Glutaraldehyde-treated Bovine Pericardium Research Articles

Aortic valve neocuspidization using autologous versus bovine pericardium: Ozaki versus Batista.

The average living age of the population is constantly increasing and so is the incidence and prevalence of aortic valve disease. Surgical aortic valve replacement (SAVR) is the current gold standard treatment. Nevertheless, the use of prosthetic valves in SAVR is associated with issues that impact patients' quality of life. Aortic valve neocuspidization (AV Neo) offers a means to solve this dilemma by minimizing foreign valve tissue. AV Neo can either be performed using glutaraldehyde-treated autologous pericardium (Ozaki procedure) or bovine pericardium (Batista procedure). This commentary aims to discuss the recent study by Chan and colleagues which highlighted the surgical approach, clinical outcomes, and limitations of the Ozaki procedure, and compare this to the Batista procedure. A comprehensive literature search was performed using multiple electronic databases including PubMed, Ovid, Embase, and Scopus to collate the relevant research evidence. Although the Ozaki procedure can achieve favorable results whilst mainly avoiding the need for life-long oral anticoagulation with mechanical valves, it still has several limitations that may hinder results. AV Neo using glutaraldehyde-treated bovine pericardium, developed by pioneer cardiac surgeon Dr. Randas J. Vilela Batista, yields superior clinical outcomes to Ozaki's, including excellent survival, lower complications, and minimal need for reoperation as well as shorter operative times. AV Neo offers a means to perform SAVR whilst escaping the prosthetic valve issues. However, the Batista procedure has shown beyond doubt that it can be considered the superior approach for AV Neo over the Ozaki procedure.

A residual stiffness-based model for the fatigue damage of biological soft tissues

Biologically-derived and chemically-treated collagenous tissues such as glutaraldehyde-treated bovine pericardium (GLBP) are widely used in many medical applications. The long-term cyclic loading-induced tissue fatigue damage has been identified as one of the primary factors limiting the durability of such medical devices and an in-depth understanding of the fatigue behaviors of biological tissues is critical to increase device durability. However, a limited number of fatigue damage experiments were performed on biological tissues due to complexity and time-consuming nature of such fatigue experiments. Consequently, accurate constitutive models for fatigue damage are also lacking. In this study, we performed a rigorous fatigue experiment on GLBP tissues. The stress, strain and permanent set at a maximum of 8 different fatigue cycles, up to 15 million cycles, were obtained, which demonstrated a nonlinear stress softening and a nonlinear permanent set accumulation. Based on the experimental data, we developed a novel residual stiffness-based fatigue model. The fatigue model considers the fatigue-induced reduction of initial stiffness and stiffening effect, in contrast to our previous damage-based model that only considered the fatigue-induced reduction of the initial stiffness. Moreover, a new constitutive relation was proposed to describe how the fatigue life (the cycle number at failure) depends on the equivalent strain, analogous to the stress versus fatigue life (S-N) curve for traditional engineering material. The new fatigue model can characterize the stress softening and nonlinear permanent set effects when referring to the pre-fatigued configuration. It can also describe the nonlinear stress stiffening effect when referring to the post-fatigued configuration. The model predictions are in good agreement with the experiment. The experimental results and the novel model could be applied to fatigue analyses of medical devices to improve the durability.

In situ tissue regeneration using a warp-knitted fabric in the canine aorta and inferior vena cava.

