The Potential of Prolonged Tissue Culture to Reduce Stress Generation and Retraction in Engineered Heart Valve Tissues

Vlimmeren, Maa Marijke van; Driessen-Mol, Anita Anita; Oomens, Cwj Cees; Baaijens, Fpt Frank

doi:10.1089/ten.tec.2012.0100

Cited by 8 publications

(6 citation statements)

References 38 publications

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“…The initial thinning can be ascribed to the Poisson effect, as the samples are plastically deformed in the in-plane directions. The slight thickening of the samples could be a direct consequence of subsequent tissue formation on top of the scaffold (figure 6), which was also observed by van Vlimmeren et al [51] in statically cultured samples containing the same cells, after four weeks of culture.…”

Section: Geometrical Equilibrium Is Dependent On Initial Scaffold Thicknesssupporting

confidence: 73%

Initial scaffold thickness affects the emergence of a geometrical and mechanical equilibrium in engineered cardiovascular tissues

Kelle

Oomen

Broek

et al. 2018

J. R. Soc. Interface.

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In situ cardiovascular tissue-engineering can potentially address the shortcomings of the current replacement therapies, in particular, their inability to grow and remodel. In native tissues, it is widely accepted that physiological growth and remodelling occur to maintain a homeostatic mechanical state to conserve its function, regardless of changes in the mechanical environment. A similar homeostatic state should be reached for tissue-engineered (TE) prostheses to ensure proper functioning. For in situ tissue-engineering approaches obtaining such a state greatly relies on the initial scaffold design parameters. In this study, it is investigated if the simple scaffold design parameter initial thickness, influences the emergence of a mechanical and geometrical equilibrium state in in vitro TE constructs, which resemble thin cardiovascular tissues such as heart valves and arteries. Towards this end, two sample groups with different initial thicknesses of myofibroblast-seeded polycaprolactone-bisurea constructs were cultured for three weeks under dynamic loading conditions, while tracking geometrical and mechanical changes temporally using non-destructive ultrasound imaging. A mechanical equilibrium was reached in both groups, although at different magnitudes of the investigated mechanical quantities. Interestingly, a geometrically stable state was only established in the thicker constructs, while the thinner constructs’ length continuously increased. This demonstrates that reaching geometrical and mechanical stability in TE constructs is highly dependent on functional scaffold design.

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Section: Geometrical Equilibrium Is Dependent On Initial Scaffold Thicknesssupporting

confidence: 73%

Initial scaffold thickness affects the emergence of a geometrical and mechanical equilibrium in engineered cardiovascular tissues

Kelle

Oomen

Broek

et al. 2018

J. R. Soc. Interface.

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“…Cellular stress development has also been examined in endogenously produced extracellular matrices. 44 , 46 – 48 Even though 3D studies are more relevant for tissue engineering, extracting (individual) cell stress is challenging due to the complexity of the environment in which the cells reside. 2D studies with cells cultured on substrates may therefore be more suitable for providing the fundamental insights into stress fiber remodeling and cellular stress development.…”

Section: Introductionmentioning

confidence: 99%

Intrinsic Cell Stress is Independent of Organization in Engineered Cell Sheets

Loosdregt

Dekker

Alford

et al. 2016

Cardiovasc Eng Tech

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Understanding cell contractility is of fundamental importance for cardiovascular tissue engineering, due to its major impact on the tissue’s mechanical properties as well as the development of permanent dimensional changes, e.g., by contraction or dilatation of the tissue. Previous attempts to quantify contractile cellular stresses mostly used strongly aligned monolayers of cells, which might not represent the actual organization in engineered cardiovascular tissues such as heart valves. In the present study, therefore, we investigated whether differences in organization affect the magnitude of intrinsic stress generated by individual myofibroblasts, a frequently used cell source for in vitro engineered heart valves. Four different monolayer organizations were created via micro-contact printing of fibronectin lines on thin PDMS films, ranging from strongly anisotropic to isotropic. Thin film curvature, cell density, and actin stress fiber distribution were quantified, and subsequently, intrinsic stress and contractility of the monolayers were determined by incorporating these data into sample-specific finite element models. Our data indicate that the intrinsic stress exerted by the monolayers in each group correlates with cell density. Additionally, after normalizing for cell density and accounting for differences in alignment, no consistent differences in intrinsic contractility were found between the different monolayer organizations, suggesting that the intrinsic stress exerted by individual myofibroblasts is independent of the organization. Consequently, this study emphasizes the importance of choosing proper architectural properties for scaffolds in cardiovascular tissue engineering, as these directly affect the stresses in the tissue, which play a crucial role in both the functionality and remodeling of (engineered) cardiovascular tissues.

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“…Since then, PGA, PGA/PLA hybrids, and their copolymer PLGA have been used in a variety of studies regarding the fabrication of functional, bioresorbable leaflet scaffolds . More recent studies have utilized these scaffolds to observe cellular behavior and mechanical properties . One group studied bone marrow stem cells seeded on PGA:PLLA scaffolds under different stress conditions, such as steady flow, cyclic flexure, and a combination of the two conditions, and found that the cells exhibited endothelial and myofibroblast phenotypes similar to valves under a combination of steady flow and cyclic flexure .…”

Section: Application Of Biomaterials To Heart Valve Tissue Engineeringmentioning

confidence: 99%

“…One group studied bone marrow stem cells seeded on PGA:PLLA scaffolds under different stress conditions, such as steady flow, cyclic flexure, and a combination of the two conditions, and found that the cells exhibited endothelial and myofibroblast phenotypes similar to valves under a combination of steady flow and cyclic flexure . Another group found that prolonged tissue culture reduced retraction of the tissue engineered leaflets that typically lose mechanical integrity due to rapid degradation of the PGA scaffold, and suggested that this resulted from an increased amount of GAGs in the tissue …”

Section: Application Of Biomaterials To Heart Valve Tissue Engineeringmentioning

confidence: 99%

Developing a Clinically Relevant Tissue Engineered Heart Valve—A Review of Current Approaches

Nachlas

Davis

2017

Adv Healthcare Materials

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Tissue engineered heart valves (TEHVs) have the potential to address the shortcomings of current implants through the combination of cells and bioactive biomaterials that promote growth and proper mechanical function in physiological conditions. The ideal TEHV should be anti-thrombogenic, biocompatible, durable, and resistant to calcification, and should exhibit a physiological hemodynamic profile. In addition, TEHVs may possess the capability to integrate and grow with somatic growth, eliminating the need for multiple surgeries children must undergo. Thus, this review assesses clinically available heart valve prostheses, outlines the design criteria for developing a heart valve, and evaluates three types of biomaterials (decellularized, natural, and synthetic) for tissue engineering heart valves. While significant progress has been made in biomaterials and fabrication techniques, a viable tissue engineered heart valve has yet to be translated into a clinical product. Thus, current strategies and future perspectives are also discussed to facilitate the development of new approaches and considerations for heart valve tissue engineering.

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The Potential of Prolonged Tissue Culture to Reduce Stress Generation and Retraction in Engineered Heart Valve Tissues

Cited by 8 publications

References 38 publications

Initial scaffold thickness affects the emergence of a geometrical and mechanical equilibrium in engineered cardiovascular tissues

Initial scaffold thickness affects the emergence of a geometrical and mechanical equilibrium in engineered cardiovascular tissues

Intrinsic Cell Stress is Independent of Organization in Engineered Cell Sheets

Developing a Clinically Relevant Tissue Engineered Heart Valve—A Review of Current Approaches

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