the uniformity criteria over particle morphology and size. To overcome these issues, the preparation procedure was divided to two stages: dicalcium phosphate platelets synthesized in the first step were used as a precursor for the synthesis of 1D HA in the second stage. Despite the elongated particle morphologies, both the precursor and the final product exhibited excellent biocompatibility and caused no reduction of viability when tested against osteoblastic MC3T3-E1 cells in 2D culture up to the concentration of 2.6 mg/cm 2 . X-ray powder diffraction combined with a range of electron microscopies and laser diffraction analyses was used to elucidate the formation mechanism and the microstructure of the final particles. The two-step synthesis involved a more direct transformation of DCP to 1D HA with the average diameter of 37 nm and the aspect ratio exceeding 100:1. The comparison of crystalline domain sizes along different crystallographic directions showed no signs of significant anisotropy, while indicating that individual nanowires are ordered in bundles in the b crystallographic direction of the P 6 3/ m space group of HA. Intermediate processes, e.g., dehydration of dicalcium phosphate, are critical for the formation of 1D HA alongside other key aspects of this phase transformation, it must be investigated in more detail in the continuous design of smart HA micro- and nano-structures with advanced therapeutic potentials. [ABSTRACT FROM AUTHOR]

Despite the long history of nanoparticulate calcium phosphate (CaP) as a non-viral transfection agent, there has been limited success in attempts to optimize its properties for transfection comparable in efficiency to that of viral vectors. Here we focus on the optimization of: (a) CaP nanoparticle precipitation conditions, predominantly supersaturation and Ca/P molar ratios; (b) transfection conditions, mainly the concentrations of the carrier and plasmid DNA; (c) the presence of surface additives, including citrate anion and cationic poly( l -lysine) (PLL). CaP nanoparticles significantly improved transfection with plasmid DNA encoding enhanced green fluorescent protein (eGFP) in pre-osteoblastic MC3T3-E1 cells compared to a commercial non-viral carrier. At the same time they elicited significantly lesser cytotoxicity than the commercial carrier. Plasmid DNA acted as a nucleation promoter, decreasing the nucleation lag time of metastable CaP solutions and leading to a higher rate of nucleation and a lower size of the precipitated particles. The degree of supersaturation (DS) of 15 was found to be more optimal for transfection than that of 12.5 or 17.5 and higher. Because CaP particles precipitated at DS 15 were spherical, while DS 17.5 and 21 yielded acicular particles, it was concluded that spherical particle morphologies were more conducive to transfection than the anisotropic ones. Even though the yield at DS 15 was 10 and 100 times lower than that at DS 17.5 and 21, respectively, transfection rates were higher using CaP nanoparticle colloids prepared at DS 15 than using those made at higher or lower DS, indicating that the right particle morphology can outweigh the difference in the amount of the carrier, even when this difference is close to 100×. In contrast to the commercial carrier, the concentration of CaP-pDNA delivered to the cells was directly proportional to the transfection rate. Osteosarcoma K7M2 cells were four times more easily transfectable with CaP nanoparticles than the MC3T3-E1 cells. The addition of citrate increased the transfection rate at lower concentrations; however, a complete redispersal of CaP-pDNA nanoparticles at higher concentrations of citrate coincided with a complete diminishment of transfection, implying the benefits of partial aggregation of CaP nanoparticles carrying pDNA. In contrast, PLL delayed transfection initially, but enhanced it at longer time points (⩾96 h), leading to the conclusion that both citrate and PLL could exert positive effects on transfection: citrate if added at low concentrations and PLL to extend transfection over longer periods of time. [ABSTRACT FROM AUTHOR]

Composite biomaterials comprising nanostructured hydroxyapatite (HAp) have an enormous potential for natural bone tissue reparation, filling and augmentation. Chitosan (Ch) as a naturally derived polymer has many physicochemical and biological properties that make it an attractive material for use in bone tissue engineering. On the other hand, poly-D,L-lactide-co-glycolide (PLGA) is a synthetic polymer with a long history of use in sustained drug delivery and tissue engineering. However, while chitosan can disrupt the cell membrane integrity and may induce blood thrombosis, PLGA releases acidic byproducts that may cause tissue inflammation and interfere with the healing process. One of the strategies to improve the biocompatibility of Ch and PLGA is to combine them with compounds that exhibit complementary properties. In this study we present the synthesis and characterization, as well as in vitro and in vivo analyses of a nanoparticulate form of HAp coated with two different polymeric systems: (a) Ch and (b) a Ch-PLGA polymer blend. Solvent/non-solvent precipitation and freeze-drying were used for synthesis and processing, respectively, whereas thermogravimetry coupled with mass spectrometry was used for phase identification purposes in the coating process. HAp/Ch composite particles exhibited the highest antimicrobial activity against all four microbial strains tested in this work, but after the reconstruction of the bone defect they also caused inflammatory reactions in the newly formed tissue where the defect had lain. Coating HAp with a polymeric blend composed of Ch and PLGA led to a decrease in the reactivity and antimicrobial activity of the composite particles, but also to an increase in the quality of the newly formed bone tissue in the reconstructed defect area. [ABSTRACT FROM AUTHOR]

