Development and Characterization of Novel Biomimetic Composite Scaffolds Based on Bioglass‐Collagen‐Hyaluronic Acid‐Phosphatidylserine for Tissue Engineering Applications

Summary: Biomimetic scaffolds are appealing products for the repair of bone defects using tissue engineering strategies. The present study prepared novel biomimetic composite scaffolds with similar composite to natural bone using bioactive glass, collagen, hyaluronic acid, and phosphatidylserine. The microstructure, swelling ratio, biodegradability, and biomineralization characteristic of the composite scaffolds with and without hyaluronic acid and phosphatidylserine were compared and analyzed by SEM/EDAX, XRD, and FTIR techniques and in vitro test, and the properties can be influenced by 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide (EDC)/N‐hydroxysuccinimide (NHS) crosslinking. The optimized properties of the crosslinked composite scaffolds observed in this study show the possibility of their use of bioactive and bioresorbable scaffolds in bone tissue engineering.

SEM micrographs of BG‐COL‐HYA‐PS composite scaffolds after immersion in SBF for 1 d.     

Fabrication of Polylactide‐Based Biodegradable Thermoset Scaffolds for Tissue Engineering Applications

The fabrication of tissue engineering scaffolds based on the polymerization of crosslinked polylactide using leaching and batch foaming to generate well‐controlled and interconnected biodegradable polymer scaffolds is reported. The scaffold fabrication parameters are studied in relation to the interpore connectivity, pore morphology, and structural stability of the crosslinked PLA scaffold. In vitro cell culture and in vitro degradation are used to analyze the biocompatibility and biodegradability of the scaffolds. The new crosslinked PLA thermoset scaffolds are highly suitable for bone tissue engineering applications due to their complex internal architecture, thermal stability, and biocompatibility.

     

The Cyclic Cystine Ladder of Theta‐Defensins as a Stable,Bifunctional Scaffold: A Proof‐of‐Concept Study Using the Integrin‐Binding RGD Motif.

Peptides have the specificity and size required to target the protein–protein interactions involved in many diseases. Some cyclic peptides have been utilised as scaffolds for peptide drugs because of their stability; however, other cyclic peptide scaffolds remain to be explored. θ‐Defensins are cyclic peptides from mammals; they are characterised by a cyclic cystine ladder motif and have low haemolytic and cytotoxic activity. Here we demonstrate the potential of the cyclic cystine ladder as a scaffold for peptide drug design by introducing the integrin‐binding Arg‐Gly‐Asp (RGD) motif into the θ‐defensin RTD‐1. The most active analogue had an IC₅₀ of 18 nM for the α_vβ₃ integrin as well as high serum stability, thus demonstrating that a desired bioactivity can be imparted to the cyclic cystine ladder. This study highlights how θ‐defensins can provide a stable and conformationally restrained scaffold for bioactive epitopes in a β‐strand or turn conformation. Furthermore, the symmetry of the cyclic cystine ladder presents the opportunity to design peptides with dual bioactive epitopes to increase activity and specificity.     

A method for determination of time‐ and temperature‐dependences of stress threshold of linear–nonlinear viscoelastic transition: Energy‐Based Approach

A methodology for determination of time‐ and temperature‐dependences of stress threshold of linear–nonlinear viscoelastic transition is proposed and validated by example of uniaxial creep of epoxy resin. Energy approach is applied for characterization of the region of linear viscoelasticity (LVE) and the threshold of LVE is given in the stress–strain representation as the master curve independent of time and temperature. Time‐ and temperature‐dependences of the stress threshold are calculated by extending LVE theory and time–temperature superposition principles (TTSP) to the energy relations. Reasonable agreement between experimental data and calculations is obtained. It is shown that number of tests required for characterization of LVE region in a wide range of test time and temperatures can be considerably reduced by applying the proposed methodology. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Development and Preliminary Testing of Porcine Blood-Derived Endothelial-like Cells for Vascular Tissue Engineering Applications: Protocol Optimisation and Seeding of Decellularised Human Saphenous Veins

Functional endothelial cells (EC) are a critical interface between blood vessels and the thrombogenic flowing blood. Disruption of this layer can lead to early thrombosis, inflammation, vessel restenosis, and, following coronary (CABG) or peripheral (PABG) artery bypass graft surgery, vein graft failure. Blood-derived ECs have shown potential for vascular tissue engineering applications. Here, we show the development and preliminary testing of a method for deriving porcine endothelial-like cells from blood obtained under clinical conditions for use in translational research. The derived cells show cobblestone morphology and expression of EC markers, similar to those seen in isolated porcine aortic ECs (PAEC), and when exposed to increasing shear stress, they remain viable and show mRNA expression of EC markers similar to PAEC. In addition, we confirm the feasibility of seeding endothelial-like cells onto a decellularised human vein scaffold with approximately 90% lumen coverage at lower passages, and show that increasing cell passage results in reduced endothelial coverage.     

