Bone tissue response to plasma-nitrided titanium implant surfaces

A current goal of dental implant research is the development of titanium (Ti) surfaces to improve osseointegration. Plasma nitriding treatments generate surfaces that favor osteoblast differentiation, a key event to the process of osteogenesis. Based on this, it is possible to hypothesize that plasma-nitrided Ti implants may positively impact osseointegration. Objective The aim of this study was to evaluate the in vivo bone response to Ti surfaces modified by plasma-nitriding treatments. Material and Methods Surface treatments consisted of 20% N2 and 80% H2, 450°C and 1.5 mbar during 1 h for planar and 3 h for hollow cathode. Untreated surface was used as control. Ten implants of each surface were placed into rabbit tibiae and 6 weeks post-implantation they were harvested for histological and histomorphometric analyses. Results Bone formation was observed in contact with all implants without statistically significant differences among the evaluated surfaces in terms of bone-to-implant contact, bone area between threads, and bone area within the mirror area. Conclusion Our results indicate that plasma nitriding treatments generate Ti implants that induce similar bone response to the untreated ones. Thus, as these treatments improve the physico-chemical properties of Ti without affecting its biocompatibility, they could be combined with modifications that favor bone formation in order to develop new implant surfaces

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

Implementation of the “loaded implant” model in the rat using a miniaturized setup - description of the method and first results

Objective : To miniaturize the “loaded implant” model to permit its application to small rodents. In this model, two titanium implants are placed 8 mm apart with their heads protruding from the skin and are forced together by a dedicated actuator. To assess the effect of (i) the post-implantation healing period and the duration of stimulation and (ii) the intratissular strain level on the microtomographical bone parameters BV/TV, Tb.N., Tb.Th. and BIC. Materials and methods : Implants, 1 × 8 mm, were machined, inserted into the tibiae of rats and activated. A total of 123 animals were used. In series 1, the implants were left to heal for 2/4 weeks and then loaded to generate intratissular strains of 1125 ± 5% με for 4/8 weeks. Series 2 had their implants loaded to 750, 1500 and 2250 ± 5% με, respectively. Results : Bone to implant contact increased upon loading. In series 1, no difference was observed regarding the duration of healing or the stimulation period. In series 2, at 750 με, the bone parameters did not differ from baseline. At 1500 με, all four parameters increased. At 2250 με, three of four parameters decreased relative to 1500 με. Conclusions : (i) The loaded implant model can be miniaturized to the millimeter range; (ii) in the present model, implant activation beyond 4 weeks did not affect the bone parameters; (iii) mechanical stimulation increased bone to implant contact by up to 20%; (iv) the results obtained are consistent with the concept of an anabolic effect from 750 to 1500 με and deleterious effects at strains in the 2250 με range; and (v) strains at 2250 με did not lead to implant dis-integration

Implementation of the "loaded implant" model in the rat using a miniaturized setup - description of the method and first results

Objective To miniaturize the loaded implant model to permit its application to small rodents. In this model, two titanium implants are placed 8 mm apart with their heads protruding from the skin and are forced together by a dedicated actuator. To assess the effect of (i) the post-implantation healing period and the duration of stimulation and (ii) the intratissular strain level on the microtomographical bone parameters BV/TV, Tb.N., Tb.Th. and BIC. Materials and methods Implants, 1 x 8 mm, were machined, inserted into the tibiae of rats and activated. A total of 123 animals were used. In series 1, the implants were left to heal for 2/4 weeks and then loaded to generate intratissular strains of 1125 +/- 5% mu e for 4/8 weeks. Series 2 had their implants loaded to 750, 1500 and 2250 +/- 5% mu e, respectively. Results Bone to implant contact increased upon loading. In series 1, no difference was observed regarding the duration of healing or the stimulation period. In series 2, at 750 mu e, the bone parameters did not differ from baseline. At 1500 mu e, all four parameters increased. At 2250 mu e, three of four parameters decreased relative to 1500 mu e. Conclusions (i) The loaded implant model can be miniaturized to the millimeter range; (ii) in the present model, implant activation beyond 4 weeks did not affect the bone parameters; (iii) mechanical stimulation increased bone to implant contact by up to 20%; (iv) the results obtained are consistent with the concept of an anabolic effect from 750 to 1500 mu e and deleterious effects at strains in the 2250 mu e range; and (v) strains at 2250 mu e did not lead to implant dis-integration