Artículos SCI

A set of powdered cermets based on (Ti,Ta,Nb)C _xN _1-x carbonitride solid solutions were synthesized from mixtures of elemental powders by a mechanically induced self-sustaining reaction (MSR) method and subsequently sintered using a pressureless method. Differing nominal compositions of the hard phase were used, and the nature of the metallic-binder phase (Co, Ni, or Co-Ni) was varied. For comparative purposes, the design of the material was performed using two different synthesis pathways. The composition and microstructure of the ceramic and binder phases before and after sintering were analyzed and related to the microhardness of the material, which was found to increase with increasing contiguity of the hard phase and with decreasing particle size.The samples synthesized in one step (SERIES 2) showed higher microhardness and a more homogeneous microstructure with smaller particle size of the hard phase due to the presence of Ti, Ta, and Nb in the molten binder that hindered ceramic growth during liquid phase sintering.

Liver fibrosis is a reversible pathology characterized by the up-regulated secretion and deposition of ECM proteins and inhibitors of metalloproteinases, which increase the stiffness and viscosity of this organ. Since recent studies have shown that fibrosis preceded the generation of hepatocellular carcinomas, we hypothesize that liver fibrosis could play a role as a mechanism for restricting uncontrolled cell proliferation, inducing the mortality of cancer cells and subsequent development of primary tumours.

With this purpose, in this work we analysed in vitro how the modulation of stiffness can influence proliferation, viability and aggregation of hepatocarcinoma cells (HepG(2)) embedded in 3D micromilieus mimicking values of elasticity of fibrotic liver tissues.

Experiments were performed by immobilizing up to 10 HepG(2) cells within microcapsules made of 0.8%, 1.0% and 1.4% w/v alginate which, besides having values of elasticity from the lower-healthy to the upper-fibrotic range liver tissues, lacked domains for proteases, mimicking the micromilieu existing in hepatic primary tumours.

Our results show that entrapped cells exhibited a short duplication phase followed by an irreversible decay stage, in which cell mortality could be mediated by two mechanisms: mechanical stress, in the case of cells entrapped in a stiffer micromilieu; and mass transfer limitations produced by pore coarsening at the interface cell-matrix, in softer micromilieus.

According to the authors' knowledge, this work represents the first attempt to elucidate the role of liver fibrosis during Hepatocarcinoma pathologies, suggesting that the generation of a non-biodegradable and mechanically unfavourable environment surrounding cancer cells could control the proliferation, migration of metastatic cells and the subsequent development of primary tumours.