Gustavo A. Abraham

Crosslinkable PEO-PPO-PEO-based reverse thermo-responsive gels as potentially injectable materials

This paper describes the functionalization and crosslinking of PluronicRTM derivatives in aqueous solution at 37° C. Pluronic dimethacrylate was obtained by reacting native PEO-PPO-PEO triblocks with methacryloyl chloride and then crosslinking them by free radical polymerization at 37° C, using a redox system. The resulting gel and its rheological behavior were characterized by different techniques. The swelling study of the crosslinked polymer was indicative of its reverse thermo-responsive behavior, as illustrated by the almost 800% water uptake of the polymer at 37° C, as opposed to the 1600% attained by the polymer at 25° C. As expected, while the Pluronic dimethacrylate gel displayed an E c value of 142.5 ± 29.7 kPa at 37° C, the crosslinked system attained a Youngs modulus three times higher: 415.2 ± 45.7 kPa. Finally, the environmental SEM analysis revealed the porous microstructure of the crosslinked gels.

Hydrophilic hybrid IPNs of segmented polyurethanes and copolymers of vinylpyrrolidone for applications in medicine

The preparation and biocompatibility properties of thermoplastic apparent interpenetrating polymer networks (T-IPNs) of a segmented polyurethaneurea, Biospan (BS), and vinylpyrrolidone-dimethylacrylamide (VP-DMAm) copolymers, are described. The biological interaction between the obtained materials and blood was studied by in vitro methods. The addition of the VP-DMAm copolymers to form T-IPNs with BS substantially increased the equilibrium water uptake and water diffusion coefficients. Investigation of the proteins adsorption, platelet adhesion, thrombus formation and factor XII activation is presented. Investigations of the proteins adsorption of the BS/VP-DMAm T-IPNs surfaces show that the segmented polyurethane (BS) containing VP-DMAm copolymers with higher VP content adsorb more albumin than fibrinogen and gamma-globulin. The platelets adhesion, thrombus formation and factor XII activation are effectively suppressed with respect to the segmented polyurethane when VP-DMAm copolymers with high VP contents are incorporated into BS as T-IPNs.

Effect of the hard segment chemistry and structure on the thermal and mechanical properties of novel biomedical segmented poly(esterurethanes)

Two series of biomedical segmented polyurethanes (SPU) based on poly(ε-caprolactone) diol (PCL diol), 1,6-hexamethylene diisocyanate (HDI) or l-lysine methyl ester diisocyanate (LDI) and three novel chain extenders, were synthesized and characterized. Chain extenders containing urea groups or an aromatic amino-acid derivative were incorporated in the SPU formulation to strengthen the hard segment interactions through either bidentate hydrogen bonding or π-stacking interactions, respectively. By varying the composition of the hard segment (diisocyanate and chain extender), its structure was varied to investigate the structure-property relationships. The different chemical composition and symmetry of hard segment modulated the phase separation of soft and hard domains, as demonstrated by the thermal behavior. Hard segment association was more enhanced by using a combination of symmetric diisocyanate and urea-diol chain extenders. The hard segment cohesion had an important effect on the observed mechanical behavior. Polyurethanes synthesized using HDI (Series H) were stronger than those obtained using LDI (Series L). The latter SPU exhibited no tendency to undergo cold-drawing and the lowest ultimate properties. Incorporation of the aromatic chain extender produced opposite effects, resulting in polyurethanes with the highest elongation and tearing energy (Series H) and the lowest strain at break (Series L). Since the synthesized biodegradable SPU possess a range of thermal and mechanical properties, these materials may hold potential for use in soft tissue engineering scaffold applications.

Immobilization of a nonsteroidal antiinflammatory drug onto commercial segmented polyurethane surface to improve haemocompatibility properties.

