title: Neoinnervation and neovascularization of acellular pericardial-derived scaffolds in myocardial infarcts.
abstract: Engineered bioimplants for cardiac repair require functional vascularization and innervation for proper integration with the surrounding myocardium. The aim of this work was to study nerve sprouting and neovascularization in an acellular pericardial-derived scaffold used as a myocardial bioimplant. To this end, 17 swine were submitted to a myocardial infarction followed by implantation of a decellularized human pericardial-derived scaffold. After 30 days, animals were sacrificed and hearts were analyzed with hematoxylin/eosin and Masson's and Gallego's modified trichrome staining. Immunohistochemistry was carried out to detect nerve fibers within the cardiac bioimplant by using βIII tubulin and S100 labeling. Isolectin B4, smooth muscle actin, CD31, von Willebrand factor, cardiac troponin I, and elastin antibodies were used to study scaffold vascularization. Transmission electron microscopy was performed to confirm the presence of vascular and nervous ultrastructures. Left ventricular ejection fraction (LVEF), cardiac output (CO), stroke volume, end-diastolic volume, end-systolic volume, end-diastolic wall mass, and infarct size were assessed by using magnetic resonance imaging (MRI). Newly formed nerve fibers composed of several amyelinated axons as the afferent nerve endings of the heart were identified by immunohistochemistry. Additionally, neovessel formation occurred spontaneously as small and large isolectin B4-positive blood vessels within the scaffold. In summary, this study demonstrates for the first time the neoformation of vessels and nerves in cell-free cardiac scaffolds applied over infarcted tissue. Moreover, MRI analysis showed a significant improvement in LVEF (P = 0.03) and CO (P = 0.01) and a 43 % decrease in infarct size (P = 0.007).
authors.affiliation: ICREC Research Program, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Camí de les Escoles s/n, Badalona, Barcelona, 08916, Spain. cgalvez@igtp.cat.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gálvez-Montón
authors.affiliation: Pathology Department, Hospital Universitari Germans Trias i Pujol Ctra. Canyet, s/n,, Badalona, Barcelona, 08916, Spain. maiteffig@gmail.com.|Center of Regenerative Medicine in Barcelona, Dr. Aiguader, 88, Barcelona, 08003, Spain. maiteffig@gmail.com.
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Fernandez-Figueras
authors.affiliation: Center of Regenerative Medicine in Barcelona, Dr. Aiguader, 88, Barcelona, 08003, Spain. mmarti@cmrb.eu.|Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Baldiri Reixac, 10, Barcelona, 08028, Spain. mmarti@cmrb.eu.
authors.forename: Mercè
authors.initials: M
authors.lastname: Martí
authors.affiliation: ICREC Research Program, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Camí de les Escoles s/n, Badalona, Barcelona, 08916, Spain. csoler@igtp.cat.
authors.forename: Carolina
authors.initials: C
authors.lastname: Soler-Botija
authors.affiliation: ICREC Research Program, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Camí de les Escoles s/n, Badalona, Barcelona, 08916, Spain. sroura@igtp.cat.
authors.forename: Santiago
authors.initials: S
authors.lastname: Roura
authors.affiliation: ICREC Research Program, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Camí de les Escoles s/n, Badalona, Barcelona, 08916, Spain. iperea@igtp.cat.
authors.forename: Isaac
authors.initials: I
authors.lastname: Perea-Gil
authors.affiliation: ICREC Research Program, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Camí de les Escoles s/n, Badalona, Barcelona, 08916, Spain. cprat@igtp.cat.
authors.forename: Cristina
authors.initials: C
authors.lastname: Prat-Vidal
authors.affiliation: ICREC Research Program, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Camí de les Escoles s/n, Badalona, Barcelona, 08916, Spain. allucia@igtp.cat.
authors.forename: Aida
authors.initials: A
authors.lastname: Llucià-Valldeperas
authors.affiliation: Center of Regenerative Medicine in Barcelona, Dr. Aiguader, 88, Barcelona, 08003, Spain. araya@cmrb.eu.|Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Baldiri Reixac, 10, Barcelona, 08028, Spain. araya@cmrb.eu.|Institute for Bioengineering of Catalonia (IBEC) and Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. araya@cmrb.eu.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Raya
authors.affiliation: ICREC Research Program, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Camí de les Escoles s/n, Badalona, Barcelona, 08916, Spain. abayes.germanstrias@gencat.cat.|Department of Medicine, Universitat Autònoma de Barcelona (UAB), Ctra. de Canyet, s/n, Barcelona, Spain, 08916. abayes.germanstrias@gencat.cat.|Cardiology Service, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain. abayes.germanstrias@gencat.cat.
authors.forename: Antoni
authors.initials: A
authors.lastname: Bayes-Genis
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000502:physiology; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism; D009389:Neovascularization, Pathologic; D010496:Pericardium / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D009418:S100 Proteins / Q000378:metabolism; D013552:Swine; D054457:Tissue Scaffolds; D014404:Tubulin / Q000378:metabolism; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D009418:S100 Proteins; D014404:Tubulin