Design and fabrication of 3D‐plotted polymeric scaffolds in functional tissue engineering

Regenerating the load‐bearing tissues requires 3D scaffolds that balance the temporary mechanical function with the biological requirements. In functional tissue engineering, designing scaffolds with biomimetic mechanical properties could promote tissue ingrowth since the cells are sensitive to their local mechanical environment. This work aims to design scaffolds that mimic the mechanical response of the biological tissues under physiological loading conditions. Poly(L ‐lactide) (PLLA) scaffolds with varying porosities and pore sizes were made by the 3D‐plotting technique. The scaffolds were tested under unconfined ramp compression to compare their stress profile under load with that of bovine cartilage. A comparison between the material parameters estimated for the scaffolds and for the bovine cartilage based on the biphasic theory enabled the definition of an optimum window for the porosity and pore size of these constructs. Moreover, the finite element prediction for the stress distribution inside the scaffolds, surrounded by the host cartilaginous tissue, demonstrated a negligible perturbation of the stress field at the site of implantation. The finite element modeling tools in combination with the developed methodology for optimal porosity/pore size determination can be used to improve the design of biomimetic scaffolds. POLYM. ENG. SCI., 47:608–618, 2007. © 2007 Society of Plastics Engineers.     

A modified thermodynamic insight to deliquescence of a void‐containing nanocrystal confirmed by MD simulation

Existence of voids in crystalline structures can affect their physical and chemical properties considerably. When the size of the crystal reaches to nanoscale, experimental determination of its void fraction is difficult. In this work, a molecular dynamics approach is introduced to find equilibrium void fractions of a simple cubic (CsCl) and fcc (KCl) nanocrystals by determination of their deliquescence relative humidity (DRH) for different sizes and void fractions and extrapolation of the results to the bulk limit. To confirm the simulation results, the size dependency of DRH to the nanoparticle size was studied thermodynamically by inclusion of size‐dependent density of water nanodroplet which leads to a simple homographic equation. This method proposes the equilibrium void percents of CsCl and KCl nanoparticles to be 10 and 15%, respectively, which are obtained by extrapolation of the results to the bulk limit. The success of obtained Möbius function was also confirmed by fitting it to experimental data for deliquescence of NaCl nanoparticles which implies the importance of considering density of water nanodroplet as a size dependent quantity. Also, using the mentioned thermodynamic approach, void dependency of deliquescence for the nanoparticles was found to be as a quasi‐linear trend which is compatible with the simulation results. It is noticeable that the approach used this work for determination of equilibrium void fraction is only valid if the utilized force fields are accurate. © 2016 American Institute of Chemical Engineers AIChE J, 62: 4066–4077, 2016     

A modeling approach to the effect of resin characteristics on parison formation in extrusion blow molding

The most critical stage in the extrusion blow‐molding process is the parison formation, as the dimensions of the blow‐molded part are directly related to the parison dimensions. The swelling due to stress relaxation and sagging due to gravity are strongly influenced by the resin characteristics, die geometry, and operating conditions. These factors significantly affect the parison dimensions. This could lead to a considerable amount of time and cost through trial and error experiments to get the desired parison dimensions based upon variations in the resin characteristics, die geometry, and operating conditions. The availability of a modeling technique ensures a more accurate prediction of the entire blow‐molding process, as the proper prediction of the parison formation is the input for the remaining process phases. This study considers both the simulated and the experimental effects of various high‐density polyethylene resin grades on parison dimensions. The resins were tested using three different sets of die geometries and operating conditions. The target parison length was achieved by adjusting the extrusion time for a preset die gap opening. The finite element software BlowParison® was used to predict the parison formation, taking into account the swell and sag. Good agreements were found between the predicted parison dimensions and the experimental data. POLYM. ENG. SCI., 2009. Published by Society of Plastics Engineers     

Modeling of complex parison formation in extrusion blow molding: Effect of medium to large die heads and fuel tank geometry

This work presents the effect of die geometry and die gap opening on the extrudate swell phenomenon, in complex parison formation using the vertical wall distribution system (VWDS) and partial wall distribution system (PWDS). The BlowParison^© software from IMI is used to predict the parison formation for a combined VWDS/PWDS system, accounting for swell, sag, and nonisothermal effects. This software couples a fluid mechanics approach to represent the die flow, with a solid mechanics approach to represent the parison behavior outside the die, and a mathematical swell model to account for the pronounced elongational and shear stresses at high Weissenberg numbers. The emphasis is placed on experimental validation of the predicted parison dimensions using four diverging die geometries and different sets of VWDS/PWDS profiles. The experimental and predicted weight profiles for a dissected fuel tank are also presented. Both experimental and simulation results suggest a strong dependence of extrudate swell to the die geometry in the die land zone. The results also demonstrate the validity of the numerical predictions for part design purposes given the multitude of experimental validations presented in this work. POLYM. ENG. SCI., 2009. Published by the Society of Plastics Engineers     

Effects of rotation speed and time,as solvent removal parameters,on the physico-chemical properties of prepared α-tocopherol nanoemulsions using solvent-displacement technique

Food Science and Biotechnology - A bottom-up approach based on solvent-displacement technique was used to prepare α-tocopherol nanoemulsions. Effects of two main evaporation parameters namely,...     

