Controlled Cyclic Stretching of Tissue Engineered Heart Valves: Effects on Mechanical Properties and ECM Organization

2008 ◽  
Author(s):  
Zeeshan H. Syedain ◽  
Robert T. Tranquillo
Keyword(s):  
Mechanical Properties ◽  
Strain Amplitude ◽  
Heart Valves ◽  
Dermal Fibroblasts ◽  
Fibrin Gels ◽  
Cyclic Stretching ◽  
Tissue Constructs ◽  
Cell Sources ◽  
Tissue Engineered Heart Valves

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.

Simulation of the Role of Oscillatory Shear Stress on Mesenchymal Stem Cell Proliferation and Extracellular Matrix Production in Engineered Heart Valve Tissue Formation

2013 ◽  
Author(s):  
João S. Soares ◽  
Trung B. Le ◽  
Fotis Sotiropoulos ◽  
Michael S. Sacks
Keyword(s):  
Extracellular Matrix ◽  
Heart Valves ◽  
Structural Evolution ◽  
Biodegradable Scaffolds ◽  
Cell Sources ◽  
Hemodynamic Performance ◽  
Tissue Engineered Heart Valves ◽  
Oscillatory Shear Stress

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].

Novel Tissue-Engineered Heart Valve

2013 ◽  
Author(s):  
Zeeshan Syedain ◽  
Lee Meier ◽  
Jay Reimer ◽  
Robert Tranquillo
Keyword(s):  
Heart Valve ◽  
Heart Valves ◽  
Pediatric Patients ◽  
Dermal Fibroblasts ◽  
Pulse Flow ◽  
Novel Approach ◽  
Fibrin Scaffold ◽  
Tissue Engineered Heart Valve ◽  
Tissue Engineered Heart Valves

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.

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
Keyword(s):  
Heart Valves ◽  
Tissue Engineered Heart Valves

scholarly journals Characterization of Dermal Fibroblasts as a Cell Source for Pediatric Tissue Engineered Heart Valves

2014 ◽  
Vol 1 (2) ◽  
pp. 146-162 ◽  
Author(s):  
Monica Fahrenholtz ◽  
Huiwen Liu ◽  
Debra Kearney ◽  
Lalita Wadhwa ◽  
Charles Fraser ◽  
...  
Keyword(s):  
Heart Valves ◽  
Dermal Fibroblasts ◽  
Cell Source ◽  
A Cell ◽  
Tissue Engineered Heart Valves

In Vivo Remodeling and Structural Characterization of Fibrin-Based Tissue-Engineered Heart Valves in the Adult Sheep Model

2009 ◽  
Vol 15 (10) ◽  
pp. 2965-2976 ◽  
Author(s):  
Thomas C. Flanagan ◽  
Jörg S. Sachweh ◽  
Julia Frese ◽  
Heike Schnöring ◽  
Nina Gronloh ◽  
...  
Keyword(s):  
Structural Characterization ◽  
Heart Valves ◽  
Sheep Model ◽  
Adult Sheep ◽  
Tissue Engineered Heart Valves

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.

The tropoelastin and lysyl oxidase treatments increased the content of insoluble elastin in bioprosthetic heart valves

2018 ◽  
Vol 33 (5) ◽  
pp. 637-646 ◽  
Author(s):  
Yang Lei ◽  
Yushun Xia ◽  
Yunbing Wang
Keyword(s):  
Mechanical Properties ◽  
Heart Valves ◽  
Lysyl Oxidase ◽  
Heart Diseases ◽  
Epigallocatechin Gallate ◽  
Bioprosthetic Heart Valves ◽  
Valvular Heart Diseases ◽  
Preparation Strategy ◽  
Implantation Model

Valvular heart diseases lead to over 300,000 heart valve replacements worldwide each year. Commercially available bioprosthetic heart valves (BHVs) are mostly made from porcine or bovine pericardiums which were crosslinked by glutaraldehyde (GLUT). However, valve failures can occur within 10 years due to progressive degradation and calcification. GLUT could crosslink collagen but it fails to stabilize elastin. In this current study, we developed a new BHVs preparation strategy named as “GLUT/TE/LOXL/EGCG” that utilizes exogenous tropoelastin (TE)/lysyl oxidase (LOXL) and epigallocatechin gallate (EGCG) to increase the elastin content as well as the stabilization of elastin. The feeding ratios of tropoelastin and lysyl oxidase were optimized. The contents of desmosine and insoluble elastin, biomechanics, cytotoxicity, hemocompatibility, in vivo componential stability and anti-calcification potential were characterized. Pericardiums with increased elastin content had improved the mechanical properties. GLUT/TE/LOXL/EGCG-treated pericardiums had similar cytotoxicity and coagulation properties compared to GLUT and GLUT/EGCG control. We demonstrated that GLUT/TE/LOXL/EGCG-treated pericardiums had high amount of insoluble elastin in 90 days’ rat subdermal implantation model, and better resistance for calcification. This new tropoelastin and lysyl oxidase treatments strategy would be a promising method to make BHVs which have better structural stability and anti-calcification properties.

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.

scholarly journals Yak Pericardium as an Alternative Biomaterial for Transcatheter Heart Valves

2021 ◽  
Vol 9 ◽  
Author(s):  
Mingzhe Song ◽  
Zhenjie Tang ◽  
Yuhong Liu ◽  
Xinlong Xie ◽  
Xiaoke Qi ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Heart Valves ◽  
Amino Acid Content ◽  
Bovine Pericardium ◽  
Elastic Fibers ◽  
Transcatheter Aortic Valve ◽  
Transcatheter Heart Valve ◽  
Valve Implantation ◽  
Porcine Pericardium

Transcatheter aortic valve implantation (TAVI) has received much attention and development in the past decade due to its lower risk of complication and infections compared to a traditional open thoracotomy. However, the current commercial transcatheter heart valve does not fully meet clinical needs; therefore, new biological materials must be found in order to meet these requirements. We have discovered a new type of biological material, the yak pericardium. This current research studied its extracellular matrix structure, composition, mechanical properties, and amino acid content. Folding experiment was carried out to analyze the structure and mechanics after folding. We also conducted a subcutaneous embedding experiment to analyze the inflammatory response and calcification after implantation. Australian bovine pericardium, local bovine pericardium, and porcine pericardium were used as controls. The overall structure of the yak pericardium is flat, the collagen runs regularly, it has superior mechanical properties, and the average thickness is significantly lower than that of the Australian bovine and the local bovine pericardium control groups. The yak pericardium has a higher content of elastic fibers, showing that it has a better compression resistance effect during the folding experiment as well as having less expression of transplantation-related antigens. We conducted in vivo experiments and found that the yak pericardium has less inflammation and a lower degree of calcification. In summary, the yak pericardium, which is thin and strong, has lower immunogenicity and outstanding anti-calcification effects may be an excellent candidate valve leaflet material for TAVI.

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