A method has been developed in which a layer of p-aminosalicylic acid (4-amino-2-hydroxybenzoic acid) (PAS), a water soluble pharmaceutical compound of the nonsteroidal anti-inflammatory drug (NSAID) class with antiaggregant platelet activity, is covalently immobilized onto a segmented polyurethane, Biospan (SPU) surface. Thus, SPU surfaces were modified by grafting of hexamethylenediisocyanate. and the free isocyanate remaining on the SPU surface were then coupled through a condensation reaction to amine groups of p-aminosalicylic acid. The bonding of PAS from aqueous solution onto SPU surface was studied by ATR-FTIR. UV and fluorescence spectroscopy. Plateau levels of coupled PAS were reached within 1.2 microg/cm2 using PAS solution concentrations of 1mg/ ml. The surface wettability of the polymeric films measured by contact angle indicate that the introduction of the PAS turns the surface more hydrophilic (theta(water) = 43.1 +/- 2.1) relatively to the original SPU films (theta(water) = 70.3 +/- 1.9). The in vitro albumin (BSA) adsorption shows that the PAS-SPU films adsorb more BSA (250/microgmm2) than the original SPU (112 microg mm2). Thrombogenicity was assessed by measuring the thrombus formation and platelet adhesion of the SPU containing PAS relatively to nonmodified SPU surfaces. The polymeric surfaces with immobilized PAS had better nonthrombogenic characteristics as indicated by the low platelet adhesion, high adsorption of albumin relatively to fibrinogen and low thrombus formation, making them potentially good candidates for biomedical applications.

Physical and mechanical behavior of sterilized biomedical segmented polyurethanes

Changes in the physical and mechanical behavior induced by two sterilization methods, gamma irradiation and ethylene oxide, were determined on two commercial medical-grade segmented polyurethanes. The two materials have different chemical composition: one is an aromatic poly(ether urethane urea), BiospanTM, and the other an aliphatic ether-free polyurethane, ChronoflexTM. Properties before and after sterilization procedures were compared resulting in specific structural changes for each formulation. The thermal and mechanical properties were examined using differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), stress–strain measurements, and its hysteresis cycle. Molecular weight measurements were performed by gel permeation chromatography (GPC). Sterilized Biospan samples showed a decrease in the soft-segment glass transition temperature (Tg,s) and an increase in the soft segment crystallization heat along the quenching process. Sterilized Chronoflex materials showed the opposite behavior. The hysteresis percent and residual strain percent increased after sterilization. The same effect was observed when irradiation dose and strain level increased. Surface analysis performed by scanning electron microscopy showed magnification of original surface defects after sterilization.

Segmented poly(esterurethane urea)s from novel urea–diol chain extenders: Synthesis, characterization and in vitro biological properties

This work describes the preparation, physicochemical characterization, mechanical properties and in vitro biological properties of two bioresorbable aliphatic segmented poly(esterurethane urea)s (SPEUU) based on poly(epsilon-caprolactone) diol (PCL diol), 1,6-hexamethylene diisocyanate and two novel urea-diol chain extenders. To strengthen the interactions through hydrogen bonding in the hard segments of SPEUU, novel chain extenders containing urea groups were synthesized and used in the SPEUU formulation. The different chemical structures of the chain extenders modulated the phase separation of soft and hard segments, as demonstrated by the thermal behavior. The hard segment association was enhanced using a diurea-diol chain extender. The biological interactions between the obtained materials and blood were studied by in vitro methods. Research on the protein adsorption, platelet adhesion and thrombus formation is presented. Studies of protein adsorption onto polymeric surfaces showed that SPEUU adsorbed more albumin than fibrinogen. Studies on platelet adhesion and thrombus formation of SPEUU-coated coverslips indicated the antithrombogenic behavior of these surfaces. The synthesized SPEUU revealed no signs of cytotoxicity to Chinese hamster ovary cells, showing satisfactory cytocompatibility.

Resistive‐type humidity sensors based on PVP–Co and PVP–I2 complexes

Poly(vinylpyrrolidone) films containing cobalt chloride or iodine were investigated to obtain information on their possible use as a humidity sensor element. FTIR and UV-VIS spectroscopies were used to characterize the PVP-I 2 and PVP-Co complexes. Infrared spectroscopy revealed a structural change of both shape and intensity of the carbonyl and lactam bands, indicating the formation of an ion-coordination polymer. The J-E curves for pure PVP, PVP-I 2 , and PVP-Co films obey ohms law at low voltages, deviate from the linear response at higher voltages, and finally display breakdown behavior. An increase in current density of the PVP matrix with iodine or cobalt doping is attributed to the formation of charge transfer complexes. The observed hysteresis of the I-V characteristics implies that there was some standing voltage in the film, which could be attributed to a disorientation of polar side groups of PVP. The electrical conductivities of the polymeric complexes were very sensitive to environmental humidity. An explanation of the humidity-sensing behavior of the PVP-I 2 and PVP-Co complexes is presented.