The development of new materials with antibacterial properties and the scope to decrease or eliminate the excessive antibiotic use is an urgent priority due to the growing antibiotic resistance-related mortalities. New bone substitute materials with intrinsic antibacterial characteristics are highly requested for various clinical applications. In this study, the choice of copper ions as substitutes for calcium in tricalcium phosphate (TCP) has been justified by their pronounced broad-spectrum antibacterial properties. Copper-substituted TCP (Cu-TCP) ceramics with the copper content of 1.4 and 0.1 wt% were synthesized by mechano-chemical activation. X-ray diffraction (XRD) analyses established that both pure and copper-containing compounds adopted the structure of whitlockite (β-TCP). XRD and electron paramagnetic resonance (EPR) spectroscopy revealed the partial isovalent substitution of calcium ions with copper ions in the β-TCP lattice. With the use of infrared and EPR spectroscopies, it was detected that carbonate ions got incorporated into the β-TCP structure during the synthesis procedure. By releasing the tension in the M(5)O6 octahedron consequential to the lower Ca O bond length than the corresponding sum of ionic radii, the substitution of calcium with smaller copper ions stabilizes the structure of β-TCP. As concluded form the thermal analyses, the introduction of Cu prevented the polymorphic transformation of β- to α-TCP. At the same time, the introduction of Cu to the β-TCP structure enhanced the crystal growth and porosity of the ceramics, which had a positive effect on the cytocompatibility of the material. The MTT colorimetric assay showed that the metabolic activity of the mouse fibroblast NCTC L929 cell line during 24 h of incubation with 3-day extracts from Cu-TCP (1.4 wt%) and β-TCP pellets in the cell culture medium was similar to the negative control, indicating the absence of any inhibitory effects on cells. The seeding and the growth of human dental pulp stem cells on the surface of Cu-TCP (1.4 wt%) and β-TCP ceramics also showed the absence of any signs of cytotoxicity. Finally, microbiological assays demonstrated the antibacterial activity of Cu-TCP ceramics against Escherichia coli and Salmonella enteritidis , whereas β-TCP did not exhibit such an activity. Overall, the addition of Cu ions to β-TCP improves its antibacterial properties without diminishing the biocompatibility of the material, thus making it more attractive than pure β-TCP for clinical applications such as synthetic bone grafts and orthopaedic implant coatings. [Display omitted] • Copper-substituted tricalcium phosphate ceramic (Cu-TCP) was prepared by mechanochemical activation • Cu introduction into β-TCP structure had stabilizing effect and enhanced crystal growth and porosity of ceramics • Assays on the metabolic activity of NCTC L929 showed the absence of any cytotoxic effect of these materials on cells • Seeding and growth of human dental pulp stem cells confirmed the absence of any cytotoxicity • Cu-TCP ceramics exhibited the antibacterial effect against E. coli and S. enteritidis. [ABSTRACT FROM AUTHOR]

Abstract: Biodegradable poly(d,l-lactide-co-glycolide) (PLGA) and bioactive hydroxyapatite (HAp) are selected for the formation of a multifunctional system with the specific core-shell structure to be applied as a carrier of a drug. As a result, both components of PLGA/HAp core-shells are able to capture one part of the drug. Polymeric shells consisting of small nanospheres up to 20nm in size act as a matrix in which one part of the drug is dispersed. In the same time, ceramic cores are formed of rod-like hydroxyapatite particles at the surface of which another part of the drug is adsorbed onto the interface between the polymer and the ceramics. The content of the loaded drug, as well as the selected solvent/non-solvent system, have a crucial influence on the resulting PLGA/HAp morphology and, finally, unimodal distribution of core-shells is obtained. The redistribution of the drug between the organic and inorganic parts of the material is expected to provide an interesting contribution to the kinetics of the drug release resulting in non-typical two-step drug release. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which emerged in December 2019 and caused the coronavirus disease 2019 (COVID-19) pandemic, took the world by surprise with an unprecedented public health emergency. Since this pandemic began, extraordinary efforts have been made by scientists to understand the pathogenesis of COVID-19, and to fight the infection by providing various preventive, diagnostic and treatment opportunities based on either novel hypotheses or past experiences. Despite all the achievements, COVID-19 continues to be an accelerating health threat with no specifically approved vaccine or therapy. This review highlights the recent advances in COVID-19 infection, with a particular emphasis on nanomedicine applications that can help in the development of effective vaccines or therapeutics against COVID-19. A novel future perspective has been proposed in this review based on utilizing polymersome nano-objects for effectively suppressing the cytokine storm, which may reduce the severity of COVID-19 infection. [ABSTRACT FROM AUTHOR]

