A Novel Bioreactor for Tissue Engineered Heart Valves Based on Controlled Cyclic Stretching

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

The tissue-engineered heart valve (TEHV) is considered a promising alternative for valve replacement, especially in pediatric patients. To date, most TEHVs have been cultured in pulse-flow bioreactors to generate mechanical loads and deformations leading to tissue growth (1, 2). Our approach has been to apply controlled mechanical stretching to induce tissue growth (3). In this study, a novel controlled cyclic stretch bioreactor is presented to enhance functional properties of TEHVs.

Author(s):  
Zeeshan Syedain ◽  
Lee Meier ◽  
Jay Reimer ◽  
Robert Tranquillo

Tissue-engineered heart valves (TEHV) have the potential to revolutionize valve replacements therapies, especially for pediatric patients. While much progress has been made toward implanting a TEHV, a major limitation to date has been in vivo leaflet retraction due to the contractile nature of the cells transplanted within the TEHV. This phenomenon has been problematic in numerous studies, particularly for approaches employing the use of a fibrin scaffold (Syedain et al. 2011, Flanagan et al. 2009). Additional challenges in the development of a TEHV include designing a 3D mold that allows for proper coaptation and functionality of engineered leaflets. Herein, we present a novel approach for developing a TEHV from a decellularized engineered tube fabricated from fibrin that is remodeled by entrapped dermal fibroblasts, and matured using a custom pulse flow-stretch bioreactor. This approach has the potential to deliver an off-the-shelf engineered heart valve that exhibits the ability to be readily recellularized in contrast to current clinically employed tissue-based valve replacements.


2000 ◽  
Author(s):  
Michael S. Sacks ◽  
Sanjay Kaushal ◽  
John E. Mayer

Abstract The need for improved heart valve prostheses is especially critical in pediatric applications, where growth and remodeling are essential. Tissue engineered heart valves (TEHV) have functioned in the pulmonary circulation of growing lambs for up to four months [1], and thus can potentially overcome limitations of current bioprosthetic heart valves. Despite these promising results, significant questions remain. In particular, the role of scaffold mechanical properties in optimal extra-cellular matrix development, as well as TEHV durability, are largely unexplored. We have previously demonstrated flexure testing as a sensitive and critical test for BHV tissue mechanical property evaluation [2]. The following study was conducted to determine the feasibility of using this technique to provide fundamental information required for optimizing TEHV scaffold designs.


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.


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).


Biomaterials ◽  
2009 ◽  
Vol 30 (25) ◽  
pp. 4078-4084 ◽  
Author(s):  
Zeeshan H. Syedain ◽  
Robert T. Tranquillo

2010 ◽  
Vol 58 (S 01) ◽  
Author(s):  
PM Dohmen ◽  
A Lembcke ◽  
S Holinski ◽  
JP Braun ◽  
W Konertz

2008 ◽  
Vol 56 (S 1) ◽  
Author(s):  
S Cebotari ◽  
I Tudorache ◽  
A Lichtenberg ◽  
E Cheptanaru ◽  
S Barnaciuc ◽  
...  

Author(s):  
Valery L Visser ◽  
Polina Zaytseva ◽  
Sarah E Motta ◽  
Sandra Loerakker ◽  
Simon P Hoerstrup ◽  
...  

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