Shahab Faghihi

Measurement of the uniaxial mechanical properties of healthy and atherosclerotic human coronary arteries.

Atherosclerosis is a common arterial disease which alters the stiffness of arterial wall. Arterial stiffness is related to many cardiovascular diseases. In this investigation, maximum stress and strain as well as physiological and maximum elastic modulus of 22 human coronary arteries are measured. In addition, the force-displacement diagram of human coronary artery is obtained to discern the alterations between the healthy and atherosclerotic arterial wall stiffness. The age of each specimen and its effect on the elastic modulus of human coronary arteries is also considered. Twenty-two human coronary arteries, including eight atherosclerotic and fourteen healthy arteries are excised within 5 hours post-mortem. Samples are mounted on a tensile-testing machine and force is applied until breakage occurs. Elastic modulus coefficient of each specimen is calculated to compare the stiffness of healthy and atherosclerotic coronary arteries. The results show that the atherosclerotic arteries bear 44.55% more stress and 34.61% less strain compared to the healthy ones. The physiological and maximum elastic moduli of healthy arteries are 2.53 and 2.91 times higher than that of atherosclerotic arteries, respectively. The age of specimens show no correlation with the arterial wall stiffness. A combination of biomechanics and mathematics is used to characterize the mechanical properties of human coronary arteries. These results could be utilized to understand the extension and rupture mechanism of coronary arteries and has implications for interventions and surgeries, including balloon-angioplasty, bypass, and stenting.

A finite element investigation on plaque vulnerability in realistic healthy and atherosclerotic human coronary arteries

Atherosclerosis is the most common arterial disease. It has been shown that stresses that are induced during blood circulation can cause plaque rupture and, in turn, lead to thrombosis and stroke. In this study, finite element method is used to predict plaque vulnerability based on peak plaque stress using human samples. A total of 23 healthy and atherosclerotic human coronary arteries of 14 healthy and 9 atherosclerotic patients are excised within 5 h postmortem. The samples are mounted on an uniaxial tensile test machine, and the obtained mechanical properties are used in two-dimensional and three-dimensional finite element models. The results including the Neo–Hookean hyperelastic coefficients of the samples as well as peak plaque stresses are analyzed. The results indicate that the atherosclerotic human coronary arteries have significantly (p < 0.05) higher stiffness compared with the healthy ones. The hypocellular plaque also has the highest stress values and, as a result, is most likely (vulnerable) to rupture, while the calcified type has the lowest stress values and, consequently, is expected to remain stable. The results could be used in the plaque vulnerability anticipation and have clinical implications in interventions and surgeries, including balloon angioplasty, bypass, and stenting.

Graphene oxide/poly(acrylic acid)/gelatin nanocomposite hydrogel: experimental and numerical validation of hyperelastic model.

Owing to excellent thermal and mechanical properties, graphene-based nanomaterials have recently attracted intensive attention for a wide range of applications, including biosensors, bioseparation, drug release vehicle, and tissue engineering. In this study, the effects of graphene oxide nanosheet (GONS) content on the linear (tensile strength and strain) and nonlinear (hyperelastic coefficients) mechanical properties of poly(acrylic acid) (PAA)/gelatin (Gel) hydrogels are evaluated. The GONS with different content (0.1, 0.3, and 0.5 wt.%) is added into the prepared PAA/Gel hydrogels and composite hydrogels are subjected to a series of tensile and stress relaxation tests. Hyperelastic strain energy density functions (SEDFs) are calibrated using uniaxial experimental data. The potential ability of different hyperelastic constitutive equations (Neo-Hookean, Yeoh, and Mooney-Rivlin) to define the nonlinear mechanical behavior of hydrogels is verified by finite element (FE) simulations. The results show that the tensile strength (71%) and elongation at break (26%) of composite hydrogels are significantly increased by the addition of GONS (0.3 wt.%). The experimental data is well fitted with those predicted by the FE models. The Yeoh material model accurately defines the nonlinear behavior of hydrogels which can be used for further biomechanical simulations of hydrogels. This finding might have implications not only for the improvement of the mechanical properties of composite hydrogels but also for the fabrication of polymeric substrate materials suitable for tissue engineering applications.

