BMM MachOne多功能生物力学测试系统做大鼠主动脉切面应力松弛和分析成功案例，大鼠主动脉切面张力试验机，大鼠主动脉切片的动态力学测试
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VASCULAR (VEIN AND ARTERY)
The vascular system is the network of blood vessels including arteries, veins and capillaries that allow blood flow to and from the heart. The structure of the blood vessel walls is mainly composed of endothelial cells, elastin, collagen and smooth muscle cells. The mechanical properties of the different components of the vascular system are studied to learn about: their structural function in the body, the effects of pathologies in blood vessels mechanics and related clinical issues, development in the structural modelling of blood vessels and research in blood vessels physiology.
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VASCULAR (VEIN AND ARTERY)
The vascular system is the network of blood vessels including arteries, veins and capillaries that allow blood flow to and from the heart. The structure of the blood vessel walls is mainly composed of endothelial cells, elastin, collagen and smooth muscle cells. The mechanical properties of the different components of the vascular system are studied to learn about: their structural function in the body, the effects of pathologies in blood vessels mechanics and related clinical issues, development in the structural modelling of blood vessels and research in blood vessels physiology.
文献资料Literature (12)
使用 BMM MachOne多功能生物力学测试系统 的文献案例
Differential roles of endothelin-1 in angiotensin II-induced atherosclerosis and aortic aneurysms in apolipoprotein E-null miceSuen RS, Rampersad SN, Stewart DJ and Courtman DWThe American journal of pathology, 179(3), 1549-1559. (2011)
Because both endothelin-1 (ET-1) and angiotensin II (AngII) are independent mediators of arterial remodeling, we sought to determine the role of ET receptor inhibition in AngII-accelerated atherosclerosis and aortic aneurysm formation. We administered saline or AngII and/or bosentan, an endothelin receptor antagonist (ERA) for 7, 14, or 28 days to 6-week- and 6-month-old apolipoprotein E-knockout mice. AngII treatment increased aortic atherosclerosis, which was reduced by ERA. ET-1 immunostaining was localized to macrophage-rich regions in aneurysmal vessels. ERA did not prevent AngII-induced aneurysm formation but instead may have increased aneurysm incidence. In AngII-treated animals with aneurysms, ERA had a profound effect on the non-aneurysmal thoracic aorta via increasing wall thickness, collagen/elastin ratio, wall stiffness, and viscous responses. These observations were confirmed in acute in vitro collagen sheet production models in which ERA inhibited AngII's dose-dependent effect on collagen type 1 ? 1 (COL1A1) gene transcription. However, chronic treatment reduced matrix metalloproteinase 2 mRNA expression but enhanced COL3A1, tissue inhibitor of metalloproteinase 1 (TIMP-1), and TIMP-2 mRNA expressions. These data confirm a role for the ET system in AngII accelerated atherosclerosis but suggest that ERA therapy is not protective against the formation of AngII-induced aneurysms and can paradoxically stimulate a chronic arterial matrix remodeling response.Read More
Heightened aberrant deposition of hard-wearing elastin in conduit arteries of prehypertensive SHR is associated with increased stiffness and inward remodelingArribas SM, Briones AM, Bellingham C, Gonzalez MC, Salaices M, Liu K, Wang Y and Hinek AAm J Physiol Heart Circ Physiol, 2008, 295(6), H2299-2307
Elastin is a major component of conduit arteries and a key determinant of vascular viscoelastic properties. Aberrant organization of elastic lamellae has been reported in resistance vessels from spontaneously hypertensive rats (SHR) before the development of hypertension. Hence, we have characterized the content and organization of elastic lamellae in conduit vessels of neonatal SHR in detail, comparing the carotid arteries from 1-wk-old SHR with those from Wistar-Kyoto (WKY) and Sprague Dawley (SD) rats. The general structure and mechanics were studied by pressure myography, and the internal elastic lamina organization was determined by confocal microscopy. Cyanide bromide-insoluble elastin scaffolds were also prepared from 1-mo-old SHR and WKY aortas to assess their weight, amino acid composition, three-dimensional lamellar organization, and mechanical characteristics. Carotid arteries from 1-wk-old SHR exhibited narrower lumen and greater intrinsic stiffness than those from their WKY and SD counterparts. These aberrations were associated with heightened elastin content and with a striking reduction in the size of the fenestrae present in the elastic lamellae. The elastin scaffolds isolated from SHR aortas also exhibited increased relative weight and stiffness, as well as the presence of peculiar trabeculae inside the fenestra that reduced their size. We suggest that the excessive and aberrant elastin deposited in SHR vessels during perinatal development alters their mechanical properties. Such abnormalities are likely to compromise vessel expansion during a critical period of growth and, at later stages, they could compromise hemodynamic function and participate in the development of systemic hypertension. Keywords: remodeling; hypertension; elastic lamellae; fenestrae; spontaneously hypertensive rats