The Tunable Porous Structure of Gelatin–Bioglass Nanocomposite Scaffolds for Bone Tissue Engineering Applications: Physicochemical,Mechanical, and In Vitro Properties

Unidirectional freeze‐casting method is used to fabricate gelatin–bioglass nanoparticles (BGNPs) scaffolds. Transmission electron microscopy (TEM) images show that sol–gel prepared BGNPs are distributed throughout the scaffold with diameters of less than 10 nm. Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetric are used to evaluate the physicochemical properties of BGNPs. Scanning electron microscopy (SEM) micrographs present an oriented porous structure and a homogeneous distribution of BGNPs in the gelatin matrix. The lamellar‐type structure indicates an improvement of mechanical strength and absorption capacity of the scaffolds. Increasing the concentration of BGNPs from 0 to 50 wt% have no noticeable effect on pore orientation, but decreases porosity and pore size distribution. Increase in BGNPs content improves the compressive strength. The absorption and biodegradation rate reduces with augmentation in BGNPs concentration. Bioactivity is evaluated through apatite formation after immersion of the nanocomposites in simulated body fluid and is verified by SEM–energy‐dispersive X‐ray spectroscopy (EDS), an element map analysis, X‐ray powder diffractometer, and FTIR spectrum. SEM images and methyl thiazolyl tetrazolium assay confirm the biocompatibility of scaffolds and the supportive behavior of nanocomposites in cellular spreading. The results show that gelatin–(30 wt%)bioglass nanocomposites have incipient physicochemical and biological properties.     

Effect of Silicone Carbide on the Elastic Properties of Starch‐Based Composites: A Three‐Phase Model

The effect of a rigid filler on the elastic properties of starch‐based composites is investigated. Thermomolding of the targeted composite is conducted using a starch matrix with varying silicone carbide content. Mechanical testing reveals that the composite's Young modulus cannot be rationalized using two‐phase analytical models. The effect of a weak interphase region is highlighted using a finite‐element model that assumes the generation of virtual microstructures. Numerical results are discussed by describing the influence of the structural and interphase parameters on the composite's elastic modulus. Identification of optimal interphase parameters quantitatively demonstrates the weak adhesion between intrinsic phases for all studied filler fractions.

     

Impact of a Stereocentre Inversion in Cyclic Lipodepsipeptides from the Viscosin Group: A Comparative Study of the Viscosinamide and Pseudodesmin Conformation and Self‐Assembly

The viscosin group covers a series of cyclic lipodepsipeptides (CLPs) produced by Pseudomonas bacteria, with a range of biological functions and antimicrobial activities. Their oligopeptide moieties are composed of both L ‐ and D ‐amino acids. Remarkably, the Leu5 amino acid—centrally located in the nonapeptide sequence—is the sole residue found to possess either an L or D configuration, depending on the producing strain. The impact of this D /L switch on the solution conformation was investigated by NMR‐restrained molecular modelling of the epimers pseudodesmin A and viscosinamide A. Although the backbone fold remained unaffected, the D /L switch adjusted the segregation between hydrophobic and hydrophilic residues, and thus the amphipathicity. It also influenced the self‐assembly capacity in organic solvents. Additionally, several new minor variants of viscosinamide A from Pseudomonas fluorescens DR54 were identified, and an NMR assay is proposed to assess the presence of either an L ‐ or D ‐Leu5.     

Lactosamine‐Based Derivatives as Tools to Delineate the Biological Functions of Galectins: Application to Skin Tissue Repair

Galectins have been recognized as potential novel therapeutic targets for the numerous fundamental biological processes in which they are involved. Galectins are key players in homeostasis, and as such their expression and function are finely tuned in vivo. Thus, their modes of action are complex and remain largely unexplored, partly because of the lack of dedicated tools. We thus designed galectin inhibitors from a lactosamine core, functionalized at key C2 and C3′ positions by aromatic substituents to ensure both high affinity and selectivity, and equipped with a spacer that can be modified on demand to further modulate their physico‐chemical properties. As a proof‐of‐concept, galectin‐3 was selectively targeted. The efficacy of the synthesized di‐aromatic lactosamine tools was shown in cellular assays to modulate collective epithelial cell migration and to interfere with actin/cortactin localization.     

