No abstract

Biomaterials respond to sterilization methods differently. Steam sterilization might decrease the performance of thermoplastic polyether-urethane (TPU); however, the effect of different gamma-radiation doses on this polymer is contradictory in present literature. The purpose of this study was to investigate the differences between irradiative doses in comparison with steam sterilization on a porous TPU scaffold produced by a new processing method. No significant differences in the surface chemical structure were found with attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) analysis when comparing with the sterilization methods. The molecular weight (M(w)) had a net increase from 11.5 +/- 0.039 to 13.2 +/- 0.072 kDa by gamma-sterilization from 10 to 60 kGy. The samples that were irradiated (>60 kGy) had also an increase in polydispersity index (PDI; 1.45 +/- 0.007) in comparison with the nonsterile ones (1.31 +/- 0.017), which indicate branching. Liquid chromatography/mass spectroscopy (LC/MS) analysis showed that there was a correlation between the concentration of the breakdown product, methyl dianiline, and cytotoxicity. The concentration of this compound was found to be four times higher in steam-sterilized sample (1.3 +/- 0.01 ppb) compared with that of the polymer sample gamma-sterilized at 10 kGy (0.3 +/- 0.01 ppb). The cytotoxicity of TPU was found to decrease with higher radiation doses, and was significantly higher for the steam-sterilized samples. It is recommended that TPU produced with the described foaming method should be sterilized by gamma-irradiation at 25 kGy or higher doses.

The problem of moisture in polymer processing is known to any polymer engineer, as air bubbles may be formed. Hence granulates are generally dried prior to manufacturing. This study tried to develop a novel processing methods for scaffolds with controlled moisture content in thermoplastic polyurethane. The common foaming agents for polyurethane are organic solvents, whose residues remaining in the scaffold may be harmful to adherent cells, protein growth factors or nearby tissues. Water was used as a foaming agent and NaCl was used as porogens to achieve an open-cell structure. The polyether-polyurethane samples were processed in a heated press, and achieved a porosity of 64%. The pore size ranged between 50 and 500 microm. Human fibroblasts adhered and proliferate in the scaffold. A non-toxic production process was developed to manufacture a porous structure with a thermoplastic polyether-polyurethane. The process enables a mass-production of samples with adjustable pore size and porosity. In contrast to an existing method (solvent casting), the processing of the samples was not limited by its thickness. The process parameters, which attribute mostly to the pore building, were filling volume, temperature, NaCl-concentration and water-uptake rate.

Prediction of the prognosis for metastatic breast cancer patients depends on molecular subtypes similar to those found in patients with primary breast cancer. Several studies have shown that estrogen receptor (ER) and progesterone receptor (PR) status determine the course of the disease and the prognosis. As Ki-67 helps to differentiate molecular subtypes in patients with primary breast cancer, the aim of this study was to assess the prognostic relevance of Ki-67 in the primary tumor in relation to its prognostic relevance for patients with metastatic breast cancer. A total of 467 patients with invasive breast cancer were identified in the database of a single breast cancer center, in whom Ki-67 had been assessed in tumor material from the breast at the time of the primary diagnosis and who had developed a metastasis at any time during the subsequent course. For these patients, tumor and patient characteristics were used to determine prognostic factors relative to overall survival after the diagnosis of distant metastases. Ki-67 was added to this model to investigate whether this might improve the prediction of overall survival. In the multivariate Cox model, age at diagnosis, body mass index, nodal status, tumor size, ER and PR status, and time from diagnosis to metastasis were identified as relevant prognostic factors. Adding Ki-67 to the model improved the prediction of overall survival. There was also a significant and relevant interaction with the PR status. In patients with a low-proliferation primary tumor, a high level of PR expression would indicate an extraordinarily good prognosis (HR 0.39; 95 % CI, 0.23-0.66). In patients with higher-proliferation primary tumors, PR status was not capable of differentiating prognostic groups. Ki-67 is useful in addition to known prognostic factors for breast cancer. It is able to indicate a group of women with a poorer prognosis, specifically in the group of patients with PR-positive breast cancer.

A large-scale scaffold processing method with injection molding has been successfully developed. Water was used as a foaming agent for the new technique. NaCl was used as a porogen to achieve an open-cell structure. Organic solvents, which are common foaming agents for polyurethane, where not used. Toxic remains in the polymer were therefore prevented. Biocompatibility tested gave a mean optical density of 81% from WST-1 proliferation assay. In comparison to the previously study processing method, hot pressing (Haugen H, Ried V, Brunner M, Will J, Wintermantel E. J Mater Sci: Mater Med2004;15:343-346), the current scaffolds had an increase of 20% of the mean optical density. Cell seeding showed that human fibroblasts adhered to the surface and proliferated. The spread of the adhered fibroblasts was uniform on the surface. A quantitative MTT analysis proved that there was a significant (p < 0.01) increase in the OD level after 7 and 14 days of incubation. This cell layer thickened with increased incubation time from 7 to 14 days (p < 0.05) and had typical fibroblast morphology.