Ehsan Fallahiarezoudar

A review of: Application of synthetic scaffold in tissue engineering heart valves

The four heart valves represented in the mammalian hearts are responsible for maintaining unidirectional, non-hinder blood flow. The heart valve leaflets synchronically open and close approximately 4 million times a year and more than 3 billion times during the life. Valvular heart dysfunction is a significant cause of morbidity and mortality around the world. When one of the valves malfunctions, the medical choice is may be to replace the original valves with an artificial one. Currently, the mechanical and biological artificial valves are clinically used with some drawbacks. Tissue engineering heart valve concept represents a new technique to enhance the current model. In tissue engineering method, a three-dimensional scaffold is fabricated as the template for neo-tissue development. Appropriate cells are seeded to the matrix in vitro. Various approaches have been investigated either in scaffold biomaterials and fabrication techniques or cell source and cultivation methods. The available results of ongoing experiments indicate a promising future in this area (particularly in combination of bone marrow stem cells with synthetic scaffold), which can eliminate the need for lifelong anti-coagulation medication, durability and reoperation problems.

Application of response surface methodology in optimization of electrospinning process to fabricate (ferrofluid/polyvinyl alcohol) magnetic nanofibers

Magnetic nanofibers are composed of good dispersion of magnetic nanoparticles along an organic material. Magnetic nanofibers are potentially useful for composite reinforcement, bio-medical and tissue engineering. Nanofibers with the thinner diameter have to result in higher rigidity and tensile strength due to better alignments of lamellae along the fiber axis. In this study, the performance of electrospinning process was explained using response surface methodology (RSM) during fabrication of magnetic nanofibers using polyvinyl alcohol (PVA) as a shelter for (γ-Fe2O3) nanoparticles where the parameters investigated were flow rate, applied voltage, distance between needle and collector and collector rotating speed. The response variable was diameter distribution. The two parameters flow rate and applied voltage in primary evaluation were distinguished as significant factors. Central composite design was applied to optimize the variable of diameter distribution. Quadratic estimated model developed for diameter distribution indicated the optimum conditions to be flow rate of 0.25 ml/h at voltage of 45 kV while the distance and rotating speed are at 8 cm and 1500 rps respectively. The obtained model was verified successfully by the confirmation experiments.

Influence of Process Factors on Diameter of Core (γ-Fe2O3)/Shell (Polyvinyl Alcohol) Structure Magnetic Nanofibers During Co-Axial Electrospinning

In this study, magnetic nanofibers were fabricated using polyvinyl alcohol (PVA) as a shelter for (γ-Fe2O3) magnetic nanoparticles suspension. Two-level full factorial experiments with center and augmented axial points were performed where process parameters studied were flow rate, applied voltage, distance between needle and collector, and collector rotating speed. The response variables analyzed were morphology and fiber diameter distribution. The model obtained from the experimental design revealed that the flow rate, voltage, the two-way interaction of these factors and the second order effect of flow rate-A2 were significant in determining nanofiber diameters. Nanofibers with smaller diameters tend to have higher tensile strength contributed by the better alignment of lamellae along the fibers axis and molecular orientation. The fabricated (γ-Fe2O3)/PVA nanofibers were ultra-fine with nano size diameter within the range of approximately 280–500 nm. GRAPHICAL ABSTRACT

Fabrication (Ferrofluid/Polyvinyl Alcohol) Magnetic Nanofibers via Co-Axial Electrospinning

Magnetic nanofibers were fabricated using polyvinyl alcohol as a shelter for magnetic nanoparticles suspension. The transformation process from ferrofluid and polyvinyl alcohol solution to magnetic nanofibers has been investigated where the response variable analyzed was morphology. The results obtained from the high resolution transmission electron microscopy observation revealed that the flow rate and voltage have significant effect on desirable morphology. Nanofibers with fancy morphology and better aligned order tend to have higher elasticity contributed by the better alignment of lamellae along the fibers axis and molecular orientation. The fabricated nanofibers were ultra-fine with nanosize diameter within the range of approximately 290–380 nm.

