The goal of this work is to make an injectable physically and chemically cross-linking NIPAAmbased copolymer system for endovascular embolization. A copolymer with N-isopropylacrylamide (NIPAAm) and hydroxyethyl methacrylate (HEMA) was synthesized and converted to poly (NIPAAm-co-HEMA-acrylate) functionalized with olefins. When poly(NIPAAm-co-HEMAacrylate) was mixed with pentaerythritol tetrakis 3-mercaptopropionate (QT) stoichiometrically in 0.1 N PBS solution of pH 7.4, it formed a temperature-sensitive hydrogel with low swelling through the Michael-Type Addition reaction and showed improved elastic properties at low frequency compared to physical gelation. This material could be useful for applications requiring water-soluble injection but lower swelling and lower creep properties than available with other soluble in situgelling materials.
Signaling events mediate many processes that act during embryogenesis to initiate the program of early development. Within the cell many of these changes are mediated through the activation or inactivation of kinases and phosphatases. Protein kinase C (PKC) is one kinase that has been shown to be involved in at least two developmental transitions during early development, fertilization and embryonic compaction. PKC is a family of kinases whose various isotypes have differing requirements for activation of the kinase that include the availability of calcium, diacylglycerol, and negatively charged phospholipids. The presence of more than one isotype in an egg or blastomere of the embryo would provide the possibility that different isotypes mediate distinct signaling pathways in the cells. To address this possibility the different isotypes of PKC were examined at the mRNA and protein levels during preimplantation development in the mouse. Our results demonstrate that seven isotypes of PKC are present during preimplantation development in mouse, some are of maternal origin and others appear after fertilization. Two isotypes have a stage-dependent nuclear localization. In addition, within each blastomere PKC isotypes occupy different subcellular locations in a stage-dependent fashion.
A thermosensitive, injectable and bioresorbable polymer hydrogel, Poly(N-isopropylacrylamide-co-dimethyl-γ-butyrolactone acrylate-co-acrylic acid) (poly(NDBA)), was synthesized by radical copolymerization with 7.00 mol.% dimethyl-γ-butyrolactone acrylate in tetrahydrofuran (THF). The chemical composition was determined by acid titration in conjunction with 1H NMR quantification. The molecular weight and polydispersity were determined by gel permeation chromatography (GPC) in conjunction with static light scattering. The degradation properties of the polymer hydrogel were characterized using differential scanning calorimetry (DSC), percentage mass loss, cloud point test and swelling ratio over time. It was found that the initial LCST of the polymer is between room temperature and body temperature and that it takes about 2 weeks for the LCST to surpasses body temperature under physiological conditions. An indirect cytotoxicity test indicated that this copolymer has relatively low cytotoxicity as seen with 3T3 fibroblast cells. The in vivo-gelation and degradation study showed good agreement with in vitro-degradation findings and no detrimental effects to adjacent tissues were observed after the complete dissolution of the polymer.
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