Modeling of Magnetic Scaffolds as Drug Delivery Platforms for Tissue Engineering and Cancer Therapy

Magnetic scaffolds (MagSs) are magneto-responsive devices obtained by the combination of traditional biomaterials (e.g., polymers, bioceramics, and bioglasses) and magnetic nanoparticles. This work analyzes the literature about MagSs used as drug delivery systems for tissue repair and cancer treatment. These devices can be used as innovative drugs and/or biomolecules delivery systems. Through the application of a static or dynamic stimulus, MagSs can trigger drug release in a controlled and remote way. However, most of MagSs used as drug delivery systems are not optimized and properly modeled, causing a local inhomogeneous distribution of the drug’s concentration and burst release. Few physical–mathematical models have been presented to study and analyze different MagSs, with the lack of a systematic vision. In this work, we propose a modeling framework. We modeled the experimental data of drug release from different MagSs, under various magnetic field types, taken from the literature. The data were fitted to a modified Gompertz equation and to the Korsmeyer–Peppas model (KPM). The correlation coefficient (R2) and the root mean square error (RMSE) were the figures of merit used to evaluate the fitting quality. It has been found that the Gompertz model can fit most of the drug delivery cases, with an average RMSE below 0.01 and R2>0.9 . This quantitative interpretation of existing experimental data can foster the design and use of MagSs for drug delivery applications

On the Effect of Complex Permeability and Thermal Material Properties for 3D-CFD Simulation of PEM Fuel Cells

Fuel cells are considered a key technology to decarbonize the power generation sector, thanks to the absence of pollutants emissions related to the direct chemical-electric energy conversion, their high global efficiency, and the possibility for on-board electricity production, overcoming the storage limits of batteries. An example of the renewed interest towards fuel cells is the research in Proton Exchange Membrane Fuel Cell (PEMFC) in the automotive sector, as a candidate alternative to fossil fuels-fed internal combustion engines (ICEs). The complex interplay of electrochemical and physical phenomena concurring in PEMFC makes their understanding and optimization a challenging task. This is a field of active research thanks to the development of advanced CAE tools, e.g., 3D-CFD simulations of non-isothermal reactive flows, in which all the relevant physics is numerically solved, allowing to identify governing mechanisms as well as system bottlenecks. Among the multiple complex aspects, the material property characterization of PEMFC components is one of the major modelling challenges for modern CAE tools. This is usually provided as a set of boundary conditions for the numerical model, having a large impact on the simulated results which is often motivated by an oversimplification of materials characteristics. Examples of commonly overlooked aspects are direction-independent thermal/flow properties for fibrous materials, the neglection on the deformed (compressed) status, and the simplified contact approach. All of these might alter the key parameters (e.g., water management) and mislead designers' conclusions on PEMFC optimization. In this paper three-dimensional CFD simulations are used to weight the impact of orthotropic diffusion layer properties on both flow distribution and heat transfer. In the first part, a simplified test case from literature is created and used to investigate the flow convection/diffusion balance in the gas diffusion layer considering the orthotropic permeability typical of pressed fibrous layers. Differences with respect to the still widely used isotropic permeability will be assessed, and implications on channel bypass and mass transport to the catalyst layer will be provided. In the second part, the analysis moves to the use of orthotropic thermal conductivity for the fibrous gas diffusion layers, which is another commonly discarded aspect despite being well documented in literature. A critical analysis of heat transfer routes between parts of different heat capacity (membrane, diffusion layers, solid plates) and thermal field for all the components will be assessed. Finally, thermal contact resistance between adjacent pressed materials will be applied. The altered thermal pathways for heat removal will be critically analyzed, as well as the differences in temperature distribution and their implication on electricity production and water management. This hierarchical flow/thermal analysis will provide guidelines for more accurate 3D-CFD models for a deeper understanding of flow and heat dynamics in PEMFC

Experimental measurements and CFD modelling of hydroxyapatite scaffolds in perfusion bioreactors for bone regeneration

In the field of bone tissue engineering, particular interest is devoted to the development of 3D cultures to study bone cell proliferation under conditions similar to in vivo ones, e.g. by artificially producing mechanical stresses promoting a biological response (mechanotransduction). Of particular relevance in this context are the effects generated by the flow shear stress, which governs the nutrients delivery rate to the growing cells and which can be controlled in perfusion reactors. However, the introduction of 3D scaffolds complicates the direct measurement of the generated shear stress on the adhered cells inside the matrix, thus jeopardizing the potential of using multi-dimensional matrices. In this study, an anisotropic hydroxyapatite-based set of scaffolds is considered as a 3D biomimetic support for bone cells deposition and growth. Measurements of sample-specific flow resistance are carried out using a perfusion system, accompanied by a visual characterization of the material structure. From the obtained results, a subset of three samples is reproduced using 3D-Computational Fluid Dynamics (CFD) techniques and the models are validated by virtually replicating the flow resistance measurement. Once a good agreement is found, the analysis of flow-induced shear stress on the inner B-HA structure is carried out based on simulation results. Finally, a statistical analysis leads to a simplified expression to correlate the flow resistance with the entity and extensions of wall shear stress inside the scaffold. The study applies CFD to overcome the limitations of experiments, allowing for an advancement in multi-dimensional cell cultures by elucidating the flow conditions in 3D reactors

