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Intermittent straining accelerates the development of tissue properties in engineered heart valve tissue

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Author: Rubbens, M.P. · Mol, A. · Boerboom, R.A. · Bank, R.A. · Baaijens, F.P.T. · Bouten, C.V.C.
Institution: TNO Industrie en Techniek TNO Kwaliteit van Leven
Source:Tissue Engineering - Part A, 5, 15, 999-1008
Identifier: 241515
doi: doi:10.1089/ten.tea.2007.0396
Keywords: Biology · Biomedical Research · Collagen matrices · Constrained controls · Cross-link densities · Faster rates · Heart valves · Human heart · In-vitro · In-vivo · Innovative method · Limiting factors · Mechanical conditioning · Model system · Organized structure · Temporal variation · Tissue architecture · Tissue properties · Tissue-engineered heart · Biomechanics · Cell culture · Collagen · Density (specific gravity) · Mechanical properties · Network architecture · Tissue · Tissue engineering · Valves (mechanical) · collagen · article · collagen synthesis · controlled study · cross linking · heart valve · human · human cell · human tissue · morphology · priority journal · quantitative analysis · tissue culture · tissue engineering · Biomechanics · Bioprosthesis · Cells, Cultured · Collagen · Cross-Linking Reagents · Fibroblasts · Heart Valve Prosthesis · Humans · Models, Cardiovascular · Myocytes, Smooth Muscle · Time Factors · Tissue Engineering · Tissue Scaffolds


Tissue-engineered heart valves lack sufficient amounts of functionally organized structures and consequently do not meet in vivo mechanical demands. To optimize tissue architecture and hence improve mechanical properties, various in vitro mechanical conditioning protocols have been proposed, of which intermittent straining is most promising in terms of tissue properties. We hypothesize that this is due to an improved collagen matrix synthesis, maturation, and organization, triggered by periodic straining of cells. To test this hypothesis, we studied the effect of intermittent versus constrained conditioning with time (2-4 weeks), using a novel model system of human heart valve tissue. Temporal variations in collagen production, cross-link density, and mechanical properties were quantified in engineered heart valve tissue, cyclically strained for 3-h periods, alternated with 3-h periods rest. In addition, an innovative method for vital collagen imaging was used to monitor collagen organization. Intermittent straining resulted in increased collagen production, cross-link densities, collagen organization, and mechanical properties at faster rates, as compared to constrained controls, leading to stronger tissues in shorter culture periods. This is of utmost importance for heart valve tissue engineering, where insufficient mechanical properties are currently the main limiting factor. © 2009, Mary Ann Liebert, Inc.