Readily Available Tissue-Engineered Vascular Grafts

Dahl, Shannon L. M.; Kypson, Alan P.; Lawson, Jeffrey H.; Blum, Juliana L.; Strader, J.T.; Li, Yuling; Manson, Roberto J.; Tente, William E.; DiBernardo, Louis R.; Hensley, Michael Taylor; Carter, Riley; Williams, Tiare P.; Prichard, Heather L.; Dey, Margaret S.; Begelman, Keith G.; Niklason, Laura E.

doi:10.1126/scitranslmed.3001426

Cited by 503 publications

(529 citation statements)

References 48 publications

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“…22 Recently, the decellularization process has been utilized to develop acellular TEVG and circumvent this obstacle. 6 The nonimmunogenic properties of allogeneic extracellular matrix have been characterized in multiple animal models. 6,23,24 In this study, we utilized the ovine femoral artery model to evaluate completely biological, acellular TEVG made from fibrin remodeling by allogeneic fibroblasts in vitro as a potential solution for the clinical need of small-diameter arterial grafts.…”

Section: Discussionmentioning

confidence: 99%

“…1 Various approaches have been used to fabricate TEVG, [3][4][5][6][7][8][9] recently reviewed. 3 Most notably in terms of clinical promise, TEVGs derived from rolling a fibroblastproduced ''cell sheet'' into a tube 5,7,8,10 and from smooth muscle cells (SMCs) seeded onto a degradable synthetic polymer tube 4,6,9 have resulted in successful implantation. In contrast to these approaches, our approach utilizes the biopolymer fibrin (in hydrogel form) as the starting scaffold, 11 which eliminates risk of any adverse host reaction to residual synthetic material.…”

Section: Introductionmentioning

confidence: 99%

“…The recellularization of the grafts from both the lumenal and ablumenal surfaces is similar to that reported for other TEVG implants to date. 6,8 After 24 weeks, all grafts (4/4) were completely recellularized. In contrast, the presence of an acellular region up to 1 year has been reported.…”

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confidence: 99%

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Implantation of Completely Biological Engineered Grafts Following Decellularization into the Sheep Femoral Artery

Syedain

Meier

Lahti

et al. 2014

Tissue Engineering Part A

129

108

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The performance of completely biological, decellularized engineered allografts in a sheep model was evaluated to establish clinical potential of these unique arterial allografts. The 4-mm-diameter, 2-3-cm-long grafts were fabricated from fibrin gel remodeled into an aligned tissue tube in vitro by ovine dermal fibroblasts. Decellularization and subsequent storage had little effect on graft properties, with burst pressure exceeding 4000 mmHg and the same compliance as the ovine femoral artery. Grafts were implanted interpositionally in the femoral artery of six sheep (n = 9), with contralateral sham controls (n = 3). At 8 weeks (n = 5) and 24 weeks (n = 4), all grafts were patent and showed no evidence of dilatation or mineralization. Mid-graft lumen diameter was unchanged. Extensive recellularization occurred, with most cells expressing aSMA. Endothelialization was complete by 24 weeks with elastin deposition evident. These completely biological grafts possessed circumferential alignment/mechanical anisotropy characteristic of native arteries and were cultured only 5 weeks prior to decellularization and storage as ''off-the-shelf'' grafts.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Implantation of Completely Biological Engineered Grafts Following Decellularization into the Sheep Femoral Artery

Syedain

Meier

Lahti

et al. 2014

Tissue Engineering Part A

129

108

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show abstract

“…Autologous tissue-engineered solutions have the major advantage of not requiring immunosuppression, but clinical applications are limited to static organs and tissues, such as skin, or those that can function through passive movement alone, such as trachea, heart valves, blood vessels, and bladder (4,7,12). The field continues to expand and tissue bioengineering has provided, or is close to delivering, functional human organ replacements elsewhere (6,7,(13)(14)(15)(16)(17).…”

mentioning

confidence: 99%

Immunomodulatory effect of a decellularized skeletal muscle scaffold in a discordant xenotransplantation model

Fishman

Lowdell

Urbani³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

184

137

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Decellularized (acellular) scaffolds, composed of natural extracellular matrix, form the basis of an emerging generation of tissueengineered organ and tissue replacements capable of transforming healthcare. Prime requirements for allogeneic, or xenogeneic, decellularized scaffolds are biocompatibility and absence of rejection. The humoral immune response to decellularized scaffolds has been well documented, but there is a lack of data on the cellmediated immune response toward them in vitro and in vivo. Skeletal muscle scaffolds were decellularized, characterized in vitro, and xenotransplanted. The cellular immune response toward scaffolds was evaluated by immunohistochemistry and quantified stereologically. T-cell proliferation and cytokines, as assessed by flow cytometry using carboxy-fluorescein diacetate succinimidyl ester dye and cytometric bead array, formed an in vitro surrogate marker and correlate of the in vivo host immune response toward the scaffold. Decellularized scaffolds were free of major histocompatibility complex class I and II antigens and were found to exert anti-inflammatory and immunosuppressive effects, as evidenced by delayed biodegradation time in vivo; reduced sensitized T-cell proliferative activity in vitro; reduced IL-2, IFN-γ, and raised IL-10 levels in cell-culture supernatants; polarization of the macrophage response in vivo toward an M2 phenotype; and improved survival of donor-derived xenogeneic cells at 2 and 4 wk in vivo. Decellularized scaffolds polarize host responses away from a classical TH1-proinflammatory profile and appear to down-regulate T-cell xeno responses and TH1 effector function by inducing a state of peripheral T-cell hyporesponsiveness. These results have substantial implications for the future clinical application of tissue-engineered therapies.

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“…Implantation of a decellularized valve would represent a different approach, as it would require seeding of new non-contractile cells or the attraction of endogenous cells in vivo to ensure a viable implant. It is, however, a promising approach as decellularized valves have already shown functionality in vivo (Simon et al 2003;Cebotari et al 2006;Erdbrugger et al 2006;Hopkins et al 2009) and it is currently under investigation for tissue engineered constructs as well (Dahl et al 2011).…”

Section: Passive and Active Components In Tissue Retractionmentioning

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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Readily Available Tissue-Engineered Vascular Grafts

Cited by 503 publications

References 48 publications

Implantation of Completely Biological Engineered Grafts Following Decellularization into the Sheep Femoral Artery

Implantation of Completely Biological Engineered Grafts Following Decellularization into the Sheep Femoral Artery

Immunomodulatory effect of a decellularized skeletal muscle scaffold in a discordant xenotransplantation model

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

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