title: Intramyocardial injection of a synthetic hydrogel with delivery of bFGF and IGF1 in a rat model of ischemic cardiomyopathy.
abstract: It is increasingly appreciated that the properties of a biomaterial used in intramyocardial injection therapy influence the outcomes of infarcted hearts that are treated. In this report the extended in vivo efficacy of a thermally responsive material that can deliver dual growth factors while providing a slow degradation time and high mechanical stiffness is examined. Copolymers consisting of N-isopropylacrylamide, 2-hydroxyethyl methacrylate, and degradable methacrylate polylactide were synthesized. The release of bioactive basic fibroblast growth factor (bFGF) and insulin-like growth factor 1 (IGF1) from the gel and loaded poly(lactide-co-glycolide) microparticles was assessed. Hydrogel with or without loaded growth factors was injected into 2 week-old infarcts in Lewis rats and animals were followed for 16 weeks. The hydrogel released bioactive bFGF and IGF1 as shown by mitogenic effects on rat smooth muscle cells in vitro. Cardiac function and geometry were improved for 16 weeks after hydrogel injection compared to saline injection. Despite demonstrating that left ventricular levels of bFGF and IGF1 were elevated for two weeks after injection of growth factor loaded gels, both functional and histological assessment showed no added benefit to inclusion of these proteins. This result points to the complexity of designing appropriate materials for this application and suggests that the nature of the material alone, without exogenous growth factors, has a direct ability to influence cardiac remodeling.
authors.affiliation: Department of Bioengineering and ‡McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania 15219, United States.
authors.forename: Devin M
authors.initials: DM
authors.lastname: Nelson
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Hashizume
authors.forename: Tomo
authors.initials: T
authors.lastname: Yoshizumi
authors.forename: Anna K
authors.initials: AK
authors.lastname: Blakney
authors.forename: Zuwei
authors.initials: Z
authors.lastname: Ma
authors.forename: William R
authors.initials: WR
authors.lastname: Wagner
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage; D007273:Injections, Intramuscular; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: C548904:insulin-like growth factor-1, rat; D016222:Fibroblast Growth Factor 2; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007334:Insulin-Like Growth Factor I