Tissue Engineering of Pulmonary Heart Valves on Allogenic Acellular Matrix Conduits

Circulation ◽  
2000 ◽  
Vol 102 (suppl_3) ◽  
Author(s):  
Gustav Steinhoff ◽  
Ulrich Stock ◽  
Najibulla Karim ◽  
Heike Mertsching ◽  
Adine Timke ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Endothelial Cells ◽  
Heart Valve ◽  
Heart Valves ◽  
Sheep Model ◽  
Control Valves ◽  
Acellular Matrix ◽  
Valve Tissue

Background —Tissue engineering using in vitro–cultivated autologous vascular wall cells is a new approach to biological heart valve replacement. In the present study, we analyzed a new concept to process allogenic acellular matrix scaffolds of pulmonary heart valves after in vitro seeding with the use of autologous cells in a sheep model. Methods and Results —Allogenic heart valve conduits were acellularized by a 48-hour trypsin/EDTA incubation to extract endothelial cells and myofibroblasts. The acellularization procedure resulted in an almost complete removal of cells. After that procedure, a static reseeding of the upper surface of the valve was performed sequentially with autologous myofibroblasts for 6 days and endothelial cells for 2 days, resulting in a patchy cellular restitution on the valve surface. The in vivo function was tested in a sheep model of orthotopic pulmonary valve conduit transplantation. Three of 4 unseeded control valves and 5 of 6 tissue-engineered valves showed normal function up to 3 months. Unseeded allogenic acellular control valves showed partial degeneration (2 of 4 valves) and no interstitial valve tissue reconstitution. Tissue-engineered valves showed complete histological restitution of valve tissue and confluent endothelial surface coverage in all cases. Immunohistological analysis revealed cellular reconstitution of endothelial cells (von Willebrand factor), myofibroblasts (α-actin), and matrix synthesis (procollagen I). There were histological signs of inflammatory reactions to subvalvar muscle leading to calcifications, but these were not found in valve and pulmonary artery tissue. Conclusions —The in vitro tissue-engineering approach using acellular matrix conduits leads to the in vivo reconstitution of viable heart valve tissue.

Tissue Engineering of Pulmonary Heart Valves on Allogenic Acellular Matrix Conduits : In Vivo Restoration of Valve Tissue

Circulation ◽  
2000 ◽  
Vol 102 (Supplement 3) ◽  
pp. III-50-III-55 ◽  
Author(s):  
G. Steinhoff ◽  
U. Stock ◽  
N. Karim ◽  
H. Mertsching ◽  
A. Timke ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Heart Valves ◽  
Acellular Matrix ◽  
Valve Tissue

scholarly journals Tissue Engineering Heart Valves – a Review of More than Two Decades into Preclinical and Clinical Testing for Obtaining the Next Generation of Heart Valve Substitutes

2021 ◽  
Vol 31 (3) ◽  
pp. 501-510
Author(s):  
Dan SIMIONESCU ◽  
◽  
Marius Mihai HARPA ◽  
Codrut OPRITA ◽  
Ionela MOVILEANU ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Heart Valve ◽  
Heart Valves ◽  
Research Work ◽  
Heart Valve Disease ◽  
Next Generation ◽  
Clinical Scenarios ◽  
Mechanical Prostheses

Well documented shortcomings of current heart valve substitutes – biological and mechanical prostheses make them imperfect choices for patients diagnosed with heart valve disease, in need for a cardiac valve replacement. Regenerative Medicine and Tissue Engineering represent the research grounds of the next generation of valvular prostheses – Tissue Engineering Heart Valves (TEHV). Mimicking the structure and function of the native valves, TEHVs are three dimensional structures obtained in laboratories encompassing scaffolds (natural and synthetic), cells (stem cells and differentiated cells) and bioreactors. The literature stipulates two major heart valve regeneration paradigms, differing in the manner of autologous cells repopulation of the scaffolds; in vitro, or in vivo, respectively. During the past two decades, multidisciplinary both in vitro and in vitro research work was performed and published. In vivo experience comprises preclinical tests in experimental animal model and cautious limited clinical translation in patients. Despite initial encouraging results, translation of their usage in large clinical scenarios represents the most important challenge that needs to be overcome. This review purpose is to outline the most remarkable preclinical and clinical results of TEHV evaluation along with the lessons learnt from all this experience.