Recent Progress on the Design and Applications of Polysaccharide‐Based Graft Copolymer Hydrogels as Adsorbents for Wastewater Purification

Gum polysaccharides are one of the most abundant bio‐based polymers. They are generally derived from plants as exudates or from microorganisms and have diverse applications in many industries, especially in the food industries where they are used as emulsifiers and thickeners. In their natural form, gum polysaccharides have poor mechanical and physical properties; therefore, they are frequently modified with various synthetic monomers such as acrylamide and acrylic acid using graft copolymerization. Graft copolymerization is one of the most trusted and widely used synthetic methods for the modification of gum polysaccharides. Gum polysaccharides modified in this way have improved mechanical and physicochemical properties. Furthermore, gum polysaccharides contain a variety of functional groups, for example, carboxylic acid and hydroxyl groups; therefore, they have been used extensively as adsorbents for the removal of different impurities from wastewater such as toxic heavy metal cations and synthetic dyes. Here, the chemical and physical properties of gum polysaccharides, different methods of graft copolymerization, and the use of graft copolymer gum‐polysaccharide‐based hydrogels are reviewed in detail for the removal of toxic heavy metal cations and synthetic dyes from aqueous solutions.

     

2′‐Bispyrene‐Modified 2′‐O‐Methyl RNA Probes as Useful Tools for the Detection of RNA: Synthesis,Fluorescent Properties,and Duplex Stability

The synthesis and properties two series of new 2′‐O‐methyl RNA probes, each containing a single insertion of a 2′‐bispyrenylmethylphosphorodiamidate derivative of a nucleotide (U, C, A, and G), are described. As demonstrated by UV melting studies, the probes form stable complexes with model RNAs and DNAs. Significant increases (up to 21‐fold) in pyrene excimer fluorescence intensity were observed upon binding of most of the probes with complementary RNAs, but not with DNAs. The fluorescence spectra are independent of the nature of the modified nucleotides. The nucleotides on the 5′‐side of the modified nucleotide have no effect on the fluorescence spectra, whereas the natures of the two nucleotides on the 3′‐side are important: CC, CG, and UC dinucleotide units on the 3′‐side of the modified nucleotide provide the maximum increases in excimer fluorescence intensity. This study suggests that these 2′‐bispyrene‐labeled 2′‐O‐methyl RNA probes might be useful tools for detection of RNAs.     

Aromatic Core Extension in the Series of N‐Cyclic Bay‐Substituted Perylene G‐Quadruplex Ligands: Increased Telomere Damage,Antitumor Activity,and Strong Selectivity for Neoplastic over Healthy Cells

Based on previous work on both perylene and coronene derivatives as G‐quadruplex binders, a novel chimeric compound was designed: N,N′‐bis[2‐(1‐piperidino)‐ethyl]‐1‐(1‐piperidinyl)‐6‐[2‐(1‐piperidino)‐ethyl]‐benzo[ghi]perylene‐3,4:9,10‐tetracarboxylic diimide (EMICORON), having one piperidinyl group bound to the perylene bay area (positions 1, 12 and 6, 7 of the aromatic core), sufficient to guarantee good selectivity, and an extended aromatic core able to increase the stacking interactions with the terminal tetrad of the G‐quadruplex. The obtained “chimera” molecule, EMICORON, rapidly triggers extensive DNA damage of telomeres, associated with the delocalization of telomeric protein protection of telomeres 1 (POT1), and efficiently limits the growth of both telomerase‐positive and ‐negative tumor cells. Notably, the biological effects of EMICORON are more potent than those of the previously described perylene derivative (PPL3C), and more interestingly, EMICORON appears to be detrimental to transformed and tumor cells, while normal fibroblasts expressing telomerase remain unaffected. These results identify a new promising G‐quadruplex ligand, structurally and biologically similar on one side to coronene and on the other side to a bay‐monosubstituted perylene, that warrants further studies.     

Two‐Phase Hydroformylation of Higher Olefins Using Randomly Methylated α‐Cyclodextrin as Mass Transfer Promoter: A Smart Solution for Preserving the Intrinsic Properties of the Rhodium/Trisulfonated Triphenylphosphine Catalytic System

The two‐phase hydroformylation of higher olefins with the rhodium/trisulfonated triphenylphosphine catalytic system in the presence of various chemically modified α‐cyclodextrins has been investigated. These cyclodextrins allowed us to increase greatly the reaction rate and the chemoselectivity of the reaction but, contrary to what has been observed previously with the chemically modified β‐cyclodextrins, the linear to branched aldehydes ratio was not affected by the presence of α‐cyclodextrin derivatives. Indeed, the latter was found to be similar to that obtained without any mass transfer promoter, suggesting that the catalytic species are stable in the presence of α‐cyclodextrin derivatives.     

