Mathematical modelling of the degradation behaviour of biodegradable metals.

A mathematical model for the biodegradation of magnesium is developed in this study to inspect the corrosion behaviour of biodegradable implants. The aim of this study was to provide a suitable framework for the assessment of the corrosion rate of magnesium which includes the process of formation/dissolution of the protective film. The model is intended to aid the design of implants with suitable geometries. The level-set method is used to follow the changing geometry of the implants during the corrosion process. A system of partial differential equations is formulated based on the physical and chemical processes that occur at the implant-medium boundary in order to simulate the effect of the formation of a protective film on the degradation rate. The experimental data from the literature on the corrosion of a high-purity magnesium sample immersed in simulated body fluid is used to calibrate the model. The model is then used to predict the degradation behaviour of a porous orthopaedic implant. The model successfully reproduces the precipitation of the corrosion products on the magnesium surface and the effect on the degradation rate. It can be used to simulate the implant degradation and the formation of the corrosion products on the surface of biodegradable magnesium implants with complex geometries.

In situ structural analysis of calcium aluminosilicate glasses under high pressure.

In situ micro-Raman spectroscopy was used to investigate the structural evolution of OH(-)-free calcium aluminosilicate glasses, under high pressure and at room temperature. Evaluation was made of the role of the SiO2 concentration in percalcic join systems, for Al/(Al + Si) in the approximate range from 0.9 to 0.2. Under high pressure, the intensity of the main band related to the bending mode of bridging oxygen ([Formula: see text][T-O-T], where T = Si or Al) decreased gradually, suggesting that the bonds were severely altered or even destroyed. In Si-rich glasses, compression induced a transformation of Q (n) species to Q (n-1). In the case of Al-rich glass, the Al in the smallest Q (n) units evolved from tetrahedral to higher-coordinated Al (([5])Al and ([6])Al). Permanent structural changes were observed in samples recovered from the highest pressure of around 15 GPa and, particularly for Si-rich samples, the recovered structure showed an increase of three-membered rings in the Si/Al tetrahedral network.

In silico regenerative medicine: how computational tools allow regulatory and financial challenges to be addressed in a volatile market.

The cell therapy market is a highly volatile one, due to the use of disruptive technologies, the current economic situation and the small size of the market. In such a market, companies as well as academic research institutes are in need of tools to advance their understanding and, at the same time, reduce their R&D costs, increase product quality and productivity, and reduce the time to market. An additional difficulty is the regulatory path that needs to be followed, which is challenging in the case of cell-based therapeutic products and should rely on the implementation of quality by design (QbD) principles. In silico modelling is a tool that allows the above-mentioned challenges to be addressed in the field of regenerative medicine. This review discusses such in silico models and focuses more specifically on the bioprocess. Three (clusters of) examples related to this subject are discussed. The first example comes from the pharmaceutical engineering field where QbD principles and their implementation through the use of in silico models are both a regulatory and economic necessity. The second example is related to the production of red blood cells. The described in silico model is mainly used to investigate the manufacturing process of the cell-therapeutic product, and pays special attention to the economic viability of the process. Finally, we describe the set-up of a model capturing essential events in the development of a tissue-engineered combination product in the context of bone tissue engineering. For each of the examples, a short introduction to some economic aspects is given, followed by a description of the in silico tool or tools that have been developed to allow the implementation of QbD principles and optimal design.

Coupling curvature-dependent and shear stress-stimulated neotissue growth in dynamic bioreactor cultures: a 3D computational model of a complete scaffold.

The main challenge in tissue engineering consists in understanding and controlling the growth process of in vitro cultured neotissues toward obtaining functional tissues. Computational models can provide crucial information on appropriate bioreactor and scaffold design but also on the bioprocess environment and culture conditions. In this study, the development of a 3D model using the level set method to capture the growth of a microporous neotissue domain in a dynamic culture environment (perfusion bioreactor) was pursued. In our model, neotissue growth velocity was influenced by scaffold geometry as well as by flow- induced shear stresses. The neotissue was modeled as a homogenous porous medium with a given permeability, and the Brinkman equation was used to calculate the flow profile in both neotissue and void space. Neotissue growth was modeled until the scaffold void volume was filled, thus capturing already established experimental observations, in particular the differences between scaffold filling under different flow regimes. This tool is envisaged as a scaffold shape and bioprocess optimization tool with predictive capacities. It will allow controlling fluid flow during long-term culture, whereby neotissue growth alters flow patterns, in order to provide shear stress profiles and magnitudes across the whole scaffold volume influencing, in turn, the neotissue growth.

A three-dimensional computational fluid dynamics model of shear stress distribution during neotissue growth in a perfusion bioreactor.

