In the development of artificial cancellous bones, two major factors need to be considered: the integrity of the overall structure and its permeability. Whilst there have been many studies analysing the mechanical properties of artificial and natural cancellous bones, permeability studies, especially those using numerical simulation, are scarce. In this study, idealised cancellous bones were simulated from the morphological indices of natural cancellous bone. Three different orientations were also simulated to compare the anisotropic nature of the structure. Computational fluid dynamics methods were used to analyse fluid flow through the cancellous structures. A constant mass flow rate was used to determine the intrinsic permeability of the virtual specimens. The results showed similar permeability of the prismatic plate-and-rod model to the natural cancellous bone. The tetrakaidecahedral rod model had the highest permeability under simulated blood flow conditions, but the plate counterpart had the lowest. Analyses on the anisotropy of the virtual specimens showed the highest permeability for the horizontal orientation. Linear relationships were found between permeability and the two physical properties, porosity and bone surface area.
CTP Synthase (CTPS) is a metabolic enzyme that is recognized as a catalyst for nucleotide, phospholipid and sialoglycoprotein production. Though the structural characteristics and regulatory mechanisms of CTPS are well-understood, little is known regarding the extent of its involvement during the early developmental stages of vertebrates. Zebrafish carries two CTPS genes, annotated as ctps1a and ctps1b. Phylogenetic analyses show that both genes had diverged from homologues in the ancestral Actinopterygii, Oreochromis niloticus. Conservation of common CTPS-catalytic regions further establishes that both proteins are likely to be functionally similar to hsaCTPS. Here, we show that ctps1a is more critical throughout the initial period of embryonic development than ctps1b. The effects of concurrent partial knockdown are dependent on ctps1a vs ctps1b dosage ratios. When these are equally attenuated, abnormal phenotypes acquired prior to the pharyngula period disappear in hatchlings (48hpf); however, if either gene is more attenuated than the other, these only become more pronounced in advanced stages. Generally, disruption to normal ctps1a or ctps1b expression levels by morpholinos culminates in the distortion of the early spinal column as well as multiple-tissue oedema. Other effects include slower growth rates, increased mortality rates and impaired structural formation of the young fish's extremities. Embryos grown in DON, a glutamine-analogue drug and CTPS antagonist, also exhibit similar characteristics, thus strengthening the validity of the morpholino-induced phenotypes observed. Together, our results demonstrate the importance of CTPS for the development of zebrafish embryos, as well as a disparity in activity and overall importance amongst isozymes.