ε-Caprolactone/ZnCl2 complex formation: Characterization and ring-opening polymerization mechanism

e-Caprolactone (e-CL) has been mixed with ZnCl2 at different mol ratios. The resulting complex was characterized through 1H and 13C NMR spectroscopy in bulk and in solutions, differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD), and optical microscopy. Ring-opening polymerization of e-caprolactone [M] using ZnCl2 as an initiator [I] at different monomer/initiator ratios has been successfully performed in xylene. The molecular weight of poly(e-caprolactone) (PCL) as measured by gel permeation chromatografy (GPC) was found to depend linearly on the [M]/[I] ratio. Theoretical calculations were carried out to understand the geometry of the complex and the operating ring-opening mechanism. Both experimental and computational results and the presence of methylene–chloride end group, confirmed by NMR, are in agreement with a coordination–insertion mechanism for the ring-opening polymerization proposed in this article.

Optimization of poly(L-lactic acid)/segmented polyurethane electrospinning process for the production of bilayered small-diameter nanofibrous tubular structures.

The present study is focused on the electrospinning process as a versatile technique to obtain nanofibrous tubular structures for potential applications in vascular tissue engineering. A bilayered scaffolding structure composed of poly(L-lactic acid) (PLLA)/bioresorbable segmented polyurethane (SPEU) blends for small-diameter (5mm) vascular bypass grafts was obtained by multilayering electrospinning. Polymer blend ratios were chosen to mimic the media and adventitia layers. The influence of the different electrospinning parameters into the fiber formation, fiber morphology and fiber mean diameter for PLLA, SPEU and two PLLA/SPEU blends were studied. Flat and two-parallel plate collectors were used to analyze the effect of the electrostatic field on the PLLA nanofiber alignment in the rotating mandrel. Membrane topography resulted in random or aligned nanofibrous structures depending on the auxiliary collector setup used. Finally, composition, surface hydrophilicity, thermal properties and morphology of nanofibrous scaffolds were characterized and discussed. Since the development of tissue engineered microvascular prostheses is still a challenge, the prepared scaffolding tubular structures are promising candidates for vascular tissue engineering.

Physicochemical and antimicrobial properties of boron-complexed polyglycerol–chitosan dendrimers

A polyglycerol with dendritic structure (PGLD) was synthesized by ring-opening polymerization of deprotonated glycidol using a polyglycerol as core functionality in a step-growth process. Then, PGLD reacted with O-carboxymethylated chitosan to obtain PGLD-chitosan dendrimer (PGLD-Ch). After the reaction of PGLD-Ch with boric acid, there was a marked increase in the bulk viscosity evidencing physically that boron can initiate a charge transfer complex formation, (PGLD-Ch)B. Gel permeation chromatography analysis was used to characterize the molecular weight and the polydispersivity of the synthesized PGLD-Ch. A dendritic structure with a molecular mass of 16.7 kDa and a narrow polydispersity (M w/M n = 1.05) was obtained. 1H-NMR and 13C-NMR measurements were employed to assess the degree of branching in PGLD. The obtained value of 0.85 indicates the tendency toward a dentritic structure for PGLD. The glass transition temperature values of (PGLD-Ch)B membranes containing 10% and 30% PGLD were −19°C and −26°C, respectively, which favor its potential use as surface coating of several polymers. The in vitro cytotoxicity was evaluated using the minimum essential medium elution test assay. Extracts of boroncomplexed PGLD exhibited lower cytotoxicity than the controls, suggesting that the material has an improved biocompatibility. Antibacterial studies of (PGLD-Ch)B against Staphylococcus aureus and Pseudomonas aeruginosa showed a significant activity. Our study confirms and supports the effectiveness of (PGLD-Ch)B as an antimicrobial coating due to its capacity in suppressing the bacterial proliferation. The best in vivo response was found for (PGLD-Ch)B-30 membranes, which exhibited higher synthesis of collagen fibers than PGLD-ChB-10.