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Abstract
Cardiac tissue engineering, which combines cells and biomaterials, is promising for limiting the sequelae of myocardial infarction (MI). We assessed myocardial function and scar evolution after implanting an engineered bioactive impedance graft (EBIG) in a swine MI model. The EBIG comprises a scaffold of decellularized human pericardium, green fluorescent protein-labeled porcine adipose tissue-derived progenitor cells (pATPCs), and a customized-design electrical impedance spectroscopy (EIS) monitoring system. Cardiac function was evaluated noninvasively by using magnetic resonance imaging (MRI). Scar healing was evaluated by using the EIS system within the implanted graft. Additionally, infarct size, fibrosis, and inflammation were explored by histopathology. Upon sacrifice 1 month after the intervention, MRI detected a significant improvement in left ventricular ejection fraction (7.5% ± 4.9% vs. 1.4% ± 3.7%; p = .038) and stroke volume (11.5 ± 5.9 ml vs. 3 ± 4.5 ml; p = .019) in EBIG-treated animals. Noninvasive EIS data analysis showed differences in both impedance magnitude ratio (−0.02 ± 0.04 per day vs. −0.48 ± 0.07 per day; p = .002) and phase angle slope (−0.18° ± 0.24° per day vs. −3.52° ± 0.84° per day; p = .004) in EBIG compared with control animals. Moreover, in EBIG-treated animals, the infarct size was 48% smaller (3.4% ± 0.6% vs. 6.5% ± 1%; p = .015), less inflammation was found by means of CD25+ lymphocytes (0.65 ± 0.12 vs. 1.26 ± 0.2; p = .006), and a lower collagen I/III ratio was detected (0.49 ± 0.06 vs. 1.66 ± 0.5; p = .019). An EBIG composed of acellular pericardium refilled with pATPCs significantly reduced infarct size and improved cardiac function in a preclinical model of MI. Noninvasive EIS monitoring was useful for tracking differential scar healing in EBIG-treated animals, which was confirmed by less inflammation and altered collagen deposit. S
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Details
1 ICREC (Heart Failure and Cardiac Regeneration) Research Programme, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain;
2 Electronic and Biomedical Instrumentation Group, Electronic Engineering Department, Universitat Politècnica de Catalunya, Barcelona, Spain
3 Jesús Usón Minimally Invasive Surgery Centre, Cáceres, Spain
4 ICREC (Heart Failure and Cardiac Regeneration) Research Programme, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain;; Center of Regenerative Medicine in Barcelona, Barcelona, Spain
5 ICREC (Heart Failure and Cardiac Regeneration) Research Programme, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain;; Cardiology Service, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain;; Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain