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Sci Rep. 2018 Apr 30;8(1):6708. doi: 10.1038/s41598-018-25115-2.

Head-to-head comparison of two engineered cardiac grafts for myocardial repair: From scaffold characterization to pre-clinical testing.

Author information

1
ICREC Research Program, Health Science Research Institute Germans Trias i Pujol, Badalona, Spain.
2
CIBER de Enfermedades Cardiovasculares, Madrid, Spain.
3
Centre of Regenerative Medicine in Barcelona, Barcelona, Spain.
4
Biophysics and Bioengineering Unit, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
5
Institute for Bioengineering of Catalonia, The Barcelona Institute of Science and Technology, Barcelona, Spain.
6
CIBER de Enfermedades Respiratorias, Madrid, Spain.
7
Anaxomics Biotech, Barcelona, Spain.
8
Flow Cytometry Facility, Germans Trias i Pujol Research Institute, Campus Can Ruti, Badalona, Spain.
9
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
10
ICREC Research Program, Health Science Research Institute Germans Trias i Pujol, Badalona, Spain. abayesgenis@gmail.com.
11
CIBER de Enfermedades Cardiovasculares, Madrid, Spain. abayesgenis@gmail.com.
12
Cardiology Service, Germans Trias i Pujol University Hospital, Badalona, Spain. abayesgenis@gmail.com.
13
Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain. abayesgenis@gmail.com.

Abstract

Cardiac tissue engineering, which combines cells and supportive scaffolds, is an emerging treatment for restoring cardiac function after myocardial infarction (MI), although, the optimal construct remains a challenge. We developed two engineered cardiac grafts, based on decellularized scaffolds from myocardial and pericardial tissues and repopulated them with adipose tissue mesenchymal stem cells (ATMSCs). The structure, macromechanical and micromechanical scaffold properties were preserved upon the decellularization and recellularization processes, except for recellularized myocardium micromechanics that was ∼2-fold stiffer than native tissue and decellularized scaffolds. Proteome characterization of the two acellular matrices showed enrichment of matrisome proteins and major cardiac extracellular matrix components, considerably higher for the recellularized pericardium. Moreover, the pericardial scaffold demonstrated better cell penetrance and retention, as well as a bigger pore size. Both engineered cardiac grafts were further evaluated in pre-clinical MI swine models. Forty days after graft implantation, swine treated with the engineered cardiac grafts showed significant ventricular function recovery. Irrespective of the scaffold origin or cell recolonization, all scaffolds integrated with the underlying myocardium and showed signs of neovascularization and nerve sprouting. Collectively, engineered cardiac grafts -with pericardial or myocardial scaffolds- were effective in restoring cardiac function post-MI, and pericardial scaffolds showed better structural integrity and recolonization capability.

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