Porous Silica Beads Supported TEMPO and Adsorbed NOx (PSB‐TEMPO/NOx): An Efficient Heterogeneous Catalytic System for the Oxidation of Alcohols under Mild Conditions

The combination of NO_x gas which is stored in the pore canals of porous silica beads (PSB) with a heterogeneous catalyst, PSB‐supported 2,2,6,6‐tetramethylpiperdine 1‐oxyl (PSB‐TEMPO, 1 ), afforded a highly efficient, widely applicable, and efficiently recyclable approach for the selective aerobic oxidation of alcohols. This novel catalytic system (PSB‐TEMPO/NO_x) can be employed in the oxidation of a wide range of alcohols to their corresponding aldehydes and ketones with selectivities as high as 99% at complete conversions under mild conditions. O₂ is the terminal oxidant. PSB‐TEMPO can be recycled for more than 10 times without significant loss of activity.     

A Crystalline Catalyst Based on a Porous Metal‐Organic Framework and 12‐Tungstosilicic Acid: Particle Size Control by Hydrothermal Synthesis for the Formation of Dimethyl Ether

The strategy for obtaining a crystalline catalyst based on a porous copper‐based metal‐organic framework and 12‐tungstosilicic acid with different particle sizes is reported. Through the control of hydrothermal synthesis and some simple treatments, catalyst samples with average particle diameters of 23, 105, and 450 μm, respectively, were prepared. This crystal catalyst has both the Brønsted acidity of 12‐tungstosilicic acid and the Lewis acidity of the copper‐based metal‐organic framework, and has high density of accessible acid sites. Its catalytic activity was fully assessed in the dehydration of methanol to dimethyl ether. The effect of particle size on the catalytic activity of catalyst was studied, in order to select the particle size appropriate for avoiding the diffusion limitation in heterogeneous gas‐phase catalysis. In the selective dehydration of methanol to dimethyl ether, this catalyst exhibited higher catalytic activity than the copper‐based metal‐organic framework, γ‐alumina, and γ‐alumina‐supported 12‐tungstosilicic acid catalysts. It showed high catalytic performances, even at higher space velocity or in the presence of excess water. In addition, the catalyst was also preliminarily assessed in the formation of ethyl acetate from acetic acid and ethylene. It also exhibited a high activity which was comparable with that of silica‐supported 12‐tungstosilicic acid catalyst.     

Nanostructure and properties of proton‐conducting sulfonated poly(ether ether ketone) (SPEEK) and zirconia–SPEEK hybrid membranes for direct alcohol fuel cells: effect of the nature of swelling solvent and incorporation of heteropolyacid

The influence, on membrane nanostructure and properties, of water or ethanol as swelling solvent of sulfonated poly(ether ether ketone) (SPEEK) and zirconia–SPEEK hybrid membranes prepared using the sol–gel process has been investigated. Independent of the solvent, small‐angle X‐ray scattering measurements reveal the existence of a two‐level hierarchical structure in SPEEK of greater sulfonation level, consisting of solvent‐swelled spatially correlated primary SO₃H‐rich ionic clusters of around 15 Å in size, forming larger secondary aggregates well dispersed in the PEEK matrix. The size of the primary nanodomains and the connectivity between domains are determining parameters for protonic conductivity, solvent swelling ability and permeability of the membranes. For both SPEEK and zirconia–SPEEK membranes containing ethanol, the pronounced affinity of ethanol molecules with SPEEK leads to an increase in the size of ionic clusters and of the number of connecting channels between clusters compared to membranes containing water. This promotes solvent swelling and proton conductivity. The increase in permeability to water induced by incorporation of ethanol in place of water in both polymeric and hybrid membranes is less in the hybrid membranes. This result suggests that the potential use of zirconia–SPEEK hybrid membranes in direct alcohol fuel cells is more promising than that of pure SPEEK, due not only to the less probable alcohol and water penetration in the membranes associated with their lower permeability, but also to the fact that an eventual penetration of alcohol in hybrid membranes should reduce the risk of cathode flooding compared to zirconia‐free SPEEK membranes. Copyright © 2011 Society of Chemical Industry