Composite 3D printed scaffold with structured electrospun nanofibers promotes chondrocyte adhesion and infiltration.

Additive manufacturing, also called 3D printing, is an effective method for preparing scaffolds with defined structure and porosity. The disadvantage of the technique is the excessive smoothness of the printed fibers, which does not support cell adhesion. In the present study, a 3D printed scaffold was combined with electrospun classic or structured nanofibers to promote cell adhesion. Structured nanofibers were used to improve the infiltration of cells into the scaffold. Electrospun layers were connected to 3D printed fibers by gluing, thus enabling the fabrication of scaffolds with unlimited thickness. The composite 3D printed/nanofibrous scaffolds were seeded with primary chondrocytes and tested in vitro for cell adhesion, proliferation and differentiation. The experiment showed excellent cell infiltration, viability, and good cell proliferation. On the other hand, partial chondrocyte dedifferentiation was shown. Other materials supporting chondrogenic differentiation will be investigated in future studies.

The combination of nanofibrous and microfibrous materials for enhancement of cell infiltration and in vivo bone tissue formation.

Fibrous scaffolds are desired in tissue engineering applications for their ability to mimic extracellular matrix. In this study we compared fibrous scaffolds prepared from polycaprolactone using three different fabrication methods, electrospinning (ES), electro-blowing and melt-blown combined with ES. Scaffolds differed in morphology, fiber diameters and pore sizes. Mesenchymal stem cell adhesion, proliferation and osteogenic differentiation on scaffolds was evaluated. The most promising scaffold was shown to be melt-blown in combination with ES which combined properties of both technologies. Microfibers enabled good cell infiltration and nanofibers enhanced cell adhesion. This scaffold was used for further testing in critical sized defects in rabbits. New bone tissue formation occurred from the side of the treated defects, compared to a control group where only fat tissue was present. Polycaprolactone fibrous scaffold prepared using a combination of melt-blown and ES technology seems to be promising for bone regeneration. The practical application of results is connected with enormous production capacity and low cost of materials produced by melt-blown technology, compared to other bone scaffold fabrication methods.

Female sexual hormones influence motor behaviour in rats after lesion of the entopeduncular nucleus.

In rats bearing a unilateral lesion of the entopeduncular nucleus, female sexual hormones administered daily for fifteen days can decrease the rate of circling and the motility counts recorded after an injection of apomorphine 0.5 mg/kg, s.c. This suggests that female hormones can decrease the response to dopaminergic agonists in the basal ganglia possibly by affecting the sensitivity of the receptors. This may have interesting clinical applications especially in Parkinson's disease and tardive dyskinesias.

[Histopathologic and neurochemical correlations as a function of lesions of the locus coeruleus region in the cat (I)]. / Correlations histopathologiques et neurochimiques en fonction de lesions de la region du locus coeruleus chez le chat. (Part I).

Unilateral lesions in the area of the loci coeruleus and subcoeruleus in the cat are associated with a significant and sustained decrease of noradrenaline (NA) in the ipsilateral cerebral cortex without any important change in the concentrations of NA in the contralateral cortex and in the spinal cord of both sides. The serotonin (5-HT) concentrations of the spinal cord and cerebral cortex of both sides remained unchanged in the same groups of animals. Bilateral lesions in the same area result also in a marked decrease of NA in the cerebral cortex of both sides. The latter lesions also result in slight decreases of NA in the hypothalamus and of NA and 5-HT in the spinal cord but the NA and 5-HT concentrations of the striatum and thalamus and the 5-HT concentrations of the cerebral cortex and hypothalamus are unmodified by such lesions. Unilateral lesions of the area immediately rostral to the locus coeruleus (praelocus lesions) result in a very significant decrease of NA in the ipsilateral cerebral cortex without any change of NA in the contralateral cerebral cortex and spinal cord of both sides. Similar lesions produced bilaterally in another group of cats resulted in marked decreases of NA in the cerebral cortex of both sides and a slight decrease of NA in the thalamus without any change of NA in the striatum, hypothalamus and spinal cord and of 5-HT in the cerebral cortex. In the same group of animals with lesions which, however, extended more closely to the midline than in cats with locus coeruleus lesions, 5-HT is markedly decreased in the striatum and thalamus and slightly decreased in the hypothalamus and spinal cord. These results support the view that the noradrenergic coeruleo-cortical pathway is made up of fibers which originate in the loci coeruleus and subcoeruleus and predominantly end ipsilaterally to their origin in the cerebral cortex. Ascending NA fibers ending in the thalamus appear to originate from NA neurons located more laterally in the upper pons and more specifically at the level of the parabrachial nuclei.

Effect of estrogens on apomorphine-induced circling behavior in the rat.

The effect of administration of estrogens parenterally for 1 week was tested on apomorphine-induced circling in a group of castrated female rats with a lesion of the left entopednucluar nucleus. We observed a significant decrease in the number of turns per minute in estrogen-treated animals as compared with controls. Our tentative explanation is that estrogens decrease the sensitivity of dopamine receptors in the striatum.

Effects of 1694 and other dopaminergic agents on circling behavior.

One hour after the administration of 40 mg/kg of amineptine chlorydrate (1694) the HVA concentration in the striatum was increased but the concentrations of DA, NA, 5HT and 5-HIAA in the striatum, cortex, thalamus-hypothalamus and pons-midbrain of rats were not significantly altered. Unilateral lesioning at the level of the entopeduncular nucleus in cats and rats resulted in spontaneously occurring ipsiversive circling behavior in the two species. However circling was more sustained in cats than in rats. Apomorphine, d-amphetamine, methamphetamine, L-dopa and piribedil (ET-495) exaggerated the ipsiversive circling. 1694 (amineptine chlorydrate), a new agent, was comparatively more active than L-dopa and ET-495 and less active than apomorphine, d-amphetamine and methamphetamine. Although in higher doses (30--40 mg/kg), 1694 caused increased exploratory activity it was not associated with any stereotypy. Its biochemical and pharmacological effects are comparable to those of d-amphetamine and methamphetamine. Removal of the contralateral (with respect to the side of the entopeduncular lesion) motor cortex in the lesioned cat abolished spontaneous and drug-induced circling movements. The results of this and of previous studies support the idea that these dopaminergic agents act on the striopallidal system of the intact side which is no longer properly counterbalanced by the corresponding system of the lesioned side. Although this experimental model is useful to determine the degree of dopaminergic activity of various chemical agents it does not duplicate the motor disorders encountered in parkinsonism which are associated with a decreased concentration of dopamine.