Jung Ran Kim

Biological Affinity and Biodegradability of Poly(propylene carbonate) Prepared from Copolymerization of Carbon Dioxide with Propylene Oxide

In this study we investigated bacterial and cell adhesion to poly(propylene carbonate) (PPC) films, that had been synthesized by the copolymerization of carbon dioxide (a global warming chemical) with propylene oxide. We also assessed the biocompatibility and biodegradability of the filmsin vivo, and their oxidative degradation in vitro. The bacteria adhered to the smooth, hydrophobic PPC surface after 4 h incubation.Pseudomonas aeruginosa andEnterococcus faecalis had the highest levels of adhesion,Escherichia coli andStaphylococcus aureus had the lowest levels, andStaphylococcus epidermidis was intermediate. In contrast, there was no adhesion of human cells (cell line HEp-2) to the PPC films, due to the hydrophobicity and dimensional instability of the surface. On the other hand, the PPC films exhibited good biocompatibility in the mouse subcutaneous environment. Moreover, contrary to expectation the PPC films degraded in the mouse subcutaneous environment. This is the first experimental confirmation that PPC can undergo surface erosion biodegradationin vivo. The observed biodegradability of PPC may have resulted from enzymatic hydrolysis and oxidative degradation processes. In contrast, the PPC films showed resistance to oxidative degradationin vitro. Overall, PPC revealed high affinity to bioorganisms and also good biodegradability.

The biocompatability of mesoporous inorganic-organic hybrid resin films with ionic and hydrophilic characteristics.

New mesoporous silicate-titania resin systems hybridized with 4,5-dihydroxy-m-benzenedisulfonic acid and poly(ethylene glycol)-dimethacrylate component were developed. These inorganic-organic hybrid resins were found to reveal highly controlled ionic and hydrophilic surface with excellent durability and adhesion onto various substrates. The resin films revealed high resistance to nonspecific adsorption of fibrinogen and to adherence by several bacterial pathogens such as Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis. Furthermore, excellent biocompatibility of the developed resins was proved by both HEp-2 cell adhesion in vitro and subcutaneous implantation in mice. The inorganic-organic hybrid resins are strongly promising for biomedical applications including biomedical devices and biosensors.

Well-defined DNA-mimic brush polymers bearing adenine moieties: synthesis, layer-by-layer self-assembly, and biocompatibility.

Two new DNA-mimicking brush polymers were synthesized: poly[oxy(11-(3-(9-adeninyl)propionato)-undecanyl-1-thiomethyl)ethylene] (PECH-AP) and poly[oxy(11-(5-(9-adenylethyloxy)-4-oxopentanoato)undecanyl-1-thiomethyl)ethylene] (PECH-AS). These polymers were found to be thermally stable up to 220 °C and could be applied easily by conventional coating processes to produce good quality films. Interestingly, both brush polymers formed molecular multibilayer structures to provide an adenine-rich surface. Despite the structural similarities, PECH-AS surprisingly exhibited higher hydrophilicity and better water sorption properties than PECH-AP. These differences were attributed to the chemical structures in the bristles of the polymers. The adenine-rich surfaces of the polymer films demonstrated selective protein adsorption, suppressed bacterial adherence, facilitated HEp-2 cell adhesion, and exhibited good biocompatibility in mice. However, the high hydrophilicity and good water sorption characteristics of the PECH-AS film suggest that this brush polymer is better suited to applications requiring good biocompatibility and reduced chance of bacterial infection compared with the PECH-AP film.

The biocompatibility of self-assembled brush polymers bearing glycine derivatives

We have synthesized brush polymers with various glycine derivatives as the end groups of their long alkyl bristles. The polymers are thermally stable up to 170-210 degrees C and form good quality films through conventional spin- or dip-coating and subsequent drying. Interestingly, the thin films of these brush polymers exhibit different molecular multi-layer structures that arise through the efficient self-assembly of the bristles with glycine derivative end groups. These brush polymer films have hydrophilic surfaces and exhibit some water sorption. The extent of the water sorption by these films depends upon the nature of the glycine derivatives in the bristle end. These films not only repel fibrinogen molecules and platelets from their surfaces, but also have high resistance to bacterial adherence. Moreover, the films were found to provide conducive surface environments for the successful anchoring and growth of HEp-2 cells, and to exhibit excellent biocompatibility in mice. These brush polymers have potential uses in biomedical applications including medical devices, especially blood contacting devices such as catheters, stents, blood vessels, and biosensors, due to their enhanced biocompatibility and the reduced possibility of post-operative infection.

