Toward 3D-bioprinting of an endocrine pancreas: A building-block concept for bioartificial insulin-secreting tissue.

Three-dimensional bioprinting of an endocrine pancreas is a promising future curative treatment for patients with insulin secretion deficiency. In this study, we present an end-to-end concept from the molecular to the macroscopic level. Building-blocks for a hybrid scaffold device of hydrogel and functionalized polycaprolactone were manufactured by 3D-(bio)printing. Pseudoislet formation from INS-1 cells after bioprinting resulted in a viable and proliferative experimental model. Transcriptomics showed an upregulation of proliferative and ß-cell-specific signaling cascades, downregulation of apoptotic pathways, overexpression of extracellular matrix proteins, and VEGF induced by pseudoislet formation and 3D-culture. Co-culture with endothelial cells created a natural cellular niche with enhanced insulin secretion after glucose stimulation. Survival and function of pseudoislets after explantation and extensive scaffold vascularization of both hydrogel and heparinized polycaprolactone were demonstrated in vivo. Computer simulations of oxygen, glucose and insulin flows were used to evaluate scaffold architectures and Langerhans islets at a future perivascular transplantation site.

Free energy model for solid high-pressure phases of carbon.

Analytic free energy models for three solid high-pressure phases--diamond, body centered cubic phase with eight atoms in the unit cell (BC8), and simple cubic (SC)--are developed using density functional theory. We explicitly include anharmonic effects by performing molecular dynamics simulations and investigate their density and temperature dependence in detail. Anharmonicity in the nuclear motion shifts the phase transitions significantly compared to the harmonic approximation. Furthermore, we apply a thermodynamically constrained correction that brings the equation of state in accordance with diamond anvil cell experiments. The performance of our thermodynamic functions is validated against Hugoniot experiments.

Superionic Phases of the 1:1 Water-Ammonia Mixture.

We report four structures for the 1:1 water-ammonia mixture showing superionic behavior at high temperature with the space groups P4/nmm, Ima2, Pma2, and Pm, which have been identified from evolutionary random structure search calculations at 0 K. Analyzing the respective pair distribution functions and diffusive properties the superionic phase is found to be stable in a temperature range between 1000 and 6000 K for pressures up to 800 GPa. We propose a high-pressure phase diagram of the water-ammonia mixture for the first time and compare the self-diffusion coefficients in the mixture to the ones found in water and ammonia. Finally, possible implications on the interior structure of the giant planets Uranus and Neptune are discussed.