Functional Tissue-Engineered Valves from Cell-Remodeled Fibrin with Commissural Alignment of Cell-Produced Collagen

Robinson, Patrick G; Johnson, Sandra; Evans, Michael; Barocas, Victor H.; Tranquillo, Robert T.

doi:10.1089/ten.2007.0148

Cited by 25 publications

(34 citation statements)

References 43 publications

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“…The final concentrations of the suspension were 6.6mg/ml fibrinogen, 1.1 U/ml thrombin, 5.0 mM Ca ++ , and 500,000 cells/ml. Suspensions were well mixed by pipette action and injected into bi-leaflet VE molds as described previously [18]. …”

Section: Methodsmentioning

confidence: 99%

“…The collagen content was quantified with the hydroxyproline assay assuming 7.46 µg of collagen per 1 µg of hydroxyproline [18]. The sample volume was calculated using the measured length, width, and thickness of the strips (as described above in uniaxial testing).…”

Section: Methodsmentioning

confidence: 99%

“…Our laboratory’s approach to TEHV fabrication is based on the entrapment of dermal fibroblasts into fibrin gel within a mold, which, following static incubation in the mold, yields the gross geometry and alignment patterns of the native aortic valve [18]. The dermal fibroblast is used because it is a readily available source and generates extensive remodeling of fibrin into a collagenous tissue with tensile mechanical properties approaching those of native tissue [18].…”

Section: Introductionmentioning

confidence: 99%

“…The dermal fibroblast is used because it is a readily available source and generates extensive remodeling of fibrin into a collagenous tissue with tensile mechanical properties approaching those of native tissue [18]. Dermal fibroblasts have also been successfully used for a vascular graft in clinical studies [19].…”

Section: Introductionmentioning

confidence: 99%

“…By using molds with two or three channels cut into the central mandrel, bi- and tri-leaflet VEs have been fabricated. The current study is focused on bi-leaflet VEs for comparison to previous results [18]. …”

Section: Introductionmentioning

confidence: 99%

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Controlled cyclic stretch bioreactor for tissue-engineered heart valves

Syedain

Tranquillo

2009

Biomaterials

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A tissue-engineered heart valve (TEHV) represents the ultimate valve replacement, especially for juvenile patients given its growth potential. To date, most TEHV bioreactors have been developed based on pulsed flow of culture medium through the valve lumen to induce strain in the leaflets. Using a strategy for controlled cyclic stretching of tubular constructs reported previously, we developed a controlled cyclic stretch bioreactor for TEHVs that leads to improved tensile and compositional properties. The TEHV is mounted inside a latex tube, which is then cyclically pressurized with culture medium. The root and leaflets stretch commensurately with the latex, the stretching being dictated by the stiffer latex and thus controllable. Medium is also perfused through the lumen at a slow rate in a flow loop to provide nutrient delivery. Fibrin-based TEHVs prepared with human dermal fibroblasts were subjected to three weeks of cyclic stretching with incrementally increasing strain amplitude. The TEHV possessed the tensile stiffness and stiffness anisotropy of leaflets from sheep pulmonary valves and could withstand cyclic pulmonary pressures with similar distension as for a sheep pulmonary artery.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Controlled cyclic stretch bioreactor for tissue-engineered heart valves

Syedain

Tranquillo

2009

Biomaterials

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Scale‐dependent fiber kinematics of elastomeric electrospun scaffolds for soft tissue engineering

Stella

Wagner

Sacks

2009

J Biomedical Materials Res

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Electrospun poly(ester urethane)urea (PEUU) scaffolds contain complex multiscale hierarchical structures that work simultaneously to produce unique macrolevel mechanical behaviors. In this study, we focused on quantifying key multiscale scaffold structural features to elucidate the mechanisms by which these scaffolds function to emulate native tissue tensile behavior. Fiber alignment was modulated via increasing rotational velocity of the collecting mandrel, and the resultant specimens were imaged using SEM under controlled biaxial strain. From the SEM images, fiber splay, tortuosity, and diameter were quantified in the unstrained and deformed configurations. Results indicated that not only fiber alignment increased with mandrel velocity but also, paradoxically, tortuosity increased concurrently with mandrel velocity and was highly correlated with fiber orientation. At microlevel scales (1–10 μm), local scaffold deformation behavior was observed to be highly heterogeneous, while increasing the scale resulted in an increasingly homogenous strain field. From our comprehensive measurements, we determined that the transition scale from heterogenous to homogeneous-like behavior to be ~1 mm. Moreover, while electrospun PEUU scaffolds exhibit complex deformations at the microscale, the larger scale structural features of the fibrous network allow them to behave as long-fiber composites that deform in an affine-like manner. This study underscores the importance of understanding the structure–function relationships in elastomeric fibrous scaffolds, and in particular allowed us to link microscale deformations with mechanisms that allow them to successfully simulate soft tissue mechanical behavior.

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The future of heart valve replacement: recent developments and translational challenges for heart valve tissue engineering

Fioretta

Dijkman

Emmert

et al. 2017

J Tissue Eng Regen Med

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Heart valve replacement is often the only solution for patients suffering from valvular heart disease. However, currently available valve replacements require either life-long anticoagulation or are associated with valve degeneration and calcification. Moreover, they are suboptimal for young patients, because they do not adapt to the somatic growth. Tissue-engineering has been proposed as a promising approach to fulfil the urgent need for heart valve replacements with regenerative and growth capacity. This review will start with an overview on the currently available valve substitutes and the techniques for heart valve replacement. The main focus will be on the evolution of and different approaches for heart valve tissue engineering, namely the in vitro, in vivo and in situ approaches. More specifically, several heart valve tissue-engineering studies will be discussed with regard to their shortcomings or successes and their possible suitability for novel minimally invasive implantation techniques. As in situ heart valve tissue engineering based on cell-free functionalized starter materials is considered to be a promising approach for clinical translation, this review will also analyse the techniques used to tune the inflammatory response and cell recruitment upon implantation in order to stir a favourable outcome: controlling the blood-material interface, regulating the cytokine release, and influencing cell adhesion and differentiation. In the last section, the authors provide their opinion about the future developments and the challenges towards clinical translation and adaptation of heart valve tissue engineering for valve replacement.

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Functional Tissue-Engineered Valves from Cell-Remodeled Fibrin with Commissural Alignment of Cell-Produced Collagen

Cited by 25 publications

References 43 publications

Controlled cyclic stretch bioreactor for tissue-engineered heart valves

Controlled cyclic stretch bioreactor for tissue-engineered heart valves

Scale‐dependent fiber kinematics of elastomeric electrospun scaffolds for soft tissue engineering

The future of heart valve replacement: recent developments and translational challenges for heart valve tissue engineering

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