Porcine Aortic Wall Research Articles

Non-destructive 3D characterization of the blood vessel wall microstructure in different species and blood vessel types using contrast-enhanced microCT and comparison with synthetic vascular grafts

To improve the current treatment for vascular diseases, such as vascular grafts, intravascular stents, and balloon angioplasty intervention, the evaluation of the native blood vessel microstructure in full 3D could be beneficial. For this purpose, we used contrast-enhanced X-ray microfocus computed tomography (CECT): a combination of X-ray microfocus computed tomography (microCT) and contrast-enhancing staining agents (CESAs) containing high atomic number elements. In this work, we performed a comparative study based on staining time and contrast-enhancement of 2 CESAs: Monolacunary and 1:2 Hafnium-substituted Wells-Dawson polyoxometalate (Mono-WD POM and Hf-WD POM, respectively) for imaging of the porcine aorta. After showing the advantages of Hf-WD POM in terms of contrast enhancement, we expanded our imaging to other species (rat, porcine, and human) and other types of blood vessels (porcine aorta, femoral artery, and vena cava), clearly indicating microstructural differences between different types of blood vessels and different species. We then showed the possibility to extract useful 3D quantitative information from the rat and porcine aortic wall, potentially to be used for computational modeling or for future design optimization of graft materials. Finally, a structural comparison with existing synthetic vascular grafts was made. This information will allow to better understand the in vivo functioning of native blood vessels and to improve the current disease treatments. STATEMENT OF SIGNIFICANCE: Synthetic vascular grafts, used as treatment for some cardiovascular diseases, still often fail clinically, potentially because of a mismatch in mechanical behaviour between the native blood vessel and the graft. To better understand the causes of this mismatch, we studied the full 3D microstructure of blood vessels. For this, we identified Hafnium-substituted Wells-Dawson polyoxometalate as contrast-enhancing staining agent to perform contrast-enhanced X-ray microfocus computed tomography. This technique allowed to show important differences in the microstructure of different types of blood vessels and in different species, as well as with that of synthetic grafts. This information can lead to a better understanding of the functioning of blood vessels and will allow to improve current disease treatments, such as vascular grafts.

Importance of experimental evaluation of structural parameters for constitutive modelling of aorta

The study compares stresses and strains in the aortic wall derived using different constitutive models for various stress-strain conditions. Structure-based constitutive models with two fibre families with (GOH) and without (HGO) dispersion of collagen fibres are compared. The constitutive models were fitted to data from equibiaxial tension tests of two separated layers of the porcine aortic wall. The initial fit was evaluated with unrestricted parameters and subsequently, the mean angles of the fibre families and the angular dispersion were fixed to the values obtained from histology. Surprisingly, none of the tested models was capable to provide a good quality fit with histologically obtained structural parameters. Fitting the HGO model to experimental data resulted in two fibre families under angles close to ±45°, while the GOH model resulted in a nearly isotropic fibre distribution. These results indicate that both of these models suffer from the absence of isotropic strain stiffening. After having modified both models with corresponding additional members based on the Yeoh model of matrix, we obtained a perfect fit to the measured data while keeping the structural histology-based parameters. Finally, significant differences in compliance and resulting stresses and strains between different models are shown by means of simulations of uniaxial tension test, equibiaxial tension tests and inflation of the aorta.

Experimental Investigation of the Anisotropic Mechanical Response of the Porcine Thoracic Aorta.

Knowledge of the mechanical properties of blood vessels and determining appropriate constitutive relations are essential in developing methodologies for accurate prognosis of vascular diseases. We examine the directional variation of the mechanical properties of the porcine thoracic aorta by performing uniaxial extension tests on dumbbell-shaped specimens cut at five different orientations with respect to the circumferential direction of the aorta. Specimens in all the orientations considered exhibit a nonlinear constitutive response that is typical of collagenous soft tissues. Shear strain under uniaxial extension demonstrates clearly discernible anisotropy of the mechanical response of the porcine aorta, and samples oriented at 45[Formula: see text] and 60[Formula: see text] with respect to the circumferential direction show a peculiar crescent-shaped shear strain-nominal stretch response not displayed by axial and circumferential specimens. Failure stress indicates decreasing tensile strength of the porcine aortic wall from the circumferential direction to the longitudinal direction. Furthermore, we determine the material parameters for the four-fiber-family and Gasser-Holzapfel-Ogden models from the mechanical response data of the circumferential and longitudinal specimens. It is shown how the material parameters derived from the uniaxial tests on circumferential and longitudinal specimens are insufficient to characterize the response of off-axis specimens.

