Complete dynamic repopulation of decellularized heart valves by application of defined physical signals—an in vitro study

Schenke‐Layland, Katja; Opitz, Florian; Groß, Michael; Doring, Charles; Kj, Halbhuber; Schirrmeister, F.; Wahlers, T; Stock, Ulrich A.

doi:10.1016/j.cardiores.2003.09.002

Cited by 119 publications

(62 citation statements)

References 33 publications

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“…It has become increasingly clear that the assumption that xenoantigens are likely to be cell-associated is not valid. Our findings further emphasize that treatment of unfixed xenogeneic tissues for tissue engineering applications must shift from a paradigm of "decellularization" to one of "antigen removal" [9][10][11][12][14][15][16][17][18][19][20][21][22][23][24][25][26]. Current or future antigen removal or antigen masking treatments will need to account for both cellular and extracellular matrix antigens.…”

Section: Discussionmentioning

confidence: 99%

“…Because tissues are unfixed in this application, it is necessary to remove graft antigenicity prior to implantation. Numerous physical and chemical treatments designed to decrease the immunogenicity of unfixed xenogeneic biomaterials have been investigated [9,11,12,[14][15][16][17][18][19][20][21][22][23][24][25][26]. These treatments have generally been characterized as tissue "decellularization", based on the assumption that antigens mediating an immune response to the graft would likely be cell-associated.…”

Section: Introductionmentioning

confidence: 99%

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Immunoproteomic identification of bovine pericardium xenoantigens

et al. 2008

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Bovine pericardium is an important biomaterial with current application in glutaraldehyde-fixed bioprosthetic heart valves and possible future application as an unfixed biological scaffold for tissue engineering. The importance of both humoral and cell-mediated rejection responses toward fixed and unfixed xenogeneic tissues has become increasingly apparent. However, the full scope and specific identities of bovine pericardium proteins that can elicit an immune response remain largely unknown. In this study, an immunoproteomic approach was used to survey bovine pericardium proteins for their ability to elicit a humoral immune response in rabbits. A two-stage protein extraction protocol was used to separate bovine pericardium proteins into water-and lipid-soluble fractions. Two-dimensional gel electrophoresis was performed to separate the proteins from each fraction. Western blots were generated from two-dimensional gels of both bovine pericardium protein fractions. These blots were probed with serum from rabbits immunized with bovine pericardium and a secondary antibody was used to assess for IgG positivity. Western blots were compared to duplicate two-dimensional gels and proteins in matched spots were identified by tandem mass spectrometry. Thirty-one putative protein antigens were identified, eight of which are known to be antigenic from previous studies. All of the putative antigens demonstrated progressive staining intensity with increasing days of post-exposure serum. Identified antigenic proteins represented a variety of functional and structural protein types, and included both cellular and matrix proteins. The results of this study have implications for the use of bovine pericardium as a biomaterial in bioprostheses and tissue engineering applications, as well as xenotransplantation in general.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunoproteomic identification of bovine pericardium xenoantigens

et al. 2008

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“…Other histological evaluations of decellularized bovine pericardium, which we did not include in this study, confirmed the efficacy of the method. Note that this result is not always obtained as was reported by SCHENKE-LAYLAND et al [30] who described "almost complete" decellularization in porcine valves treated by enzymatic digestion using tripsin.…”

Section: Discussionmentioning

confidence: 56%

Comparação entre o pericárdio bovino decelularizado e o pericárdio bovino convencional utilizado na confecção de biopróteses valvares cardíacas

