Computational modelling to reduce outcome variability in tissue-engineered heart valves

Abstract The need for improved heart valve prostheses is especially critical in pediatric applications, where growth and remodeling are essential. Tissue engineered heart valves (TEHV) have functioned in the pulmonary circulation of growing lambs for up to four months [1], and thus can potentially overcome limitations of current bioprosthetic heart valves. Despite these promising results, significant questions remain. In particular, the role of scaffold mechanical properties in optimal extra-cellular matrix development, as well as TEHV durability, are largely unexplored. We have previously demonstrated flexure testing as a sensitive and critical test for BHV tissue mechanical property evaluation [2]. The following study was conducted to determine the feasibility of using this technique to provide fundamental information required for optimizing TEHV scaffold designs.

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Dental Pulp Stem Cells for Tissue Engineered Heart Valve

Indian Journal of Animal Research ◽

10.18805/ijar.b-1224 ◽

2020 ◽

Author(s):

Soontaree Petchdee ◽

Wilairat Chumsing ◽

Suruk Udomsom ◽

Kittiya Thunsiri

Keyword(s):

Stem Cells ◽

Mitral Valve ◽

Heart Valve ◽

Heart Valves ◽

Cell Types ◽

Tensile Tests ◽

Deciduous Teeth ◽

Essential Information ◽

Acquired Heart Disease ◽

Tissue Engineered Heart Valves

Myxomatous mitral valve degeneration is the most acquired heart disease in dogs. To reduce the clinical progression of mitral valve degeneration and achieve the hemodynamic outcomes, many medical or surgical treatments have been motivated. The objectives of this study is to investigate the suitability of puppy deciduous teeth stem cells as a cell source for tissue engineered heart valves in dog with degenerative valve disease. Puppy deciduous teeth stem cells (pDSCs) were seeded on the scaffolds which made from polylactic acid (PLA), polycaprolactone (PLC) and silicone. The mechanical properties of the tissue engineered heart valves leaflets were characterized by biaxial tensile tests. Results showed that, deciduous teeth stem cells capable of differentiating into a variety of cell types. However, the ability of puppy deciduous teeth stem cells to differentiate declined with increasing passage number which correspond to the number of protein surface marker detection have been shown to decrease substantially by the fifth passage. PLA scaffold is significantly higher tensile strength than other materials. However, silicone showed the highest flaccidity. The results from this study may provide high regenerative capability and the essential information for future directions of heart valve tissue engineering.

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Abstract 219: Induced Pluripotent Stem Cells as a Potential Cell Source for Tissue Engineered Heart Valves

Circulation Research ◽

10.1161/res.119.suppl_1.219 ◽

2016 ◽

Vol 119 (suppl_1) ◽

Author(s):

Aline L Yonezawa ◽

Monalisa Singh ◽

David Safranski ◽

Kenneth M Dupont ◽

Chunhui Xu ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Heart Valves ◽

3D Culture ◽

Polyethylene Glycol Diacrylate ◽

Glycol Diacrylate ◽

Cell Source ◽

Induced Pluripotent ◽

Tissue Engineered Heart Valves

Despite recent advances in tissue engineered heart valves (TEHV), one of the major challenges is finding a suitable cell source for seeding TEHV scaffolds. Native heart valves are durable because valve interstitial cells (VICs) maintain tissue homeostasis by synthesizing and remodeling the extracellular matrix. In this study, we demonstrate that induced pluripotent stem cells (iPSCs) can be derived into induced mesenchymal stem cells (iMSCs) using our feeder-free protocol and then further differentiated into VICs using a 3D cell culture environment. The differentiation efficiency was quantified using flow cytometry, immunohistochemistry staining, RT-PCR, and trilineage differentiation. In addition, iMSCs were encapsulated in polyethylene (glycol) diacrylate (PEGDA) hydrogels of varying stiffness, grafted with adhesion peptide (RGDS), to promote cell proliferation, remodeling, and further differentiation into VIC-like cells. VICs phenotype was characterized by the expression of αSMA, vimentin, F-actin, and the ECM production after 7, 14, and 21 days. The results demonstrated that using our feeder-free differentiation protocol, iMSCs were differentiated from iPSCs. Our iMSCs had a 99.9% and 99.4% positive expression for MSC markers CD90 and CD44, respectively. As expected, there was 0.019% expression of CD45, which is a hematopoietic marker. In addition, iMSCs differentiated into adipogenic, chondrogenic, and osteogenic. When MSC derived cells were encapsulated in PEGDA hydrogels that mimic the leaflet modulus, we observed expression of αSMA and F-actin after 7 days. Thus, the results from this study suggest that iPSCs can be a suitable cell source for TEHV by using a feeder-free differentiation approach and 3D culture.