Intramural Distributions of GAGs and Collagen vs. Opening Angle of the Intact Porcine Aortic Wall.

The heterogeneity and contribution of collagen and elastin to residual stresses have been thoroughly studied, but more recently, glycosaminoglycans (GAGs) also emerged as potential regulators. In this study, the opening angle of aortic rings (an indicator of circumferential residual stresses) and the mural distributions of sulfated GAGs (sGAG), collagen, and elastin were quantified in the ascending, aortic arch and descending thoracic regions of 5- to 6-month-old pigs. The opening angle correlated positively with the aortic ring's mean radius and thickness, with good and moderate correlations respectively. The correlations between the sGAG, collagen, elastin, and collagen:sGAG ratio and the opening angle were evaluated to identify aortic compositional factors that could play roles in regulating circumferential residual stresses. The total collagen:sGAG ratio displayed the strongest correlation with the opening angle (r = -0.715, p < 0.001), followed by the total sGAG content which demonstrated a good correlation (r = 0.623, p < 0.001). Additionally, the intramural gradients of collagen, sGAG and collagen:sGAG correlated moderately with the opening angle. We propose that, in addition to the individual role sGAG play through their content and intramural gradient, the interaction between collagen and sGAG should be considered when evaluating circumferential residual stresses in the aorta.

Immobilized Bisphosphonates as Potential Inhibitors of Bioprosthetic Calcification: Effects on Various Xenogeneic Cardiovascular Tissues.

Calcification is the major factor limiting the clinical use of bioprostheses. It may be prevented by the immobilization of bisphosphonic compounds (BPs) on the biomaterial. In this study, we assessed the accumulation and structure of calcium phosphate deposits in collagen-rich bovine pericardium (Pe) and elastin-rich porcine aortic wall (Ao) and bovine jugular vein wall (Ve) cross-linked with glutaraldehyde (GA) or diepoxy compound (DE). These tissues were then modified with pamidronic (PAM) acid or 2-(2′-carboxyethylamino)ethylidene-1,1-bisphosphonic (CEABA) acid. Tissue transformations were studied using Fourier-transform infrared spectroscopy. After subcutaneous implantation of the biomaterials in 220 rats, calcification dynamics were examined using atomic absorption spectrophotometry, light microscopy after von Kossa staining, and scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy The calcium content in all GA-cross-linked tissues and DE-cross-linked Ao increased to 100–160 mg/g on day 60 after implantation. BPs prevented the accumulation of phosphates on the surface of all materials and most effectively inhibited calcification in GA-cross-linked Ao and DE-cross-linked Pe. PAM containing -OH in the R1 group was more effective than CEABA containing -H in R1. The calcification-inhibitory effect of BPs may be realized through their ability to block nucleation and prevent the growth of hydroxyapatite crystals.

Mechanical properties of native and decellularized aortic wall after long-term storage in biocide solutions

Objective: to determine the optimal method for long-term wet storage of donor material (50 days after collection), with maximum ability to preserve the original mechanical characteristics.Materials and methods. Porcine aortic wall fragments were used as objects of study. Half of the original material underwent detergent-based decellularization. The entire material (native and processed) was placed for 50 days in biocidal solutions: complex alcohol solution; ethanol and glycerol mixture; antibiotics mixture. Then the tests for mechanical strength of native and decellularized samples were carried out by the method of uniaxial longitudinal and circumferential stress.Results. Storage of native material in all media resulted in a significant increase in tensile strength. In the «complex alcohol solution», «ethanol and glycerol mixture», and «antibiotic mixture» group, tensile strength increased by 1.38-, 1.72- and 1.62-fold compared to the native control in circumferential tension. Also, in the «complex alcohol solution» group, the decellularized material was 1.57-fold stronger than the native in circumferential tension. In the «antibiotic mixture» group, the decellularized material was 1.33-fold less strong than the native in longitudinal tension. According to elongation to rupture data, significantly greater plasticity was noted in the «ethanol-glycerol» storage group for the decellularized aortic wall compared to the control group (1.5-fold). Young’s modulus did not reliably differ from those of control in all experimental groups regardless of the stress direction. Notably, decellularized specimens clearly tended to be stiffer under circumferential stress.Conclusion. Detergent-based decellularization of the porcine aortic wall and subsequent storage of these samples in our chosen experimental solutions for 50 days does not significantly affect the elastic properties of the material. Our proposed treatment methods partially increase the stiffness of the material after storage in alcohol-containing solutions.

