Teaching Medical Devices through Interactive Innovation: Challenges and Rewards.

Medical devices are manmade objects existing at the interface between numerous disciplines. They range from as simple as medical gloves to as complex as artificial limbs. This versatility of medical devices and their inherent interdisciplinary nature means that academic courses on them are attended by cohorts of students from varieties of academic backgrounds, who bring with them similarly broad spectra of interests. To satisfy the learning expectations of each and every student in such diverse classes is a daunting task for the instructor. After many years of teaching medical devices at undergraduate and graduate levels at three different universities in the states of Illinois and California, I have come up with an instructional method that solves this challenge by engaging students in the co-creation of the curriculum via selection of their own medical devices of interest and presentation to the class for collective analysis. The threefold presentations are designed so that they reflect an ascent along the hierarchy of a learning taxonomy extending from foundational concepts to critical assessment of knowledge to creative displays of it. In such a way, the students are acquainted with the ability of critical and creative thinking at the expense of rote memorization or inculcation and are prepared to enter the field of medical devices as innovation-centered individuals. The specifics of this new method of instruction are reported here, with the hope that they will be useful to fellow instructors in any interdisciplinary course that benefits from a balance between the rigorous coverage of the instructional material pertaining to engineering and medicine and the flexible selection of topics that comply with students' individual interests.

Tracking the pipeline: immunoinformatics and the COVID-19 vaccine design.

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.

Exploration of potential inhibitors for SARS-CoV-2 Mpro considering its mutants via structure-based drug design, molecular docking, MD simulations, MM/PBSA, and DFT calculations.

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.

Hydroxyapatite as a scavenger of reactive radiolysis species in graphene liquid cells forin situelectron microscopy.

Liquid cell electron microscopy is an imaging technique allowing for the investigation of the interaction of liquids and solids at nanoscopic length scales. Suchin situobservations 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-Å-2s-1. With the measured threshold dose for the bubble formation in pure water equaling 9 e-Å-2s-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.

Pulsed laser deposition temperature effects on strontium-substituted hydroxyapatite thin films for biomedical implants.

Substituting small molecule drugs with abundant and easily affordable ions may have positive effects on the way countless disease treatments are approached. The interest in strontium cation in bone therapies soared in the wake of the success of strontium ranelate in the treatment of osteoporosis. A new method for producing thin strontium-containing hydroxyapatite (Sr-HA, Ca9Sr(PO4)6(OH)2) films as coatings that render bioinert titanium implant bioactive is reported here. The method is based on the combination of a mechanochemical synthesis of Sr-HA targets and their deposition in form of thin films on top of titanium with the use of laser ablation at low pressure. The films were 1-2 µm in thickness and their formation was studied at different temperatures, including 25, 300, and 500 °C. Highly crystalline Sr-HA target transformed during pulsed laser deposition to a fully amorphous film, whose degree of long-range order recovered with temperature. Particle edges became somewhat sharper and surface roughness moderately increased with temperature, but the (Ca+Sr)/P atomic ratio, which increased 1.5 times during the film formation, remained approximately constant at different temperatures. Despite the mostly amorphous structure of the coatings, their affinity for capturing atmospheric carbon dioxide and accommodating it as carbonate ions that replace both phosphates and hydroxyls of HA was confirmed in an X-ray photoelectron spectroscopic analysis. As the film deposition temperature increased, the lattice voids got reduced in concentration and the structure gradually "closed," becoming more compact and entailing a linear increase in microhardness with temperature, by 0.03 GPa/°C for the entire 25-500 °C range. Biocompatibility and bioactivity of Sr-HA thin films deposited on titanium were confirmed in an interaction with dental pulp stem cells, suggesting that these coatings, regardless of the processing temperature, may be viable candidates for the surface components of metallic bone implants.

X-ray photoelectron and ion scattering spectroscopic surface analyses of amorphous and crystalline calcium phosphate nanoparticles with different chemical histories.

Abundant hydration, diffusivity, and volatile phase composition render the surface of calcium phosphates (CPs) a complex dynamic region. Three CP powders were analyzed using X-ray photoelectron spectroscopy (XPS) and ion scattering spectroscopy (ISS) with regard to their surface compositions and fine structures: hydroxyapatite (HAp), amorphous CP (ACP), and a CP formed under the same conditions as ACP but allowed to ripen into HAp (ACP → HAp). XPS analyses revealed that the Ca/P atomic ratio in the 2-10 nm-thick layers of the nanoparticle surface was somewhat lower than the stoichiometric ratio for all the three CPs. However, it was still lower for ACP and ACP → HAp than that for HAp, indicating the incongruent dissolution of all the surfaces and also greater instability and higher solubility of ACP and ACP → HAp as compared to those of HAp. Consequently, as indicated by both XPS and ISS, the amount of adventitious carbon bound to HAp was higher than that on ACP or ACP → HAp. The binding energies of the most intense XPS lines of all the three main atomic elements in HAp, i.e., O1s, P2p, and Ca2p downshifted for HAp as compared to those for ACP and ACP → HAp, supporting the premise of similarity in the surface structures between the two CP powders with a common amorphous precursor and kinetic path of formation. The ISS analysis, which investigated the 1-2 topmost atomic layers of the surface, indicated a higher level of heterogeneity of the oxygen states. This coincided with 40Ca accounting for over 80% atoms in this uppermost atomic layer of the surface of all three CPs. Ca-O bonds were particularly dominant in the topmost surface layer of ACP, where the Ca/P atomic ratio was an order of magnitude higher than that in ACP → HAp or HAp. A thermodynamic explanation and structural model of the surface accounting for the overabundance of Ca2+ in the topmost layer and the overall depletion of it elsewhere are provided in the discussion. Overall, the combined results of XPS and ISS analyses demonstrate a similarity between the surfaces of the two different forms of HAp as compared to that for ACP, but also a definite impression of the traces of their formation history on them.