STUDY OF PLAQUE VULNERABILITY IN CORONARY ARTERY USING MOONEY–RIVLIN MODEL: A COMBINATION OF FINITE ELEMENT AND EXPERIMENTAL METHOD

Atherosclerosis is a disease in which plaque builds up inside arteries. It is also considered as one of the most serious and common forms of cardiovascular disease which can lead to heart attack and stroke. In the current research, finite element method is used to anticipate plaque vulnerability based on peak plaque stress using human samples. A total of 23 healthy and atherosclerotic human coronary arteries, including 14 healthy and 9 atherosclerotic are removed within 5 h postmortem. The samples are mounted on a uniaxial tensile test machine and the obtained mechanical properties are used in finite element models. The results, including the Mooney–Rivlin hyperelastic constants of the samples as well as peak plaque stresses, are computed. It is demonstrated that the atherosclerotic human coronary arteries have significantly (p < 0.05) higher stiffness compared to healthy ones. The hypocellular plaque, in addition, has the highest stress values compared to the cellular and calcified ones and, consequently, is so prone to rupture. The calcified plaque type, nevertheless, has the lowest stress values and, remains stable. The results of this study can be used in the plaque vulnerability prediction and could have clinical implications for interventions and surgeries, such as balloon angioplasty, bypass and stenting.

Measurement of the uniaxial mechanical properties of rat brains infected by Plasmodium berghei ANKA

Degenerative and demyelinating diseases are known to alter the mechanical properties of brain tissue. While few studies have characterized these biomechanical changes, it is clear that accurate characterization of the mechanical properties of diseased brain tissue could be a substantial asset to neuronavigation and surgery simulation through haptic devices. In this study, samples of brain tissue from rats infected with Plasmodium berghei ANKA, an African murine malaria parasite, are evaluated using a uniaxial tensile test machine. Infected brains having different levels of parasitemia are mounted on the testing machine and extended until failure of the tissue. The stress–strain curve of each sample is obtained and compared to healthy rat brain tissue. Young’s modulus of each sample is extracted from the Hookean part of the stress–strain diagram. Young’s modulus of rats’ brain shows considerable difference among the samples having various levels of parasitemia compared with the controls. For instance, the brains with 0% (control), 1.5%, and 9% parasitemia showed a Young’s modulus of 46.15, 54.54, and 266.67 kPa, respectively. This suggests sequestration of the stiffened and less deformable parasitized red blood cells in the brain microvasculature.

RETRACTED: Hyperelastic mechanical behavior of rat brain infected by Plasmodium berghei ANKA – Experimental testing and constitutive modeling