Treatment with bisphosphonates to mitigate calcification of elastin-containing bioprosthetic materials.

This study evaluated the ability of bisphosphonates (BPAs) of different molecular structures to mitigate the calcification of porcine aortic wall (PAW) and bovine jugular vein wall (BJVW). Tissues cross-linked with glutaraldehyde (GA) or diepoxide (DE) were modified with pamidronic acid (PAM), alendronic acid (ALE), neridronic acid (NER) (type 1 BPAs); 2-(2'-carboxyethylamino)ethylidene-1,1-bisphosphonic acid (CEABA), 2-(5-carboxypentylamino)ethylidene-1,1-bisphosphonic acid (CPABA) (type 2); and zoledronic acid (ZOL) (type 3). After implanting the tissue samples subcutaneously in 100 rats, calcification was examined using atomic absorption spectrophotometry (60-day explants) and light microscopy after von Kossa staining (10- and 30-day explants). The calcium contents in GA-BJVW and GA- and DE-PAW increased up to 100-120 mg/g after 60 days, while being 3 times lower in DE-BJVW. In modified and nonmodified PAW samples, calcium phosphates appeared by day 10 and were associated with elastic fibers and devitalized cellular elements. In all groups of BJVW samples, mineralization began in elastic fibers near the subendothelial layer. In addition, calcified collagen was found in the GA-BJVW samples. Minimal calcification was found in GA-PAW treated with type 1 BPAs and CEABA. For DE-PAW and GA-BJVW, the calcium level significantly decreased with PAM and CEABA. Meanwhile, ALE and NER were effective for DE-BJVW.

Effects of biocidal solutions and wet tissue treatment on the biological properties of porcine aortic wall

Aim.To evaluate the effects of long-term wet treatment of porcine aortic wall fragments with biocidal solutions (glutaraldehyde, antibiotics, alcohol-glycerin mixture, complex alcohol solution (CAS)) on the severity of degradation of samples’ connective matrix and their long-term ability to accumulate calcium during subcutaneous implantation in laboratory rats (1 and 3 months).Methods.Histological analysis of freshly collected material was performed after 50 days of treatment with various biocidal solutions and after subcutaneous implantation of samples in small laboratory animals at 1 and 3 months. Calcium was measured with the atomic absorption spectroscopy after 3 months of subcutaneous implantation.Results.Histological analysis reported that connective matrix of samples treated with glutaraldehyde, antibiotics, and CAS was similar to the native one (with the exception of partial loss of cellular components in samples). After 1 month of implantation, a moderate degradation of connective tissue was found. The treatment with the alcohol-glycerin mixture was associated with the most severe degradation. After 3 months of implantation, glutaraldehyde-treated samples had the most preserved connective matrix, while alcohol-glycerin-treated samples demonstrated severe connective matrix injury. However, severe calcific deposits were found in samples treated with glutaraldehyde, whereas mild ones were detected in samples treated with alcohol-glycerin. Atomic absorption spectroscopy reported that calcific deposits in Cas- and alcohol-glycerin-treated samples were 2.3 and 1.8 times lower than those in glutaraldehyde-treated samples. The calcium content in samples treated with antibiotics did not differ significantly from those in glutaraldehyde-treated samplesConclusion.The comprehensive analysis of the effects of various treatment media on the stability of connective matrix to subsequent degradation and its ability to accumulate calcium found that CAS was the most preferred medium for long-term wet treatment of xenoprosthetic vascular tissue.

