Collagen Fiber Volume Fraction Research Articles

Effect of anti-IL17 and/or Rho-kinase inhibitor treatments on vascular remodeling induced by chronic allergic pulmonary inflammation.

Background and aims:Expansion and morphological dysregulation of the bronchial vascular network occurs in asthmatic airways. Interleukin (IL) -17 and Rho-kinase (ROCK) are known to act in inflammation control and remodeling. Modulation of Rho-kinase proteins and IL-17 may be a promising approach for the treatment of asthma through the control of angiogenesis. Our objective was to analyze the effects of treatment with anti-IL17 and/or Rho-kinase inhibitor on vascular changes in mice with chronic allergic pulmonary inflammation.Methods:Sixty-four BALB/c mice, with pulmonary inflammation induced by ovalbumin were treated with anti-IL17A (7.5/µg per dose, intraperitoneal) and/or Rho-kinase inhibitor (Y-27632-10 mg/kg, intranasal), 1 h before each ovalbumin challenge (22, 24, 26, and 28/days). Control animals were made to inhale saline. At the end of the protocol, lungs were removed, and morphometric analysis was performed to quantify vascular inflammatory, remodeling, and oxidative stress responses.Results:Anti-IL17 or Rho-kinase inhibitor reduced the number of CD4+, CD8+, dendritic cells, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, Rho-kinase 1 and 2, transforming growth factor (TGF-β), vascular endothelial growth factor (VEGF), nuclear factor (NF)-KappaB, iNOS, metalloproteinase (MMP)-9, MMP-12, metalloproteinase inhibitor-1 (TIMP-1), FOXP-3, signal transducer and activator of transcription 1 (STAT1) and phospho-STAT1-positive cells, and actin, endothelin-1, isoprostane, biglycan, decorin, fibronectin and the collagen fibers volume fraction compared with the ovalbumin group (p < 0.05). The combination treatment, when compared with anti-IL17, resulted in potentiation of decrease in the number of IL1β- and dendritic cells-positive cells. When we compared the OVA-RHO inhibitor-anti-IL17 with OVA-RHO inhibitor we found a reduction in the number of CD8+ and IL-17, TGF-β, and phospho-STAT1-positive cells and endothelin-1 in the vessels (p < 0.05). There was an attenuation in the number of ROCK 2-positive cells in the group with the combined treatment when compared with anti-IL17 or Rho-kinase inhibitor-treated groups (p < 0.05).Conclusion:We observed no difference in angiogenesis after treatment with Rho-kinase inhibitor and anti-IL17. Although the treatments did not show differences in angiogenesis, they showed differences in the markers involved in the angiogenesis process contributing to inflammation control and vascular remodeling. The reviews of this paper are available via the supplemental material section.

Mesenchymal stem cell–derived microvesicles alleviate pulmonary arterial hypertension by regulating renin-angiotensin system

In recent years, microvesicles (MVs) derived from mesenchymal stem cells (MSCs) have been proved to be able to improve the outcome of pulmonary arterial hypertension (PAH) in many respects, but the underlying mechanisms of it still remain unclear. Because the renin-angiotensin system (RAS) has been found to be closely related to PAH, the present study was designed to investigate whether the effect of MSC-derived MVs on PAH was correlated with RAS. MVs were isolated and purified from bone marrow MSCs. PAH rat models were established by a single intraperitoneal injection of 1% monocrotaline (MCT, 50 mg/Kg). In vivo study, after 3 weeks of MCT exposure, Nor group and PAH group were injected with 0.5 mL saline every 2 days through tail vein, whereas MVs group was injected with 0.5 mL saline containing 30μg MVs and A-779 + MVs group injected with 0.5 mL saline containing 120μg A-779 and 30μg MVs until 5 weeks of MCT exposure. Whereafter all the groups were analyzed for hemodynamic evaluation, right ventricular hypertrophy index, pulmonary vessel wall thickness index and pulmonary vessel lumen area index, the inflammation score, the collagen fiber volume fraction, the levels of Ang-(1-7) and Ang-Ⅱin plasma and lung tissue, and the mRNA levels of ACE2 and ACE in the lung tissue. MVs derived from MSCs relieved the pulmonary artery pressure, right ventricular hypertrophy index, pulmonary vessel wall thickness index, pulmonary vessel lumen area index, the inflammation score, and the collagen fiber volume fraction. Moreover, in MVs group, ACE2 mRNA in the lung tissues and plasma levels of Ang-(1-7) were both upregulated compared with PAH group. On the contrary, ACE and Ang-II were decreased compared with PAH group. However, the enhanced protective effects observed in MVs group were diminished by the use of A-779, an inhibitor of Mas receptor in ACE2-Ang-(1-7)-Mas axis. MVs derived from bone marrow MSCs can exert beneficial effects against MCT-induced PAH in vivo, meanwhile shifting the balance from ACE-Ang-II-AT1R axis toward the ACE2-Ang-(1–7)-Mas axis, which might be one of the possible therapeutic mechanisms for MVs subcellular treatment.

