A microphysiological system combining electrospun fibers and electrical stimulation for the maturation of highly anisotropic cardiac tissue
he creation of cardiac tissue models for preclinical testing is still a non-solved problem in drug discovery, due to the limitations related to the in vitro replication of cardiac tissue complexity. Among these limitations, the difficulty of mimicking the functional properties of the myocardium due...
| Autores: | , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universitat Politècnica de Catalunya (UPC) |
| Repositorio: | UPCommons. Portal del coneixement obert de la UPC |
| Idioma: | inglés |
| OAI Identifier: | oai:upcommons.upc.edu:2117/361587 |
| Acceso en línea: | https://hdl.handle.net/2117/361587 https://dx.doi.org/10.1088/1758-5090/abff12 |
| Access Level: | acceso abierto |
| Palabra clave: | Electronics in cardiology Microphysiological system In vitro models Heart-on-a-chip Cardiac tissue engineering Electrospinning Electrònica en cardiologia Àrees temàtiques de la UPC::Enginyeria biomèdica::Electrònica biomèdica::Electrònica en cardiologia |
| Sumario: | he creation of cardiac tissue models for preclinical testing is still a non-solved problem in drug discovery, due to the limitations related to the in vitro replication of cardiac tissue complexity. Among these limitations, the difficulty of mimicking the functional properties of the myocardium due to the immaturity of the used cells hampers the obtention of reliable results that could be translated into human patients. In vivo models are the current gold standard to test new treatments, although it is widely acknowledged that the used animals are unable to fully recapitulate human physiology, which often leads to failures during clinical trials. In the present work, we present a microfluidic platform that aims to provide a range of signaling cues to immature cardiac cells to drive them towards an adult phenotype. The device combines topographical electrospun nanofibers with electrical stimulation in a microfabricated system. We validated our platform using a co-culture of neonatal mouse cardiomyocytes and cardiac fibroblasts, showing that it allows us to control the degree of anisotropy of the cardiac tissue inside the microdevice in a cost-effective way. Moreover, a 3D computational model of the electrical field was created and validated to demonstrate that our platform is able to closely match the distribution obtained with the gold standard (planar electrode technology) using inexpensive rod-shaped biocompatible stainless-steel electrodes. The functionality of the electrical stimulation was shown to induce a higher expression of the tight junction protein Cx-43, as well as the upregulation of several key genes involved in conductive and structural cardiac properties. These results validate our platform as a powerful tool for the tissue engineering community due to its low cost, high imaging compatibility, versatility, and high-throughput configuration capabilities. |
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