Biomaterials used for the manufacture of biomedical devices must have suitable surface properties avoiding bacterial colonization and/or proliferation. Most biomaterial-related infections start during the surgery. Bacteria can begin colonization of the surface of a device right after implantation or in the next few hours. This time may also be sufficient to begin the deterioration of a biodegradable implant. This work explores the surface changes that hydrophobic films of poly(lactic) acid reinforced with Mg particles, prepared by solving-casting, undergone after in vitro degradation at different times. Hydrophobicity, surface tension, zeta potential, topography, and elemental composition were obtained from new and aged films. The initial degradation for 4 h was combined with unspecific bacterial adhesion and viability tests to check if degraded films are more or less susceptible to be contaminated. The degradation of the films decreases their hydrophobicity and causes the appearance of a biocompatible layer, composed mainly of magnesium phosphate. The release of Mg2+ is very acute at the beginning of the degradation process, and such positive charges may favor the electrostatic approach and attachment of Staphylococci. However, all bacteria attached on the films containing Mg particles appeared damaged, ensuring the bacteriostatic effect of these films, even after the first hours of their degradation.
The high rates of tumor recurrence and progression represent a major clinical problem in non-muscle invasive bladder cancer. Previous data showed that EZH2-dependent signaling mediates these processes, whereas the frequent alterations of PIK3CA gene (copy gains and mutations) are predictive of reduced recurrence. Here we show, using clinical samples and bladder cancer cell lines, a functional interaction between EZH2- and PIK3CA-dependent signaling pathways. PIK3CA alterations mediated, on the one hand, the increased expression of two miRNAs, miR-101 and miR-138, which posttranscriptionally downregulate EZH2 expression. On the other hand, PIK3CA alterations facilitate the activation of Akt which phosphorylates EZH2 on Ser21, precluding the trimethylation of histone H3 in K27. Remarkably the increased expression of miR101 or miR138 and the expression of Ser21-phosphorylated EZH2 are good prognostic factors regarding non-muscle invasive bladder cancer recurrence and progression. Collectively, this study provides molecular evidences indicating that the gene expression rewiring occurring in primary bladder tumors, associated with increased EZH2 expression and activity and mediating the increased recurrence and progression risk, are prevented by PIK3CA-dependent signaling. This molecular process may have deep implications in the management of bladder cancer patients and in the design of novel molecularly targeted therapeutic approaches.
The use of active components in biomaterials improves the properties of existing ones and makes it possible to obtain new devices with antibacterial properties that prevent infections after implantation, thus guaranteeing the success of the implant. In this work, cetyltrimethylammonium bromide (CTAB) and magnesium particles were incorporated into polylactic acid (PLA) films to assess the extent to which progressive aging of the new surfaces resists bacterial colonization processes. For this purpose, the films’ surface was characterized by contact angle measurements, ToF-SIMS and AFM, and adhesion, viability and biofilm growth of Staphylococcus epidermidis bacteria on these films were also evaluated. The results show that the inclusion of Mg and CTAB in PLA films changes their surface properties both before and after aging and also modifies bacterial adhesion on the polymer. Complete bactericidal activity is exhibited on non-degraded films and films with CTAB. This antibacterial behavior is maintained after degradation for three months in the case of films containing a higher amount of CTAB.
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