Successful decellularization of thick-walled tissue: Highlighting pitfalls and the need for a multifactorial approach

Decellularization of thick tissue is challenging and varying. Therefore, we tried to establish a multifactorial approach for reliable aortic wall decellularization. Porcine aortic walls were decellularized according to different procedures. Decellularization was performed for 24 (G1), 48 (G2), and 72 h (G3) with a solution of 0.5% desoxycholate and 0.5% dodecyl sulfate. The procedure was characterized using intermittent washing steps, the inclusion of sonication as well as DNase and α-galactosidase treatment. The decellularization efficiency was measured by the evaluation of 4',6-diamidino-2-phenylindole and hematoxylin and eosin staining and quantitative DNA assays. Pentachrome and picrosirius red staining, scanning electron microscopy as well as glycosaminoglycan assays were performed to evaluate the effect of the procedure on the extracellular matrix. 4',6-Diamidino-2-phenylindole and hematoxylin and eosin staining revealed a large amount of remaining nuclei in all groups. However, consecutive DNase treatment had a significant effect. While the remaining DNA was detected in some samples of G1 and G2, samples of G3 were fully decellularized. Glycosaminoglycan content was significantly reduced to 50% after 24 h (G1) but remained constant for G2 and G3. Picrosirius red staining revealed an intact and stable collagen network without any visible defects. Pentachrome staining substantiated these results. Nonetheless, the fiber network remains intact, which could be confirmed by reflection electron microscopy analysis. In this study, we developed a procedure that grants successful decellularization of porcine aortic wall while maintaining the fibrous microstructure. We highlighted the significant effect of DNase and α-galactosidase treatment. In addition, we could show the need for a multifactorial treatment and comprehensive evaluation protocols for thick tissue decellularization.

Three-Dimensional Full-Field Strain Measurements across a Whole Porcine Aorta Subjected to Tensile Loading Using Optical Coherence Tomography–Digital Volume Correlation

Optical Coherence Tomography (OCT) combined with Digital Volume Correlation (DVC) is a suitable technique to investigate the biomechanical behavior of biological tissues at the microscale. However, to characterize the whole thickness of large human or porcine arteries, the use of osmotic tissue clearing agents, such as propylene glycol, is unavoidable due to intrinsic tissue scattering of light. The mechanical response of biological tissues immersed in tissue clearing agents has been poorly investigated so far. Nevertheless, understanding the mechanisms of tissue clearing could be helpful for developing safe optical-clearing methods for possible in vivo applications. The goal of the present work is to combine OCT and DVC to measure displacement and strain fields in porcine aortic tissues immersed in polypropylene glycol and subjected to stress-relaxation uniaxial tension. Displacement and strain fields are measured across the whole thickness of the porcine aortic wall for the first time. Measurement uncertainties and optimal OCT-DVC parameters are determined to define useful technical recommendations for future similar analyses. It is known that the main effect of polypropylene glycol is a significant increase of collagen fibril packing density due to important loss of water (dehydratation). It results in a pronounced stiffening of the aortic tensile response when compared to the response of the same tissue immersed in PBS. This effect is reversible when the aortic tissue is removed from polypropylene glycol and immersed again in PBS. Another effect is a dramatic reduction of the Poisson’s effect during tensile loading. But the OCT-DVC measured strain fields also reveal heterogeneities of this effect among the different layers of the aorta. It appears that the reduced Poisson’s effect is concentrated in the media layer, whereas the adventitia and intima layer keep a usual Poisson’s effect of nearly incompressible tissues. It is concluded that further work should be conducted on how the smooth muscle cells highly present in the media layer are affected by polypropylene glycol immersion for a better understanding of these effects.

In search of the best xenogeneic material for a paediatric conduit: an experimental study.

