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[Display omitted] • Novel porous scaffolds have been developed that mimic the mechanical and fluid properties of cancellous bone. • The new porous scaffolds have high specific surface area and controllable surface curvatures. • The design methodology is suitable for modifying the internal microstructure of computed tomography medical images. • The design methodology allows for the development of bone-like scaffolds with continuous but graduated material properties. • The properties of the scaffolds depend on the direction of their trabeculae, their total porosity, and their bone surface. The design of novel biomimetic bone tissue scaffolds (BTS) using computer aided design (CAD) technology is challenging additive manufacturing technologies. At the microstructure level, BTS should mimic bone histomorphometry and assure optimum mass transport and mechanical properties. In this study, a novel BTS has been designed, by using a parametric and variational CAD method, to model a bio-inspired and interconnected porous structure. The mechanical (elastic modulus) and the fluid mass transport (permeability) properties have been computed and compared to other implicit surfaces modelling scaffolds. The results showed that the new BTS could be tuned during the design stage to match the microstructure and the histomorphometry properties of trabecular bone. Those with porosities between 0.7 and 0.9 and highly smooth curvatures were the most appropriates. The new BTS, once appropriately designed, could be made/manufactured by 3D printing technology with an internal microstructure mimicking the local bone properties of the selected bone volumes of interest, for example, those coming from computed tomography medical images. [ABSTRACT FROM AUTHOR]

Abstract: The nuclear factor of activated T cells (NFAT) family of transcription factors is pivotal for T lymphocyte functionality. All relevant NFAT activation events upon T cells stimulation such as nuclear translocation, DNA binding, and transcriptional activity have been shown to be dictated by its phosphorylation state. Here, we provide evidence for a novel post-translational modification that regulates NFAT. Indeed, NFATc1 and NFATc2 are poly(ADP-ribosyl)ated by poly-ADP-ribose polymerase-1 (PARP-1). Moreover, we have also found a physical interaction between PARP-1 and both NFATc1 and NFATc2. Interestingly, PARP is activated during T cell stimulation in the absence of DNA damage, leading to ADP-ribose polymers formation and transfer to nuclear acceptor proteins. Our data suggest that poly(ADP-ribosyl)ation modulates the activation of NFAT in T cells, as PARP inhibition causes an increase in NFAT-dependent transactivation and a delay in NFAT nuclear export. Poly(ADP-ribosyl)ation will expedited NFAT export from the nucleus directly or by priming/facilitating NFAT phosphorylation. Altogether, these data point to PARP-1 and poly(ADP-ribosyl)ation as a novel regulatory mechanism of NFAT at nuclear level, suggesting a potential use of PARP as a new therapeutic target in the modulation of NFAT. [Copyright &y& Elsevier]