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Longitudinal Stent Deformation: Importance of Stent Type and Stent AppositionPitne, M, van Niekerk E, Dokos S, Pelletier M and Walsh WRAmerican Journal of Biomedical Engineering, 3(3), 63-69. (2013)
Information on stent longitudinal strength is limited to benchtop models using unconstrained stents, consequently having uncertain clinical significance. This study investigated the effects of stent apposition and tube (artery) compliance on stent stability. Multilink Vision, Multilink 8, Promus Element, Driver and Integrity were examined. Stent size was 3/18 mm or closest length. Four scenarios were tested: in three the stents were well deployed and in the final test, stents were purposely severely malapposed. In the well-deployed models, three tubes with different compliance were tested. Stents were compressed by applying a single point force. Malapposed stents compressed extensively at 50 and 100 gm., especially Element, which deformed double the amount of the other stents. At higher forces (150 gm.), the magnitude of difference was reduced. Stent apposition had a profound protective effect and limited differences between stents. Stiffer tubes provided more protection to stent deformation. All stents are vulnerable to deformation when severely malapposed but the Element is significantly more so. Well-apposed stents are considerably more resistant to longitudinal compression such that differences between stents become minimal. More rigid tubes offered greater protection. Clinical implications regarding stent sizing and postdilation strategy are significant.
Keywords: Coronary Stents, Longitudinal Compression, Apposition, Vessel Compliance
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Infarcted rat myocardium: Data from biaxial tensile and uniaxial compressive testing and analysis of collagen fibre orientationSirry MS, Butler JR, Patnaik SS, Brazile B, Bertucci R, Claude A, McLaughlin R, Davies NH and Liao JData in Brief 8 (2016) 1338–1343
Myocardial infarction was experimentally induced in rat hearts and harvested immediately, 7, 14 and 28 days after the infarction induction. Anterior wall infarct samples underwent biaxial tensile and uniaxial compressive testing. Orientation of collagen fibres was analysed following mechanical testing. In this paper, we present the tensile and compressive stress–strain raw data, the calculated tensile and compressive moduli and the measured angles of collagen orientation. The presented data is associated with the research article titled “Characterisation of the mechanical properties of infarcted myocardium in the rat under biaxial tension and uniaxial compression”. Read More
A new radiopaque embolizing agent for the treatment of endoleaks after endovascular repair: Influence of contrast agent on chitosan thermogel propertiesCoutu JM, Fatimi A, Berrahmoune S, Soulez G and Lerouge SJournal of Biomedical Materials Research Part B: Applied Biomaterials, 101(1), 153-161. (2013)
A new injectable radiopaque embolizing agent has been developed, based on chitosan thermogelling properties. Different commercial contrast agents (Isovue®, Visipaque®, and Conray®) were associated with chitosan-?-glycerophosphate. Their impact on gelation kinetic, mechanical properties, radiopacity, and cytotoxicity was tested to evaluate the best candidate and its feasibility for the treatment of endoleaks after endovascular aneurysm repair (EVAR). Addition of contrast agents did not prevent gelation at body temperature, but it significantly increased the viscosity of the solution before gelation, delayed gelation, and reduced the gelation rate. However, using chitosan with a high degree of deacetylation and 20 vol % contrast agent made it possible to obtain a gel with rapid gelation that was visible during X-ray based guided intervention. Hydrogels exhibit relatively low mechanical properties, which are only slightly modified by the addition of contrast agents. In vitro studies