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  • Ovid Technologies (Wolters Kluwer Health)  (6)
  • 1
    Online Resource
    Online Resource
    Abstract 5838: Successful Replacement of Aortic Valves by Decellularized Allografts in the Sheep: First Long-Term Results
    Ovid Technologies (Wolters Kluwer Health) ; 2008
    In:  Circulation Vol. 118, No. suppl_18 ( 2008-10-28)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 118, No. suppl_18 ( 2008-10-28)
    Abstract: Immunogenicity of human allografts leads to gradual valve degeneration. Pulmonal cell-free valvular scaffolds obtained by methods of tissue engineering have proved to induce in-vivo guided tissue regeneration and represent a promising valve substitute especially for children. Here we describe the successful orthotopic implantation of decellularized aortic valves in the systemic circulation in sheep. Allogenic detergent decellularized (0.5% sodium deoxycholate/0.5% SDS) aortic valve (AV) conduits (n = 12) were implanted orthotopically as root replacement in lambs (35–45 kg). Fresh native AV conduits served as controls (n = 6). After three and nine months follow-up the valves were investigated for functionality by echocardiography, for morphology and histological appearance. Decellularization resulted in complete loss of cells in AV wall, cusp and myocardial cuff, no influence on scaffold microarchitecture was observed. During 9 months follow-up no signs of conduit dilatation, aortic stenosis (transvalvular gradient max. 6.1 ± 5.1mmHg) or reduction of cusp mobility were observed in the decellularized group. Regurgitation in these valves was trivial in all cases. The grafts showed no histological signs of rejection and partial repopulation of the valvular scaffolds with autologous cells. In contrast, control animals developed mild to severe AV insufficiency. Histological investigation revealed significant calcific degeneration and massive rejection of these valves. Decellularized AV conduits may represent a durable AV substitute resistant to high systemic pressure. Furthermore, cell-removal prevents the allograft valve from immunologic deterioration and early graft degeneration.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.118.suppl_18.S_1013-a
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2008
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  • 2
    Online Resource
    Online Resource
    Construction of Autologous Human Heart Valves Based on an Acellular Allograft Matrix
    Ovid Technologies (Wolters Kluwer Health) ; 2002
    In:  Circulation Vol. 106, No. 12_suppl_1 ( 2002-09-24)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 106, No. 12_suppl_1 ( 2002-09-24)
    Abstract: Objective Tissue engineered heart valves based on polymeric or xenogeneic matrices have several disadvantages, such as instability of biodegradable polymeric scaffolds, unknown transfer of animal related infectious diseases, and xenogeneic rejection patterns. To overcome these limitations we developed tissue engineered heart valves based on human matrices reseeded with autologous cells. Methods and Results Aortic (n=5) and pulmonary (n=6) human allografts were harvested from cadavers (6.2±3.1 hours after death) under sterile conditions. Homografts stored in Earle’s Medium 199 enriched with 100 IU/mL Penicillin-Streptomycin for 2 to 28 days (mean 7.3±10.2 days) showed partially preserved cellular viability (MTT assay) and morphological integrity of the extracellular matrix (H-E staining). For decellularization, valves were treated with Trypsin/EDTA resulting in cell-free scaffolds (DNA-assay) with preserved extracellular matrix (confocal microscopy). Primary human venous endothelial cells (HEC) were cultivated and labeled with carboxy-fluorescein diacetate-succinimidyl ester in vitro. After recellularization under fluid conditions, EC were detected on the luminal surfaces of the matrix. They appeared as a monolayer of positively labeled cells for PECAM-1, VE-cadherin and Flk-1. Reseeded EC on the acellular allograft scaffold exhibited high metabolic activity (MTT assay). Conclusions Earle’s Medium 199 enriched with low concentration of antibiotics represents an excellent medium for long time preservation of extracellular matrix. After complete acellularization with Trypsin/EDTA, recellularization under shear stress conditions of the allogeneic scaffold results in the formation of a viable confluent HEC monolayer. These results represent a promising step toward the construction of autologous heart valves based on acellular human allograft matrix.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.cir.0000032900.55215.85
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2002
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  • 3
    Online Resource
    Online Resource
    BIOLOGICAL VASCULARIZED MATRIX FOR BLADDER TISSUE ENGINEERING: MATRIX PREPARATION, RESEEDING TECHNIQUE AND SHORT-TERM IMPLANTATION IN A PORCINE MODEL
    Ovid Technologies (Wolters Kluwer Health) ; 2005
    In:  Journal of Urology Vol. 173, No. 1 ( 2005-01), p. 276-280
    Details
    In: Journal of Urology, Ovid Technologies (Wolters Kluwer Health), Vol. 173, No. 1 ( 2005-01), p. 276-280
    Type of Medium: Online Resource
    ISSN: 0022-5347 , 1527-3792
    URL: Article
    DOI: 10.1097/01.ju.0000145882.80339.18
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2005
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  • 4
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    Use of Fresh Decellularized Allografts for Pulmonary Valve Replacement May Reduce the Reoperation Rate in Children and Young Adults : Early Report
    Ovid Technologies (Wolters Kluwer Health) ; 2011
    In:  Circulation Vol. 124, No. 11_suppl_1 ( 2011-09-13)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 124, No. 11_suppl_1 ( 2011-09-13)