The following article has been included in a multiple retraction: Karimi A, Navidbakhsh M, Beigzadeh B, et al. Hyperelastic mechanical behavior of rat brain infected by Plasmodium berghei ANKA – experimental testing and constitutive modelling. Int J Damage Mech 2014;23:857–871, DOI: 10.1177/1056789513514072. In 2015 SAGE became aware of author misconduct concerning the suspected fabrication of identities, as well as the impersonation of legitimate individuals, to manipulate the peer review process across three separate journal publications. SAGE and the journal Editors immediately launched an investigation and have decided to retract the following articles for reasons of author misconduct. Alireza Karimi was the submitting author on 12 of the articles. SAGE regrets the academic record was compromised by manipulation of the peer review process and apologises to readers. OnlineFirst articles (these articles will not be published in an issue) International Journal of Damage Mechanics Karimi A, Navidbakhsh M and Razaghi R. Dynamic finite element simulation of the human head damage mechanics protected by polyvinyl alcohol sponge. Int J Damage Mech, first published on 15 May 2014, DOI: 10.1177/1056789514535945. Journal of Thermoplastic Composite Materials Karimi A, Navidbakhsh M and Haghpanahi M. Constitutive model for numerical analysis of polyvinyl alcohol sponge under different strain rates. J Thermoplast Compos Mater, first published on 15 January 2014, DOI: 10.1177/0892705713520176. Karimi A, Navidbakhsh M, Yousefi H et al. An experimental study on the elastic modulus of gelatin hydrogels using different stress–strain definitions. J Thermoplast Compos Mater, first published on 29 April 2014, DOI: 10.1177/0892705714533377. Elhamian MM, Alizadeh M, Shokrieh MM, et al. An innovative three-dimensional biphasic-laminated composite model for articular cartilage tissue. J Thermoplast Compos Mater, first published on 1 February 2015, DOI: 10.1177/0892705715569821. Perfusion Karimi A, Navidbakhsh M, Yamada H, et al. A comparative study on the quasilinear viscoelastic mechanical properties of the umbilical artery and the umbilical vein. Perfusion, first published on 22 May 2014, DOI: 10.1177/0267659114536761. Tehrani P, Rahmani S, Karimi A, et al. A novel cardiac assist device (AVICENA): a numerical study to compute the generated power. Perfusion, first published on 19 August 2014, DOI: 10.1177/ 0267659114547943. Elhamian SMM, Alizadeh M, Shokrieh MM, et al. The effect of collagen fiber volume fraction on the mechanical properties of articular cartilage by micromechanics models. Perfusion, first published on 20 August 2014, DOI: 10.1177/0267659114547942. Razaghi R, Karimi A, Navidbakhsh M, et al. Determination of the vulnerable plaque in a stenotic human coronary artery – finite element modelling. Perfusion, first published on 28 October 2014, DOI: 10.1177/0267659114557720. Articles published in an issue International Journal of Damage Mechanics Karimi A, Navidbakhsh M, Beigzadeh B, et al. Hyperelastic mechanical behavior of rat brain infected by Plasmodium berghei ANKA – experimental testing and constitutive modelling. Int J Damage Mech 2014;23:857–871, DOI: 10.1177/1056789513514072. Perfusion Karimi A, Navidbakhsh M and Faghihi S. A comparative study on plaque vulnerability using constitutive equations. Perfusion, 2014;29:178–183, DOI: 10.1177/0267659113502835. Abdi M, Karimi A, Navidbakhsh M, et al. Modeling of cerebral aneurysm using equivalent electrical circuit (Lumped Model). Perfusion 2014;29:142–152, DOI: 10.1177/0267659113498617. Karimi A, Navidbakhsh M and Faghihi S. Fabrication and mechanical characterization of a polyvinyl alcohol sponge for tissue engineering applications. Perfusion 2014;29:231–237, DOI: 10.1177/ 0267659113513823. Karimi A, Navidbakhsh M, Yousefi H, et al. Experimental and numerical study on the mechanical behavior of rat brain tissue. Perfusion 2014;29:307–314, DOI: 10.1177/0267659114522088.

Synthesis and evaluation of PEG-O-chitosan nanoparticles for delivery of poor water soluble drugs: Ibuprofen

Current methods for preparation of PEGylated chitosan have limitations such as harsh de protecting step and several purification cycles. In the present study, a facile new method for conjugating methoxy polyethylene glycol (mPEG) to chitosan under mild condition is introduced to improve water solubility of chitosan and control the release of poor water soluble drugs. The method consists of chitosan modification by grafting the C6 position of chitosan to mPEG which is confirmed by Fourier transformed-infrared (FT-IR) and proton nuclear magnetic resonance ((1)HNMR) analyses. The amine groups at the C2 position of chitosan are protected using sodium dodecylsulfate (SDS) which is removed by dialyzing the precipitation against Tris solution. The chemical structure of the prepared polymer is characterized by FTIR and (1)HNMR. The synthesized polymer is then employed to prepare nanoparticles which are characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), scanning electron microscopy (SEM), and dynamic light scattering (DLS) for their size and morphology. The nanoparticles are used for encapsulation of ibuprofen followed by in vitro release investigation in gastrointestinal and simulated biological fluids. The chitosan nanoparticles are used as control. The PEGylated nanoparticles show a particle size of 80 nm with spherical morphology. The results clearly show that drug release from PEGylated chitosan nanoparticles is remarkably slower than chitosan. In addition, drug encapsulation and encapsulation efficiency in PEGylated nanoparticles are dependent on the amount of drug added to the formulation being significantly higher than chitosan nanoparticles. This study provides an efficient, novel, and facile method for preparing a nano carrier system for delivery of water insoluble drugs.

