Controlled cyclic stretch bioreactor for tissue-engineered heart valves

Syedain, Zeeshan H.; Tranquillo, Robert T.

doi:10.1016/j.biomaterials.2009.04.027

Cited by 93 publications

(82 citation statements)

References 35 publications

(40 reference statements)

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“…53 In the second approach, the tubular construct is cyclically stretched and distended with incremental strain amplitude, frequency and duty cycle. Syedain and colleagues have clearly show that cyclic distension/stretching can be used to improve mechanical and biochemical properties and structural organization of tissue-engineered tubular constructs, 54 especially with a protocol of increasing frequency and duty cycle in time. Both approaches were realized, viable constructs were conditioned in bioreactors for 21 days and clear ECM proteins deposition was observed for all of them, mostly with a longitudinal orientation as a result of the dynamic conditioning.…”

Section: Weber Et Almentioning

confidence: 99%

Tissue-Engineered Fibrin-Based Heart Valve with a Tubular Leaflet Design

Weber

Heta

Moreira

et al. 2014

Tissue Engineering Part C: Methods

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The general approach in heart valve tissue engineering is to mimic the shape of the native valve in the attempt to recreate the natural haemodynamics. In this article, we report the fabrication of the first tissue-engineered heart valve (TEHV) based on a tubular leaflet design, where the function of the leaflets of semilunar heart valves is performed by a simple tubular construct sutured along a circumferential line at the root and at three single points at the sinotubular junction. The tubular design is a recent development in pericardial (nonviable) bioprostheses, which has attracted interest because of the simplicity of the construction and the reliability of the implantation technique. Here we push the potential of the concept further from the fabrication and material point of view to realize the tube-in-tube valve: an autologous, living HV with remodelling and growing capability, physiological haemocompatibility, simple to construct and fast to implant. We developed two different fabrication/conditioning procedures and produced fibrin-based constructs embedding cells from the ovine umbilical cord artery according to the two different approaches. Tissue formation was confirmed by histology and immunohistology. The design of the tube-in-tube foresees the possibility of using a textile coscaffold (here demonstrated with a warp-knitted mesh) to achieve enhanced mechanical properties in vision of implantation in the aortic position. The tube-in-tube represents an attractive alternative to the conventional design of TEHVs aiming at reproducing the valvular geometry.

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Section: Weber Et Almentioning

confidence: 99%

Tissue-Engineered Fibrin-Based Heart Valve with a Tubular Leaflet Design

Weber

Heta

Moreira

et al. 2014

Tissue Engineering Part C: Methods

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“…27 In brief, the bioreactor consists of a distensible latex tube, in which the VE is mounted, and two flow circuits for controlled stretching (via cyclic lumen pressurization) and nutrient supply (via slow, steady recirculation). The culture medium in the perfusion loop's reservoir was changed three times per week.…”

Section: Controlled Cyclic Stretching Bioreactormentioning

confidence: 99%

“…18 More recently, we have shown that our strategy of incremental strain amplitude cyclic stretching 28 can be implemented in a bioreactor for TEHV. 27 Bi-leaflet VE made from human fibroblasts were obtained after 3 weeks of cyclic stretching, possessing anisotropic tensile properties in the leaflets comparable to those in sheep pulmonary valve leaflets. While utilizing human cells to engineer a VE for implantation in the ovine model requires the use of immunosuppressants, which may interfere with the natural remodeling process, the approach of using human cells in an immunosuppressed animal model and moving to clinical trials has been successfully achieved with vascular grafts, which like the VE are also completely biological and based on tissue grown from human dermal fibroblasts.…”

Section: Introductionmentioning

confidence: 99%

“…11,12,14 The VE also could withstand cyclic pulmonary pressures with similar distension as for a sheep pulmonary artery. 27 Since VE do not possess the tri-layer organization of native leaflets, which is true for all implanted TEHV reported to date, whether a tri-leaflet VE is superior to a bi-leaflet VE is unknown since the biomechanics of leaflet bending are different in VE leaflets vs. native leaflets. Moreover, it is known that the progressions of fibrosis, calcification, and severity of stenosis are less rapid in valves with more equal-sized leaflets based on assessment of explanted bi-leaflet aortic valves from patients.…”

Section: Introductionmentioning

confidence: 99%

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Implantation of a Tissue-engineered Heart Valve from Human Fibroblasts Exhibiting Short Term Function in the Sheep Pulmonary Artery