scholarly journals In vivo cellularization of a cross-linked matrix by intraperitoneal implantation: a new tool in heart valve tissue engineering

2007 ◽  
Vol 28 (11) ◽  
pp. 1389-1396 ◽  
Author(s):  
G. De Visscher ◽  
I. Vranken ◽  
A. Lebacq ◽  
C. Van Kerrebroeck ◽  
J. Ganame ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Heart Valve ◽  
Valve Tissue ◽  
Heart Valve Tissue ◽  
Heart Valve Tissue Engineering

scholarly journals A Three-Dimensional Collagen-Elastin Scaffold for Heart Valve Tissue Engineering

2018 ◽  
Vol 5 (3) ◽  
pp. 69 ◽  
Author(s):  
Xinmei Wang ◽  
Mir Ali ◽  
Carla Lacerda
Keyword(s):  
Tissue Engineering ◽  
Endothelial Cells ◽  
Heart Valves ◽  
Current Knowledge ◽  
Three Dimensional ◽  
Stimuli Responsive ◽  
Integrin Β1 ◽  
Mesenchymal Transition ◽  
3D Collagen

Since most of the body’s extracellular matrix (ECM) is composed of collagen and elastin, we believe the choice of these materials is key for the future and promise of tissue engineering. Once it is known how elastin content of ECM guides cellular behavior (in 2D or 3D), one will be able to harness the power of collagen-elastin microenvironments to design and engineer stimuli-responsive tissues. Moreover, the implementation of such matrices to promote endothelial-mesenchymal transition of primary endothelial cells constitutes a powerful tool to engineer 3D tissues. Here, we design a 3D collagen-elastin scaffold to mimic the native ECM of heart valves, by providing the strength of collagen layers, as well as elasticity. Valve interstitial cells (VICs) were encapsulated in the collagen-elastin hydrogels and valve endothelial cells (VECs) cultured onto the surface to create an in vitro 3D VEC-VIC co-culture. Over a seven-day period, VICs had stable expression levels of integrin β1 and F-actin and continuously proliferated, while cell morphology changed to more elongated. VECs maintained endothelial phenotype up to day five, as indicated by low expression of F-actin and integrin β1, while transformed VECs accounted for less than 7% of the total VECs in culture. On day seven, over 20% VECs were transformed to mesenchymal phenotype, indicated by increased actin filaments and higher expression of integrin β1. These findings demonstrate that our 3D collagen-elastin scaffolds provided a novel tool to study cell-cell or cell-matrix interactions in vitro, promoting advances in the current knowledge of valvular endothelial cell mesenchymal transition.

scholarly journals Preclinical Testing of Living Tissue-Engineered Heart Valves for Pediatric Patients, Challenges and Opportunities

2021 ◽  
Vol 8 ◽  
Author(s):  
Ionela Movileanu ◽  
Marius Harpa ◽  
Hussam Al Hussein ◽  
Lucian Harceaga ◽  
Alexandru Chertes ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Cell Fate ◽  
Heart Valve ◽  
Pediatric Patients ◽  
Living Tissue ◽  
Congenital Diseases ◽  
Challenges And Opportunities