The development of calcification-resistant bioprosthetic materials is a very important challenge for paediatric surgery. The subcutaneous implantation in rats is the well-known first-stage model for this kind of research. Using this model, we aimed to compare calcification of the porcine aortic wall and bovine pericardium and jugular vein wall cross-linked with glutaraldehyde (GA) and ethylene glycol diglycidyl ether (DE). We also determined the efficacy of DE-preserved tissue modification with 2-(2-carboxyethylamino)ethylidene-1,1-bisphosphonic acid (CEABA). Three groups of each biomaterial were evaluated: GA-treated, DE-treated and DE + CEABA-treated. The microstructure of non-implanted biomaterials was assessed by light microscopy after Picro Mallory staining; the phosphorus content of the DE and DE + CEABA samples was assessed by atomic emission spectrometry. Samples were implanted subcutaneously into young rats for 10 and 60 days. The explant end-point included quantitative calcification assessment by atomic absorption spectrophotometry and light microscopy examination after von Kossa staining. All GA-treated biomaterials had a high calcium-binding capacity (>100 μg/mg dry tissue). DE preservation decreased the vein wall and pericardium calcium content by 4- and 40-fold, respectively, but was ineffective for the aortic wall. The calculated CEABA content was almost equal in the vein wall and pericardium (17.7 and 18.5 μM/g) and slightly less in the aortic wall (15 μM/g) (P = 0.011). CEABA effectively reduced mineralization in the DE aortic wall and DE pericardium to 10.1 (7.8-21.1) and 0.95 (0.57-1.38) μg/mg but had no effect in the DE vein wall. Mineralization in the GA- and DE-treated aortic and vein walls was predominantly associated with elastin. CEABA modification decreased elastin calcification but did not block it completely. Each xenogeneic material requires individual anticalcification strategy. DE + CEABA pretreatment demonstrates a high mineralization-blocking efficacy for the bovine pericardium and should be employed to further develop the paediatric pericardial conduit. Aortic wall calcification cannot be blocked completely using this strategy.

Ferroelectricity and piezoelectricity in soft biological tissue: Porcine aortic walls revisited

Recently reported piezoresponse force microscopy (PFM) measurements have proposed that porcine aortic walls are ferroelectric. This finding may have great implications for understanding biophysical properties of cardiovascular diseases such as arteriosclerosis. However, the complex anatomical structure of the aortic wall with different extracellular matrices appears unlikely to be ferroelectric. The reason is that a prerequisite for ferroelectricity, which is the spontaneous switching of the polarization, is a polar crystal structure of the material. Although the PFM measurements were performed locally, the phase-voltage hysteresis loops could be reproduced at different positions on the tissue, suggesting that the whole aorta is ferroelectric. To corroborate this hypothesis, we analyzed entire pieces of porcine aorta globally, both with electrical and electromechanical measurements. We show that there is no hysteresis in the electric displacement as well as in the longitudinal strain as a function of applied electric field and that the strain depends on the electric field squared. By using the experimentally determined quasi-static permittivity and Young's modulus of the fixated aorta, we show that the strain can quantitatively be explained by Maxwell stress and electrostriction, meaning that the aortic wall is neither piezoelectric nor ferroelectric, but behaves as a regular dielectric material.

Tissue-engineering acellular scaffolds-The significant influence of physical and procedural decellularization factors.

The importance of decellularized medical products has significantly increased during the last years. In this paper, we evaluated the effects of selected physical and procedural decellularization (DC) factors with the aim to systematically assess their influence on DC results. 72 porcine aortic walls (AW) were divided into three groups and exposed to a DC solution for 4 h and 8 h, either continuously or in repeated cycles. The AW were rocked (90bpm), whirled (10 l/min), sonicated (120W, 45 kHz) or exposed to a combination of these treatments, followed by 10 washing cycles. Defining successful DC as removal of nuclei while keeping an intact extracellular matrix (ECM), we equalized the efficiency to the penetration depth (PD), obtained by DAPI fluorescence and H&E staining. Additionally, we performed scanning electron microscopy (SEM), Pentachrome and Picrosirius-Red staining. Results showed that significantly higher DC depths are achieved on outer compared to inner surfaces (61 ± 7%; p < 0.001). Furthermore, the PD showed a high time dependency for all samples. Compared to continuous rocking, we achieved a significant increase in the DC efficiency through cyclic treatments ( ∼ 43%), whirling ( ∼ 19%) and sonication ( ∼ 49%). The combined treatment supported these results. In all procedures, a skeletonized but intact Collagen fibrous network was obtained as confirmed by SEM analysis. In conclusion, we systematically identified essential factors to significantly enhance DC procedures. We highly recommend considering these factors in future DC protocols. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 153-162, 2018.