Costa¹,

Pomerantzeff²,

Braile³

et al. 2005

Rev Bras Cir Cardiovasc

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Introduction: In this paper, our objective was to compare the decellularized and conventional pericardium mechanical resistance and also its capability of inducing inflammatory response in an animal experimental model.Methods: In order to study these properties, we divided the pericardia into two groups: Group I -pericardium conventionally treated with GTA and Group II -pericardium previously decellularized and then treated with GTA in the conventional way. After the chemical treatment, Group II samples were histologically evaluated to confirm the efficacy of the decellularization process. Then, only for the analysis of mechanical resistance, pericardia were divided in: Groups 1 (conventional pericardia with criteria of approval), 2 (conventional pericardial with criteria of rejection) and 3 (decellularized pericardia). The capacity of inducing inflammatory response was tested in a rat experimental model using 50 Wistar rats, in which rats of each group received patches of the pericardia in the abdomen. Our third step of analysis was to manufacture three decellularized pericardium bioprostheses which were submitted to hydrodynamic evaluation together with a conventional bioprosthesis test.Results: The histological analysis showed complete decellularization. Mechanical resistance gave statistical differences in the "tension of rupture" and "tenacity index" tests. We found no difference in the inflammatory activity in the animal model. Hydrodynamic performance was similar and all prostheses reached 150 million cycles. The final histological analysis assessed the standard microscopic pattern and no rupture or abnormal fragmentation was caused by mechanical stress. Conclusion:The decellularization technique maintains the physical resistance of the pericardium when compared with the conventionally prepared pericardium. And also, there was no difference in both groups regarding to inflammatory response studied in the animal model. Descriptors: Heart valve prosthesis. Bioprosthesis. Pericarduim. Comparative study. Comparação entre o pericárdio bovino decelularizado e o pericárdio bovino convencional utilizado na confecção de biopróteses valvares cardíacasComparison between the decellularized bovine pericardium and the conventional bovine pericardium used in the manufacture of cardiac bioprostheses 15 COSTA, JNL ET AL -Comparison between the decellularized bovine pericardium and the conventional bovine pericardium used in the manufacture of cardiac bioprostheses Braz J Cardiovasc Surg 2005; 20(1):14-22

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“…These systems either apply mechanical loading in a wide physiological range, mimicking both systole as well as diastole, 9,15,32 or are characterized by simulation of the systolic or opening phase of the cardiac cycle. 17,31,35,42 However, the diastolic phase or closing phase represents the load bearing phase of the cardiac cycle, in which most strain is applied to the heart valve tissue. The positive effect of cyclic tissue straining on the developing construct has been demonstrated in recent studies.…”

Section: Introductionmentioning

confidence: 99%

Real Time, Non-Invasive Assessment of Leaflet Deformation in Heart Valve Tissue Engineering

et al. 2008

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Abstract-In heart valve tissue engineering, most bioreactors try to mimic physiological flow and operate with a preset transvalvular pressure applied to the tissue. The induced deformations are unknown and can vary during culturing as a consequence of changing mechanical properties of the engineered construct. Real-time measurement and control of local tissue strains are desired to systematically study the effects of mechanical loading on tissue development and, consequently, to design an optimal conditioning protocol. In this study, a method is presented to assess local tissue strains in heart valve leaflets during culturing. We hypothesize that local tissue strains can be determined from volumetric deformation. Volumetric deformation is defined as the amount of fluid displaced by the deformed heart valve leaflets in a stented configuration, and is measured, noninvasively, using a flow sensor. A numerical model is employed to relate volumetric deformation to local tissue strains in various regions of the leaflets (e.g. belly and commissures). The flow-based deformation measurement method was validated and its functionality was demonstrated in a tissue engineering experiment. Tri-leaflet, stented heart valves were cultured in vitro and during mechanical conditioning, realistic values for volumetric and local deformation were obtained.

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Complete dynamic repopulation of decellularized heart valves by application of defined physical signals—an in vitro study

Abstract: This study demonstrated the superiority of the hydrodynamic approach of cellular reseeding to replace decellularized porcine heart valves with ovine cells with almost complete preservation of extracellular matrix integrity.

Cited by 119 publications

References 33 publications

Immunoproteomic identification of bovine pericardium xenoantigens

Immunoproteomic identification of bovine pericardium xenoantigens

Comparação entre o pericárdio bovino decelularizado e o pericárdio bovino convencional utilizado na confecção de biopróteses valvares cardíacas

Real Time, Non-Invasive Assessment of Leaflet Deformation in Heart Valve Tissue Engineering

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