resumo
The use of engineered cardiac tissue for high-throughput drug screening/toxicology assessment remains largely unexplored. Here we propose a scaffold that mimics aspects of cardiac extracellular matrix while preserving the contractility of cardiomyocytes. The scaffold is based on a poly(caprolactone) (PCL) nanofilm with magnetic properties (MNF, standing for magnetic nanofilm) coated with a layer of piezoelectric (PIEZO) microfibers of poly(vinylidene fluoride-trifluoroethylene) (MNF+PIEZO). The nanofilm creates a flexible support for cell contraction and the aligned PIEZO microfibers deposited on top of the nanofilm creates conditions for cell alignment and electrical stimulation of the seeded cells. Our results indicate that MNF+PIEZO scaffold promotes rat and human cardiac cell attachment and alignment, maintains the ratio of cell populations overtime, promotes cell-cell communication and metabolic maturation, and preserves cardiomyocyte (CM) contractility for at least 12 days. The engineered cardiac construct showed high toxicity against doxorubicin, a cardiotoxic molecule, and responded to compounds that modulate CM contraction such as epinephrine, propranolol and heptanol. (C) 2017 The Authors. Published by Elsevier Ltd.
palavras-chave
CELL-DERIVED CARDIOMYOCYTES; ENGINEERED HEART-TISSUE; ELECTRICAL-STIMULATION; CARDIAC TISSUE; IN-VITRO; SCAFFOLDS; MATURATION; MYOCYTES; CARDIOTOXICITY; DOXORUBICIN
categoria
Engineering; Materials Science
autores
Gouveia, PJ; Rosa, S; Ricotti, L; Abecasis, B; Almeida, HV; Monteiro, L; Nunes, J; Carvalho, FS; Serra, M; Luchkin, S; Kholkin, AL; Alves, PM; Oliveira, PJ; Carvalho, R; Menciassi, A; das Neves, RP; Ferreira, LS
nossos autores
Andrei Kholkin
Investigador Principal
Sergey Luchkin
Estudante de doutoramentoagradecimentos
This work was supported by funds from FEDER through COMPETE program and Fundacao para a Ciencia e a Tecnologia (FCT) (EXPL/DTP-FTO/0570/2012, MITP-TB/ECE/0013/2013 to S. R. and L.F., and PTDC/SAU-ENB/113696/2009 to R.P.N.; SFRH/BD/51197/2010 and SFRH/BPD/79323/2011 to P.G. and S.R., respectively), as well as ERA Chair project, ERA@UC, European Union's Horizon 2020 research and innovation program under grant agreement No 669088. NMR data was collected at the UC-NMR facility which is supported in part by FEDER e European Regional Development Fund through the COMPETE Programme (Operational Programme for Competitiveness) and by National Funds through FCT e Fundacao para a Ciencia e a Tecnologia (Portuguese Foundation for Science and Technology) through grants REEQ/481/QUI/2006, RECI/QEQ-QFI/0168/2012, CENTRO-07-CT62-FEDER-002012, and Rede Nacional de Ressonancia Magnetica Nuclear (RNRMN). The authors also would like to acknowledge the help of Tommaso Mazzochi for the finite model simulations. The authors declare no conflict of interest to disclose.