Mesoporous bioactive glasses. I. Synthesis and structural characterization

Highly ordered mesoporous bioactive glasses (MBGs) with different compositions have been synthesized by a combination of surfactant templating, sol-gel method and evaporation-induced self-assembly (EISA) processes. The texture properties and compositional homogeneity of MBGs have been characterized and compared with conventional bioactive glasses (BGs) synthesized in the absence of surfactants by evaporation method. The formation mechanism (pore - composition dependence) and compositional homogeneity in the case of MBG materials are different from those in conventional BGs. Unlike conventional sol-gel-derived BGs that shows a direct correlation between their composition and pore architecture, MBGs with different compositions may possess similar pore volume and uniformly distributed pore size when the same structure-directing agent is utilized. The framework of MBG is homogeneously distributed in composition at the nanoscale and the inorganic species generally exists in the form of amorphous phase. MBGs calcined at temperatures

Mesoporous nanocrystalline zirconia with lamellar and MSU structure

Without introduction of any stabilizer, the mesoporous nanocrystalline zirconia with lamellar and MSU structure was obtained via solid state reaction coupled with surfactant templating method. The phase, surface area and pore structure of zirconia prepared with this novel method could be designed, tailored and controlled by varying synthesis parameters. The phase transformation was controlled by particle size. The mesostructure possesses nanocrystalline pore wall, which renders it more thermally stable than amorphous framework. The results suggest strongly that in solid state synthesis system mesostructure formation still follow the supramolecular self-assembly mechanism. The lamellar and reverse hexagonal structure could be transformed at different OH-/Zr molar ratios in order to sustain the low surface energy of the mesophases. The lamellar structure was preferred at higher OH-/Zr molar ratios but reverse hexagonal was at low ratios.

Comparative Analysis of Structural and Morphological Properties of Large-Pore Periodic Mesoporous Organosilicas and Pure Silicas

A systematic study on the structural properties and external morphologies of large-pore mesoporous organosilicas synthesized using triblock copolymer EO20PO70EO20 as a template under low-acid conditions was carried out. By employing the characterization techniques of SAXS, FE-SEM, and physical adsorption of N-2 in combination with alpha(s)-plot method, the structural properties and external morphologies of large-pore mesoporous organosilicas were critically examined and compared with that of their pure-silica counterparts synthesized under similar conditions. It has been observed that unlike mesoporous pure silicas, the structural and morphological properties of mesoporous organosilicas are highly acid-sensitive. High-quality mesoporous organosilicas can only be obtained from synthesis gels with the molar ratios of HCl/H2O between 7.08 x 10(-4) and 6.33 x 10(-3), whereas mesoporous pure silicas with well-ordered structure can be obtained in a wider range of acid concentration. Simply by adjusting the HCl/H2O molar ratios, the micro-, meso-, and macroporosities of the organosilica materials can be finely tuned without obvious effect on their structural order. Such a behavior is closely related to their acid-controlled morphological evolution: from necklacelike fibers to cobweb-supported pearl-like particles and to nanosized particulates.

Towards the preparative and large-scale precision manafacture of virus-like particles

Virus-like particles (VLPs) are of interest in vaccination, gene therapy and drug delivery, but their potential has yet to be fully realized. This is because existing laboratory processes, when scaled, do not easily give a compositionally and architecturally consistent product. Research suggests that new process routes might ultimately be based on chemical processing by self-assembly, involving the precision manufacture of precursor capsomeres followed by in vitro VLP self-assembly and scale-up to required levels. A synergistic interaction of biomolecular design and bioprocess engineering (i.e. biomolecular engineering) is required if these alternative process routes and, thus, the promise of new VLP products, are to be realized.

