Lubrication by charged polymers.

Long-ranged forces between surfaces in a liquid control effects from colloid stability to biolubrication, and can be modified either by steric factors due to flexible polymers, or by surface charge effects. In particular, neutral polymer 'brushes' may lead to a massive reduction in sliding friction between the surfaces to which they are attached, whereas hydrated ions can act as extremely efficient lubricants between sliding charged surfaces. Here we show that brushes of charged polymers (polyelectrolytes) attached to surfaces rubbing across an aqueous medium result in superior lubrication compared to other polymeric surfactants. Effective friction coefficients with polyelectrolyte brushes in water are lower than about 0.0006-0.001 even at low sliding velocities and at pressures of up to several atmospheres (typical of those in living systems). We attribute this to the exceptional resistance to mutual interpenetration displayed by the compressed, counterion-swollen brushes, together with the fluidity of the hydration layers surrounding the charged, rubbing polymer segments. Our findings may have implications for biolubrication effects, which are important in the design of lubricated surfaces in artificial implants, and in understanding frictional processes in biological systems.

Stabilized mixed micelles with a temperature-responsive core and a functional shell.

Formation and stabilization of multiresponsive micelles with a mixed poly(ethylene oxide)/polyelectrolyte shell and a temperature-responsive poly(propylene oxide) core were studied. Various poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers were mixed with poly(acrylic acid)-block-poly(propylene oxide)-block-poly(acrylic acid) (PAA-PPO-PAA) or poly(dimethylaminoethyl methacrylate)-block-poly(propylene oxide)-block-poly(dimethylaminoethyl methacrylate) (PDMAEMA-PPO-PDMAEMA) triblock copolymers. The micelles formed by binary mixtures of well-defined compositions at a specific pH were additionally stabilized by loading with pentaerythritol tetraacrylate (PETA), that was polymerized and cross-linked "in situ" with UV assistance. Depending on both the composition of the copolymers and the experimental conditions, either spherical or wormlike "stabilized polymeric micelles with a mixed shell" (SPMMS) were observed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The SPMMS that contained PAA blocks in the shell were pH-sensitive, such that a reversible transition from well-dispersed SPMMS to precipitate could be promoted. In contrast, the SPMMS with a PEO/PDMAEMA mixed shell remained well-dispersed in the 2-11 pH range. Finally, SPMMS were successfully exploited as templates for the preparation of Ag nanoparticles (Ag NPs).

Synthesis of biodegradable poly-epsilon-caprolactone microspheres by dispersion ring-opening polymerization in supercritical carbon dioxide.

A series of fluorinated diblock and triblock copolymers of poly(epsilon-caprolactone) and poly(heptadecafluorodecylacrylate) were prepared by combining ring-opening polymerization of epsilon-CL and atom transfer radical polymerization of the acrylate. These copolymers with well-controlled molecular weight and composition were characterized by (1)H NMR spectroscopy and used as stabilizers for the dispersion ring-opening polymerization of epsilon-CL in supercritical carbon dioxide. The effect of composition and architecture of the polymeric stabilizers on the stabilization of PCL microspheres was investigated. Finally, purification of PCL was successfully implemented by reactive supercritical fluid extraction of the tin catalyst.

Copper bromide complexed by fluorinated macroligands: towards microspheres by ATRP of vinyl monomers in scCO2.

We report the successful synthesis of poly(methyl methacrylate) (PMMA) by atom transfer radical polymerization using a catalyst ligated to a polymeric ligand having a dual role, i.e., the complexation of the copper salt and the stabilization of the growing PMMA particles; at the end of the polymerization, the catalyst is removed by supercritical fluid extraction leading to PMMA microspheres with low residual catalyst content.

Copolymers of epsilon-caprolactone and quaternized epsilon-caprolactone as gene carriers.

