Off-the-shelf human decellularized tissue-engineered heart valves in a non-human primate model

Weber, Benedikt; Dijkman, Petra E.; Scherman, Jacques; Sanders, Bart; Emmert, Maximilian Y.; Grünenfelder, Jürg; Verbeek, Renier; Bracher, Mona; Black, Melanie; Franz, Thomas; Kortsmit, Jeroen; Modregger, Peter; Peter, Silvia; Stampanoni, Marco; Robert, Jérôme; Kehl, Debora; Doeselaar, Marina van; Schweiger, Martin; Brokopp, Chad E.; Wälchli, Thomas; Falk, Volkmar; Zilla, Peter; Driessen-Mol, Anita Anita; Baaijens, Fpt Frank; Hoerstrup, Simon P.

doi:10.1016/j.biomaterials.2013.04.059

Cited by 172 publications

(147 citation statements)

References 35 publications

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“…20 Reviewing all data collected on implantation of acellular roots, Ingham and collaborators concluded recently that incomplete valve decellularization is associated with severe graft failure. 21 Other experimental approaches to building tissueengineered valves include use of cell-seeded biodegradable polymers (synthetic or fibrin-based, molded in the shape of an aortic valve root) to generate a homogeneous, isotropic collagenous structure lacking elastic fibers, before implantation, 22,23 implantation of stent-mounted acellular valves seeded with vascular fibroblasts or stem cells, 24 as well as use of polymers 22,25 and layered composites. 13,14,26 Creating structures as heterogeneous as that of the aortic roots using a bottom-up approach (such as three-dimensional printing 27 ) is quite difficult and requires major technological advances.…”

Section: Introductionmentioning

confidence: 99%

“…Taken together, none of the above referenced approaches satisfied the design criteria. 22,[28][29][30] Learning from these data, we hypothesized that decellularized xenogeneic aortic valve roots could serve as excellent scaffolds for heart valve tissue engineering. However, careful structural and functional consideration has to be given to each segment of the root.…”

Section: Introductionmentioning

confidence: 99%

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Functional Heart Valve Scaffolds Obtained by Complete Decellularization of Porcine Aortic Roots in a Novel Differential Pressure Gradient Perfusion System

Sierad

Shaw

Bina

et al. 2015

Tissue Engineering Part C: Methods

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There is a great need for living valve replacements for patients of all ages. Such constructs could be built by tissue engineering, with perspective of the unique structure and biology of the aortic root. The aortic valve root is composed of several different tissues, and careful structural and functional consideration has to be given to each segment and component. Previous work has shown that immersion techniques are inadequate for wholeroot decellularization, with the aortic wall segment being particularly resistant to decellularization. The aim of this study was to develop a differential pressure gradient perfusion system capable of being rigorous enough to decellularize the aortic root wall while gentle enough to preserve the integrity of the cusps. Fresh porcine aortic roots have been subjected to various regimens of perfusion decellularization using detergents and enzymes and results compared to immersion decellularized roots. Success criteria for evaluation of each root segment (cusp, muscle, sinus, wall) for decellularization completeness, tissue integrity, and valve functionality were defined using complementary methods of cell analysis (histology with nuclear and matrix stains and DNA analysis), biomechanics (biaxial and bending tests), and physiologic heart valve bioreactor testing (with advanced image analysis of open-close cycles and geometric orifice area measurement). Fully acellular porcine roots treated with the optimized method exhibited preserved macroscopic structures and microscopic matrix components, which translated into conserved anisotropic mechanical properties, including bending and excellent valve functionality when tested in aortic flow and pressure conditions. This study highlighted the importance of (1) adapting decellularization methods to specific target tissues, (2) combining several methods of cell analysis compared to relying solely on histology, (3) developing relevant valve-specific mechanical tests, and (4) in vitro testing of valve functionality.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Functional Heart Valve Scaffolds Obtained by Complete Decellularization of Porcine Aortic Roots in a Novel Differential Pressure Gradient Perfusion System

Sierad

Shaw

Bina

et al. 2015

Tissue Engineering Part C: Methods

View full text Add to dashboard Cite

show abstract

“…An ideal tissue engineered heart valve (TEHV) should encompass several characteristics: good hemodynamics, appropriate valve geometry, high durability, non-immunogenicity, non-inflammatory, non-thrombogenic and non-calcifying (1,3). Additionally, for young patients, it should have the ability to grow and adapt with the patient's somatic growth (2,(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Pulmonary heart valve replacement using stabilized acellular xenogeneic scaffolds; effects of seeding with autologous stem cells

Harpa

Movileanu

Sierad³

et al. 2015

Revista Romana De Medicina De Laborator

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“…Decellularized TEHVs based on biodegradable synthetic materials may serve as suitable replacement of allografts and xenografts, but preclinical study in nonhuman primate and ovine models are characterized by valvular regurgitation due to leaflet shortening and reduced leaflet coaptation. [16][17][18][19] Although decellularized allograft heart valves have been used as TEHV scaffolds with success, 4,5 little is known about the cellular and molecular mechanisms underlying neotissue formation in these TEHVs. To study the mechanisms leading to neotissue formation in decellularized heart valve grafts, we established a mouse model of pulmonary valve transplant 6 and subsequently implanted decellularized mice pulmonary heart valves into isogenic mice recipients.…”

Section: Discussionmentioning

confidence: 99%

Hemodynamic Characterization of a Mouse Model for Investigating the Cellular and Molecular Mechanisms of Neotissue Formation in Tissue-Engineered Heart Valves

James

Tara

et al. 2015

Tissue Engineering Part C: Methods

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Decellularized allograft heart valves have been used as tissue-engineered heart valve (TEHV) scaffolds with promising results; however, little is known about the cellular mechanisms underlying TEHV neotissue formation. To better understand this phenomenon, we developed a murine model of decellularized pulmonary heart valve transplantation using a hemodynamically unloaded heart transplant model. Furthermore, because the hemodynamics of blood flow through a heart valve may influence morphology and subsequent function, we describe a modified loaded heterotopic heart transplant model that led to an increase in blood flow through the pulmonary valve. We report host cell infiltration and endothelialization of implanted decellularized pulmonary valves (dPV) and provide an experimental approach for the study of TEHVs using mouse models.

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Off-the-shelf human decellularized tissue-engineered heart valves in a non-human primate model

Cited by 172 publications

References 35 publications

Functional Heart Valve Scaffolds Obtained by Complete Decellularization of Porcine Aortic Roots in a Novel Differential Pressure Gradient Perfusion System

Functional Heart Valve Scaffolds Obtained by Complete Decellularization of Porcine Aortic Roots in a Novel Differential Pressure Gradient Perfusion System

Pulmonary heart valve replacement using stabilized acellular xenogeneic scaffolds; effects of seeding with autologous stem cells

Hemodynamic Characterization of a Mouse Model for Investigating the Cellular and Molecular Mechanisms of Neotissue Formation in Tissue-Engineered Heart Valves

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