Modeling of reaction-diffusion transport into a core-shell geometry

Fickian diffusion into a core-shell geometry is modeled. The interior core mimics pancreatic Langerhan islets and the exterior shell acts as inert protection. The consumption of oxygen diffusing into the cells is approximated using Michaelis-Menten kinetics. The problem is transformed to dimensionless units and solved numerically. Two regimes are identified, one that is diffusion limited and the other consumption limited. A regression is fit that describes the concentration at the center of the cells as a function of the relevant physical parameters. It is determined that, in a cell culture environment, the cells will remain viable as long as the islet has a radius of around $142 \mu m$ or less and the encapsulating shell has a radius of less than approximately $283 \mu m$. When the islet is on the order of $100 \mu m$ it is possible for the cells to remain viable in environments with as little as $4.6\times10^{-2} mol/m^{-3}$ $O_2$. These results indicate such an encapsulation scheme may be used to prepare artificial pancreas to treat diabetes

High-Pressure Catalytic Reactions of C6 Hydrocarbons on PlatinumSingle-Crystals and nanoparticles: A Sum Frequency Generation VibrationalSpectroscopic and Kinetic Study

Catalytic reactions of cyclohexene, benzene, n-hexane, 2-methylpentane, 3-methylpentane, and 1-hexene on platinum catalysts were monitored in situ via sum frequency generation (SFG) vibrational spectroscopy and gas chromatography (GC). SFG is a surface specific vibrational spectroscopic tool capable of monitoring submonolayer coverages under reaction conditions without gas-phase interference. SFG was used to identify the surface intermediates present during catalytic processes on Pt(111) and Pt(100) single-crystals and on cubic and cuboctahedra Pt nanoparticles in the Torr pressure regime and at high temperatures (300K-450K). At low pressures (<10{sup -6} Torr), cyclohexene hydrogenated and dehydrogenates to form cyclohexyl (C{sub 6}H{sub 11}) and {pi}-allyl C{sub 6}H{sub 9}, respectively, on Pt(100). Increasing pressures to 1.5 Torr form cyclohexyl, {pi}-allyl C{sub 6}H{sub 9}, and 1,4-cyclohexadiene, illustrating the necessity to investigate catalytic reactions at high-pressures. Simultaneously, GC was used to acquire turnover rates that were correlated to reactive intermediates observed spectroscopically. Benzene hydrogenation on Pt(111) and Pt(100) illustrated structure sensitivity via both vibrational spectroscopy and kinetics. Both cyclohexane and cyclohexene were produced on Pt(111), while only cyclohexane was formed on Pt(100). Additionally, {pi}-allyl c-C{sub 6}H{sub 9} was found only on Pt(100), indicating that cyclohexene rapidly dehydrogenates on the (100) surface. The structure insensitive production of cyclohexane was found to exhibit a compensation effect and was analyzed using the selective energy transfer (SET) model. The SET model suggests that the Pt-H system donates energy to the E{sub 2u} mode of free benzene, which leads to catalysis. Linear C{sub 6} (n-hexane, 2-methylpentane, 3-methylpentane, and 1-hexene) hydrocarbons were also investigated in the presence and absence of excess hydrogen on Pt(100). Based on spectroscopic signatures, mechanisms for catalytic isomerization and dehydrocyclization of n-hexane were identified. The structure sensitivity of benzene hydrogenation on shape controlled platinum nanoparticles was also studied. The nanoparticles showed similar selectivities to those found for Pt(111) and Pt(100) single-crystals. Additionally, the nanoparticles have lower activation energies than their single-crystal counterparts

Effect of Surface Modification and Macrophage Phenotype on Particle Internalization

Material properties play a key role in the cellular internalization of polymeric particles. In the present study, we have investigated the effects of material characteristics such as water contact angle, zeta potential, melting temperature, and alternative activation of complement on particle internalization for pro-inflammatory, pro-angiogenic, and naïve macrophages by using biopolymers (∼600 nm), functionalized with 13 different molecules. Understanding how material parameters influence particle internalization for different macrophage phenotypes is important for targeted delivery to specific cell populations. Here, we demonstrate that material parameters affect the alternative pathway of complement activation as well as particle internalization for different macrophage phenotypes. Here, we show that the quantitative structure–activity relationship method (QSAR) previously used to predict physiochemical properties of materials can be applied to targeting different macrophage phenotypes. These findings demonstrated that targeted drug delivery to macrophages could be achieved by exploiting material parameters

