Variation in Tissue Outcome of Ovine and Human Engineered Heart Valve Constructs: Relevance for Tissue Engineering

Geemen, Daphne van; Driessen-Mol, Anita Anita; Grootzwagers, Leonie G M; Soekhradj-Soechit, R Sarita; Vis, Paul W. Riem; Baaijens, Fpt Frank; Bouten, Cvc Carlijn

doi:10.2217/rme.11.100

Cited by 21 publications

(13 citation statements)

References 41 publications

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“…A number of synthetic (poly-glycolic acid, polylactic acid, poly-4-hydroxybutyrate, polyhydroxyalkanoate) (Sodian, Hoerstrup et al 2000; Sutherland, Perry et al 2005; Balguid, Mol et al 2009; Gottlieb, Kunal et al 2010; Ramaswamy, Gottlieb et al 2010; Sales, Mettler et al 2010; Schmidt, Dijkman et al 2010; Sodian, Schaefermeier et al 2010; Eckert, Mikulis et al 2011; van Geemen, Driessen-Mol et al 2012) and biological polymeric (collagen I, fibrin) (Neidert and Tranquillo 2006; Robinson, Johnson et al 2007; Flanagan, Sachweh et al 2009) scaffolds have been created, mechanically conditioned in vitro , and tested in animal models. In the longest such trial to date (8 months within a growing sheep model), engineered valves (leaflet + conduit) were still functional but mildly stenotic, suggesting that the leaflets lacked sufficient compliance (Sutherland, Perry et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds

et al. 2012

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The aortic valve exhibits complex three-dimensional (3D) anatomy and heterogeneity essential for long-term efficient biomechanical function. These are, however, challenging to mimic in de novo engineered living tissue valve strategies. We present a novel simultaneous 3D-printing/photocrosslinking technique for rapidly engineering complex, heterogeneous aortic valve scaffolds. Native anatomic and axisymmetric aortic valve geometries (root wall and tri-leaflets) with 12 to 22 mm inner diameters (ID) were 3D printed with poly-ethylene glycol-diacrylate (PEG-DA) hydrogels (700 or 8000 MW) supplemented with alginate. 3D printing geometric accuracy was quantified and compared using Micro-CT. Porcine aortic valve interstitial cells (PAVIC) seeded scaffolds were cultured for up to 21 days. Results showed that blended PEG-DA scaffolds could achieve over 10-fold range in elastic modulus (5.3±0.9 to 74.6±1.5 kPa). 3D printing times for valve conduits with mechanically contrasting hydrogels were optimized to 14 to 45 minutes, increasing linearly with conduit diameter. Larger printed valves had greater shape fidelity (93.3±2.6, 85.1±2.0, and 73.3±5.2% for 22, 17, and 12 mm ID porcine valves; 89.1±4.0, 84.1±5.6, and 66.6±5.2% for simplified valves). PAVIC seeded scaffolds maintained near 100% viability over 21 days. These results demonstrate that 3D hydrogel printing with controlled photocrosslinking can rapidly fabricate anatomical heterogeneous valve conduits that support cell engraftment.

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Section: Introductionmentioning

confidence: 99%

Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds

et al. 2012

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“…Although these studies seem promising and the use of human AFCs in vitro or in immunodeficient rodent models represents an important step, more extensive in vivo experiments using autologous AFCs in immunocompetent experimental models seem mandatory before a first human clinical application. In addition, when dealing with tissue‐engineered constructs the assessment of the ex vivo engineered constructs in biomechanical environments comparable to the human physiology seems obligatory (van Geemen et al ., ). Therefore, several groups have started isolating and characterizing autologous amniotic fluid‐derived cells from different large animal models, including porcine (Chen et al ., ) or equine (Park et al ., ) materno‐fetal models.…”

Section: Discussionmentioning

confidence: 97%

“…This seems crucial in order to assess the adequate in vivo functionality of implanted constructs and cells, but also in order to exclude potential adverse effects. While extensive preclinical research in non‐human primates has raised ethical concerns, the ovine model represents one of the most accepted and broadly used preclinical in vivo models for therapeutic approaches (van Geemen et al ., ). Among others, it has been established as a standard model for preclinical evaluation of haematopoietic stem cell transplantations (Porada et al ., ), orthopaedic implants (Schneider et al ., ), therapeutic cloning (Berardino, ), fertility treatment (Byun et al ., ), prenatal therapeutic interventions (Lapa Pedreira et al ., ), fetal stem cell injections (Schoeberlein et al ., , Emmert et al ., ), as well as any cardiovascular device in vivo assessment due to its advanced calcification and degeneration properties (Barnhart et al ., ).…”