Poly(ethyleneimine) functionalized carbon nanotubes as efficient nano-vector for transfecting mesenchymal stem cells

For gene and drug delivery applications, carbon nanotubes (CNTs) have to be functionalized in order to become compatible with aqueous media and bind with genetic materials. In this study, combination of polyethyleneimine (PEI) grafted multi-walled carbon nanotubes (PEI-g-MWCNTs) and chitosan substrate is used as an efficient gene delivery system for transfection of hard-to-transfect bone marrow mesenchymal stem cells (BMSCs) with enhanced green fluorescent protein (EGFP) gene. Fourier transform infrared (FT-IR) spectra, dynamic light scattering (DLS) analysis and zeta potential measurements are used to characterize binding of PEI, particle size distribution and colloidal stability of the functionalized CNTs, respectively. DNA binding affinity, cellular uptake, transfection efficiency and possible cytotoxicity are also tested by agarose gel electrophoresis, flow cytometry, cytochemisty and MTT assay. The results demonstrate that cytotoxic effect of PEI-g-MWCNTs is negligible under optimal transfection condition. In consistency with high cellular uptake (>82%), PEI-g-MWCNTs give higher delivery of EGFP into the BMSCs which results in a more sustained expression of the model gene (EGFP) in short-term culture. These results suggest that PEI-g-MWCNTs in corporation with chitosan substrates would be a promising delivery system for BMSCs, a cell type with relevancy in the regenerative medicine and clinical applications.

Dual-functionalized graphene oxide for enhanced siRNA delivery to breast cancer cells.

The aim of this study is to improve hydrocolloid stability and siRNA transfection ability of a reduced graphene oxide (rGO) based nano-carrier using a phospholipid-based amphiphilic polymer (PL-PEG) and cell penetrating peptide (CPPs). The dual functionalized nano-carrier is comprehensively characterized for its chemical structure, size, surface charge and morphology as well as thermal stability. The nano-carrier cytocompatibility, siRNA condensation ability both in the presence and absence of enzyme, endosomal buffering capacity, cellular uptake and intracellular localization are also assessed. The siRNA loaded nano-carrier is used for internalization to MCF-7 cells and its gene silencing ability is compared with AllStars Hs Cell Death siRNA as a model gene. The nano-carrier remains stable in biological solution, exhibits excellent cytocompatibility, retards the siRNA migration and protects it against enzyme degradation. The buffering capacity analysis shows that incorporation of the peptide in nano-carrier structure would increase the resistance to endo/lysosomal like acidic condition (pH 6-4) The functionalized nano-carrier which is loaded with siRNA in an optimal N:P ratio presents superior internalization efficiency (82±5.1% compared to HiPerFect(®)), endosomal escape quality and capable of inducing cell death in MCF-7 cancer cells (51±3.1% compared to non-treated cells). The success of siRNA-based therapy is largely dependent on the safe and efficient delivery system, therefore; the dual functionalized rGO introduced here could have a great potential to be used as a carrier for siRNA delivery with relevancy in therapeutics and clinical applications.

The effect of crystallographic orientation of titanium substrate on the structure and bioperformance of hydroxyapatite coatings

This study investigates the effects of crystallographic orientation of titanium substrates on the atomic structure and biological characteristics of hydroxyapatite (HA) coatings. Samples are prepared from extruded rod and rolled sheet of commercially pure titanium having distinct distribution of crystallographic planes. Electrophoresis is used to coat titanium substrates having different microstructures. The biological performance of both HA-coated and non-coated samples is assessed by osteoblast cell attachment, proliferation, differentiation and morphological studies. X-ray diffraction (XRD) analysis of the HA-coated samples indicates the predominant orientation of (002) for HA-coated sheets compared to (211) for the HA-coated rod samples. The numbers of attached and grown cells are higher on the surface of the HA-coated sheet samples. There is also a significant difference in alkaline phosphatase activity on the HA-coated sheet samples. Scanning electron microscopy (SEM) analysis of osteoblast cells grown on HA-coated and non-coated samples demonstrates differences in morphology with respect to spreading and attachment patterns. We believe that the specific atomic structure that is induced in the HA coating by the crystallographic orientation of the sheet substrate causes orientation-dependent coordination with biomolecules and improves cellular interactions. This suggests that crystal orientation of the substrate can be used to both influence the structure of the coating material and improve and control cell-substrate interactions.