Biomolecular engineering at interfaces

A broad review of technologically focused work concerning biomolecules at interfaces is presented. The emphasis is on developments in interfacial biomolecular engineering that may have a practical impact in bioanalysis, tissue engineering, emulsion processing or bioseparations. We also review methods for fabrication in an attempt to draw out those approaches that may be useful for product manufacture, and briefly review methods for analysing the resulting interfacial nanostructures. From this review we conclude that the generation of knowledge and-innovation at the nanoscale far exceeds our ability to translate this innovation into practical outcomes addressing a market need, and that significant technological challenges exist. A particular challenge in this translation is to understand how the structural properties of biomolecules control the assembled architecture, which in turn defines product performance, and how this relationship is affected by the chosen manufacturing route. This structure-architecture-process-performance (SAPP) interaction problem is the familiar laboratory scale-up challenge in disguise. A further challenge will be to interpret biomolecular self- and directed-assembly reactions using tools of chemical reaction engineering, enabling rigorous manufacturing optimization of self-assembly laboratory techniques. We conclude that many of the technological problems facing this field are addressable using tools of modem chemical and biomolecular engineering, in conjunction with knowledge and skills from the underpinning sciences. (c) 2005 Elsevier Ltd. All rights reserved.

Molecular dynamics simulations of the hydrophobin SC3 at a hydrophobic/hydrophilic interface

Hydrophobins are small (similar to 100 aa) proteins that have an important role in the growth and development of mycelial fungi. They are surface active and, after secretion by the fungi, self-assemble into amphipathic membranes at hydrophobic/hydrophilic interfaces, reversing the hydrophobicity of the surface. In this study, molecular dynamics simulation techniques have been used to model the process by which a specific class I hydrophobin, SC3, binds to a range of hydrophobic/ hydrophilic interfaces. The structure of SC3 used in this investigation was modeled based on the crystal structure of the class II hydrophobin HFBII using the assumption that the disulfide pairings of the eight conserved cysteine residues are maintained. The proposed model for SC3 in aqueous solution is compact and globular containing primarily P-strand and coil structures. The behavior of this model of SC3 was investigated at an air/water, an oil/water, and a hydrophobic solid/water interface. It was found that SC3 preferentially binds to the interfaces via the loop region between the third and fourth cysteine residues and that binding is associated with an increase in a-helix formation in qualitative agreement with experiment. Based on a combination of the available experiment data and the current simulation studies, we propose a possible model for SC3 self-assembly on a hydrophobic solid/water interface.

Reversible active switching of the mechanical properties of a peptide film at a fluid-fluid interface

Designer peptides have recently been developed as building blocks for novel self-assembled materials with stimuli-responsive properties. To date, such materials have been based on self-assembly in bulk aqueous solution or at solid-fluid interfaces. We have designed a 21-residue peptide, AM1, as a stimuli-responsive surfactant that switches molecular architectures at a fluid-fluid interface in response to changes in bulk aqueous solution composition. In the presence of divalent zinc at neutral pH, the peptide forms a mechanically strong 'film state'. In the absence of metal ions or at acid pH, the peptide adsorbs to form a mobile 'detergent state'. The two interfacial states can be actively and reversibly switched. Switching between the two states by a change in pH or the addition of a chelating agent leads to rapid emulsion coalescence or foam collapse. This work introduces a new class of surfactants that offer an environmentally friendly approach to control the stability of interfaces in foams, emulsions and fluid-fluid interfaces more generally.

Visible light photocatalyst: Iodine-doped mesoporous titania with a bicrystalline framework

Iodine-doped (I-doped) mesoporous titania with a bicrystalline (anatase and rutile) framework was synthesized by a two-step template hydrothermal synthesis route. I-doped titania with anatase structure was also synthesized without the use of a block copolymer as a template. The resultant titania samples were characterized by X-ray diffraction, Raman spectroscopy, Fourier transform infrared, nitrogen adsorption, transmission electron microscopy, X-ray photoelectron spectroscopy, and UV-visible absorption spectroscopy. Both I-doped titania samples, with and without template, show much better photocatalytic activity than commercial P25 titania in the photodegradation of methylene blue under the irradiation of visible light (> 420 nm) and UV-visible light. Furthermore, I-doped mesoporous titania with a bicrystalline framework exhibits better activity than I-doped titania with anatase structure. The effect of rutile phase in titania on the adsorptive capacity of water and surface hydroxyl, and photocatalytic activity was investigated in detail. The excellent performance of I-doped mesoporous titania under both visible light and UV-visible light can be attributed to the combined effects of bicrystalline framework, high crystallinity, large surface area, mesoporous structure, and high visible light absorption induced by I-doping.