New copolymers of epsilon-caprolactone (CL) and gamma-bromo-epsilon-caprolactone quaternized by pyridine (Py+CL) were investigated as non-viral vectors for gene delivery. Copolymers with two molar compositions (50 Py+CL/50 CL and 80 Py+CL/20 CL), each with a diblock or a random structure, were used to prepare nanoparticulate complexes with DNA. Average size and surface charge of the complexes and extent of the complexation were measured. The DNA condensation by the copolymers was analysed by a gel retardation assay. Cytotoxicity and transfection efficiency of the copolymers were also evaluated in HeLa cells and compared with polyethylenimine 50 kDa. The size of the polyplexes was approximately 200 nm. The zeta potential first increased with the copolymer/DNA charge ratio and became positive for charge ratios in the 2-4 range depending on the type of copolymer. DNA was completely condensed within the nanoparticles and the degree of interaction was very high. Cytotoxicity and transfection efficiency were found to be comparable to polyethylenimine 50 kDa. The experimental results suggest that the novel copolymers can be used as novel gene delivery vectors.

Combination of electrografting and layer-by-layer deposition: an efficient way to tailor polymer coatings of (semi)-conductors.

This communication reports on a novel, simple and highly versatile concept, which consists in combining the advantages of two complementary and relevant techniques (i) electrografting and (ii) layer-by-layer deposition process with the goal to tailor strongly adhering coatings to (semi)-conducting surfaces imparting them with tunable specific properties.

PEGylated quaternized copolymer/DNA complexes for gene delivery.

The aim of this study was to improve the colloidal stability, decrease unspecific interactions with cells and blood components of a novel gene delivery system composed of epsilon-caprolactone and quaternized epsilon-caprolactone. For this purpose, diblock 50/50 copolymer was used to generate complexes with DNA by either the solvent evaporation technique and by dialysis. The size, surface charge and degree of interaction of the plasmid-loaded formulations were measured. Then, polyplexes were combined with a poly(CL)-b-PEG copolymer to create a hydrophilic corona on the surface of the complexes. The cytotoxicity, transfection efficiency and cellular uptake of polyplexes and their association with PEG were evaluated on HeLa cells. The dialysis method did not allow to reduce the size of complexes as compared to the solvent evaporation method. The zeta potential of polyplexes became positive from a charge ratio of 4. The degree of interaction of copolymer with plasmid DNA was very high. Cytotoxicity and transfection efficiency were found to be comparable to polyethylenimine 50 kDa. Association of polyplexes with poly(CL)-b-PEG copolymer led to a small increase in particle size and a sharp decrease of charge surface. Cytotoxicity, transfection efficiency and cellular uptake were significantly reduced relative to unshielded copolymer/DNA complexes. The PEGylated formulations may be an attractive approach for an in vivo application.

Simple method for the stretching and alignment of single adsorbed synthetic polycations.

Spin-coating of isolated positively charged macromolecules onto mica in the presence of octylamine was found to be a simple and general method of stretching and aligning the macromolecular chains. The contour length and molar mass for the stretched macromolecules can be directly measured by atomic force microscopy, which makes this method a very useful analytical tool. Moreover, the molecular height is increased by co-deposition with octylamine, which drastically improves the molecular resolution and allows even ultrathin polycations to be visualized. The reason for the key role of the octylamine is found in the formation of an ultrathin liquidlike alkylamine film, which reduces the surface energy of mica and weakens the interactions between the surface and the charged macromolecules.

Poly (D,L-lactic acid) macroporous guidance scaffolds seeded with Schwann cells genetically modified to secrete a bi-functional neurotrophin implanted in the completely transected adult rat thoracic spinal cord.