A depth dependent transversely isotropic micromechanic model of articular cartilage.

Articular cartilage owing to the variation of collagen fibers orientation through its zones has been indicated to have depth dependent mechanical properties. The aim of this study was to present an innovative micromechanics model to predict the depth dependent mechanical properties of articular cartilage as a function of collagen fibers and proteoglycan matrix mechanical properties, collagen fibers volume fraction as well as angle toward cartilage surface. The variation of collagen fibers angle toward the cartilage surface as a function of cartilage depth was computed using the micromechanics model. This function showed that the collagen fibers parallel to the cartilage surface in the superficial zone have a nonlinear angle variation in the transition zone and become perpendicular to cartilage surface in the deep zone. Depth dependent elastic modulus in perpendicular to cartilage surface plane direction was calculated using presented micromechanics model and variation function of the collagen fibers' angle. The results revealed a suitable agreement with that of the experimental measurements in different samples at different ages and races (R2=0.944). The results also showed that the elastic and aggregate modules perpendicular to the cartilage surface plane in the deep zone were 25.8 and 26.3 times higher than that of the superficial zone, respectively. These findings have implications not only for computing the depth dependent mechanical properties of any type of articular cartilage at different ages and races, but also of potential ability for developing a depth dependent transversely isotropic biphasic model to predict the accurate mechanical behavior of articular cartilage.

Retraction notice

Background: Collagen fiber volume fraction of articular cartilage alters by race and age of samples and has a key role in the mechanical behavior of articular cartilage. Methods: This study presented innovative micromechanics models to predict the mechanical properties of superficial and deep zones of any kind of articular cartilage for different races and ages as a function of cartilage component mechanical properties and collagen fiber volume fraction. Results: Collagen fiber volume fraction as a function of normalized depth of an articular cartilage sample was calculated in this study by micromechanics models from variation measurements of its axial elastic modulus. Poisson’s ratio and aggregate modulus was also computed from this function and compared to the experimental data for verification. Since collagen fiber volume fraction was reported in a huge range for different articular cartilages with different races and ages, the effect of this variation is discussed in detail in this paper. The results showed that, as the collagen volume fraction increases, the mechanical properties of articular cartilage in all planes and directions increase as well. Conclusion: Aging reduces all the elasticity mechanical properties of articular cartilage in all directions and planes.

RETRACTED: Experimental and numerical study on the mechanical behavior of rat brain tissue

Brain tissue is a very soft tissue in which the mechanical properties depend on the loading direction. While few studies have characterized these biomechanical properties, it is worth knowing that accurate characterization of the mechanical properties of brain tissue at different loading directions is a key asset for neuronavigation and surgery simulation through haptic devices. In this study, the hyperelastic mechanical properties of rat brain tissue were measured experimentally and computationally. Prepared cylindrical samples were excised from the parietal lobes of rats' brains and experimentally tested by a tensile testing machine. The effects of loading direction on the mechanical properties of brain tissue were measured by applying load on both longitudinal and circumferential directions. The general prediction ability of the proposed hyperelastic model was verified using finite element (FE) simulations of brain tissue tension experiments. The uniaxial experimental results compared well with those predicted by the FE models. The results revealed the influence of loading direction on the mechanical properties of brain tissue. The Ogden hyperelastic material model was suitably represented by the non-linear behavior of the brain tissue, which can be used in future biomechanical simulations. The hyperelastic properties of brain tissue provided here have interest to the medical research community as there are several applications where accurate characterization of these properties are crucial for an accurate outcome, such as neurosurgery, robotic surgery, haptic device design or car manufacturing to evaluate possible trauma due to an impact.

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.

RETRACTED: Fabrication and mechanical characterization of a polyvinyl alcohol sponge for tissue engineering applications

Polyvinyl alcohol (PVA) sponges are widely used for clinical applications, including ophthalmic surgical treatments, wound healing and tissue engineering. There is, however, a lack of sufficient data on the mechanical properties of PVA sponges. In this study, a biomechanical method is used to characterize the elastic modulus, maximum stress and strain as well as the swelling ratio of a fabricated PVA sponge (P-sponge) and it is compared with two commercially available PVA sponges (CENEFOM and EYETEC). The results indicate that the elastic modulus of the P-sponge is 5.32% and 13.45% lower than that of the CENEFOM and EYETEC sponges, while it bears 4.11% more and 10.37% less stress compared to the CENEFOM and EYETEC sponges, respectively. The P-sponge shows a maximum strain of 32% more than the EYETEC sponge as well as a 26.78% higher swelling ratio, which is a significantly higher absorbency compared to the CENEFOM. It is believed that the results of this study would help for a better understanding of the extension, rupture and swelling mechanism of PVA sponges, which could lead to crucial improvement in the design and application of PVA-based materials in ophthalmic and plastic surgeries as well as wound healing and tissue engineering.

