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Membranes for Modelling Cardiac Tissue Stiffness In Vitro Based on Poly(trimethylene carbonate) and Poly(ethylene glycol) Polymers

Despite the increased expenditure of the pharmaceutical industry on research and development, the number of drugs for cardiovascular diseases that reaches the market is decreasing. A major issue is the limited ability of the current in vitro and experimental animal models to accurately mimic human h...

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Autores principales: Allijn, Iris, Ribeiro, Marcelo, Poot, André, Passier, Robert, Stamatialis, Dimitrios
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650615/
https://www.ncbi.nlm.nih.gov/pubmed/33022962
http://dx.doi.org/10.3390/membranes10100274
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author Allijn, Iris
Ribeiro, Marcelo
Poot, André
Passier, Robert
Stamatialis, Dimitrios
author_facet Allijn, Iris
Ribeiro, Marcelo
Poot, André
Passier, Robert
Stamatialis, Dimitrios
author_sort Allijn, Iris
collection PubMed
description Despite the increased expenditure of the pharmaceutical industry on research and development, the number of drugs for cardiovascular diseases that reaches the market is decreasing. A major issue is the limited ability of the current in vitro and experimental animal models to accurately mimic human heart disease, which hampers testing of the efficacy of potential cardiac drugs. Moreover, many non-heart-related drugs have severe adverse cardiac effects, which is a major cause of drugs’ retraction after approval. A main hurdle of current in vitro models is their inability to mimic the stiffness of in vivo cardiac tissue. For instance, poly(styrene) petri dishes, which are often used in these models, have a Young’s modulus in the order of GPa, while the stiffness of healthy human heart tissue is <50 kPa. In pathological conditions, such as scarring and fibrosis, the stiffness of heart tissue is in the >100 kPa range. In this study, we focus on developing new membranes, with a set of properties for mimicry of cardiac tissue stiffness in vitro, based on methacrylate-functionalized macromers and triblock-copolymers of poly(trimethylene carbonate) and poly(ethylene glycol). The new membranes have Young’s moduli in the hydrated state ranging from 18 kPa (healthy tissue) to 2.5 MPa (pathological tissue), and are suitable for cell contraction studies using human pluripotent stem-cell-derived cardiomyocytes. The membranes with higher hydrophilicity have low drug adsorption and low Young’s moduli and could be suitable for drug screening applications.
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spelling pubmed-76506152020-11-10 Membranes for Modelling Cardiac Tissue Stiffness In Vitro Based on Poly(trimethylene carbonate) and Poly(ethylene glycol) Polymers Allijn, Iris Ribeiro, Marcelo Poot, André Passier, Robert Stamatialis, Dimitrios Membranes (Basel) Article Despite the increased expenditure of the pharmaceutical industry on research and development, the number of drugs for cardiovascular diseases that reaches the market is decreasing. A major issue is the limited ability of the current in vitro and experimental animal models to accurately mimic human heart disease, which hampers testing of the efficacy of potential cardiac drugs. Moreover, many non-heart-related drugs have severe adverse cardiac effects, which is a major cause of drugs’ retraction after approval. A main hurdle of current in vitro models is their inability to mimic the stiffness of in vivo cardiac tissue. For instance, poly(styrene) petri dishes, which are often used in these models, have a Young’s modulus in the order of GPa, while the stiffness of healthy human heart tissue is <50 kPa. In pathological conditions, such as scarring and fibrosis, the stiffness of heart tissue is in the >100 kPa range. In this study, we focus on developing new membranes, with a set of properties for mimicry of cardiac tissue stiffness in vitro, based on methacrylate-functionalized macromers and triblock-copolymers of poly(trimethylene carbonate) and poly(ethylene glycol). The new membranes have Young’s moduli in the hydrated state ranging from 18 kPa (healthy tissue) to 2.5 MPa (pathological tissue), and are suitable for cell contraction studies using human pluripotent stem-cell-derived cardiomyocytes. The membranes with higher hydrophilicity have low drug adsorption and low Young’s moduli and could be suitable for drug screening applications. MDPI 2020-10-03 /pmc/articles/PMC7650615/ /pubmed/33022962 http://dx.doi.org/10.3390/membranes10100274 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Allijn, Iris
Ribeiro, Marcelo
Poot, André
Passier, Robert
Stamatialis, Dimitrios
Membranes for Modelling Cardiac Tissue Stiffness In Vitro Based on Poly(trimethylene carbonate) and Poly(ethylene glycol) Polymers
title Membranes for Modelling Cardiac Tissue Stiffness In Vitro Based on Poly(trimethylene carbonate) and Poly(ethylene glycol) Polymers
title_full Membranes for Modelling Cardiac Tissue Stiffness In Vitro Based on Poly(trimethylene carbonate) and Poly(ethylene glycol) Polymers
title_fullStr Membranes for Modelling Cardiac Tissue Stiffness In Vitro Based on Poly(trimethylene carbonate) and Poly(ethylene glycol) Polymers
title_full_unstemmed Membranes for Modelling Cardiac Tissue Stiffness In Vitro Based on Poly(trimethylene carbonate) and Poly(ethylene glycol) Polymers
title_short Membranes for Modelling Cardiac Tissue Stiffness In Vitro Based on Poly(trimethylene carbonate) and Poly(ethylene glycol) Polymers
title_sort membranes for modelling cardiac tissue stiffness in vitro based on poly(trimethylene carbonate) and poly(ethylene glycol) polymers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650615/
https://www.ncbi.nlm.nih.gov/pubmed/33022962
http://dx.doi.org/10.3390/membranes10100274
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