Materials used in paediatric cardiac surgery have drawbacks of deterioration, calcification and pseudointimal proliferation resulting in haemodynamic disturbance. The aim of this study was to investigate whether these drawbacks can be overcome by in situ tissue regeneration using a newly developed synthetic hybrid fabric (SHF). The SHF is an expandable, warp-knitted fabric composed of a combination of biodegradable [poly-l-lactic acid (PLLA)] and non-biodegradable (polyethylene terephthalate) yarns. The fabric is coated with cross-linked gelatin. Mechanical properties of the SHF were compared with those of 2 commercial products: expanded polytetrafluoroethylene sheet and glutaraldehyde-treated bovine pericardium. An oval-shaped defect created in the canine descending aorta or inferior vena cava was filled with the SHF patch. After 2 weeks and 1, 3, 6 and 12 (or 24 in the inferior vena cava) months, the patch was removed for histological examination and evaluation of the remaining PLLA. The SHF exhibited satisfactory tensile and suture retention strength for surgical implantation similar to or better than the 2 commercial products. Tissue regeneration was induced with multilayered smooth muscle cells and collagen fibres on both sides of the patch, along with a mature endothelial layer and tissue connections containing vasa vasorum across the patch in the aorta and inferior vena cava. Inflammatory reactions were minimal, and no calcium deposition occurred. The molecular weight of PLLA was reduced to half at 12 months after implantation. The SHF may solve the drawbacks of the existing products. Further studies of the expandability of the SHF patch after degradation of PLLA are warranted.

A deep learning approach to estimate chemically-treated collagenous tissue nonlinear anisotropic stress-strain responses from microscopy images.

In this study, we developed, to our best knowledge, the first Deep Learning-based approach to estimate the elastic properties of collagenous tissues directly from noninvasive second harmonic generation images. The success of this study holds promise for the use of Machine Learning techniques to noninvasively and efficiently estimate the mechanical properties of many structure-based biological materials, and it also enables many potential applications such as serving as a quality control tool to select tissue for the manufacturing of medical devices (e.g. bioprosthetic heart valves).

Characterization of mechanical properties of pericardium tissue using planar biaxial tension and flexural deformation.

Flexure is an important mode of deformation for native and bioprosthetic heart valves. However, mechanical characterization of bioprosthetic leaflet materials has been done primarily through planar tensile testing. In this study, an integrated experimental and computational cantilever beam bending test was performed to characterize the flexural properties of glutaraldehyde-treated bovine and porcine pericardium of different thicknesses. A strain-invariant based structural constitutive model was used to model the pericardial mechanical behavior quantified through the bending tests of this study and the planar biaxial tests previously performed. The model parameters were optimized through an inverse finite element (FE) procedure in order to describe both sets of experimental data. The optimized material properties were implemented in FE simulations of transcatheter aortic valve (TAV) deformation. It was observed that porcine pericardium TAV leaflets experienced significantly more flexure than bovine when subjected to opening pressurization, and that the flexure may be overestimated using a constitutive model derived from purely planar tensile experimental data. Thus, modeling of a combination of flexural and biaxial tensile testing data may be necessary to more accurately describe the mechanical properties of pericardium, and to computationally investigate bioprosthetic leaflet function and design.

Long-term healing of mildly cross-linked decellularized bovine pericardial aortic patch.

Glutaraldehyde treated bovine pericardium is extensively used in cardiovascular surgery. However, frequent occurrence of failure modes, such as calcification and structural failure, has hard pressed the need for finding an alternate technology. Decellularized bovine pericardium is an emerging technology. Mildly cross-linked decellularized bovine pericardium promotes positive remodeling with insignificant calcification and acute inflammation. In the present study, mildly cross-linked decellularized bovine pericardium was evaluated as a cardiovascular patch by studying mechanical strength as well as graft remodeling, resistance to calcific degeneration and inflammatory response using long duration porcine aortic implantation. It was observed that decellularized bovine pericardium, although thinner and less elastic had equivalent tensile properties such as tensile strength and stiffness when compared to commercially available glutaraldehyde-treated bovine pericardium. It showed the potential for site appropriate remodeling evidenced by host cell incorporation, thinner neointima, graft degradation, and neocollagenisation making it suitable for vascular patch application, whereas glutaraldehyde-treated pericardium failed to integrate with host tissue through timely degradation and host cell incorporation or neocollagenization. Conversely, it elicited persistent acute inflammation and produced calcification. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2145-2152, 2017.