    Abstract: Degeneration of xenografts or homografts is a major cause for reoperation in young patients after pulmonary valve replacement. We present the early results of fresh decellularized pulmonary homografts (DPH) implantation compared with glutaraldehyde-fixed bovine jugular vein (BJV) and cryopreserved homografts (CH). Methods and Results— Thirty-eight patients with DPH in pulmonary position were consecutively evaluated during the follow-up (up to 5 years) including medical examination, echocardiography, and MRI. These patients were matched according to age and pathology and compared with BJV (n=38) and CH (n=38) recipients. In contrast to BJV and CH groups, echocardiography revealed no increase of transvalvular gradient, cusp thickening, or aneurysmatic dilatation in DPH patients. Over time, DPH valve annulus diameters converge toward normal z -values. Five-year freedom from explantation was 100% for DPH and 86±8% and 88±7% for BJV and CH conduits, respectively. Additionally, MRI investigations in 17 DPH patients with follow-up time 〉 2 years were compared with MRI data of 20 BJV recipients. Both patient groups (DPH and BJV) were at comparable ages (mean, 12.7±6.1 versus 13.0±3.0 years) and have comparable follow-up time (3.7±1.0 versus 2.7±0.9 years). In DPH patients, the mean transvalvular gradient was significantly ( P =0.001) lower (11 mm Hg) compared with the BJV group (23.2 mm Hg). Regurgitation fraction was 14±3% and 4±5% in DPH and BJV groups, respectively. In 3 DPH recipients, moderate regurgitation was documented after surgery and remained unchanged in follow-up. Conclusions— In contrast to conventional homografts and xenografts, decellularized fresh allograft valves showed improved freedom from explantation, provided low gradients in follow-up, and exhibited adaptive growth.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.110.012161
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2011
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  • 5
    Online Resource
    Online Resource
    Clinical Application of Tissue Engineered Human Heart Valves Using Autologous Progenitor Cells
    Ovid Technologies (Wolters Kluwer Health) ; 2006
    In:  Circulation Vol. 114, No. 1_supplement ( 2006-07-04)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 114, No. 1_supplement ( 2006-07-04)
    Abstract: Background— Tissue engineering (TE) of heart valves reseeded with autologous cells has been successfully performed in vitro. Here, we report our first clinical implantation of pulmonary heart valves (PV) engineered with autologous endothelial progenitor cells (EPCs) and the results of 3.5 years of follow-up. Methods and Results— Human PV allografts were decellularized (Trypsin/EDTA) and resulting scaffolds reseeded with peripheral mononuclear cells isolated from human blood. Positive stain for von Willebrand factor, CD31, and Flk-1 was observed in monolayers of cells cultivated and differentiated on the luminal surface of the scaffolds in a dynamic bioreactor system for up to 21 days, indicating endothelial nature. PV reseeded with autologous cells were implanted into 2 pediatric patients (age 13 and 11) with congenital PV failure. Postoperatively, a mild pulmonary regurgitation was documented in both children. Based on regular echocardiographic investigations, hemodynamic parameters and cardiac morphology changed in 3.5 years as follows: increase of the PV annulus diameter (18 to 22.5 mm and 22 to 26 mm, respectively), decrease of valve regurgitation (trivial/mild and trivial, respectively), decrease (16 to 9 mm Hg) or a increase (8 to 9.5 mm Hg) of mean transvalvular gradient, remained 26 mm or decreased (32 to 28 mm) right-ventricular end-diastolic diameter. The body surface area increased (1.07 to 1.42 m 2 and 1.07 to 1.46 m 2 , respectively). No signs of valve degeneration were observed in both patients. Conclusions— TE of human heart valves using autologous EPC is a feasible and safe method for pulmonary valve replacement. TE valves have the potential to remodel and grow accordingly to the somatic growth of the child.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.105.001065
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2006
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  • 6
    Online Resource
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    Preclinical Testing of Tissue-Engineered Heart Valves Re-Endothelialized Under Simulated Physiological Conditions
    Ovid Technologies (Wolters Kluwer Health) ; 2006
    In:  Circulation Vol. 114, No. 1_supplement ( 2006-07-04)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 114, No. 1_supplement ( 2006-07-04)
    Abstract: Background— The in vivo regeneration capacity of decellularized heart valve grafts is still controversial. The aim of this study was to evaluate function, morphological changes, and cellular composition of decellularized versus re-endothelialized ovine pulmonary valves (PV) after implantation into lambs for 1 or 3 months. Methods and Results— PV (n=21) were decellularized using detergents. Twelve PV were repopulated with autologous jugular veins endothelial cells (ECs) in a dynamic pulsatile bioreactor under simulated physiological conditions. Morphological evaluation before implantation included histological stainings (H & E, Movat-pentachrome, von-Kossa, DAPI), immunostainings (anti-perlecan, anti-eNOS, anti-procollagen-I, anti-SM-α-actin), electron microscopy (EM), and DNA extraction. Decellularization led to cell-free scaffolds with preserved extracellular matrix (ECM) including basement membrane. Reseeded PV (n=5) were completely covered with ECs expressing endothelial nitric oxide synthase (eNOS) and von Willebrand factor (vWF). The function of orthotopically implanted decellularized and re-endothelialized PV (n=7, each) was analyzed after 1 and 3 months by echocardiography and revealed no differences in competence between both groups. A confluent EC monolayer expressing eNOS/vWF was only found in re-endothelialized PV but not in decellularized PV, whereas the valve matrices were comparable repopulated with interstitial cells expressing SM-α-actin and procollagen-I. More thrombotic and neointima formations were observed in decellularized PV. No signs of calcification were detected in both PV types. Conclusion— In vitro re-endothelialization of detergent-decellularized valves with autologous ECs under simulated physiological conditions significantly improves total EC valve coverage 3 months after implantation, whereas the valve repopulation with interstitial cells in vivo occurs most likely by cell migration inside the scaffold.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.105.001206
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2006
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