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Wet-Spun Polycaprolactone Scaffolds Provide Customizable Anisotropic Viscoelastic Mechanics for Engineered Cardiac Tissues

Myocardial infarction is a leading cause of death worldwide and has severe consequences including irreversible damage to the myocardium, which can lead to heart failure. Cardiac tissue engineering aims to re-engineer the infarcted myocardium using tissues made from human-induced pluripotent stem cel...

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Autores principales: Schmitt, Phillip R., Dwyer, Kiera D., Minor, Alicia J., Coulombe, Kareen L. K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9657938/
https://www.ncbi.nlm.nih.gov/pubmed/36365565
http://dx.doi.org/10.3390/polym14214571
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author Schmitt, Phillip R.
Dwyer, Kiera D.
Minor, Alicia J.
Coulombe, Kareen L. K.
author_facet Schmitt, Phillip R.
Dwyer, Kiera D.
Minor, Alicia J.
Coulombe, Kareen L. K.
author_sort Schmitt, Phillip R.
collection PubMed
description Myocardial infarction is a leading cause of death worldwide and has severe consequences including irreversible damage to the myocardium, which can lead to heart failure. Cardiac tissue engineering aims to re-engineer the infarcted myocardium using tissues made from human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to regenerate heart muscle and restore contractile function via an implantable epicardial patch. The current limitations of this technology include both biomanufacturing challenges in maintaining tissue integrity during implantation and biological challenges in inducing cell alignment, maturation, and coordinated electromechanical function, which, when overcome, may be able to prevent adverse cardiac remodeling through mechanical support in the injured heart to facilitate regeneration. Polymer scaffolds serve to mechanically reinforce both engineered and host tissues. Here, we introduce a novel biodegradable, customizable scaffold composed of wet-spun polycaprolactone (PCL) microfibers to strengthen engineered tissues and provide an anisotropic mechanical environment to promote engineered tissue formation. We developed a wet-spinning process to produce consistent fibers which are then collected on an automated mandrel that precisely controls the angle of intersection of fibers and their spacing to generate mechanically anisotropic scaffolds. Through optimization of the wet-spinning process, we tuned the fiber diameter to 339 ± 31 µm and 105 ± 9 µm and achieved a high degree of fidelity in the fiber structure within the scaffold (fiber angle within 1.8° of prediction). Through degradation and mechanical testing, we demonstrate the ability to maintain scaffold mechanical integrity as well as tune the mechanical environment of the scaffold through structure (Young’s modulus of 120.8 ± 1.90 MPa for 0° scaffolds, 60.34 ± 11.41 MPa for 30° scaffolds, 73.59 ± 3.167 MPa for 60° scaffolds, and 49.31 ± 6.90 MPa for 90° scaffolds), while observing decreased hysteresis in angled vs. parallel scaffolds. Further, we embedded the fibrous PCL scaffolds in a collagen hydrogel mixed with hiPSC-CMs to form engineered cardiac tissue with high cell survival, tissue compaction, and active contractility of the hiPSC-CMs. Through this work, we develop and optimize a versatile biomanufacturing process to generate customizable PCL fibrous scaffolds which can be readily utilized to guide engineered tissue formation and function.
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spelling pubmed-96579382022-11-15 Wet-Spun Polycaprolactone Scaffolds Provide Customizable Anisotropic Viscoelastic Mechanics for Engineered Cardiac Tissues Schmitt, Phillip R. Dwyer, Kiera D. Minor, Alicia J. Coulombe, Kareen L. K. Polymers (Basel) Article Myocardial infarction is a leading cause of death worldwide and has severe consequences including irreversible damage to the myocardium, which can lead to heart failure. Cardiac tissue engineering aims to re-engineer the infarcted myocardium using tissues made from human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to regenerate heart muscle and restore contractile function via an implantable epicardial patch. The current limitations of this technology include both biomanufacturing challenges in maintaining tissue integrity during implantation and biological challenges in inducing cell alignment, maturation, and coordinated electromechanical function, which, when overcome, may be able to prevent adverse cardiac remodeling through mechanical support in the injured heart to facilitate regeneration. Polymer scaffolds serve to mechanically reinforce both engineered and host tissues. Here, we introduce a novel biodegradable, customizable scaffold composed of wet-spun polycaprolactone (PCL) microfibers to strengthen engineered tissues and provide an anisotropic mechanical environment to promote engineered tissue formation. We developed a wet-spinning process to produce consistent fibers which are then collected on an automated mandrel that precisely controls the angle of intersection of fibers and their spacing to generate mechanically anisotropic scaffolds. Through optimization of the wet-spinning process, we tuned the fiber diameter to 339 ± 31 µm and 105 ± 9 µm and achieved a high degree of fidelity in the fiber structure within the scaffold (fiber angle within 1.8° of prediction). Through degradation and mechanical testing, we demonstrate the ability to maintain scaffold mechanical integrity as well as tune the mechanical environment of the scaffold through structure (Young’s modulus of 120.8 ± 1.90 MPa for 0° scaffolds, 60.34 ± 11.41 MPa for 30° scaffolds, 73.59 ± 3.167 MPa for 60° scaffolds, and 49.31 ± 6.90 MPa for 90° scaffolds), while observing decreased hysteresis in angled vs. parallel scaffolds. Further, we embedded the fibrous PCL scaffolds in a collagen hydrogel mixed with hiPSC-CMs to form engineered cardiac tissue with high cell survival, tissue compaction, and active contractility of the hiPSC-CMs. Through this work, we develop and optimize a versatile biomanufacturing process to generate customizable PCL fibrous scaffolds which can be readily utilized to guide engineered tissue formation and function. MDPI 2022-10-28 /pmc/articles/PMC9657938/ /pubmed/36365565 http://dx.doi.org/10.3390/polym14214571 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schmitt, Phillip R.
Dwyer, Kiera D.
Minor, Alicia J.
Coulombe, Kareen L. K.
Wet-Spun Polycaprolactone Scaffolds Provide Customizable Anisotropic Viscoelastic Mechanics for Engineered Cardiac Tissues
title Wet-Spun Polycaprolactone Scaffolds Provide Customizable Anisotropic Viscoelastic Mechanics for Engineered Cardiac Tissues
title_full Wet-Spun Polycaprolactone Scaffolds Provide Customizable Anisotropic Viscoelastic Mechanics for Engineered Cardiac Tissues
title_fullStr Wet-Spun Polycaprolactone Scaffolds Provide Customizable Anisotropic Viscoelastic Mechanics for Engineered Cardiac Tissues
title_full_unstemmed Wet-Spun Polycaprolactone Scaffolds Provide Customizable Anisotropic Viscoelastic Mechanics for Engineered Cardiac Tissues
title_short Wet-Spun Polycaprolactone Scaffolds Provide Customizable Anisotropic Viscoelastic Mechanics for Engineered Cardiac Tissues
title_sort wet-spun polycaprolactone scaffolds provide customizable anisotropic viscoelastic mechanics for engineered cardiac tissues
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9657938/
https://www.ncbi.nlm.nih.gov/pubmed/36365565
http://dx.doi.org/10.3390/polym14214571
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