The use of ions as therapeutic agents has the potential to minimize the use of small-molecule drugs and biologics for the same purpose, thus providing a potentially more economic and less adverse means of treating, ameliorating or preventing a number of diseases. Hydroxyapatite (HAp) is a solid compound capable of accommodating foreign ions with a broad range of sizes and charges and its properties can dramatically change with the incorporation of these ionic additives. While most ionic substitutes in HAp have been monatomic cations, their lesser atomic weight, higher diffusivity, chaotropy and a lesser residence time on surfaces theoretically makes them prone to exert a lesser influence on the material/cell interaction than the more kosmotropic oxyanions. Selenite ion as an anionic substitution in HAp was explored in this study for its ability to affect the short-range and the long-range crystalline symmetry and solubility as well as for its ability to affect the osteoclast activity. We combined microstructural, crystallographic and spectroscopic analyses with quantum mechanical calculations to understand the structural effects of doping HAp with selenite. Integration of selenite ions into the crystal structure of HAp elongated the crystals along the c-axis, but isotropically lowered the crystallinity. It also increased the roughness of the material in direct proportion with the content of the selenite dopant, thus having a potentially positive effect on cell adhesion and integration with the host tissue. Selenite in total acted as a crystal structure breaker, but was also able to bring about symmetry at the local and global scales within specific concentration windows, indicating a variety of often mutually antagonistic crystallographic effects that it can induce in a concentration-dependent manner. Experimental determination of the lattice strain coupled with ab initio calculations on three different forms of carbonated HAp (A-type, B-type, AB-type) demonstrated that selenite ions initially substitute carbonates in the crystal structure of carbonated HAp, before substituting phosphates at higher concentrations. The most energetically favored selenite-doped HAp is of AB-type, followed by the B-type and only then by the A-type. This order of stability was entailed by the variation in the geometry and orientation of both the selenite ion and its neighboring phosphates and/or carbonates. The incorporation of selenite in different types of carbonated HAp also caused variations of different thermodynamic parameters, including entropy, enthalpy, heat capacity, and the Gibbs free energy. Solubility of HAp accommodating 1.2 wt% of selenite was 2.5 times higher than that of undoped HAp and the ensuing release of the selenite ion was directly responsible for inhibiting RAW264.7 osteoclasts. Dose-response curves demonstrated that the inhibition of osteoclasts was directly proportional to the concentration of selenite-doped HAp and to the selenite content in it. Meanwhile, selenite-doped HAp had a significantly less adverse effect on osteoblastic K7M2 and MC3T3-E1 cells than on RAW264.7 osteoclasts. The therapeutically promising osteoblast vs. osteoclast selectivity of inhibition was absent when the cells were challenged with undoped HAp, indicating that it is caused by selenite ions in HAp rather than by HAp alone. It is concluded that like three oxygens building the selenite pyramid, the coupling of (1) experimental materials science, (2) quantum mechanical modeling and (3) biological assaying is a triad from which a deeper understanding of ion-doped HAp and other biomaterials can emanate. • Selenite exerts antagonistic crystallographic effects in a concentration-dependent manner. • Selenite preferentially replaces carbonate in the lattice of carbonated HAp, before substituting phosphate. • Solubility of HAp increases with accommodation of selenite. • Inhibition of RAW264.7 osteoclasts is directly proportional to the selenite content in HAp. • The inhibitory effect is absent in osteoblastic K7M2 and MC3T3-E1 cells. [ABSTRACT FROM AUTHOR]

A self-setting bone cement containing β-tricalcium phosphate (TCP) supplemented with boron nitride nanotubes (BNNTs, 1 wt%) was synthesized and analyzed in situ for its kinetics of hardening and selected physicochemical and biological properties. Moderately delayed due to the presence of BNNTs, the hardening reaction involved the transformation of the TCP precursor to the dicalcium phosphate (DCPD) product. In spite of the short-lived chemical transformations in the cement upon its hardening, the structural changes in it were extended. As a result, the compressive strength increased from day 1 to day 7 of the hardening reaction and the presence of BNNTs further increased it by ~25%. Fitting of the time-resolved energy-dispersive diffractometric data to the Johnson-Mehl-Avrami-Kolmogorov crystallization kinetics model conformed to the one-dimensional nucleation at a variable rate during the growth of elongated DCPD crystals from round TCP grains. For the first seven days of growth of human mesenchymal stem cells (hMSCs) on the cement, no difference in their proliferation was observed compared to the control. However, between the 7th and the 21st day, the cell proliferation decreased compared to the control because of the ongoing stem cell differentiation toward the osteoblast phenotype. This differentiation was accompanied by the higher expression of alkaline phosphatase, an early marker of hMSC differentiation into a pre-osteoblast phenotype. The TCP cement supplemented with BNNTs was able to thwart the production of reactive oxygen species (ROS) in hMSCs treated with H 2 O 2 /Fe2+ and bring the ROS levels down to the concentrations detected in the control cells, indicating the good capability of the material to protect the cells against the ROS-associated damage. Simultaneously, the cement increased the expression of mediators of inflammation in a co-culture of osteoblasts and macrophages, thus attesting to the direct reciprocity between the degrees of inflammation and stimulated new bone production. Unlabelled Image • Selfsetting bone cement based on βtricalcium phosphate with boron nitride nanotubes • 3D diffraction patterns and in situ analysis of crystallization kinetics • Compressive strength of the cement increased by 25%. • Cement protects human mesenchymal stem cells against reactive oxygen species damage. • Cement increases inflammation mediator expression and stimulates new bone growth. [ABSTRACT FROM AUTHOR]