Experimental assessment and predictive model of the performance of Ti-based nanofluids

The need for innovative propulsion technologies (e.g., fuel cells) in the mobility sector is posing a higher-than-ever burden on thermal management. When low operative temperature shall be ensured, dissipation of a significant amount of heat is requested, together with limited temperature variation of the coolant; mobile applications also yield limitations in terms of space available for cooling subsystems. Nanofluids have recently become one of the most promising solutions to replace conventional coolants. However, the prediction of their effectiveness in terms of heat-transfer enhancement and required pumping power still appears a challenge, being limited by the lack of a general methodology that assesses them simultaneously in various flow regimes. To this end, an experiment was developed to compare a conventional coolant (ethylene glycol/water) and a TiO2-based nanofluid (1% particle loading), focusing on heat transfer and pressure loss. The experimental dataset was used as an input for a physical model based on two independent figures of merit, aiming at an a priori evaluation of the potential simultaneous gain in heat transfer and parasitic power. The model showed conditions of combined gain specifically for the laminar flow regime, whereas turbulent flows proved inherently associated to higher pumping power; overall, criteria are presented to evaluate nanofluid performance as compared to that of conventional coolants. The model is generally applicable to the design of cooling systems and emphasizes laminar flow regime as promising in conjunction with the use of nanofluids, proposing indices for a quantitative a priori evaluation and leading to an advancement with respect to an a posteriori assessment of their performance

Site specific replacements of a single loop nucleoside with a dibenzyl linker may switch the activity of TBA from anticoagulant to antiproliferative

Many antiproliferative G-quadruplexes (G4s) arise from the folding of GT-rich strands. Among these, the Thrombin Binding Aptamer (TBA), as a rare example, adopts a monomolecular well-defined G4 structure. Nevertheless, the potential anticancer properties of TBA are severely hampered by its anticoagulant action and, consequently, no related studies have appeared so far in the literature. We wish to report here that suitable chemical modifications in the TBA sequence can preserve its antiproliferative over anticoagulant activity. Particularly, we replaced one residue of the TT or TGT loops with a dibenzyl linker to develop seven new quadruplex-forming TBA based sequences (TBA-bs), which were studied for their structural (CD, CD melting, 1D NMR) and biological (fibrinogen, PT and MTT assays) properties. The three-dimensional structures of the TBA-bs modified at T13 (TBA-bs13) or T12 (TBA-bs12), the former endowed with selective antiproliferative activity, and the latter acting as potently as TBA in both coagulation and MTT assays, were further studied by 2D NMR restrained molecular mechanics. The comparative structural analyses indicated that neither the stability, nor the topology of the G4s, but the different localization of the two benzene rings of the linker was responsible for the loss of the antithrombin activity for TBA-bs13

A 14-3-3γ dimer-based scaffold bridges CtBP1-S/BARS to PI(4)KIIIβ to regulate post-Golgi carrier formation

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Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Application of an Ageing Model to a Hydrogen-Fuelled PEM Fuel Cell

Hydrogen is one of the most promising energy vectors for achieving the decarbonization of the propulsion systems market. Polymer Electrolyte Membrane Fuel Cell system (PEMFCs) stand out in this panorama, thanks to reduced activation times and low temperatures of use, easily adapting to the needs of the sector. In this paper, a multi-phase, multi-component and non-isothermal 3D-CFD model is proposed to simulate the effects of PEMFC ageing, limiting the system durability due to slow membrane corrosion and loss of material performance and properties degradation, resulting in a reduced current density under equal voltage. The model is applied both in 1D and 3D frameworks implementing a validated model from literature, allowing to estimate the useful life of the cell as a function of parameters such as the degradation rate and the crossover rate. Simulations are carried out at different membrane thicknesses and for different membrane conductivities, using a hydrogen-fuelled serpentine-type PEM fuel cell. The study relevance lies in the possibility to investigate the critical aspects limiting PEMFC system durability, as well as the optimal conditions of use, and it allows to identify corrective design actions

Numerical comparison between conventional and interdigitated flow fields in Proton Exchange Membrane Fuel Cells (PEMFCs)

The recent trend towards the decarbonization of the energy system has renewed the scientific community's interest in fuel cells. These devices have the potential to eliminate, or greatly reduce, the production of greenhouse gases. Polymeric Electrolyte Membrane Fuel Cells (PEMFC) are among the most promising technologies in this regard, being suited for various applications in stationary power plants, vehicles, and portable power devices. The critical issues in PEMFC are the limitation of oxygen transport through the air cathode and water management at high current density operation, which could be largely limited by modifying the design of the reactant supplier channels. In this paper, a three-dimensional CFD approach is used to compare straight and interdigitated flow fields, focusing on the increased current density and improved water management in the diffusion and catalyst layers for the interdigitated design. The simulation results show that the fluid is forced to flow through the porous layers, promoting a convection-type transport, leading to better water removal from the porous layers as well as to increased transport rates of reactants/products to/from the catalyst layers. This leads to reduced concentration overpotentials, and it shows the potential of simulation-driven design for high energy density PEMFC systems