Optically active vinyl polymers containing fluorescent groups, 2. Synthesis of optically active vinyl carbazole derivatives

Synthesis and characterization of (S)-3-sec-butyl-9-vinylcarbazole ( 7 ), (S)-9-(2-methylbutyl)-2-vinylcarbazole ( 14 ), and (S)-9-(2-methylbutyl)-3-vinylcarbazole ( 18 ) are described in detail.     

Synthesis and Characterization of Segmented Poly(ether ester)s Containing H‐Bonding Units

A series of poly(ether ester)s containing different H‐bonding units (amide, carbamate, urea) was prepared by polycondensation in bulk, using Ti(OBu)₄ as a catalyst. The copolymers were obtained starting from PEG1000, 1,4‐butanediol, and a symmetrical, bis‐ester terminated monomer carrying H‐bonding units. These materials were designed for biomedical applications, in which ultimate biodegradability of the materials is required. The influence of the nature of the H‐bonding unit and of the length of the methylene spacer between H‐bonding groups on the thermal and solubility properties of copolymers was investigated. Amide containing copolymers were more thermally stable than ones containing carbamate, consistent with the observed behavior of the corresponding monomers. In most cases, differential scanning calorimetry (DSC) traces were quite complex because of phase separation and dependent on the applied cooling rate. Copolymers containing urea bonds were less soluble in most organic solvents, but their thermal properties were not significantly different than their amide containing counterparts.

Synthesis of amide‐based diester monomers.     

Additive manufacturing techniques for the production of tissue engineering constructs

‘Additive manufacturing’ (AM) refers to a class of manufacturing processes based on the building of a solid object from three‐dimensional (3D) model data by joining materials, usually layer upon layer. Among the vast array of techniques developed for the production of tissue‐engineering (TE) scaffolds, AM techniques are gaining great interest for their suitability in achieving complex shapes and microstructures with a high degree of automation, good accuracy and reproducibility. In addition, the possibility of rapidly producing tissue‐engineered constructs meeting patient's specific requirements, in terms of tissue defect size and geometry as well as autologous biological features, makes them a powerful way of enhancing clinical routine procedures. This paper gives an extensive overview of different AM techniques classes (i.e. stereolithography, selective laser sintering, 3D printing, melt–extrusion‐based techniques, solution/slurry extrusion‐based techniques, and tissue and organ printing) employed for the development of tissue‐engineered constructs made of different materials (i.e. polymeric, ceramic and composite, alone or in combination with bioactive agents), by highlighting their principles and technological solutions. Copyright © 2012 John Wiley & Sons, Ltd.     

Distribution of exogenous [125I]-3-iodothyronamine in mouse in vivo: relationship with trace amine-associated receptors

3-Iodothyronamine (T1AM) is a novel chemical messenger, structurally related to thyroid hormone, able to interact with G protein-coupled receptors known as trace amine-associated receptors (TAARs). Little is known about the physiological role of T1AM. In this prospective, we synthesized [125I]-T1AM and explored its distribution in mouse after injecting in the tail vein at a physiological concentration (0.3?nM). The expression of the nine TAAR subtypes was evaluated by quantitative real-time PCR. [125I]-T1AM was taken up by each organ. A significant increase in tissue vs blood concentration occurred in gallbladder, stomach, intestine, liver, and kidney. Tissue radioactivity decreased exponentially over time, consistent with biliary and urinary excretion, and after 24?h, 75% of the residual radioactivity was detected in liver, muscle, and adipose tissue. TAARs were expressed only at trace amounts in most of the tissues, the exceptions being TAAR1 in stomach and testis and TAAR8 in intestine, spleen, and testis. Thus, while T1AM has a systemic distribution, TAARs are only expressed in certain tissues suggesting that other high-affinity molecular targets besides TAARs exist.     

Design,Preparation, and Characterization of Thermoresponsive Hybrid Nanogels Using a Novel Ulvan‐Acrylate Crosslinker as Potential Carriers for Protein Encapsulation

The aim of the present study is the design and development of thermoresponsive nanogels based on ulvan, a sulphated heteropolysaccharide of algal origins with unique biological and chemical properties. Hybrid nanogels are successfully synthesized by means of UV‐initiated radical copolymerization of N‐vinylcaprolactam with an ulvan derivate as a novel crosslinker. In nanogels, the ulvan‐grafted poly(N‐vinylcaprolactam) chains represent the thermoresponsive component. The most promising candidates, selected after a thorough physical–chemical characterization of nanogels in terms of size and responsivity to thermal variation at physiological conditions, are loaded with bovine serum albumin (BSA) as model bioactive compound. The developed nanogels display BAS loading efficiency values similar to those obtained by using synthetic crosslinkers, and thus indicating the suitability of the developed ulvan‐acrylate to act as novel macromolecular crosslinker for thermoresponsive nanogels preparation.     