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PCV92 - EARLY HEALTH TECHNOLOGY ASSESSMENT OF TISSUE-ENGINEERED HEART VALVES IN THE AORTIC POSITION IN ELDERLY PATIENTS

Value in Health ◽

10.1016/j.jval.2018.09.638 ◽

2018 ◽

Vol 21 ◽

pp. S108

Author(s):

S. Huygens ◽

I. Corro Ramos ◽

C. Bouten ◽

J. Kluin ◽

H. Takkenberg ◽

...

Keyword(s):

Elderly Patients ◽

Health Technology Assessment ◽

Technology Assessment ◽

Heart Valves ◽

Health Technology ◽

Early Health Technology Assessment ◽

Early Health ◽

Tissue Engineered Heart Valves

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Determination of antibiotics and detergent residues in decellularized tissue-engineered heart valves using LC–MS/MS

Cell and Tissue Banking ◽

10.1007/s10561-020-09856-x ◽

2020 ◽

Vol 21 (4) ◽

pp. 573-584

Author(s):

Leticia Kraft ◽

Victoria Stadler Tasca Ribeiro ◽

Luciana Cristina Ferretti de Nazareno Wollmann ◽

Paula Hansen Suss ◽

Felipe Francisco Tuon

Keyword(s):

Heart Valves ◽

Decellularized Tissue ◽

Tissue Engineered Heart Valves

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In Situ Remodeling Overrules Bioinspired Scaffold Architecture of Supramolecular Elastomeric Tissue-Engineered Heart Valves

JACC Basic to Translational Science ◽

10.1016/j.jacbts.2020.09.011 ◽

2020 ◽

Vol 5 (12) ◽

pp. 1187-1206

Author(s):

Marcelle Uiterwijk ◽

Anthal I.P.M. Smits ◽

Daphne van Geemen ◽

Bas van Klarenbosch ◽

Sylvia Dekker ◽

...

Keyword(s):

Heart Valves ◽

Scaffold Architecture ◽

Tissue Engineered Heart Valves

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Decellularized tissue-engineered heart valves calcification: what do animal and clinical studies tell us?

Journal of Materials Science Materials in Medicine ◽

10.1007/s10856-020-06462-x ◽

2020 ◽

Vol 31 (12) ◽

Author(s):

Adel F. Badria ◽

Petros G. Koutsoukos ◽

Dimosthenis Mavrilas

Keyword(s):

Heart Valve ◽

Clinical Studies ◽

Heart Valves ◽

Early Stage ◽

Anticoagulation Therapy ◽

Complex Nature ◽

In Silico Studies ◽

Decellularized Tissue ◽

Tissue Engineered Heart Valves

AbstractCardiovascular diseases are the first cause of death worldwide. Among different heart malfunctions, heart valve failure due to calcification is still a challenging problem. While drug-dependent treatment for the early stage calcification could slow down its progression, heart valve replacement is inevitable in the late stages. Currently, heart valve replacements involve mainly two types of substitutes: mechanical and biological heart valves. Despite their significant advantages in restoring the cardiac function, both types of valves suffered from serious drawbacks in the long term. On the one hand, the mechanical one showed non-physiological hemodynamics and the need for the chronic anticoagulation therapy. On the other hand, the biological one showed stenosis and/or regurgitation due to calcification. Nowadays, new promising heart valve substitutes have emerged, known as decellularized tissue-engineered heart valves (dTEHV). Decellularized tissues of different types have been widely tested in bioprosthetic and tissue-engineered valves because of their superior biomechanics, biocompatibility, and biomimetic material composition. Such advantages allow successful cell attachment, growth and function leading finally to a living regenerative valvular tissue in vivo. Yet, there are no comprehensive studies that are covering the performance of dTEHV scaffolds in terms of their efficiency for the calcification problem. In this review article, we sought to answer the question of whether decellularized heart valves calcify or not. Also, which factors make them calcify and which ones lower and/or prevent their calcification. In addition, the review discussed the possible mechanisms for dTEHV calcification in comparison to the calcification in the native and bioprosthetic heart valves. For this purpose, we did a retrospective study for all the published work of decellularized heart valves. Only animal and clinical studies were included in this review. Those animal and clinical studies were further subcategorized into 4 categories for each depending on the effect of decellularization on calcification. Due to the complex nature of calcification in heart valves, other in vitro and in silico studies were not included. Finally, we compared the different results and summed up all the solid findings of whether decellularized heart valves calcify or not. Based on our review, the selection of the proper heart valve tissue sources (no immunological provoking residues), decellularization technique (no damaged exposed residues of the decellularized tissues, no remnants of dead cells, no remnants of decellularizing agents) and implantation techniques (avoiding suturing during the surgical implantation) could provide a perfect anticalcification potential even without in vitro cell seeding or additional scaffold treatment.

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