In vitro degradation and in vivo biocompatibility study of a new linear poly(urethane urea).

Segmented poly(urethane urea)s (PUUs) with hard segments derived only from methyl 2,6-diisocyantohexanoate (LDI) without the use of a chain extender have previously been described. These materials, which contain hard segments with multiple urea linkages, show exceptionally high strain capability (1600-4700%). In the study reported here, the rate and effect of hydrolysis of these materials were determined for gamma-sterilized and nonsterilized samples. Materials investigated contained PCL, PTMC, P(TMC-co-CL), P(CL-co-DLLA), or P(TMC-co-DLLA) as soft segments and, as well as their mechanical properties, changes in mass, inherent viscosity (I.V.), and thermal properties were studied over 20 weeks. Results showed that the degradation rate was dependant on the soft segment structure, with a higher rate of degradation for the polyester-dominating PUUs exhibiting a substantial loss in I.V. A tendency of reduction of tensile strength and strain hardening was seen for all samples. Also, loss in elongation at break was detected, for PUU-P(CL-DLLA) it went from 1600% to 830% in 10 weeks. Gamma radiation caused an initial loss in I.V. and induced more rapid hydrolysis compared with nonsterilized samples, except for PUU-PTMC. A cytotoxicity test using human fibroblasts demonstrated that the material supports cell viability. In addition, an in vivo biocompatibility study showed a typical foreign body reaction after 1 and 6 weeks.

Dietary supplementation with carbonate increases expression of ornithine decarboxylase and proliferation in gastric mucosa in a rat model of gastric cancer.

Dietary factors play essential roles in gastric carcinogenesis. We recently found that dietary supplementation with NaHCO(3) significantly increased the development of gastric cancer in a rat gastric stump model. Here, we analysed nontransformed gastric mucosa for expression of the cancer-related proteins cyclooxygenase-2 (COX-2) and ornithine decarboxylase (ODC), and we examined the relationship between expression levels of those proteins and mucosal proliferation. Research has shown that COX-2 is upregulated in gastric mucosal inflammation and is strongly associated with gastrointestinal cancer. ODC is the key enzyme in polyamine synthesis and a regulator of cell proliferation. We performed gastric resections on 48 Wistar rats to induce spontaneous gastric cancer; half of these animals were given a normal diet, and the other half received a diet supplemented with NaHCO(3). Twenty-four unoperated rats served as a control group. The surgical procedure per se led to a significant rise in mucosal expression of COX-2 and an associated increase in cell proliferation. However, the COX-2 level in gastric mucosa was not further affected by dietary supplementation of carbonate. Interestingly, nontransformed gastric mucosa in the operated rats receiving a carbonate-supplemented diet showed a pronounced increase in ODC expression that was strongly correlated with a further enhanced cell proliferation. These results indicate that carbonate ions, which represent a major constituent of intestinal reflux into the stomach, increase the expression of ODC and thereby enhance cell proliferation in nontransformed mucosa, and consequently elevate the risk of gastric cancer.

Pore size in implanted polypropylene filters is critical for tissue organization.

Widely different implant materials induce surprisingly similar tissue reactions in vivo in contrast to their in vitro responses. Increasing attention has recently been given to the surface texture of the material. When both the material composition and the surface topography are varied, the surface topography seems to be the predominant factor for the induced tissue response. The present study addresses differences in the tissue response to commercially available Millipore mesh filters of polypropylene with pore sizes of 0.6, 10.0 or 30.0 microm. The Millipore filters with adjacent tissue were directly sectioned in a cryostat and evaluated via an immunofluorescence technique with double and triple staining, allowing simultaneous analysis of different antigens in tissue sections. These results show that macrophages, total cells, necrotic cells, nitric oxygen distribution, early angiogenesis, and capsule thickness were influenced by the surface structure. Implants with pore sizes of 0.6 microm, where entrance of inflammatory cells was inhibited, induce the most pronounced foreign body capsule formation. The 10- and 30-microm filters, in contrast, had large amounts of macrophages inside the filter structure, although very few inflammatory cells were found outside the filters. The inflammatory cells within the filters appeared not to influence the foreign body capsule induction. The critical factor for the formation of a foreign body capsule seems to be the localization of implant-close macrophages. Whether this is due to differences in cell activation or in signal transduction to collagen-synthesizing fibroblasts remains an open question.

Tissue reactions evoked by porous and plane surfaces made out of silicon and titanium.

Square-shaped silicon or titanium implants with plane or porous surfaces surrounded by a rim of silicone were implanted in the rat abdominal wall for evaluation of the tissue response after one, six, or 12 weeks. Cell damage was identified as increased membrane permeability using fluorescence microscopy by injection of propidium iodide prior to the killing of the rats. Capsule thickness and immunohistochemical quantification of macrophages were used as a further measure of the foreign-body reaction. There were no significant differences in capsular cell densities for macrophages, total cells (macrophages, fibroblasts, and other cells), or necrotic cells at the different time points for the four surfaces studied. However, significant differences in the kinetics of the response were found between plane surfaces compared with porous ones. Both types of plane surfaces developed a significant increase in capsule thickness over time in contrast to the porous implants. Porous silicon displayed a significant decrease in total cells in the reactive capsule over time. Furthermore, porous silicon and titanium surfaces displayed a significant decrease in total cell numbers at the implant interface between six and 12 weeks. The present study demonstrated that implanted silicon elicited soft-tissue reactions comparable to that of titanium.