RETRACTED: Modeling of cerebral aneurysm using equivalent electrical circuit (Lumped Model)

The circle of Willis (CoW) is a key asset in brain performance as it supports adequate blood supply to the brain. The lumped method (electrical equivalent circuits) is a useful model to simulate the process of the human cardiovascular system. In this study, the whole cardiovascular system is modeled, using an equivalent electrical circuit to investigate an aneurysm in an artery. The cerebrovascular system consists of 29 compartments, which includes the CoW. Each vessel is modeled by a resistor, a capacitor and an inductor. Using MATLAB Simulink, the left and right ventricles are modeled by controlled voltage sources and diodes. The effects of the left internal carotid artery aneurysm (Fusiform) on the pressure of the efferent arteries in the circle of Willis are studied. The modeling results are entirely in agreement with the available clinical observations. The results of the present study may have clinical implications for modeling different cardiovascular diseases, such as arterial stiffness and atherosclerosis.

Langevin dynamics modeling of the water diffusion tensor in partially aligned collagen networks

In this work, a Langevin dynamics model of the diffusion of water in articular cartilage was developed. Numerical simulations of the translational dynamics of water molecules and their interaction with collagen fibers were used to study the quantitative relationship between the organization of the collagen fiber network and the diffusion tensor of water in model cartilage. Langevin dynamics was used to simulate water diffusion in both ordered and partially disordered cartilage models. In addition, an analytical approach was developed to estimate the diffusion tensor for a network comprising a given distribution of fiber orientations. The key findings are that (1) an approximately linear relationship was observed between collagen volume fraction and the fractional anisotropy of the diffusion tensor in fiber networks of a given degree of alignment, (2) for any given fiber volume fraction, fractional anisotropy follows a fiber alignment dependency similar to the square of the second Legendre polynomial of cos(θ), with the minimum anisotropy occurring at approximately the magic angle (θ(MA)), and (3) a decrease in the principal eigenvalue and an increase in the transverse eigenvalues is observed as the fiber orientation angle θ progresses from 0° to 90°. The corresponding diffusion ellipsoids are prolate for θ<θ(MA), spherical for θ≈θ(MA), and oblate for θ>θ(MA). Expansion of the model to include discrimination between the combined effects of alignment disorder and collagen fiber volume fraction on the diffusion tensor is discussed.

SPARC/Osteonectin Functions to Maintain Homeostasis of the Collagenous Extracellular Matrix in the Periodontal Ligament

Expression of secreted protein acidic and rich in cysteine (SPARC)/osteonectin, a collagen-binding matricellular protein, is frequently associated with tissues with high rates of collagen turnover, such as bone. In the oral cavity, expression of SPARC/osteonectin has been localized to the periodontal ligament (PDL), a collagen-rich tissue with high rates of collagen turnover. The PDL is critical for tooth position within the alveolar bone and for absorbing forces generated by chewing. To characterize the function of SPARC/osteonectin in PDL, SPARC/osteonectin expression in murine PDL was evaluated by immunochemistry at 1, 4, 6, and >18 months. Highest levels of SPARC/osteonectin were detected at 1 and >18 months, with decreased levels associated with adult (4-6 months) PDL. To determine whether the absence of SPARC/osteonectin expression influenced cellular and fibrillar collagen content in PDL, PDL of SPARC-null mice was evaluated using histological stains and compared with that of wild-type (WT). Our results demonstrated decreased numbers of nuclei in PDL of SPARC-null mice at 1 month. In addition, decreased collagen volume fractions were found at 1 and >18 months and decreases in thick collagen fiber volume fraction were detected at 4, 6, and >18 months in SPARC-null PDL. The greatest differences in cell number and in collagen content between SPARC-null and WT PDL coincided with ages at which levels of SPARC/osteonectin expression were highest in WT PDL, at 1 and >18 months. These results support the hypothesis that SPARC/osteonectin is critical in the control of tissue collagen content and indicate that SPARC/osteonectin is necessary for PDL homeostasis.

Micromechanical modeling of the epimysium of the skeletal muscles

A micromechanical model has been developed to investigate the mechanical properties of the epimysium. In the present model, the collagen fibers in the epimysium are embedded randomly in the ground substance. Two parallel wavy collagen fibers and the surrounding ground substance are used as the repeat unit (unit cell), and the epimysium is considered as an aggregate of unit cells. Each unit cell is distributed in the epimysium with some different angle to the muscle fiber direction. The model allows the progressive straightening of the collagen fiber as well as the effects of fiber reorientation. The predictions of the model compare favorably against experiment. The effects of the collagen fiber volume fraction, collagen fiber waviness at the rest length and the mechanical properties of the collagen fibers and the ground substance are analyzed. This model allows the analysis of mechanical behavior of most soft tissues if appropriate experimental data are available.