Bicuspid aortic valve hemodynamics does not promote remodeling in porcine aortic wall concavity.

To investigate the role of type-I left-right bicuspid aortic valve (LR-BAV) hemodynamic stresses in the remodeling of the thoracic ascending aorta (AA) concavity, in the absence of underlying genetic or structural defects. Transient wall shear stress (WSS) profiles in the concavity of tricuspid aortic valve (TAV) and LR-BAV AAs were obtained computationally. Tissue specimens excised from the concavity of normal (non-dilated) porcine AAs were subjected for 48 h to those stress environments using a shear stress bioreactor. Tissue remodeling was characterized in terms of matrix metalloproteinase (MMP) expression and activity via immunostaining and gelatin zymography. Immunostaining semi-quantification results indicated no significant difference in MMP-2 and MMP-9 expression between the tissue groups exposed to TAV and LR-BAV AA WSS (P = 0.80 and P = 0.19, respectively). Zymography densitometry revealed no difference in MMP-2 activity (total activity, active form and latent form) between the groups subjected to TAV AA and LR-BAV AA WSS (P = 0.08, P = 0.15 and P = 0.59, respectively). The hemodynamic stress environment present in the concavity of type-I LR-BAV AA does not cause any significant change in proteolytic enzyme expression and activity as compared to that present in the TAV AA.

Suitability of the rat subdermal model for tissue engineering of heart valves.

BackgroundTissue engineering (TE) is a promising approach to overcome problems associated with biological heart valve prosthesis. Currently several animal models are used to advance this method. The rat subdermal model is uncomplicated and widely used, but its suitability for TE has not yet been shown.Material/MethodsUsing the rat subdermal model we implanted two decellularized porcine aortic wall specimens (of which one was endothelialized) and one native porcine aortic wall specimen in 30 Lewis rats, respectively. Endothelial cells (EC) were harvested from the rat jugular veins. After explantation Hematoxylin/Eosin-staining, CD-68-positive cell staining, fibroblast-staining and Von-Willebrand factor staining were performed.ResultsAll animals survived without complications. Endothelialization was confirmed to be effective by Giemsa staining. Histological evaluation of specimens in Hematoxylin/Eosin staining showed significant decrease (p<0.05) of inflammatory reaction (confirmed by CD-68-positive cell staining) after decellularization. All specimens showed strongest inflammatory reactions at areas of destroyed extracellular matrix. Fibroblasts could be detected in all specimens, with strongest infiltration in decellularized specimens (p<0.05). Surrounding endothelialized specimens had no monolayer of endothelial cells, but a higher density of blood vessels occurred (p<0.05).ConclusionsThe subdermal model provides excellent contact of host tissue with implanted specimens leading to rapid cellular infiltration; therefore, we could ascertain reduced inflammatory response to decellularized tissue. Due to the subdermal position, an absence of blood stream and mechanical stress occurs, which influences cellular repopulation; therefore, endothelialization did not lead to an EC monolayer, but rather to increased vascularization. Thus, the model appears ideal for investigating basic biological compatibility, but further questions must be researched using other models.

Cells derived from porcine aorta tunica media show mesenchymal stromal-like cell properties in in vitro culture

Several studies have already described the presence of specialized niches of precursor cells in vasculature wall, and it has been shown that these populations share several features with mesenchymal stromal cells (MSCs). Considering the relevance of MSCs in the cardiovascular physiopathology and regenerative medicine, and the usefulness of the pig animal model in this field, we reported a new method for MSC-like cell isolation from pig aorta. Filling the vessel with a collagenase solution for 40 min, all endothelial cells were detached and discarded and then collagenase treatment was repeated for 4 h to digest approximately one-third of the tunica media. The ability of our method to select a population of MSC-like cells from tunica media could be ascribed in part to the elimination of contaminant cells from the intimal layer and in part to the overnight culture in the high antibiotic/antimycotic condition and to the starvation step. Aortic-derived cells show an elongated, spindle shape, fibroblast-like morphology, as reported for MSCs, stain positively for CD44, CD56, CD90, and CD105; stain negatively for CD34 and CD45; and express CD73 mRNA. Moreover, these cells show the classical mesenchymal trilineage differentiation potential. Under our in vitro culture conditions, aortic-derived cells share some phenotypical features with pericytes and are able to take part in the formation of network-like structures if cocultured with human umbilical vein endothelial cells. In conclusion, our work reports a simple and highly suitable method for obtaining large numbers of precursor MSC-like cells derived from the porcine aortic wall.

