Reproduction of Kinematic Behavior of Elastic Lamellae in the Thoracic Aortic Media

Author(s):  
Atsutaka Tamura ◽  
Yuya Kato

The thickening of the aortic wall is a mechanical adaptation to the prolonged increase in intravascular pressure resulting from hypertension, which is regulated by the smooth muscle cell layer (SML) and the elastic lamina (EL). Herein, we built a simplified computational model of the aortic media composed of SML and EL and simulated the phenomenon of EL undulation or EL buckling at no-load condition (in vitro) by releasing compressive prestress assigned to the EL. Using the design of experiments approach, we found that the prestress assigned to the EL, the thickness of the EL, and a coupled or interspace connecting length between the SML and the EL are significantly influential factors in representing EL buckling at the unloaded state. We also found that the degree of EL waviness and the change in residual stresses within the SML and the EL are inversely correlated. Furthermore, by increasing the stiffness of the SML, we successfully reconstructed the disappearance of EL undulation at 25% stretch, replicating the dilation of a normal aorta under physiological loading conditions. It can be expected that these findings will help unveil the roles of the SML and the EL in maintaining the mechanical homeostasis of the arterial wall.

Author(s):  
Atsutaka Tamura ◽  
Yuya Kato

Abstract Mathematical modeling of the thoracic aorta is important for understanding the development and progression of various cardiovascular diseases, helping to detect extraordinary stress distributions of the hypertensive aortic wall, even in early stages. However, it is difficult to ensure the biofidelity of biological materials in formulating a mathematical model. In a freshly isolated aortic media, composed mainly of smooth muscle cell layers (SMLs) and elastic laminae (ELs), circumferential EL waviness and longitudinal EL undulation are often observed because of the structural “buckling” of ELs. This is considered to be closely associated with residual stresses of SMLs and ELs in the aortic wall but the mechanism underlying such EL buckling behavior remains unclear. In the present study, a series of numerical simulations were designed to identify effective mechanical parameters to reproduce EL buckling in the aortic media. We found that prestress initially administered to ELs in the circumferential and axial directions, and the predefined internodal distance, which couples the SML and EL, are essential to computationally reconstruct the circumferential EL waviness and the longitudinal EL undulation in an unloaded state. We also proposed a set of equations based on the numerical results and successfully predicted EL buckling behaviors of the aorta in vitro.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Liyuan Zhang ◽  
Xiaomei Lin ◽  
Ting Wang ◽  
Wei Guo ◽  
Yuan Lu

AbstractCell-free protein synthesis (CFPS) systems have become an ideal choice for pathway prototyping, protein production, and biosensing, due to their high controllability, tolerance, stability, and ability to produce proteins in a short time. At present, the widely used CFPS systems are mainly based on Escherichia coli strain. Bacillus subtilis, Corynebacterium glutamate, and Vibrio natriegens are potential chassis cells for many biotechnological applications with their respective characteristics. Therefore, to expand the platform of the CFPS systems and options for protein production, four prokaryotes, E. coli, B. subtilis, C. glutamate, and V. natriegens were selected as host organisms to construct the CFPS systems and be compared. Moreover, the process parameters of the CFPS system were optimized, including the codon usage, plasmid synthesis competent cell selection, plasmid concentration, ribosomal binding site (RBS), and CFPS system reagent components. By optimizing and comparing the main influencing factors of different CFPS systems, the systems can be optimized directly for the most influential factors to further improve the protein yield of the systems. In addition, to demonstrate the applicability of the CFPS systems, it was proved that the four CFPS systems all had the potential to produce therapeutic proteins, and they could produce the receptor-binding domain (RBD) protein of SARS-CoV-2 with functional activity. They not only could expand the potential options for in vitro protein production, but also could increase the application range of the system by expanding the cell-free protein synthesis platform.