Increased expression of cyclin D1, cyclin E and p21Cip1 associated with decreased expression of p27Kip1 in chemically induced rat mammary carcinogenesis

We induced rat mammary tumors in 7‐week‐old female Sprague‐Dawley rats by intragastric administration of 7,12‐dimethylbenz(a)anthracene (DMBA), and analyzed by immunohistochemistry the expression of cyclin D1, cyclin E, p21Cip1, and p27Kip1 in carcinomas, atypical tumors, and benign tumors as well as normal mammary glands from the control group. Proliferation status was assessed by immunohistochemistry using bromodeoxyuridine (BrdU). A sequential increase in cyclin D1‐, cyclin E‐, and p21Cip1‐positive epithelial cells was observed from normal mammary glands, to atypical tumors, to carcinomas. In contrast, carcinomas showed a significantly lower number of epithelial cells immunoreactive to p27Kip1 when compared with atypical tumors, benign tumors and normal mammary glands. The immunoreactivities of BrdU, cyclin D1, cyclin E, and p21Cip1 were positively correlated, whereas that of p27Kip1 appeared inversely correlated to those of the others. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) and western blot analysis were also performed to determine the mRNA and protein levels of cyclins and cyclin‐dependent kinase inhibitors in tumors and normal mammary glands. The protein levels for cyclin D1, cyclin E and p21Cip1 in carcinomas and atypical tumors were significantly higher than those in benign tumors, while normal mammary glands showed negligible expression. On RT‐PCR, tumors showed higher mRNA levels of cyclin D1 and cyclin E than those of normal mammary glands. Our results suggest that rat mammary carcinogenesis involves increased expression of cyclin D1, cyclin E, and p21Cip1, associated with decreased expression of p27Kip1

Bacterial Adhesion, Cell Adhesion and Biocompatibility of Nafion Films

We investigated bioadhesion (bacterial and cell adhesion) and biocompatibility of poly(tetrafluoroethylene-co-perfluoro-3,6-dioxa-4-methyl-7-octenesulfonic acid) (Nafion™) and compared the results with those obtained with poly(vinylidene fluoride-co-hexafluoropropylene) (PVFHFP). When incubated with bacteria for 4 h to 7 days, Nafion film exhibited scarce bacterial adhesion at 6 h, after which the adhesion gradually increasing to relatively low levels. In contrast, significant bacterial adhesion to PVFHFP film was observed at 4 h, and much higher adhesion levels were shown thereafter. Although HEp-2 human cells adhered normally to both films, reaching confluence in 7–8 days, the cells adhered to Nafion appeared more lively and stable than those to PVFHFP. Subcutaneous implantation in mice revealed that Nafion elicited a mild acute inflammatory reaction without chronic inflammation or tissue necrosis, indicating excellent biocompatibility in mice. PVFHFP, however, provoked a moderate and prolonged acute inflammatory response. These differences in the biological characteristics of Nafion and PVFHFP films may be attributable to the differences in the chemical and physical natures of these polymer films. Nafion film provided a sufficiently solid support, expressing a high surface charge density and good water-wettability. In summary, Nafion is suitable for use in biomedical applications that require biocompatibility with a reduced possibility of post-operative infections.

New self-assembled brush glycopolymers: Synthesis, structure and properties

A new series of chemically well-defined brush glycopolymers consisting of a polyoxyethylene backbone and bristles bearing glycosyl and methyl end groups was synthesized with various compositions. The glycopolymers were thermally stable up 200 °C and were soluble in a variety of common solvents. The brush polymer films formed multibilayer structures, the layers of which were stacked along the direction normal to the film plane so as to display a glycosyl group-rich surface or a methyl group-rich surface or their mixture, depending on the bristle end group composition. The multibilayer structures were stabilized by the self-assembly of the bristles via lateral packing. The glycosyl-rich surface played a critical role in enhancing the surface hydrophilicity and water sorption to a certain level; thus, the glycopolymer films easily formed a hydration layer to a certain depth on the film surface. The hydrophilic surfaces and hydration layer efficiently prevented protein adsorption onto the brush glycopolymers and suppressed bacterial adherence while promoting mammalian cell adhesion and displaying excellent biocompatibility in an in vivo mouse study.

Biocompatible characteristics of sulfobetaine-containing brush polymers

AbstractA series of well-defined brush polymers, poly(oxy(11-(3-sulfonylpropyltrimethyl-glycinyl)undecylesterthiomethyl) ethylene-co-oxy(n-dodecylthio-methyl)ethylene)s (PECH-DMAPSm, where m is the mol% of the DMAPS [sulfobetaine] end group) were synthesized. The thermal properties and phase transitions of these polymers were investigated. The polymers were thermally stable up to 185 °C and were found to form favorably into multibilayer structures, always providing hydrophilic, zwitterionic sulfobetaine end groups at the film surface. Because of the presence of these sulfobetaine groups at the surface, the polymer films promoted HEp-2 cell adhesion and revealed biocompatibility in mice but significantly suppressed protein adsorption. These results collectively indicate that the sulfobetaine-containing brush polymers are suitable for use in biomedical applications, including medical devices and biosensors that require biocompatibility.

Spontaneous Regression of Hepatocellular Carcinoma: –A Case Report–

Spontaneous regression of cancer is a rare phenomenon seldom described in patients with hepatocellular carcinoma. A 54-year-old Korean woman suffered from cytologically-proved advanced hepatocellular carcinoma, for which she received no treatment. Papanicolaou’s smears revealed high cellularity. Many clusters of polygonal cells showed long, thick anastomosing cords covered by flattened endothelial cells. The polygonal cells showed small hepatocytoid appearance, characterized by increased nuclear/cytoplasmic ratio. She remained in good clinical condition and, at 4 years of follow-up, the hepatocellular carcinoma could not be visualized radiologically. To date, only 14 case reports of apparently spontaneous regression of hepatocellular carcinoma have been published in the English literature. The mechanisms underlying this intriguing phenomenon remain unknown.