Difference of xenoreactive immune response and patterns of calcification of porcine and bovine tissues in alpha-gal KO and wild type mouse implantation model

Methods The various xenogeneic tissues (porcine pericardium, aortic valve, aortic wall and bovine pericardium, aortic valve, aortic wall) were fixed in 0.5% glutaraldehyde solution and implanted into the subcutaneous tissue of the wild type-mouse and the KO mouse for 3 months. The implanted mice were harvested and studied for the histopathology, amounts of calcification and immune responses by serum ELISA.

Mechanical impairment of the aortic media caused by vasa vasorum dysfunction: a potential key element in the pathogenesis of aortic dissection in hypertensive patients

We read with great interest the recent paper of Osada et al. [1] regarding the role of the vasa vasorum (VV) in the triggering process of aortic dissection. The authors evaluated the history and histopathology of 21 patients with thoracic aortic dissection and discussed some intriguing findings that we would like to comment upon. Although ‘hypertension and advanced age seem to be major predisposing factors for aortic dissection’ [1], a pertinent plausible pathogenetic mechanism is still lacking. Some years ago, we proposed such a mechanism after we investigated the structural and mechanical alterations of the porcine aortic wall, resulting from impairment of VV flow [2]. That study demonstrated that impaired aortic wall blood supply leads to (a) structural abnormalities of the outer media and (b) increased aortic stiffness. As diffusion from the lumen is inadequate to supply the whole thickness of the aortic wall with oxygen and nutrients, our pathogenetic model suggests that a decreased VV flow reportedly occurring in arterial hypertension [3]would nutritionally disadvantage the outer media with unfavourable implications on its mechanical characteristics. Thus, the aortic media will act, from a mechanical perspective, as a two-phase material, i.e. a sufficiently nourished inner part with normal elasticity and an ischaemic outer part with increased stiffness. We found the borderline between these parts to be quite sharp in pigs, with a microscopical outset of dissection often observed at this point. Accordingly, we speculated that interlaminar shear stresses develop at that borderline in hypertensive patients [4], eventually leading to detachment of the layers and aortic dissection [2]. Our team thanks Osada et al. for referencing our work. We were content to see several of their findings supporting our pathogenetic concept. First, the striking histopathological similarities between their clinical and our experimental specimens sustain the idea of ischaemic outer media in chronic hypertension. They report ‘atrophy of the smooth muscle cells’ along with ‘clear abnormalities in the elastic laminae, including fragmentation, and

Transesophageal Echocardiographic Imaging of Aortic Valve Replacement Using Autologous Glutaraldehyde-Treated Pericardium

Transesophageal Echocardiographic Imaging of Aortic Valve Replacement Using Autologous Glutaraldehyde-Treated Pericardium

Biological ferroelectricity uncovered in aortic walls by piezoresponse force microscopy.

Many biological tissues are piezoelectric and pyroelectric with spontaneous polarization. Ferroelectricity, however, has not been reported in soft biological tissues yet. Using piezoresponse force microscopy, we discover that the porcine aortic walls are not only piezoelectric, but also ferroelectric, with the piezoelectric coefficient in the order of 1 pm/V and coercive voltage approximately 10 V. Through detailed switching spectroscopy mapping and relaxation studies, we also find that the polarization of the aortic walls is internally biased outward, and the inward polarization switched by a negative voltage is unstable, reversing spontaneously to the more stable outward orientation shortly after the switching voltage is removed. The discovery of ferroelectricity in soft biological tissues adds an important dimension to their biophysical properties, and could have physiological implications as well.