have demonstrated rapid release of contrast agents from hydrogels when immersed in a saline solution (>50% within 4 h). This is suitable for embolization, as radiopacity is required only to follow the embolization procedure, while long-term radiopacity would hamper further imaging and endoleak detection. Cytotoxicity and osmolality testing of extracts demonstrated some toxicity of products released by the gel during the first few hours, which is mainly related to their hypertonicity. After the first 24 h incubation, hydrogels released no more cytotoxic compounds, suggesting that the hydrogel rapidly becomes biocompatible. Altogether, this study suggests that the new radiopaque thermogels present interesting characteristics as embolizing agents for EVAR, although their mechanical properties require improvement.Read More
The Aortic Wrap Procedure - A Surgical Method of Treating Age-Related Aortic Dilatation and StiffnessIliopoulos JPhD Thesis, University of New South Wales, Sydney. (2006)
Introduction: There is progressive stiffening and dilatation of the aorta and large elastic arteries with aging as a result of the repetitive cyclic stress they are exposed to throughout life. Aortic stiffening has a number of detrimental effects including an increase in aortic pulse wave velocity and early wave reflection, isolated systolic hypertension, ventricular-vascular mismatch, impaired coronary blood flow reserve, and is the fundamental cause of heart failure in the elderly. The aim of this thesis is to provide proof of concept for the aortic wrap procedure; a surgical treatment of stiffening and dilatation of the ascending aorta with aging. The surgical procedure involves wrapping an elastic material around the ascending aorta of elderly patients, to reduce the stiffness and diameter of the ascending aorta towards that seen in youth.
Methods: Proof of concept is investigated in the following studies.
1. The effect of the elastic wrap on the in-vivo stiffness of the normal aorta.
2. The effect of the elastic wrap on the in-vivo stiffness of the dilated and stiffened aorta.
3. The effect of the elastic wrap on the in-vitro stiffness of the aged human ascending aorta and on aortic pressure.
4. The effect of wrapping the aged human ascending aorta on pulse pressure (mathematical model).
5. The effect of chronic implantation on the structure of the normal aorta.
6. The mechanical properties of the ovine thoracic aorta and the elastic wrap material.
Results:
1. Elastic wrap application increased the in-vivo stiffness of the normal aorta.
2. Elastic wrap application decreased the stiffness of the stiffened and dilated aorta.
3. Elastic wrap application decreased the in-vitro stiffness of the elderly human ascending aorta and pulse pressure.
4. A reduction in ascending aortic stiffness was sufficient to reduce ascending aortic pulse pressure.
Conclusion: Application of the elastic wrap to the aged human ascending aorta is expected to reduce aortic stiffness, as well as systolic and pulse pressure, and to increase diastolic pressure with a reduction in cardiac load. The aortic wrap procedure may be an effective surgical procedure for the treatment of heart failure and isolated systolic hypertension.
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Methods: Proof of concept is investigated in the following studies.
1. The effect of the elastic wrap on the in-vivo stiffness of the normal aorta.
2. The effect of the elastic wrap on the in-vivo stiffness of the dilated and stiffened aorta.
3. The effect of the elastic wrap on the in-vitro stiffness of the aged human ascending aorta and on aortic pressure.
4. The effect of wrapping the aged human ascending aorta on pulse pressure (mathematical model).
5. The effect of chronic implantation on the structure of the normal aorta.
6. The mechanical properties of the ovine thoracic aorta and the elastic wrap material.
Results:
1. Elastic wrap application increased the in-vivo stiffness of the normal aorta.
2. Elastic wrap application decreased the stiffness of the stiffened and dilated aorta.
3. Elastic wrap application decreased the in-vitro stiffness of the elderly human ascending aorta and pulse pressure.
4. A reduction in ascending aortic stiffness was sufficient to reduce ascending aortic pulse pressure.
Conclusion: Application of the elastic wrap to the aged human ascending aorta is expected to reduce aortic stiffness, as well as systolic and pulse pressure, and to increase diastolic pressure with a reduction in cardiac load. The aortic wrap procedure may be an effective surgical procedure for the treatment of heart failure and isolated systolic hypertension.