Generic Technique to Generate Large Branched DNA Complexes

The inherent self-recognition properties of DNA have led to its use as a scaffold for various nanotechnology self-assembly applications, with macromolecular complexes, metallic and semiconducting nanoparticles, proteins, inter alia, being assembled onto a designed DNA scaffold. Such structures may typically comprise a number of DNA molecules organized into macromolecules. Many studies have used synthetic methods to produce the constituent DNA molecules, but this typically constrains the molecules to be no longer than around 100 base pairs (30 nm). However, applications that require larger self-assembling DNA complexes, several tens of nanometers or more, need to be generated by other techniques. Here, we present a generic technique to generate large linear, branched, and/or circular DNA macromolecular complexes. The effectiveness of this technique is demonstrated here by the use of Lambda Bacteriophage DNA as a template to generate single- and double-branched DNA structures approximately 120 nm in size.

A blank slate? Layer-by-layer deposition of hyaluronic acid and chitosan onto various surfaces

Although poly(alpha-hydroxy esters), especially the PLGA family of lactic acid/glycolic acid copolymers, have many properties which make them promising materials for tissue engineering, the inherent chemistry of surfaces made from these particular polymers is problematic. In vivo, they promote a strong foreign-body response as a result of nonspecific adsorption and denaturation of serum proteins, which generally results in the formation of a nonfunctional fibrous capsule. Surface modification post-production of the scaffolds is an often-utilized approach to solving this problem, conceptually allowing the formation of a scaffold with mechanical properties defined by the bulk material and molecular-level interactions defined by the modified surface properties. A promising concept is the so-called blank slate: essentially a surface that is rendered resistant to nonspecific protein adsorption but can be readily activated to covalently bind bio-functional molecules such as extracellular matrix proteins, growth factors or polysaccharides. This study focuses on the use of the quartz crystal microbalance (QCM) to follow the layer-by-layer (LbL) electrostatic deposition of high molecular weight hyaluronic acid and chitosan onto PLGA surfaces rendered positively charged by aminolysis, to form a robust, protein-resistant coating. We further show that this surface may be further functionalized via the covalent attachment of collagen IV, which may then be used as a template for the self-assembly of basement membrane components from dilute Matrigel. The response of NIH-3T3 fibroblasts to these surfaces was also followed and shown to closely parallel the results observed in the QCM.

Prophylactic HPV vaccines: Underlying mechanisms

Human papillomavirus virus-like particles (HPV VLP) can be generated by the synthesis and self-assembly in vitro of the major virus capsid protein L1. HPV L1 VLPs are morphologically and antigenically almost identical to native virions, and this technology has been exploited to produce HPV L1 VLP subunit vaccines. The vaccines elicit high titres of anti-L I VLP antibodies that persist at levels 10 times that of natural infections for at least 48 months. At present the assumption is that the protection achieved by these vaccines against incident HPV infection and HPV-associated ano-genital pathology is mediated via serum neutralising Immunoglobulin G (IgG). However, since there have been very few vaccine failures thus far, immune correlates of protection have not been established. The available evidence is that the immunodominant neutralising antibodies generated by L1 VLPs are type-specific and are not cross-neutralising, although highly homologous HPV pairs share minor cross-neutralisation epitopes. Important issues remaining to be addressed include the duration of protection and genotype replacement. (c) 2006 Elsevier Ltd. All rights reserved.

