Performance and Morphology of Decellularized Pulmonary Valves Implanted in Juvenile Sheep

Brown University, Providence, Rhode Island, United States
The Annals of thoracic surgery (Impact Factor: 3.85). 07/2011; 92(1):131-7. DOI: 10.1016/j.athoracsur.2011.03.039
Source: PubMed


Because of cryopreserved heart valve-mediated immune responses, decellularized allograft valves are an attractive option in children and young adults. The objective of this study was to investigate the performance and morphologic features of decellularized pulmonary valves implanted in the right ventricular outflow tract of juvenile sheep.
Right ventricular outflow tract reconstructions in juvenile sheep (160±9 days) using cryopreserved pulmonary allografts (n=6), porcine aortic root bioprostheses (n=4), or detergent/enzyme-decellularized pulmonary allografts (n=8) were performed. Valve performance (echocardiography) and morphologic features (gross, radiographic, and histologic examination) were evaluated 20 weeks after implantation.
Decellularization reduced DNA in valve cusps by 99.3%. Bioprosthetic valves had the largest peak and mean gradients versus decellularized valves (p=0.03; p<0.001) and cryopreserved valves (p=0.01; p=0.001), which were similar (p=0.45; p=0.40). Regurgitation was minimal and similar for all groups (p=0.16). No cusp calcification was observed in any valve type. Arterial wall calcification was present in cryopreserved and bioprosthetic grafts but not in decellularized valves. No autologous recellularization or inflammation occurred in bioprostheses, whereas cellularity progressively decreased in cryopreserved grafts. Autologous recellularization was present in decellularized arterial walls and variably extending into the cusps.
Cryopreserved and decellularized graft hemodynamic performance was comparable. Autologous recellularization of the decellularized pulmonary arterial wall was consistently observed, with variable cusp recellularization. As demonstrated in this study, decellularized allograft valves have the potential for autologous recellularization.

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    • "Heart valve bioprostheses engineered to be immunologically inert and mechanically durable with the ability to grow, repair, and regenerate could solve these problems[13,17]. Decellularization of heart valves reduces surface antigenicity, preserves mechanical properties, maintains natural extracellular matrix (ECM) characteristics , and produces a scaffold that is theoretically capable of being repopulated with native vascular cells1617182021222324252627. However, decellularization does not completely eliminate the immune mediated degeneration of some tissue valve grafts[12,14,17,25,28]. "
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    ABSTRACT: The long term efficacy of tissue based heart valve grafts may be limited by progressive degeneration characterized by immune mediated inflammation and calcification. To avoid this degeneration, decellularized heart valves with functionalized surfaces capable of rapid in vivo endothelialization have been developed. The aim of this study is to examine the capacity of CD133 antibody-conjugated valve tissue to capture circulating endothelial progenitor cells (EPCs). Decellularized human pulmonary valve tissue was conjugated with CD133 antibody at varying concentrations and exposed to CD133 expressing NTERA-2 cl.D1 (NT2) cells in a microflow chamber. The amount of CD133 antibody conjugated on the valve tissue surface and the number of NT2 cells captured in the presence of shear stress was measured. Both the amount of CD133 antibody conjugated to the valve leaflet surface and the number of adherent NT2 cells increased as the concentration of CD133 antibody present in the surface immobilization procedure increased. The data presented in this study support the hypothesis that the rate of CD133(+) cell adhesion in the presence of shear stress to decellularized heart valve tissue functionalized by CD133 antibody conjugation increases as the quantity of CD133 antibody conjugated to the tissue surface increases.
    No preview · Article · Sep 2015 · Biomedical Materials
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    ABSTRACT: Decellularized allografts are promising options for pediatric valve replacement due to reduced immunogenicity and the potential for in vivo autologous recellularization, extracellular matrix (ECM) remodeling and re-endothelialization, which may be enhanced with post-decellularization processing steps. This study investigated the performance and morphology of decellularized and ECM conditioned pulmonary valves implanted in the right ventricular outflow tracts (RVOT) of juvenile sheep. RVOT reconstructions in juvenile sheep using cryopreserved pulmonary allografts (Cryo; n = 2), porcine aortic root bioprostheses (Biopros; n = 2) or decellularized/ECM conditioned pulmonary allografts (Conditioned; n = 4) were performed. Valve performance and morphology were evaluated at 20 weeks after implant. Uniaxial tensile testing was performed on a subset of unimplanted valves from each group. At explant, Biopros had significantly higher peak/mean gradients vs. Conditioned and Cryo, which were similar. No cusp calcification occurred in any valve; arterial wall calcification was present only in Cryo (mild/moderate) and Biopros (severe). No autologous recellularization or inflammation occurred in Biopros; cellularity was decreased in Cryo. Autologous recellularization was present in Conditioned arterial walls and variably extending into the cusps, with consistent cusp re-endothelialization. Conditioned valves had reduced cusp extensibility, increased stiffness and similar tensile strength vs. Cryo. Although Conditioned valves were slightly stiffer and less extensible than Cryo valves, their hemodynamic performance was comparable, indicating they behave as functional heart valves immediately following implant. Because both autologous recellularization and re-endothelialization were seen, ECM conditioning shows promise for encouraging renewal of the cellularity of decellularized allograft valves without the need for pre-implant endothelial cell seeding.
    Full-text · Article · Jun 2012
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    ABSTRACT: In the development of tissue-engineered heart valves based on allograft decellularized extracellular matrix scaffolds, the material properties of the implant should be ideally comparable to the native semilunar valves. This investigation of the viscoelastic properties of the three functional aortic/pulmonary valve tissues (leaflets, sinus wall, and great vessel wall) was undertaken to establish normative values for fresh samples of human valves and to compare these properties after various steps in creating scaffolds for subsequent bioreactor-based seeding protocols. Torsional wave methods were used to measure the viscoelastic properties. Since preclinical surgical implant validation studies require relevant animal models, the tests reported here also include results for three pairs of both ovine and baboon aortic and pulmonary valves. For human aortic valves, four cryopreserved valves were compared with four decellularized scaffolds. Because of organ and heart valve transplant scarcity for pulmonary valves, only three cryopreserved and two decellularized pulmonary valves were tested. Leaflets are relatively soft. Loss angles are similar for all tissue samples. Regardless of species, the decellularization process used in this study has little effect on viscoelastic properties.
    Full-text · Article · Sep 2011 · Tissue Engineering Part A
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