Bone tissue engineering strategies use flow through perfusion bioreactors to apply mechanical stimuli to cells seeded on porous scaffolds. Cells grow on the scaffold surface but also by bridging the scaffold pores leading a fully filled scaffold following the scaffold's geometric characteristics. Current computational fluid dynamic approaches for tissue engineering bioreactor systems have been mostly carried out for empty scaffolds. The effect of 3D cell growth and extracellular matrix formation (termed in this study as neotissue growth), on its surrounding fluid flow field is a challenge yet to be tackled. In this work a combined approach was followed linking curvature driven cell growth to fluid dynamics modeling. The level-set method (LSM) was employed to capture neotissue growth driven by curvature, while the Stokes and Darcy equations, combined in the Brinkman equation, provided information regarding the distribution of the shear stress profile at the neotissue/medium interface and within the neotissue itself during growth. The neotissue was assumed to be micro-porous allowing flow through its structure while at the same time allowing the simulation of complete scaffold filling without numerical convergence issues. The results show a significant difference in the amplitude of shear stress for cells located within the micro-porous neo-tissue or at the neotissue/medium interface, demonstrating the importance of taking along the neotissue in the calculation of the mechanical stimulation of cells during culture.The presented computational framework is used on different scaffold pore geometries demonstrating its potential to be used a design as tool for scaffold architecture taking into account the growing neotissue. Biotechnol. Bioeng. 2015;112: 2591-2600. © 2015 Wiley Periodicals, Inc.

Synthesis and luminescent properties of La(1-x)Nd(x)P5O14 nanocrystals.

La(1-x)Nd(x)P5O14 nanocrystals were synthesized using a coprecipitation method. Their structure and morphology were determined. The luminescence and excitation spectra of La(1-x)Nd(x)P5O14 nanocrystals were measured in the entire range of Nd(3+) concentration. It was found that the relative intensities of absorption transitions increased significantly with concentration due to the cooperative interactions. The effect of concentration on fluorescence transitions was investigated. It was found that the intensity of the (4)F3/2 → (4)I11/2 transition significantly increased with concentration relative to the resonant (4)F3/2 → (4)I9/2 transition almost three times due to strong reabsorption. The concentration quenching of fluorescence was discussed in terms of the Yokota-Tanimoto model.

Thermally driven dual-frequency Q-switching of Nd:YGd2Sc2Al2GaO12 ceramic laser.

Multi-wavelength operation of Q-switched Nd-doped YGd(2)Sc(2)Al(2)GaO(12) garnet ceramic lasers has been investigated. Dual-wavelength emission around ~1.06 µm has been demonstrated both in the actively and passively Q-switched configurations. The ratio of output energy between the two laser wavelengths was driven by the temperature elevation caused by pumping. Passively Q-switched operation yields dual-frequency emission of two unsynchronized laser pulses carried by distinct transverse modes whereas active Q-switched configuration offers the possibility of synchronizing emission at the two wavelengths.

A computational model for cell/ECM growth on 3D surfaces using the level set method: a bone tissue engineering case study.

Three-dimensional open porous scaffolds are commonly used in tissue engineering (TE) applications to provide an initial template for cell attachment and subsequent cell growth and construct development. The macroscopic geometry of the scaffold is key in determining the kinetics of cell growth and thus in vitro 'tissue' formation. In this study, we developed a computational framework based on the level set methodology to predict curvature-dependent growth of the cell/extracellular matrix domain within TE constructs. Scaffolds with various geometries (hexagonal, square, triangular) and pore sizes (500 and 1,000 [Formula: see text]m) were produced in-house by additive manufacturing, seeded with human periosteum-derived cells and cultured under static conditions for 14 days. Using the projected tissue area as an output measure, the comparison between the experimental and the numerical results demonstrated a good qualitative and quantitative behavior of the framework. The model in its current form is able to provide important spatio-temporal information on final shape and speed of pore-filling of tissue-engineered constructs by cells and extracellular matrix during static culture.

Tunable color temperature of Ce3+/Eu2+, 3+ co-doped low silica aluminosilicate glasses for white lighting.

In this paper we report results of tunable lighting in Ce(3+)/Eu(2+,3+) doped low silica calcium aluminosilicate glass. Optical spectroscopy experiments indicate that there is a red color compensation from Eu(2+) and Eu(3+) to the green emission from Ce(3+), resulting in a broad and tunable emission spectra depending on the excitation wavelength. This result analysed in the CIE 1976 color diagram shows a close distance from the Plank emission and a correlated color temperature, varying from 5200 to 3500K. This indicates that our system can be easily excited by GaN based blue LEDs, being an interesting phosphor for white lighting devices.

High values of gain cross section and luminescence quantum efficiency in OH(-)-free Ti3+-doped low-silica calcium aluminosilicate glass.

We recently reported that Ti(3+)-doped low-silica calcium aluminosilicate glass presents long luminescence lifetime (170 micros) and broad emission band (190 nm) shifted toward the visible region when compared with those from Ti(3+):sapphire single crystal and Ti(3+)-doped glasses [Phys. Rev. Lett.100, 027402 (2008)]. Here we demonstrate that this glass also shows high values of both gain cross section (approximately 4.7 x 10(-19) cm(2)) and luminescence quantum efficiency (approximately 70%). By comparing these values with those for Ti(3+):sapphire crystal, we can conclude that the studied Ti(3+)-doped glass is a promising system for tunable solid-state lasers.

Long fluorescence lifetime of Ti3+-doped low silica calcium aluminosilicate glass.

This Letter reports the formation of Ti3+ in OH- free aluminosilicate glass melted under vacuum condition, with a very long lifetime (170 micros) and broad emission band shifted towards the visible region. This lifetime value was attributed to the trapping of the excited electrons by the glass defects and detrapping by thermal energy, and it is 2 orders of magnitude higher than those published for Ti3+ doped materials. Our results suggest that this glass is a promising system to overcome the challenge of extending the spectral range of traditional tunable solid state lasers towards the visible region.