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Cellularized collagen gels for tissue engineered vascular wall: in vitro models alternative to in vivo testingLoy C, Meghezi S, Seifu DG, Pezzoli D , Bono N , Levesque L, Drouin B and Mantovani DPoster #P.0616 on Thursday May 19 from 15:00 to 16:30 in room 220BCD (P3) during World Biomaterials Congress, Montreal, May 2016.
Introduction: Type I collagen-gels, as scaffolds for vascular tissue engineering, have a high potential for supporting and guiding vascular cells in the regeneration process. With this in mind, our project was to develop a set of easy-to-prepare collagen-based in vitro vascular wall models and experimental techniques to thoroughly characterize them.
Materials and Methods: Cellularized collagen gels were prepared by mixing vascular cells (106cells/ml) with a type I collagen solution (4g/L) as described before and molded both in flat and tubular geometries. ECs were seeded on the surface of tubular constructs at the density of 8x105cells/cm2 using a homemade rotating bioreactor. Mono-culture (SMCs), bi-culture (SMCs and ECs) and tri-culture (FBs, SMCs and ECs) multilayered models were developed. The viscoelastic properties were studied on disk shaped constructs by compression test using MachOne (BMM Inc), whereas on tubular constructs by stress-relaxation tests using ElectroPuls E1000 (Instron Corporation) longitudinally and circumferentially. Protein expression by SMCs was investigated by western blot and the blood compatibility of constructs by clotting time assays. Tubular constructs were cultured in Instron Tissue Engineering & Regenerative Medicine (TERM) bioreactors with dynamic stimulations.
Results and Discussion: Mono-, bi- and tri-culture models of vascular wall composed of collagen and vascular cells in flat disk and tubular geometries were developed. The structure and cellular distribution of the tri-culture models closely matched those of native vascular wall, reproducing tunica intima, tunica media and tunica adventitia. Altogether, the models allowed to investigate the multiple intimate relationships existing among vascular cells. Importantly, SMCs and FBs remodeled the constructs by contracting the structure. A functional monolayer of ECs (Fig. 1) with anticoagulant properties was achieved.
Viscoelastic properties were assessed through stepwise stress relaxation tests by stretching the sample at 10% strain, and maintained constant for 600s while monitoring the stress and the same procedure was repeated until 80% strain was achieved. It showed that the total stress (peak at the beginning of the relaxation, Fig. 2 green line) increased with the number of cellularised collagen layers, while the elastic properties (value at the end of relaxation, Fig. 2 red line) remained the same (Fig. 2). Anisotropic mechanical properties in longitudinal and circumferential directions were observed. Tubular constructs, strong enough to be transferred and cultured into the Instron-TERM bioreactor (Fig. 3) were obtained after 1 week static conditioning . Cyclic mechanical stimulations (0-50 mmHg, 1 Hz) allowed to further improve the mechanical properties of the constructs.
Viscoelastic properties were assessed through stepwise stress relaxation tests by stretching the sample at 10% strain, and maintained constant for 600s while monitoring the stress and the same procedure was repeated until 80% strain was achieved. It showed that the total stress (peak at the beginning of the relaxation, Fig. 2 green line) increased with the number of cellularised collagen layers, while the elastic properties (value at the end of relaxation, Fig. 2 red line) remained the same (Fig. 2). Anisotropic mechanical properties in longitudinal and circumferential directions were observed. Tubular constructs, strong enough to be transferred and cultured into the Instron-TERM bioreactor (Fig. 3) were obtained after 1 week static conditioning . Cyclic mechanical stimulations (0-50 mmHg, 1 Hz) allowed to further improve the mechanical properties of the constructs.
