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In tissue engineering, the ability to manipulate scaffold design characteristics is important to achieve functional tissue regeneration. In this study, degradable polar hydrophobic ionic polyurethane (D-PHI) porous scaffolds were synthesized using a lysine-based divinyl oligomer (DVO). Optimization studies on the DVO and D-PHI scaffold synthesis were conducted to maximize isocyanate and methacrylate monomer conversion, respectively. D-PHI scaffold properties were manipulated through the introduction of a lysine-based cross-linker. Specifically, increasing D-PHI cross-linker concentration resulted in an increase of the elastic modulus (0.5-21 MPa), a decrease of the elongation-at-yield (45-5%) and a reduction of scaffold swelling (170-100%). Based on a preliminary study with A10 vascular smooth muscle cells, D-PHI scaffolds demonstrated the ability to support cell adhesion and growth during 2 weeks of culture, suggesting their potential suitability for longer term vascular tissue engineering. The versatility of the D-PHI properties may allow for the tailoring of cell-material interaction and ultimately functional tissue regeneration.

In the normal breast, hepatocyte growth factor (HGF) is primarily expressed by stromal cells, and stimulates in a paracrine manner epithelial cells expressing the HGF receptor (Met). In invasive human breast carcinomas, HGF and Met are frequently overexpressed, possibly establishing an autocrine HGF/Met loop that promotes tumour cell invasion. However, the mechanisms leading to autocrine HGF expression in carcinoma cells are not known. We previously demonstrated a cooperative effect between c-Src and Stat3 in the activation of HGF transcription in mammary carcinoma cells. The present report defines a novel Stat3 consensus site at nt À95 in the HGF promoter that is highly conserved in human and mouse, and is required for c-Src and Stat3 to activate HGF transcription in breast epithelial cells. DNA-protein binding studies demonstrated high affinity binding of a Stat3-containing complex to the nt À95 site. Endogenous Stat3 binding to this region of the HGF promoter in carcinoma cells expressing HGF was demonstrated using a chromatin immunoprecipitation assay. In addition, coexpression of Stat3 and activated c-Src caused increased expression of endogenous HGF mRNA and protein and marked cell scattering in breast epithelial cells. Our results delineate a novel c-Src/Stat3-dependent mechanism that regulates HGF promoter activity, and is linked to transformation of mammary epithelial cells.

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