Syedain

Lahti

Johnson

et al. 2011

Cardiovasc Eng Tech

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Abstract-We have previously demonstrated the feasibility of fabricating a fibrin-based tissue-engineered heart valve (TEHV) using neonatal human dermal fibroblasts (nhDF), including leaflets with structural and mechanical anisotropy similar to native leaflets. The aim here was to evaluate the performance of this TEHV in a pilot study using the sheep model. Bi-leaflet TEHV were conditioned in a cyclic stretching bioreactor, then implanted within a polymeric sleeve interpositionally into the pulmonary artery of four sheep, with the pulmonary valve either left intact or rendered incompetent. Heparin and immunosuppression were administered for the duration. Echocardiography was performed at implantation and at 4 and 8 weeks. Explants were examined histologically, biochemically, and mechanically. In all sheep, echocardiography at implantation showed coapting leaflets, with minimal valve regurgitation and no turbulence. Orifice area and pressure gradients at systole approached the native pulmonary valve values. Echocardiography at 4 weeks revealed both leaflets functional with moderate regurgitation and turbulence in three sheep; in one sheep, only one leaflet was evident. Explanted leaflets had thickness and tensile properties comparable to the implanted leaflets. There was extensive endothelialization of the root lumenal surface. In the two sheep continued to 8 weeks, only one shortened leaflet remained in both cases. Immunocytochemistry indicated this was due to sustained tissue contraction caused by the nhDF and not by the invading host cells, which included a subpopulation consistent with bone marrow-derived cells. Short-term success was thus achieved in terms of excellent valve function at implantation and some valve function for at least 4 weeks; however, an apparent progressive tissue contraction needs to be resolved for long-term success.

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“…For pediatric patients this would prevent dangerous re-operations throughout their childhood to accommodate growth. Over the last decade, bioreactor systems inducing mechanical conditioning and flow profiles have improved in vitro tissue formation (Flanagan et al 2007;Mol et al 2005;Kortsmit et al 2009;Ruel and Lachance 2009;Syedain and Tranquillo 2009). Moreover, in vivo animal studies have demonstrated the feasibility of heart valve tissue engineering, showing remodeling into native-like structures Sodian et al 2000;Stock et al 2000;Sutherland et al 2005;Gottlieb et al 2010;Schmidt et al 2010;Flanagan et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Passive and active contributions to generated force and retraction in heart valve tissue engineering

Vlimmeren

Driessen-Mol

Oomens

et al. 2012

Biomech Model Mechanobiol

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In tissue engineered heart valves, cell-mediated stress development during culture results in leaflet retraction at time of implantation. This tissue retraction is partly active due to traction forces exerted by the cells and partly passive due to release of residual stress in the extracellular matrix and the cells. Within this study, we unraveled the passive and active contributions of cells and matrix to generated force and retraction in engineered heart valve tissues. Tissue engineered rectangular strips, fabricated from PGA/P4HB scaffolds and seeded with human myofibroblasts, were cultured for 4 weeks, after which the cellular contribution was changed at different levels. Elimination of the active cellular traction forces was achieved with Cytochalasin D and inhibition of the Rho-associated kinase pathway. Both active and passive cellular contributions were eliminated by lysation and/or decellularization of the tissue. Maximum cell activity was reached by increasing the fetal bovine serum concentration to 50%. The generated force decreased ∼20% after elimination of the active cellular component, ∼25% when the passive cellular component was removed as well and remained unaffected by increased serum concentrations. Passive retraction accounted for ∼60% of total retraction, of which ∼15% was residual stress in the matrix and ∼45% was passive cell retraction. Cell traction forces accounted for the remainder ∼40% of the retraction. Full activation of the cells increased retraction by ∼45%. These results illustrate the importance of the cells in the process of tissue retraction, not only actively retracting the tissue, but also in a passive manner to a large extent.

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Controlled cyclic stretch bioreactor for tissue-engineered heart valves

Cited by 93 publications

References 35 publications

Tissue-Engineered Fibrin-Based Heart Valve with a Tubular Leaflet Design

Tissue-Engineered Fibrin-Based Heart Valve with a Tubular Leaflet Design

Implantation of a Tissue-engineered Heart Valve from Human Fibroblasts Exhibiting Short Term Function in the Sheep Pulmonary Artery

Passive and active contributions to generated force and retraction in heart valve tissue engineering

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