Conclusions: Herein, we engineered a platform of in vitro collagen gel-based vascular wall tissue models that can be used for physiological genomics studies. Sets of techniques were also developed to maturation and functional characterization of these structures biologically as well as mechanically. Furthermore, these models can serve as platforms for tightly controlled, high-content screening of drugs and devices in pharmacodynamic analyses.
The effects of frequency on matrix remodeling induced in dynamically strained collagen-based cellularised scaffoldsLevesque L, Loy C, Lainé A, Bono N, Drouin B and Mantovani DOral.238.51 on Wed May 19 from 16:30 to 18:30 in room 519 during World Biomaterials Congress, Montreal, May 2016
Introduction: In vascular tissue engineering, the understanding of cells behavior inside matrices and under pseudo-physiological treatment is of upmost importance in order to develop arteries and arterial wall models. Indeed, extracted collagen has low mechanical properties and is unable to withstand physiological pressure. Cells has the ability to remodel the collagen thus leading to reinforcement of the matrix. Moreover, they are able to produce their own matrix. It has been also shown that cells alone behave differently under different frequencies[1]. However, little has been studied on cells within matrices and their behavior under diverse frequencies. Therefore, the aim of this work was to investigate the effect of the frequency of a dynamical strain applied to collagen based cellularised scaffolds.
Materials and Method: HUASMC (5 X 105 cells/ml) were embedded in collagen type 1 gels (4 mg/ml) and moulded into rectangular shape geometry in a 6 wells silicone membrane plate (flexercell International Corporation, Burlington, NC, USA) as described before[2]. Dynamic 5% strain at 1 Hz and gradual frequency was applied to the samples. The mechanical properties of the samples were assessed by compression relaxation test using a MachOne (BMM Inc., Laval, Canada) apparatus. The remodeling and behavior of the cells were assessed by FV-1200 confocal microscopy (Olympus, Richmond Hill, Canada) and histology staining. RT-qPCR will also be used to investigate the production of collagen and elastin and the phenotype of the HUASMCs.
Results and Discussion: Collagen type 1 gels do not show residual stresses when submitted to step-by-step compression relaxation tests. However, the same tests performed on collagen gels colonized with HUASMC and dynamically strained have generated residual stresses (Fig. 1).Hence, cells densify the collagen network by adhering to the collagen fibers and exerting traction forces. An alignment in the direction of the strain of the HUASMCs within the collagen gels was also observed by both the histology and the confocal microscopy images. However, the alignment seems less pronounce with gradual frequencies. A greater remodeling of dynamic strain samples seems to be shown by the RT-qPCR analyses as well as the production of collagen and elastin.
Conclusion: In this work, it was shown that the frequency applied to 3D collagen matrices with embedded cells influences cell behavior in the remodeling of the construct. The investigation have shown that physiological (1Hz) frequency seems to show better elastic modulus, a greater alignment of the cells and adequate phenotype for the remodeling of the matrix and the production of extracellular matrix.