Mapping the calcification of bovine pericardium in rat model by enhanced micro-computed tomography

The calcification initiation and progression of bioprosthetic heart valve were investigated in a rat model by enhanced micro-computed tomography, together with histologic study and scanning electron microscope analysis. The implantation data at early stage showed apparent dendritic patterns in the radiographic images for the glutaraldehyde-treated bovine pericardium and this dendritic pattern was verified to be associated with the vessel distribution in the tissue. Histologic study and scanning electron microscope analysis both indicated that the calcium deposits in the pericardium vessels regions were more grievous than those scattered in the collagen fibers in the first two weeks after implantation. Subsequently, calcification spreaded and the entire sample was severely calcified in 60 days.

Simulation of long-term fatigue damage in bioprosthetic heart valves: effects of leaflet and stent elastic properties

One of the major failure modes of bioprosthetic heart valves (BHVs) is noncalcific structural deterioration due to fatigue of the tissue leaflets; yet, the mechanisms of fatigue are not well understood. BHV durability is primarily assessed based on visual inspection of the leaflets following accelerated wear testing. In this study, we developed a computational framework to simulate BHV leaflet fatigue, which is both efficient and quantitative, making it an attractive alternative to traditional accelerated wear testing. We utilize a phenomenological soft tissue fatigue damage model developed previously to describe the stress softening and permanent set of the glutaraldehyde-treated bovine pericardium leaflets in BHVs subjected to cyclic loading. A parametric study was conducted to determine the effects of altered leaflet and stent elastic properties on the fatigue of the leaflets. The simulation results show that heterogeneity of the leaflet elastic properties, poor leaflet coaptation, and little stent-tip deflection may accelerate leaflet fatigue, which agrees with clinical findings. Therefore, the developed framework may be an invaluable tool for evaluating leaflet durability in new tissue valve designs, including traditional BHVs as well as new transcatheter valves.

Modeling of long-term fatigue damage of soft tissue with stress softening and permanent set effects

One of the major failure modes of bioprosthetic heart valves is non-calcific structural deterioration due to fatigue of the tissue leaflets. Experimental methods to characterize tissue fatigue properties are complex and time-consuming. A constitutive fatigue model that could be calibrated by isolated material tests would be ideal for investigating the effects of more complex loading conditions. However, there is a lack of tissue fatigue damage models in the literature. To address these limitations, in this study, a phenomenological constitutive model was developed to describe the stress softening and permanent set effects of tissue subjected to long-term cyclic loading. The model was used to capture characteristic uniaxial fatigue data for glutaraldehyde-treated bovine pericardium and was then implemented into finite element software. The simulated fatigue response agreed well with the experimental data and thus demonstrates feasibility of this approach.

Establishing a swine model to compare vascular prostheses in a contaminated field

ObjectivePatch arteriotomies are performed during many vascular procedures. Whereas synthetic materials are generally felt to be inappropriate for infected environments, the suitability of glutaraldehyde-treated bovine pericardium (GBP), a biologic material, in such instances is unknown. Our main objectives were to develop an animal model to study vascular prostheses while comparing the infectability of polyester (Dacron) and GBP in a topically infected environment. MethodsTwenty-three pigs underwent transabdominal patch arteriotomy of the infrarenal aorta with either Dacron or GBP. The patches were inoculated with sterile saline (1 per group), Staphylococcus aureus 104 colony-forming units (CFUs) (4 per group), or S. aureus 105 CFUs (6 per group). At 3 wk, the animals were euthanized, and the patches were removed via a left retroperitoneal approach. Specimens were collected for microbiologic and histologic analysis. ResultsOne animal from each group inoculated with 105 CFUs died during the study period, and another died immediately postoperatively of an airway complication. All aortas were patent and without evidence of pseudoaneurysm formation. Gross abscesses were found in 4/6 Dacron and 5/6 GBP animals receiving 105 CFUs. Similarly, 4/6 animals implanted with Dacron and 5/6 animals implanted with GBP had positive tissue cultures. A histologic grading system of inflammation substantiated the culture results. ConclusionsNo significant difference exists between Dacron and GBP to resist bacterial infection at 3 wk. We have established a reproducible in vivo model to study arterial patch materials in a topically infected environment.