Composite structures are at the frontier of materials science and engineering and polymeric/ceramic composites present one of their most prospective subsets. Prior studies have shown both improvements and deteriorations of properties of polymers upon the addition of ceramic phases to them, but not many studies have dealt with the direct comparison of chemically distinct inorganic additives. The goal of this study was to compare the properties of ε-polycaprolactone (PCL) thin films supplemented with alumina, graphene, carbonated hydroxyapatite or titania particles, individually, in identical amounts (12 wt%). The composite films were analyzed for their phase composition, grain size, morphology, surface roughness, porosity, cell response, mechanical properties and electrochemical performance. Each additive imparted one or more physical or biological properties onto PCL better than others. Thus, alumina increased the microhardness of the films better than any other additive, with the resulting values exceeding 10 MPa. It also led to the formation of a composite with the least porosity and the greatest stability to degradation in simulated body fluid based on open circuit potential (OCP) measurements and electrochemical impedance spectroscopy (EIS). Titania made the surface of PCL roughest, which in combination with its high porosity explained why it was the most conducive to the growth of human fibroblasts, alongside being most prone to degradation in wet, corrosive environments and having the highest Poisson's ratio. Graphene, in contrast, made the surface of PCL smoothest and the bulk structure most porous, but also most conductive, with the OCP of −37 mV. The OCP of PCL supplemented with carbonated hydroxyapatite had the highest OCP of −134 mV and also the highest mechanical moduli, including the longitudinal (781 MPa), the shear (106 MPa), the bulk (639 MPa), and the elastic (300 MPa). The only benefit of the deposition of multilayered PCL films supplemented with all four inorganic additives was to enable a relatively high resistance to degradation. This study demonstrates that the properties of thin PCL films could be effectively optimized through the simple choice of appropriate inorganic additives dispersed in them. There is no single additive that proves ideal for improving all the properties of interest in PCL thin films, but their choice should be adjusted to the actual application. One such method of compositional optimization could prove crucial in the effort to develop biocomposites for superior performance in tissue engineering applications. [ABSTRACT FROM AUTHOR]

The necessity for finding a compromise between mechanical and biological properties of biomaterials spurs the investigation of the new methods to control and optimize scaffold processing for tissue engineering applications. A scaffold composed of ε-polycaprolactone fibers reinforced with carbonated hydroxyapatite (CHAP) dually doped with selenite oxyanions (Se) and cationic gold (Au) was synthesized using the electrospinning technique and studied at different contents of Au. Despite the fact that the amount of the Au dopant was relatively low, variations to it induced significant microstructural changes, affecting the cell response and mechanical properties in return. Au nanoparticles segregated as a separate, ternary phase at the highest Au content, corresponding to x = 0.8 in the Au x Ca 10−1.5x (PO 4) 5.8 (SeO 2) 0.2−x (CO 3) x (OH) 2 stoichiometric formula of Au/Se-CHAP. Their appearance coincided with a rapid degeneration in the density and adhesion of osteoblastic cells grown on the scaffolds. In spite of this adverse effect, the cell spreading and proliferation improved with increasing the amount of the Au dopant in the Au/Se-CHAP particles of the scaffold in the x = 0.0–0.6 range, suggesting that the biological effects of Au in the ionic and in the nanoparticulate form on the implant integration process may be diametrically opposite. The addition of Au had a dramatic effect on some mechanical properties, such as toughness and strain at break, which were both reduced twice upon the introduction of Au into Se-CHAP at the lowest amount (x = 0.2) compared to the Au-free composite. The significant variation of physical and biological properties of these composite scaffolds with trace changes in the content of the Au dopant inside the ceramic filler particles is promising, as it provides a new, relatively subtle avenue for tailoring the properties of tissue engineering scaffolds for their intended biomedical applications. [ABSTRACT FROM AUTHOR]