TiN x O y coatings facilitate the initial adhesion of osteoblasts to create a suitable environment for their proliferation and the recruitment of endothelial cells.

Titanium-nitride-oxide coatings (TiN x O y ) improve osseointegration of endosseous implants. The exact mechanisms by which these effects are mediated are poorly understood except for an increase of osteoblast proliferation while a high degree of differentiation is maintained. One hypothesis holds that TiN x O y facilitates the initial spreading and adhesion of the osteoblasts. The aim of this work was to investigate the molecular mechanisms of osteoblast adhesion on TiN x O y as compared to microrough titanium SLA. A global view of the osseointegrative process, that is, taking into account other cell groups, especially endothelial cells, is also presented. To this aim, gene expression and focal adhesion analysis, cocultures and wound assays were performed early after seeding, from 6 h to 3 days. We demonstrated that TiN x O y coatings enhance osteoblast adhesion and spreading when compared to the standard microrough titanium. The integrin ß1, either in association with α1 or with α2 plays a central role in these mechanisms. TiN x O y coatings optimize the process of osseointegration by acting at several levels, especially by upregulating osteoblast adhesion and proliferation, but also by supporting neovascularization and the development of a suitable inflammatory environment.

Effect of different surface treatments on the hydrothermal degradation of a 3Y-TZP ceramic for dental implants.

OBJECTIVES: Implant surface modifications are intended to enhance bone integration. The objective of this study was to assess the effect of different surface treatments on the resistance to hydrothermal degradation, hardness and elastic modulus of a 3Y-TZP ceramic used for dental implants. METHODS: Samples grouped according to their surface morphologies (AS, as-sintered; C, coated; P, dry-polished; R, roughened; PA, polished and annealed; RA, roughened and annealed) were subjected to accelerated hydrothermal degradation (LTD) by exposure to water steam (134°C, 2bars) for 100h. The t-m phase transformation was quantified by grazing incidence X-ray diffraction (GIXDR) and by combined focused ion beam and scanning electron microscopy (FIB-SEM). Elastic modulus and hardness before- and after prolonged aging (100h) were assessed by nanoindentation. RESULTS: AS and C specimens presented a better resistance to hydrothermal degradation than P and R samples. After prolonged aging, the depth of the monoclinic transformed layer ranged from 11µm to 14µm. Hydrothermal degradation led to a significant decrease of elastic modulus and hardness. SIGNIFICANCE: Surface treatments affected the resistance to hydrothermal degradation of the 3Y-TZP ceramic. Dry mechanical surface modifications should be avoided since a high t-m transformation rate associated to the initial monoclinic content was observed. Annealing was useful to reverse the initial t-m transformation, but did not improve the resistance to hydrothermal degradation.

Titanium nitride oxide coating on rough titanium stimulates the proliferation of human primary osteoblasts.

OBJECTIVES: Titanium is widely used in contemporary endosseous implantology and there is considerable thrust to further promote osseointegration by implant surface modifications. The aim of this study was to evaluate the effect of a titanium-nitride-oxide (TiNOx) coating on commercially pure microroughened titanium by assessing the proliferation and differentiation of human primary osteoblasts. MATERIALS AND METHODS: Cell proliferation, gene expression, alkaline phosphatase activity, osteoprotegerin and osteocalcin secretion were analyzed for a time course of 3 weeks, with or without additional stimulation by 1.25(OH)(2) vitamin D(3) 100 nM. RESULTS: A 1.5-fold increase in the proliferation rate of cells grown on TiNOx-coated titanium as compared with uncoated surfaces was observed. SEM views indicated that the cells' normal morphology with their numerous extensions was maintained. The differentiation process on the TiNOx surface was only affected to a minor degree and translated into a slight delay in osteoblast maturation when compared to uncoated titanium. CONCLUSION: Pending confirmation of these results in vivo, TiNOx coatings could potentially accelerate and enhance osseointegration.

Lentiviral PU.1 overexpression restores differentiation in myeloid leukemic blasts.

PU.1, a transcription factor of the ETS family, plays a pivotal role in normal hematopoiesis, and particularly in myeloid differentiation. Altered PU.1 function is possibly implicated in leukemogenesis, as PU.1 gene mutations were identified in some patients with acute myeloid leukemia (AML) and as several oncogenic products (AML1-ETO, promyelocytic leukemia-retinoic acid receptor alpha, FMS-like receptor tyrosine kinase 3 internal tandem duplication) are associated with PU.1 downregulation. To demonstrate directly a role of PU.1 in the blocked differentiation of leukemic blasts, we transduced cells from myeloid cell lines and primary blasts from AML patients with a lentivector encoding PU.1. In NB4 cells we obtained increases in PU.1 mRNA and protein, comparable to increases obtained with all-trans retinoic acid-stimulation. Transduced cells showed increased myelomonocytic surface antigen expression, decreased proliferation rates and increased apoptosis. Similar results were obtained in primary AML blasts from 12 patients. These phenotypic changes are characteristic of restored blast differentiation. PU.1 should therefore constitute an interesting target for therapeutic intervention in AML.

Secretion of the trefoil factor TFF3 from the isolated vascularly perfused rat colon.

The trefoil factor TFF3 is a peptide predominantly produced by mucus-secreting cells in the small and large intestines. It has been implicated in intestinal protection and repair. The mechanisms that govern TFF3 secretion are poorly understood. The aim of this study was, therefore, to evaluate the influence of neurotransmitters, hormonal peptides and mediators of inflammation on the release of TFF3. For this purpose, an isolated vascularly perfused rat colon preparation was used. After a bolus administration of 1 ml isotonic saline into the lumen, TFF3 secretion was induced by a 30-min intra-arterial infusion of the compounds to be tested. TFF3 was evaluated in the luminal effluent using a newly developed radioimmunoassay. TFF3 was barely detected in crude luminal samples. In contrast, dithiothreitol (DTT) treatment of the effluent revealed TFF3 immunoreactivity, which amounted to about 0.3 pmol min(-1) cm(-1) in the basal state. Gel chromatography of DTT-treated luminal samples revealed a single peak that co-eluted with the monomeric form of TFF3. TFF3 was not detected in the portal effluent. Bethanechol (10(-6)-10(-4) M), vasoactive intestinal peptide (VIP, 10(-8)-10(-7) M) or bombesin (10(-8)-10(-7) M) induced a dose-dependent release of TFF3. In contrast, substance P evoked a modest release of TFF3, whereas calcitonin gene-related peptide (CGRP), somatostatin, neurotensin or peptide YY (PYY) did not modify TFF3 secretion. The degranulator compound bromolasalocid, 16,16-dimethyl PGE2 (dmPGE2) or interleukin-1-beta (IL-1-beta) also evoked a marked release of TFF3. In conclusion, TFF3 in the colonic effluent is present in a complex. This association presumably involves a disulfide bond. Additionally, the present results suggest a role for enteric nervous system and resident immune cells in mediation of colonic TFF3 secretion.