Additive manufacturing of poly[(R)‐3‐hydroxybutyrate‐co‐(R)‐3‐hydroxyhexanoate] scaffolds for engineered bone development

A wide range of poly(hydroxyalkanoate)s (PHAs), a class of biodegradable polyesters produced by various bacteria grown under unbalanced conditions, have been proposed for the fabrication of tissue‐engineering scaffolds. In this study, the manufacture of poly[(R)‐3‐hydroxybutyrate‐co‐(R)‐3‐hydroxyhexanoate] (or PHBHHx) scaffolds, by means of an additive manufacturing technique based on a computer‐controlled wet‐spinning system, was investigated. By optimizing the processing parameters, three‐dimensional scaffolds with different internal architectures were fabricated, based on a layer‐by‐layer approach. The resulting scaffolds were characterized by scanning electron microscopy, which showed good control over the fibre alignment and a fully interconnected porous network, with porosity in the range 79–88%, fibre diameter 47–76 µm and pore size 123–789 µm. Moreover, the resulting fibres presented an internal porosity connected to the external fibre surface as a consequence of the phase‐inversion process governing the solidification of the polymer solution. Scaffold compressive modulus and yield stress and strain could be varied in a certain range by changing the architectural parameters. Cell‐culture experiments employing the MC3T3‐E1 murine pre‐osteoblast cell line showed good cell proliferation after 21 days of culture. The PHBHHx scaffolds demonstrated promising results in terms of cell differentiation towards an osteoblast phenotype. Copyright © 2014 John Wiley & Sons, Ltd.     

RGD‐mimic polyamidoamine–montmorillonite composites with tunable stiffness as scaffolds for bone tissue‐engineering applications

This paper reports on the development of montmorillonite (MMT)‐reinforced hydrogels, based on a peptidomimetic polyamidoamine carrying guanidine pendants (AGMA1), as substrates for the osteo‐induction of osteoblast precursor cells. AGMA1 hydrogels of various degrees of crosslinking responded favourably to MMT reinforcement, giving rise to composite hydrogels with shear storage modulus G′, when fully swollen in water, up to 200 kPa, i.e. 20 times higher than the virgin hydrogels and of the same order or higher than other hydrogel‐based composites proposed for orthopaedic applications. This significant improvement was ascribed to the effective interpenetration between the polymer matrix and the inorganic filler. AGMA1–MMT hydrogels, when evaluated as scaffolds for the osteogenic differentiation of mouse calvaria‐derived pre‐osteoblastic MC3T3‐E1 cells, proved able to support cell adhesion and proliferation and clearly induced differentiation towards the osteoblastic phenotype, as indicated by different markers. In addition, AGMA1–MMT hydrogels proved completely degradable in aqueous media at pH 7.4 and did not provide any evidence of cytotoxicity. The experimental evidence suggests that AGMA1–MMT composites definitely warrant potential as scaffolds for osteoblast culture and bone grafts. Copyright © 2016 John Wiley & Sons, Ltd.     

Synthesis and properties of co-isotactic copolymers of functional vinyl aromatic monomers with chiral α-olefins

Optically active co-isotactic copolymers of α-olefins, like (R)-3,7-dimethyl-1-octene ( 1 ) or (S)-4-methyl-1-hexene ( 2 ), with functional para-substituted styrenes were obtained by both copolymerization in the presence of Ziegler-Natta catalysts and by chemical modification of the copolymers of styrene ( 5 ) with 1 or 2 . By the first mentioned route copolymers of 4-iodostyrene ( 3 ) and propyl 4-vinylbenzenesulfonate ( 4 ) were prepared in satisfying yields. Fractionation by solvent extraction as well as the physical properties of the polymeric products, guarantee for the formation of co-isotactic copolymer macromolecules. By the other route co-isotactic copolymers of 1 or 2 with several para-substituted styrenes (like 4-halo, 4-chloromethyl, 4-diphenylphosphino, 4-diphenylphosphinomethyl, and 4-alkylammoniomethyl chloride derivatives) were prepared under conditions which do not give appreciable racemization of the chiral centers present in the main chain as well as in the lateral chain of the starting copolymers of styrene with α-olefins. The reported data provide a useful way to attain stereoregular and chiral macromolecular materials, bearing either electron donor or chemically active functional groups, inserted in a highly homogeneous conformational environment.