title: Bioengineering the infarcted heart by applying bio-inspired materials.
abstract: Induction of cardiac muscle regeneration following myocardial infarction (MI) represents a major challenge in cardiovascular therapy, as the current clinical approaches are limited in their ability to regenerate a new muscle tissue and to replace infarcted myocardium. Here, we describe the conception of two strategies based on bio-inspired materials, aimed at myocardial repair after MI. In the first strategy, alginate biomaterial was designed with affinity-binding moieties, enabling the binding of heparin-binding proteins and their controlled presentation and release. The combined features of this unique alginate hydrogel, as a temporary extracellular matrix replacement and a depot for bio-molecules such as insulin-like growth factor-1 and hepatocyte growth factor, led to improvements in cardiac structure and function, as demonstrated by the biomaterial's abilities to thicken the scar and prevent left-ventricular remodeling and dilatation. Endogenous regeneration occurring at the infarct as manifested by the enhanced angiogenesis, cardiomyocyte proliferation, and appearance of cardiac-related stem cells is likely to have contributed to this. In the second strategy, phosphatidylserine (PS)-presenting liposomes were developed to mimic apoptotic cells bodies, specifically their capability of immunomodulating activated macrophages into anti-inflammatory state. In a rat model of acute MI, targeting of PS-presenting liposomes to infarct macrophages after injection via the femoral vein was demonstrated by magnetic resonance imaging. The treatment promoted angiogenesis, the preservation of small scars, and prevention of ventricular dilatation and remodeling. Collectively, the two bio-inspired material-based strategies presented herein represent unique and clinical accessible approaches for myocardial infarct repair.
authors.affiliation: The Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva, PO Box 653, 84105, Israel. ruvinove@bgu.ac.il
authors.forename: Emil
authors.initials: E
authors.lastname: Ruvinov
authors.forename: Tamar
authors.initials: T
authors.lastname: Harel-Adar
authors.forename: Smadar
authors.initials: S
authors.lastname: Cohen
mesh_terms: D000464:Alginates; D000818:Animals; D001672:Biocompatible Materials; D057005:Bioengineering / Q000379:methods*; D004195:Disease Models, Animal; D004337:Drug Carriers; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D007267:Injections; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008081:Liposomes; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009203:Myocardial Infarction / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D018919:Neovascularization, Physiologic; D010718:Phosphatidylserines; D051381:Rats; D012038:Regeneration; D044968:Regenerative Medicine / Q000379:methods*; D013997:Time Factors; D054457:Tissue Scaffolds; D020257:Ventricular Remodeling
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D004337:Drug Carriers; D016326:Extracellular Matrix Proteins; D006603:Hexuronic Acids; D036341:Intercellular Signaling Peptides and Proteins; D008081:Liposomes; D010718:Phosphatidylserines; D020723:Glucuronic Acid