Performance evaluation of a petrol station queuing system

A case study was simulated to provide a realistic depiction of an operating system.Investigated factors were number of pump, number of cashier and IATs.2-level full factorial experiments were used for further analysis of simulation.The performance of a service industry queuing system has been analyzed.The influential parameters on queue length and sales rate have been obtained. The main goal of this paper was to develop an integrated simulation-design of experiments (DOE) model to optimize a petrol station queuing system and sales rate. Initially, the petrol station operating system was simulated using Witness 2014 simulation software?. Then, the responses of simulation were deployed as the input of DOE. Two-level full factorial experiments with center points were performed where the simulated model parameter studied were number of pump, number of cashier and inter arrival times (IATs). The response variables analyzed were queue length and sales rate. The obtained model from experimental design revealed that number of cashier and inter arrival time were significant in determining the queue length while all the factors and their interaction were significantly affecting the sales rate.

Fabricating high mechanical strength γ-Fe2O3 nanoparticles filled poly(vinyl alcohol) nanofiber using electrospinning process potentially for tissue engineering scaffold

The use of electrospinning has gained substantial interest in the development of tissue engineering scaffolds due to its ability to produce nanoscale fibers which can mimic the geometry of extracellular tissues. Besides geometry, mechanical property is one of the main elements to be considered when developing tissue engineering scaffolds. In this study, the electrospinning process parameter settings were varied in order to find the optimum setting which can produce electrospun nanofibrous mats with good mechanical properties. Maghemite (γ-Fe2O3) was mixed with poly(vinyl alcohol) and then electrospun to form nanofibers. The five input variable factors involved were nanoparticles content, voltage, flow rate, spinning distance, and rotating speed, while the response variable considered was Young’s modulus. The performance of electrospinning process was systematically screened and optimized using response surface methodology. This work truly demonstrated the sequential nature of designed experimentation. Additionally, the application of various designs of experiment techniques and concepts was also demonstrated. Results revealed that electrospun nanofibrous mats with maximum Young’s modulus (273.51 MPa) was obtained at optimum input settings: 9 v/v% nanoparticle content, 35 kV voltage, 2 mL/h volume flow rate, 8 cm spinning distance, and 3539 r/min of rotating speed. The model was verified successfully by performing confirmation experiments. The nanofibers characterization demonstrated that the nanoparticles were well dispersed inside the nanofibers, and it also showed that the presence of defects on the nanofibers can decrease their mechanical strength. The biocompatibility performance was also evaluated and it was proven that the presence of γ-Fe2O3 enhanced the cell viability and cell growth rate. The developed poly(vinyl alcohol)/γ-Fe2O3 electrospun nanofiber mat has a good potential for tissue engineering scaffolds.

3D Biofabrication of Thermoplastic Polyurethane (TPU)/Poly-l-lactic Acid (PLLA) Electrospun Nanofibers Containing Maghemite (γ-Fe2O3) for Tissue Engineering Aortic Heart Valve

Valvular dysfunction as the prominent reason of heart failure may causes morbidity and mortality around the world. The inability of human body to regenerate the defected heart valves necessitates the development of the artificial prosthesis to be replaced. Besides, the lack of capacity to grow, repair or remodel of an artificial valves and biological difficulty such as infection or inflammation make the development of tissue engineering heart valve (TEHV) concept. This research presented the use of compound of poly-l-lactic acid (PLLA), thermoplastic polyurethane (TPU) and maghemite nanoparticle (γ-Fe2O3) as the potential biomaterials to develop three-dimensional (3D) aortic heart valve scaffold. Electrospinning was used for fabricating the 3D scaffold. The steepest ascent followed by the response surface methodology was used to optimize the electrospinning parameters involved in terms of elastic modulus. The structural and porosity properties of fabricated scaffold were characterized using FE-SEM and liquid displacement technique, respectively. The 3D scaffold was then seeded with aortic smooth muscle cells (AOSMCs) and biological behavior in terms of cell attachment and proliferation during 34 days of incubation was characterized using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and confocal laser microscopy. Furthermore, the mechanical properties in terms of elastic modulus and stiffness were investigated after cell seeding through macro-indentation test. The analysis indicated the formation of ultrafine quality of nanofibers with diameter distribution of 178 ± 45 nm and 90.72% porosity. In terms of cell proliferation, the results exhibited desirable proliferation (109.32 ± 3.22% compared to the control) of cells over the 3D scaffold in 34 days of incubation. The elastic modulus and stiffness index after cell seeding were founded to be 22.78 ± 2.12 MPa and 1490.9 ± 12 Nmm2, respectively. Overall, the fabricated 3D scaffold exhibits desirable structural, biological and mechanical properties and has the potential to be used in vivo.

