Photocrosslinkable hydrogel for myocyte cell culture and injection

被引:98
作者
Yeo, Yoon
Geng, Wenliang
Ito, Taichi
Kohane, Daniel S.
Burdick, Jason A.
Radisic, Milica [1 ]
机构
[1] Univ Toronto, Inst Biomat & Biomed Engn, Dept Chem Engn & Appl Chem, Toronto, ON, Canada
[2] MIT, Dept Chem Engn, Cambridge, MA 02139 USA
[3] Massachusetts Gen Hosp, Pediat Intens Care Unit, Boston, MA USA
[4] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA
关键词
heart; cell injection; cardiomyocyte; myocardial infarction; RGD; photocrosslinkable hydrogel;
D O I
10.1002/jbm.b.30667
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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-H2O (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. (c) 2006 Wiley Periodicals, Inc.
引用
收藏
页码:312 / 322
页数:11
相关论文
共 37 条
[21]   Regenerating the heart [J].
Laflamme, MA ;
Murry, CE .
NATURE BIOTECHNOLOGY, 2005, 23 (07) :845-856
[22]   Comparative effects of basic fibroblast growth factor and vascular endothelial growth factor on coronary collateral development and the arterial response to injury [J].
Lazarous, DF ;
Shou, M ;
Scheinowitz, M ;
Hodge, E ;
Thirumurti, V ;
Kitsiou, AN ;
Stiber, JA ;
Lobo, AD ;
Hunsberger, S ;
Guetta, E ;
Epstein, SE ;
Unger, EF .
CIRCULATION, 1996, 94 (05) :1074-1082
[23]   Survival and development of neonatal rat cardiomyocytes transplanted into adult myocardium [J].
Müller-Ehmsen, J ;
Whittaker, P ;
Kloner, RA ;
Dow, JS ;
Sakoda, T ;
Long, TI ;
Laird, PW ;
Kedes, L .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2002, 34 (02) :107-116
[24]   Rebuilding a damaged heart -: Long-term survival of transplanted neonatal rat cardiomyocytes after myocardial infarction and effect on cardiac function [J].
Müller-Ehmsen, J ;
Peterson, KL ;
Kedes, L ;
Whittaker, P ;
Dow, JS ;
Long, TI ;
Laird, PW ;
Kloner, RA .
CIRCULATION, 2002, 105 (14) :1720-1726
[25]  
Ono K, 2000, J BIOMED MATER RES, V49, P289
[26]   High-density seeding of myocyte cells for cardiac tissue engineering [J].
Radisic, M ;
Euloth, M ;
Yang, LM ;
Langer, R ;
Freed, LE ;
Vunjak-Novakovic, G .
BIOTECHNOLOGY AND BIOENGINEERING, 2003, 82 (04) :403-414
[27]   Cellular cardiomyoplasty - cardiomyocytes, skeletal myoblasts, or stem cells for regenerating myocardium and treatment of heart failure? [J].
Reffelmann, T ;
Kloner, RA .
CARDIOVASCULAR RESEARCH, 2003, 58 (02) :358-368
[28]   Survival, integration, and differentiation of cardiomyocyte grafts - A study in normal and injured rat hearts [J].
Reinecke, H ;
Zhang, M ;
Bartosek, T ;
Murry, CE .
CIRCULATION, 1999, 100 (02) :193-202
[29]  
Reinlib L, 2000, CIRCULATION, V101, pE182
[30]  
Risbud MV, 2001, J BIOMED MATER RES, V57, P300, DOI 10.1002/1097-4636(200111)57:2<300::AID-JBM1171>3.0.CO