Continental extension: From core complexes to rigid block faulting

Extension of overthickened continental crust is commonly characterized by an early core complex stage of extension followed by a later stage of crustal-scale rigid block faulting. These two stages are clearly recognized during the extensional destruction of the Alpine orogen in northeast Corsica, where rigid block faulting overprinting core complex formation eventually led to crustal separation and the formation of a new oceanic backarc basin (the Ligurian Sea). Here we investigate the geodynamic evolution of continental extension by using a novel, fully coupled thermomechanical numerical model of the continental crust. We consider that the dynamic evolution is governed by fault weakening, which is generated by the evolution of the natural-state variables (i.e., pressure, deviatoric stress, temperature, and strain rate) and their associated energy fluxes. Our results show the appearance of a detachment layer that controls the initial separation of the brittle crust on characteristic listric faults, and a core complex formation that is exhuming strongly deformed rocks of the detachment zone and relatively undeformed crustal cores. This process is followed by a transitional period, characterized by an apparent tectonic quiescence, in which deformation is not localized and energy stored in the upper crust is transferred downward and causes self-organized mobilization of the lower crust. Eventually, the entire crust ruptures on major crosscutting faults, shifting the tectonic regime from core complex formation to wholesale rigid block faulting.

PFG-NMR measurements of the self-diffusion coefficients of water in equilibrium poly(HEMA-co-THFMA) hydrogels

The self-diffusion coefficients for water in a series of copolymers of 2-hydroxyethyl methacrylate, HEMA, and tetrahydrofurfuryl methacrylate, THFMA, swollen with water to their equilibrium states have been studied at 310 K using PFG-NMR. The self-diffusion coefficients calculated from the Stejskal-Tanner equation, D-obs, for all of the hydrated polymers were found to be dependent on the NMR storage time, as a result of spin exchange between the proton reservoirs of the water and the polymers, reaching an equilibrium plateau value at long storage times. The true values of the diffusion coefficients were calculated from the values of D-obs, in the plateau regions by applying a correction for the fraction of water protons present, obtained from the equilibrium water contents of the gels. The true self-diffusion coefficient for water in polyHEMA obtained at 310 K by this method was 5.5 x 10(-10) m(2) s(-1). For the copolymers containing 20% HEMA or more a single value of the self-diffusion coefficient was found, which was somewhat larger than the corresponding values obtained for the macroscopic diffusion coefficient from sorption measurements. For polyTHFMA and copolymers containing less than 20% HEMA, the PFG-NMR stimulated echo attenuation decay curves and the log-attenuation plots were characteristic of the presence of two diffusing water species. The self-diffusion coefficients of water in the equilibrium-hydrated copolymers were found to be dependent on the copolymer composition, decreasing with increasing THFMA content.

Assembly of Human Papillomavirus Type-16 Virus-Like Particles: Multifactorial Study of Assembly and Competing Aggregation

Pentameric capsomeres of human papillomavirus capsid protein L1 expressed in Escherichia coli self-assemble into virus-like particles (VLPs) in vitro. A multifactorial experimental design was used to explore a wide range of solution conditions to optimize the assembly process. The degree of assembly was measured using an enzyme-linked immunosorbent assay, and a high-throughput turbidity assay was developed to monitor competing aggregation. The presence of zinc ions in the assembly buffer greatly increased the incidence of aggregation and had to be excluded from the experiment for meaningful analysis. Assembly of VLPs was optimal at a pH of about 6.5, calcium and sodium ions had no measurable effect, and dithiothreitol and glutathione inhibited assembly. Tryptophan fluorescence spectroscopy demonstrated that an increase in urea concentration reduced the rate of VLP formation but had no effect on the final concentration of assembled VLPs. This study demonstrates the use of the hanging-drop vapor-diffusion crystallization method to screen for conditions that promote aggregation and the use of tryptophan fluorescence spectroscopy for real-time monitoring of the assembly process.