title: Polymeric electrospun scaffolds: neuregulin encapsulation and biocompatibility studies in a model of myocardial ischemia.
abstract: Cardiovascular disease represents one of the major health challenges in modern times and is the number one cause of death globally. Thus, numerous studies are under way to identify effective cell- and/or growth factor (GF)-based therapies for repairing damaged cardiac tissue. In this regard, improving the engraftment or survival of regenerative cells and prolonging GF exposure have become fundamental goals in advancing these therapeutic approaches. Biomaterials have emerged as innovative scaffolds for the delivery of both cells and proteins in tissue engineering applications. In the present study, electrospinning was used to generate smooth homogenous polymeric fibers, which consisted of a poly(lactic-co-glycolic acid) (PLGA)/NCO-sP(EO-stat-PO) polymer blend encapsulating the cardioactive GF, Neuregulin-1 (Nrg). We evaluated the biocompatibility and degradation of this Nrg-containing biomaterial in a rat model of myocardial ischemia. Histological analysis revealed the presence of an initial acute inflammatory response after implantation, which was followed by a chronic inflammatory phase, characterized by the presence of giant cells. Notably, the scaffold remained in the heart after 3 months. Furthermore, an increase in the M2:M1 macrophage ratio following implantation suggested the induction of constructive tissue remodeling. Taken together, the combination of Nrg-encapsulating scaffolds with cells capable of inducing cardiac regeneration could represent an ambitious and promising therapeutic strategy for repairing diseased or damaged myocardial tissue.
authors.affiliation: 1 Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra , Pamplona, Spain .
authors.forename: Teresa
authors.initials: T
authors.lastname: Simón-Yarza
authors.forename: Angela
authors.initials: A
authors.lastname: Rossi
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Heffels
authors.forename: Felipe
authors.initials: F
authors.lastname: Prósper
authors.forename: Jürgen
authors.initials: J
authors.lastname: Groll
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Blanco-Prieto
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D016764:Cell Polarity / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D019344:Lactic Acid / Q000737:chemistry*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008422:Materials Testing; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology; D020890:Neuregulin-1 / Q000494:pharmacology / Q000627:therapeutic use*; D010641:Phenotype; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; C094131:NRG1 protein, human; D020890:Neuregulin-1; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid