Moisture-cured silicone-urethanes-candidate materials for tissue engineering: a biocompatibility study in vitro.

This study was performed to verify the response of human bone-derived cells (HBDCs) to moisture-cured silicone-urethanes (mcSUUs) in vitro, as the first step toward using them as scaffolds for bone tissue engineering. Good surgical handling, tissue cavity filling, stable mechanical properties, and potentially improved oxygen supply to cells after implantation justify the investigation of these nondegradable elastomers. A set of various mcSUUs were obtained by moisture-curing NCO-terminated prepolymers, synthesized from oligomeric siloxane diols of two different oligosiloxane chain lengths, and two different diisocyanates (MDI and IPDI), using two different NCO/OH molar ratios. Dibutyltindilaurate (DBTL) or N-dimethylethanolamine (N-met) served as catalysts. After 7 days of culture, cell number, viability, and alkaline phosphatase (ALP) activity were determined, and after 21 days, cell viability and collagen production were determined. Material characteristics significantly influenced the cell response. The mcSUUs prepared with DBTL (widely used in the syntheses of biomaterials) were cytotoxic. The MDI-based mcSUUs were significantly more favored by HBDCs than the IPDI-based ones in all performed tests. MDI-based material with low 2/1 NCO/OH and short chain length was the best support for cells, comparable with tissue-culture polystyrene (with ALP activity even higher). HBDCs cultured on porous scaffolds from this mcSUU produced a tissue-like structure in culture. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

Heme oxygenase-1 protects tumor cells against photodynamic therapy-mediated cytotoxicity.

Photodynamic therapy is a promising antitumor treatment modality approved for the management of both early and advanced tumors. The mechanisms of its antitumor action include generation of singlet oxygen and reactive oxygen species that directly damage tumor cells and tumor vasculature. A number of mechanisms seem to be involved in the protective responses to PDT that include activation of transcription factors, heat shock proteins, antioxidant enzymes and antiapoptotic pathways. Elucidation of these mechanisms might result in the design of more effective combination strategies to improve the antitumor efficacy of PDT. Using DNA microarray analysis to identify stress-related genes induced by Photofrin-mediated PDT in colon adenocarcinoma C-26 cells, we observed a marked induction of heme oxygenase-1 (HO-1). Induction of HO-1 with hemin or stable transfection of C-26 with a plasmid vector encoding HO-1 increased resistance of tumor cells to PDT-mediated cytotoxicity. On the other hand, zinc (II) protoporphyrin IX, an HO-1 inhibitor, markedly augmented PDT-mediated cytotoxicity towards C-26 and human ovarian carcinoma MDAH2774 cells. Neither bilirubin, biliverdin nor carbon monoxide, direct products of HO-1 catalysed heme degradation, was responsible for cytoprotection. Importantly, desferrioxamine, a potent iron chelator significantly potentiated cytotoxic effects of PDT. Altogether our results indicate that HO-1 is involved in an important protective mechanism against PDT-mediated phototoxicity and administration of HO-1 inhibitors might be an effective way to potentiate antitumor effectiveness of PDT.