Optimization and development of Maghemite (γ-Fe2O3) filled poly-l-lactic acid (PLLA)/thermoplastic polyurethane (TPU) electrospun nanofibers using Taguchi orthogonal array for tissue engineering heart valve

Tissue engineering (TE) is an advanced principle to develop a neotissue that can resemble the original tissue characteristics with the capacity to grow, to repair and to remodel in vivo. This research proposed the optimization and development of nanofiber based scaffold using the new mixture of maghemite (γ-Fe2O3) filled poly-l-lactic acid (PLLA)/thermoplastic polyurethane (TPU) for tissue engineering heart valve (TEHV). The chemical, structural, biological and mechanical properties of nanofiber based scaffold were characterized in terms of morphology, porosity, biocompatibility and mechanical behaviour. Two-level Taguchi experimental design (L8) was performed to optimize the electrospun mats in terms of elastic modulus using uniaxial tensile test where the studied parameters were flow rate, voltage, percentage of maghemite nanoparticles in the content, solution concentration and collector rotating speed. Each run was extended with an outer array to consider the noise factors. The signal-to-noise ratio analysis indicated the contribution percent as follow; Solution concentration>voltage>maghemite %>rotating speed>flow rate. The optimum elastic modulus founded to be 28.13±0.37MPa in such a way that the tensile strain was 31.72% which provided desirability for TEHV. An empirical model was extracted and verified using confirmation test. Furthermore, an ultrafine quality of electrospun nanofibers with 80.32% porosity was fabricated. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and cell attachment using human aortic smooth muscle cells exhibited desirable migration and proliferation over the electrospun mats. The interaction between blood content and the electrospun mats indicated a mutual adaption in terms of clotting time and hemolysis percent. Overall, the fabricated scaffold has the potential to provide the required properties of aortic heart valve.

Novel Processing Technique to Produce Three Dimensional Polyvinyl Alcohol/Maghemite Nanofiber Scaffold Suitable for Hard Tissues

Fabrication of three dimensional (3D) tissue engineering scaffolds, particularly for hard tissues remains a challenge. Electrospinning has been used to fabricate scaffolds made from polymeric materials which are suitable for hard tissues. The electrospun scaffolds also have structural arrangement that mimics the natural extracellular matrix. However, electrospinning has a limitation in terms of scaffold layer thickness that it can fabricate. Combining electrospinning with other processes is the way forward, and in this proposed technique, the basic shape of the scaffold is obtained by a fused deposition modelling (FDM) three dimensional (3D) printing machine using the partially hydrolysed polyvinyl alcohol (PVA) as the filament material. The 3D printed PVA becomes a template to be placed inside a mould which is then filled with the fully hydrolysed PVA/maghemite (γ-Fe2O3) solution. After the content in the mould solidified, the mould is opened and the content is freeze dried and immersed in water to dissolve the template. The 3D structure made of PVA/maghemite is then layered by electrospun PVA/maghemite fibers, resulting in 3D tissue engineering scaffold made from PVA/maghemite. The morphology and mechanical properties (strength and stiffness) were analysed and in vitro tests by degradation test and cell penetration were also performed. It was revealed that internally, the 3D scaffold has milli- and microporous structures whilst externally; it has a nanoporous structure as a result of the electrospun layer. The 3D scaffold has a compressive strength of 78.7 ± 0.6 MPa and a Young’s modulus of 1.43 ± 0.82 GPa, which are within the expected range for hard tissue engineering scaffolds. Initial biocompatibility tests on cell penetration revealed that the scaffold can support growth of human fibroblast cells. Overall, the proposed processing technique which combines 3D printing process, thermal inversion phase separation (TIPS) method and electrospinning process has the potential for producing hard tissue engineering 3D scaffolds.