Introduction: Pediatric patients with cardiac congenital diseases require heart valve implants that can grow with their natural somatic increase in size. Current artificial valves perform poorly in children and cannot grow; thus, living-tissue-engineered valves capable of sustaining matrix homeostasis could overcome the current drawbacks of artificial prostheses and minimize the need for repeat surgeries.Materials and Methods: To prepare living-tissue-engineered valves, we produced completely acellular ovine pulmonary valves by perfusion. We then collected autologous adipose tissue, isolated stem cells, and differentiated them into fibroblasts and separately into endothelial cells. We seeded the fibroblasts in the cusp interstitium and onto the root adventitia and the endothelial cells inside the lumen, conditioned the living valves in dedicated pulmonary heart valve bioreactors, and pursued orthotopic implantation of autologous cell-seeded valves with 6 months follow-up. Unseeded valves served as controls.Results: Perfusion decellularization yielded acellular pulmonary valves that were stable, no degradable in vivo, cell friendly and biocompatible, had excellent hemodynamics, were not immunogenic or inflammatory, non thrombogenic, did not calcify in juvenile sheep, and served as substrates for cell repopulation. Autologous adipose-derived stem cells were easy to isolate and differentiate into fibroblasts and endothelial-like cells. Cell-seeded valves exhibited preserved viability after progressive bioreactor conditioning and functioned well in vivo for 6 months. At explantation, the implants and anastomoses were intact, and the valve root was well integrated into host tissues; valve leaflets were unchanged in size, non fibrotic, supple, and functional. Numerous cells positive for a-smooth muscle cell actin were found mostly in the sinus, base, and the fibrosa of the leaflets, and most surfaces were covered by endothelial cells, indicating a strong potential for repopulation of the scaffold.Conclusions: Tissue-engineered living valves can be generated in vitro using the approach described here. The technology is not trivial and can provide numerous challenges and opportunities, which are discussed in detail in this paper. Overall, we concluded that cell seeding did not negatively affect tissue-engineered heart valve (TEHV) performance as they exhibited as good hemodynamic performance as acellular valves in this model. Further understanding of cell fate after implantation and the timeline of repopulation of acellular scaffolds will help us evaluate the translational potential of this technology.

Tissue engineering of heart valves: Monocyte chemotactic activity in decellularized heart valve tissue

2004 ◽  
Vol 52 (S 1) ◽  
Author(s):  
E Rieder ◽  
MT Kasimir ◽  
G Seebacher ◽  
E Wolner ◽  
P Simon ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Heart Valve ◽  
Heart Valves ◽  
Chemotactic Activity ◽  
Valve Tissue ◽  
Heart Valve Tissue

scholarly journals Polyisobutylene-Based Thermoplastic Elastomers for Manufacturing Polymeric Heart Valve Leaflets: In Vitro and In Vivo Results

2019 ◽  
Vol 9 (22) ◽  
pp. 4773 ◽  
Author(s):  
Evgeny Ovcharenko ◽  
Maria Rezvova ◽  
Pavel Nikishau ◽  
Sergei Kostjuk ◽  
Tatiana Glushkova ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Heart Valve ◽  
Heart Valves ◽  
Reference Sample ◽  
Sample Surface ◽  
Thermoplastic Elastomers ◽  
Water Contact ◽  
Promising Alternative

Superior polymers represent a promising alternative to mechanical and biological materials commonly used for manufacturing artificial heart valves. The study is aimed at assessing poly(styrene-block-isobutylene-block-styrene) (SIBS) properties and comparing them with polytetrafluoroethylene (Gore-texTM, a reference sample). Surface topography of both materials was evaluated with scanning electron microscopy and atomic force microscopy. The mechanical properties were measured under uniaxial tension. The water contact angle was estimated to evaluate hydrophilicity/hydrophobicity of the study samples. Materials’ hemocompatibility was evaluated using cell lines (Ea.hy 926), donor blood, and in vivo. SIBS possess a regular surface relief. It is hydrophobic and has lower strength as compared to Gore-texTM (3.51 MPa vs. 13.2/23.8 MPa). SIBS and Gore-texTM have similar hemocompatibility (hemolysis, adhesion, and platelet aggregation). The subcutaneous rat implantation reports that SIBS has a lower tendency towards calcification (0.39 mg/g) compared with Gore-texTM (1.29 mg/g). SIBS is a highly hemocompatible material with a promising potential for manufacturing heart valve leaflets, but its mechanical properties require further improvements. The possible options include the reinforcement with nanofillers and introductions of new chains in its structure.