A Swine Model for the Evaluation of Glutaraldehyde-Treated Bovine Pericardium and Dacron Arterial Patches in a Topically Infected Environment

A Swine Model for the Evaluation of Glutaraldehyde-Treated Bovine Pericardium and Dacron Arterial Patches in a Topically Infected Environment

Glutaraldehyde treatment elicits toxic response compared to decellularization in bovine pericardium

Glutaraldehyde-stabilized bovine pericardium is used for clinical application since 1970s because of its desirable features such as less immunogenicity and acceptable durability. However, a propensity for calcification is reported on account of glutaraldehyde treatment. In this study, commercially available glutaraldehyde cross-linked bovine pericardium was evaluated for its in vitro cytotoxic effect, macrophage activation, and in vivo toxic response in comparison to decellularized bovine pericardium. Glutaraldehyde-treated bovine pericardium and its extract were observed to be cytotoxic and it also caused significant inflammatory cytokine release from activated macrophages. Significant antibody response, calcification response, necrotic, and inflammatory response were noticed in glutaraldehyde-treated bovine pericardium in comparison to decellularized bovine pericardium in a rat subcutaneous implantation model. Glutaraldehyde-treated bovine pericardium also failed in acute systemic toxicity testing and intracutaneous irritation testing as per ISO 10993. With respect to healing and implant remodeling, total lack of host tissue incorporation and angiogenesis was noticed in glutaraldehyde-treated bovine pericardium compared to excellent host fibroblast incorporation and angiogenesis within the implant in decellularized bovine pericardium. In conclusion, using in vitro and in vivo techniques, this study has demonstrated that glutaraldehyde-treated bovine pericardium elicits toxic response compared to decellularized bovine pericardium which is not congenial for long-term implant performance.

Effect of Freeze-Drying on the Mechanical, Physical and Morphological Properties of Glutaraldehyde-Treated Bovine Pericardium: Evaluation of Freeze-Dried Treated Bovine Pericardium Properties

Biomaterials have been widely used in the field of regenerative medicine. Bovine pericardium tissue has been successfully used as a bioprosthetic material in manufacturing heart valves, but studies concerning the tissue are ongoing in order to improve its storage, preservation and transportation. This article provides an overview of the characteristics of bovine pericardium tissue chemically treated after the freeze-drying process. These characteristics are essential to evaluate the changes or damage to the tissue during the process.The mechanical properties of the tissue were analyzed by three different methods due to its anisotropic characteristics. The physical properties were analyzed by a colorimetric method, while the morphological properties were evaluated by scanning electron microscopy (SEM).The freeze-dried bovine pericardium showed no significant change in its mechanical properties. There was no significant change in the elasticity of the tissue (p>0.05) and no color change. In addition, SEM analysis showed that the freeze-dried samples did not suffer structural collapse.It was concluded that glutaraldehyde-treated bovine pericardium tissue showed no significant change in its properties after the freeze-drying process.

The micromechanical behavior of lyophilized glutaraldehyde-treated bovine pericardium under uniaxial tension

The micromechanical behavior of lyophilized glutaraldehyde bovine pericardium undergoing uniaxial tension was studied by digital image correlation. The experiments were conducted simultaneously at macromechanical and micromechanical levels, to correlate the mechanical response of this biomaterial at different scales. From the experiments, displacement and force data were acquired; in addition, an image sequence of each sample surface was registered with a high-definition camera. With the images, it was possible to obtain the vector displacement field between pairs of images and then the in-plane strain was calculated. The secant and final moduli of this material were obtained at macromechanical and micromechanical levels. A good agreement between the micro and macro moduli was observed. This analysis is a useful alternative technique for studying this biomaterial when local properties are needed for medical applications.

