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 (1)H- and quantitative (13)C-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.

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Properties and biocompatibility of a series of thermoplastic poly(urethane-siloxane)s (TPUSs) based on α,ω-dihydroxy ethoxy propyl poly(dimethylsiloxane) (PDMS) for potential biomedical application were studied. Thin films of TPUSs with a different PDMS soft segment content were characterized by (1) H NMR, quantitative (13) C NMR, Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), contact angle, and water absorption measurements. Different techniques (FTIR, AFM, and DMA) showed that decrease of PDMS content promotes microphase separation in TPUSs. Samples with a higher PDMS content have more hydrophobic surface and better waterproof performances, but lower degree of crystallinity. Biocompatibility of TPUSs was examined after attachment of endothelial cells to the untreated copolymer surface or surface pretreated with multicomponent protein mixture, and by using competitive protein adsorption assay. TPUSs did not exhibit any cytotoxicity toward endothelial cells, as measured by lactate dehydrogenase and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assays. The untreated and proteins preadsorbed TPUS samples favored endothelial cells adhesion and growth, indicating good biocompatibility. All TPUSs adsorbed more albumin than fibrinogen in competitive protein adsorption experiment, which is feature regarded as beneficial for biocompatibility. The results indicate that TPUSs have good surface, thermo-mechanical, and biocompatible properties, which can be tailored for biomedical application requirements by adequate selection of the soft/hard segments ratio of the copolymers.

Combined treatment with chloroquine and calorie restriction might be useful in cancer therapy.

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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.

The role of the main intracellular energy sensor adenosine monophosphate (AMP)-activated protein kinase (AMPK) in the induction of autophagic response and cell death was investigated in SH-SY5Y human neuroblastoma cells exposed to the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA). The induction of autophagy in SH-SY5Y cells was demonstrated by acridine orange staining of intracellular acidic vesicles, the presence of autophagosome- and autophagolysosome-like vesicles confirmed by transmission electron microscopy, as well as by microtubule-associated protein 1 light-chain 3 (LC3) conversion and p62 degradation detected by immunoblotting. 6-OHDA induced phosphorylation of AMPK and its target Raptor, followed by the dephosphorylation of the major autophagy inhibitor mammalian target of rapamycin (mTOR) and its substrate p70S6 kinase (S6K). 6-OHDA treatment failed to suppress mTOR/S6K phosphorylation and to increase LC3 conversion, p62 degradation and cytoplasmatic acidification in neuroblastoma cells in which AMPK expression was downregulated by RNA interference. Transfection of SH-SY5Y cells with AMPK or LC3β shRNA, as well as treatment with pharmacological autophagy inhibitors suppressed, while mTOR inhibitor rapamycin potentiated 6-OHDA-induced oxidative stress and apoptotic cell death. 6-OHDA induced phosphorylation of p38 mitogen-activated protein (MAP) kinase in an AMPK-dependent manner, and pharmacological inhibition of p38 MAP kinase reduced neurotoxicity, but not AMPK activation and autophagy triggered by 6-OHDA. Finally, the antioxidant N-acetyl cysteine antagonized 6-OHDA-induced activation of AMPK, p38 and autophagy. These data suggest that oxidative stress-mediated AMPK/mTOR-dependent autophagy and AMPK/p38-dependent apoptosis could be valid therapeutic targets for neuroprotection.

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