2008 ◽  
Vol 399 ◽  
pp. 205-210
Author(s):  
Dan Ioan Stoia ◽  
Nicolae Faur ◽  
Mirela Toth-Taşcău ◽  
Laurenţiu Culea

The paper describes the biomechanical behavior of a cervical implanted unit (CIU) in two conditions: during the physiological and extreme loading. In order to reveal these behaviors, the anatomical structure composed by the C2 and C3 cervical vertebras was implanted using a plate-screws metal structure. The implant was design to perform dynamical, by allowing longitudinal, transversal and rotational movements. The physiological conditions were simulated by the pulsatory negative loading, while the extreme loading was simulated by the alternant symmetrical loading. The tests reveal two behaviors: the durability of the CIU in the physiological loading conditions and the failure of the structure under extreme load.


2006 ◽  
Vol 14 (10) ◽  
pp. 993
Author(s):  
Tie-Sheng Zheng ◽  
Ya-Na Wang ◽  
Ai-Ping Zong

Author(s):  
Atsutaka Tamura ◽  
Koki Matsumoto

Abstract The mechanical and structural characteristics of aortic media have profound effects on the physiology and pathophysiology of an aorta. However, many aspects of the aortic tissue remain poorly understood, partly due to the intrinsic layered wall structure and regionally varying residual stresses. Our recent works have demonstrated that a mechanical interaction between the elastic lamina (EL) and smooth muscle layer in the aortic media can be computationally reproduced using a simplified finite element (FE) model. However, it is questionable whether the simplified FE model we created was representative of the structure of a real medial wall and its modeling technique would be applicable to develop a more sophisticated and structure-based aortic FE model. This study aimed to computationally represent EL buckling in the aortic medial ring at an unloaded state and successfully reproduced transmural variation in EL waviness across the aortic wall. We also aimed at confirming the inner and outer layers of the medial wall are subjected to compressive and tensile residual stresses, respectively, at the unloaded state, implying that the ring model will open spontaneously when it is radially cut. Moreover, the computed residual stresses were found to be within the reasonable range of the predicted values, 1–10 kPa, supporting the validity of our modeling approach. Although further study is required, the information obtained here will greatly help improve the understanding of basic aortic physiology and pathophysiology, while simultaneously providing a basis for more sophisticated computational modeling of the aorta.


2022 ◽  
Vol 11 (6) ◽  
pp. 751-758
Author(s):  
Nadia REGOUAT ◽  
Cheboub Amina ◽  
Hadj-Bekkouche Fatima

Sexual hormones are determinant players in cardiovascular diseases. The aim of this study was to investigate the effects of testosterone deficiency, induced by castration, on oxidative status and the histopathology of the aor-tic media tunica. The experiments were undertaken on a batch of 30 Wistar males’ rats randomised into 3 groups, 10 control (Con), 10 castrated (Cas) and 10 castrated then supplemented with testosterone (Cas-T). Our results showed that testosterone deficiency induced a significant decrease in myeloperoxidase activity (19,95 ± 1, 79 vs 34,86 ± 1,13, p˂0,0001) this was maintained even after testosterone replacement. Furthermore, testosterone deficiency decreased the antioxidant capacity by reducing GSH in plasma (0,118 ± 0,003 vs 0,15 ± 0,011, p˂0,05). Our results also indicate that testos-terone supplementation leads to a significant increase in ceruloplasmin lev-els (62,37 ± 15,89 vs 148,12 ± 27,77, p ˂0.05). The histomorphometric exami-nation of the aortic tunica media in castrated rats showed a significant de-crease of media thickness (274,7 ± 2,96 vs 317,6 ± 5,19, p ˂0.0001) and VSMC count (108,1 ± 6,47 vs 130 ± 6,147, p ˂ 0.05) associated with damaged and broken elastic lamina. Testosterone supplementation restores the media thickness and the count of VSMC. Our findings demonstrate that testos-terone deficiency leads to a decrease in the count of VSMC and a rupture of elastic lamina. Testosterone altered the plasma oxidative status through ac-tions on GSH, MPO and ceruloplasmin.