Freeze-dried poly(D,L-lactic acid) macroporous scaffold filled with a fibrin solution containing Schwann cells (SCs) lentivirally transduced to produce and secrete D15A, a bi-functional neurotrophin with brain-derived neurotrophic factor and neurotrophin-3 activity, and to express green fluorescent protein (GFP) were implanted in the completely transected adult rat thoracic spinal cord. Control rats were similarly injured and then implanted with scaffolds containing the fibrin solution with SCs lentivirally transduced to produce express GFP only or with the fibrin solution only. Transgene production and biological activity in vitro, SC survival within the scaffold in vitro and in vivo, scaffold integration, axonal regeneration and myelination, and hind limb motor function were analyzed at 1, 2, and 6 weeks after implantation. In vitro, lentivirally transduced SCs produced 87.5 ng/24 h/10(6) cells of D15A as measured by neurotrophin-3 activity in ELISA. The secreted D15A was biologically active as evidenced by its promotion of neurite outgrowth of dorsal root ganglion neurons in culture. In vitro, SCs expressing GFP were present in the scaffolds for up to 6 h, the end of a typical surgery session. Implantation of SC-seeded scaffolds caused modest loss of spinal nervous tissue. Reactive astrocytes and chondroitin sulfate glycosaminoglycans were present in spinal tissue adjacent to the scaffold. Vascularization of the scaffold was ongoing at 1 week post-implantation. There were no apparent differences in scaffold integration and blood vessel formation between groups. A decreasing number of implanted (GFP-positive) SCs were found within the scaffold during the first 3 days after implantation. Apoptosis was identified as one of the mechanisms of cell death. At 1 week and later time points after implantation, few of the implanted SCs were present in the scaffold. Neurofilament-positive axons were found in the scaffold. At 6 weeks post-grafting, myelinated axons were observed within and at the external surface of the scaffold. Axons did not grow from the scaffold into the caudal cord. All groups demonstrated a similar improvement of hind limb motor function. Our findings demonstrated that few seeded SCs survived in vivo, which could account for the modest axonal regeneration response into and across the scaffold. For the development of SC-seeded macroporous scaffolds that effectively promote axonal regeneration in the injured spinal cord, the survival and/or total number of SCs in the scaffold needs to be improved.

Ultrathin transparent conductive films of polymer-modified multiwalled carbon nanotubes.

Deposition of multiwalled carbon nanotubes modified by poly(2-vinylpyridine) (CNT-g-P2VP) from aqueous dispersions at low pH is an effective method to prepare homogeneous ultrathin films with a tunable CNTs density. A percolation threshold of 0.25 mug/cm2 and a critical exponent alpha = 1.24 have been found from dc conductivity measurements. The sheet resistance value agrees with the percolation theory for 2D films. According to AFM and electrical measurements, even when only 5% of the surface is covered by CNT-g-P2VPs, the sheet resistance is of the order of 1 MOmega/sq, which indicates that conductivity is imparted by a network of an ultralow density. When the film transmittance decreases down to approximately 70% at 550 nm, the occupied surface area is approximately 15% and sheet resistance falls down to approximately 90 kOmega/sq. These data show that undesired in-plane clustering does not occur upon the dispersion casting of the films and that high-quality networks of CNT-g-P2VPs are built up. The electrosteric stabilization of the CNT-g-P2VP dispersions in water at low pH is at the origin of this desired behavior. Although the multiwalled CNT films prepared in this work are less conductive and less transparent than the SWNTs films, they could find applications, e.g., in touch screens, reflective displays, EMI shielding, and static charge dissipation.

Supported cobalt mediated radical polymerization (SCMRP) of vinyl acetate and recycling of the cobalt complex.

Cobalt complexes supported on silica and Merrifield resin are effective mediators for the controlled radical polymerization of vinyl acetate.

Limitations in transplantation of astroglia-biomatrix bridges to stimulate corticospinal axon regrowth across large spinal lesion gaps.

