Vesna V. Antić

In Vitro Biocompatibility Evaluation of Novel Urethane–Siloxane Co-Polymers Based on Poly(ϵ-Caprolactone)-block-Poly(Dimethylsiloxane)-block-Poly(ϵ-Caprolactone)

Abstract Novel polyurethane co-polymers (TPUs), based on poly(ϵ-caprolactone)-block-poly(dimethylsiloxane)-block-poly(ϵ-caprolactone) (PCL-PDMS-PCL) as soft segment and 4,4’-methylenediphenyl diisocyanate (MDI) and 1,4-butanediol (BD) as hard segment, were synthesized and evaluated for biomedical applications. The content of hard segments (HS) in the polymer chains was varied from 9 to 63 wt%. The influence of the content and length of the HS on the thermal, surface, mechanical properties and biocompatibility was investigated. The structure, composition and HS length were examined using 1H- and quantitative 13C-NMR spectroscopy. DSC results implied that the synthesized TPUs were semicrystalline polymers in which both the hard MDI/BD and soft PCL-PDMS-PCL segments participated. It was found that an increase in the average HS length (from 1.2 to 14.4 MDI/BD units) was accompanied by an increase in the crystallinity of the hard segments, storage moduli, hydrophilicity and degree of microphase separation of the co-polymers. Depending on the HS content, a gradual variation in surface properties of co-polymers was revealed by FT-IR, AFM and static water contact angle measurements. The in vitro biocompatibility of co-polymers was evaluated using the endothelial EA.hy926 cell line and protein adsorption on the polyurethane films. All synthesized TPUs adsorbed more albumin than fibrinogen from multicomponent protein mixture, which may indicate biocompatibility. The polyurethane films with high HS content and/or high roughness coefficient exhibit good surface properties and biocompatible behavior, which was confirmed by non-toxic effects to cells and good cell adhesion. Therefore, the non-cytotoxic chemistry of the co-polymers makes them good candidates for further development as biomedical implants.

Synthesis of α,ω-dicarboxypropyl oligodimethylsiloxanes by ion-exchange resin catalyzed equilibration polymerization

Abstract A series of α,ω-dicarboxypropyl oligodimethylsiloxanes of predetermined molecular weights was synthesized from octamethylcyclotetrasiloxane, D 4 , and 1,3-bis-(3-carboxypropyl)tetramethyldisiloxane (BCPTMDS) by a heterogeneously catalyzed equilibration polymerization reaction using a macroporous cation-exchange resin as an acidic catalyst. The structure of the obtained linear oligomers was verified by IR, 1 H- and 13 C-NMR spectroscopy, while their molecular weights were determined by 1 H-NMR spectroscopy, vapor pressure osmometry, functional group analysis and gel permeation chromatography. It was shown that the expected target molecular weights, ranging between 600 and 3500, were achieved with a satisfactory accuracy.

Poly(urethane‐dimethylsiloxane) copolymers displaying a range of soft segment contents, noncytotoxic chemistry, and nonadherent properties toward endothelial cells

Polyurethane copolymers based on α,ω-dihydroxypropyl poly(dimethylsiloxane) (PDMS) with a range of soft segment contents were prepared by two-stage polymerization, and their microstructures, thermal, thermomechanical, and surface properties, as well as in vitro hemo- and cytocompatibility were evaluated. All utilized characterization methods confirmed the existence of moderately microphase separated structures with the appearance of some microphase mixing between segments as the PDMS (i.e., soft segment) content increased. Copolymers showed higher crystallinity, storage moduli, surface roughness, and surface free energy, but less hydrophobicity with decreasing PDMS content. Biocompatibility of copolymers was evaluated using an endothelial EA.hy926 cell line by direct contact, an extraction method and after pretreatment of copolymers with multicomponent protein mixture, as well as by a competitive protein adsorption assay. Copolymers showed no toxic effect to endothelial cells and all copolymers, except that with the lowest PDMS content, exhibited resistance to endothelial cell adhesion, suggesting their unsuitability for long-term biomedical devices which particularly require re-endothelialization. All copolymers exhibited excellent resistance to fibrinogen adsorption and adsorbed more albumin than fibrinogen in the competitive adsorption assay, suggesting their good hemocompatibility. The noncytotoxic chemistry of these synthesized materials, combined with their nonadherent properties which are inhospitable to cell attachment and growth, underlie the need for further investigations to clarify their potential for use in short-term biomedical devices.

Influence of the chemical structure of poly(urea-urethane-siloxane)s on their morphological, surface and thermal properties

Segmented poly(urethane-urea-siloxane)s (PUUS) were synthesized using 4,4′-methylenediphenyl diisocyanate (MDI) and ethylene diamine (ED) as the hard segment components and hydroxypropyl-terminated poly(dimethylsiloxane) (PDMS) as the soft segment component, where the hard segment content ranged from 38 to 65 wt%. Segmented PUUSs were prepared by a two-step polymerization procedure in tetrahydrofuran/N-methylpyrrolidone (THF/NMP) mixture with a large proportion of polar solvent. The structure, composition and hard segment length were determined by 13C NMR and two-dimensional correlation spectroscopy. Thermal, mechanical, small-angle X-ray scattering and hydrogen bonding analyses indicated the formation of the microphase-separated copolymers with high tensile strength. Globular superstructures observed in the copolymer films by scanning electron microscopy (SEM) and atomic force microscopy (AFM) were probably arisen from the microstructural organization of the MDI-ED segments, depending on their content and length. The PUUS copolymers showed high water resistance and became more hydrophobic with increasing weight fraction of PDMS.

The effect of the polar solvents on the synthesis of poly(urethane-urea-siloxane)s

Segmented poly(urethane-urea-siloxanes) (PUUS) based on 4,4’- methylene diphenyl diisocyanate-ethylene diamine (MDI-ED) hard segments and hidroxypropyl-terminated poly(dimethylsiloxane) (PDMS, M n =1000 g mol-1) soft segments were prepared under various experimental conditions. The copolymers with constant molar ratio of hard and soft segments (PDMS:MDI:ED = 1:2:1; 20 wt. % of the hard segments) were synthesized in two different solvent mixtures, by two-step polyaddition procedure. The first one was THF/DMAc with different co-solvent ratio (1/1, 1/2 and 1/9, v/v), whereas the second one was THF/NMP (1/9, v/v). The reaction conditions were optimized by varying the co-solvents ratio, the concentration of the catalyst, the initial monomer concentration, as well as the time of the first and the second step of reaction. The effect of the experimental conditions on the size of PUUS was investigated by gel permeation chromatography (GPC) and viscometry of the dilute solutions [η]. The copolymers with the highest molecular weights were obtained in the THF/NMP mixture (1/9, v/v). The structure and composition of the copolymers were determined by 1H NMR and FTIR spectroscopy. The morphology of the synthesized copolymers was investigated by atomic force microscopy (AFM), while the thermal properties were studied by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The surface properties were evaluated by measuring the water contact angle (WCA). The copolymers showed phase separated microstructure and were stable up to 200°C in nitrogen.