Biomimetic strategies to engineer mineralised human tissues

In the last few years, many reports have been describing promising biocompatible and biodegradable materials that can mimic in a certain extent the multidimensional hierarchical structure of bone, while are also capable of releasing bioactive agents or drugs in a controlled manner. Despite these great advances, new developments in the design and fabrication technologies are required to address the need to engineer suitable biomimetic materials in order tune cells functions, i.e. enhance cell-biomaterial interactions, and promote cell adhesion, proliferation, and differentiation ability. Scaffolds, hydrogels, fibres and composite materials are the most commonly used as biomimetics for bone tissue engineering. Dynamic systems such as bioreactors have also been attracting great deal of attention as it allows developing a wide range of novel in vitro strategies for the homogeneous coating of scaffolds and prosthesis with ceramics, and production of biomimetic constructs, prior its implantation in the body. Herein, it is overviewed the biomimetic strategies for bone tissue engineering, recent developments and future trends. Conventional and more recent processing methodologies are also described.

Looking for mechanisms regulating lung growth in CDH: rat and human studies

Tese de Doutoramento em Ciências da Saúde

Lower NPAS3 expression during the later stages of abnormal lung development in rat congenital diaphragmatic hernia

Purpose Congenital diaphragmatic hernia (CDH) is characterized by a developmental defect in the diaphragm, pulmonary hypoplasia and pulmonary hypertension. NPAS3 is a PAS domain transcription factor regulating Drosophila tracheogenesis. NPAS3 null mice develop pulmonary hypoplasia in utero and die after birth due to respiratory failure. We aimed to evaluate NPAS3 expres- sion during normal and abnormal lung development due to CDH. Methods CDH was induced by administering 100 mg/ml nitrofen to time-pregnant dams on embryonic day (E) 9 of gestation. Lungs were isolated on E15, E18 and E21 and NPAS3 localization was determined by immunohisto- chemistry and quantified using Western blotting. Results We found that only E21 hypoplastic CDH lungs have reduced expression of NPAS3 in the terminal sac- cules. Western blotting confirmed the down-regulation of NPAS3 protein in the nitrofen-induced hypoplastic lungs. Conclusions We demonstrate for the first time that ni- trofen-induced hypoplastic CDH lungs have reduced NPAS3 expression in the terminal saccules during the later stages of abnormal lung development. Our findings suggest that NPAS3 is associated with pulmonary hypoplasia in CDH.

Stress induced risk-aversion is reverted by D2/D3 agonist in the rat

Stress exposure triggers cognitive and behavioral impairments that influence decision-making processes. Decisions under a context of uncertainty require complex reward-prediction processes that are known to be mediated by the mesocorticolimbic dopamine (DA) system in brain areas sensitive to the deleterious effects of chronic stress, in particular the orbitofrontal cortex (OFC). Using a decision-making task, we show that chronic stress biases risk-based decision-making to safer behaviors. This decision-making pattern is associated with an increased activation of the lateral part of the OFC and with morphological changes in pyramidal neurons specifically recruited by this task. Additionally, stress exposure induces a hypodopaminergic status accompanied by increased mRNA levels of the dopamine receptor type 2 (Drd2) in the OFC; importantly, treatment with a D2/D3 agonist quinpirole reverts the shift to safer behaviors induced by stress on risky decision-making. These results suggest that the brain mechanisms related to risk-based decision-making are altered after chronic stress, but can be modulated by manipulation of dopaminergic transmission.