The Relevance of Large Strains in Functional Tissue Engineering of Heart Valves

Mol, Anita; Bouten, Cvc Carlijn; Zünd, Gregor; Günter, Christina Irene; Visjager, Jeroen F.; Turina, Marko; Baaijens, F.P.T.; Hoerstrup, Simon P.

doi:10.1055/s-2003-38993

Cited by 97 publications

(57 citation statements)

References 18 publications

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“…The application of mechanical stimulation to 3-D cultures (whether these are engineered tissues intended for regenerative medicine or simpler models intended for mechanobiology studies) is intended to mimic physiological conditions since most native tissues bear varying levels of strain, which significantly regulates their matrix composition and microstructure. Indeed, various engineered tissues such as heart valves, vascular tissues, and cartilage are commonly grown under physiologically-mimicking mechanical conditions in an attempt to achieve native tissue-like properties [9][10][11]. Similarly, collagenous matrices that have been grown under mechanical stimulation demonstrate improvements in cell alignment and collagen fibrillar orientation and packing [12].…”

Section: Introductionmentioning

confidence: 99%

Influence of cyclic strain and decorin deficiency on 3D cellularized collagen matrices

et al. 2008

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Cyclic strain evokes the expression of the small leucine-rich proteoglycans decorin and biglycan in 2-D cultures and native tissues. However, strain dependent expression of these proteoglycans has not been demonstrated in engineered tissues. We hypothesized that the absence of decorin may compromise the effect of cyclic strain on the development of engineered tissues. Thus, we investigated the contribution of decorin to tissue organization in cyclically-strained collagen gels relative to statically-cultured controls. Decorin null (Dcn −/− ) and wild-type murine embryonic fibroblasts were seeded within collagen gels and mechanically conditioned using a Flexcell ® Tissue Train ® culture system. After eight days, the cyclically-strained samples demonstrated greater collagen fibril density, proteoglycan content, and material strength for both cell types. On the other hand, increases in cell density, collagen fibril diameter, and biglycan expression were observed only in the cyclically-strained gels seeded with Dcn −/− cells. Although cyclic strain caused an elevation in proteoglycan expression regardless of cell type, the type of proteoglycan differed between groups: the Dcn −/− cell-seeded gels produced an excess of biglycan not found in the wild-type controls. These results suggest that decorin-mediated tissue organization is strongly dependent upon tissue type and mechanical environment.

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Section: Introductionmentioning

confidence: 99%

Influence of cyclic strain and decorin deficiency on 3D cellularized collagen matrices

et al. 2008

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“…Exposure of the tissue engineered leaflets to mechanical stimulation (cyclic strain) resulted in stronger but less pliable tissues compared with only perfused tissues, in agreement with other studies. 24 This observation indicates the positive effect of mechanical stimulation on the mechanical strength and may be related to a higher degree of cross-links among the collagen fibers. The mechanical strength of tissue engineered leaflets did not reach physiological values 4 during the investigated in vitro cultivation time period.…”

Section: Discussionmentioning

confidence: 90%

“…This may be explained by the uncompleted collagen production suggesting further improvement of the mechanical loading protocol in vitro. 24,25 This will be investigated in future studies and the functionality of the engineered tissues in vivo will have to be demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Living Autologous Heart Valves Engineered From Human Prenatally Harvested Progenitors

et al. 2006

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Background-Heart valve tissue engineering is a promising strategy to overcome the lack of autologous growing replacements, particularly for the repair of congenital malformations. Here, we present a novel concept using human prenatal progenitor cells as new and exclusive cell source to generate autologous implants ready for use at birth. Methods and Results-Human fetal mesenchymal progenitors were isolated from routinely sampled prenatal chorionic villus specimens and expanded in vitro. A portion was cryopreserved. After phenotyping and genotyping, cells were seeded onto synthetic biodegradable leaflet scaffolds (nϭ12) and conditioned in a bioreactor. After 21 days, leaflets were endothelialized with umbilical cord blood-derived endothelial progenitor cells and conditioned for additional 7 days. Resulting tissues were analyzed by histology, immunohistochemistry, biochemistry (amounts of extracellular matrix, DNA), mechanical testing, and scanning electron microscopy (SEM) and were compared with native neonatal heart valve leaflets. Fresh and cryopreserved cells showed comparable myofibroblast-like phenotypes. Genotyping confirmed their fetal origin. Neo-tissues exhibited organization, cell phenotypes, extracellular matrix production, and DNA content comparable to their native counterparts. Leaflet surfaces were covered with functional endothelia. SEM showed cellular distribution throughout the polymer and smooth surfaces. Mechanical profiles approximated those of native heart valves. Conclusions-Prenatal

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“…No studies are known in which deformation of tissue engineered heart valves was determined in such a way. The research in literature that has been performed includes studies in which relatively simple tissue engineered constructs, 2D geometries 10,11,24 or blood vessels 22,23 instead of heart valves were subjected to preset deformational changes. Mechanical stimulation in these bioreactor systems shows strong similarity to the way load is applied by uni-or biaxial stretching devices.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, an increase in ultimate tensile strength and tissue stiffness is observed, compared to static control. 21,24,28,29,38,39 In a recently developed bioreactor concept, the Diastolic Pulse Duplicator (DPD), 25 dynamic strains were induced in the heart valve leaflets by applying a dynamic pressure difference over the closed valve. The strain-based conditioning approach was tested by culturing human heart valve leaflets in vitro.…”

Section: Introductionmentioning

confidence: 99%

Real Time, Non-Invasive Assessment of Leaflet Deformation in Heart Valve Tissue Engineering

et al. 2008

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Abstract-In heart valve tissue engineering, most bioreactors try to mimic physiological flow and operate with a preset transvalvular pressure applied to the tissue. The induced deformations are unknown and can vary during culturing as a consequence of changing mechanical properties of the engineered construct. Real-time measurement and control of local tissue strains are desired to systematically study the effects of mechanical loading on tissue development and, consequently, to design an optimal conditioning protocol. In this study, a method is presented to assess local tissue strains in heart valve leaflets during culturing. We hypothesize that local tissue strains can be determined from volumetric deformation. Volumetric deformation is defined as the amount of fluid displaced by the deformed heart valve leaflets in a stented configuration, and is measured, noninvasively, using a flow sensor. A numerical model is employed to relate volumetric deformation to local tissue strains in various regions of the leaflets (e.g. belly and commissures). The flow-based deformation measurement method was validated and its functionality was demonstrated in a tissue engineering experiment. Tri-leaflet, stented heart valves were cultured in vitro and during mechanical conditioning, realistic values for volumetric and local deformation were obtained.

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The Relevance of Large Strains in Functional Tissue Engineering of Heart Valves

Abstract: The results demonstrate the significance of large strains in promoting tissue formation. This study may provide a methodological basis for tissue engineering of heart valves appropriate for systemic pressure applications.

Cited by 97 publications

References 18 publications

Influence of cyclic strain and decorin deficiency on 3D cellularized collagen matrices

Influence of cyclic strain and decorin deficiency on 3D cellularized collagen matrices

Living Autologous Heart Valves Engineered From Human Prenatally Harvested Progenitors

Real Time, Non-Invasive Assessment of Leaflet Deformation in Heart Valve Tissue Engineering

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