Section: Introductionmentioning

confidence: 97%

In vitrofabrication of autologous living tissue-engineered vascular grafts based on prenatally harvested ovine amniotic fluid-derived stem cells

Weber

Kehl

Bleul

et al. 2013

J Tissue Eng Regen Med

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Amniotic fluid cells (AFCs) have been proposed as a valuable source for tissue engineering and regenerative medicine. However, before clinical implementation, rigorous evaluation of this cell source in clinically relevant animal models accepted by regulatory authorities is indispensable. Today, the ovine model represents one of the most accepted preclinical animal models, in particular for cardiovascular applications. Here, we investigate the isolation and use of autologous ovine AFCs as cell source for cardiovascular tissue engineering applications. Fetal fluids were aspirated in vivo from pregnant ewes (n = 9) and from explanted uteri post mortem at different gestational ages (n = 91). Amniotic non-allantoic fluid nature was evaluated biochemically and in vivo samples were compared with post mortem reference samples. Isolated cells revealed an immunohistochemical phenotype similar to ovine bone marrow-derived mesenchymal stem cells (MSCs) and showed expression of stem cell factors described for embryonic stem cells, such as NANOG and STAT-3. Isolated ovine amniotic fluid-derived MSCs were screened for numeric chromosomal aberrations and successfully differentiated into several mesodermal phenotypes. Myofibroblastic ovine AFC lineages were then successfully used for the in vitro fabrication of small- and large-diameter tissue-engineered vascular grafts (n = 10) and cardiovascular patches (n = 34), laying the foundation for the use of this relevant pre-clinical in vivo assessment model for future amniotic fluid cell-based therapeutic applications.

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“…Although this has been demonstrated in long‐term animal studies [2], studies in humans have yet to be performed to evaluate the efficacy of this approach. Recent studies by our group have demonstrated differences in cardiovascular tissues engineered from human and ovine cells [3]. This further indicates the relevance of specific, deviating culture protocols for either ovine or human engineered tissues and emphasizes that results obtained with either species cannot be easily compared.…”

Section: Introductionmentioning

confidence: 96%

Sequential use of human‐derived medium supplements favours cardiovascular tissue engineering

Vis

Sluijter

Soekhradj-Soechit

et al. 2012

J Cellular Molecular Medi

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For clinical application of tissue engineering strategies, the use of animal-derived serum in culture medium is not recommended, because it can evoke immune responses in patients. We previously observed that human platelet-lysate (PL) is favourable for cell expansion, but generates weaker tissue as compared to culture in foetal bovine serum (FBS). We investigated if human serum (HS) is a better human supplement to increase tissue strength. Cells were isolated from venous grafts of 10 patients and expanded in media supplemented with PL or HS, to determine proliferation rates and expression of genes related to collagen production and maturation. Zymography was used to assess protease expression. Collagen contraction assays were used as a two-dimensional (2D) model for matrix contraction. As a prove of principle, 3D tissue culture and tensile testing was performed for two patients, to determine tissue strength. Cell proliferation was lower in HS-supplemented medium than in PL medium. The HS cells produced less active matrix metallo-proteinase 2 (MMP2) and showed increased matrix contraction as indicated by gel contraction assays and 3D-tissue culture. Tensile testing showed increased strength for tissues cultured in HS when compared to PL. This effect was more pronounced if cells were sequentially cultured in PL, followed by tissue culture in HS. These data suggest that sequential use of PL and HS as substitutes for FBS in culture medium for cardiovascular tissue engineering results in improved cell proliferation and tissue mechanical properties, as compared to use of PL or HS apart.

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Variation in Tissue Outcome of Ovine and Human Engineered Heart Valve Constructs: Relevance for Tissue Engineering

Cited by 21 publications

References 41 publications

Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds

Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds

In vitrofabrication of autologous living tissue-engineered vascular grafts based on prenatally harvested ovine amniotic fluid-derived stem cells

Sequential use of human‐derived medium supplements favours cardiovascular tissue engineering

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