Visualizing Different Crystalline States during the Infrared Imaging of Calcium Phosphates.

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 and 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 ß-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.

Hydroxyapatite as a biomaterial - a gift that keeps on giving.

The synthetic analogue to biogenic apatite, hydroxyapatite (HA) has a number of physicochemical properties that make it an attractive candidate for diagnosis, treatment of disease and augmentation of biological tissues. Here we describe some of the recent studies on HA, which may provide bases for a number of new medical applications. The content of this review is divided to different medical application modes utilizing HA, including tissue engineering, medical implants, controlled drug delivery, gene therapies, cancer therapies and bioimaging. A number of advantages of HA over other biomaterials emerge from this discourse, including (i) biocompatibility, (ii) bioactivity, (iii) relatively simple synthesis protocols for the fabrication of nanoparticles with specific sizes and shapes, (iv) smart response to environmental stimuli, (v) facile functionalization and surface modification through noncovalent interactions, and (vi) the capacity for being simultaneously loaded with a wide range of therapeutic agents and switched to bioimaging modalities for uses in theranostics. A special section is dedicated to analysis of the safety of particulate HA as a component of parenterally administrable medications. It is concluded that despite the fact that many benefits come with the usage of HA, its deficiencies and potential side effects must be addressed before the translation to the clinical domain is pursued. Although HA has been known in the biomaterials world as the exemplar of safety, this safety proves to be the function of size, morphology, surface ligands and other structural and compositional parameters defining the particles. For this reason, each HA, especially when it comes in a novel structural form, must be treated anew from the safety research angle before being allowed to enter the clinical stage.

Waiting for Aπαταω: 250 Years Later.

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.

Insights into the kinetics of thermally induced crystallization of amorphous calcium phosphate.

Transformations between amorphous and crystalline apatite mechanistically govern some of the most essential processes in bone metabolism, including biomineralization and bone remodeling. Fundamental understanding of this phase transition can help us gain control over the formation and dissolution of boney tissues in vivo and utilize that knowledge for various therapeutic ends. Crystallization of hydroxyapatite (HAp) and two tricalcium phosphate (TCP) polymorphs from the metastable precursor, amorphous calcium phosphate (ACP) was here studied kinetically and mechanistically using thermal analyses, X-ray diffraction and Fourier-transform infrared spectroscopy. Crystallization was detected in the differential thermal analysis as the exothermic peak at 639.5 °C at the slowest heating regimen of 5 °C min-1, while a combination of different kinetics models, including Augis-Bennett, Borchardt-Daniels, Johnson-Mehl-Avrami, Kissinger, Ozawa and Piloyan, yielded activation energies in the 435-450 kJ mol-1 range. Dehydrated ACP required a significant energy input to transform to HAp, thus indirectly proving the key role that structural water plays in this process in a biological setting. The phase transformation at high temperatures involved preformed nuclei and was solely due to their 3D growth, contrasting the edge-controlled nucleation derived earlier as the mechanism of growth in the solution. Crystallization was in both cases accompanied by the formation of needle-shape crystals of HAp through aggregation of ultrafine spherical units of ACP. Relationship between crystallinity and the heating rate was detected only for the initially amorphous structure, indicating a more intense and coherent lattice ordering process in annealed ACP than in HAp. Despite that, crystallization disobeyed the rule of inverse proportionality between the thermal energy required for the relaxation of defects and the level of strain, as the recovery rate of the initially poorly crystalline HAp was higher than that of ACP.

Is there a relationship between solubility and resorbability of different calcium phosphate phases in vitro?

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), ß-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.

Amelogenin in Enamel Tissue Engineering.