Regrowth of injured axons across rather small spinal cord lesion gaps and subsequent functional recovery has been obtained after many interventions. Long-distance regeneration of injured axons across clinically relevant large spinal lesion gaps is relatively unexplored. Here, we aimed at stimulating long-distance regrowth of the injured corticospinal (CS) tract. During development, an oriented framework of immature astrocytes is important for correct CS axon outgrowth. Furthermore, a continuous growth promoting substrate may be needed to maintain a CS axon regrowth response across relatively large spinal lesion gaps. Hence, we acutely transplanted poly(D,L)-lactide matrices, which after seeded with immature astrocytes render aligned astrocyte-biomatrix complexes (R. Deumens, et al. Alignment of glial cells stimulates directional neurite growth of CNS neurons in vitro. Neuroscience 125 (3) (2004) 591-604), into 2-mm long dorsal hemisection lesion gaps. In order to create a growth promoting continuum, astrocyte suspensions were also injected rostral and caudal to the lesion gap. During 2 months, locomotion was continuously monitored. Histological analysis showed that astrocytes injected into host spinal tissue survived, but did not migrate. None of the astrocytes on the biomatrices survived within the lesion gap. BDA-labeled CS axons did not penetrate the graft. However, directly rostral to the lesion gap, 120.9+/-38.5% of the BDA-labeled CS axons were present in contrast to 12.8+/-3.9% in untreated control animals. The observed anatomical changes were not accompanied by locomotor improvements as analyzed with the BBB and CatWalk. We conclude that although multifactorial strategies may be needed to stimulate long-distance CS axon regrowth, future studies should focus on enhancing the viability of cell/biomatrix complexes within large spinal lesion gaps.

Surface modification of metallic cardiovascular stents by strongly adhering aliphatic polyester coatings.

This article reports on a novel two-step strategy for the coating of cardiovascular stents by strongly adhering biocompatible and biodegradable aliphatic polyesters. First, a precoating of poly(ethylacrylate) (PEA) was electrografted onto the metallic substrate by cathodic reduction of the parent monomer in dimethylformamide (DMF). The electrodeposition of PEA, in a good solvent of it, was confirmed by both Infra-red and Raman spectroscopies. The pendant ester groups of PEA were then chemically reduced into aluminum alkoxides, able to initiate the ring-opening polymerization (ROP) of either D,L-lactide (LA) or epsilon-caprolactone (CL). Growth of biodegradable PLA or PCL coatings from the adhering precoating was confirmed by both Infra-red and Raman spectroscopies, and directly observed by scanning electron microscopy (SEM). This type of coating can act as an anchoring layer for the subsequent casting of drug-loaded polyester films allowing the controlled release of antiproliferative agents for the treatment of in-stent restenosis.

An easy and economically viable route for the decoration of carbon nanotubes by magnetite nanoparticles, and their orientation in a magnetic field.

A simple, cheap and tunable approach for the decoration of carbon nanotubes by magnetite nanoparticles and their orientation in a magnetic field is reported.

Combination of ring-opening polymerization and "click" chemistry towards functionalization of aliphatic polyesters.

Azide pendent groups of aliphatic polyesters have been derivatized into tertiary amines, ammonium salts and poly(ethylene oxide) grafts. The experimental conditions have been optimized (organic solvent, 35 degrees C), such that the aliphatic polyesters are not degraded, including even poly(lactide) which is very sensitive to attack by weak nucleophiles.

In vitro and in vivo analysis of macroporous biodegradable poly(D,L-lactide-co-glycolide) scaffolds containing bioactive glass.

Recent studies have demonstrated the angiogenic potential of 45S5 Bioglass. However, it is not known whether the angiogenic properties of Bioglass remain when the bioactive glass particles are incorporated into polymer composites. The objectives of the current study were to investigate the angiogenic properties of 45S5 Bioglass particles incorporated into biodegradable polymer composites. In vitro studies demonstrated that fibroblasts cultured on discs consisting of specific quantities of Bioglass particles mixed into poly(D,L-lactide-co-glycolide) secreted significantly increased quantities of vascular endothelial growth factor. The optimal quantity of Bioglass particles determined from the in vitro experiments was incorporated into three-dimensional macroporous poly(D,L-lactide-co-glycolide) foam scaffolds. The foam scaffolds were fabricated using either compression molding or thermally induced phase separation processes. The foams were implanted subcutaneously into mice for periods of up to 6 weeks. Histological assessment was used to determine the area of granulation tissue around the foams, and the number of blood vessels within the granulation tissue was counted. The presence of Bioglass particles in the foams produced a sustained increase in the area of granulation tissue surrounding the foams. The number of blood vessels surrounding the neat foams was reduced after 2 weeks of implantation; however, compression-molded foams containing Bioglass after 4 and 6 weeks of implantation had significantly more blood vessels surrounding the foams compared with foams containing no Bioglass at the same time points. These results indicate that composite polymer foam scaffolds containing Bioglass particles retain granulation tissue and blood vessels surrounding the implanted foams. The use of this polymer composite for tissue engineering scaffolds might provide a novel approach for ensuring adequate vascular supply to the implanted device.