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Mechanically resilient injectable scaffolds for intramuscular stem cell delivery and cytokine releaseYoung SA, Sherman SE, Cooper TT, Brown C, Anjum F, Hess DA. Flynn LE and Amsden BGBiomaterials. doi: https://doi.org/10.1016/j.biomaterials.2018.01.008 (2018)
A promising strategy for treating peripheral ischemia involves the delivery of stem cells to promote angiogenesis through paracrine signaling. Treatment success depends on cell localization, retention, and survival within the mechanically dynamic intramuscular (IM) environment. Herein we describe an injectable, in situ-gelling hydrogel for the IM delivery of adipose-derived stem/stromal cells (ASCs), specifically designed to withstand the dynamic loading conditions of the lower limb and facilitate cytokine release from encapsulated cells. Copolymers of poly(trimethylene carbonate)-b-poly(ethylene glycol)-b-poly(trimethylene carbonate) diacrylate were used to modulate the properties of methacrylated glycol chitosan hydrogels crosslinked by thermally-initiated polymerization using ammonium persulfate and N,N,N?,N?-tetramethylethylenediamine. The scaffolds had an ultimate compressive strain over 75% and maintained mechanical properties during compressive fatigue testing at physiological levels. Rapid crosslinking (<3?min) was achieved at low initiator concentration (5?mM). Following injection and crosslinking within the scaffolds, human ASCs demonstrated high viability (>90%) over two weeks in culture under both normoxia and hypoxia. Release of angiogenic and chemotactic cytokines was enhanced from encapsulated cells under sustained hypoxia, in comparison to normoxic and tissue culture polystyrene controls. When delivered by IM injection in a mouse model of hindlimb ischemia, human ASCs were well retained in the scaffold over 28 days and significantly increased the IM vascular density compared to untreated controls.Read More
Fibronectin promotes elastin deposition, elasticity and mechanical strength in cellularised collagen-based scaffoldsPezzoli, Daniele; Di Paolo, Joseph; Kumra, Heena; Fois, Giulia; Candiani, Gabriele; Reinhardt, Dieter P.; Mantovani, DiegoBiomaterials Volume 180, October 2018, Pages 130-142 https://doi.org/10.1016/j.biomaterials.2018.07.013
One of the tightest bottlenecks in vascular tissue engineering (vTE) is the lack of strength and elasticity of engineered vascular wall models caused by limited elastic fiber deposition. In this study, flat and tubular collagen gel-based scaffolds were cellularised with vascular smooth muscle cells (SMCs) and supplemented with human plasma fibronectin (FN), a known master organizer of several extracellular matrix (ECM) fiber systems. The consequences of FN on construct maturation was investigated in terms of geometrical contraction, viscoelastic mechanical properties and deposition of elastic fiber proteins. FN was retained in the constructs and promoted deposition of elastin by SMCs as well as of several proteins required for elastogenesis such as fibrillin-1, lysyl oxidase, fibulin-4 and latent TGF-? binding protein-4. Notably, gel contraction, tensile equilibrium elastic modulus and elasticity were strongly improved in tubular engineered tissues, approaching the behaviour of native arteries. In conclusion, this study demonstrates that FN exerts pivotal roles in directing SMC-mediated remodeling of scaffolds toward the production of a physiological-like, elastin-containing ECM with excellent mechanical properties. The developed FN-supplemented systems are promising for tissue engineering applications where the generation of mature elastic tissue is desired and represent valuable advanced in vitro models to investigate elastogenesis.Read More
MachOne - Dynamic Mechanical Testing (MA056-SOP04-D v1)Hadjab I and Quenneville EBMM Inc. Laval (QC), Canada, Effective Date: December 3rd, 2014
Purpose
This document describes a standard method to assess the frequency behavior of the dynamic mechanical properties of material through the complex Young’s (E*) or shear (G*) modulus using the MachOne mechanical tester. Analysis of the measurement results is part of a companion document (SW186-SOP04-D).
This document describes a standard method to assess the frequency behavior of the dynamic mechanical properties of material through the complex Young’s (E*) or shear (G*) modulus using the MachOne mechanical tester. Analysis of the measurement results is part of a companion document (SW186-SOP04-D).
Scope
This method can be applied on any type of material as long as sample’ shape and dimension are compatible with the specifications presented in the material section and that the involved displacements, strain rates, forces or torques remain within tester specifications.
Cross-Linked Elastin-like Polypeptide Membranes as a Model for Medial Arterial CalcificationO. Gourgas, L. D. Muiznieks, D. G.Bello, A. Nanci, S.Sharpe and M. CerrutiPublication Date:June 21, 2019 https://doi.org/10.1021/acs.biomac.9b00417