Perfusion Bioreactor for Vascular Tissue Engineering with Capacities for Longitudinal Stretch

Mironov, Vladimir; Kasyanov, Vladimir; McAllister, Kelly; Oliver, Sherrell; Sistino, J.J.; Markwald, Roger R.

doi:10.1097/00001665-200305000-00012

Cited by 51 publications

(33 citation statements)

References 19 publications

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“…19,28,34 Pulsatile flow through the vessel lumen represents the blood stream and due to the pulsatile character of the flow, mimicking the cardiac output at every heartbeat, the blood vessel wall is strained. More complex systems, ensuring exact physiological conditions, have been developed for both blood vessels 14,15,30 and heart valves 5,7,23 and can be used for testing purposes as well.…”

Section: Introductionmentioning

confidence: 99%

Tissue Engineering of Human Heart Valve Leaflets: A Novel Bioreactor for a Strain-Based Conditioning Approach

et al. 2005

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Abstract-Current mechanical conditioning approaches for heart valve tissue engineering concentrate on mimicking the opening and closing behavior of the leaflets, either or not in combination with tissue straining. This study describes a novel approach by mimicking only the diastolic phase of the cardiac cycle, resulting in tissue straining. A novel, yet simplified, bioreactor system was developed for this purpose by applying a dynamic pressure difference over a closed tissue engineered valve, thereby inducing dynamic strains within the leaflets. Besides the use of dynamic strains, the developing leaflet tissues were exposed to prestrain induced by the use of a stented geometry. To demonstrate the feasibility of this strain-based conditioning approach, human heart valve leaflets were engineered and their mechanial behavior evaluated. The actual dynamic strain magnitude in the leaflets over time was estimated using numerical analyses. Preliminary results showed superior tissue formation and non-linear tissuelike mechanical properties in the strained valves when compared to non-loaded tissue strips. In conclusion, the strain-based conditioning approach, using both prestrain and dynamic strains, offers new possibilities for bioreactor design and optimization of tissue properties towards a tissue-engineered aortic human heart valve replacement.

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Section: Introductionmentioning

confidence: 99%

Tissue Engineering of Human Heart Valve Leaflets: A Novel Bioreactor for a Strain-Based Conditioning Approach

et al. 2005

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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%

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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“…11 However, this system was not able to support the in vitro growth of biologically based TEVs. Similarly, Zaucha et al constructed a computer-controlled bioreactor system that applied shortterm biaxial stretching to collagen-based TEVs.…”

Section: Introductionmentioning

confidence: 97%

Design and Use of a Novel Bioreactor for Regeneration of Biaxially Stretched Tissue-Engineered Vessels

Huang

Lee

Calle

et al. 2015

Tissue Engineering Part C: Methods

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Conventional bioreactors are used to enhance extracellular matrix (ECM) production and mechanical strength of tissue-engineered vessels (TEVs) by applying circumferential strain, which is uniaxial stretching. However, the resulting TEVs still suffer from inadequate mechanical properties, where rupture strengths and compliance values are still very different from native arteries. The biomechanical milieu of native arteries consists of both circumferential and axial loading. Therefore, to better simulate the physiological stresses acting on native arteries, we built a novel bioreactor system to enable biaxial stretching of engineered arteries during culture. This new bioreactor system allows for independent control of circumferential and axial stretching parameters, such as displacement and beat rate. The assembly and setup processes for this biaxial bioreactor system are reliable with a success rate greater than 75% for completion of long-term sterile culture. This bioreactor also supports side-by-side assessments of TEVs that are cultured under three types of mechanical conditions (static, uniaxial, and biaxial), all within the same biochemical environment. Using this bioreactor, we examined the impact of biaxial stretching on arterial wall remodeling of TEVs. Biaxial TEVs developed the greatest wall thickness compared with static and uniaxial TEVs. Unlike uniaxial loading, biaxial loading led to undulated collagen fibers that are commonly found in native arteries. More importantly, the biaxial TEVs developed the most mature elastin in the ECM, both qualitatively and quantitatively. The presence of mature extracellular elastin along with the undulated collagen fibers may contribute to the observed vascular compliance in the biaxial TEVs. The current work shows that biaxial stretching is a novel and promising means to improve TEV generation. Furthermore, this novel system allows us to optimize biomechanical conditioning by unraveling the interrelationships among the applied mechanical stress, the resulting ECM properties, and the mechanics of TEVs.

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Perfusion Bioreactor for Vascular Tissue Engineering with Capacities for Longitudinal Stretch

Cited by 51 publications

References 19 publications

Tissue Engineering of Human Heart Valve Leaflets: A Novel Bioreactor for a Strain-Based Conditioning Approach

Tissue Engineering of Human Heart Valve Leaflets: A Novel Bioreactor for a Strain-Based Conditioning Approach

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

Design and Use of a Novel Bioreactor for Regeneration of Biaxially Stretched Tissue-Engineered Vessels

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