Freeze-dried poly(D,L-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord.

The effects of poly(D,L-lactic acid) macroporous guidance scaffolds (foams) with or without brain-derived neurotrophic factor (BDNF) on tissue sparing, neuronal survival, axonal regeneration, and behavioral improvements of the hindlimbs following implantation in the transected adult rat thoracic spinal cord were studied. The foams were embedded in fibrin glue containing acidic-fibroblast growth factor. One group of animals received fibrin glue with acidic-fibroblast growth factor only. The foams were prepared by a thermally induced polymer-solvent phase separation process and contained longitudinally oriented macropores connected to each other by a network of micropores. Both foams and fibrin only resulted in a similar gliotic and inflammatory response in the cord-implant interfaces. With BDNF foam, up to 20% more NeuN-positive cells in the spinal nervous tissue close to the rostral but not caudal spinal cord-implant interface survived than with control foam or fibrin only at 4 and 8 weeks after implantation. Semithin plastic sections and electron microcopy revealed that cells and axons more rapidly invaded BDNF foam than control foam. Also, BDNF foam contained almost twice as many blood vessels than control foam at 8 weeks after implantation. Tissue sparing was similar in all three implantation paradigms; approximately 42% of tissue was spared in the rostral cord and approximately 37% in the caudal cord at 8 weeks post grafting. The number of myelinated and unmyelinated axons was low and not different between the two types of foams. Many more axons were found in the fibrin only graft. Serotonergic axons were not found in any of the implants and none of the axons regenerated into the caudal spinal cord. The behavioral improvements in the hindlimbs were similar in all groups. These findings indicated that foam is well tolerated within the injured spinal cord and that the addition of BDNF promotes cell survival and angiogenesis. However, the overall axonal regeneration response is low. Future research should explore the use of poly(D,L-lactic acid) foams, with or without axonal growth-promoting factors, seeded with Schwann cells to enhance the axonal regeneration and myelination response.

Noncovalent functionalization of multi-walled carbon nanotubes by pyrene containing polymers.

Multi-walled carbon nanotubes (MWNTs) have been solubilized in water and in various organic solvents by noncovalent side-wall functionalization by pyrene containing polymers.

Electrochemical Synthesis of Polypyrrole Nanowires.

Through a hole in a poly(ethyl acrylate) (PEA) layer that is electrochemically grafted to the surface of a vitreous carbon electrode-that is the route that must be taken by a growing polypyrrole nanowire in the electropolymerization of pyrrole. Chain growth is controlled by diffusion of the monomer through the DMF-swollen PEA layer, which acts as a template for the formation of nanowires (shown in the picture) with diameters of 400-1000 nm and lengths of up to 300 µm.

Core-Shell-Corona Micelles with a Responsive Shell.

A reactor for the synthesis of gold nanoparticles is one of the uses of a poly(styrene)-block-poly(2-vinylpyridine)-block-poly(ethylene oxide) triblock copolymer (PS-b-P2VP-b-PEO) which forms core-shell-corona micelles in water. Very low polydispersity spherical micelles are observed that consist of a PS core surrounded by a pH-sensitive P2VP shell and a corona of PEO chains end-capped by a hydroxyl group. The corona can act as a site for attaching responsive or sensing molecules.