Photocrosslinkable chitosan modified with angiopoietin-1 peptide, QHREDGS, promotes survival of neonatal rat heart cells.
Myocardial infarction (MI) results in the death of cardiomyocytes (CM), which causes scar formation and pathological remodeling of the heart. The delivery of healthy myocytes or bone marrow cells reduces pathological remodeling after MI, however, current cell injection methods have low cell survival rates and high cell loss. The main objective of this work was to develop a novel hydrogel that can promote survival of CMs. Photocrosslinkable azidobenzoic acid modified chitosan (Az-chitosan) was conjugated with the angiopoietin-1-derived peptide, QHREDGS. This novel peptide is thought to mediate attachment and survival responses of CM to angiopoietin-1 via integrin binding. Thin layers of Az-chitosan, Az-chitosan-QHREDGS, and Az-chitosan-DGQESHR (scrambled peptide control) were spin coated on glass slides and photocrosslinked with application of UV light (365 nm). Neonatal rat heart cells cultured up to 5 days, demonstrated significantly higher attachment and viability on Az-chitosan-QHREDGS compared to cells on other hydrogel controls. Surfaces were also stained for the CM-specific marker troponin I, demonstrating significantly higher percentage of CMs on Az-chitosan-QHREDGS compared to Az-chitosan. The cells cultivated on Az-chitosan-QHREDGS demonstrated significantly lower levels of caspase 3/7 activation after taxol treatment in comparison to cells cultivated on the control hydrogels, glass substrate, or Az-chitosan linked to RGD, an established integrin binding peptide that did not protect against apoptosis. Thus, Az-chitosan-QHREDGS supports attachment and survival of neonatal rat heart cells.
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada.
Fiona
F
Rask
Susan M
SM
Dallabrida
Nesreen S
NS
Ismail
Zohreh
Z
Amoozgar
Yoon
Y
Yeo
Maria A
MA
Rupnick
Milica
M
Radisic
D000595:Amino Acid Sequence; D042683:Angiopoietin-1 / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001386:Azides / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D048271:Chitosan / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties / Q000187:drug effects; D019210:Troponin I / Q000378:metabolism; D014466:Ultraviolet Rays
D042683:Angiopoietin-1; D001386:Azides; D003432:Cross-Linking Reagents; D010455:Peptides; D019210:Troponin I; C087164:4-azidobenzoic acid; D048271:Chitosan