CURRENT DEVELOPMENTS AND FUTURE CHALLENGES FOR THE CREATION OF AORTIC HEART VALVE

2008 ◽  
Vol 08 (01) ◽  
pp. 1-15 ◽  
Author(s):  
YOS S. MORSI ◽  
CYNTHIA S. WONG
Keyword(s):  
Heart Valve ◽  
Heart Valves ◽  
Mechanical Characteristics ◽  
Polyglycolic Acid ◽  
Cellular Interactions ◽  
Trimethylene Carbonate ◽  
The Creation ◽  
Tissue Engineered Heart Valves

The concept of tissue-engineered heart valves offers an alternative to current heart valve replacements that is capable of addressing shortcomings such as life-long administration of anticoagulants, inadequate durability, and inability to grow. Since tissue engineering is a multifaceted area, studies conducted have focused on different aspects such as hemodynamics, cellular interactions and mechanisms, scaffold designs, and mechanical characteristics in the form of both in vitro and in vivo investigations. This review concentrates on the advancements of scaffold materials and manufacturing processes, and on cell–scaffold interactions. Aside from the commonly used materials, polyglycolic acid and polylactic acid, novel polymers such as hydrogels and trimethylene carbonate-based polymers are being developed to simulate the natural mechanical characteristics of heart valves. Electrospinning has been examined as a new manufacturing technique that has the potential to facilitate tissue formation via increased surface area. The type of cells utilized for seeding onto the scaffolds is another factor to take into consideration; currently, stem cells are of great interest because of their potential to differentiate into various types of cells. Although extensive studies have been conducted, the creation of a fully functional heart valve that is clinically applicable still requires further investigation due to the complexity and intricacies of the heart valve.

In Vitro Hydrodynamic Evaluation of a Scaffold for Heart Valve Tissue Engineering

2018 ◽  
Vol 43 (2) ◽  
pp. 195-198 ◽  
Author(s):  
Ovandir Bazan ◽  
Márcia M. O. Simbara ◽  
Jayme P. Ortiz ◽  
Sonia M. Malmonge ◽  
Aron Andrade ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Heart Valve ◽  
Valve Tissue ◽  
Heart Valve Tissue ◽  
Heart Valve Tissue Engineering ◽  
Hydrodynamic Evaluation

scholarly journals Recellularization of decellularized heart valves: Progress toward the tissue-engineered heart valve

2017 ◽  
Vol 8 ◽  
pp. 204173141772632 ◽  
Author(s):  
Mitchell C VeDepo ◽  
Michael S Detamore ◽  
Richard A Hopkins ◽  
Gabriel L Converse
Keyword(s):  
Heart Valve ◽  
Heart Valves ◽  
Mechanical Conditioning ◽  
New Era ◽  
Processing Strategies ◽  
Tissue Engineered Heart Valve ◽  
Tissue Engineered Heart Valves

The tissue-engineered heart valve portends a new era in the field of valve replacement. Decellularized heart valves are of great interest as a scaffold for the tissue-engineered heart valve due to their naturally bioactive composition, clinical relevance as a stand-alone implant, and partial recellularization in vivo. However, a significant challenge remains in realizing the tissue-engineered heart valve: assuring consistent recellularization of the entire valve leaflets by phenotypically appropriate cells. Many creative strategies have pursued complete biological valve recellularization; however, identifying the optimal recellularization method, including in situ or in vitro recellularization and chemical and/or mechanical conditioning, has proven difficult. Furthermore, while many studies have focused on individual parameters for increasing valve interstitial recellularization, a general understanding of the interacting dynamics is likely necessary to achieve success. Therefore, the purpose of this review is to explore and compare the various processing strategies used for the decellularization and subsequent recellularization of tissue-engineered heart valves.

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