Tissue engineered heart valves re-endothelialized under simulated physiological conditions: Preclinical testing

Lichtenberg, A.; Tudorache, I; Cebotari, S; Suprunov, M; Goerler, Heidi; Brandes, Gudrun; Hilfiker, Andres; Haverich, Axel

doi:10.1055/s-2006-925636

Cited by 28 publications

(32 citation statements)

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“…Finally, in vivo studies will be required to study and improve the mechanical properties of tissue‐engineered grafts. However, pulsatile flow and physiological shear stress (10,45,46) as well as best culture‐medium conditions will be directions of future research in vitro. Deeper understanding of cellular differentiation and communication may enable us to achieve improved bioartificial vessel properties before implanting those autologous constructs in vivo in the near future.…”

Section: Discussionmentioning

confidence: 99%

Tissue Engineering Human Small‐Caliber Autologous Vessels Using a Xenogenous Decellularized Connective Tissue Matrix Approach: Preclinical Comparative Biomechanical Studies

Schmiedl

Cebotari

et al. 2011

Artificial Organs

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Suggesting that bioartificial vascular scaffolds cannot but tissue-engineered vessels can withstand biomechanical stress, we developed in vitro methods for preclinical biological material testings. The aim of the study was to evaluate the influence of revitalization of xenogenous scaffolds on biomechanical stability of tissue-engineered vessels. For measurement of radial distensibility, a salt-solution inflation method was used. The longitudinal tensile strength test (DIN 50145) was applied on bone-shaped specimen: tensile/tear strength (SigmaB/R), elongation at maximum yield stress/rupture (DeltaB/R), and modulus of elasticity were determined of native (NAs; n = 6), decellularized (DAs; n = 6), and decellularized carotid arteries reseeded with human vascular smooth muscle cells and human vascular endothelial cells (RAs; n = 7). Radial distensibility of DAs was significantly lower (113%) than for NAs (135%) (P < 0.001) or RAs (127%) (P = 0.018). At levels of 120 mm Hg and more, decellularized matrices burst (120, 160 [n = 2] and 200 mm Hg). Although RAs withstood levels up to 300 mm Hg, ANOVA revealed a significant difference from NA (P = 0.018). Compared with native vessels (NAs), SigmaB/R values were lower in DAs (44%; 57%) (P = 0.014 and P = 0.002, respectively) and were significantly higher in RAs (71%; 83%) (both P < 0.001). Similarly, DeltaB/R values were much higher in DAs compared with NAs (94%; 88%) (P < 0.001) and RAs (87%; 103%) (P < 0.001), but equivalent in NAs and RAs. Modulus of elasticity (2.6/1.1/3.7 to 16.6 N/mm(2)) of NAs, DAs, RAs was comparable (P = 0.088). Using newly developed in vitro methods for small-caliber vascular graft testing, this study proved that revitalization of decellularized connective tissue scaffolds led to vascular graft stability able to withstand biomechanical stress mimicking the human circulation. This tissue engineering approach provides a sufficiently stable autologized graft.

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Section: Discussionmentioning

confidence: 99%

Tissue Engineering Human Small‐Caliber Autologous Vessels Using a Xenogenous Decellularized Connective Tissue Matrix Approach: Preclinical Comparative Biomechanical Studies

Schmiedl

Cebotari

et al. 2011

Artificial Organs

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“…These studies have reported that no endothelial cells were detected on the valve surface even 1 month after DHV transplantation. Only inhomogeneous clusters of cells covered the basement membrane of the DHVs 3 months after transplantation (Lichtenberg, Tudorache, et al, ). Studies on in vitro recellularization of decellularized leaflets showed that it took approximately 4 weeks of static culture to reach only 2% of recellularization compared to native tissue as well as 4–6 weeks of bioreactor culture to achieve substantial recellularization (Schmidt, Stock, & Hoerstrup, ).…”

Section: Discussionmentioning

confidence: 99%

Improving the biological function of decellularized heart valves through integration of protein tethering and three‐dimensional cell seeding in a bioreactor

Namiri

Ashtiani

Abbasalizadeh

et al. 2017

J Tissue Eng Regen Med

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Decellularized xenogeneic heart valves (DHVs) are promising products for valve replacement. However, the widespread clinical application of such products is limited due to the risk of immune reaction, progressive degeneration, inflammation, and calcification. Here, we have developed an optimized decellularization protocol for a xenogeneic heart valve. We improved the biological function of DHVs by protein tethering onto DHV and three-dimensional (3D) cell seeding in a bioreactor. Our results showed that heart valves treated with a Triton X-100 and sodium deoxycholate-based protocol were completely cell-free, with preserved biochemical and biomechanical properties. The immobilization of stromal derived factor-1α (SDF-1α) and basic fibroblast growth factor on DHV significantly improved recellularization with endothelial progenitor cells under the 3D culture condition in the bioreactor compared to static culture conditions. Cell phenotype analysis showed higher fibroblast-like cells and less myofibroblast-like cells in both protein-tethered DHVs. However, SDF-DHV significantly enhanced recellularization both in vitro and in vivo compared to basic fibroblast growth factor DHV and demonstrated less inflammatory cell infiltration. SDF-DHV had less calcification and platelet adhesion. Altogether, integration of SDF-1α immobilization and 3D cell seeding in a bioreactor might provide a novel, promising approach for production of functional heart valves.

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“…Moreover, the application of ECs in an allogeneic setting is being extended to other fields. Recently, it was demonstrated that reendothelialization of mechanical devices was shown to improve their function, as ECs promote biocompatibility and hemocompatibility and prevent chalk deposition and material erosion . However, as the collection of adequate numbers of autologous ECs is often insufficient, the use of allogeneic cells is often inevitable.…”

Section: Discussionmentioning

confidence: 99%

“…Endothelial cells (ECs) have moved into the spotlight in recent years, not only because of their likely involvement in organ rejection, but also due to their ability to promote the proper functionality and hemocompatibility of biomedical devices and scaffolds for tissue engineering 1‐3. Due to the scarcity of autologous ECs, reendothelialization is mainly based on the use of partially HLA‐mismatched allogeneic ECs.…”

mentioning

confidence: 99%

Semaphorin 3A alters endothelial cell immunogenicity by regulating Class II transactivator activity circuits

et al. 2014

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Tissue engineered heart valves re-endothelialized under simulated physiological conditions: Preclinical testing

Cited by 28 publications

References 0 publications

Tissue Engineering Human Small‐Caliber Autologous Vessels Using a Xenogenous Decellularized Connective Tissue Matrix Approach: Preclinical Comparative Biomechanical Studies

Tissue Engineering Human Small‐Caliber Autologous Vessels Using a Xenogenous Decellularized Connective Tissue Matrix Approach: Preclinical Comparative Biomechanical Studies

Improving the biological function of decellularized heart valves through integration of protein tethering and three‐dimensional cell seeding in a bioreactor

Semaphorin 3A alters endothelial cell immunogenicity by regulating Class II transactivator activity circuits

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