title: Differential efficacy of gels derived from small intestinal submucosa as an injectable biomaterial for myocardial infarct repair.
abstract: Injectable biomaterials have been recently investigated as a therapeutic approach for cardiac repair. Porcine-derived small intestinal submucosa (SIS) material is currently used in the clinic to promote accelerated wound healing for a variety of disorders. In this study, we hypothesized that gels derived from SIS extracellular matrix would be advantageous as an injectable material for cardiac repair. We evaluated 2 forms of SIS gel, types B (SIS-B) and C (SIS-C), for their ability to provide a therapeutic effect when injected directly into ischemic myocardium using a murine model of an acute myocardial infarction. Echocardiography analysis at both 2 and 6 weeks after infarction demonstrated preservation of end-systolic left ventricular geometry and improvement of cardiac contractility in the hearts injected with SIS-B when compared with control hearts injected with saline. However, the SIS-C gel provided no functional efficacy in comparison with control. Histological analysis revealed that SIS-B reduced infarct size and induced angiogenesis relative to control, whereas injection of SIS-C had minimal effect on these histological parameters. Characterization of both gels revealed differential growth factor content with SIS-B exhibiting higher levels of basic fibroblast growth factor than SIS-C, which may explain, at least in part, the differential histological and functional results. This study suggests that SIS gel offers therapeutic potential as an injectable material for the repair of ischemic myocardium. Further understanding of SIS gel characteristics, such as biological and physical properties, that are critical determinants of efficacy would be important for optimization of this biomaterial for cardiac repair.
authors.affiliation: Stem Cell Research Center, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Masaho
authors.initials: M
authors.lastname: Okada
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Payne
authors.forename: Hideki
authors.initials: H
authors.lastname: Oshima
authors.forename: Nobuo
authors.initials: N
authors.lastname: Momoi
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Tobita
authors.forename: Johnny
authors.initials: J
authors.lastname: Huard
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004452:Echocardiography; D005782:Gels / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects; D007267:Injections; D007413:Intestinal Mucosa / Q000737:chemistry*; D007421:Intestine, Small / Q000033:anatomy & histology*; D008297:Male; D008422:Materials Testing; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D013552:Swine; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D001672:Biocompatible Materials; D005782:Gels