Exploring future C++ features within a geometric modeling context

The development of the C++ programming language and its standard library has undergone a renaissance since the introduction of the C++11 standard, making the language more relevant than ever, through modern features, simplification and expansion of the standard library. Comparing past and future feature sets (C++17, C++20, ...) similar to comparing different programming languages. In this article we look at how new and upcoming features of the language can be utilized to ease the development of domain specific application areas through features such as generic programming, compile-time polymorphism and type-safety. We provide representative examples by application to differential geometry by modeling hierarchical structure for parametric object evaluation

Influence of Polymer Chemistry on Cytokine Secretion from Polarized Macrophages

Of central importance to tissue engineering and drug delivery is identifying polymer parameters that increase or decrease specific cytokines in response to biomaterials. In this study, we have interrogated the effects of material descriptors and material characteristics on pro-inflammatory, pro-angiogenic, and naïve macrophages using polymeric particles (∼600 nm), functionalized with 13 different moieties. We characterized tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) secretion for the three macrophage populations and used the quantitative structure–activity relationship method (QSAR) to accurately predict cytokine secretion for the different macrophage phenotypes. The findings presented here demonstrate that altering cellular responses to polymers can be achieved through exploiting material parameters. For pro-inflammatory macrophages, polarity and the ability to hydrogen bond appear to significantly impact TNF-α secretion while charge impacted pro-angiogenic macrophages. Naïve cells were impacted by charge in a similar manner as the pro-angiogenic cells; however, hydrophilicity also increased TNF-α secretion in these cells. For IL-10 secretion, hydrogen bonding was very negatively correlated with pro-inflammatory cells, whereas it was positively correlated with pro-angiogenic cells

How crosslinking Mechanisms of Methacrylated Gellan Gum Hydrogels Alter Macrophage Phenotype

In tissue engineering scaffolds, macrophages play a critical role in determining the host response to implanted biomaterials. Macrophage phenotype is dynamic throughout the host response, and a balance of phenotypes is essential for timely progression from injury to proper wound healing. Therefore, it is important to predict how materials will modulate the response of macrophages. In this study, we investigated the effect of methacrylated gellan gum hydrogels on macrophage phenotype and proliferation with the ultimate goal of improving rational design of biomedical implants. Naïve, along with classically and alternatively activated RAW 264.7 macrophages were seeded on methacrylated gellan gum hydrogels that were fabricated with different thiol-ene ratios and crosslinking mechanisms. Live/dead assays showed that all hydrogels supported cell attachment and proliferation. Stiffer substrates enhanced anti-inflammatory production of nitrites from both naïve and classically activated macrophages compared to the softer substrates. Moreover, arginine and CD206 expression – markers for alternatively activated macrophages – were inhibited by higher thiol content. Introducing ionic crosslinks using calcium did not influence the proliferation or polarization for any of the three macrophage phenotypes. Our results suggest that the macrophage phenotype shift from M1 to M2 is controlled by the different crosslinking mechanisms, physical properties, and the chemistry of methacrylated gellan gum hydrogels

Investigating the Synergistic Effects of Combined Modified Alginates on Macrophage Phenotype

Understanding macrophage responses to biomaterials is crucial to the success of implanted medical devices, tissue engineering scaffolds, and drug delivery vehicles. Cellular responses to materials may depend synergistically on multiple surface chemistries, due to the polyvalent nature of cell–ligand interactions. Previous work in our lab found that different surface functionalities of chemically modified alginate could sway macrophage phenotype toward either the pro-inflammatory or pro-angiogenic phenotype. Using these findings, this research aims to understand the relationship between combined material surface chemistries and macrophage phenotype. Tumor necrosis factor-α (TNF-α) secretion, nitrite production, and arginase activity were measured and used to determine the ability of the materials to alter macrophage phenotype. Cooperative relationships between pairwise modifications of alginate were determined by calculating synergy values for the aforementioned molecules. Several materials appeared to improve M1 to M2 macrophage reprogramming capabilities, giving valuable insight into the complexity of surface chemistries needed for optimal incorporation and survival of implanted biomaterials