Hypoelastic soft tissues

In Part I, a novel hypoelastic framework for soft-tissues was presented. One of the hallmarks of this new theory is that the well-known exponential behavior of soft-tissues arises consistently and spontaneously from the integration of a rate based formulation. In Part II, we examine the application of this framework to the problem of biaxial kinematics, which are common in experimental soft-tissue characterization. We confine our attention to an isotropic formulation in order to highlight the distinction between non-linearity and anisotropy. In order to provide a sound foundation for the membrane extension of our earlier hypoelastic framework, the kinematics and kinetics of in-plane biaxial extension are revisited, and some enhancements are provided. Specifically, the conventional stress-to-traction mapping for this boundary value problem is shown to violate the conservation of angular momentum. In response, we provide a corrected mapping. In addition, a novel means for applying loads to in-plane biaxial experiments is proposed. An isotropic, isochoric, hypoelastic, constitutive model is applied to an in-plane biaxial experiment done on glutaraldehyde treated bovine pericardium. The experiment is comprised of eight protocols that radially probe the biaxial plane. Considering its simplicity (two adjustable parameters) the model does a reasonably good job of describing the non-linear normal responses observed in these experimental data, which are more prevalent than are the anisotropic responses exhibited by this tissue.

Resistência tensional do pericárdio bovino fixado em glutaraldeído comparada com a da veia safena magna

CONTEXTO: O uso do pericárdio bovino como remendo na endarterectomia de carótida é uma alternativa à veia safena magna. As vantagens do pericárdio incluem facilidade de obtenção, menor tempo operatório e principalmente menor índice de ruptura. OBJETIVO: Avaliar a resistência tensional do pericárdio bovino tratado com glutaraldeído e compará-la com a da veia safena magna. MÉTODOS: Os remendos de pericárdio bovino (grupo I, n = 20) e de veia safena magna (grupo II, n = 20) foram recortados em dimensões iguais (50 x 5 mm) e preparados de modo habitual a sua utilização. Os grupos foram submetidos a ensaio de tração e comparados em relação a força de ruptura, força máxima e tensão de ruptura utilizando-se o teste t de Student. A correlação da espessura do remendo com a força de ruptura também foi analisada utilizando-se o coeficiente de correlação linear de Pearson. RESULTADOS: Os parâmetros força de ruptura e força máxima foram significativamente maiores no grupo dos remendos de pericárdio bovino: 1,97 versus 1,36 kgf (p = 0,001230) e 2,27 versus 1,51 kgf (p = 0,0001087), respectivamente. A tensão de ruptura média para o material pericárdio bovino também foi maior (193,99±43,05 versus 49,19±22,96 kgf/cm², p = 7,603e-16) do que na veia safena. A correlação entre a espessura e a força de ruptura foi considerada moderada (r = 0,5032993) para o pericárdio bovino e baixa (r = 0,3062166) para o grupo da veia safena. CONCLUSÃO: Os autores concluem que a resistência do pericárdio bovino à ruptura foi considerada adequada neste estudo, e é significativamente maior que a da veia safena magna, retirada da região da coxa. Além disso, a espessura do remendo em ambos os grupos não apresenta boa correlação com sua resistência a ruptura.

“Less Stented” Bovine Pericardial Xenograft: A New Concept

The in vitro hemodynamic behavior of a bovine pericardium xenograft with discontinuity of the annular support, named the "Less Stented" bovine pericardial xenograft, was analyzed. A "Less Stented" bovine pericardial xenograft consisting of a glutaraldehyde-treated bovine pericardium prosthesis manufactured in Braile Biomédica Ltd, São José do Rio Preto, São Paulo, Brazil, was used according to the same protocols of the stented bioprosthesis manufacturer. Bovine pericardial xenografts were tested in a pulse simulator and analyzed in a cardiac simulator, with respect to the transvalvular gradient, regurgitant fraction and leakage volume, discharge coefficient, performance, and efficiency index. Analyses were performed by Pearson's correlation test and simple linear regression. The transvalvular gradients ranged between 6.37 and 11.62 mm Hg with a mean flow between 4.39 and 7.96 L/min, giving a good correlation (0.8291) on the regression curve with an increase in flow. The regurgitant fraction ranged between 10.95 and 17.94% and leakage volume between 4.49 and 7.87%. The discharge coefficient, performance, and efficiency index showed favorable behavior with the flow increase, with good correlation coefficient (0.9385, 0.9332, and 0.9024, respectively). The initial results of the "Less Stented" bovine pericardial xenograft size 25 analyses demonstrated a satisfactory in vitro performance. Evaluations of the hemodynamic performance of small size "Less Stented" bovine pericardial xenograft should be made to clarify the biological behavior of this new xenograft.