2020 ◽  
Vol 117 (41) ◽  
pp. 25532-25542 ◽  
Author(s):  
Jonathan D. Winkelman ◽  
Caitlin A. Anderson ◽  
Cristian Suarez ◽  
David R. Kovar ◽  
Margaret L. Gardel

The actin cytoskeleton assembles into diverse load-bearing networks, including stress fibers (SFs), muscle sarcomeres, and the cytokinetic ring to both generate and sense mechanical forces. The LIM (Lin11, Isl- 1, and Mec-3) domain family is functionally diverse, but most members can associate with the actin cytoskeleton with apparent force sensitivity. Zyxin rapidly localizes via its LIM domains to failing SFs in cells, known as strain sites, to initiate SF repair and maintain mechanical homeostasis. The mechanism by which these LIM domains associate with stress fiber strain sites (SFSS) is not known. Additionally, it is unknown how widespread strain sensing is within the LIM protein family. We identify that the LIM domain-containing region of 18 proteins from the Zyxin, Paxillin, Tes, and Enigma proteins accumulate to SFSS. Moreover, the LIM domain region from the fission yeast protein paxillin like 1 (Pxl1) also localizes to SFSS in mammalian cells, suggesting that the strain sensing mechanism is ancient and highly conserved. We then used sequence and domain analysis to demonstrate that tandem LIM domains contribute additively, for SFSS localization. Employing in vitro reconstitution, we show that the LIM domain-containing region from mammalian zyxin and fission yeast Pxl1 binds to mechanically stressed F-actin networks but does not associate with relaxed actin filaments. We propose that tandem LIM domains recognize an F-actin conformation that is rare in the relaxed state but is enriched in the presence of mechanical stress.


Author(s):  
Chitra Gupta ◽  
VIJAY JUYAL ◽  
Upendra Nagaich

Objective: The present study emphasizes the synthesis, optimization, and evaluation of ocular in-situ gel for ophthalmic drug delivery against conjunctivitis. Methods: Pre-formulation studies on the drug and polymers were carried out, which included the study of various physicochemical properties of the drug and drug-polymer compatibility studies. The 12 different formulations were further pre-optimised by Taguchi method for determining the number of influential factors. Furthermore, the formulation optimization was done by using ‘Box–Behnken’ design (BBD) (Design expert 10 software) for assessing the effect of formulation variables on product characteristics viz. viscosity, gelation temperature (GT), and mean release time (MRT). About 13 suggested runs of the experiment were carried out and formulations were optimised. Finally, three batches of the optimised formulation were prepared and evaluated for in vitro drug release, isotonicity of formulation, anti-microbial potential, ocular irritancy, and accelerated stability testing. Results: Pre-formulation study confirmed the purity, solubility, and compatibility of drug measured by λmax, partition coefficient, stability study, and Fourier-transform infrared spectroscopy (FTIR) analysis. Taguchi screening method suggested about 12 different formulations and 3 most prominent influential factors including viscosity, GT, and drug release. 13 different formulations designed based on ‘BBD’ method were further optimised by considering the most influential factors suggested by Taguchi screening. The in vitro evaluation of the optimised formulation gave satisfactory results in terms of drug release, and anti-microbial activity. It was found to be isotonic with no ocular irritancy. Further, the preparation immediately transformed from sol to gel upon administration into cul-de-sac region of the eye due to multi-dimensional approaches utilised for in-situ gel formation namely temperature change Pluronic, ion sensitivity due to Gellan-gum, pH sensitivity because of Carbopol. Conclusion: The optimised in-situ gelling ocular drug formulation showed promising potency for ophthalmic drug delivery with no irritancy due to the multifactorial mechanism.


1987 ◽  
Vol 16 (1) ◽  
pp. 23-27 ◽  
Author(s):  
M M Gola ◽  
A Gugliotta

The work continues and completes an earlier work (Gola and Gugliotta, 1982). The refined model of a special transducer-stem is here used, after implantation in a dry bone, for two purposes. First, to confirm a recent numerical finding which states a stress equivalence between physiological loads on a prosthesis-femur system and a simplified load condition, more desirable for testing purposes. Second, the separate effects of throchanteric muscle forces and of femural head forces on the stresses in the prosthetic stem are shown at various angles; superposition of effects compares well with the physiological loading case.


Author(s):  
A. Sigalas ◽  
B. Kokkas ◽  
M. Kotoula ◽  
A. Kouyoumtzis ◽  
V. Mirtsou-Fidani
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