The effects of peptide-based modification of alginate on left ventricular remodeling and function after myocardial infarction.
Adverse cardiac remodeling and dysfunction after myocardial infarction (MI) is associated with (BioLineRx, BL-1040 myocardial implant) excessive damage to the extracellular matrix. Biomaterials, such as the in situ-forming alginate hydrogel, provide temporary support and attenuate these processes. Here, we tested the effects of decorating alginate biomaterial with cell adhesion peptides, containing the sequences RGD and YIGSR, or a non-specific peptide (RGE), in terms of therapeutic outcome soon after MI. The biomaterial (i.e., both unmodified and peptide-modified alginate) solutions retained the ability to flow after cross-linking with calcium ions, and could be injected into 7-day infarcts, where they underwent phase transition into hydrogels. Serial echocardiography studies performed before and 60 days after treatment showed that alginate modification with the peptides reduced the therapeutical effects of the hydrogel, as revealed by the extent of scar thickness, left ventricle dilatation and function. Histology and immunohistochemistry revealed no significant differences in blood vessel density, scar thickness, myofibroblast or macrophage infiltration or cell proliferation between the experimental groups BioLineRx BL-1040 myocardial implant. Our studies thus reveal that the chemical and physical traits of the biomaterial can affect its therapeutical efficacy in attenuating left ventricle remodeling and function, post-MI.
Department of Biotechnology Engineering, Ben-Gurion University of Negev, Beer Sheva, Israel.
Orna
O
Tsur-Gang
Emil
E
Ruvinov
Natalie
N
Landa
Radka
R
Holbova
Micha S
MS
Feinberg
Jonathan
J
Leor
Smadar
S
Cohen
D000199:Actins / Q000032:analysis; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D000831:Animals, Newborn; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D020100:Hydrogels / Q000737:chemistry / Q000627:therapeutic use; D007150:Immunohistochemistry; D008422:Materials Testing; D009130:Muscle, Smooth / Q000737:chemistry; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology*; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
D000199:Actins; D000464:Alginates; D001672:Biocompatible Materials; D020100:Hydrogels; D009842:Oligopeptides; D010455:Peptides; D018809:Proliferating Cell Nuclear Antigen; C112658:arginyl-glycyl-glutamic acid; C047981:arginyl-glycyl-aspartic acid