In this chapter the basic premises, the recent findings and the future challenges in the use of amelogenin for enamel tissue engineering are being discoursed on. Results emerging from the experiments performed to assess the fundamental physicochemical mechanisms of the interaction of amelogenin, the main protein of the enamel matrix, and the growing crystals of apatite, are mentioned, alongside a moderately comprehensive literature review of the subject at hand. The clinical importance of understanding this protein/mineral interaction at the nanoscale are highlighted as well as the potential for tooth enamel to act as an excellent model system for studying some of the essential aspects of biomineralization processes in general. The dominant paradigm stating that amelogenin directs the uniaxial growth of apatite crystals in enamel by slowing down the growth of (hk0) faces on which it adheres is being questioned based on the results demonstrating the ability of amelogenin to promote the nucleation and crystal growth of apatite under constant titration conditions designed to mimic those present in the developing enamel matrix. The role of numerous minor components of the enamel matrix is being highlighted as essential and impossible to compensate for by utilizing its more abundant ingredients only. It is concluded that the three major aspects of amelogenesis outlined hereby--(1) the assembly of amelogenin and other enamel matrix proteins, (2) the proteolytic activity, and (3) crystallization--need to be in precise synergy with each other in order for the grounds for the proper imitation of amelogenesis in the lab to be created.

Toward chronopharmaceutical drug delivery patches and biomaterial coatings for the facilitation of wound healing.

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.

Polymeric Nanoparticles for Wound Healing.

Skin injury is one of the most prevalent lesions in humans, and many such wounds, including deep burns and chronic skin wounds, are notoriously difficult to heal. It has been established by medical practitioners that current wound therapies are not perfectly effective and are far from satisfactory. Meanwhile, nanotechnologies have made it possible to develop pharmaceutical formulations that can elevate the effectiveness of conventional pharmacotherapies to entirely new heights. Most nanostructured biomaterials used to treat wounds, including those that have helped establish this fascinating subject, have been polymeric. The bibliographic analysis presented here shows a steady growth in the research output of studies on the use of polymeric nanoparticles in wound healing therapies. This article provides an overview of polymeric nanoparticles for the treatment of wounds with an emphasis on different chemistries and polymer-drug combinations that have been proven the most effective. The wound age, pathophysiology, wound healing treatments of the present and past, as well as the physicochemical nature and methods for the synthesis of polymeric nanoparticles, are all covered in the opening parts of the review. The existing polymeric nano-drug delivery systems with the greatest promise for wound healing and skin regeneration are subsequently addressed and their potentials summarized.

Nanoparticles of cobalt-substituted hydroxyapatite in regeneration of mandibular osteoporotic bones.

Indications exist that paramagnetic calcium phosphates may be able to promote regeneration of bone faster than their regular, diamagnetic counterparts. In this study, analyzed was the influence of paramagnetic cobalt-substituted hydroxyapatite nanoparticles on osteoporotic alveolar bone regeneration in rats. Simultaneously, biocompatibility of the material was tested in vitro, on osteoblastic MC3T3-E1 and epithelial Caco-2 cells in culture. The material was shown to be biocompatible and nontoxic when added to epithelial monolayers in vitro, while it caused a substantial decrease in the cell viability as well as deformation of the cytoskeleton and cell morphology when incubated with the osteoblastic cells. In the course of 6 months after the implantation of the material containing different amounts of cobalt, ranging from 5 to 12 wt%, in the osteoporotic alveolar bone of the lower jaw, the following parameters were investigated: histopathological parameters, alkaline phosphatase and alveolar bone density. The best result in terms of osteoporotic bone tissue regeneration was observed for hydroxyapatite nanoparticles with the largest content of cobalt ions. The histological analysis showed a high level of reparatory ability of the nanoparticulate material implanted in the bone defect, paralleled by a corresponding increase in the alveolar bone density. The combined effect of growth factors from autologous plasma admixed to cobalt-substituted hydroxyapatite was furthermore shown to have a crucial effect on the augmented osteoporotic bone regeneration upon the implantation of the biomaterial investigated in this study.

Supplementation of Polymeric Reservoirs with Redox-Responsive Metallic Nanoparticles as a New Concept for the Smart Delivery of Insulin in Diabetes.

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.

Natural sciences and chess: A romantic relationship missing from higher education curricula.

Chess is a game that delicately weaves analytical thinking around artistic experience, yet recent conversions of STEM (Science-Technology-Engineering-Mathematics) to STEAM (Science-Technology-Engineering-Art-Mathematics) have omitted adding chess as an elementary coursework to K-12 and higher education curricula. Chess, as per arguments presented in this essay, can be considered as a language and a tool for furthering the development of artistic skills among scientists and analytical, pattern-recognition skills among artists. It can also serve as a missing link between science and art in STEAM curricula thanks to its finding itself halfway between the two. A handful of analogies are drawn here from chess, illustrated sporadically with positions from real-life chess games and converted to lessons in creativity for students in natural sciences. The discussion centered around these analogies is reinforced by a literature review of studies conducted over the past 80 years to assess the effect of exposing students to lessons in chess on their learning in distant domains. Overall, great benefits can emerge from complementing science education with chess and it is hoped that chess will become an integral part of basic education in primary schools and universities worldwide in the near future.

Lessons from the history of inorganic nanoparticles for inhalable diagnostics and therapeutics.

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.

Grand Challenges in Materials Science: A Special Issue.

Materials science has and will continue to be a science at a crossroads [...].

Tunable Release of Calcium from Chitosan-Coated Bioglass.

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.