Structure-function studies on positions 17, 18, and 21 replacement analogues of glucagon: the importance of charged residues and salt bridges in glucagon biological activity

We have designed and synthesized eight compounds 2-9 which incorporate various amino acid residues in positions 17, 18, and 21 of the glucagon molecule: 2, [Lys17]glucagon amide; 3, [Lys18]glucagon amide; 4, [Nle17,Lys18,Glu21]glucagon amide; 5, [Orn17,18, Glu21]glucagon amide; 6, [d-Arg17]glucagon; 7, [d-Arg18]glucagon; 8, [d-Phe17]glucagon; and 9, [d-Phe18]glucagon. Compared to glucagon (IC50 = 1.5 nM), analogues 2-9 were found to have binding affinity IC50 values (in nM) of 0.7, 4.1, 1.0, 2.0, 5.0, 25.0, 43.0, and 32.0, respectively. When these compounds were tested for their ability to stimulate adenylate cyclase (AC) activity, they were found to be full or partial agonists having maximum stimulation values of 100, 100, 100, 100, 87, 78, 94, and 100%, respectively. On the basis of the X-ray crystal structure of [Lys17,18,Glu21]glucagon amide reported here, the ability to form a salt bridge between Lys18 and Glu21 is probably key to their increased binding and second messenger activities. Among the eight analogues synthesized here, only analogue 4 preserves the ability to form a salt bridge between Lys18 and Glu21. However, since these modifications are minor they do not seem to change the amphiphilic character of the C-terminus, allowing these analogues to reach 78-100% stimulation in the adenylate cyclase assay. Biological data from analogues 6-9 supports the idea that position 18 of glucagon may influence binding only, while position 17 may influence both receptor recognition and transduction.     

The effect of secondary nanofiller on mechanical properties and formulation optimization of HDPE/nanoclay/nanoCaCO3 hybrid nanocomposites using response surface methodology

Mechanical properties were evaluated in high-density polyethylene (HDPE) containing plate-like nanoclay (NC) and particulate nano calcium carbonate (nCaCO₃). A two-step melt mixing method was utilized to prepare nanocomposites withNC/nCaCO₃ hybrid content varying from 7 to 15 wt%. Optimization of the morphological, rheological and mechanical characteristics was carried out via Response Surface Methodology by considering nanofiller loadings and compatibilizer (PE-g-MA) content as independent variables. The findings revealed that a nanocomposite composed of 9 wt% PE-g-MA, 3.5 wt%NC, and 10 wt%nCaCO₃ was optimal. This composition exhibited 50% enhancement in Young's modulus and 8% improvement in yield strength over neat HDPE. Despite the reduced impact strength in all of the prepared nanocomposites, the incorporation ofnCaCO₃ prevented a sudden decrease in the toughness caused by the nanoclay. Further, the fracture behavior observed by scanning electron microscopy (SEM) images suggested that nCaCO₃ activated new toughening mechanisms.     

Low level cyclic adenosine 3',5'-monophosphate accumulation analysis of [des-His1, des- Phe6, Glu9] glucagon-NH2 identifies glucagon antagonists from weak partial agonists/antagonists

[des-His1, des-Phe6,Glu9]Glucagon-NH2 is a newly designed glucagon antagonist. This analog has a binding IC50 of 48 nM (compared to glucagon IC50 of 1.5 nM) and demonstrates pure antagonism in an adenylate cyclase assay. Although the number of glucagon antagonists has grown rapidly recently, closer examination suggested that many of these antagonists retained very low, almost imperceptible levels of cAMP accumulation that were sufficient to elicit an in vivo biological response. To investigate more carefully this secondary biological signal, we measured cAMP accumulation in a revised assay using isolated hepatocytes in the presence of the phosphodiesterase (PDE) inhibitor Rolipram. The PDE inhibitors Rolipram and isobutyl-1-methylxanthine (IBMX) increased the sensitivity of the cAMP accumulation assay from approximately 10-fold for the native hormone to 35-fold above basal levels. On the other hand, amrinone, another PDE inhibitor, did not affect the cAMP accumulation caused by glucagon. The use of PDE inhibitors indicated that three glucagon analogs that had previously been reported to have strong antagonist properties in classical adenylate cyclase assays were actually weak partial agonists in this new assay system. [N alpha-Trinitrophenyl-His1, homo-Arg12]glucagon, [des-amino-His1,D-Phe4,Tyr5, Arg12, Lys17,18,Glu21]glucagon, and [des-His1,Glu9]glucagon-NH2 demonstrated 233%, 21%, and 5.5% cAMP accumulation relative to the native hormone in the presence of 25 microM Rolipram. On the other hand, [des-His1,des-Phe6,Glu9]glucagon-NH2, a newly designed glucagon antagonist, did not activate adenylate cyclase in the presence of Rolipram up to a maximal physiological concentration of 1 microM, indicating that it was a pure antagonist of glucagon-induced adenylate cyclase activity and also the first one in this class. This compound and others were tested in a glycogen phosphorylase assay. As [des-His1,des- Phe6,Glu9]glucagon-NH2 did not activate phosphorylase activity, it was chosen as our candidate for in vivo testing in streptozotocin-induced diabetic rats. An initial dose of 0.75 mg/kg was found to cause the greatest lowering of blood glucose levels (to 63% of the initial levels in 15 min) when the bolus was followed by continuous infusion of 25 micrograms/kgxmin for 1 h.