Effects of collagen fiber orientation on the response of biologically derived soft tissue biomaterials to cyclic loading

In the present study, the effects of initial collagen fiber orientation on the medium-term (up to 50 x 10(6) cycles) fatigue response of heart valve soft tissue biomaterials was investigated. Glutaraldehyde treated bovine pericardium (GLBP), preselected for uniform structure and collagen fiber orientation, was used as the representative heart valve biomaterial. Using specialized instrumentation, GLBP specimens were subjected to cyclic tensile loading to maximum stress levels of 500 +/- 50 kPa at a frequency of 22 Hz. Two sample groups were examined, one with the preferred collagen fiber direction parallel (PD) and perpendicular (XD) to the direction of applied strain. The primary findings indicated that GLBP fatigue response was highly sensitive to the direction of loading with respect to fiber orientation. Specifically, when loading perpendicular to the preferred collagen fiber orientation, fiber reorientation is the dominant mechanism. In contrast, when loaded parallel to the preferred fiber direction a reduction in both collagen fiber crimp and fiber reorientation occurred. Moreover, alterations in the degree and direction of mechanical anisotropy can be inducted by cyclic loading when specimens are loaded perpendicular to the preferred fiber direction. Fourier Transform Infrared Spectroscopy (FT-IR) results indicate that molecular-level damage to collagen occurs in both groups after only 20 x 10(6) cycles. Taken as a whole, the results of this study suggest that initial collagen orientation plays a critical role in bioprosthetic heart valve biomaterial fatigue response.

Functional analysis of bioprosthetic heart valves

Glutaraldehyde-treated bovine pericardium is used successfully as bioprosthetic material in the manufacturing of heart valves leaflets. The mechanical properties of bovine pericardial aortic valve leaflets seem to influence its mechanical behaviour and the failure mechanisms. In this study the effect of orthotropy on tricuspid bioprosthetic aortic valve was analysed, using a three-dimensional finite element model, during the entire cardiac cycle. Multiaxial tensile tests were also performed to determine the anisotropy of pericardium. Seven different models of the same valve were analysed using different values of mechanical characteristics from one leaflet to another, considering pericardium as an orthotropic material. The results showed that even a small difference between values along the two axes of orthotropy can negatively influence leaflets performance as regard both displacement and stress distribution. Leaflets of bovine pericardium bioprostheses could be manufactured to be similar to natural human heart valves reproducing their well-known anisotropy. In this way it could be possible to improve the manufacturing process, durability and function of pericardial bioprosthetic valves.

The effects of collagen fiber orientation on the flexural properties of pericardial heterograft biomaterials

Improving cardiac valve bioprostheses (BHV) utilizing heterograft biomaterials requires a better understanding of their mechanical behavior. Flexure is a major mode of deformation for BHV leaflets during valve operation, inducing more complex deformation patterns within the tissue compared to tensile loads. In this study, we investigated the relation between collagen fiber preferred direction and the resulting flexural properties of native and glutaraldehyde-treated bovine pericardium. 20 mm×4 mm strips were cut from the presorted sheets of bovine pericardium and divided into four groups: two directions of collagen fiber orientation in two groups of native and chemically treated specimens. Specimens were flexed in two different directions using a three-point bending technique (ASAIO J. 45(1999)59) and their flexural mechanical response compared. Results indicated that: (1) the relationship between the applied flexing moment and change of curvature of specimens was non-linear in both native and chemically fixed groups, (2) there were no directional differences in flexural properties when the bovine pericardium is flexed towards either the epi-pericardial or visceral surfaces in both native and chemically fixed specimens, (3) native and chemically fixed bovine pericardium were stiffer when flexed perpendicular to local preferred collagen fiber direction, and (4) chemical fixation increased the flexural rigidity of bovine pericardium. Results of this study indicate that the flexural properties of bovine pericardium are dominated by inter-fiber cross-links as opposed to the stiffness of the collagen fibers themselves. These findings can be used to guide the development of novel chemical treatment methods that seek to optimize biomechanical properties of heterograft biomaterials.