Photocrosslinkable hydrogel for myocyte cell culture and injection.
Conventional treatment options for myocardial infarction are limited by the inability of mature myocardium to regenerate after injury. Although functional improvements after injection of cells and growth factors have been demonstrated, the clinical utility of this procedure has been hampered by poor cell localization, low survival, and rapid clearance of injected growth factors. The main objective of this study was to evaluate the applicability of a hydrogel, based on photocrosslinkable chitosan and acryloyl-poly(ethylene glycol)-RGDS (Az-chitosan/Acr-PEG-RGD) for myocyte cell culture and myocardial injection. Chitosan was modified with photoreactive azidobenzoic acid and Acr-PEG-RGD was synthesized by reacting YRGDS with an equimolar amount of acryloyl-PEG-N-hydroxysuccinimide. For injection and encapsulation each polymer was dissolved in Di-H(2)O (pH 6.4), the solutions were mixed and crosslinked by UV application (4 mW/cm(2)). C2C12 myoblasts proliferated and differentiated on hydrogels containing 5 mM RGD but not on the pure photocrosslinked chitosan. In vitro, the crosslinked hydrogels retained 80% of encapsulated VEGF for 24 days. Live/dead staining of neonatal rat cardiomyocytes encapsulated into Az-chitosan/Acr-PEG-RGD hydrogels indicated high cell viability upon UV crosslinking. Ex vivo, we localized the hydrogel on the surface and in the ventricle wall of an adult rat heart by brief (2 min) UV light application.
Yeo
Yoon
Y
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Geng
Wenliang
W
Ito
Taichi
T
Kohane
Daniel S
DS
Burdick
Jason A
JA
Radisic
Milica
M
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival; D048271:Chitosan / Q000737:chemistry; D003432:Cross-Linking Reagents; D020100:Hydrogels / Q000737:chemistry; D008422:Materials Testing; D051379:Mice; D008855:Microscopy, Electron, Scanning; D032342:Muscle Cells / Q000166:cytology* / Q000637:transplantation*; D009203:Myocardial Infarction / Q000628:therapy; D032383:Myocytes, Cardiac / Q000166:cytology / Q000637:transplantation; D009842:Oligopeptides / Q000737:chemistry; D010777:Photochemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014466:Ultraviolet Rays; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage
D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D020100:Hydrogels; D009842:Oligopeptides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D048271:Chitosan