In vivo repopulation of tissue engineered heart valves

2010 ◽  
Vol 58 (S 01) ◽  
Author(s):  
PM Dohmen ◽  
A Lembcke ◽  
S Holinski ◽  
JP Braun ◽  
W Konertz
Author(s):  
João S. Soares ◽  
Trung B. Le ◽  
Fotis Sotiropoulos ◽  
Michael S. Sacks

Living tissue engineered heart valves (TEHV) may circumvent ongoing problems in pediatric valve replacements, offering optimum hemodynamic performance and the potential for growth, remodeling, and self-repair [1]. TEHV have been constructed by seeding vascular-derived autologous cells onto biodegradable scaffolds and exhibited enhanced extracellular matrix (ECM) development when cultured under pulsatile flow conditions in-vitro [2]. After functioning successfully for up to 8 months in the pulmonary circulation of growing lambs, TEHV underwent extensive in vivo remodeling and structural evolution and have demonstrated the feasibility of engineering living heart valves in vitro [3]. The employment of novel cell sources, which are clinically obtainable in principle such as bone marrow-derived mesenchymal stem cells (MSCs), is key to achieve viable clinical application [4].


2009 ◽  
Vol 15 (10) ◽  
pp. 2965-2976 ◽  
Author(s):  
Thomas C. Flanagan ◽  
Jörg S. Sachweh ◽  
Julia Frese ◽  
Heike Schnöring ◽  
Nina Gronloh ◽  
...  

2008 ◽  
Vol 08 (01) ◽  
pp. 1-15 ◽  
Author(s):  
YOS S. MORSI ◽  
CYNTHIA S. WONG

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.


Author(s):  
Zeeshan H. Syedain ◽  
Robert T. Tranquillo

Tissue engineering provides a means to create fully functional tissue-equivalents that can grow, repair and remodel in vivo. Our laboratory’s approach to fabricating artery- and heart valve-equivalents utilizes cell-seeded fibrin gels. However, even after 4–5 weeks of static incubation, the mechanical properties of these constructs are below those of native tissue. Previous studies in our laboratory have shown a significant role of mechanical stretching in improving properties of collagen-based tissue constructs (Isenberg and Tranquillo, 2003). We examined the effects of cyclic distention (CD) of cell-seeded fibrin-based tubular constructs (TC) and valve-equivalents (VE) after five weeks of culture. We used human dermal fibroblasts and porcine valve interstitial cells as the cell sources. Circumferential strain amplitudes from 2.5% to 15% were applied to evaluate the effects of CD on remodeling of the TC. We further hypothesized that during long-term conditioning, cells adapt to CD of constant strain amplitude, diminishing the remodeling into tissue. We tested this hypothesis by applying step-wise incremental CD (ICD) from 5%–15% strain amplitude and compared this group to a set of samples subject to CD of constant strain amplitude in this range. Based on the outcome of the cyclic distension study with tubular constructs, we applied CD to VE in a novel bioreactor.


2017 ◽  
Vol 8 ◽  
pp. 204173141772632 ◽  
Author(s):  
Mitchell C VeDepo ◽  
Michael S Detamore ◽  
Richard A Hopkins ◽  
Gabriel L Converse

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.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Doerthe Schmidt ◽  
Christine Mariani ◽  
Arja Puolakka ◽  
Marja Rissanen ◽  
Jens Kelm ◽  
...  

Background : A clinically relevant heart valve tissue engineering concept requires minimally invasive techniques for both cell harvest and valve implantation. Here, we present first experiences with autologous tissue engineered heart valves fabricated from composite self-expandable biodegradable scaffolds and adult stem cells implanted by minimally invasive procedures in a sheep model. Methods : Sandwich-structured heart valve scaffolds (n= 12) were fabricated from non-woven PLDLA meshes coated with electrospun PLDLA nanofibers and integrated in self-expanding nitinol stents. Scaffolds were seeded with either autologous ovine bone marrow (BMC; n= 4) or jugular vein-derived cells (JVC; n= 8) and cultured in bioreactors. After 9d, heart valves were endothelialized with autologous peripheral blood-derived endothelial progenitor cells and jugular vein-derived endothelial cells, respectively. After additional 3d, heart valves (n= 6) were implanted trans-apically in pulmonary position. Controls were analysed (n= 6) as to tissue formation and composition (histology, biochemical assays). Mechanical properties were determined by tensile tests. In vivo performance was assessed by echocardiography up to 4 weeks. Results : Histology revealed cell attachment and ingrowth into the scaffold material resulting in layered tissues with endothelialized, eNOS positive surfaces. Amounts of GAG and cell number were similar in all heart valves, comparable to native tissues. Collagen production was higher in BMC based heart valves compared to JVC-derived tissues (Hydroyproline amount 34% vs. 20% of native tissues). Mechanical profiles demonstrated physiological tissue strength (max. tensile stress 0.41± 0.21 MPa) but less elasticity (E-Moduli 1.89± 0.79 MPa) independent of the cell source. Echocardiography displayed in vivo functionality (transvalvular mean pressure gradient 10.36± 3.17 mm/Hg) with more flexibility of BMC based heart valves leaflets. Conclusions : These results demonstrate that heart valve tissue engineering based on a minimally invasive technique for both cell harvest and valve implantation is feasible. This clinically relevant approach is currently investigated in long-term animal studies.


Author(s):  
Martijn A. J. Cox ◽  
Jeroen Kortsmit ◽  
Carlijn V. C. Bouten ◽  
Frank P. T. Baaijens

Over the last few years, research interest in tissue engineering as an alternative for current treatment and replacement strategies for cardiovascular and heart valve diseases has significantly increased. For a tissue engineered heart valve to be functional, it should be able to withstand the high pressures and flows that occur in vivo. Nature’s solution for this challenge can be found in the complex collagen fiber architecture of the native aortic valve (Fig. 1).


2015 ◽  
Vol 21 (15-16) ◽  
pp. 2206-2215 ◽  
Author(s):  
Samaneh Ghazanfari ◽  
Anita Driessen-Mol ◽  
Bart Sanders ◽  
Petra E. Dijkman ◽  
Simon P. Hoerstrup ◽  
...  

2018 ◽  
Vol 114 (suppl_1) ◽  
pp. S114-S114
Author(s):  
K Zlabinger ◽  
D Lukovic ◽  
A Gugerell ◽  
J Winkler ◽  
A Spannbauer ◽  
...  

Author(s):  
Chad E. Eckert ◽  
Brandon T. Mikulis ◽  
Dane Gerneke ◽  
Ian LeGrice ◽  
Danielle Gottlieb ◽  
...  

Tissue engineered heart valves (TEHV) have received much attention as a potential pediatric valve replacement therapy, offering a variety of prospective long-term functional improvements over current options. Early in vivo and in vitro efforts have produced TEHV showing increasingly equivalent mechanical and structural properties compared to native valves [1]. Despite these advances, a significant gap in the literature exists regarding detailed 3D structural information of TEHV prior to implantation (in vitro) and after implantation (explants) as well as that of the native valve. The present work was performed to provide high resolution 3D structural data of implanted TEHV, the native pulmonary valve (PV), and pre-implant scaffold to develop an accurate understanding of developing tissue.


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